Download Dra. Wanda G. Vélez Andújar - Asociacion Medica de Puerto Rico

BOLETIN
Médico Científico de la Asociación Médica de Puerto Rico
Año 106 Número 2 - Abril a Junio de 2014
CONTENIDO
3 Mensaje del Presidente
Dra Wanda G. Vélez Andújar
Original Articles/Articulos Originales
4 ESTUDIO DESCRIPTIVO EPIDEMIOLÓGICO DE LAS CARACTERÍSTICAS CLÍNICAS DE LA BRONQUIOLITIS AGUDA EN
PACIENTES ADMITIDOS A LA UNIDAD PEDIÁTRICA DEL HOSPITAL MANATÍ MEDICAL CENTER
Zidnia M. Colón Blanco MD, Christian S. Colón Rivera MD, Migdalis Matos González MD, Brenda L. Pérez Valentín MD, Renato Rivera
Fernández MD, Isamir Santiago Méndez MD, Vielka Cintron MD
9 ANEMIA MANAGEMENT AMONG HEMODYALISIS PATIENTS AT THE UNIVERSITY HOSPITAL IN PUERTO RICO
Ileana E. Ocasio MD, Hector Diaz MD, José L. Cangiano MD, Rafael Báez MD, Erick Suárez PhD
OF HELICOBACTER PYLORI INFECTION IN HISPANIC PATIENTS WITH ANEMIA
13 ROLE
Melissa Ortiz MD, Bárbara Rosado-Carrión MD, Rafael Bredy MD
EPTIFIBATIDE: Gender related complications in a Hispanic population
19 Pamela Reyes Guerrero MD, Milton Carrero Quiñones MD, Rafael Bredy MD
Case Report/Reporte de Casos
TETANUS FOLLOWING PENETRATING EYE TRAUMA: A Case Report
25 CEPHALIC
Esteban Del Pilar Morales MD, Jorge Bertrán Pasarell MD, Zaydalee Cardona Rodriguez MD, Juan Carlos Almodovar Mercado MD, Alejandro Figueroa Navarro MD
MANIFESTATIONS OF ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC BONE MARROW TRANS30 OCULAR
PLANT
Betsy Colón-Acevedo MD, Lilia Rivera-Román MD, Nicole Candelario MD, Julio Sánchez MD
EOSINOPHILIC LEUKEMIA: A rare cause of Hypereosinophilic Syndrome
33 CHRONIC
Cristina Ortiz MD, Madeline Jimenez MD, Nelson A. Matos MD
JAUNDICE AND CHOLESTASIS IN A MIDDLE AGED WOMAN: A Case Report
37 VITILIGO,
Vanessa Seiglie MD, Viviana Freire MD, Bárbara Rosado-Carrión MD, Rafael Bredy MD, Carla Lozada MD
LARGE PALPABLE CERVICAL MASSES: Not always a malignant or infectious process
42 BILATERAL
Luis A. Figueroa-Jiménez MD, Mónica Santiago-Casiano MD, Emmanuel González-Irizarry MD, Amy González-Marquez MD, William
Cáceres-Perkins MD, Mildred Padilla-Ferrer MD, Anarda González MD4, Verόnica Santiago-Casiano MS
46 PRIMARY CLEAR CELL CARCINOMA OF THE LUNG WITH SALIVARY GLAND TYPE FEATURES
Miguel Albino-González MD, Haydee González-Hidalgo MD, Modesto González Del Rosario MD, Noel Totti-Veray MD, Carmen M.
Gurrea MD, Juan Vilaro MD, Amy Lee González-Márquez MD
49 ADENOCARCINOMA IN THE ILEOSTOMY OF A PATIENT WITH LONG-STANDING ULCERATIVE COLITIS: A Case Report and
Review of the Literature
Ada N. Acosta Martínez MD, Francisco Juame Anselmi, MD, Axel Baez-Torres MD, Rubén Alvarez MD, Norman Ramirez-Lluch MD,
Heriberto Sánchez MD
Review Articles/Artículos de Reseña
53 NEUROMONITOREO MULTIMODAL EN TRAUMA CRANEOENCEFALICO SEVERO: Estado del Arte
Juan José Gutiérrez-Paternina, Hernando Raphael Alvis-Miranda, Gabriel Alcalá-Cerra, Andrés M. Rubiano, Luis Rafael Moscote-Salazar
Historic Article/Artículo Histórico
60 DERIVADOS DE SANGRE EN PUERTO RICO: Historia de los Servicios de Transfusión y Estimado del Consumo de Unidades de Sangre
Raúl H. Morales-Borges MD
Catalogado en Cumulative Index e Index Medicus Listed
in Cumulative Index
and Index Medicus
No. ISSN-0004-4849.
Registrado en Latindex -Sistema Regional de Información en
Línea para Revistas
Científicas de América
Latina, el Caribe, España y Portugal
OFICINAS ADMINISTRATIVAS:
Asociación Médica de Puerto Rico
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Tel 787-721-6969 • Fax: 787- 724-5208 - Email: [email protected]
ANUNCIOS EN BOLETIN, WEBSITEy NEWSLETTER:
Tel.: (787) 721-6939 Ext. Informártica - [email protected] - Web
Site: www.asocmedpr.org
Ilustración digital de cubierta y diseño gráfico realizados por Juan Laborde-Crocela en la Oficina de Informática de la AMPR. Impreso en los talleres
gráficos digitales de la Asociación Médica de Puerto Rico - E-mail:[email protected]
Pintura de la portada:
La resurrección de Lázaro de Franz
Karl Eduard von Gebhardt (18381925)
Mensaje del Presidente
Asociacion Medica de Puerto Rico
Junta de Directores 2013/2014
Dra. Wanda G. Velez Andujar
Presidente
Dr. Ricardo Marrero Santiago
Dr. Eliud López Vélez
Presidente electo
Dr. Natalio Izquierdo Encarnación
Presidente saliente
Dr. José R. Villamil Rodríguez
Tesorero
Vicepres. Cámara Delegados
Dr. Gonzalo González Liboy
Delegado AMA
Dr. Rolance G. Chavier Roper
Delegado AMA
Dra. Ilsa Figueroa
Dr. Luis A. Román Irizarry
Secretaria
Delegado Alt. AMA
Dra. Hilda Ocasio Maldonado
Vicepresidente AMPR
Dr. Rafael Fernández Feliberti
Dr. Raúl A. Yordán
Delegado Alterno AMA
Dr. Salvador Torrós Romeu
Vicepresidente AMPR
Pres. Distrito Este
Dr. Jaime M. Díaz Hernandez
Vicepresidente AMPR
Dr. Benigno López López
Dra. Mildred R. Arché
Pres. Distrito Central
Dr. Rubén Rivera Carrión
Pres. Cámara Delegados
Pres. Distrito Sur
A
Dra. Wanda G. Vélez Andújar
Aquí les ofrecemos otra edición de nuestra muy bien
apreciada revista "Boletín". Una vez más, la Junta Editora ha
puesto todo su empeño en preparar una edición de excelencia
y calidad recogiendo las mejores investigaciones del momento. La Asociación Médica siente un profundo agradecimiento
hacia todos los miembros de la Junta Editora por su esfuerzo y
compromiso para con toda la comunidad científica de nuestro
país. Gracias a personas como ellos, nuestro equipo de prensa
y a los autores de tan excelentes trabajos, es que hemos tenido
este gran logro que de tanto orgullo nos llena.
Boletín es la única revista científica de su clase en Puerto Rico
y muy posiblemente en todo el Caribe. Fue fundada en el 1903
y desde entonces ha sido publicada ininterrumpidamente. Está
registrada en el Index Medicus del National Library of Medicine del Congreso de los Estados Unidos. Esta publicación es
un eslabón más para brindar a nuestros socios y a todos los
médicos del país la ventaja de estar al tanto de las investigaciones corrientes. Es otro ángulo en la prestación de un mejor servicio a nuestros pacientes, y por ende, al país completo.
¡Este es nuestro compromiso!
Aprovecho para anticiparles que estaremos publicando Perspectiva Médica. Esta publicación tiene el objetivo de actualizar al
lector más allá del ámbito científico, tales como proyectos de
ley, leyes aprobadas y un sinnúmero de otras cosas más que
nos incumben no sólo como profesionales sino también como
ciudadanos.
Los invitamos a su lanzamiento que será el sábado, 13 de
septiembre de 2014, a las 7:00 p.m., en nuestra Casa Sede. La
Junta Editora de Perspectiva Médica está a cargo del Dr. Luis
J. Lugo Vélez (Infectólogo y Abogado). Por favor llamen al
(787)721-6969 y reserven su espacio para que nos acompañen
ese día. ¡Los Esperamos!
Dr. Humberto Lugo Vicente
Presidente de la Junta Editora del Boletin
2 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 3
Original Articles/Articulos Originales
RESUMEN
Las infecciones respiratorias agudas constituyen la primera
causa de consulta infantil tanto en oficinas médicas como en
emergencias pediátricas. La bronquiolitis es una enfermedad
respiratoria vírica aguda que afecta alrededor del 10% de los
lactantes cada año, especialmente menores de dos años. El
objetivo de este trabajo fue identificar las características demográficas y epidemiológicas así como los factores de riesgo asociados al desarrollo de Bronquiolitis en la población
admitida al Hospital Manatí Medical Center (HMMC). Adicionalmente establecer las bases para el desarrollo de estrategias de prevención primaria de hospitalizaciones y complicaciones en el área de atención de nuestro Hospital. Un estudio
ESTUDIO DESCRIPTIVO
EPIDEMIOLÓGICO DE
LAS CARACTERÍSTICAS
CLÍNICAS DE LA
BRONQUIOLITIS
AGUDA EN PACIENTES
ADMITIDOS A LA
UNIDAD PEDIÁTRICA
DEL HOSPITAL MANATÍ
MEDICAL CENTER
Zidnia M. Colón Blanco MDa
Christian S. Colón Rivera MDa
Migdalis Matos González MDa
Brenda L. Pérez Valentín MDa
Renato Rivera Fernández MDa
Isamir Santiago Méndez MDa
Vielka Cintron MDb*
4 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Programa de Residencia de Medicina de Familia, Departamento de Educación Médica, Hospital Manatí Medical Center,
Manatí, Puerto Rico
b
Departamento de Educación Médica, Hospital Manatí Medical
Center, Manatí, Puerto Rico
*Autor correspondiente: Vielka Cintrón MD - Departamento de
Educación Médica - PO Box 1142, Manatí, P.R. 00674. Email:
[email protected]
Resultados de este estudio fueron presentados en la Convención
de Médicos de Familia en Abril de 2011, San Juan, PR.
a
por McConnochie los más aceptados (2). Una
radiografía de tórax puede ser necesaria cuandel HMMC en Manatí, Puerto Rico entre enero y diciembre
do se considere la presencia de una complide 2009. Un total de 508 niños fueron incluidos siendo un
cación o se esté estableciendo otros diagnósti58% de los mismos del sexo masculino con edad y peso procos diferenciales. La detección del antígeno
medio de 12 ± 5,3 meses y 8,1 ±1,4 kg, respectivamente. Fue
de VSR puede ser realizada por técnicas de
inmunofluorescencia con secreciones de la
observado una predisposición mayor a la enfermedad por el
nasofaringe (6). En la mayoría de los niños,
sexo masculino, así como una relación estadísticamente sigla bronquiolitis es una enfermedad auto limnificativa entre la lactancia materna y el desarrollo de protecitante y puede ser manejada en la residencia
ción contra la enfermedad. No se observó relación entre el
del paciente. Sin embargo para niños con
nacimiento prematuro y el hábito de fumar de los padres con
factores de riesgo considerables o severos,
el desarrollo de la enfermedad aunque este último factor inincluyendo enfermedades concomitantes
fluencia la duración de la estadía intrahospitalaria. Los meses
o preexistentes, bajo peso, prematuridad o
de Octubre y Noviembre fueron los de mayor incidencia. La
desnutrición el manejo de la infección debe
presencia de virus sincitial respiratorio se confirmó en 67%
ser supervisado por un entorno médico (7).
de los casos de bronquiolitis analizados.
La terapia es principalmente de apoyo donde
la oxigenación y la hidratación constituyen el
pilar fundamental. En ocasiones se precisa de
terapia intravenosa y en casos severos ventiPalabras índices: estudio, descriptivo, epidemiológico, bronquilación mecánica. Los medicamentos bronolitis, aguda, pediatría
codilatadores pueden producir cierto efecto en algunos
niños así como el anticolinérgico bromuro de ipratropio.
INTRODUCCIÓN
Aunque produce cierta mejoría, el uso de adrenalina nebulizada en estos casos continua siendo controversial debido
Las infecciones respiratorias agudas constituyen la prim- al efecto rebote aumentando el cuadro obstructivo de las
era causa de consulta infantil tanto en las oficinas médi- vías respiratorias (7). En general, el tratamiento de la broncas como en las emergencias pediátricas. La bronquiolitis quiolitis se ha modificado poco a lo largo de los años y
es una enfermedad respiratoria vírica aguda caracterizada en muchos casos la efectividad de la estrategia terapéutica
por la obstrucción de las pequeñas vías aéreas. Se define utilizada carece de evidencias concluyentes (1, 7). Hasta
como un cuadro agudo de dificultad respiratoria con sib- la fecha no existe una vacuna disponible para prevenir la
ilancias, con o sin aumento del trabajo respiratorio, den- infección por el VSR sin embargo la profilaxis con palivtro de un proceso catarral de vías aéreas superiores en izumab, un anticuerpo monoclonal, en lactantes con alto
niños menores de dos años (1). Según McConnochie, la riesgo ofrece una reducción de la hospitalización de 45bronquiolitis se define como un primer episodio agudo 55% (1, 7). Por otro lado el uso de medidas de control de
de sibilancias, en el contexto de un cuadro respiratorio infecciones puede reducir la transmisión nosocomial de
de origen viral (2). Aproximadamente entre el 60-80% infecciones del VSR (1, 7).
de los casos es causada por el virus respiratorio sincitial
(VRS). Otros causantes incluyen parainfluenza, adeno- Considerando que la rápida identificación y manejo del invirus, influenza, metapneumovirus humano, coronavirus, fante a riesgo determina su evolución y rápida recuperación
virus de la parotiditis, rinovirus y ocasionalmente entero- este trabajo tiene como principal objetivo identificar las
virus y virus del sarampión (1). Los adenovirus suelen características demográficas y epidemiológicas así como
ser los causantes de los cuadros más graves y floridos de los factores de riesgo asociados al desarrollo de Bronquiolbronquiolitis.
itis en la población admitida a al Centro Medico de Manatí.
Adicionalmente este trabajo pretende establecer las bases
Cada año alrededor del 10% de los lactantes tienen bron- para el desarrollo de estrategias de prevención primaria de
quiolitis con una mayor incidencia entre los dos y 6 meses hospitalizaciones y complicaciones en el área de atención
de edad requiriendo hospitalización entre el 2 y 5 % de los de nuestro Hospital.
casos en niños menores de 12 meses (1). Aunque puede
ser desarrollada en cualquier época del año la bronquiolitis es más frecuente en el período de noviembre a abril en
el hemisferio norte (1, 3). Existen varios factores de ries- MATERIALES Y METODOS
go para el desarrollo de la enfermedad entre ellos, edad
menor de seis meses, falta de lactancia materna, hacina- Un estudio retrospectivo descriptivo fue conducido en la
miento, asistencia a guarderías y familiares fumadores. unidad de pediatría del Hospital ‘Manatí Medical Center’
Los factores de riesgo para una mayor severidad de la en Manatí, Puerto Rico. El estudio incluyó 508 pacientes
enfermedad son edad menor de tres meses, antecedente menores de 24 meses evaluados en la sala de emergencias y
de nacimiento prematuro y presencia de enfermedades admitidos por primera vez a la unidad pediátrica, en el períoasociadas como cardiopatías congénitas, enfermedad pul- do entre enero y diciembre de 2009, con los códigos ICD de
monar o neuromuscular crónicas o inmunodeficiencias diagnósticos 466.1 y 466.11 de acuerdo al CIE, Clasificación
(4, 5). El diagnóstico se determina fundamentalmente por Estadística Internacional de Enfermedades y otros probel examen clínico, siendo los criterios clásicos descritos lemas de salud (WHO, 2010). Infantes con condiciones de
L
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 5
inmunodeficiencia (Síndrome de Inmunodeficiencia Adquirida, pacientes con trasplante de órganos o medula
ósea), enfermedades cardíacas congénitas, condiciones
respiratorias existentes tales como: displasia broncopulmonar, secuestro pulmonar, enfisema lobar congénito,
malformación adenomatoidea quística pulmonar congénita y malformaciones arteriovenosas así como con historial
de alergias, enfermedades neuromusculares y anomalías
genéticas (Síndrome de Down y Síndrome de Edwards)
fueron excluidos del estudio. El protocolo fue examinado
por el Comité de Ética Institucional y la necesidad de consentimiento informado no fue necesario debido a la naturaleza observacional y anónima del estudio.
Los expedientes de los pacientes fueron evaluados y los
datos colectados con la ayuda de un formulario diseñado
para tal, conteniendo la edad, sexo, peso, edad gestacional, patrones de alimentación, factores de riesgo, tiempo de
desarrollo de síntomas, presencia de VSR, manifestaciones
clínicas, hallazgos radiológicos, oxigenación en sangre,
tratamiento y complicaciones asociadas.
Los datos obtenidos fueron analizados estadísticamente,
Chi-X2, ANOVA (T-test) y pruebas de proporción fueron
utilizadas cuando apropiadas con un valor de p menor o
igual a 0.05 como estadísticamente significativo. El programa estadístico SPSS 20.0 (IBM® SPSS®, Chicago, IL,
USA) fue usado para el análisis.
RESULTADOS Y DISCUSIÓN
madre al niño. Nuestro estudio confirma la falta de lactancia materna como uno de los factores de riesgo a diferencia
de los estudios realizado por Arif et al. (10) y Unyan et al.
(9) donde hasta el 66% y 91% de los pacientes, respectivamente, habían sido alimentados exclusivamente con leche
materna.
Tabla 1. Distribución de casos por parámetros
demográficos en la población estudiada en la
unidad de pediatría del Hospital Manatí Medical
Center en el período entre enero y diciembre de
2009.
Un 84% de los infantes nacieron a las 37 semanas o más de
gestación y de padres no fumadores (92%). Existe la opinión de que los infantes más pequeños, especialmente los
prematuros, son más susceptibles a las infecciones virales
como resultado de la falta de transferencia de anticuerpos
transplacentario (12). Sin embargo, en nuestro estudio no
fue observada una relación entre el nacimiento prematuro y
el desarrollo de bronquiolitis como reportado previamente
por otros autores (9-12). Con respecto al factor de riesgo
padres fumadores, fue encontrada una relación estadísticamente significativa (p = 0.001) entre esta variable y la
presencia de sibilancias como manifestación clínica. Ninguna otra manifestación clínica fue significativamente relacionada con el hábito de fumar de los padres. Igualmente,
el aumento en la estadía intrahospitalaria está relacionada
con el hecho de los padres ser fumadores (p = 0.03).
sibilancias (86%) y tos (84%) seguidas
de dificultad respiratoria (55%) y fiebre (46%). Estos resultados son consistentes con los encontrados por Arif et al.
(10) donde las sibilancias fueron encontradas en 98.7% de los niños y la dificultad respiratoria en 97.5%. Al evaluar
los reportes de radiografía de pecho los
hallazgos radiológicos (ver Figura 1B)
más comunes encontrados fueron engrosamiento perihilar (38%) e hiperaireación (31%). En 15% de los pacientes
los resultados de las radiografías fue
negativo y en un 8% fueron encontrados
otros hallazgos tales como, neumonitis
y engrosamiento de vasos sanguíneos.
El análisis de los casos de bronquiolitis de acuerdo a la
estación del año reflejó que el 66% de los casos ocurrieron
en otoño e invierno siendo Octubre (17%) y Noviembre
(16%) los meses de mayor incidencia. Aunque cabe señalar
que en todos los meses del año se presentaron casos con
bronquiolitis aguda nuestro estudio confirma resultados
previos que el riesgo de bronquiolitis es de acuerdo a la
estación del año. Según el estudio realizado por Koehoorn et al. la mayor incidencia de bronquiolitis aguda (47%)
ocurrió en invierno, entre los meses de Diciembre y Febrero (12). Con relación a la estación del año y las manifestaciones clínicas solo fue encontrada una relación significativa en el caso de la presencia de aleteo nasal (p = 0.04)
y la dificultad respiratoria (p = 0.05) como manifestación
clínica. No fue observada una relación directa entre alguno
de los hallazgos radiológicos evaluados o la duración de la
estadía intrahospitalaria y la estación del año.
La media de la estadía intrahospitalaria fue de 3 ± 0.6 días (ver Figura 1C).
Sin embargo los pacientes con complicaciones o infecciones asociadas estuvieron admitidos por más tiempo a
la unidad pediátrica con media de 5 ±
0.9 días. Entre las infecciones secundarias más comunes encontradas en los
infantes estudiados se encuentran: neumonía (71%), otitis media (17%) e infecciones del tracto urinario (9%). Se
observó que el VSR como agente causal
de bronquiolitis aguda aumenta el riesgo de desarrollar infecciones secundarias (p = 0.02). Adicionalmente cuando
se comparó sexo, días de admisión y
complicaciones asociados se encontró
una relación estadísticamente significativa entre estas variables (p = 0.05).
Pacientes masculinos tienen una mayor
predisposición para presentar complicaciones asociadas por lo que sus estadías
intrahospitalaria es mayor.
La bronquiolitis aguda es una de las infecciones del tracto respiratorio bajo más comunes en los infantes. El presente estudio documenta las características demográficas
y clínicas de esa infección en el Hospital ‘Manatí Medical
Center’ en el período entre enero y diciembre de 2009. Un
total de 508 niños fueron incluidos en el estudio, un 58%
de los mismos fueron del sexo masculino y la edad y peso
promedio fueron de 12 ± 5,3 meses y 8,1 ±1,4 kg, respectivamente. Las principales características demográficas y
hallazgos clínicos y radiológicos de la población estudiada
se encuentran reflejados en la Tabla 1 y Figura 1, respectivamente.
De acuerdo a la literatura científica uno de los patógenos
más comunes para esta infección es el virus respiratorio
El valor de la edad promedio en nuestro estudio está en sincitial. Este virus fue detectado en el 67% de los infantes
concordancia con lo reportado por Iqbal et al. (11) que en- (n=340) en este trabajo contrariamente al estudio de Koecontraron un promedio de edad de 11,3 ± 5,6 meses sin hoorn et al. donde no hubo confirmación de VSR en ninguembargo difiere de los valores reportados por Unyan et al. no de los casos de bronquiolitis (12). Los casos VSR posi(9) y Arif et al. (10) con promedios de edad de 6,9 ± 3,4 y tivos se distribuyeron de la siguiente manera dependiendo
5,4 ± 9,4 meses, respectivamente. La diferencia observada de la estación del año: Primavera (24%), Verano (9%),
con estos estudios podría explicarse por el menor tamaño Otoño (42%) e Invierno (23%). Cuando comparamos los
de la muestra usada en ellos. Similarmente a lo encontrado grupos VSR positivos y VSR negativos se encontró una
por otros autores (9-11) fue observada una predisposición diferencia altamente significativa (p = 0.001) en cuanto la
a la enfermedad por el sexo masculino (p= 0,002).
estación del año y la presencia de sibilancia como manifestación clínica.
Como reflejado en la Tabla 1 la mayoría de los infantes
(75%) fueron alimentados exclusivamente con fórmula y Tomando en consideración que el diagnóstico de la bronsolo un 15% con leche materna. Existe una relación es- quiolitis es clínico, es importante para el médico primatadísticamente significativa (p ≤ 0.03) entre infantes cuya rio conocer las manifestaciones más comunes en los inalimentación es exclusivamente con leche materna y el de- fantes en su área geográfica. Como puede ser observado
sarrollo de protección contra la enfermedad. Este hecho en la Figura 1 (A) las manifestaciones clínicas más frepuede se explicado por la trasferencia de anticuerpos de la cuentes en la población al momento de la admisión fueron
6 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
A
B
Otra de las variables evaluadas en nuestro estudio fue el tratamiento recibido
por los pacientes. Al 99% de los pacientes se le administró broncodilatadores
como parte del manejo médico. A un
95% se le ordenó esteroides, mientras
que el 92% recibió antitusivos, 44% se
Figura 1. Principales hallazgos clínicos (A) y
radiológicos (B) y duración de la estadía intrahospitalaria (C) en la población estudiada en la
unidad de pediatría del Hospital Manatí Medical
Center en el período entre enero y diciembre de
2009.
C
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 7
les comenzó con antibióticos, 10% aminofilina y un 9%
estuvo con oxígeno suplementario. Utilizando el modelo
de regresión para comparar el tratamiento médico con la
respuesta clínica de los pacientes no se encontró correlación significativa. No obstante esta área de estudio puede
ser de gran interés para futuras investigaciones.
CONCLUSIONES
Los resultados obtenidos en este estudio son de gran importancia para los médicos de atención primaria del área
atendida por nuestro Hospital ya que provee las evidencias
para la intervención, orientación, prevención y/o reducción
del riesgo y la severidad de los casos de bronquiolitis aguda entre los infantes. Adicionalmente, la información recogida permitirá la implementación de estrategias para la
modificación de factores de riesgo como el hábito de fumar
o falta de lactancia materna. Futuros trabajos deberán explorar más profundamente la relación entre el tratamiento
médico y la respuesta clínica de los pacientes así como el
efecto de la condición socioeconómica y la exposición ambiental en el desarrollo de bronquiolitis en infantes.
BIBLIOGRAFIA
1. Marin D, Herbert LM. Respiratory Syncytial Virus Infection
in Children. Am Fam Physician. 2011; 83 (2):141-146.
2. McConnochie KM. Bronchiolitis. What´s in the name? Am J
Dis Child. 1993; 137:11-3.
3. Thompson WW, Shay DK, Weintraub E, Brammer, L Cox,
N Anderson LJ, Fukuda, K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA.
2003; 289 (2):179-86.
4. Thomas M, Bedford-Russell A, Sharland M. Hospitalisation
for RSV infection in ex-preterm infants—implications for use of
RSV immune globulin. Arch Dis Child. 2000; 83:122-127.
5. Kneyber MCJ, Steyerberg EW, de Groot R, Moll HA. Longterm effects of respiratory syncytial virus (RSV) bronchiolitis in
infants and young children: a quantitative review. Acta Pediatrc.
2000; 89 (6): 654-660.
6. Breese CH, Powell KR, MacDonald NE, et al. Respiratory
Syncytial Viral Infection in Children with Compromised Immune
Function. N. Engl J Med. 1986; 315:77-81.
Anemia Management Among
Hemodyalisis Patients At
The University Hospital In
Puerto Rico
7. Clinical Practice Guideline. Diagnosis and Management of
Bronchiolitis. Pediatrics. 2006; 118:1774-1793.
8. WHO. International Classification of Diseases ICD-10, 2010.
Disponible en: http://www.who.int/classifications/icd/en/.
9. Uyan AP, Ozyurek H, Keskin M, Afsar Y, Yilmaz E. Comparison of two different bronchodilators in the treatment of acute
bronchiolitis. Internet Journal of Pediatrics and Neonatology.
2003; 3,1.
10. Ayesha A, Tajammul A. Acute Bronchiolitis - a clinical study.
Pak Paed J Dec 1998; 22(4):175-7.
11. Iqbal SMJ, Afzal MF, Sultan M, Acute bronchiolitis: epidemiological and clinical study. ANNALS; 2009: 15, 203 - 205.
12. Koehoorn M, Karr CJ, Demers PA, Lencar C, Tamburic L,
Brauer M. Descriptive epidemiological features of bronchiolitis in a population-based cohort. Pediatrics. 2008; 122: 1196
-1203.
Ileana E. Ocasio MDa*
Hector Diaz MDa
José L. Cangiano MDa
Rafael Báez MDa
Erick Suárez PhDb
ABSTRACT
Acute respiratory infections are the main reason for pediatric visits both to physician’s offices and emergency
departments. Bronchiolitis is an acute viral respiratory disease that affects about 10% of infants each year and mostly
those under age two. The aim of this study was to identify demographic, epidemiological characteristics and risk
factors associated with cases of bronchiolitis admitted to
the Manatí Medical Center (MMC). In addition, we tried
to establish the basis for the development of strategies to
prevent of hospitalizations and complications in our Institution. A retrospective descriptive study was conducted in
the pediatric wing of MMC in Manatí, Puerto Rico between
January and December 2009. A total of 508 children were
included, 58 % of them male. The average age and weight
were 12 ± 5.3 months and 8.1 ± 1.4 kg, respectively. We
observed a higher predisposition among males as well as
a statistically significant relationship between breastfeeding and protection from the disease. No relationship was
observed between preterm birth and the parents' smoking
habit and the development of the disease. However, the
latter factor influences the length of hospital stay. The risk
of bronchiolitis was seasonal with a peak between October
and November. The presence of respiratory syncitial virus
was confirmed in 67 % of the cases.
E
a
Internal Medicine Department, Nephrology Section, UPR School of
Medicine, Medical Sciences Campus, San Juan, Puerto Rico.
b
Epidemiology and Biostatistics Department, UPR School of Medicine,
Medical Sciences Campus, San Juan, Puerto Rico
*Corresponding autor: Ileana E Ocasio MD - Altos de la Fuente St.#1
E14, Caguas, PR 00727. E-mail: [email protected]
ABSTRACT
End-stage renal disease is frequently complicated with anemia. Iron deficiency anemia occurs in most
hemodialysis patients secondary to increased iron demand driven by the accelerated erythropoiesis that
occurs when stimulating agents are administered as treatment of the anemia. The purpose of this study
was to determine the prevalence of anemia and iron stores in patients undergoing hemodialysis at our
unit; identify their treatment and effectiveness. Medical records of fifty-three patients undergoing ambulatory hemodialysis were evaluated for three months. Patient’s hemoglobin, ferritin, iron, total iron
binding capacity and percent transferrin saturation were recorded. 91% patients had arterial hypertension
and 62% were diabetic. The prevalence of anemia was 34%, 57% and 47% during the three-month period
respectively. Only 21% of the population had transferrin saturation less than 20% and none had ferritin
below 200 ng/ml. Throughout the study, the majority of patients were managed with combination of
iron and erythropoietin stimulating agents (ESAs). The prevalence of anemia remained elevated despite
treatment with iron and ESAs. However, 56% of anemic patients throughout the three months showed
an increase in hemoglobin levels by the end of the observation period. 53% of patients were treated with
iron alone or with ESAs for the three consecutive month periods and only two had transferrin saturation
less than 20%. In our population, ESAs low responsiveness is not related to iron deficiency but to the
morbidity of their disease.
Index words: anemia, hemodyalisis, University, Hospital, Puerto Rico
Ediciones Médicas
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INTRODUCTION
Anemia is a frequent complication of chronic kidney disease (CKD) and end-stage renal disease (ESRD), especially
patients receiving hemodialysis as renal replacement therapy (1). Iron deficiency anemia will occur in the majority
of hemodialysis patients due to inadequate intake of dietary
iron, ongoing blood losses from dialyzer and tubing during
hemodialysis procedure, blood losses at the time of dialysis needle placement and removal, constant blood sampling
and gastrointestinal blood loss.
In patients receiving erythropoietin-stimulating agents
(ESAs), iron deficiency is the most common cause of low
responsiveness. This is secondary to an increased iron demand driven by the accelerated erythropoiesis that occurs
upon administration. There is exhaustion of bone marrow
iron stores and inability to deliver sufficient iron to support
normoblastproliferation and maturation (3).
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 9
Periodical assessment of iron stores in patients undergoing hemodialysis is a challenge since renal disease; intermittent blood loss and red blood cells transfusions render
iron balance unstable (3). Anemia and iron deficiency
assessment is performed monthly at our hemodialysis
unit, where we determine hemoglobin/hematocrit levels,
transferrin saturation and serum ferritin in order to assess
the need of intravenous iron and/or ESA as a therapeutic
approach.
The Kidney Dialysis Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation Anemia Guidelines recommend hemoglobin levels between 11-12 g/dl,
a minimum hematocrit levels of 33%, a transferrin saturation (TSAT) of 20% or more and a serum ferritin concentration of more than 100 ng/dl in non-hemodialysis
and 200 ng/dl in hemodialysis patients (4). These recommendations are based on the Correction of Hemoglobin
and Outcomes in Renal insufficiency trial (CHOIR Trial)
and the Trial to Reduce cardiovascular Endpoints with
Aranesp Therapy study (TREAT Study), which ascertain
that further elevation of hemoglobin levels, have been
associated with increased cardiovascular adverse events
(5, 6). Anemia treatment protocol at our hemodialysis
unit follows these goals. Intravenous iron is started when
TSAT is less than 20% and discontinued when TSAT is
over 50% or Ferritin levels over 1,200 ng/ml. ESAs are
administered with hemoglobin levels below 10 g/dl and
discontinued if hemoglobin levels rise above 12 g/dl.
METHODS
We conducted a retrospective study in fifty-three patients
receiving ambulatory hemodialysis three times per week at
the Nephrology Section of the University District Hospital
of the Medical Sciences Campus in San Juan Puerto Rico.
Their files were evaluated for three consecutive months:
November 2011 through January 2012. Demographic information and laboratory data that permitted anemia and
iron storage assessment were obtained (hemoglobin, hematocrit, ferritin, iron, total iron binding capacity, reticulocyte count). Patients needed to have laboratory data under
study for the three months period. Patients hospitalized,
with a bleeding episode or with an ongoing infectious process were excluded from the study.
Once protocol was submitted and approved by the Institutional Review Board, data was tabulated using Microsoft
Excel 2010. Contingency tables were used to determine
the prevalence of the anemia in our hemodialysis patients.
A statistical summary of the iron stores was developed
using mean, median, percentiles and dispersion measurements (standard deviation, range, interquartile range) by
different treatments.
RESULTS
The study included 22 females and 31 males. The mean
age was 52 years. Arterial hypertension and diabetes mellitus were the most common comorbidities among hemodialysis patients with a prevalence of 91% and 62%,
respectively. The prevalence of patients with hemoglobin
levels below 11 g/dl was 34% in November 2011, 57% in
December 2011 and 47% in January 2012.
Although there are recent guidelines of anemia treatment
in patients with ESRD, this topic remains under study
and a number of patients treated according to guidelines
do not achieve hemoglobin/hematocrit goal. This may be
due to body iron constant loss, adequate iron balance is
not achieved when ESA is administered or from subopti- Only 21% of the population had a TSAT of less than 20%.
28 (53%) patients were treated with iron for the three conmal dose or route of administration of iron or ESA.
secutive months and only two (7%) had a TSAT of less
There is additional documented evidence that patients on than 20%. No patient in our study had a ferritin level below
hemodialysis should be treated with iron therapy at levels 200 ng/ml.
of TSAT between 20-30%. This might increase levels of
Eighteen patients (34%) remained with hemoglobin less
hemoglobin requiring a lesser dose of ESAs (7).
than 11 g/dl throughout the three months. Ten of these 18
ESAs low responsiveness in hemodialysis patients is de- patients (56%) showed an increase in hemoglobin levels at
fined as a continue need for greater than 300 IU/kg per the end of the three months.
week of intravenous erythropoietin or 1.5 μg/kg per week
of intravenous darbopoietin (4). The potential for iron de- Twenty-one patients were treated with the combination
ficiency to block or slow response to ESAs heightens the of intravenous iron and ESAs for the three consecutive
need to assess body iron reserves accurately before cor- months (See Figures 1 and 2). Eleven (52%) of these
recting anemia (8). It is important to investigate and know patients remained with hemoglobin levels below 11 g/dl
these parameters to conclude if stipulated guidelines cor- (OR=2.25 p=0.2668).
relate with a hemoglobin/hematocrit goal achievement at
our hemodialysis unit.
DISCUSSION
Related studies concluded that the integration of intravenous iron and ESAs therapy into standard anemia man- Untreated iron deficiency is a known cause of low reagement has resulted in target hemoglobin levels in most sponsiveness to ESAs in CKD. Treatment with oral and
ESRD patients. Anemia correction has been proved to re- intravenous iron can readily correct the anemia. The asduce morbidity, mortality and number of hospitalization sessment of iron status in hemodialysis is of great imporin ESRD patients. It has also improved their quality of tance to define the presence or absence of stored iron and
the availability of iron to support ongoing erythropoiesis.
life, cognitive function and physical activity (9).
The serum ferritin test is the most commonly used test for
10 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
evaluating iron stores. Levels less than 30 ng/ml indicate
severe iron deficiency, however, there are reports that even
at serum ferritin levels of less than 100 ng/ml most chronic
kidney disease patients have low bone marrow iron stores
[4]. The TSAT is indicative of iron availability to support
erythropoiesis. Values less than 20% indicate poor iron
availability.
A retrospective analysis of 53 patients undergoing hemodialysis at the Nephrology Section of the University
District Hospital of the Medical Sciences Campus in San
Juan Puerto Rico demonstrated an increased prevalence
of anemia despite treatment with ESAs and iron supplementation. In our study, more than 50% of ESRD patients
have hemoglobin levels less than 11 g/dl. The prevalence
of anemia remained elevated
despite treatment. However
56% of patients with hemoglobin levels less than 11 g/
dl showed an increase in hemoglobin levels during the
observation period. Using
NKF-KDOQI guidelines [4] as
a base in our hemodialysis unit
anemia protocol, 21 patients
were treated with the combination of ESAs and intravenous
iron but eleven of these patients
remained anemic despite combination therapy. Of these eleven patients, two were unable to
increase TSAT (hence with iron
deficiency anemia) and the remaining nine patients showed
ESAs low responsiveness with
a TSAT more than 20%.
Given the recent documented
evidence that starting intravenous iron therapy with TSAT
between 20-30% might increase hemoglobin levels, this
may be an adjustment to make
in our current anemia management protocol in an attempt to
decrease ESAs low responsiveness.
Given that the minority of patients in our population had
iron deficiency, ESAs low responsiveness in our population
may not be exclusively related
to iron deficiency but to other
etiologies such as chronic disease (highly prevalent arterial
hypertension and diabetes mellitus), hyperparathyroidism, inflammatory processes, nutrient
deficiencies, inadequate hemodialysis and ESAs antibody formation (1, 10, 11, 12, 13).
REFERENCES
1. Coladonato JA, Frankenfield DL, Reddan DN, Klassen PS, Szczech
LA, Johnson CA, Owen WF: Trends in Anemia Management among
US Hemodialysis Patients. J Am Soc Nephrology 13: 1288-1295, 2002
2. Nissenson AR, Strobos J: Iron deficiency in patients with renal disease. Kidney International 55: S18-S21, 1999
3. Moreb J, Popovtzer MM, Friedlander MM, Konijn AM: Evaluation
of iron status in patients on chronic hemodialysis: relative usefulness
of bone marrow hemosiderin, serum ferritin, transferrin saturation,
mean corpuscular volume and red cell protoporphyrin. Nephron 35:
196-200, 1983
4. NKF-KDOQI Clinical practice guidelines and Clinical Practice
Recommendations for Anemia in Chronic Kidney Disease. American
Journal of Kidney Diseases, Vol 47, No 5, Suppl 3, May 2007
5. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M,
Reddan D: Correction of Anemia with Epoietin Alfa in Chronic Kidney Disease (CHOIR Trial). N Engl J Med 355:2085-2098, 2006
Figure 1: Treatment of patients with Hemoglobin levels less than 11g/dl.
Figure 2: Treatment of patients with Hemoglobin levels above 11g/dl.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 11
6. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, Zeeuw D, Eckardt
KU, Feyzi JM, Ivanovichet al: A Trial of Darbopoietin Alfa in Type 2
Diabetes and Chronic Kidney Disease (TREAT Study). N Engl J Med
361: 2019-2032, 2009
7. Coyne DW, Kapoian T, Suki W, Singh AK, Moran, JE, Dahl NV and
Rizkala AR: Ferric Gluconate Is Highly Efficacious in Anemic Hemodialysis Patients with High Serum Ferritin and Low Transferrin Saturation: Results of the Dialysis Patients’ Response to IV Iron with Elevated
Ferritin (DRIVE) Study. J Am SocNephrol, 2007
8. Van Wyck DB, Stivelman JC, Ruiz J, Kirlin LF, Katz MA Ogden DA:
Iron status in patients receiving erythropoietin for dialysis-associated
anemia. Kidney International 35:712-716, 1989
9. Hörl WF: Iron therapy for renal anemia: how much needed, how
much harmful? PedriatrNephrol 22: 480-489, 2007
10. Maldore F, Lowrie E, Brugnara C, Lew NL, Lazarus M, Bridges K,
Owen WF: Anemia in hemodialysis patients: Variables affecting this
outcome predictor. J Am SocNephrol 8: 1921-1929, 1997
11. Kaloantar-Zadeh K, Kleiner M, Dunne E, Ahern K, Nelson M,
Koslowe R, Luft FC: Total iron binding capacity-estimated transferrin
correlates with the nutritional subjective global assessment in hemodialysis patients. Am J Kidney Dis 31: 263-272, 1998
12. Ifudu O, Feldman J, Friedman EA: The intensity of hemodialysis
and the response to erythropoietin in patients with end stage renal disease. NEngl J Med 334: 420-425, 1996
13. Johnson DW, Pollock CA and Macdougall IC: Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology 12: 321-330, 2007
14. Kaufman JS, Reda DJ, Fye CL, Goldfarb DS, Henderson WG,
Kleinman JG, Vaamonde CA: Subcutaneous compared to intravenous
epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study group on erythropoietin in hemodialysis patients. N Engl J Med 339: 578-583, 1998
15. McClellan WM, Frankenfield DL, Wish JB, Rocco MV, Johnson
CA, Owen WF: Subcutaneous erythropoietin results in lower dose and
equivalent hematocrit levels among adult hemodialysis patients: Results from the 1998 ESRD Core Indicators Project. Am J Kidney Dis
37: E36, 2001
16. Coyne DW: It’s time to compare anemia management strategies in
Hemodialysis. Clin J Am SocNephrol 5: 740-742, 2010
17. Fishbane S, Kowalski EA, Imbriano LJ, Maesaka JK: The evaluation of iron status in hemodialysis patients. J Am SocNephrol 7: 26542657, 1996
18. Coyne DW: Hepcidin: clinical utility as a diagnostic tool and therapeutic target. Kidney International 80: 240-244, 2011
19. Singh H, Reed J, Noble S, Cangiano JL, Van Wyck DB: Effect of
intravenous iron sucrose in peritoneal dialysis patients who receive
erythropoiesis-stimulating agents for anemia: a randomized, controlled
trial. Clin J Am SocNephrol 1 (3): 475-482, 2006
20. Strippoli GF, Craig JC, Manno C, Schena FP: Hemoglobin targets
for the anemia of chronic diasease: a meta-analysis of randomized controlled trials. J Am SocNephrol 15: 3154-3165, 2004
21. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M,
Reddan D: Correction of anemia with epoetinalfa in chronic kidney disease. N Engl J Med 355 (20): 2085-2098, 2006
22. Rosner B: Fundamentals of Biostatistics. Duxbury Press, 6th edition, USA, 2005
ROLE OF HELICOBACTER PYLORI
INFECTION IN
HISPANIC
PATIENTS
WITH ANEMIA
RESUMEN
La enfermedad renal terminal se complica frecuentemente
con anemia. La anemia ferropénica se produce en la mayoría de los pacientes de hemodiálisis secundario a una
mayor demanda de hierro impulsado por eritropoyesis
acelerada que se produce cuando agentes estimulantes se
administran en el tratamiento de la anemia . El objetivo de
este trabajo fue determinar la prevalencia de anemia y los
depósitos de hierro en pacientes sometidos a hemodiálisis
en nuestra unidad, identificar su tratamiento y eficacia. Los
registros médicos de 53 pacientes sometidos a hemodiálisis
ambulatoria fueron evaluados por tres meses consecutivos.
La hemoglobina del paciente, ferritina, hierro, capacidad
de unión del hierro total y el porcentaje de saturación de
transferina se registraron. 91% de los pacientes tenían hipertensión arterial y el 62% eran diabéticos . La prevalencia de anemia fue del 34%, 57% y 47% en los tres meses
respectivamente. Sólo el 21% de la población tenía una
saturación de transferina inferior al 20% y ninguno tenia
ferritina por debajo de 200 ng/ml. A lo largo del estudio,
la mayoría de los pacientes fueron tratados con la combinación de hierro y agentes estimuladores de eritropoyetina
(AEE). La prevalencia de la anemia siguió siendo elevada a pesar del tratamiento con hierro y AEE. Sin embargo, 56% de los pacientes anémicos a lo largo de los tres
meses mostró un aumento en los niveles de hemoglobina
al final del período de observación. 53% de los pacientes
fueron tratados con hierro solo o con AEE para los tres
meses consecutivos y sólo dos tenían una saturación de
transferina menor de 20%. En nuestra población, AEE de
baja reactividad no puede ser completamente relacionados
con deficiencia de hierro pero debido a complicaciones de
su enfermedad .
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Informes e inscripción: (787) 721-6969
Programa completo en https://asocmedpr.org
12 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Melissa Ortiz MDa*
Bárbara Rosado-Carrión MDb
Rafael Bredy MDb
Internal Medicine Residency Program, Damas Hospital, Ponce, Puerto Rico.
Internal Medicine Department, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
*Corresponding author: Melissa Ortiz MD - 2213 Ponce By Pass, Ponce, PR 00731. E-mail: [email protected]
a
b
P
ABSTRACT
Pernicious anemia represents the final phase of a process that begins with Helicobacter pylori-associated
gastritis and evolves through progressive levels of atrophy until loss of parietal cell mass. Numerous studies
have suggested an association between H. pylori infection, unexplained iron deficiency anemia and cobalamin deficiency. Our research question was to determine whether there is an association between with H.
pylori infection and development of anemia in Hispanic patients. This cross sectional pilot study involved
data analysis of individual from years 2010-2012 examining the association between H. pylori infection and
hemoglobin levels in patients with Hispanic ethnicity. A total of 189 records were evaluated, of which 33 fulfilled the inclusion criteria. The study sample was divided in two groups. Group-A: 5 subjects with H. pylori
infection and anemia; Group-B: 28 patients with H. pylori without anemia. Fisher exact test applied between
categorical variables to determine the statistical significance of symptoms comparing anemic vs. non-anemic
H. pylori infected patients yielded a p = 0.0027. In addition, restoration of anemia in two subjects following
eradication therapy without previous iron or cobalamin replacement therapy suggested a potential role of this
bacterium in the development of anemia in Hispanics. In conclusion, from the results of this study a potential
association between Helicobacter pylori infection and anemia in Hispanic patients is suggested. Restoration
of hemoglobin after eradication of bacteria further supports this concept.
Index words: helicobacter, pylori, infection, Hispanic, anemia
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 13
Abbreviations:
a. Gastro esophageal reflux disease (GERD)
b. Iron deficiency anemia (IDA)
c. Non-Hispanic whites (NHW)
d. gastro intestinal (GI)
e. Proton pump inhibitor (PPI)
f. esophagus gastro duodenoscopy (EGD)
INTRODUCTION
Helicobacter pylori is a spiral shaped gram negative bacterium- first isolated by Marshal and Warren in 1983 on
the luminal surface of the gastric epithelium (1). It induces chronic inflammation of the underlying mucosa (2-4).
Helicobacter pylori remains one of the most common infections affecting humans worldwide and has been associated with various conditions involving the gastrointestinal
tract such as peptic ulcer disease, Gastro esophageal reflux
disease (GERD), dyspepsia, gastric malignancies, chronic
gastritis and nutritional deficiencies (involving iron or vitamin B-12) (4).
It has been demonstrated that the risk of Helicobacter pylori infection varies across different geographic regions,
racial/ethnic groups and household characteristics. In one
study examining the seroprevalence of Helicobacter pylori
infection of adults in the United States it was found that the
overall rate was 32.7% (5,6). Seroprevalence for H. pylori
among non-Hispanic blacks and Mexican Americans was
higher than among non-Hispanic whites (51.1%, 57.9%,
and 26.9% respectively), and an increase in prevalence
with age occurred for each ethnic group but was greater
for non-Hispanic whites than for other groups (6). A higher
prevalence of H. pylori was found with male sex, greater
household crowding, being foreign born, less education,
lower income, not having a cat in the household, living in
a nonmetropolitan area, farm occupation, younger age at
first sexual intercourse, fewer lifetime sex partners and less
alcohol consumption in the population studied (6). Another study done at the San Francisco Bay Area to quantify
contributions of household and environmental factors to
H. pylori infection among several generations of Hispanics, found that the prevalence of H. pylori in immigrants
was higher 31.4% compared to first- and second- generation US born Hispanics (9.1% and 3.1% respectively) (7).
This study showed that the risk of H. pylori infection in
Hispanics declined with increasing generations in the US
and that having at least one infected parent and low educational attainment in the household were independently
associated with higher risk of infection, thus supporting
the hypothesis that both household characteristics and
birth-country origin environment contribute to higher risk
of infection in immigrants (7).
malignancy. However, endoscopic studies are frequently
unrevealing and the cause of iron deficiency remains unclear in a significant proportion of cases (9). The prevalence of iron deficiency anemia in the US is more than
two-times greater in Mexican American females than in
non-Hispanic white females of childbearing age (2049 yrs.) (10). A study using data from the third National
Health and Nutrition Examination Survey found that the
prevalence of iron deficiency, anemia was 2.7, 1.5 and 2.7
times greater in Mexican, and non-Hispanic white females
respectively (10). Although risk factors such as high parity,
low iron intake, poverty or ethnicity were associated with
anemia in Hispanic females, the high prevalence of H. pylori infection of these population should be considered as
another possible risk factor for the anemia.
Vitamin B12, also known as cobalamin, is essential for
DNA replication and normal nerve cell activity. Vitamin
B12 deficiency often goes undetected, with manifestations
that range from asymptomatic to a wide spectrum of hematologic and/or neuropsychiatric features (11). Etiologies
include pernicious anemia (common cause of cobalamin
deficiency), intestinal disorders, drugs, inadequate dietary
intake, and H. pylori infection. Pernicious anemia represent the final phase of a process that begins with H. pylori-associated gastritis and evolves through progressive
levels of atrophy until parietal cell mass is entirely loss
(12). Numerous studies have suggested a potential association between H. pylori infection and unexplained iron
deficiency anemia as well as cobalamin deficiency. One
study found that H. pylori infection was associated with
a 40% increase in the prevalence of iron deficiency and
was associated with an important decrease in levels of serum ferritin across the entire US population (13). Other
epidemiological studies have further supported this association between H. pylori infection and low iron stores,
and have shown resolution of refractory cases of anemia
after H. pylori therapy. The pathogenesis in iron deficiency
seems to be multifactorial including reduced intestinal iron
absorption as result of decreased acid secretion, increased
iron loss due to gastro intestinal bleeding and utilization of
iron by the bacteria. In contrast, the mechanism proposed
for vitamin B12 deficiency in H. pylori infections is cobalamin malabsorption as result of gastritis. In a study from
Turkey involving 138 patients with vitamin B12 deficiency, H. pylori was detected in 77 patients and eradication
of infection successfully improved the anemia and serum
vitamin B12 levels in 31 of 77 infected patients (12).
patients with anemia that are also infected with the organism, it would be of great relevancy to determine if they
would benefit from early eradication of the bacteria with
improvement of hemoglobin values and avoidance of complications associated with H. pylori infection, including
malignancy. Of interest would also be to assess what are
the risk factors for acquiring H. pylori infection (such as
poverty, hygiene, house crowding or ethnicity), and determine if the prevalence of infection varies within geographic region.
METHODS and PROCEDURE
This cross sectional pilot study involves secondary data
analysis of individual sets from years 2010-2012 to examine the association between H. pylori infection and hemoglobin levels in patients with Hispanic ethnicity. The study
was conducted at Gastroenterology clinic from March to
May 2012 at Ponce, Puerto Rico. Male and female Hispanic patients from 21-89 years of age were included and a
detailed history, physical examination, and laboratory data
was examined and collected.
Selection criteria for enrollment in this study were:
A: Helicobacter pylori infection:
(a) histological evidence of H. pylori on examination of
gastric biopsy specimens.
(b) positive fecal antigen test for H. pylori.
B: CBC for evaluation of Hemoglobin/Hematocrit values
and identify patients with Anemia [diagnosed using the
World Health Organization limits for hemoglobin (male
13g/dL; female 12g/dL) and hematocrit (male 0.39; female
0.36)].
C: Presence of either low ferritin (normal values in females: 15-200ng/mL; males: 30-40 ng/mL), or vitamin
B12 deficiency (serum B12 level ≤ 200 g/mL).
Exclusion criteria for this study were:
A: patients with anemia and primary diseases such as diabetes, cancer, pernicious anemia, myeloproliferative disease, malabsorption, aplastic anemia, renal and hepatic
insufficiency, or other explainable cause.
B: history of stomach or small bowel surgery.
C: pregnant or alcoholic patients.
D: patients with vegetarian lifestyle.
Finally, infection with H. pylori has been associated with
malignancy, specifically between 74-78% of all stomach
cancers worldwide. One study about the incidence and
mortality rates of infection related cancers (such as stomach, liver and cervical) in Puerto Rico (PR) and in the US
found a higher incidence of stomach cancer in PR compared to non-Hispanic whites suggesting a higher prevalence of stomach cancer risk factors in this population,
including H. pylori infection (14).
Iron deficiency, a common cause of anemia both in developed and underdeveloped nations, affects an estimated
500-600 million persons (8). Established causes of iron
deficiency include inadequate iron intake, chronic blood
loss, malabsorption, hemolysis, or a combination of these
factors (9). Iron deficiency anemia (IDA) is often an in- Our research question was to determine whether there is
dication for GI evaluation seeking causes associated with an association between infection with H. pylori and the depotential blood loss such as ulcers, angiodysplasias and velopment of anemia in Hispanic patients. By identifying
14 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 15
E: patients who had received prior H pylori eradication
therapy. Records of patients with positive Helicobacter pylori infection were examined for evaluation of hemoglobin
and hematocrit levels on CBC and also to verify if other
labs such as cobalamin and ferritin levels were available
to determine the presence of Anemia and nutritional deficiencies.
Degree of colonization by Helicobacter pylori was also
determined by esophagus-gastro-duodenoscopy (EGD)
histology report to establish if Mild, Moderate or Severe
Colonization was present. Other factors such as gender,
age, city, common symptoms, PPI / H2 Blocker use, and
anatomic region affected by the organism were also evaluated for potential risk factors and common characteristics
that may be found in patients affected with the infection.
The mean and standard deviation was calculated for age,
hemoglobin and hematocrit values. Categorical statistical
analysis of collected data was done using the Fisher exact
test and a p-value of 0.05 was considered as statistically
significant.
RESULTS
A total of 189 records were evaluated, of which 33 fulfilled
the inclusion criteria. These included 27 (82%) females
and 6 (18%) males (see Figure 1).
16 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
The study sample was divided in 2 groups.
Group-A: 5 subjects with H. pylori infection (HP +) and anemia; Group-B: 28 patients with H. pylori but without anemia.
The observed symptoms in the H. pylori
infected group included epigastric pain in
nine (32%) patients, dyspepsia in 9 (32%),
acid reflux in 6 (22%) and other symptoms
such as abdominal discomfort / distention,
weight loss, hoarseness and vomits in 4
(14%) patients (see Table 1).
H. pylori were detected in thirty-two out of
the 33 patients (97%) by histological examination and in 1 patient (3%) by fecal
antigen test. Average age of H. pylori (+)
with anemia (56.2 ± 14.6) was slight higher
from those H pylori (+) but without anemia
(54.0 ± 13.4). The mean value of hemoglobin level was similar in both infected and
non-infected patients with anemia (11.3
± 0.99 vs. 11.2 ± 0.73). Regarding other
labs such as ferritin and vitamin B12, only
3 subjects from Group A had labs available, of these only 2 subjects had normal
ferritin and cobalamin; 1 patient presented
with vitamin B12 deficiency. In Group B,
only 1 subject had low cobalamin levels,
while 3 other subjects had normal ferritin
and vitamin B12 values. Two out of the 5
patients with anemia and HP (+) had an
available CBC post H. pylori therapy and
demonstrated improved hemoglobin and
hematocrit levels with eradication of bacteria. These two subjects were not receiving iron, vitamin B12 or folic acid prior to
eradication of the bacteria.
Of the total patients infected with H. pylori the degree of DISCUSSION
colonization found on EGD was the following: 43% subjects with severe, 24% moderate, 27% mild, and two sub- In the present pilot study we screened H. pylori infected
jects (2%) with undetermined (see Figure 2).
subjects and evaluated hemoglobin status in order to determine whether an increase in frequency of anemia could be
In both anemic and non-anemic patients infected with H. found in patients with Hispanic ethnicity. Analysis of conpylori, the degree of colonization by this organism was se- tingency between categorical data resulted in a p < 0.01;
vere and confined to the gastric corpus. The majority of this value is considered statistically significant. Thus a cainfected subjects (55%) had not been receiving previous sual relationship can be depicted between infection with
therapy with either PPI or H2 Blocker prior to infection this bacterium and development of anemia in Hispanic
with this bacterium. Only 12% of patients had previous patients. In addition, restoration of anemia in two subjects
PPI therapy; 24% subjects had previous therapy with H2 following eradication therapy without previous iron or coBlocker, and 9% subjects were receiving both drugs prior balamin replacement therapy, further suggests a potential
to EGD performance and determination of H. pylori sta- role of this bacterium in the development of anemia in Histus. Out of the 33 patients infected with H. pylori, only 1 panics.
had focal intestinal metaplasia localized in the antrum (see
Figure 3).
As previously described in the literature, an increase in
prevalence of disease occurs with increasing age, which
Fisher exact test was applied between categorical variables correlates with our findings. In a study done by Everhart et
to determine the statistical significance of symptoms when al. (6), higher prevalence of H. pylori was found with male
compare anemic vs. non-anemic H. pylori infected pa- sex. This did not correlate with our population, since the
tients, yielding a p-value of 0.0027.
majority of affected subjects were females. This raises the
question whether cultural and ethnicity of Hispanics from
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 17
Caribbean origin is responsible for the difference in gender
found in our subjects. Other characteristics such as socioeconomic status, education, occupation and household
living were not available.
Studies regarding proton pump inhibitor therapy have suggested a change in the pattern of H. pylori induced gastritis, causing it to move from the antrum into the more
proximal corpus mucosa of the stomach inducing a more
body predominant gastritis. In a study by Uemura et al, the
strongest risk factor for cancer in H. pylori infection was
the presence of corpus predominant gastritis and that this
was a greater risk factor than either atrophy or intestinal
metaplasia (15-19). In our investigation, only four subjects
were receiving PPI therapy, of which 1 had moderate colonization at antrum, 1 had mild colonization at body, 1 with
moderate colonization at body and 1 with severe colonization at antrum/corpus; this correlated with the effects of
PPI to induce a gastritis involving the stomach body. Even
though the majority of patients were not receiving previous
PPI therapy, results on EGD of a severe gastritis confined
to the corpus without evidence of intestinal metaplasia,
raised the concern whether this finding accounts as a risk
factor for the high incidence of stomach cancer found in
Hispanic patients from Puerto Rico.
7. Chiaojung J. Tsai et al. Helicobacter pylori infection in Different
Generations of Hispanics in the San Francisco Bay Area. Am J Epidemiol 2005; 162: 351-357
8. DeMaeyer E, Adiels-Tegman M. The prevalence of anaemia in the
world. World Health Stat Q 1985; 38:302-16
9. DuBois Suja, M.D., Kearney David J. M.D., Iron deficiency Anemia
and Helicobacter pylori Infection: A Review of the Evidence. Am J Gastroenterol 2005; 100:453-459
10. Amy L Frith-Terhune, et al. Iron deficiency anemia: higher prevalence in Mexican American than in non-Hispanic white females in the
third National Health and Nutrition Examination Survey, 1988-1994.
Am J Clin Nutr October 2000 vol. 72 no. 4 963-968
11. Bikha Ram Devrajani, Shaikh Muhammad Zaman, et al. Helicobacter pylori: A Cause of Vitamin B12 Deficiency (A Hospital Based
Multidisciplinary Study). World Appl Sci J, 12 (9): 1378-1381, 2011
12. Kaptan K, Beyan C, Ural AU, et al. Helicobacter pylori-is it a novel causative agent in Vitamin B12 deficiency? Arch Intern Med 2000;
160:1349-1353
13. Cardenas Victor M, Mulla Zuber D, et al. Iron Deficiency and Helicobacter pylori infection in the United States. Am J Epidemol 2006;
163: 127-134
14. Ortiz Ana, et al. Incidence and mortality rates of selected infection-related cancers in Puerto Rico and in the United States. Infectious
Agents and Cancer 2010, 5:10
15. Unemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori
infection and the development of gastric cancer. N Engl J Med 2001;
345: 784-9
16. Labenz J, Blum AL, Bayerdorffer E, el al. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997; 112: 1442-7
17. McColl K E L, El-Omar E, Gillen D. Interactions between H pylori
infection, gastric acid secretion and anti-secretory therapy. British Medical Bulletin 1998;54 (No.1); 121-138
18. Kuipers EJ, Lundell L, Klinkenberg EC, et al. Atrophic gastritis and
Helicobacter pylori infection in patients with reflux esophagitis treated
with omeprazole or fundoplication. N Engl J Med 1996;334: 1018-22
19. Pounder RE, Williams MP. Omeprazole and accelerated onset of
atrophic gastritis. Gastroenterology 2000;118: 238-9
Finally, some limitations found in our study was the unavailability of further information to determine common
socioeconomic and environmental factors in our population that can predispose to H. pylori infection such as
income, house crowding, hygiene, education and cultural practices which have been previously described in the
literature. Another limitation in our study was the small RESUMEN
volume of subjects with anemia and HP (+), thus further
investigations should be done with a larger population to La anemia perniciosa representa la fase final de un proverify if same results can be obtained.
ceso que comienza con gastritis por Helicobacter pylori y
evoluciona a través de niveles progresivos de atrofia hasIn conclusion, from the results of this study a potential ta que la masa de células parietales se pierde totalmente.
association between Helicobacter pylori infection and Numerosos estudios han sugerido una posible asociación
anemia in Hispanic patients is suggested. Restoration of entre infección por H. pylori y la anemia por deficiencia
hemoglobin after eradication of bacteria further supports de hierro, así como la deficiencia de cobalamina. Nuesthis. Hence it is of great importance as physicians to seek tra pregunta de investigación fue determinar si existe una
infection with H. pylori in patients with recurrent, refracto- asociación entre la infección por H. pylori y el desarrollo
ry of undetermined cause of anemia, as early eradication of de la anemia en pacientes hispanos. Este estudio piloto reinfection can help restore hemoglobin values and decrease visó expedientes de los años 2010-2012 y examinó la asoserious complications such as high incidence of gastric ciación entre la infección por H. pylori y los niveles de
cancer associated with this disease.
hemoglobina en pacientes hispanos. Se evaluaron un total
de 189 expedientes, de los cuales 33 cumplieron con los
REFERENCES
criterios de inclusión. La muestra de estudio se dividió en 2
grupos. Grupo A: 5 sujetos con infección por H. pylori (HP
1. Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithe+) y anemia; Grupo B : 28 pacientes con H. pylori, sin anelium in active chronic gastritis. Lancet 1983; 1:1273-5.
2. McColl Keneth E. L., M.D. Helicobacter pylori Infection. N Engl J mia. La prueba exacta de Fisher se aplicó entre variables
categóricas para determinar la significación estadística al
Med 2010;362:1597-604
3. Crowe Sheila E, M.D. Bacteriology and epidemiology of Helico- comparar los síntomas de los pacientes con infección por
bacter pylori infection. www.uptodate.com
H. pylori anémicos vs no anémicos, dando un valor signif4. Peterson WL, Frederick AM, Cave DR, et al. Helicobacter pylori-related disease: Guidelines for testing and treatment. Arch Intern Med icativo de p = 0,0027. La restauración de la anemia en dos
sujetos después de la terapia de erradicación de H. pylori
2000; 160:1285-91.
5. Chey William D., Wong Benjamin C.Y., et al. American College of sin hierro anterior o terapia de reemplazo de cobalamina
Gastroenterology Guideline on the Management of Helicobacter pylori sugiere un papel potencial de esta bacteria en el desarrollo
Infection. Am J Gastroenterol 2007; 102:1808-1825.
6. Everhart JE et al. Seroprevalence and ethnic differences in Helico- de la anemia en los hispanos. En conclusión, los resultados
bacter pylori infection among adults in the United States. J Infect Dis de este estudio sugieren una posible asociación entre la infección por H. pylori y anemia en pacientes hispanos.
2000 Apr; 18 (4): 1359-63
18 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
EPTIFIBATIDE:
Gender related
complications in a
Hispanic population
Pamela Reyes Guerrero MDab*
Milton Carrero Quiñones MDa
Rafael Bredy MDb
Mayagüez Medical Center, Internal Medicine Department, Mayagüez, Puerto Rico.
Ponce School of Medicine & Health Sciences Teaching Consortium, Ponce, Puerto Rico.
*Corresponding author: Pamela Reyes Guerrero, MD - 1901 Laliza, Alturas de Mayagüez
Mayagüez, PR 00682. E-mail: [email protected]
a
b
O
ABSTRACT
One of the most common indications of Eptifibatide, a GP IIb/IIIa inhibitor,
is non-ST segment elevation myocardial infarction (NSTEMI) due to its
great antiplatelet activity. The aim of this study was to find out if there are
gender discrepancies when comparing complications in Hispanics treated
with Eptifibatide. Methods: A cross-sectional study. 116 medical records
with diagnosis of NSTEMI managed with Eptifibatide during 2010-2012
were included. Bleeding, thrombocytopenia, new ischemia, anemia and
death were variables compared. Results: The most common complication
was death. There were four cases of bleeding, all of them occurred in the
female gender, reaching a statistically significant difference compared to
male gender (p = 0.0173); 8% of patients had thrombocytopenia; 9% had
new ischemia during hospitalization; 13% died; 19% of patients developed anemia including the four cases of bleeding. Conclusion: Bleeding
occurred only in women, and this difference was statistically significant
when compared to males. More studies emphasizing the differences in Eptifibatide complications by gender are needed. Furthermore, it would be
important to compare these results to non-Hispanic women. The difference
found in the other complications analyzed was not statistically significant.
Index words: eptifibatide, gender, complications, hispanic, population
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 19
E
INTRODUCTION
Eptifibatide is a cyclic heptapeptide that has a high-affinity
for the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets inhibiting platelet aggregation.
Eptifibatide has been studied in several clinical trials, but
the most important were specifically three placebo-controlled, randomized studies. The Platelet Glycoprotein IIb/
IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy study (PURSUIT) evaluated patients with
acute coronary syndromes: unstable angina (UA) or nonST elevation myocardial infarction (NSTEMI) (1). Two
other studies, the Enhanced Suppression of the Platelet IIb/
IIIa Receptor with Integrilin Therapy (ESPIRIT) and the
Integrillin to Minimize Platelet Aggregation and Prevent
Coronary Thrombosis II (IMPACT II), evaluated patients
about to undergo percutaneous coronary interventions
(PCI) (2, 3).
PURSUIT was a 726-center, 27-country, double blind,
randomized, placebo-controlled study in 10,948 patients
presenting with unstable angina (UA) or NSTEMI. Patient
age ranged from 20 to 94 years, and 65% were male. The
patients were 89% Caucasian, 6% Hispanic, and 5% Black,
recruited in the United States and Canada (40%), Western
Europe (39%), Eastern Europe (16%), and Latin America
(5%) (1). Eptifibatide reduced the incidence of endpoint
events such as death or myocardial infarction (MI) at 3,
7 and 30 days (1). This study was very important helping
Eptifibatide obtaining FDA approval.
Although the treatment was consistent among most subgroups in this study (PURSUIT), it differed between women and men. In women, the 95 percent confidence interval was compatible with the existence of no effect, small
beneficial effect, or a detrimental effect. This information
is very important, as currently, Eptifibatide has the same
indications for women and men. An important point is that
the majority of these women that participated in the PURSUIT study were Caucasians (1). No sex difference has
been seen in other trials of Eptifibatide.
In the ISAR-REACT 4 trial, which compared bivalirudin
to heparin plus GP IIb/IIIa inhibitor in non-ST elevation
MI patients receiving aspirin and clopidogrel, the rate of
death, recurrent MI, or urgent target-vessel revascularization was similar between the two groups, but bleeding occurred significantly more often in those receiving heparin
plus glycoprotein IIb/IIIa inhibitor, but no difference was
found by gender (5).
with NSTEMI is associated with a significant reduction in
the incidence of death or myocardial infarction (6).
According to the US cost-effectiveness analysis about
70% of the acquisition costs of Eptifibatide are offset by
the reduced medical resource consumption during the first
year (6), one of the most important reasons why this medication is recommended in non-ST elevation acute coronary
syndromes.
In addition to platelet aggregation, GP IIb/IIIa antagonism
has the ability to induce dissolution of platelet-rich clot by
disrupting fibrinogen-platelet interaction; an action termed
“dethrombosis” (7).
As we can see, there are several clinical studies that have
demonstrated the efficacy of Eptifibatide, but, as mentioned above, there is still the doubt previously established
by the PURSUIT study, in terms of unclear benefits of this
medication in women.
The aim of this study was to compare the complications of
Eptifibatide between Hispanic females and males, to find
out if there is any difference.
Research Question: Is there any difference in Eptifibatide
complications when we treat Hispanic females and males?
Aims of this study:
Identify Hispanic patients with NSTEMI treated with Eptifibatide in our institution.
Separate population by gender (Male vs. Female).
Measure morbidity and mortality in both groups.
Compare the complication rate of Eptifibatide between
Hispanic women and men.
Identify difference, if any, between both groups, and if it is
statistically significant or not.
Justification: If any difference is found in the complications
of Eptifibatide between Hispanic women and men treated for NSTEMI, current clinical treatment for NSTEMI
should be reviewed.
MATERIALS AND METHODS
This is a single center, cross sectional analysis. The location of our study was at Mayagüez Medical Center, in Mayagüez, Puerto Rico. All the medical records from patients
diagnosed with NSTEMI during a twenty-four months period (2010-2012) were reviewed. A total of 232 medical
records were reviewed in order to determine the most frequent complications of Eptifibatide in Hispanic patients.
Then, we included five variables to analyzed: Bleeding,
new ischemia, anemia, thrombocytopenia and death. The
time period for data collection was from December 2010
to December 2012.
Three intravenous GP IIb/IIIa inhibitors are currently
available for clinical use: Abciximab, Tirofiban, and Eptifibatide. A meta-analysis of eight prospective trials involving 14,644 patients undergoing a PCI compared the efficacy and safety of these three drugs and the conclusion was
that, at optimal doses, they have comparable efficacy. A The inclusion criteria of the population of the study were
common complication compared to placebo, was bleeding. adult Hispanic males and females diagnosed with NSTEMI
and treated with Eptifibatide during a 24-month period
Several large, randomized, controlled trials show that Ep- (December 2010 - December 2012) in our medical institutifibatide as adjunctive therapy to standard care in patients tion (Mayagüez Medical Center).
20 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
We excluded all those patients diagnosed with NSTEMI that were
not treated with Eptifibatide. We
also excluded those patients with
altered coagulation profile that
suggested a coagulation disorder
or other medication toxicity, like
anticoagulants. Patient with concomitant acute renal failure were
also excluded.
Finally, we included 116 patients
and excluded 116. From these
116 patients included, 67 were of
male gender and 49 were of female
gender (see Figure 1). All of the
patients included were Hispanics,
males and females, from 21- 90
years old (see Figure 2). Pearson’s
chi-square and Fisher’s exact test
were used to analyze results.
RESULTS
During the study period, four out of
116 (3.5%) patients had bleeding
as a complication; all of them were
of female gender (p value= 0.0173,
CI: 0.0000-0.7875). Of these four
episodes of bleeding, there were
three gastrointestinal bleedings and
one epistaxis (see Figure 3).
All of these patients were treated
with the same medications, aspirin, clopidogrel and low molecular
weight heparin (LMWH). None of
them had thrombocytopenia.
Nine (8%) patients developed
thrombocytopenia; four of them
were of female gender (p value=
0.8892; CI: 0.1839-4.8437). All of
them were managed with aspirin,
clopidogrel and LMWH (see Figure 4).
There was no stroke or intracranial
hemorrhage reported during hospitalization in any of the 116 patients
of our study.
Eleven (9%) patients developed a
new myocardial ischemia episode
during hospitalization. Seven of
them were female gender (p value=0.1311; CI: 0.0775-1.6218)
(see Figure 5). Five patients with
new ischemia, died; 4 of them due
to a new MI and the other one from
sepsis. Four of them were of female gender.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 21
Fifteen (13%) patients died.
Five of them were of female
gender (p value= 0.4541;
CI: 0.4402-6.1647). Causes
of death were heparin-induced thrombocytopenia =
1, sepsis/septic shock = 2,
cardiogenic shock = 2, MI =
7, arrhythmia = 1, and Pneumonia = 2 (see Figure 6).
Anemia was defined by the
lowering of serum hemoglobin levels of at least 2 g/dL
during hospitalization. There
were 22 patients who developed anemia during hospitalization, including the four
who had active bleeding.
The other 18 patients did not
have any documented cause
of anemia. From the total of
22 patients who had anemia,
there were 13 females and
9 males, but there were no
statistically significant difference (p value= 0.0755)
(see Figure 7).
DISCUSSION
Coronary heart disease
(CHD) is a major cause of
death and disability in developed countries. Although
CHD mortality rates have
declined over the past four
decades in the United States,
it remains responsible for
about one-third of all deaths
in individuals over age thirty-five (8, 9). It has been estimated that nearly one-half
of all middle-aged men and
one-third of middle-aged
women in the United States
will develop some manifestation of CHD (10).
Coronary heart disease is one
of the most common leading
cause of death in Hispanic
and non-Hispanic population. In 2011, only 15.4% of
Hispanic (or Latinos) age 18
and older met the 2008 Federal Physical Activity.
Physical inactivity, inadequate diet, smoking, obesity are some of the negative
factors that contribute to
22 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
As a final recommendation, while using Eptifibatide, serum hemoglobin level should be monitored closely, and even
more in Hispanic females; If any sign of
bleeding occurs, look for the specific origin and consider to hold this medication if
necessary.
REFERENCES
1. Inhibition of platelet glycoprotein Iib/IIIa with
eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators Platelet
Glycoprotein Iib/IIIa in unstable angina: Receptor
supression using integrillin therapy. N Engl J Med.
1998;339(7):436-443.
2. ESPRIT Investigators. Enhanced Suppression of
the Platelet IIb/IIIa Receptor with Integrilin Therapy.
Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised,
placebo-controlled trial. Lancet 2000; 356:2037.
the development of coronary heart disease and its equivalents. According to an American Heart Association report
in 2013, Puerto Rican Americans had the highest hypertension-related death rate among all Hispanic subpopulations
(154.0), (PA) Guidelines (11).
The incidence and prevalence of myocardial infarction
increases progressively in older women, especially after
the age of forty-five (12). Currently, medical treatment for
NSTEMI is the same for women and men. As we mentioned before, GP IIb/IIIa inhibitors have been studied and
its efficacy has been also demonstrated in several studies,
but there is still in doubt its efficacy and/or safety in women as per the results of the PURSUIT study. Our variables
were bleeding, new ischemia, thrombocytopenia, anemia
and death.
Bleeding occurred only in women, none of them died
during their hospitalization. This is the first study that finds
such a relevant difference in Hispanic females compared
to Hispanic males. More data relevant to complications
between females and males in other races and/or ethnicities is missing in the literature. It would be important to
investigate more, in order to find out if the propensity of
Hispanic females to bleed with the use of Eptifibatide is
related to genetics, race/ethnicity or if it is 100% related to
female gender.
The difference found in the other complications analyzed
was not statistically significant. There is a need to investigate what is the cause of anemia in patients treated with
Eptifibatide. We can evaluate and investigate with images
if necessary, to rule out retroperitoneal hematomas or any
other cause.
It would be very important to see if these results are reproducible; one of our limitations was that this was a retrospective analysis, and now we are more enthusiastic to
perform a prospective analysis with similar endpoints,
focusing in complications of Eptifibatide in Hispanic patients.
3. THE IMPACT-II Investigators. Randomized placebo-controlled trials of effect of eptifibatide on complications on percutaneous coronary
intervention: IMPACT-II. Lancet 1997; 349: 1422-8.
4. Kleiman NS, Lincoff AM, Flaker GC, et al. Early percutaneous
coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT
Investigators. Circulation 2000; 101:751.
5. Kastrati A, Neumann FJ, Schulz S, et al. Abciximab and heparin
versus bivalirudin for non-ST-elevation myocardial infarction. N Engl
J Med 2011; 365:1980.
6. Ibrahim Shah, Shakeel O Khan, Surender Malhotra, Tim Fischell.
Eptifibatide: The evidence for its role in the management of acute coronary syndromes. Core Evid; volume 4; 49-65.
7. P. Anondo Stangl, MD. And Sarah Lewis, MD. Review of Currently
Available GP IIb/IIIa Inhibitors and Their Role in Peripheral Vascular
Interventions. Seminars in Interventional Radiology. 2010 December;
27 (4): 412-421).
8. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke
statistics--2008 update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee. Circulation
2008; 117:e25.
9. Lloyd-Jones D, Adams RJ, Brown TM, et al. Executive summary: heart disease and stroke statistics--2010 update: a report from the
American Heart Association. Circulation 2010; 121:948.
10. Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of
developing coronary heart disease. Lancet 1999; 353:89.
11. Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB,
Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM,
Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS,
Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein
J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; on behalf
of the American Heart Association Statistics;Committee and Stroke
Statistics Subcommittee. Heart disease and stroke statistics—2013
update: A report from the American Heart Association.Circulation.2013;127:e6-e245.
12. Maddox TM, Reid KJ, Spertus JA, et al. Angina at 1 year after
myocardial infarction: prevalence and associated findings. Arch Intern
Med 2008; 168:1310.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 23
Case Report/Reporte de Casos
13. Batchelor WB, Tolleson TR, Huang Y, et al. Randomized comparison
of platelet inhibition with abciximab, tiRofiban and eptifibatide during
percutaneous coronary intervention in acute coronary syndromes: the
COMPARE trial. Comparison Of Measurements of Platelet aggregation
with Aggrastat, Reopro, and Eptifibatide. Circulation 2002; 106:1470.
14. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol 1997; 80:11B.
15. Sabatine MS, Jang IK. The use of glycoprotein IIb/IIIa inhibitors in
patients with coronary artery disease. Am J Med 2000; 109:224.
16. Brener SJ, Zeymer U, Adgey AA, et al. Eptifibatide and low-dose
tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO
AMI) trial. J Am Coll Cardiol 2002; 39:377.
17. Harrington RA, Kleiman NS, Kottke-Marchant K, et al. Immediate
and reversible platelet inhibition after intravenous administration of a
peptide glycoprotein IIb/IIIa inhibitor during percutaneous coro-
nary intervention. Am J Cardiol 1995; 76:1222.
RESUMEN
Una de las indicaciones más comunes del Eptifibatide,
un inhibidor de la Glicoproteina IIb/IIIa, es el infarto al
miocardio sin elevación del segmento ST debido a su capacidad antiplaquetaria. Un estudio clínico encontró que
las mujeres no norteamericanas que participaron sufrieron
más complicaciones. El objetivo de este estudio clínico fue comparar si hay diferencia en las complicaciones
del Eptifibatide en pacientes Hispanos si las comparamos
por género. Métodos: Un estudio de corte transversal. Se
incluyeron 116 expedientes médicos con diagnóstico de
infarto al miocardio sin elevación de ST tratados con Eptifibatide durante dos años consecutivos (2010-2012). Resultados: La complicación más común fue muerte. Hubo
cuatro casos de sangrado, los cuales fueron todos del género femenino, siendo ésta una diferencia estadísticamente
significativa al compararse con el género masculino (p
value= 0.0173); 8% desarrolló trombocitopenia; 9% sufrió
nuevamente isquemia miocárdica; 13% murió; 19% desarrolló anemia. Conclusión: Se necesitan más estudios que
hagan énfasis en las complicaciones del Eptifibatide y que
evalúen si existen diferencias según el género. A raíz de
lo analizado en este estudio clínico, existe la necesidad de
evaluar por qué las mujeres Hispanas son más propensas
que los hombres Hispanos a sangrar con el uso de Eptifibatide; Más aún, se debe realizar este mismo análisis con
otras razas para ver si tiene algo que ver la raza, genética o
simplemente las diferencias en género.
CEPHALIC TETANUS
FOLLOWING PENETRATING
EYE TRAUMA:
A Case Report
Esteban Del Pilar Morales MDa*
Jorge Bertrán Pasarell MDa
Zaydalee Cardona Rodriguez MDa
Juan Carlos Almodovar Mercado MDb
Alejandro Figueroa Navarro MDc
Infectious Diseases Department, University Hospital, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
Ophthalmology Department, University Hospital, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
c
Internal Medicine Department, University Hospital, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
*Corresponding author: Esteban Del Pilar Morales MD - Infectious Diseases Department, University Hospital, University of
Puerto Rico School of Medicine, San Juan, Puerto Rico 00936. E-mail: [email protected]
a
b
ABSTRACT
Tetanus is a potentially life-threatening infection characterized by muscle spasms. Cephalic tetanus is limited to muscles and nerves in the head
and can occur after trauma to this area. Because of the rarity of cephalic
tetanus clinicians may be unfamiliar with the clinical presentation unsuspecting of the diagnosis.
Index words: cephalic, tetanus, penetrating, eye, trauma
24 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 25
T
INTRODUCTION
Tetanus is a vaccine-preventable disease and a rare condition in developed countries around the world (1). It remains an important cause of death worldwide with a very
high case mortality, especially in the underdeveloped world
(2-9). Caused by an exotoxin, tetanospasmin, produced by
Clostridium tetani, it manifest as a generalized or localized
form in which the spasms and rigidity are the hallmark of
the disease. Localized tetanus is rare, the cephalic form,
even more so occasionally occurring as a complication
of otitis media or following craniofacial injuries (2, 3).
In cephalic tetanus, paralysis of cranial nerves rather than
spasms predominates but progression to generalized tetanus is not uncommon (5). We present the case of a man
who developed cephalic tetanus following eye trauma.
Case History
We present the case of a 57-year-old Republican Dominican man with history of gout presenting after one month
evolution of pain over his right eye. Patient referred that,
approximately one month ago, he was struck in the right
eye by an unknown material while using a mechanical
trimmer near a palm tree. Even though he felt a stinging
sensation over the area, he could not perceive nor retrieve
any material after inspection. Since symptoms quickly resolved, he forwent any medical evaluation at that time. Fifteen days after this incident the patient begun noticing pain
around his right eye with associated blurry vision, followed
by yellow-greenish secretions and erythema. At this time
patient sought medical attention and a pre-orbital cellulitis
was diagnosed. Patient was prescribed Ciprofloxacin 500
mg orally twice daily for seven days and discharged home.
Patient failed to notice any improvement, prompting a second evaluation at the Emergency Room.
prompting evaluation by the Infectious Disease section.
Further history taken at the moment revealed the patient
did not received any adult immunizations and could not
recall if he was vaccinated during childhood while still
living in the Dominican Republic. Given patient’s presentation of trismus and exposure for one month to wooden
material within his eye, cephalic tetanus was suspected and
empiric therapy was begun with a dose of 6,000 units intramuscularly of tetanus immune globulin (TIG) as well as
active immunization with tetanus/diphtheria toxoid. Initial
antibiotherapy was kept. Patient quickly began to resolve
his trismus over a period of several days. Patient required
use of assistance device to help with opening mouth as per
maxillofacial surgery recommendation. Patient was able
to be discharge 21 days later from the hospital with resolved orbital cellulitis and greatly improved opening of
his mouth.
DISCUSSION
Tetanus is a potentially life-threatening infection resulting
from inoculation with Clostridium tetani spores characterized by muscle spasms. The clinical features of tetanus and
its relationship to traumatic injuries have been well established. Diagnosis is made clinically, without confirmatory
test available (6). While it remains a problem in developing countries, the condition is rare in the developed world.
The most frequent presenting symptoms are trismus and
dysphagia, due to the spasmodic contraction of the masticatory muscles, usually followed by generalization of the
condition. Although the incubation period is usually short,
with a mean of eight days from inoculation, it has been
reported that illness may occur even months after exposure
(8). The recognition of the presenting signs of cephalic
tetanus allowed the prompt management of the infection.
However, because of the rarity of this condition clinicians
may be unfamiliar with the clinical presentation, and be
Evaluation during this visit showed no improvement in unsuspecting of the diagnosis (9).
eye secretions and progression of erythema and swelling
around periorbital area. Laboratories revealed a normal Epidemiology
complete blood count with white blood cell count at 6.72 Tetanus incidence rates have declined steadily over the
cells/mL (reference range 4.00-11.00) with normal differ- last 70 years. Thirty-one cases of tetanus annually were
ential. The rest of his blood work was within normal limits. reported on average from 2000 to 2007, with a very low
A chest radiograph showed normal findings for age. Brain incidence in 2009 (0.01 cases per 100,000) (10-13). The
and orbit magnetic resonance imagining (MRI) were per- death-to-case ratio has declined from 30% to approximateformed which revealed is a 5 cm long foreign body cours- ly 10% in recent years. Still, in the last 10 years, 233 cases
ing through the inferior aspect of the orbital cavity out of tetanus have been reported with a case fatality of 13%.
through the inferolateral wall with the tip in the infratem- Most patients were above 50 years of age and males. Herporal fossa. MRI also showed soft tissue edema, swelling oin users, particularly persons who inject them subcutaneand enhancement of the temporalis muscle with abundant ously, appear to be at high risk for tetanus (13). Practically
inflammatory changes involving both intra and extraconal all cases were in patients who have either never been vaccompartments (see Figure 1). Patient was admitted and cinated, or who completed a primary series but have not
started on antibiotherapy for orbital cellulitis with Vanco- had a booster in the following ten years.
mycin 1 gram IV every 12 hours and Piperacillin/Tazobactam 3.3375 grams IV every 6 hours. Patient was promptly Risk Factors and Pathogenesis
taken to the operating room by the ophthalmology service, Several risk factors are usually required to develop tetanus.
where they removed a 4-5 cm piece of wood, which was Among them a penetrating injury, co-infection with other
embedded in the patient’s right orbital cavity (see Figure bacteria, devitalized tissue, presence of a foreign body and
2). During evaluation by anesthesiology, the patient was localized ischemia. Clostridium tetani spores transform
noted to have increased muscle tone over masseters mus- into the vegetative state in presence of anaerobic condicles, making intubation for surgery difficult. This problem tions usually found in devitalized tissue and ischemia of
became more pronounced after patient was taken to ward, the wound. Production of tetanospasmin initially occurs
26 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Figure 1: Maxillofacial MRI. Foreign body noted within the right infraorbital fossa approximately 5cm in length (A); closer evaluation again shows foreign body with surrounding edema (B).
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 27
locally, but soon reaches receptors in the spinal cord and
brainstem via retrograde axonal transport. After reaching
the spinal cord and brainstem, the toxin binds tightly and
irreversibly to receptors at these sites, tetanus toxin blocks
neurotransmission by its cleaving action on membrane
proteins involved in neuroexocytosis (14). This causes
disinhibition of neurons that modulate excitatory impulses
from the motor cortex resulting in increased muscle tone,
painful spasms, and widespread autonomic instability. Recovery requires the growth of new nerve terminals, which
explains the prolonged duration of tetanus (15). Clinical
disease usually lasts four to six weeks.
Treatment
Management should be begun as soon as the condition is
suspected, preferably in an Intensive Care Unit setting,
given increased mortality as time progresses (10). Wound
cleansing and debridement is paramount to eliminate source
of toxin production. Most antibiotherapy with coverage for
Gram positives organisms may be used, but metronidazole,
cephalosporins, penicillins, doxycycline and vancomycin
have all been used successfully (11). Inhibition of circulating toxin is also paramount in an attempt to avoid further
damage by the toxin. This may be achieved by the use of
tetanus immunoglobulin (12). Patients with tetanus should
receive active immunization with a total of three doses of
tetanus and diphtheria toxoid spaced at least two weeks
apart, commencing immediately upon diagnosis.
sedation.
Differential Diagnosis
Other diagnosis must be ruled out as part of the evaluation
for tetanus (see Table 1). Given this patient’s occupation,
exposure to strychnine must be considered. Given lack of
prodromal signs of the condition (mydriasis, hypervigilance, anxiety, hyperreflexia, clonus, and stiffness of the
facial and neck muscles) and subsequent negative blood
levels, this could adequately be ruled out in this patient.
Another possibility could have been trismus secondary
toa dental infection. However, the presence of an obvious
dental abscess could not be identified by either physical
exam or imagining studies positively ruling it out. There
was also the possibility of drug-induced dystonias or neuroleptic malignant syndrome. As patient’s history showed,
he did not take nor received any medications that might
have induced such a reaction, ruling both conditions out.
CONCLUSION
This case illustrates the importance of maintaining a high
degree of suspicion for tetanus in patients with adequate
history and physical findings to ensure a prompt diagnosis
so further complication may be avoided.
Aside from managing the infectious etiology of the condition, its effect on the patient must also be managed.
To control musculoskeletal
spasms, benzodiazepines are
highly recommended given
dual effect of spasms control
and sedative effect. Neuromuscular blocking agents
may be considered if benzodiazepines do not adequately
manage spasms. One must
be cautious when using pancuronium given inhibition of
catecholamine uptake that
may lead to worsening of
autonomic dysfunction. It is
advisable to give the patient a
rest from these drugs once a
day in order to be able to examine their neurological status. Baclofen has been used intrathecally to control muscle REFERENCES
spasms and rigidity (15).
Autonomic dysfunction may be managed with adrenergic
blockade and inhibition of autonomic reactivity, magnesium sulfate (0.5 to 1.0 mg/kg per hour) been the most
commonly used and beta-blockers with alpha blocking activity, such as labetalol (0.25 to 1.0 mg/min), frequently
employed in the treatment of these patients (15). Continuous infusion with morphine sulfate is also frequently used
to manage autonomic dysfunction, as well as to induce
1. Alhaji, MA; Mustapha, MG; “Recurrent generalized tetanus: a case
report,” Tropical Doctor, vol. 41, no. 2, pp. 127–128, 2011.
2. Asgaonkar, DS; Kulkarni, VK; Yadav, S; Dalvi, A; “Cephalic tetanus:
a rare form of localised tetanus,” Bombay Hospital Journal, vol. 44, no.
1, pp. 121–122, 2002.
3. Ogun, OA; Ashaye, AO; Oba, SO; “Cephalic tetanus: a case report
of a rare complication of orbito-ocular injury in a Nigerian,” Nigerian
Journal of Ophthalmology, vol. 13, no. 1, pp. 32–35, 2005.
4. Cook, TM; Protheroe, RT; Hnadel, JM; “Tetanus: A Review of Literature”; British Journal Of Anaesthesia 87 (3): 477-87 (2001)
5. Alhaji, MA; Abdulhafiz, U; Atuanya, CI; Bukar, FL; “Cephalic Tetanus:
28 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Figure 2: Wooden material removed from infraorbital fossa
during surgery measuring around
5cm in length
A Case Report Case”; Reports in Infectious Diseases, Volume 2011, Article ID
780209
6. Reddy P, Bleck TP. Clostridium
tetani(Tetanus). In: Mandell GL, Bennett
JE, Dolan R, eds. Mandell, Douglas, and
Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Orlando, FL:
Saunders Elsevier; 2009:chap 244.
7. Bleck TP. Tetanus: pathophysiology,
management, and prophylaxis. Dis Mon
1991; 37: 545-603
8. Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry 2000;
69:292. PMID 10945801
9. Fusetti S, Ghirotto C, Ferronato G. A case of cephalic tetanus
in a developed country. Int J Immunopathol Pharmacol. 2013 JanMar;26(1):273-7 PMID 23527734
10. Brauner JS, Vieira SR, Bleck TP. Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil. Intensive Care
Med 2002; 28:930. PMID 12122532
11. Johnson EA, Summanen P, Finegold SM. Clostridium. In: Manual
of Clinical Microbiology, 9th edition, Murray PR, Baron EJ, Jorgensen
JH, et al (Eds), ASM Press, Washington DC 2007. Vol 1, p.889.
12. Miranda-Filho Dde B, Ximenes RA, Barone AA, et al. Randomised
controlled trial of tetanus treatment with antitetanus immunoglobulin
by the intrathecal or intramuscular route. BMJ 2004; 328:615. PMID
15003976
13. CDC. Tetanus Surveillance—United States, 2001-2008. MMWR
Surveill Summ 2011; 60:12.
14. Caccin P, Rossetto O, Rigoni M, et al. VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes. FEBS Lett 2003; 542:132.
15. Otero-Maldonado M, Bosques-Rosado M, Soto-Malavé R, DelizRoldán B, Bertrán-Pasarell J, Vargas-Otero P. Tetanus is still present in
the 21st century: case report and review of literature. Bol Asoc Med P
R. 2011 Apr-Jun;103(2):41-7.
RESUMEN
El tétano es una infección potencialmente letal
caracterizada por espasmos musculares. El tétano cefálico se limita a los músculos y nervios de
la cabeza y ocurre luego de trauma en esta región
anatómica. Debido a la rareza de esta condición los
clínicos se han dejado de familiarizar con la presentación clínica dejando de sospechar en su posibilidad diagnóstica.
Instituto de Educación Médica
de la Asociación Médica de Puerto Rico
Proveedor oficial de créditos de educación continua reconocidos por la Junta de Licenciamiento de
Disciplina Médica. Realizamos jornadas científicas y acreditamos a otras instituciones
[email protected]
(787) 721-6969
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 29
OCULAR MANIFESTATIONS OF
ACUTE GRAFT VERSUS HOST
DISEASE AFTER ALLOGENEIC
BONE MARROW TRANSPLANT
Betsy Colón-Acevedo MDa*
Lilia Rivera-Román MDa
Nicole Candelario MDb
Julio Sánchez MDb
a
Department of Ophthalmology, UPR School of Medicine, Puerto Rico Health Science Center, San Juan, Puerto
Rico.
b
Department of Dermatology, UPR School of Medicine, Puerto Rico Health Science Center, San Juan, Puerto
Rico.
*Corresponding author: Betsy Colón-Acevedo MD – 510 S. LaSalle Street, Apt 1410, Durham, NC 27705.
E-mail: [email protected]
ABSTRACT
A 17-year-old-male with Sickle Cell Disease underwent allogenic bone marrow transplant. Two years after the transplant the patient developed violaceous lichenoid papules coalescing into plaques over the face and upper extremities complaining of decrease visual acuity, foreign body sensation, and
eye pain. A slit lamp examination showed injected conjunctiva, superficial
punctate keratopathy and decreased baseline Schirmmer test. Dermatologic
evaluation and biopsy demonstrated chronic graft versus host disease along
with the diagnosis of secondary keratoconjunctivitis sicca.
H
Index words: ocular, acute, graft, host, disease, allogeneic, bone, marrow,
transplant
INTRODUCTION & PATHOPHYSIOLOGY
classified as acute, occurring within 100 days after transplantation, and chronic, occurring beyond 100 days after
Hematopoietic stem cell transplantation (HSCT) is an es- transplantation and often seen after tapering or withdrawal
tablished treatment used for hematologic malignancies, of immunosuppressive therapy.
aplastic anemia and an increase number of metabolic and
immunodeficiency disorders (1). The donor cells used in Acute GVHD reflects an exaggerated inflammatory retransplants can be from self (autologous), monozygotic spond performed by the donor lymphocytes activated by
twin (syngenic) or another HLA-matched individual (al- the recipient tissue. According to the literature Acute
GVHD is a reaction that occur in three phases: 1- antigen
logeneic).
presenting cell (APC) activation, 2- activation and proliferGraft versus host disease GVHD is one of the major causes ation of donor T-cells, and 3- destruction of recipient tissue
of morbidity and mortality in allogeneic stem cell trans- (organs). Acute GVHD can further be divided in Classic
plantation, occurring in 25 to 70% of patients. It can be GVHD with skin involvement (maculopapular rash)
30 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
GI involvement (nausea, vomiting, anorexia, diarrhea),
and liver involvement (cholestasis) occurring within 100
days post-transplantation or following donor lymphocyte
infusions (DLI), or Persistent, recurrent, late GVHD which
presents with features of classic acute GVHD as described
above, without diagnostic or distinctive signs of chronic
GVHD and occurring within 100 days post-transplantation
or post-DLI (2-6)
epitheliopathy resulting in infected/non-infected stromal
ulceration attributed to dry-eye syndrome. Symptoms reported by patients presenting with ocular GVHD resemble
those seen in dry eye disease, including irritation, itchiness,
grittiness, foreign-body sensation, burning, excessive tearing, light sensitivity, pain, redness, and blurring of vision.
Conjunctivitis can be found in the acute and chronic
GVHD setting being graded 0-4 according to clinical findings. In Acute GVHD, Grade 0 = no finding; Grade 2 =
hyperemia; Grade 3 = hyperemia with serosanguinous discharge; Grade 4 = pseudomembranous conjunctivitis with
corneal epithelial sloughing. Pseudomembranous conjunctivitis has been considered a marker of systemic involvement associated with a poor prognosis.
Ocular acute GVHD often affects the lacrimal glands, the
conjunctiva, lids (including Meibomian glands), and the
cornea but can also involve the sclera and posterior pole.
It can simulate other autoimmune disease being keratoconjunctivitis sicca the most common manifestation.
In this case report, we describe ocular manifestations associated with chronic GVHD, which were diagnosed cliniChronic GVHD pathophysiology remains poorly under- cally and histologically after dermatologic biopsy.
stood. Nevertheless, it can be classified in Classic chronic GVHD without features of acute GVHD, and Overlap Case History
syndrome, in which features of acute and chronic GVHD
occur concomitantly (6). It should be noted that the re- A 17 year-old-male with Sickle cell disease was submitted
currence or new onset of characteristic skin, GI, or liver to allogeneic bone marrow transplant due to severe hemapathology in the absence of classic histological or clini- tologic crisis. Patient medications included Leviracetam
cal signs of chronic GVHD should be classified as acute 20 mg orally every 12 hours for major depression, PredGVHD irrespective of the same or other organ affected (6). nisone 25mg orally for GVHD prophylaxis, and Aspirin.
Two years after the transplant patient developed violaGVHD occurs in allogenic transplantation setting where ceous papules and plaques over the face and upper extremthe donor cells react to the host antigen, resulting in cell ities (see Figure 1). Skin biopsy was obtained and revealed
damage to a variety of organs, including the skin, liver, a band-like lymphocytic infiltrate in the dermo-epidermal
gastrointestinal tract, lungs, mouth, and eyes (2). Ocular junction with vacuolar alteration of the basal layer consissurface disease remains the most common cause of long- tent with GVHD
term morbidity in GVHD.
The patient complained of decreased visual acuity, foreign
OCULAR GVHD
body sensation, and eye pain. Patient’s best-corrected visual acuity was 20/40 in both eyes. A slit lamp examination
Ocular GVHD affects 40 to 60% of patients receiving al- (SLE) showed injected conjunctiva, no pseudomembrane
lo-HSCT, and ocular complications occur in 60 to 90% of formation, and superficial punctuate keratopathy. Tear
transplant recipients (6). It may affect the ocular surface braking up time (TBU) was decreased (< 6 both eyes) , de(cornea & conjunctiva) and lacrimal glands through in- creased tear meniscus (< 1 mm), and Schirmer's test withflammation and cicatricial scarring or dysfunction of the out anesthesia was decreased (right eye: 8 mm/5min; left
meibomian glands. Usually, it does not produce visual im- eye: 5mm/5min). We diagnosed the ocular manifestations
pairment, but it can affect activities of daily living.
as keratoconjunctivitis sicca secondary to chronic GVHD.
Patient was treated with topical cyclophosphamide and
Ocular GVHD is not common in acute GVHD but if pres- steroids, which produced improvement of symptoms and
ent it indicative of poor survival prognosis. It usually af- visual acuity.
fects the cornea and conjunctivas that are immunologic
targets.
DISCUSSION
The proposed mechanism of action is a T-cell related inflammatory process of the ocular tissues. Apoptosis and fibrosis of the lacrimal glands are currently thought to cause
the dry eye, and ocular surface disease in ocular GVHD.
For these reason the main therapeutic aim is treatment of
both inflammation and dryness to relieve patient’s symptoms and maintain ocular integrity and function (3).
For Chronic GVHD, Grade 0 = no findings; Grade 1 = hyperemia; Grade 3 = palpebral conjunctival fibrovascular
changes with or without epithelial sloughing; Grade 4 =
palpebral conjunctival fibrovascular changes involving 25
to 75% of total surface area. Involvement of 75% of total
surface area can occur with or without cicatricial entropi- There are no specific symptoms or clinical signs of ocular
on.
chronic GVHD. Typical symptoms include dry eye, irritation, itchiness, grittiness, foreign body sensation, epiphora,
Dry-eye syndrome or keratoconjunctivitis sicca (KCS) pain, redness and blurred vision. The severity of the ocular
remains the most common ocular complication following surface disease depends on the involvement of the differallo-HSCT, in both in the acute and chronic GVHD setting ent ocular tissues, and the amount of tear film deficiency.
with most ocular complications, such as persistent corneal If the tear composition (mucus, aqueous and lipid layers),
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 31
Figure 1: Violaceous papules and plaques on face.
is affected, then the patient will complain of dry eye resulting in ocular surface disease and chronic inflammation.
Long-term complications include corneal neovascularization, corneal scarring and cataract formation with loss of
vision.
Topical treatment plays a major role in ocular chronic GVHD. Lubrication of the ocular surface and topical
immunosuppressive drugs in combination with systemic therapy play an important role in the management of
these patients. Another treatment alternative for these patients include the use of the Boston scleral lenses known
as PROSE (prosthetic replacement of the ocular surface
ecosystem).
REFERENCES
(1) Anderson, Nicholas and Regillo, Carl. Ocular manifestation of graft versus host disease. Current opinion in Ophthalmology 2004, 15:503-507.
(2) Kim, Stella. Update on ocular graft versus host disease.
Current opinion in Ophthalmology 2004, 17:344-348.
(3) Dietrich-Ntoukas, T. et al. Diagnosis and treatment of
ocular chronic graft versus host disease: report from german-autrian-swiss consensus conference on clinical practice in chronic GVHD. Cornea 2012, 31:299-309.
(4) Jing, X. et al. Graft –versus-host disease; case report
and review of literature. J La State Med Soc 2006 Jan-Feb;
158 (1):20-4.
(5) Tichell, A. et al. Late-onset keratoconjuntivitis sicca
syndrome after bone marrow transplantation: incidence
and risk factors. European group or blood and marrow
transplantation (EBMT) working party on Late effects.
Bone marrow transplant 1996 Jun; 17(6):1105-11.
(6) Hasanain Shikari, MD, DNB,1,2,3 Joseph H. Antin,
MD,4,5,6 and Reza Dana, MD, MSc, MPH. Graft-versusHost Disease: A Review. Survey of Ophthalmology MayJune 2013 Vol 58: 233-251.
RESUMEN
Un varón de 17 años de edad con anemia falciformes fue
sometido a un trasplante de médula ósea. Dos años posterior al trasplante desarrolló pápulas y placa liquenoides
de color violáceo en su rostro y extremidades superiores e
inferiores con queja principal de disminución en la agudeza visual, sensación de cuerpo extraño y dolor en los ojos.
El examen bajo lámpara de hendidura mostró conjuntiva
inyectada, queratopatía punteada superficial y disminución
de producción de lagrimas en la prueba de Schirmmer. Se
realizó una evaluación dermatológica con biopsia, la cual
concluyó que el paciente tenia enfermedad crónica del injerto contra el huésped y se obtuvo un diagnóstico de queratoconjuntivitis sicca secundario a esta condición.
32 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
CHRONIC EOSINOPHILIC
LEUKEMIA:
A rare cause of
Hypereosinophilic Syndrome
Cristina Ortiz MDa*
Madeline Jimenez MDa
Nelson A. Matos MDa
Damas Hospital Transitional Residency and Medicine Department, Ponce, Puerto Rico.
Corresponding author: Medical Education Office, Edificio Parra 2225, Suite 407, Ponce, PR, 00717-1320. E-mail: ortizfuentesmd@gmail.
com
Presented at the 60th Hospital Damas Scientific Meeting, Ponce Puerto Rico, 2012.
ABSTRACT
Hypereosinophilic syndromes are a wide group of entities. We present a 24-year-old-male with
left lower quadrant abdominal pain, elevated eosinophil counts and splenomegaly. Molecular
analysis was positive for FIP1L1-PDGFRA gene compatible with chronic eosinophilic leukemia.
He was managed with Imatinib producing resolution of the disease.
T
Index words: chronic, eosinophilic, leukemia, hypereosinophilic, syndrome
INTRODUCTION
The hypereosinophilic syndromes (HES) constitute a rare
heterogeneous group of disorders. These are defined as
persistent and marked blood eosinophilia (more than 1.5
x 109/L for more than six consecutive months), associated
with evidence of eosinophil-induced organ damage, where
other causes of hypereosinophilia such as allergic, parasitic, and malignant disorder have been excluded (1). HES
are found most commonly in males between the ages of
20-50 years old with very rare cases in children (2).
HES can be divided in several subcategories. Among
those, chronic eosinophilic leukemia (CEL) has been described with same findings as HES, plus a clonal cytogenetic abnormality. The World Health Organization (WHO)
incorporated as standard procedure for diagnosis of CEL
the presence of FIP1L1-PDGFRA gene in molecular analysis (3). Such modification promoted difficulties towards
obtaining overall prevalence of CEL. Currently, there is
no published evidence that sustains disease epidemiology
on CEL.
Nevertheless, a patient may be evaluated in routine medical exams and lead to findings that suggest unknown hypereosinophilia (4). Further evaluation is needed to avoid
eosinophil infiltration that can be produce multiple organ
damage (1).
We report a case of a young Hispanic male with hypereosinophilia positive for FIP1L1-PDGFRA gene successfully managed with Imatinib.
Case History
This is a case of a 24-year-old-male athlete who visits the
emergency room with the chief complaint of abdominal
pain three days prior to admission. He referred his pain
mainly localized in the left lower quadrant, radiating towards his inner thigh with an intensity of six out of 10
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 33
and colicky in nature. Upon further questioning he referred
he also presented difficulty urinating. Patient denied fever,
nausea, vomiting, diarrhea, constipation, hematochezia,
melena, hematuria or weight loss. Patient recalled that the
last four months he has felt weak. HIV and VDRL were
performed with a negative result.
The past medical history was positive for episodes of hypoglycemia and renal stones. He denied any allergies. He
denied smoking, illicit drugs use or alcohol consumption.
Family history was non-contributory with no first or second-degree member with cancer history.
On examination his BP was 99/52 mm Hg, heart rate 63
beats/min, respiratory rate 19 breath/min, temperature of
36.4 OC. The only remarkable finding on physical exam
was positive bowel sounds, CVA positive, abdomen Figure 1: C.T. Scan of the abdomen and pelvis: No lymphadenopanon-tender, non-distended, no guarding and no rebound thy, normal bladder, normal liver, normal adrenal glands.
tenderness. The remainder of the physical exam was normal.
His laboratories showed a WBC 12.6 K/uL, hemoglobin
9.2 g/dL, hematocrit 26.8 %, platelets 60 K/uL, neutrophils
10%, lymphocytes 17%, eosinophils 71%. Iron 69 ug/dL,
iron binding capacity 201 ug/dL and a ferritin of 429 ng/
mL.
The urinalysis showed yellow color, pH 5, leukocyte esterase negative, glucose normal, ketones negative, blood
negative, protein negative, and 2-5 hyaline casts.
A renal ultrasound revealed no evidence of hydronephrosis, nephrolithiasis or focal lesions. An incidental finding
was splenomegaly.
absolute eosinophil count of 9,124 with 61% eosinophils
and pancytopenia. These findings suggested hypereosinophilic syndrome and the patient was started on Gleevec
100 mg po daily. Bone marrow aspiration was performed
and diagnosed with chronic eosinophilic leukemia with deletion of 4q and formation of FIP1L1/PDGFR-A fusion.
Follow up visits revealed steady and progressive improvement of eosinophilia and normalized eosinophil count with
improvement of pancytopenia as well.
DISCUSSION
organ damage and this effect may be prevented by early
detection and treatment (1,2). It is clearly proven that in
many cases a diagnosis of Idiopathic Hypereosinophilic
Syndrome can be used after exclusion of common causes
and after all etiologies of hypereosinophilia have not been
ruled out yet (2).
In this case report we present a “typical” case of CEL,
where a patient shows constitutional common symptoms
as fatigue, weakness and gastrointestinal distress. As part
of workup the only two noticeable features are his elevated
eosinophil count and CT scan with incidental finding of
splenomegaly. Hematologist/oncologist staff performed a
thorough evaluation of the patient and as part of their recommendations a bone marrow biopsy and molecular analysis was made. The result of these two revealed marked
eosinophilia and the identification of FIP1L1-PDGFRA
gene. As part of our research, several case reports were
found in our literature and a comparative analysis is outline in Table 1.
Over the years little information has been reported on
HES prevalence and incidence (1). CEL is part of that
wide group of secondary causes of hypereosinophilic
syndromes (5). Several years ago there was a significant
overlap between these two entities HES and CEL, where
CEL patients were classified as idiopathic HES (5). As scientists conducted various research studies, an outstanding
discovery of several fusion gene mutations enabled a more
precise classification of HES. This contribution allowed a
separation and new branching of this pathology, where pa- Among similarities between these individuals we found
tients with the identification of FIP1L1-PDGFRA gene are (6,7,8,9):
now classified as CEL (5).
They first underwent a workup for commoner causes of
hyperosinophilia
After literature review, it has been clear that currently there They all had positive response to Imatinib treatment
is little known about how many new cases of CEL are re- They were are FIP1L1-PDGFRA gene positive
ported yearly. As part of the reported data HES has predominance in males (2). CEL may be a rare disease, but Among differences in these individuals (6,7,8,9):
the importance of its diagnosis and gene detection is based Wide range of presentation, beginning with asymptomatic
on the concern that these eosinophils may cause multiple patients, some with constitutional symptoms, and one with
HIV wasnegative, Hept A Ab IgM negative, HBsAg negative, Hept B core Ab negative, HCV Antibody negative.
Figure 1 shows the CT-Scan of the abdomen and pelvis
with no lymphadenopathy, normal bladder, normal liver, Figure 2: Bone Marrow Biopsy: Increased eosinophilic forms
normal adrenal glands, but positive for splenomegaly.
Bone Marrow Aspirate described scant cellular marrow
with marked eosinophilia, approximately 30% of cellularity. Trilineage hematopoiesis with no increase in CD34+
blasts or even dysplasia (see Figure 2).
Flow Cytometry: Increased eosinophils, approximately
26% of cellularity, with no increase in CD34+ blasts (see
Figure 3).
FISH: Cryptic deletion of 4q and formation of FIP1L1/
PDGFR-A fusion consistent with chronic eosinophilic leukemia with FIP1L1/PDGFR-A fusion, a rare neoplasm and
long-term prognosis is uncertain (see Figure 4).
The patient was started on Famotidine 20 mg po bid and
Oxycodone and Acetaminophen 5/325 mg every 4-6 hours
PRN for pain management. After a few days of admission,
the patient was consulted to the hematology oncology
service for evaluation of splenomegaly and low platelet Figure 3: Flow Cytometry: Increased eosinophils , approximately
count. Laboratory workup revealed eosinophilia with an 26 % of cellularity.
34 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Note: Our case report seen in bold letters.
Table 1: Comparative analysis.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 35
organ damage
Wide age presentation from 24 years old to 58, with a highlight that three were above the age of 50
Only one female case
No race preference observed
When this information is compared with older data, it can
be observed the wide variety of clinical presentations of
CEL (6,7,8,9). When reviewing Table 1 we see that three
out of 6 of these cases the patients were asymptomatic as
it has been reported on previous data that many patients
present only with eosinophilia (6,7,8,9).
Another contribution to the literature is that even though
the range of ages on HES has been from 20-50 years old
and CEL has been found to peak in the 40’s (10), our patient represents the youngest that was diagnosed with CEL
at 24 years old. This observation indicates that younger patients must also go through an elaborated work up if eosinophilia is found without a specific known etiology.
A point of interest illustrated in these cases in the finding
of gene fusion FIP1L1-PDGFRA and its positive response
to Imatinib treatment. This has an important clinical significance because treatment with Imatinib has demonstrated close to a 100 percent resolution of eosinophilia
in patients with a positive FIP1L1-PDGFRA gene and on
the cases presented it also showed high-resolution rate
(6,7,8,9,10). This evidence highlights the importance of
adequate diagnosis of this branch of HES, known as CEL
with FIP1L1-PDGFRA fusion gene, to implement Imatinib treatment and aim for prevention of temporary and
permanent organ damage.
7) Lambert, F., Heimann, P., Herens, C., Chariot, A., Bours, V. (2007).
A Case of FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia
with a Rare FIP1L1 Breakpoint. Retrieved July 2007, from http://www.
ncbi.nlm.nih.gov/pubmed/17591942
8) Messie, K., Vovor, A., Kueviakoe, I. M., Sallah, L. K., Agbetiafa, K.,
Segbena, A. Y. (2011). Clonal Hypereosinophilic Syndrome: Two Cases
Report in Black Men from Sub-Saharan Africa and Literature Reviews.
Retrieved January 2011, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226243/
9) Willliams, C., Kalra, S., Nath, U., Brown, N., Wilson, V., Wilkins,
B. S., Neylon, A., J. (2008). FIP1L1-PDGFRA positive chronic eosinophilic leukaemia and associated central nervous system involvement.
Retrieved February 2008, from http://jcp.bmj.com/content/61/5/677.
abstract
10) Sobecks, R.M., Theil K. (2009) Chronic Leukemias. Retrieved January 1 2009, from http://www.clevelandclinicmeded.com/medicalpubs/
diseasemanagement/hematology-oncology/chronic-leukemias/Table 1:
Comparative Analysis of CEL Case Reports.
RESUMEN
El síndrome hipereosinofílico lo comprenden una serie de
entidades. Describimos un varón de 24 años con dolor en
el cuadrante izquierdo del vientre, contaje elevado de eosinófilos y esplenomegalia. Análisis molecular revelo la
presencia del gene FIP1L1-PDGFRA compatible con el
diagnostico de leucemia eosinofílica crónica. El manejo
con Imatinib produjo resolución de su enfermedad.
VITILIGO, JAUNDICE
AND CHOLESTASIS IN
A MIDDLE AGED
WOMAN:
A Case Report
Vanessa Seiglie MDa*
Viviana Freire MDa
Bárbara Rosado-Carrión MDb
Rafael Bredy MDb
Carla Lozada MDc
Transitional Residency Program, Damas Hospital, Ponce, Puerto Rico.
Medicine Department, Damas Hospital & Ponce School of Medicine and Health Science, Ponce, Puerto Rico.
c
VA Caribbean Healthcare System.
*Corresponding author: Vanessa Seiglie MD - 2213 Ponce By Pass, Ponce, Puerto Rico 00731. E-mail: vanessa_sq@hotmail.
com
a
b
ABSTRACT
REFERENCES
Primary biliary cirrhosis with autoimmune hepatitis (PBC/AIH) overlap is characterized
by uncertain behavior and no standardized treatment. A 35 year-old-woman with vitiligo, jaundice and cholestasis fulfilled serological, biochemical and histological criteria for
PBC/AIH overlap. Treatment was initiated with conventional doses of corticosteroid and
ursodeoxycholic acid. Her condition worsened with poor biochemical hepatic response.
The course of action was altered to institute high doses of ursodiol, azathioprine and
corticosteroids for extended periods of time. This case illustrates how increased understanding of the overlap PBC/AIH leads to new interventions. Recognition of these variant forms is critical for institutional management of both disease entities.
1) Roufosse, F.E., Goldman, M., Cogan E. (2007). Hypereosinophilic
Syndromes. Retrieved September 2007, from http://www.OJRD.com/
content/2/1/37
2) Gotlib, J., Cools, J., Malone III, J., Schrier, S., Gilliland, D.G.,
Coutre, S.E. (2003). The FIP1L1-PDGFR-α fusion tyrosine kinase in
hypereosinophilic syndrome and chroic eosinophilic leukemia: implications for diagnosis, classification and management. Retrieved November 20, 2003, from http://bloodjournal.hematoloylibrary.org/content/103/8/2879.full.html
3) Eosinophilic leukemia and ideopatic hypereosinophilic syndrome
are mutually exclusive diagnoses. (2004, December 1). Retrieved December 1, 2004, from http://bloodjournal.hematologylibrary.org/content/104/12/3836.full
4) Thiele, J. (2009). Philadelphia Chromosome-Negative Chronic Myeloproliferative Disease. Retrieved August 2009, from http://www.ncbi.
nlm.nih.gov/pubmed/19605821
VIDEOS
MEDICO-CIENTIFICOS
5) Venkata, S. (2012). Hypereosinophilic Syndrome. Retrieved January
2012, from http://emedicine.medscape.com/article/202030-overview
6) Vigna, E., Lucia, E., Gentile, M., Mazzone, C., Bisconte, M.G., Gentile, C., Armentano, A., Ottaviani, E., Rondoni, M., Martinelli, G., Morabito, F. (2007). PDGFRalpha/FIP1L1-positive chronic eosinophilic
leukemia presenting with retro-orbital localization: efficacy of imatinib treatment. Retrieved April 2007, from http://www.ncbi.
nlm.nih.gov/pubmed/17549478
36 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
www.asocmedpr.org
P
Index words: vitiligo, jaundice, cholestasis, middle, aged, woman, case, report
a different genetic background which determines the clinical, biochemical and histological appearance of one autoPrimary biliary cirrhosis (PBC) and autoimmune hepatitis immune disease entity; and a representation of the middle
(AIH) are the two most prevalent autoimmune disease of of a continuous spectrum of two autoimmune diseases (1the liver and are classically viewed as distinct liver diseas- 5).
es. However patients presenting with clinical, biochemical,
serological and histological features reminiscent for both Epidemiologic data about autoimmune hepatitis in different
diseases, either simultaneously or consecutively have been ethnic groups in the United States, and particularly among
repeatedly recognized. The pathogenesis of PBC/AIH over- Hispanic group is limited (6). When talking about PBC it is
lap syndrome is debated and it remains unclear. Different known that the disease is more prevalent in non-Hispanic
pathophysiological mechanisms discussed includes: a pure white individuals, particularly women. Hispanic and Africoincidence of two independent autoimmune diseases; can American individuals often have more advanced and
INTRODUCTION
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 37
more severe disease compared with non-Hispanic white
individuals at the time of diagnosis (7). There is no robust epidemiological data on PBC/AIH overlap syndrome
in the USA or Puerto Rico. Precise prevalence of overlap
is unknown, but approximately 10% of adults with AIH or
PBC may belong in this overlap category (8). In the two
largest study using combination of AIH and PBC criteria,
the prevalence of PBC/AIH overlap among PBC patients
was in the range of 4.8 to 9.2% (3). Patients with PBC/AIH
overlap syndrome might have a more severe disease with
worse clinical outcomes compared to patients with one of
the diseases alone. This emphasizes the notion that overlap
syndrome should always be considered once PBC has been
diagnosed (9).
As separate entities each disease have their own diagnostic criteria. The diagnosis of AIH is based on the revised
original scoring system of the international autoimmune
hepatitis group (IAHG); which includes a liver biopsy with
interface hepatitis, increased aminotransferase levels, seropositivity for antinuclear antibodies (ANA) and/or smooth
muscle antibody (SMA) greater than 1:80, and the exclusion of other conditions that cause chronic hepatitis and
cirrhosis (2). The diagnosis of PBC should be suspected in
the setting of chronic cholestasis after exclusion of other
causes of chronic liver disease. The diagnosis is suspected
based on cholestasis serum liver tests and then confirmed
tests with antimitochondrial antibodies (AMA) (10). Figure 1 despicts the suggested diagnostic algorithm for patients with suspected PBC.
Because of the limited applicability of the different diagnostic scores, to AIH/PBC syndrome, another approach
based on the characteristics of PBC and AIH has been proposed and requires the presence of at least two of the 3
accepted criteria of both diseases for diagnosing AIH/PBC
overlap syndrome, whereby histologic evidence of moderate to severe lymphocytic piecemeal necrosis (interface
hepatitis) is mandatory (5). Table 1 shows the diagnostic
criteria of AIH/PBC overlap syndrome.
Although it may be difficult to distinguish AIH from PBC
on histologic grounds, accurate diagnosis is important because treatment for AIH differs from that for PBC (11).
The low prevalence of PBC/AIH has made controlled therapeutic trials difficult in these patients. Thus therapeutics
recommendations rely on the experience in the treatment
of either PBC or AIH and on retrospective, non-randomized studies (5). We present a case of a 35 year-old-woman
with AIH and PBC that fulfills the diagnostic criteria of the
overlap syndrome and had poor response to conventional
therapy along with our experience achieving remission of
disease.
Case History
A 35 year-old-woman presented to the medical clinic because of increasing yellowing of her eyes and darkening
of her skin of six months of evolution. Seeking medical
attention was delayed because the patient attributed darkening of the skin to sun exposure. Due to family members
continuous concern of her tinged sclera and skin tone she
addresses matters. Patient denied fever, nausea, general malaise, decreased appetite or weight loss, pruritus,
abdominal pain or development of dark urine during the
previous six months. On examination, the vital signs were
normal, and the conjunctivae and skin were icteric, with
no spider angiomas, palmar erythema, telangiectasia and
a depigmented irregular patch of skin approximately 3 x 3
cm with irregular borders on her right index finger. Neck
examination showed no palpable thyroid or lymphadenopathy. The abdomen was soft, without tenderness, distention or organomegaly. Neurologic exam revealed normal
attention, speech and no asterixis. The remainder of the
physical examination was normal.
Three years earlier patient was diagnosed with vitiligo only
noticeable on her right index finger, otherwise she had no
previous past medical history. She was a nulliparous women that has never received blood transfusions, undergone
body piercing, no recent travel outside of Puerto Rico, had
not smoked cigarettes nor drank alcohol, and did not use
intravenous drugs. She denied having industrial exposures,
recent swimming in rivers, and contact with ill persons or
trauma. She has been married for fifteen years. Her mother
had hypothyroidism and systemic lupus erythematous. Her
father suffered from arterial hypertension and passed away
at age 80 from a cerebrovascular stroke. She had three sisters, one diagnosed with mitral valve prolapse, one healthy
and one deceased at age 40 from a primary brain tumor;
there was no history of liver disease.
Renal function tests, plasma levels of electrolytes, amylase, lipase, glucose, calcium and urinalysis were normal.
Results for a complete blood count revealed thrombocytosis. Coagulation profile revealed elevated INR. Plasma
levels of alkaline phosphatase were 2360 units, total bilirubin 10.96 mg/dL, aminotransferases were five times the
upper normal limit and albumin 2.5 gm/dL and globulin
level 4.80 gm/dL. Other results can be seen in Table 2.
Abdominal ultrasound was unremarkable. Abdominopelvic CT-scan demonstrated a liver of homogenous density
with no intrahepatic or extra hepatic biliary duct dilation.
Viral markers for HIV, Hepatitis A, B and C were negative.
Markers for malignancy like CEA, CA 19-9, CA 125 and
AFP tumor where noncontributory. Seropositivity for Anti-Mitochondrial Antibodies 98.6 and Smooth Muscle antibody level of 38 was found. ANA titers negative (<1:80)
and Liver-Kidney microsomal antibodies also negative.
Diagnostic liver biopsy was performed showing portal triads with moderate to marked inflammatory infiltrate composed of lymphocytes and predominantly plasma cells (see
Figures 2 and 3).
Bile ducts at portal triads were surrounded by few neutrophils. Mild piecemeal necrosis and parenchymal cholestasis was present. A Trichrome and reticulin staining reveals
expansive focal necrosis with short septa, no bridging,
and no cirrhosis. Focal pericellular fibrosis was present.
A Methyl green pyronin staining reveals plasma cell infiltrates at portal spaces. A periodic Acid-Shiff stain, Iron
Stain and Copper Stain were negative. The biopsy finding
38 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Table 1. Diagnostic criteria of AIH-PBC overlap
syndrome.
j
was consistent with autoimmune
hepatitis and acute autoimmune
cholangitis.
DISCUSSION
The coexistence of PBC/AIH has
been shown to follow a severe clinical course and worse outcomes when
compared with either entity alone
(12). The diagnosis is challenging
and no standardized treatment strategy has been established (2, 10).
Exhaustive clinical evaluation and
challenge to achieve biochemical
response after proposed conventional therapy prompted us to report our
experience. During baseline presentation our patient fulfilled individual
criteria to diagnose each condition
separately (2, 10). A true overlap between PBC/AIH was recognized after using the template scoring system
proposed by IAHG. In addition, biochemical, serological, immunological data were collected at the same
time as liver histology (see Figure 4).
Several reports have concluded that
a combination of ursodeoxycholic
acid (UDCA) and corticosteroids
is required in most cases to obtain
a complete biochemical response
(12). Glucocorticoids suppress the
cell-mediated immunologic attack
against liver cells and ursodeoxycholic acid reduces concentration of
cholesterol in endogenous bile acids
accumulated. Both drugs delay histologic progression and improve biochemical indices. According to the
practice guidelines of the American
Association for the study of Liver
Disease the patient was started on
Table 2: Laboratory data.
Figure1: Suggested
diagnostic algorithm
for patients with suspected PBC
Figure 2: Liver biopsy Microscopic
view 10X of Interface Hepatitis.
j
Figure 3: Liver
biopsy 40 x interface hepatitis with
plasma cells
j
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 39
13-15 mg/kg of UDCA for PBC and daily monotherapy with prednisone 60 mg for AIH. For PBC the effect of treatment was based on the response of alkaline
phosphatase and bilirubin. For AIH the biochemical
endpoint was improvement in serum asparte aminotransferase, bilirubin and α-globulin levels. Criterias to
evaluate for remission in patients with the overlapped
syndrome remains undefined (12). We used separate
standard therapy for each condition to define improvement during the course of treatment.
4. Czaja Albert J. Overlap syndrome of primary biliary cirrhosis and 14. .Clinical Practice Guidelines: Management of Cholestatic Liver
autoinmune hepatitis: A foray across diagnostic boundaries. Journal of Disesase. European Assoc. for the study of liver Journal of hepatology
Hepatology 44(2006)251-252
2009(51) 237-267.
5. Ulrich Beuers, Kirsten M. Boberg, Roger W. Chapman, Olivier
Chazouille`res, Pietro Invernizzi, David E.J. Jones, Frank Lammert,
Albert Pare`s, Michael Trauner; European Association for the study of
liver EASL Clinical Practice Guidelines:Management of cholestatic liver diseases. Journal of hepatology 2009(51) 237-267.
Unlike conventional cases this case behaved as severe
and therapy had to be optimized in an individualized
fashion. The combination of prednisone and azathioprine is the preferred treatment for the hepatic feature rather than the use of prednisone alone, due to its
lower occurrence of corticosteroid related side effects
(2, 10). Our patient initially presented with marked
cholestasis that impaired us to add azathioprine during
the first months due to its known hepatotoxicity. After Figure: 4 Patient’s laboratory results consistent with PBC and
one month of treatment, minimal biochemical response AIH
in the levels of alkaline phosphatase (2360) bilirubin
(10.96) and aminotransferases (>200) was appreciated.
At this point, guidelines would indicate tapering down
prednisone to a maintenance therapy dose of 20 mg and
below daily (2). Ninety adults have improvements of
serum AST and bilirubin in two weeks after receiving
conventional treatment, which clearly was not our case
(13-17). The dose of prednisone could not be gradually lowered on the fourth week, a difficult decision to
face due to corticosteroid related side effects that could
harm the patient. After three months of this treatment,
corticosteroid monotherapy was changed to combination treatment consisting of azathioprine & prednisone
when bilirubin levels had lowered to less than 1.5. The
poor improvement seen at her fourth months of treatment with azathioprine 50 mg, prednisone 20 mg and
UDCA 900mg (13-15mg/kg/day) in aminotransferase
levels and alkaline phosphatase categorized this case as
a treatment failure. Treatment failure connotes worsening laboratory features despite compliance with therapy
and it justified the institution of higher doses of therapy.
The course of action was an increase of azathioprine to Fig.5 Treatment management for AIH/PBC overlap syndrome
150mg daily, UDCA to 23 mg/kg/day and prednisone to
30 mg a day (see Figure 5).
Over the course of one year of optimization there was grad- Describing these uncommon findings and pooling our exual improvement in gamma-glutamyl transferase, alkaline perience with other reports helps define new therapeutic
phosphatase, bilirubin, and aspartate aminotransferase (see interventions and characterize patients who are unlikely to
Figure 6). The average duration of treatment was 18-24 respond appropriately.
months to start evaluating for remission (2, 10). The ideal
treatment endpoint is normalization of liver tests and liver REFERENCES
tissues at 24 months. This was achieved six months later.
Our case strongly demonstrated that an increased understanding of the overlap PBC/AIH could lead to new interventions. Conventional therapy was complicated by the
refractory nature and uncertain behavior of the disease.
Areas for future research could include addressing Hispanic groups and treatment interventions specific for overlap
syndrome. The unusual institution of high doses of UDCA,
corticosteroid and azathioprine for extended periods of
time makes our experience unique.
1. Czaja Albert J.Autoimmune hepatitis and its variants syndrome. Gut
2001(49)589-594
2. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM. (June 2010). Diagnosis and Management of AIH.
AASLD Practice Guidelines. Retrieved on Nov 2011 from www.aasld.
org/practiceguidelines/Documents/AIH2010.pdf
3. Boberg, KM,. Chapman RW, Hirschfield, GM, Ansgar WL, Manns
MPOverlap Syndromes:The International Autoimmune Hepatitis
Group(IAIHG) Position Statement on a Controversial Issue. Journal of
Hepatology 2011(54)374-385
40 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
15. Czaja Albert J. Difficult Treatment Decisions in autoinmune hepatitis. World Journal of Gastroenterology 2010February 28(8)934-947.
16.
ChazoulleresO,WendumD,SerfatyL,Montembault
S,Rosmorduc O,Poupon R. Primary biliary cirrosis autoinmune hepatitis overlap síndrome: clinical features and response to therapy. Hepatology
6. Carrion Andres F. Ravi Ghanta; Olveen Carrasquillo;Paul Martin 1998(28)296-301.
Chronic liver Disease in the Hispanic Population of the United States.
Clinical Gastroenterology and Hepatology 2011(10)834-841
17. Czaja,AJ. (April 3 2012) Advances in the current treatment of autoimmune hepatitis. Digestive Diseases and Sciences. Retrieved on
7. Peters MG, Di Bisceglie AM, Kowledley KV, et al.Differences be- April 2012 from www.springerlink.com/content/mx8213681316p513/.
tween Caucasian, African American, and Hispanic patients with primary biliary cirrosis in the United States. Hepatology 2007(46)769-775
8. Poupon R, Chazouilleres O, Corpechot C, Chretien Y. Development
of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology 2006(44)85–90
9. Rust C, Beuers U. Overlap syndromes among autoimmune liver diseases. World J Gastroenterol 2008(14)3368–3373
10. Lindor KD, Gershwin ME,Kaplan M, Bergasa NV, Heathcote J.(July2009). Primary Billiary Cirrhosis. AASLD Practice Guidelines.
Retrieved on Dic 2011 from www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/PrimaryBilliaryCirrhosis7-2009.pdf
11. Washington, M. Autoimmune liver disease:overlap and outliers.
Modern Pathology 2007(20),S15-S30.
12. Chazoulliers O,Wendum D, Serfaty L,et al. Long term outcome and
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in corticosteroid-treated severe autoimmune chronic active hepatitis.
Gastroenterology1988(95)448-453.
RESUMEN
La cirrosis biliar primaria (CBP) asociada a la hepatitis
autoinmune (HAI) solapados se caracterizan por un comportamiento clínico errático donde no existe una terapia
convencional estandarizada. Una mujer de 35 años con vitiligo, ictericia y colestasis hepática llenaba los requisitos
serológicos, bioquímicos e histológicos del síndrome solapado CBP/HAI). El manejo se comenzó con dosis convencionales de corticosteroides y ácido ursodeoxicólico. Su
condición empeoro con una respuesta bioquímica hepática
pobre. Se altero el curso de manejo usando dosis altas de
ursodiol, azathioprine y corticosteroides por un periodo
largo de tiempo consiguiendo remisión. Este caso ilustra como atender los vaivenes bioquímicos del síndrome
solapado CBP/HAI con nuevas intervenciones y ayuda a
reconocer las formas variantes criticas para que las instituciones puedan manejar ambas condiciones.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 41
Including Clinical Research Trials in
Your Practice
Becoming a clinical trials investigator offers you the
following benefits:
• A greater awareness of cutting-edge therapies and the ability to access new treatments;
• A new and/or increased patient base that seeks access to state-of-the-art science and treatments
only available through clinical trials;
• Greater access to sponsored clinical trials;
• Ultimately, satisfaction from knowing that you are contributing to the advancement of cancer
care.
• Clinical trials can benefit your patients in the following ways.
• Trials within your practice allow patients additional treatment options - beyond standard care that may be on the cutting edge.
• Through a clinical trial, patients may have access to investigational agents, devices, imaging studies, technology, equipment, or novel diagnostic techniques at no additional cost.
• Clinical trial participants have expressed satisfaction and appreciation for the attention they received during the trials. Also cited, as a benefit is the close follow-up that participants receive after
treatment.
PUERTO RICO MEDICAL ASSOCIATION
BILATERAL LARGE
PALPABLE CERVICAL
MASSES: Not always a
malignant or infectious
process
Luis A. Figueroa-Jiménez MDa*
Mónica Santiago-Casiano MDb
Emmanuel González-Irizarry MDc
Amy González-Marquez MDa
William Cáceres-Perkins MDb
Mildred Padilla-Ferrer MDa
Anarda González MDd
Verόnica Santiago-Casiano MSe
Internal Medicine Department, San Juan City Hospital, San Juan, Puerto Rico.
Hematology–Medical Oncology Section, VA Caribbean Healthcare System and San Juan City Hospital, San
cuan, Puerto Rico.
c
Internal Medicine Department, VA Caribbean Healthcare System, San Juan, Puerto Rico.
d
Pathology Department, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.
e
San Juan Bautista School of Medicine, Caguas, Puerto Rico.
*Corresponding author: Luis A. Figueroa-Jiménez MD - Internal Medicine Department, San Juan City Hospital, CMMS #79 P.O. BOX 70344 San Juan, Puerto Rico 00936-8344. Email: [email protected]
a
b
ABSTRACT
Madelung’s disease is an extremely rare disorder of unknown etiology
characterized by multiple, non-encapsulated, infiltrative lipomas located
symmetrically on the trunk, neck, and proximal parts of the limbs. Approximately 200 patients have been reported in the medical literature. In
this case report we present an extremely unusual case of multiple symmetric lipomatosis compatible with Madelung’s disease.
Index words: bilateral, large, palpable, cervical, mass
42 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
M
INTRODUCTION
Madelung’s disease, also known as Multiple Symmetric
Lipomatosis or Launois-Bensaude Syndrome, is an extremely rare disorder of unknown etiology characterized
by multiple, non-encapsulated, infiltrative lipomas located
symmetrically on the trunk, neck, and proximal parts of
the limbs (1). It was first described in 1846. Since then approximately 200 patients have been reported in the medical
literature (1, 9, 11). Although the pathogenesis of lipoma
formation in Madelung’s disease remains unclear, hypothesis suggest this is a mitochondrial DNA disorder, though
the etiology still remain obscure (2-4). Most affected
patients are middle-aged males with a history of chronic
alcoholism. There is a predilection for people from the
Mediterranean with the higher incidence in Italy (5).
Figure 1: Neck of the patient disclosed; large bilateral neck
masses.
We report a case of a 61-year-old-man with a medical history of chronic alcoholism that presented a right lower extremity ulcer and incidental finding of multiples masses in
his cervico-facial, nuchal and thoracic regions that gradually enlarged over a period of six years.
Case History
This is a 61-year-old-man with past medical history of
chronic alcoholism for the last forty years, arterial hypertension and cervical and thoracic masses for the last six
years. Independent in all activities of daily living until a
month ago when he developed a gradually worsening right
lower extremity ulcer. Patient denied fever, chills, weight
loss, night sweats, anorexia, nauseas, vomiting, diarrheas,
shortness of breath, chest pain or palpitations.
Upon physical examination in the cervical region, neck
and thorax, large palpable bilateral masses were palpable.
The masses were soft, with no definite margin, and movable; there was no tenderness on palpation or associated
erythema (see Figure 1). In addition, a right medial tibia
stasis ulcer was observed. Routine laboratories were within
normal limits. An MRI of the head and neck had the following findings: multiple symmetric lipomatosis predominantly from C4-C7; the airway was patent, and no nodular enhancing components suggesting a liposarcoma (see
Figures 2 and 3). Pathology of biopsy of the neck mass
disclosed hemorrhagic, fibroconnective tissue and adipose
tissue, with associated lipodystrophy (see Figure 4).
DISCUSSION
Reports of Madelung’s disease are very rare. To the best
of our knowledge, no cases have been reported in the Hispanic population or in the Caribbean. The etiology of Madelung’s disease is still obscure. Although, is well known
that the disorder predominantly affects white males (M:F
ratio 15:1), with the incidence being highest in the Mediterranean and Italy (10). Predominantly manifests itself in
the third to fifth decade of life with history of alcoholism
up to 90% of the cases (6-8). The disease usually has biphasic course, an initial rapid growth that is followed by a
slow progressive phase (10).
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 43
Diagnosis is usually made by history and physical examination. Computed tomography, MRI and fine needle
aspiration cytology establishes the diagnosis. There has
been only one reported case of malignant transformation
in Madelung’s disease. Literature described the development of a liposarcoma( 5-6). However, reports also state
an association with malignant tumors of the digestive tract
(carcinoma of the pharynx and ceccal tumors). This was
confirmed later by the literature that reported an increased
incidence of carcinoma of the tongue and pharynx in patients with Madelung’s disease. Thus, a thorough evaluation to rule out synchronous malignancy in patients with
Madelung’s disease is mandatory (9). This can be problematic because of difficulties in distinguishing between
lipoma and well-differentiated liposarcoma. In our case
report, the pathology biopsy ruled out the possibility of
malignancy such as a liposarcoma.
Figure 2: Neck MRI disclosed marked symmetric enlargement of the adipose tissue and infiltrating in the upper thorax
without evidence of any nodular enhancing components.
There is no consensus on disease management or therapy.
Reducing alcohol consumption is recommended (7). Surgery or lipid-lowering therapy may be recommended in the
presence of symptomatic lipomas (8). For cosmetic reason, lipomatosis in Madelung's disease can be removed by
surgical excision or by liposuction techniques (12). Complete surgical removal of the tumor may jeopardize important anatomic structures because the lipomas can infiltrate
or encase these structures.
According to one report, Madelung’s disease was treated
successfully with the beta 2-agonist salbutamol, which acts
on lipolysis via adrenergic stimulation. In our case report
no action in management was taken considering that the
patient was asymptomatic.
To the best of our knowledge the occurrence of Madelung’s
disease in our patient may indicate that the disease may no
longer be solely associated with Caucasian Mediterranean
men and there are very few cases reported in Asia. Physicians in Puerto Rico should be aware of this rare entity in
alcoholic patients.
;
REFERENCES
1. J. P.Meningaud, P. Pitak-Arnnop, and J. C. Bertrand, “Multiple symmetric lipomatosis: case report and review of the literature,” Journal of
Oral and Maxillofacial Surgery, vol. 65, no. 7, pp.
1365–1369, 2007.
2. C. Plummer, et al. Multiple Symmetrical Lipomatosis — A mitochondrial disorder of brown fat. Mitochondrion 13 (2013) 269–276.
3. Lee YC, Wei YH, et al. Wernicke's encephalopathy in a patient with
multiple symmetrical lipomatosis and the A8344G mutation of mitochondrial DNA. Eur Neurol 2002;47:126-128.
4. Tomislav Bulum, et al. Madelung’s disease: Case report and review
of the literature Vuk Vrhovac University Clinic, Zagreb, Croatia. 2007
5. Andreas Gutzeit et al. Growing fatty mass in the back: diagnosis of
a multiple symmetric lipomatosis (Madelung’s disease) in association
with chronic alcoholism. Skeletal Radiol (2012) 41:489–490
6. Murphey MD, Arcara LK, Fanburg-Smith J. From the archives of the
AFIP: imaging of musculoskeletal liposarcoma with radiologic-pathologic correlation. Radiographics. 2005;25:1371– 95.
7. Smith PD, Stadelmann WK, Wassermann RJ, Kearney RE. Benign symmetric lipomatosis (Madelung’s disease). Ann Plast Surg.
1998;41:671–3.
8. Ampollini L, Carbognani P. Images in clinical medicine. Madelung’s
disease. N Engl J Med. 2011;364:465.
9. Chih-Chieh Chuang, et al. Madelung’s Disease. J Chin Med Assoc
2004;67:591-594
10. Abdurrahman Tufan, et al. An Unusual Case of Madelung’s Disease
with Multiple Atypical Fractures Vol 2012, Article ID 180506
11. Chi-Jung Tai, et al. Madelung's disease mimicking deep vein thrombosis: An unusual case. International Journal of Cardiology, 2013
12. BassettoF, et al. Surgical treatment of multiple symmetric lipomatosis with ultrasound-assisted liposuction. Ann Plast Surg 2013 May 6
RESUMEN
La enfermedad de Madelung es un desόrden extremadamente raro de etiología desconocida, caracterizado por
múltiples lipomas infiltrativos no encapsulados, localizados simétricamente en el tronco, cuello y partes próximales de las extremidades. Apróximadamente doscientos
pacientes han sido reportados en la literatura médica. Presentamos un caso extremadamente inusual de lipomatosis
simétrica múltiple compatible con la enfermedad de Madelung.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 45
Figure 3: Neck MRI disclosed no evidence of thick
septa to suggest a well-differentiated liposarcoma. The
airway was patent (see yellow arrow).
Figure 4: Hematoxylin & Eosin Stain 20x Mature adipocytes,
no evidence of malignancy.
Madelung's disease is classified in two types of lipomatosis, which is based on the distribution of fat deposits. Circumscribed masses of fatty tumors in type 1 protrude from
an otherwise lean body while the lipomatous tissue in type
2 diffuses extensively into the subcutaneous fat layer (11).
The symptoms are primarily those of disfigurement, although the patient may complain of interference with neck
motion, difficulty in obtaining a proper fit with clothing, or
in some cases respiratory difficulties (9). The fat deposits,
once present, never disappear spontaneously, and
the disease is usually progressive over a period of years
(9). Mediastinal involvement with tracheal and vena cava
compression is possible. The gastrointestinal tract may be
compressed in advanced cases, causing dyspnea and dysphagia. Massive symmetric deposition of fat leads to cosmetic deformities in the parotid region (“hamster cheeks”),
cervical region (“horse collar”) and posterior neck (“buffalo hump”) (4). In this case report, our patient was asymptomatic, however, upon physical examination, hamster
cheeks, horse collar and buffalo hump were evident.
44 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
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PRIMARY CLEAR
CELL CARCINOMA
OF THE LUNG WITH
SALIVARY GLAND
TYPE FEATURES
Miguel Albino-González MDa*
Haydee González-Hidalgo MDb
Modesto González Del Rosario MDb
Noel Totti-Veray MDb
Carmen M. Gurrea MDb
Juan Vilaro MDb
Amy Lee González-Márquez MDc
Hematology–Medical Oncology Section, VA Caribbean Healthcare System and San Juan City
Hospital, San Juan, Puerto Rico.
b
Hospital Auxilio Mutuo, San Juan, Puerto Rico.
c
Internal Medicine Department, San Juan City Hospital, San Juan, Puerto Rico.
*Corresponding Author: Miguel Albino-González MD - Hematology-Medical Oncology Section,
VA Caribbean Healthcare System and San Juan City Hospital, CMMS #79 P.O. BOX 70344 San
Juan, Puerto Rico 00936-8344. Email: [email protected]
a
ABSTRACT
Clear cell carcinoma of the lung is very rare, with few cases reported in the medical literature. Review of case studies show that these tumors have significant variation in clinical outcome, including
metastatic disease. We present a very unusual case of primary clear cell lung carcinoma of salivary
gland type.
Index words: primary, clear, cell, carcinoma, lung, salivary, gland
P
INTRODUCTION
Primary clear cell carcinoma (CCC) of the lung is a rare
disease, of unknown etiology, with few cases described in
the medical literature (1-10). It is a subtype of large cell
lung cancer according to the World Health Organization
(WHO) classification scheme (1). Upon further workup,
tumors displaying clear cell features in the lung can often be traced to a primary source outside the lungs, mainly
the kidneys or ovaries, though this is not always the case.
Review of the medical literature reveals that these tumors
have a wide range of outcomes, which range from benign
to frankly malignant. This highlights the need to understand and better characterize these tumors.
Primary salivary-type lung tumors are also very rare, accounting for a minimal percentage of all lung tumors
(0.1%). They are believed to originate from submucosal
glands of the tracheobronchial tree, likely due to structural
homology between the various exocrine glands. Common
subtypes include adenoid cystic carcinoma and mucoepidermoid carcinoma. In this disease there is a higher incidence in women than men, usually presenting with cough
and dyspnea. The carina, trachea, and main stem bronchi
are the most common sites of involvement. Favorable outcomes have been obtained with surgical treatment. However, clinical course is not always indolent and recurrence is
common in cases where complete resection is not achieved
(7). In a group of 62 patients diagnosed with primary salivary type lung cancer at Mayo Clinic in Rochester, MN,
30% had metastatic disease (9).
Case History
A 46-year-old Hispanic woman, non-smoker, with a three
year history of recurrent upper respiratory tract infections
and persistent bronchospasm poorly responsive to standard
bronchodilator therapy presented with a two week history
of worsening non-productive cough, shortness of breath
and an unintentional weight loss of 15 pounds in a three
month period. Chest X-ray was unremarkable. Secondary
to persistent symptoms a chest computed tomography (CT)
scan with intravenous contrast was performed. It revealed
an approximately 5 cm x 4 cm triangular-shaped mass extending from the anterior left lung apex to the level of the
pulmonary artery and superior aspect of the greater vessels
(see Figure 1). Bronchoscopic examination was remarkable for a left upper lobe endobronchial mass occluding the
entire apical segment.
A left upper lobectomy was subsequently performed. A 3.8
x 2.5 x 2 cm mass causing complete occlusion of the lumen
was found. Pathology revealed solid lobules of clear epithelial cells with relatively clear cytoplasm-consistent with
a clear cell tumor (see Figure 2). Modest nuclear pleomorphism was present but there was no evidence of necrosis
or relative encapsulation, suggesting a low-grade lesion.
These findings along with the fibrous strands were consistent with a diagnosis of primary clear cell lung carcinoma
of salivary gland type. Bronchial margins of resection were
involved by the tumor. Immunohistochemical analysis
was performed on the isolated tissue: positive stains were
46 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Figure 1: Chest CT scan with IV Contrast: 5 cm x 4 cm triangular-shaped mass extending from the anterior left lung
apex to the level of the pulmonary artery and superior aspect of the greater vessels.
Figure 2: Pathology: Isolated mass from left upper lobectomy: There are solid lobules of clear epithelial cells with
relatively clear cytoplasm. Fibrous strands are also noted.
Modest nuclear pleomorphism is present without necrosis
and relative encapsulation.
obtained with pancytokeratin (epithelial cell marker), C
K-7 (found in up to 100% of salivary gland tumors and lung
adenocarcinoma). Staining for CK-20 (usually positive in
transitional cell carcinoma, ovarian mucinous tumors, and
adenocarcinoma of the gastrointestinal tract) was negative. A complete workup for metastatic disease was done
with relevant imaging studies including an abdominal/pelvic-computed tomography (CT) scan and a positron-emitted tomography (PET-CT) scans, as well as tumor markers
(including CA-125). No evidence of metastases was documented and the final staging was T2N0M0.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 47
Post-operative treatment consisted of six cycles of paclitaxel and carboplatin concurrently with 3-D conformational radiotherapy (180 Gy) in 34 fractions. Patient tolerated
treatment well and has remained free of disease for 2 years;
she persists asymptomatic, with a 100% performance status, a 20-lbs. weight gain, and no evidence of local recurrence in follow-up evaluations and imaging studies at the
time this case report was written.
DISCUSSION
Although a rare disease, the latest WHO classification
scheme includes clear cell carcinoma among primary lung
tumors. This case presents a particular subtype of clear cell
carcinoma with salivary gland features. To the best of our
knowledge there are very few cases in the medical literature with this description at the moment.
Primary clear cell lung carcinoma of salivary gland type is
a very unique tumor of unknown etiology. Although favorable outcomes have been obtained with surgical resection,
these tumors have clearly demonstrated malignant potential.
2. Colby TV, Koss MN, Travis WD, eds. Tumors of salivary gland
type. Tumors of the lower respiratory tract. I n: AFIP Atlas of Tumor
Pathology. 3rd series, vol 13. Washington, DC: American Registry of
Pathology; 1995: 65–89.2
3. Edwards C, Carlile A. Clear cell carcinoma of the lung. J Clin Pathol
1985;38:880-885.
4. Gaffey MJ, Mills SE, Ritter JH. Clear cell tumors of the lower respiratory tract. Semin Diagn Pathol 1997;14:222-232.
5. Heitmiller RF, Mathisen DJ, FerryJA, Mark EJ, Grillo HC. Mucoepidermoid lung tumors. Ann Thorac Surg. 1989; 47: 394–399. CrossRef, PubMed, ChemPort, Web of Science.
6. Insae N, MD; Takayama S, MD; Nakayama M, MD; Miura H, MD;
Kimula Y, MD. Pulmonary Clear Cell Carcinoma. Journal of Surgical
Oncology, 48: 145-147. 1991.
7. Kang DY, Yoon YS, Kim HK, Choi YS, Kim K, Shim YM, Kim
J. Primary salivary gland-type lung cancer: Surgical outcomes. Lung
Cancer. 2011 May;72(2):250-4. Epub 2010 Sep 29.
8. Masahiro Kitada, Keisuke Ozawa, Kazuhiro Sato, Satoshi Hayashi,
Naoyuki Miyokawa and Tadahiro S asajima. Clear cell carcinoma of the
lung. General Thoracic and Cardiovascular Surgery Volume 58, Number 2, 87-90, DOI:10.1007/s11748-009-0471-8.
9. Molina JR, MD; Marie Christine Aubry, J. Primary salivary glandtype lung cancer Spectrum of clinical presentation, histopathologic and
prognostic factors. Cancer. Volume 110, Issue 10, pages 2253–2259, 15
November 2007.
10. Yammamato T, Takuya Yazawa, Takesaburo Ogata, Eiichi Akaogi,
Kiyofumi Mitsui. Clear cell carcinoma of the lung: a case report and
review of the literature. Lung Cancer. Volume 10, Issues 1-2, October
1993, 101-106.
In this patient we used concurrent chemotherapy and radiation after a left upper lobectomy in a patient with positive tumor margins and poor respiratory reserve, which
precluded a more extensive surgery. This case illustrates
the need to better characterize these lung tumors in order
to set standards of treatment, particularly in cases in which
there is marginal involvement, residual disease after sur- RESUMEN
gery, and/or metastatic disease.
El carcinoma de célula clara de pulmón es muy raro, con
pocos casos reportados en la literatura médica. Repaso de
REFERENCES
estos casos muestra como estos tumores tienen variaciones
1. Brambilla E, W.D. Travis, T.V. Colby, B. Corrinz, Y. Shimosato. clínicas significativas, incluyendo metástasis. Presentamos
The New World Health Organization classification of lung tumours. Eur un caso raro de carcinoma de célula clara primario del pulRespir J 2001; 18: 1059–1068.
món de tipo de glándula salivaria.
48 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
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ADENOCARCINOMA IN
THE ILEOSTOMY OF A
PATIENT WITH
LONG-STANDING
ULCERATIVE COLITIS:
A Case Report and Review
of the Literature
Ada N. Acosta Martínez MDab*
Francisco Juame Anselmi, MDab
Axel Baez-Torres MDab
Rubén Alvarez MDa
Norman Ramirez-Lluch MDc
Heriberto Sánchez MDa
Hospital de la Concepción, San Germán, Puerto Rico.
Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
c
Mayaguez Medical Center, Mayaguez, Puerto Rico.
*Corresponding author: Ada N. Acosta Martínez MD – P.O. Box 108, Boquerón, Puerto Rico, 00622. E-mail: [email protected]
a
b
ABSTRACT
Primary adenocarcinoma in a permanent ileostomy carries a poor
prognosis from other gastrointestinal malignancies. Surveillance and
identification of patient at risk for ileostomy malignancies is a challenging problem. There are not reliable biological markers. The clinical evaluation, suspicion of the disease, common presenting symptoms
including difficulty fitting the stomal appliance, bowel obstruction,
and a friable mass should be considered as part of the evaluation and
screening in a long standing terminal ileostomy. Biopsy of newly developed lesions in the periostomal area is recommended for diagnosis
and treatment. This is a case of a primary adenocarcinoma in an ileostomy forty years after total colectomy for ulcerative colitis.
Index words: adenocarcinoma, ileostomy, ulcerative, colitis
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 49
I
INTRODUCTION
Ileostomy adenocarcinoma is a rare and a late complication in patients with ulcerative colitis. The following case
is of a man with ulcerative colitis who developed signet
cell carcinoma in the ileostomy forty years after colectomy. The pathogenesis of adenocarcinoma of the ileum
at the ileostomy is not clear. It has been associated with
chronic inflammation due to ileitis, backwash ileitis, mucosal dysplasia, altered bacterial flora at the stoma site and
physical irritation of the stoma site.
Case History
A 58-years-old man with ulcerative colitis, diabetes mellitus type 2 and hypertension started with emesis, and
bloody diarrhea at age 15 years. Based on those findings
he was treated as an acute gastroenteritis. Because he continued with symptoms a sigmoidoscopy with biopsy was
performed at 16 years of age obtaining the diagnosed ulcerative colitis. He was started on steroids and sulfadiazine
with poor response to treatment. Due to continue bleeding
a total proctocolectomy with end ileostomy was performed
at 18 years old.
Figure 1: Discohesive cellular clusters and individual
cells with prominent cytoplasmic vacuolization and displaced nucleus lying in mucin pools enterostomy site
(H-E satin, X200)
Forty years after the total colectomy the patient was complaining of diffuse abdominal pain while defecating, nausea and diarrhea for the past six months getting worse with
time. He presented with increased in size of the ileostomy,
abundant secretions surrounding the stoma, and problems
with ileostomy fitting.
Physical examination was remarkable due to a coliformed
like structure that was localized between 6-9 o’clock position with a lot of associated secretions irritating the area of
the stoma.
The white blood cells were slightly elevated, the hemoglobin level was 13.6 g/dL, the platelets were 165 x 10^3.
The BUN and Cr level were 10 mg/dL and 0.66mg/dL respectively with sodium in 142 mmol/L and potasium level Figure 2: Focus of neoplastic cells involving skin abdomof 3.1 mmol/L. The PT was 12.1 secs, PTT 28.2 secs and inal wall (hematoxillin-eosin x100)
INR 1.13. The urinalysis was within normal limits and the
Carcinoembryonic antigen level was less than 0.5 ng/mL
in a range of 0-5ng/ml in smokers and 0-2.5ng/ml in non- DISCUSSION
smokers.
Primary adenocarcinoma in a terminal ileostomy is a rare
Abdominal computed tomography scan with contrast and late complication following management for ulcerdemonstrated cholelithiasis, right cortical renal 4 cm ative colitis. The literature suggests that there are thircyst, enterostomy in the right lower quadrant with a small ty-nine cases reported in literature (14). Singler and Jedd
parastomal hernia. A laparotomy was performed with re- reported the first case described in the literature in 1969
moval of the right-sided ileostomy along with the lesion (1). The incidence of small bowel malignancy in the genersurrounding it and closure of the stoma. A new left upper al population is 0.7 per 100, 000 (7,9). The ileum is mostly
quadrant ileostomy was performed. Specimen consisted of involved (49%), followed by the jejunum (29%) and duan ileostomy site that measures 5.5 cm in length x 4.5 cm odenum (22%). In contrast, adenocarcinoma of the small
in diameter and a segmented of bowel attached that mea- bowel is least commonly found in the ileum (22%), folsures 4.5 cm in length and 2.5 cm in diameter. The patho- lowed by jejunum (38%), and duodenum (40%) (7).
logic specimen demonstrated a poorly differentiated mucin
producing, signet ring type adenocarcinoma (see Figures 1 A subset of adenocarcinoma has mixed histologic patterns
including signet ring cell and mucinous histology (3-6, 18).
and 2).
Signet ring cell is a unique subtype of mucin producing
50 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
adenocarcinoma with abundant intracellular mucin and a history of colorectal cancer and the presence of backwash
compressed nucleus displaced toward the extremity of the ileitis (12). The literature review shows at least 85 percent
cell.
survivals with surgical treatment (7). Although follow up
data are sparse, a good prognosis can be expected with earThe risk of adenocarcinoma appears to be equally distrib- ly detection and resection (7, 14, 16, 17-26, 30).
uted between male and female genders (12). The average
duration of ileostomy prior to diagnosis of adenocarcino- Ileostomy adenocarcinoma is a rare and late complication
ma is approximately 27 years (7, 13, 14). The average age in long-term stoma. Education and screening is needed to
of presentation is 61.5 years with a range of 45-85 years encourage patient with ileostomy to seek medical atten(12).
tion. These tumors has a low grade of lymph involvement
and good prognosis if treat aggressively.
The etiology of ileostomy adenocarcinoma is unclear (7).
There are various hypothesis suggesting that the exposed
portion of the ileostomy to repeatedly physical trauma and REFERENCES
to chemical and physical irritation from materials or adhesive used in conjunction with ileostomy appliance pre- 1. Singler L, Jedd F L. Adenocarcinoma of the ileostomy occuring after
for ulcerative colitis: report of a case. Diseases of the Colon
disposes to chronic irritation causing metaplasia, dysplasia colectomy
and Rectu” 1969;12: 45-48.
and malignant changes (7, 8, 12, 13). In addition, bacterial
flora resembles that of normal colon with sulfomucins that 2. Borger ME, Gosens MJEM, Jeuken JWM, et al. Signet ring cell difis not found in the small intestine. The sulfomucins lead to ferenciation in mucinous colorectal carcinoma. J pathol 2007;212:278histological changes like inflammatory infiltration, colonic 286.
metaplasia, and epithelial hyperplasia (12,14).
3. Kakar S, Smyrk TC. Signet ring cell carcinoma of the colorectum:
Ulcerative colitis has an increased malignant potential. The
extension of the colitis, the length of the disease and age
of onset have been associated with the severity of the disease (7, 11, 13). Stomal complications reported occurs in
30% to 75% of patients’ including intestinal obstruction,
stenosis, prolapse of stoma, fistula, and ileitis (7, 8, 14).
Lymphoma in the ileostomy has also been reported (15).
Adenocarcinoma in the mucocutaneous junction can invade the adjacent skin and spread to regional lymph nodes
in 15 % of the patients (13, 14). The common symptoms
are difficulty fitting the stoma appliance, bowel obstruction, and bleeding (7, 8). On physical evaluation there
is a ulcerative lesion, friable mass at the mucocutaneous
junction of the ileostomy (7, 13, 14). Clinical suspicion is
highly recommended due to falsely negative biopsies. The
CEA levels have not been very helpful (14, 19).
Once the diagnosis is confirmed by biopsy, en-block excision with or without stomal relocation is the mainstay
of treatment (7, 14). Patient education and regular surveillance of patients with long-standing ileostomy is recommended for early detection of this unusual malignancy (7,
10, 11, 14, 19).
Our case represents a similar case to those reported in the
literature. The patient developed adenocarcinoma forty
years after total colectomy. The adenocarcinoma presented
as a mass lesion and the diagnosis was made by biopsy.
The CEA level was not helpful in the diagnosis, but the
clinical suspicion of the possible malignant lesion help in
the management of the patient. No metastasis was identified and the patient has been doing well after two years of
follow up. This case reinforced previous documented cases
in the literature toward the necessity of routing screening
of ileostomy sites of long duration (12). Yearly follow up
of approximately ten years after ileostomy with biopsies
are indicated in lesions at the mucocutaneous anastomosis, but earlier if coexisting risk factors like strong family
correlations between microsatellite instability, clinicopathologic features and survival. Modern Pathology 2005:18:244-249.
4. Song GA, Deng G, Bell I, et al. Mucinous carcinoma of the colorectum have distinct molecular genetic characteristics. Int J Onco
2005;26:745-750.
5. Ogino S, Brahmandam M, Cantor M, et al. Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component. Modern Pathology 2006;
19:59-68.
6. Shung CO, Seo JW, Kim K-M, Kim SW, and Park CK.Clinical significance of signet-ring cells in colorectal mucinous adenocarcinoma.
Modern Pathology 2008;21:1533-154.
7. Metzger PP, Slappy AL, Chua HK, and Menke DM. Adenocarcinoma
developing at an ileostomy: report of a case and review of the literature.
Dis Colon Rectum 2008;51(5):604-609.
8. Bedetti CD, DeRisio VJ. Primary Adenocarcinoma Arising at an Ileostomy Site: An Unusual Complication after Colectomy for Ulcerative
Colitis. Dis Colon Rectum 1986;29:572-575.
9. Barclay TH, Schapira DV. Malignant tumor of small intestine. Cancer, 1983;51:(5):878-881.
10. Deuskar J, Joshi P, Adbe U, and Railkar A. Signet Ring Cell Carcinoma of the Ileum: A Case Report and Review of Literature.The Internet Journal of Surgery 2010;.25(1)
11. Kulaylat MN, Dayton MT. Ulcerative Colitis and Cancer. Journal of
Surgical Oncology 2010;101(8):706-712.
12. Achneck HE, Wong IY, Kim PJ, Fernandez MA, et al. Ileostomy
Adenocarcinomas in the Setting of Ulcerative Colitis. J Clin Gastroenterology 2005;39(5):396-400.
13. Niaimi F Al, Lyon CC. Primary Adenocarcinoma in Peristomal
Skin: A Case Study.Ostomy wound management 2010;26:45-47.
14. Mohandas S, Lake S. Case Report Primary Adenocarcinoma of Ileostomy: Case Report with Review of the Literature. Case Reports in
Medicine 2010; Article ID 921328, 4 pages.
15. Pranesh N. Lymphoma in an ileostomy. Postgrad Med
J 2002;78(920):368-369.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 51
16.Mizushima T, Nomura M, Fujii M., et.al. Primary Colorectal SignetRing Cell Carcinoma: Clinicopathological Features and Postoperative
Survival. Surgery Today 2010;40:234-238.
17.Greenson JK. Dysplasia in inflammatory bowel disease. Semin Diagn Pathol. 2002;19(1):31-7.
18.Seretis E, Konstantinidou A, Arnogiannakis .Mucionous Colorectal
Adenocarcinoma with Signet –Ring Cells : Immunohistochemical and
Ultrastructural Study. Ultrastructural Pathology 2010;34:337-343.
19.Raithel M, Weidenhiller M, et al. Pathobiology of dysplasia in
chronic inflammatory bowel disease: Current recommendations for surveillance of dysplasia. Z gastroenterol. 2001; 39(10):861-75.
20.Liu Q, Wang CF, et al. Comparison of clinicopathological characteristic between coloreactal signet – ring cell carcinoma and mucinous
adenocarcinoma. Zhonghua Yi Xue Za Zhi. 2010;90(44):3124-6
21.Yamagami H, Oshitani N, et al. Signet Ring cell carcenoma of the jejunu diagnosed by double ballon enteroscopy. Hipathogastroenterology.
2008; 55(85):1246-8.
22.Annam V, Panduranga C, et al. Primary mucinous adenocarcinoma
in an ileostomy with adjacent skin invasion; a late complication of surgery for Ulcerative Colitis. J Gastrointest Cancer 2008;39:(1-4):138-40
23.Chen JS, Hsieh PS. et al. Clinical outcome of signet ring cell carcinoma and mucinous adenocarcinoma of the colon. Chang Gung Med.
J. 2000;33 (1 ):51-57.
24.Agabiti E, Loganathan A, et al. Cancer of ileostomy; a late complication of colectomy for ulcerative colitis. Acta Chir Bel 2005;105
(1):99-101.
25.Yamaguchi N, Isomoto H, et al. Proximal extension of backwash
ileitis in ulcerative-colitis-associates colon cancer. Med Sci Monit .
2010;16 (7) CS87-91.
27.Vieth M, Grunewald C. Adenocarcinoma in an ideal pouch after prior proctocolectomy for carcinoma in a patient with ulcerative pancolotis. Virchows Archiv 1998 ; 433(3): 281-284
28.Carey PD, Suvarna SK, et al. Primary adenocarcinoma in an ileostomy: a late complication of surgery for ulcerative colitis. Surgery 1993;
113(6): 712-5.
29.Ikeuchi H, Nakano H, et al. Intestinal cancer in Crohn’s disease”
Hepatogastrenterology 2008;55(88):2121-4.
30. Kim JS, Cheung DY, et al. A case of small intestinal signet ring cell
carcinoma in Crohn’s disease. Korean J Gastroenterol 2007;50(1):51-5.
RESUMEN
El adenocarcinoma primario en una ileostomía permanente es raros y con una prognosis pobre en comparación a
otras malignidades gastrointestinales. El cernimiento y la
identificación de pacientes a riesgo de malignidad en su
ileostomía es un reto. No hay marcadores biológicos confiables. Sin embargo, en la evaluación clínica la sospecha
de la enfermedad unido a los síntomas que se pueden presentar como la dificultad en ajuste de colostomía, obstrucción intestinal y desarrollo de masa deben ser considerados
parte de el análisis médico en pacientes con colitis ulcerativa y ileostomía de varios años. Biopsia de alguna lesión
nueva desarrollada alrededor de el área de la colostomía
es recomendado para diagnóstico y tratamiento. Este es un
caso de adenocarcinoma primario en una ileostomía luego
de 40 años de haber tenido la misma.
Review Articles/Artículos de Reseña
NEUROMONITOREO
MULTIMODAL EN TRAUMA
CRANEOENCEFALICO
SEVERO: Estado del Arte
Juan José Gutiérrez-Paterninaa
Hernando Raphael Alvis-Mirandaa
Gabriel Alcalá-Cerraa
Andrés M. Rubianob
Luis Rafael Moscote-Salazara*
a
Universidad de Cartagena, Colombia. Grupo de Investigación en Ciencias de la Salud y Neurociencias
(CISNEURO).
b
Hospital Universitario de Neiva, Colombia. Universidad Surcolombiana de Neiva. Fundación MEDITECH.
*Correspondencia: Dr. Luis Rafael Moscote-Salazar - Universidad de Cartagena, Colombia. E-mail: [email protected]
26.Yamamoto T, Maruyama Y. Mucosal inflammation in the terminal
ileum of ulcerative colitis patients: endoscopic findings and cytokine
profiles. Dig Liver Dis. 2008 ;40(4): 253-9.
52 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Including Clinical Research Trials in
Your Practice
Becoming a clinical trials investigator offers you the
following benefits:
• A greater awareness of cutting-edge therapies and the ability to access new treatments;
• A new and/or increased patient base that seeks access to state-of-the-art science and treatments
only available through clinical trials;
• Greater access to sponsored clinical trials;
• Ultimately, satisfaction from knowing that you are contributing to the advancement of cancer
care.
• Clinical trials can benefit your patients in the following ways.
• Trials within your practice allow patients additional treatment options - beyond standard care that may be on the cutting edge.
• Through a clinical trial, patients may have access to investigational agents, devices, imaging studies, technology, equipment, or novel diagnostic techniques at no additional cost.
• Clinical trial participants have expressed satisfaction and appreciation for the attention they received during the trials. Also cited, as a benefit is the close follow-up that participants receive after
treatment.
PUERTO RICO MEDICAL ASSOCIATION
RESUMEN
El trauma craneoencefálico es un problema de salud pública. La
lesión traumática cerebral severa es la primera causa de mortalidad. En el contexto de un trauma craneoencefálico severo, las
estrategias de monitorización, nos brindan la opción de conocer
las alteraciones intracraneales posterior a la lesión primaria. El
neuromonitoreo nos permite identificar el deterioro de la función
neurológica y la presencia de lesiones cerebrales secundarias que
pueden beneficiarse de una intervención terapéutica dirigida, también nos permiten conocer cambios fisiopatológicos que suceden
en un paciente con lesión cerebral, analizando los datos fisiológicos para individualizar las terapias y nos ayuda a interpretar diversas variables que finalmente nos permitan hacer un pronóstico.
Palabras indices: neuromonitoreo, multimodal, trauma, craneocefalico, severo
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 53
E
INTRODUCCION
El traumatismo cráneoencefálico (TCE) severo representa
una importante causa de morbi-mortalidad a nivel mundial,
generando un alto costo en lo que concierne a su atención
por parte del personal de la salud idóneo y al empleo de
nuevas tecnologías dirigidas a un mejor abordaje del mismo. Por ser una patología con bajas tasas de supervivencia
y con un porcentaje significativo de secuelas cognitivas y/o
motrices, cada vez más se hace importante la generación
de esfuerzos médico científicos en pro del mejoramiento
de su atención y las conductas diagnósticas y terapéuticas a
emplearse. El neuromonitoreo multimodal (NMM) es una
herramienta tecnológica desarrollada en los últimos años,
con el fin de tener una perspectiva del funcionamiento cerebral de los pacientes neurocríticos internados en la unidad de cuidado intensivo, a través de la utilización de diversos dispositivos que permiten la medición de variables
fisiológicas que pueden predecir directa o indirectamente
la gravedad de las lesiones cerebrales. Por el costo de las
técnicas y la necesidad de entrenamiento, es un recurso no
disponible en todas las unidades de cuidado intensivo, y
además no hay actualmente en la literatura científica suficiente evidencia que soporte su uso rutinario. Los objetivos
del neuromonitoreo son: identificar deterioro neurológico
y lesión cerebral secundaria que puede beneficiarse de estrategias terapéuticas dirigidas, mejorar el conocimiento
fisiopatológico de la lesión cerebral en el paciente neurocrítico, aportar datos fisiológicos para realizar un tratamiento individualizado y ayudarnos en el planteamiento
del pronóstico de cada paciente. Por esta razón, se presenta esta revisión que pretende dar a conocer los conceptos
básicos del tema.
Definición
La palabra monitorear tiene su raíz etimológica en el latín
monere que significa, advertir, aconsejar, o, que hace recordar (1-4). Bajo esta premisa debe entenderse la importancia que tiene el monitoreo de ciertas variables fisiológicas durante el manejo de pacientes críticos en las unidades
de cuidado intensivo (UCI); y en el caso de los pacientes
con TCE severo, la herramienta fundamental que constituye determinar algunos parámetros de funcionamiento
cerebral, con aras de una temprana identificación y prevención de lesión secundaria, ya que la mayoría de los
pacientes admitidos están inconscientes y su examen neurológico no es totalmente concluyente. Las técnicas para
medir estos parámetros pueden ser o no invasivas, y en
conjunto componen el NMM (5-8) (9, 10, 11, 13).
Antecedentes
Es obvio pensar que las primeras UCI no realizaban un
monitoreo neurológico tan detallado como en la actualidad. Este se basaba apenas en la exploración neurológica
y la interpretación de la variabilidad de los signos vitales
de acuerdo a la situación de cada paciente; que en la mayoría de los casos tenían lesión cerebral ya irreversible y un
pronóstico ominoso (13). Con el advenimiento de técnicas
invasivas como la medición directa de la presión en la arteria pulmonar, las presiones de llenado ventricular y el
gasto cardíaco, para la resucitación en choque cardiogénico y/o séptico, se crea una nueva era en el monitoreo
cardiovascular y se deja abierta una puerta a la realización
de nuevos procedimientos tendientes a un mejor entendimiento de la fisiopatología de otros sistemas. De esta
manera, en 1965 con el fin de medir la presión intracraneal
(PIC), se comenzó a utilizar la inserción de un catéter de
pequeño calibre dentro de los ventrículos cerebrales, convirtiéndose en una técnica de rápida divulgación y aceptación a nivel mundial hasta la fecha (15, 21).
Kety y Schmidt fueron pioneros en el cálculo del flujo sanguíneo cerebral (FSC) en humanos, usando óxido nitroso
como indicador y estimando el valor de las diferencias
arterio-yugulares del mismo (6). A partir de aquí, estudios posteriores indicaron que el FSC podía estimarse a
partir de la medición de las diferencias arterio-yugulares
de oxígeno (AVDO2) o de otras variables hemodinámicas
derivadas de la saturación de la oxihemoglobina yugular.
En 1930 se iniciaron las investigaciones de la saturación
venosa de O2 (SvjO2) a partir de punciones directas de la
vena yugular interna, que posteriormente fueron sustituidas por la punción percutánea descrita por Goetting y la
colocación de un catéter retrógrado en la vena yugular para
valorar en forma seriada la SvjO2. Actualmente se dispone
de catéteres de fibra óptica que miden la SvjO2 de manera
continua a través de un sensor fotoeléctrico que cuantifica
la cantidad de luz absorbida por la oxihemoglobina (11).
La hipertensión intracraneal es la principal causa de muerte
en los pacientes portadores de lesión traumática cerebral
y contribuye a la lesión cerebral secundaria si no es correctamente manejada. Como mencionamos previamente,
la doctrina de Monroe-Kelly propone que el cráneo rígido
está ocupado por tres volúmenes: sangre, cerebro y líquido
cefalorraquídeo, por lo menos cualquier volumen adicional, tales como hematomas, edema cerebral o hidrocefalia
resultarán en aumento de la presión intracraneal cuando
los desplazamientos compensatorios de los volúmenes
primarios han sido excedidos. La capacidad de almacenar hasta 150 cc del nuevo volumen intracraneal sin un
significativo incremento en la presión intracraneal ocurre
por desplazamiento de sangre venosa hacia la circulación
general, el desplazamiento hacia fuera del líquido cefalorraquídeo son tiempo y edad dependiente. Las personas
mayores tienden a presentar más atrofia cerebral y de esta
manera reacomodar mayor cantidad de volumen que lentamente se expande. Las personas jóvenes con procesos agudos en su contraparte se convierten en sintomáticos más
rápidamente ante los mismos procesos fisiopatológicos.
Las lesiones ocupantes de espacios serán discutidas en la
sección subsecuente y se asume que estas lesiones han sido
evacuadas quirúrgicamente. La autorregulación cerebral
anormal, el flujo sanguíneo y el edema cerebral persisten
como causa de elevación de la presión intracraneal.
Se ha demostrado en estudios clínicos que pacientes con trauma craneal con PIC mayor de 20 mm Hg,
particularmente cuando son refractarios al tratamiento tienen un peor pronóstico clínico y son más propensos a presentar síndromes de herniación cerebral.
Existe también evidencia reciente que la presión de
perfusión cerebral por debajo de 60-70 mm Hg, se asocia con disminución de oxigenación del parénquima.
54 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
cerebral alteración del metabolismo y el pronóstico El
objetivo del neuromonitoreo y el tratamiento, es por lo
menos mantener una perfusión cerebral, oxigenación y
metabolismo adecuados, además, limitar la progresión de
las presiones intracraneales elevadas, fenómenos de desaturación, edema entre otros. (3).
PPC = PAM – PIC
Como los valores de PAM normales fluctúan entre 80 y 100
mmHg y la PIC suele estar en el rango de 5 a 10 mmHg,
los valores normales de PPC se encuentran en el rango de
70 – 85 mmHg (13).
La presión intracraneal mayor a 20 mm Hg está asociada
con un incremento de la mortalidad. Algunas situaciones
intracraneales son fáciles de detectar y corregir, tales como
la progresión de las contusiones cerebrales, otros casos con
el edema cerebral difuso que corresponde a vasodilatación
o edema no son tan fáciles de detectar. La curva presión
volumen la cual describe los cambios de la presión intracraneal, corresponde a incrementos de volumen, teniendo
una configuración exponencial, respondiendo a todos los
mecanismos compensatorios tales como la redistribución
del líquido cefalorraquídeo de la región supratentorial hacia el saco espinal, de esta manera la presión intracraneal
permanecerá constante a pesar del incremento de volumen.
Cuando los mecanismos compensatorios son violentados,
la presión intracraneal aumenta rápidamente. La presión
intracraneal no puede ser fiable si está basada en estimaciones del examen clínico o por criterios radiográficos únicamente. En pacientes sospechosos de tener hipertensión
intracraneal, la monitorización intracraneal es el “gold
standard” actual para su evaluación. En la lesión traumática cerebral, indicaciones para la monitorización incluyen:
EG menor de 9, con una tomografía cerebral anormal y,
pacientes con puntaje menor de 9 con una tomografía cerebral normal pero mayores de 40 años, con hipotensión o
posturas motoras anormales.
En el caso del encéfalo, esto se traduce en:
PPC = flujo sanguíneo x resistencia vascular cerebral
PPC = FSC x RVC
Ó también
FSC = PPC / RVC
De esta última fórmula puede deducirse que la forma de
obtener un buen FSC, es reducir la resistencia vascular cerebral (RVC). Se le denomina autorregulación al proceso
de modificar el calibre de los vasos cerebrales para ajustar
la RVC y compensar los cambios de la PPC (14).
Flujo Sanguíneo Cerebral (FSC)
Este es el factor más importante para el encéfalo y no la
PPC, como muchos conciben. Como no es tan accesible
medirlo, se utiliza más frecuentemente la PPC para estimarlo. Para comprender la autorregulación del FSC, se
debe recordar que en un sistema de flujo cualquiera:
Presión = Flujo x Resistencia
Lesión cerebral primaria y secundaria
Cada vez que el tejido cerebral presenta isquemia o hemorragia, sea o no de origen traumático, desde el preciso momento en que ocurre, se produce daño celular, constituyéndose la denominada lesión cerebral primaria. Posterior a
esta última, se genera una cascada de eventos bioquímicos
intracelulares tanto a nivel cerebral como sistémicamente,
que bien pueden ser reversibles o no, y que en conjunto reLos catéteres intraventriculares acoplados a fluidos tradi- ciben el nombre de lesión cerebral secundaria (1, 10, 18).
cionales son el método estándar y tienen bajo costo, pero
pueden experimentar alteraciones o malfuncionamiento. Los mecanismos de lesión secundaria incluyen:
La fibra óptica (Integra Neuroscience-Plainsboro, NJ) y -Efecto de masa, con el consiguiente incremento de la PIC
los dispositivos con punta transductora (Codman –Ray- y desplazamiento mecánico del cerebro (doctrina de Monham, MA) pueden ser localizados en el ventrículo o en el roe-Kelly), que puede ocasionar su herniación y una morparénquima cerebral y ser adecuados para la medición du- bimortalidad significativas si no se trata.
rante varios días, pero usualmente son más costosos y no -Hipoxia, que se debe a un aporte inadecuado de oxígeno
los podemos recalibrar después de ubicados. Hay también al encéfalo lesionado causado por un fracaso ventilatorio o
sistemas que pueden monitorizar los compartimientos por circulatorio o un efecto de masa.
separado permitiendo la medición de la PIC y el drenaje de -Hipotensión y FSC inadecuado, que puede provocar un
líquido cefalorraquídeo, de este tipo es conocido el trans- aporte inadecuado de oxígeno al cerebro. Un FSC escaso
ductor Speilgelberg (Hamburg, Alemania).
también reduce el aporte de sustratos (por ej. Glucosa) al
cerebro lesionado.
En 1982, Aaslid introdujo en la práctica clínica la Ultraso- -Mecanismos celulares, incluida la insuficiencia de ennografía Doppler Transcraneal (DT) usando un dispositivo ergía, la inflamación y las cascadas “suicidas” que pueden
de 2 MHz, que medía las velocidades medias de FSC en desencadenarse a nivel celular y pueden culminar en
las arterias del polígono de Willis, y permitía la monitor- muerte celular programada (apoptosis) (14).
ización no invasiva del vasoespasmo en los enfermos con
hemorragia subaracnoidea (HSA). Con el pasar del tiempo
y los avances tecnológicos, hoy en día el DT es usado para Examen neurológico
diversos fines en otras patologías del SNC a parte de la Representa el punto de partida al NMM. Es una herramienHSA (muerte cerebral, embolismos cerebrales) (13).
ta hasta la actualidad irremplazable, útil por su disponibilidad, relativa simplicidad y rápida valoración dinámica
Conceptos Importantes de Fisiopatología del estado neuronal. Debe enfatizarse en los movimienen Trauma Cráneo-Encefálico
tos oculares, fotorreactividad pupilar y respuesta a esPresión de Perfusión Cerebral (PPC)
tímulos dolorosos, que se sintetizan en escalas de puntuComprende la diferencia existente entre la presión arterial ación clínica como la escala de coma de Glasgow (ECG),
media (PAM) y la presión intracraneal (PIC) (20):
la cual determina el grado de alerta y conexión con el
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 55
medio exterior, y puede viciarse ante la administración de
fármacos estimuladores del sistema nervioso central (opiáceos, benzodiacepinas, neurolépticos, etc.). Su constante
evaluación permite detectar la aparición y/o progresión de
la lesión cerebral secundaria (5). Tiene la limitante de no
ser totalmente válida para pacientes intubados, por lo que
juega especial importancia la escala de FOUR (del inglés,
FULL OUTLINE OF UNRESPONSIVNESS), en la que
se miden además de las tres funciones anteriores, el tipo
de respiración según sea el paciente ventilado o respire es- Tabla 1: Métodos de Neuromonitoreo.
pontáneamente (2,7).
El principal parámetro para evaluar el deterioro neurológico es la PIC Una PIC elevada debido a un incremento del
volumen intracraneal induce nuevas y lesiones secundarias
progresivas las cuales pueden inducir y mantener un círculo vicioso. El entendimiento sobre simplificado que incrementos de a PIC mayores a 20 mm Hg es de significado
patológico ha conducido a el error que Valores normales
de PIC garantizan ausencia de proceso patológicos. Se
ha establecido que alteraciones metabólicas y funcionales
preceden a incrementos de la PIC posterior a una injuria
cerebral.
Métodos de Neuromonitoreo
Pueden agruparse en grupos, atendiendo los parámetros
que buscan medir, tal como lo muestra la Tabla 1.
No obstante, no todos tienen aplicabilidad ni evidencia suficiente en el seguimiento del TEC, razón por la cual no se
tocarán en esta revisión.
ESPECTROSCOPIA CERCANA AL INFRA
RROJO
MEDICIÓN DE LA PIC
Un aumento de los valores por encima de 20 mmHg en
la fase aguda posterior a un TEC, se asocia con mayor Tabla 2: Recomendaciones para medir la PIC en TEC.
mortalidad. La guías de manejo más recientes, adoptadas
por la Brain Trauma Foundation, hacen recomendaciones
puntuales para medir este parámetro en diversos casos de
trauma craneoencefálico (Ver Tabla 2) (16).
Pese a que en la actualidad existen formas de evaluar este
parámetro de forma no invasiva (Doppler transcraneal o
ultrasonografía de nervio óptico), siguen siendo más popular las técnicas invasivas (2) a través de la inserción de
dispositivos a distintos niveles del encéfalo (ventrículos,
parénquima, espacios subdural y/o epidural). Los catéteres
intraventriculares son el estándar de oro. El dispositivo
ideal debe cumplir con características especiales: rango de
presión 0 – 100 mmHg, precisión + 2 mmHg en un rango
de 0 – 20 mmHg, error máximo del 10% en un rango de 20
a 100 mmHg. La técnica de colocación más aceptada es a
través de un trépano frontal u occipital en el hemisferio cerebral no dominante, seguido de la introducción del catéter
hasta el ventrículo y su conexión a un sistema cerrado que
permita la transducción de presión hasta el monitor, con Figura 1: Ondas de PIC.
puertos accesorios que permitan drenaje del LCR (13).
En el monitor se observa una onda con tres picos y dos
valles, relacionadas como P1 > P2 > P3 (onda de percusión, tidal y dicrótica, respectivamente). Cuando la
presión aumenta en rangos patológicos, esta relación cambia, pudiéndose ver P2>P1. Debe tenerse en cuenta que
un aumento de la presión arterial diferencial (diferencia de
la sistólica y la diastólica) también puede alterar esta relación, sin necesidad de existir hipertensión endocraneana
(2). (Figura 1).
Dentro de las complicaciones propias de la inserción del
catéter, se enumeran: infección, hemorragia, disfunción,
obstrucción y mal posicionamiento. La incidencia de hemorragia es cercana al 1.1% mientras que el riesgo de infección es del 10% y se incrementa de manera lineal con los Tabla 3: Ventajas y desventajas en diversas técnicas de
días de monitoreo (13). Existen diversas ventajas y des- evaluación de la PIC.
ventajas en relación a la medición de la PIC (Tabla 3).
56 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Esta técnica implica la transmisión de luz desde una fuente que emite luz a un sensor, y ha sido desarrollada para
la monitorización de la oxigenación cerebral, el flujo sanguíneo y el volumen sanguíneo en adultos y niños. La
espectroscopia cercana al infrarrojo tiene algunos tópicos técnicos que requieren ser mejorados, por ejemplo, la
transmisión de la luz trabaja bien en neonatos por su cráneo
y cuero cabelludo semitransparente, la monitorización del
adulto puede ser problemática debido al incremento de la
densidad del tejido cerebral. Usando esta técnica en modo
de reflectancia puede ayudar a superar este problema. Aquí
el emisor y el detector son separados por distancias específicas sobre el cuero cabelludo con la premisa que una
cantidad fija, transmitida y reflejada de luz siguen una vía
elíptica cuya profundidad es proporcional a la distancia de
la separación entre el emisor y el detector.
El oxímetro cerebral (Somanetics Inc, Troy MI, Invos
Cerebral Oximeter) es un producto usado para estimar la
saturación de oxígeno en el cerebro. Un par de transceptores ópticos son localizados en el cuero cabelludo y la
atenuación de la señal de la luz de dos longitudes de ondas
es usada para estimar la saturación regional de oxígeno.
Aunque estas mediciones pueden ayudarnos a identificar
parámetros clínicos críticos y ayudar a guiar el tratamiento, la espectroscopia cercana al infrarrojo no es una técnica
estándar ni suficiente. Estos valores los debemos tomar en
el contexto de otras mediciones y son una ayuda más en
vez de indicarnos la acción médica a seguir.
En inglés Near infrared Spectroscopy (NIRS), es una
técnica no invasiva empleada para medir la oxigenación
alrededor de múltiples regiones del cerebro. Se basa en la
transmisión y absorción de radiaciones electromagnéticas
entre 700 y 1000 nm a varias longitudes de onda, a través
del tejido cerebral, con lo cual posteriormente se determina
la diferencia en la atenuación de espectros de oxi y deoxihemoglobina. Es importante conocer que factores como
la grosura del cráneo, vaina de mielina, LCR y flujo sanguíneo extra-craneal pueden afectar la absorción de longitudes de onda y dificultar la técnica (11(12) (20).
Los sistemas de NIRS han progresado mucho desde sus
inicios, permitiendo hoy en día medir la saturación de O2
del tejido cerebral (ScO2), como resultante de la suma de
la saturación arterial, venosa y en capilares, de tal manera
que puede tenerse una idea del balance entre el suministro
y la utilización de O2. Se considera que el rango de valores
normales oscila entre 60 y 75% (11).
SATURACIÓN VENOSA YUGULAR (SjvO2)
Como el flujo cerebral disminuye, la extracción de oxigeno
se incrementa para compensar, pero inicialmente la tasa
metabólica cerebral no cambia. Las disminuciones del flujo sanguíneo superan a los mecanismos compensatorios y
la suplencia es incapaz de mantener la demanda, la rata
metabólica disminuye, y el metabolismo anaeróbico inicia
su acción. La monitorización de la SjvO2 comenzó inicialmente en 1930 como un método promisorio para detectar
cambios de oxigenación cerebral global en el postrauma,
pero subsecuentemente ha mostrado ser más difícil de lo
que inicialmente se pensó. La SjvO2 en sujetos normales
es típicamente superior a 60%. La disminución a rangos de
50% o menos están asociadas con metabolismo cerebral alterado, y valores menos de 20% están asociados con lesión
isquémica irreversible y peor pronóstico.
Se determina mediante la inserción retrógrada de un
catéter dentro de la vena yugular interna por vía central,
haciendo que la punta del mismo se posicione en el golfo
de la yugular con el fin de obtener una medida indirecta del
porcentaje de oxigenación cerebral. Sus valores normales
oscilan entre 55 y 75%, y cuando bajan demasiado, se interpreta una disminución en el flujo sanguíneo, hipoxemia
o incremento del metabolismo cerebral. En TEC cuando
sus valores son < 50% se asocian a un peor pronóstico (11).
El procedimiento se hace habitualmente del lado dominante (derecho, en la mayoría de los pacientes), teniendo
en cuenta que los estudios han mostrado una diferencia >
10% en el porcentaje de saturación a favor de este lado en
la mayoría de los pacientes. Mediante la realización de una
radiografía de columna cervical en proyección lateral, se
confirma la posición de la punta del catéter, el cual debe
verse a nivel de la apófisis mastoidea (19). A pesar de que
esta técnica tiene mucha historia, en la actualidad no hay
suficiente evidencia que sustente su impacto sobre la sobrevida de los pacientes con TEC (11).
PRESIÓN TISULAR DE OXÍGENO (PbO2)
Un abordaje más directo para medir las alteraciones
globales como focales de la oxigenación cerebral consiste
en la colección de sensores intraparenquimatosos como el
sistema Licox® (GMS-Integra-Kiel-Mielkendorf, Germany). Los sensores Licox® son pequeños y pueden ser insertados fácilmente, con un área de muestreo de aproximadamente 14 mm que ha mostrado ser adecuado. Además
provee la capacidad de medir las fluctuaciones locales de
temperatura, pues se ha demostrado que la temperatura
del sistema difiere de la temperatura central. La difusión
del oxígeno de la sangre al espacio extracelular provee
el sustrato para la medición y el sistema Licox® integra
todas las tensiones de oxígeno arteriales y venosas en el
área. La concentración de oxigeno cerebral normal varía
en los rangos de 20-40 mm Hg. Valores menores de 10-15
mm Hg deberán considerarse un signo de hipoxia tisular y
valores menores de 5-10 mm Hg son indicativos de infarto
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 57
inminente.
Una sonda con un diámetro aproximado de 0.8 mm, que se
conecta a un pequeño electrodo, es insertada en el parénquima cerebral para medir in vivo la PO2. Se conocen dos
sistemas, Licox y Neurotrend, siendo disponible para el
mercado solo el primero, que calcula la PbO2 junto con
la temperatura cerebral, en un área estimada de 7.1 – 15
mm2. Neurotrend calcula la PbCO2, el pH y la temperatura
cerebral (17). Es necesaria la realización de TC de cráneo
inmediatamente posterior al procedimiento de inserción
de la sonda, para comprobar su posición en el parénquima
cerebral. Los valores normales se encuentran en el rango
de 35 a 50 mm Hg. A continuación se resumen situaciones
relacionadas con resultados de PbO2 (3,19). (ver Tabla 4)
MICRODIÁLISIS
Tabla 4: Interpretación de resultados de PbO2
temprano de lesión cerebral isquémica (10). Algunos autores
lo han relacionado también con los altos niveles de glicerol,
llegando a la conclusión de que son predictores inminentes
de hipertensión intracraneal (4).
Doopler Transcraneal
La medición directa del flujo sanguíneo en las arterias cerebrales puede de ser valiosa en todos los casos de lesión
cerebral. Usando un transductor de ultrasonido, la velocidad de flujo puede ser medida en las principales arterias de
la base del cerebro. En alrededor de 10% de los pacientes,
la ensonación transtemporal no es posible por las barreras
anatómicas que pueden presentar algunos pacientes. El Doppler transcraneal es una técnica económica y no invasiva que
nos provee datos sobre la hemodinámica cerebral, y puede
alertar al médico tratante sobre posibles eventos deletéreos.
El Doppler transcraneal depende de una señal de pulso ultrasónica que es transmitida a través de un área delgada del
cráneo. La velocidad del flujo sanguíneo es determinada, y
el volumen del flujo puede ser calculado multiplicando la
velocidad por el área transversal del vaso. Ya que la cantidad
de flujo colateral y el diámetro del vaso actual no son conocidos, el Doppler transcraneal no puede proveer datos cuantitativos sobre la perfusión tisular regional. Los cambios en
la velocidad del flujo pueden al menos, proveernos de datos
relativos considerando los cambios en el flujo de volumen.
Típicamente, las velocidades de flujo mayores a 200 cm/
segundo indican vaso espasmo severo, estrechamiento de
los vasos e infarto inminente. La hiperemia, un fenómeno
común posterior a una lesión traumática cerebral, pude conducir a velocidades de flujo elevadas. El conocido índice de
Lindegaard o índice hemisférico (MCA/ACI Extracraneal)
puede ayudarnos a diferenciar las dos situaciones, con valores normales menores de 2 y valores críticos mayores de 3.
Después de una lesión traumática cerebral, el microambiente cerebral cambia rápidamente. La liberación de aminoácidos excitadores, el influjo de calcio, falla en las bombas
de membrana, y la acumulación de lactato son solo pocas
alteraciones que subyacen a la patobiología del neurotrauma. Algunos de estos cambios han sido reportando con el
uso de microdiálisis en humanos. Se ha reportado la correlación entre efectos clínicos adversos (presión intracraneal
elevada, hipotensión e hipoxia) e incrementos de las concentraciones dializadas (lactato, potasio, aminoácidos excitadores) o disminución (glucosa) después de una lesión
traumática cerebral. La microdiálisis cerebral consiste en
un sensor (0.62 Día) que es localizado en el parénquima
cerebral, fue utilizado inicialmente en 1980 por Mayerson
y colaboradores en modelos de enfermedad de Parkinson.
La microdiálisis cerebral se ha combinado con otras modernas técnicas de monitorización cerebral tales como sensores de PIC y PO2. El sensor es perfundido con un líquido
estéril extracelular de manera lenta permitiendo el muestreo e identificación de diversas moléculas como glucosa,
lactato, potasio, piruvato, óxido nítrico y glutamato. La
microdiálisis no es una herramienta perfecta. Uno de los
aspectos a considerar es que las mediciones corresponden
a concentraciones relativas de moléculas extracelulares y
no a concentraciones actuales, causando dificultades cuando intentamos comparar datos entre diferentes equipos y
centros. Otra desventaja es que presenta pobre resolución
temporal, investigaciones futuras nos indicarán cuáles son Tomografía con xenón
los objetivos de la aplicación de la microdiálisis en las uniLa tomografía con xenón es probablemente el método no
dades de pacientes neurocríticos.
invasivo más adecuado para determinar el flujo sanguíneo
Un fino catéter de +0.62 mm, con una membrana semi- cerebral regional y global. El xenón es una sustancia rapermeable en su punta (permite el paso de moléculas < 20 dio densa, inerte y rápidamente difusible que nos permite
kDa), es insertado en el parénquima cerebral y perfundido hacer mediciones precisas cuantitativas que son necesarias
con solución fisiológica (Hartman) por medio de una bom- para determinar valores de flujo sanguíneo. Para realizarla
ba de precisión, para filtrar moléculas de metabolitos (glu- primero se realiza una tomografía cerebral simple y después
cosa, lactato y piruvato), neurotransmisores (glutamato, se realizan tomografías seriadas mientras el paciente inhala
aspartato, GABA), y marcadores indicativos de daño cere- xenón al 28-33%, posteriormente mediante moldeamienbral (glicerol, potasio, Tau y amiloide beta) además de fár- to matemático complejo se producen valores cuantitativos
macos, a nivel del intersticio celular cada 10 – 60 minutos basados en el principio de Fick el cual postula que la entrada
(8) (19). Los valores medidos permiten determinar el esta- o salida de cualquier sustancia a un órgano es el producto
do de óxido-reducción en el microambiente intersticial, al de la diferencia arterio-venosa de esa sustancia multiplicada
igual que estimar el grado de anaerobiosis. Se acepta que por el flujo sanguíneo de ese órgano (consumo o producción
el cociente L/P (Lactato / Piruvato) > 40 es un marcador = diferencia A-V.Q).
58 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
Al igual que con otras técnicas, la tomografía con xenón
no está exenta de errores, de manera que para obtener resultados fiables los pacientes deben tener un estado cardiovascular óptimo. Dos métodos invasivos ahora están
disponibles para valorar el flujo sanguíneo cerebral local y
tienen una excelente correlación con la tomografía con xenón, el método de difusión térmica y el método de Doppler
con láser. Ambos métodos requieren craneotomía abierta
para localización de los mismos, hecho que ha limitado su
uso, además de que ambos solo pueden medir áreas focales
pequeñas de tejido cerebral, que pueden no ser la representación del estado global del flujo sanguíneo.
ELECTROENCEFALOGRAFIA CONTINUA
Es una técnica no invasiva que permite monitorizar en
tiempo real la actividad bio-eléctrica cerebral, esta técnica requiere especialistas bien entrenados para su interpretación, aunque si bien existe la electroencefalografía
cuantitativa que ha simplificado la interpretación, esta
puede ser alterada por artefactos. Las crisis no convulsiva
BTF son un problema frecuente en UCI y la identificación
temprana nos permitirá evitar la lesión neural.
CONCLUSIONES
Las intervenciones terapéuticas posterior a la lesión
traumática cerebral son influenciadas por complejas cascadas fisiopatológicas que implican alteraciones sistémicas
y locales. Por lo tanto nuestra búsqueda debe prevenir e
identificar alteraciones como la hipoxia, hipotensión, hiperventilación no controlada, anemia e hipoglicemia.
REFERENCIAS
1. Oddo M. Multimodality Neuromonitoring. Neurocritical Care Society Practice Update 2013 available in: http://www.neurocriticalcare.
org/2013-practice-update
2. Stocchetti N, Le Roux P, Vespa P, Oddo M, Citero G, Andrews PJ,
Stevens RD, Sharshar, Tacone FS, Vincent JL. Clinical Review: Neuromonitoring – an update. Critical Care 2013; 17: 201.
3. Mahajan Ch, Rath GP, Bithal PK. Advances in Neuro-Monitoring.
Anesthesia: Essays and Researches 2013; 7: 313 – 8.
4. Feyen BFE, Sener S, Jorens PG, Menovsky T, Maas AIR. Neuromonitoring in Traumatic Brain Injury. Minerva Anestesiologica 2012; 78;
8: 949 – 958.
5. Macas A, Bilskiene D, Gembickij, Zarskus A, Rimaitis M, Vilke A,
Suskeviciene I, Rugyte D, Tamasauskas A. Multimodal Neuromonitoring. Acta Médica Lituanica 2012; 19; 3: 180 – 6.
6. Kirkman MA, Smith M. Multimodal Intracranial Monitoring: Implications for Clinical Practice. Anesthesiology Clin 2012; 30: 269 – 287.
9. Subhas k, Smith M. Neuromonitoring. Anaesthesia and Intensive
Care Medicine 2011; 12; 5: 189: 189 – 193.
10. Hemphill JC, Andrews P, De Georgia M. Multimodal Monitoring
and Neurocritical Care Bioinformatics. Nat Rev Neurol 2011; 7: 451
– 60.
11. Lee SK, Goh JPS. Neuromonitoring for Traumatic Brain Injury in
Neurosurgical Intensive Care. Proceedings of Singapore Healthcare
2010; 19; 4: 319 – 333.
12. Smith M. Neuromonitoring. Anaesthesia and Intensive Care 2008;
9; 5: 182 – 192.
13. Carrillo R, Leal P. Actualidades en Terapia Intensiva Neurológica,
Primera Parte. Monitoreo Neurológico Multimodal. Revista de Investigación Médica Sur 2008; 15; 4: 266 – 277.
14. PHTLS: Soporte Vital Básico y Avanzado en el Trauma Prehospitalario. Versión Española de la 6° edición. Mosby Inc. Madrid, 2008.
15. Wartenberg KE, Schmidt JM, Mayer SA. Multimodality Monitoring
in Neurocritical Care. Crit Care Clin 2007; 23: 507 – 538.
16. Brain Trauma Foundation, AANS, CNS. Guidelines for the Management of Severe Traumatic Brain Injury 2007. 3rd Edition.
17. Brigham and Women´s Hospital Neurosurgery Group. Neuromonitoring in Neurological Critical Care. Neurocritical Care 2006; 4: 83
– 92.
18. Murthy TVSP, Bhatia P, Sandhu K, Prabhakar T, Gogna RL. Secondary Brain Injury: Prevention and Intensive Care Management. Indian Journal of Neurotrauma 2005; 2; 1: 7 – 12.
19. Gupta AK, Azami J. Focus on: Neurointensive Care, Update of Neuromonitoring. Current Anaesthesia & Critical Care 2002; 13: 120 – 128.
20. Kirkpatrick PJ, Czosnyka M, Pickard JD. Multimodal Monitoring in
Neurointensive Care. Journal of Neurology, Neurosurgery and Psychiatry 1996; 60: 131 – 139.
21. Becker DP, Miller JD, Ward JD, Greenberg RP, Young HF, Sakalas
R. The Outcome from Severe Head Injury with Early Diagnosis and
Intensive Management. J Neurosurg 1977; 47; 4: 491 – 502.
ABSTRACT
Traumatic brain injury is a public health problem and leading cause of death. In the context of a severe head injury,
monitoring strategies give us the option to analyze the posterior intracranial alterations to the primary lesion. Neuromonitoring allows us to identify the deterioration of neurological function and the presence of secondary brain injury
that may benefit from a therapeutic intervention letting us
know pathophysiological changes that occur in a patient
with brain injury. Understanding the physiological data allow to individualize therapies and interpret variables that
ultimately help us choice a better treatment.
7. Sadaka F, Patel D, Lakshmanan R. The FOUR Score Predicts Outcome in Patients after Traumatic Brain Injury. Neurocritical Care 2012;
16; 1: 95 – 101.
8. Cecil S, Chen PM, Callaway SE, Rowland SM, Adler DE, Chen JW.
Traumatic Brain Injury: Advanced Multimodal Neuromonitoring From
Theory to Clinical Practice. Crit Care Nurse 2011; 31: 25 – 37.
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 59
Historic Article/Artículo Histórico
DERIVADOS DE SANGRE
EN PUERTO RICO:
Historia de los Servicios de
Transfusión y Estimado del
Consumo de Unidades de
Sangre
Raúl H. Morales-Borges MDa*
Director Médico, Cruz Roja Americana.
*Autor Correspondiente: Raúl H. Morales-Borges MD - Cruz Roja Americana, Servicios de Sangre, PO BOX 366046,
San Juan, PR 00936-6046.
a
RESUMEN
Puerto Rico cuenta con ocho bancos de sangre de hospitales y tres comunitarios para
una población de aproximadamente cuatro millones de habitantes. La Cruz Roja viene existiendo en Puerto Rico desde el 1893 bajo los españoles pero no fue hasta el
1907 que paso a ser la Cruz Roja Americana (CRA). Desde entonces se ha estado
sirviendo a Puerto Rico y la Islas Vírgenes Americanas. Se utilizan unos 171,222 componentes de sangre de los cuales el 45% son de la CRA. Hay una serie de variantes en
la utilización y una serie de factores que nos vienen influyendo a nivel local y nacional
y es por esto que se requiere la colaboración con el plan de manejo de componentes
de sangre a nivel de cada institución hospitalaria y la implementación del máximo de
unidades requeridas por cada caso de cirugía.
Palabras claves: derivados, sangre, Puerto Rico, historia, transfusión, consumo
60 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
L
INTRODUCCION
prueba y comenzaron a disminuir los casos seguido por la
hepatitis C en los 1990’s. La prueba de HIV se comenzó a
La transfusión de productos derivados de la sangre es es- realizar a los donantes en el 1985 (5).
encial para mantener la vida de muchos seres humanos que
Con la colaboración de las Industrias Farmacéuticas, Organisufren de anemia y cáncer entre otros.
zaciones Comunitarias, Asociación Médica de Puerto Rico y
En Puerto Rico se comenzó a organizar la Cruz Roja para la Legislatura, se inauguró un nuevo edificio en los terrenos
el 1893 y muchos adelantos se dieron gracias a la Segunda del Centro Médico de Puerto Rico en el mes de agosto de
Guerra Mundial (1,2). Al iniciar el Siglo XX, nuestra po- 1984 (5). Luego debido a las presiones por la Administración
blación alcanza el millón y las principales causa de muertes de Drogas y Alimentos (FDA) en mejorar la seguridad de los
fueron la disentería, la anemia y la tuberculosis (2). Para productos de sangre, se comenzaron a realizar unos cambios
el 2012 la población estimada es de 3,667,084 personas y nuevos servicios tales como plaquetas de donantes sencil(3). Las principales causas de muerte son las enfermedades los (SDP), laboratorio de referencia de inmunohematología
cardiovasculares, el cáncer y las muertes por accidente o (IRL), plasmaferesis (TPE) y colección, procesamiento y
causa criminal. Más del 42% de los puertorriqueños tiene almacenaje de células madres de la médula ósea (HSC/P).
uno o más factores de riesgo para desarrollar enfermedad Seguido a esto se centralizaron todas las pruebas de rigor a
cardiovascular; trece de cada 100 tiene diabetes; uno de nivel nacional incluyendo la sangre colectada en PR y luego
cada 25 hombres y mujeres será diagnosticado con cáncer se envía a la Isla para su distribución. Recientemente, se cercolorectal; uno de cada 13 mujeres serán diagnosticadas raron las operaciones de colección de sangre completa en la
con cáncer de mama; y 70,000 es el estimado de personas Isla y continúan ofreciéndose los demás servicios.
con Enfermedad de Alzheimer (4). Muchas de estas personas afectadas requerirán algún componente de sangre tarde Bancos de Sangre en Puerto Rico
o temprano en el curso de su enfermedad. Es por esto que
queremos presentarle la situación histórica actual de los Hay 8 bancos de sangre de hospitales que solo pueden colectar sangre para su propio uso.
servicios de sangre en la Isla y sus proyecciones futuras.
• Manatí Medical Center
Historia de los Servicios de Sangre en • Hospital Metropolitano Cayetano Coll y Toste
• Hospital Buen Samaritano
Puerto Rico
• Mayagüez Medical Center
En 1893 se inicia la Cruz Roja en Puerto Rico, mediante • Hospital Bella Vista
la Comisión Provincial de la Cruz Roja Española, bajo el • Hospital Damas
liderato de Manuel Fernández Juncos. En el 1898 San Juan • Hospital San Lucas
fue atacado desde el mar, en unos 15 minutos la Cruz Roja • Administración Servicios Médicos de PR
comenzó a ayudar a los heridos. El Dr. José Celso Barbosa
junto a la Sra. Dolores Aybar fueron los grandes colabora- El Banco de Sangre del Centro Médico de Puerto Rico, es
el único banco de sangre puertorriqueño, creado por el Godores de ese momento (1,2).
bierno de Puerto Rico. Inició operaciones el 12 de marzo de
El Dr. Bailey Kelly Ashford, primer teniente de la Sanidad 2008.
Militar del Ejercito estadounidense, llegó a PR en julio de
1898, se enfermó de paludismo, coincide con el Huracán Hay 2 bancos de sangre comunitarios (Servicios Mutuos y
San Ciriaco del 1899, y es nombrado Director del Primer Southern Blood Bank). El Banco de Sangre de Servicios MuLaboratorio Clínico en Puerto Rico donde ahí descubre el tuos, es una institución de servicios a la comunidad puertorparásito Necator americanus causante de anemia por Un- riqueña, organizada en el 1980. Southern Blood Bank abrirá
cinariasis en noviembre de 1899 (2). Es aquí cuando se en el 2014.
activa la Cruz Roja.
CRA es un banco comunitario, pero solo estaremos colectanEn el 1907, la oficina del gobernador Beckman Winthrop do localmente el producto de plaquetas y productos especiasolicitó la constitución de una sección o sucursal de la Cruz les. Nosotros damos servicios a 42 hospitales en PR y las
Roja Americana (CRA) en Puerto Rico (1). En el 1918, las Islas Vírgenes.
oficinas centrales estaban ubicadas en el Viejo San Juan
cerca del Teatro Tapia y tenían secciones en 75 munic- ¿Con Cuantas Unidades de Sangre Cuenta
ipios de la Isla (1). En los años 1960’s los doctores José PR?
Luis Molinaris, Francisco Muñiz y Norman Maldonado se
unieron a la CRA debido a la alta incidencia de leucemias CRA distribuye aproximadamente 77,050 componentes de
agudas, anemia aplástica, desordenes hematológicos serios sangre anualmente a PR e Islas Vírgenes y se estima que discomo la hemofilia y a los casos de trauma y cirugía cardio- tribuimos el 45% de todos los productos que se necesitan en
la Isla. Estos porcentajes son estimados ya que el Departavascular existentes en esos momentos (5).
mento de Salud ni ninguna agencia recogen datos sobre colLuego surgieron los casos de hepatitis B por transfusión de ecciones de sangre en PR ni transfusiones realizadas en los
sangre causando enfermedad crónica del hígado y no fue hospitales.
(continúa en página 65)
hasta principios de los 1980’s cuando se desarrolló la
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 61
(viene de página 61)
Basados en este estimado los demás bancos de sangre anualmente producen 94,172 componentes de sangre por lo
que el total de componentes que se utiliza en PR se estima
en 171,222.
SERVICIO NO-CARDIOVASCULAR:
PRBC’s: 1992 & 1994 – 222 unidades/mes; 1996 – 230
unidades/mes
Bajó el consumo de RBC, pero subió el de plaquetas.
Plaquetas: Bajó el consumo un poco.
Para el año fiscal que terminó el 30 de junio de 2013, la
distribución de sangre por categoría de producto de Cruz Transfusión de Sangre Autóloga en Ortopedia Pediátrica por Dres. Flynn, Cintrón &
Roja fue:
Canals (8)
• RBC: 57,411
Unos 29 pacientes con procedimiento de fusión de columna
• SPD: 6,496
vertebral fueron estudiados. CRA fue quien realizó flebot• Plasma: 9,623
omía de una unidad cada 6 días si el hematocrito era más
• Cryo: 3,520
de 34%; la última flebotomía fue al menos 7 días antes de
la cirugía; donaron un promedio de 3.17 unidades (1,417
Distribución de Sangre en PR
ml), y se almacenaba por no mas de 35 días. En el 89% de
Hasta el momento continua normal y mantenemos un in- los casos la sangre autóloga fue la única transfundida. Se
ventario robusto cumpliendo con todos los pedidos, excep- demostró que es seguro, aceptable y efectivo.
to con las plaquetas cuando estuvimos en adiestramiento
de BioArch. En los últimos dos años se ha mantenido prác- Transfondo de la Utilización en Estados
ticamente igual. Actualmente seguimos la misma trayecto- Unidos de America (EUA)
ria de anos pasados.
Alguien necesita sangre cada tres segundos; transfusión
ahorra hasta 4.5 millones de estadounidenses cada año, o
Año Fiscal RBC
SDP
CRYO
FFP
más de 12.000 vidas al día (9). Es el único procedimiento
más comúnmente cobrado por utilizaciones de pacientes
FY 2012
58,730 7,034
3,513
10,839
que reciben atención hospitalaria, con cerca de 15 millones
de transfusiones de productos sanguíneos se practican anFY 2013
57,411 6,496
3,200
9,623
ualmente en los hospitales de Estados Unidos a un costo
Estudio de Estimado y Proyección del Con- de $10 a $15 millones. Cada día aproximadamente 44.000
sumo de Unidades de Sangre en PR 2005- unidades de productos sanguíneos se utilizan en hospitales
2015 por Rosario & Marin Consultores, CRL y centros de tratamiento de emergencia en todo el país para
tratar a pacientes con cáncer y otras enfermedades graves;
en el 2006 (6)
para los receptores de trasplante de órganos, y para ayudar
El consumo total de sangre en los hospitales en PR para el a salvar las vidas de accidentes y víctimas de trauma.
2005 fue de 203,451 unidades lo que equivale a una tasa
de 51.8 unidades por 1,000 habitantes. Los componentes Problemas Existentes en EUA
de sangre con el mayor volumen para el 2005 fueron RBC
con 125,551 unidades y las plaquetas con 35,630. Las ten- La falta de disponibilidad de los productos de la sangre
dencias durante el periodo del 2000 al 2005 indicaron que es un asunto relativamente bien publicitada en medicina
el consumo de plaquetas, crioprecipitado y plasma dis- transfusional. Gestión eficaz de la sangre se ve afectado
minuyeron, pero el consumo de células rojas y plaquetafer- no sólo por un déficit de donantes a nivel de emergencia
- la Cruz Roja de Estados Unidos dice que su suministro
esis (SDP) aumentaron.
nacional de sangre está en el nivel más bajo en 15 años, dePara el 2015 se proyecta que el consumo de sangre podría bido al mal tiempo y una donación de verano lento -, sino
aumentar a 212,032 – 243,375 (un 17.2%) con una tasa de también por la complejidad de la gestión de inventarios
58.2 unidades por 1,000 habitantes. Los RBC’s y SDP’s de los productos sanguíneos y disponibilidad dentro de los
hospitales y los sistemas de salud.
serían los componentes de mayor volumen de consumo.
Estudio de Utilización de componentes de
sangre en el Hospital San Pablo de Bayamon, PR del 1991 al 1996 por el Dr. Robert
Hunter-Mellado (7)
El uso excesivo o el uso inadecuado de los productos de
la sangre es un problema menos reconocido-que presenta problemas significativos de seguridad del paciente. Investigaciones recientes indican que el uso de productos de
la sangre más allá de un nivel considerado médicamente
necesario puede aumentar las tasas de complicaciones y
CIRUGIA CARDIOVASCULAR :
PRBC’s: 167 unidades– 1992; 182 unidades – 1994; 187 tiempo de hospitalización. El uso excesivo también puede
aumentar sustancialmente el costo de la atención. Aunque
unidades – 1996
45 pacientes/mes – 1992; 55 pacientes/mes – 1994; 56 pa- el costo de una unidad de glóbulos rojos es de aproximadamente $210, cuando se incluyen los costos de admincientes/mes – 1996
Relación de pacientes operados/transfundidos: 1.3 – 1992; istración y suministro, los promedios totales llegan hasta
$1,100 (9).
1.4 – 1994; 1.4 – 1996
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 65
Aunque hay muchas guías de práctica clínica para el uso
de productos de la sangre, la evidencia científica que apoya
las recomendaciones específicas no es robusto. La falta de
pruebas sólidas que apoyen prácticas específicas a menudo
conduce a la sobreexplotación de los productos sanguíneos.
La misma falta de claridad puede causar discrepancias en
cómo y cuando los cirujanos y anestesiólogos pedidos de
productos sanguíneos. No es sorprendente que los proveedores de atención muestran variaciones considerables en el
uso de productos sanguíneos.
Optimización de Ordenes de Sangre Pre-operatorias utilizando MSBOS
Un estudio de John Hopkins con Brigham and Women Hospital de Boston, MA (11) determinaron que unos
27,825 casos quirúrgicos que no requirieron ordenes de
sangre preoperatoria a través del sistema de MSBOS, el
32.7% tenían un T&S y el 9.5% T&C.
De 4,644 casos que se determinó solo el T&S, el 32.5% tuvieron un T&C ordenado. Se ahorraron $211,448 por año.
Gestión o Manejo de la sangre del paciente Resumen y Conclusiones
(9)
La CRA de PR lleva años desde sus comienzos en el 1893
Teniendo en cuenta la variación de la utilización de pro- ofreciendo sus servicios a la Isla. Con dos bancos comuductos sanguíneos que presenta este análisis, los líderes del nitarios más el de la CRA se está cubriendo la Isla y las
hospital deben revisar las prácticas y los protocolos de su Islas Vírgenes como St. Croix y St. Thomas. Tenemos que
organización para identificar los posibles residuos, man- mejorar la utilización de los productos y comenzar aplicar/
teniendo la calidad de la atención. En algunos casos, caso incentivar “PBM” y “MSBOS” en PR.
por caso, de revisión puede ser valiosa. Además, con base
en experiencias de trabajo con los hospitales miembros y CRA de PR tiene abastos de sangre suficiente para la deexpertos nacionales, se recomienda los siguientes factores manda de sus productos de sangre y estaremos siempre dicríticos para la gestión exitosa de sangre:
sponibles en cuanto a la distribución de los mismos a pesar
de los cambios acontecidos.
1. El uso de un equipo de gestión de la sangre multidisciplinario.
Hay una gran necesidad de sangre, así que no podemos
2. Trabajando en colaboración con los médicos y los ejec- darnos el lujo de cerrar bancos de sangre en la Isla sino
utivos de la cadena de suministro para explorar productos mantener los que están disponible y aunar esfuerzos entre
y procedimientos alternativos.
ellos.
3. Establecer e implementar guías de transfusión basados​​
en la evidencia.
Agradecimientos
4. Proporcionar herramientas de educación y apoyo a la decisión clínica para informar a los médicos de las directrices Estoy sumamente agradecido por la colaboración del Dr.
en tiempo real.
Norman Maldonado (Hematólogo Oncólogo y Pasado
5. El desarrollo de procesos para supervisar el cumplimien- Presidente de la Universidad de Puerto Rico) y de la Lcda.
to de las directrices y proporcionar información a los médi- Dilia Magali Borges (Gerente de Cuentas de la Región de
cos.
Puerto Rico de la Cruz Roja Americana) en la preparación
6. Supervisar la utilización de forma continua mientras se de la presentación (que fue realizada el 13 de diciembre de
mide el impacto de la mejora.
2013 en el Centro Comprensivo de Cáncer de Puerto Rico
como parte del Décimo Quinto Simposio de Leucemia,
Cambio en la política de la Medici- Mieloma y Trasplante de Médula Ósea organizado por el
na de Transfusión utilizando MSBOS Dr. Alberto López Enríquez) y el manuscrito.
(Maximum Surgical Blood Ordering Schedule)
REFERENCIAS
Un estudio de Reino Unido con la Sociedad de Hematología Británica (10) con 314 casos de cirugía menor y 227
de cirugía mayor en seis meses evaluaron: “Cross-matchto-transfusion ratio (C;T) basados en las pruebas ordenadas tales como “Group & Save” y “Type & Cross-match”.
Ellos implementaron el “MSBOS” pero solo en cirugía
colorectal y Hepatobiliar. Unas 507 unidades fueron cruzadas y 238 fueron utilizadas para un C:T ratio de 2.1:1
(utilización de RBC de 46.9%), el C:T ratio ajustado varió
ente 3.75 y 37. No cumplieron con las políticas de transfusión adecuadamente y se ordenaron productos de mas. El
estudio tiene la limitación que fue solo con casos de cirugía
hepatobiliar y colorectal, pero se ahorraron dinero al seguir
la implementación del MSBOS.
1. Maldonado NI: On Health in Puerto Rico, 2008. La Editorial Universidad de Puerto Rico.
2. Pérez I: La Salud No Tiene Precio, 2007. Publicaciones Puertorriqueñas, Inc
3. Annual Estimates of the Population for the United States, Regions,
States, and Puerto Rico: April 1, 2010 to July 1, 2012" (CSV). 2012
Population Estimates. United States Census Bureau, Population Division. December 2012. Retrieved December 24, 2012.
4. La salud de Puerto Rico en números, 11 de diciembre de 2013. http://
www.elnuevodia.com/lasaluddepuertoricoennumeros-1284125.html
5. Maldonado NI: On Health in Puerto Rico II. Healthier Living and
Other Matters, 2010. La Editorial Universidad de Puerto Rico.
6. Rosario & Marín Consultores, CRL Estudios Cualitativos y Cuantitativos, 2006. Estimado y Proyección del Consumo de Unidades de
Sangre en Puerto Rico: Aňos 2005 al 2015.
7. Hunter-Mellado R: Trends in the utilization of blood components in
San Pablo Hospital; 1991 – 1996. Boletin Asocacion Medica de Puerto
Rico 1997 Jan-Mar; 89(1-3): 4-8.
8. Flynn JM, Cintron K, Canals RM: The use of autologous blood transfusions in pediatric orthopaedic surgery. Bol Asoc Med PR 1991 May;
83(5): 192-195.
66 | BOLETIN Médico Científico de la Asociación Médica de Puerto Rico
9. Premier, October 2012. Best Practices in Blood Utilization.
https://www.premierinc.com/about/news/12-oct/blood_white_paper_207pm_10032012.pdf
10. Hall TC, Pattenden C, Hollobone C, Pollard C, Dennison AR. Blood
Transfusion Policies in Elective General Surgery: How to Optimise
Cross-Match-to-Transfusion Ratios. Transfus Med Hemother. 2013
Feb;40(1):27-31. doi: 10.1159/000345660. Epub 2013 Jan 3.
11. Frank SM, Rothschild JA, Masear CG, Rivers RJ, Merritt WT, Savage WJ, Ness PM. Optimizing preoperative blood ordering with data
acquired from an anesthesia information
ABSTRACT
Puerto Rico has eight hospital blood banks and three community blood banks for a population around four million.
The Red Cross has been in existence in Puerto Rico since
1893 under the Spanish Governance but it was not until
1907 which became the American Red Cross (ARC). Since
then it has been serving Puerto Rico and the U.S. Virgin
Islands. About 171.222 blood components, which 45% are
of the ARC, are used. There are a number of variations in
utilization and a number of factors that are influencing us
at the national and local level and that is why collaboration
is required in the management plan of blood components
at each hospital and implementation of maximum units required for each case of surgery.
En la sede de la Asociacion
Medica de Puerto Rico
Reunion de apertura
el 12 de agosto de 6 a 8pm.
TOV basado en la Biblia, con Cristo como
centro. Que consiste en una actividad orante
paso a paso y adaptado a la persona, taller
liberador y sanador a través del conocimiento
de Dios y de uno mismo.
El TOV no tiene costo de inscripción.
Para todo publico (no solo medicos)
Informes: Dra. Victoria Michelen
(787) 624-0573
BOLETIN Médico Científico de la Asociación Médica de Puerto Rico | 67
Asociación Médica de Puerto Rico
P.O. Box 9387
SAN JUAN, PR 00908-9387
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