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♦CASO CLÍNICO
An unreported case of pancreatic panniculitis in a
liver transplant patient
María Anders,1 Virginia Mariana González,2 Juan Ruiz,3 Gabriel Casas,4 Nicolás
Goldaracena,1 Federico Orozco,1 Florencia Antinucci,1 Margarita Larralde,2 Hugo Catalano,3
Emilio Quiñonez,1 Lucas McCormack,1 Ricardo Mastai1
Liver Transplant Unit.
Department of Medicine, Dermatology Division.
3
Department of Medicine, Internal Medicine Division.
4
Department of Pathology.
Hospital Alemán, Ciudad Autónoma de Buenos Aires, Argentina.
1
2
Acta Gastroenterol Latinoam 2014;44:239-242
Summary
Pancreatic panniculitis is an uncommon condition that can
occur in association with pancreatic disease. Most of the cases reported to date were associated with acute or chronic
pancreatitis and pancreas cancer. Recently, development has
been described in kidney transplant patients and secondarily
to allograft pancreatitis in a pancreas-kidney transplant recipient. Both findings suggest that immunological processes
may be involved in the pathogenesis of this entity. We report
for the first time a case of acute pancreatitis associated with
pancreatic panniculitis in a patient who underwent a liver
transplant 10 months before. A 69-year-old man with a history of epigastric pain of a few days of evolution was presented with painful subcutaneous nodules on both legs. Blood
chemistry showed raised serum amylase and lipase levels. Ultrasonography and multislice CT scan were suggestive of an
acute pancreatitis. A skin biopsy showed typical features of
pancreatic panniculitis which included lobular panniculitis
with lipocyte degeneration with ghost cells. The administration of octreotide resulted in both a rapid improvement of
symptoms and a disappearance of skin lesions. Liver transplant specialists should be aware that the pancreatic panniculitis could be a manifestation of pancreas disease in patients
who have undergone liver transplantation.
Key words. Pancreatic panniculitis, liver transplant, acute
pancreatitis, ghost cells, lipocyte degeneration.
Correspondencia: Ricardo Mastai
Unidad de Trasplante – Hospital Alemán
Avda. Pueyrredón 1640 (CP C1118AAT). Buenos Aires, Argentina.
Tel: (0054-11) 4827-7000 / Fax: (0054-11) 4827-7014
E-mail: [email protected]
Paniculitis pancreática: reporte de un
caso en un paciente trasplantado hepático
Resumen
La paniculitis pancreática es una condición poco frecuente
que puede presentarse en asociación con enfermedades pancreáticas. La mayoría de los casos reportados a la fecha se
asociaron con pancreatitis aguda o crónica, o cáncer. Recientemente, se ha descrito la enfermedad en el contexto del
trasplante renal y en forma secundaria a pancreatitis del
injerto en receptores de trasplante reno-pancreático. Ambos
hallazgos sugieren que podrían estar involucrados procesos
inmunológicos en la patogénesis de esta entidad. Se presenta
por primera vez un caso de pancreatitis aguda asociada a
paniculitis pancreática en un paciente trasplantado hepático
diez meses antes del diagnóstico. Se trata de un hombre de
69 años de edad, con una historia de dolor epigástrico de
unos pocos días de evolución que se presentó a la guardia con
nódulos subcutáneos dolorosos en ambas piernas. Los estudios
de laboratorio demostraron elevación de amilasa y lipasa en
sangre. La ecografía y la tomografía computarizada multicorte fueron sugestivos de pancreatitis aguda. Se realizó una
biopsia de piel que demostró lesiones típicas de paniculitis
pancreática como paniculitis lobular, degeneración lipocítica
y células fantasma. Con la administración de octreoctide el
paciente presentó mejoría de los síntomas con desaparición de
las lesiones cutáneas. Se sugiere que los médicos especialistas
en trasplante hepático deben ser conscientes de que la paniculitis puede ser una manifestación dermatológica de enfermedad pancreática.
Palabras claves. Paniculitis pancreática, trasplante hepático,
pancreatitis aguda, células fantasma, degeneración lipocítica.
Acta Gastroenterol Latinoam 2014;44(3)239-242
239
Pancreatic pannicultis in a liver transplant patient
Panniculitis, a group of diseases whose hallmark is
inflammation of subcutaneous adipose tissue, is a rare
complication in the setting of pancreatic disease.1, 2 The
exact pathogenic mechanism of pancreatic panniculitis is
still unknown, but release of pancreatic enzymes, such as
lipase, trypsin and amylase may be involved.2, 3
Few cases of pancreatic panniculitis in renal and pancreas-kidney transplant recipients have been reported in
the literature.4-6 However, to our knowledge, this is the
first reported case after liver transplantation. We describe
the case of a 69-year-old man who underwent liver transplantation with pancreatic panniculitis which we believe
was secondary to acute pancreatitis. Recent literature is
reviewed to further familiarize the transplant specialist
with this unique presentation.
Case report
A 69-year-old man with a longstanding history of
chronic liver disease received a liver transplant in July
2010.The patient’s postoperative course was normal and
he was discharged on the 9th day of transplantation. In
May 2011, 10 months post-transplantation, he was admitted to our hospital because of a few days history of a
pain in the right knee and ankle, associated with painful
erythematous nodules (Figure 1). The patient had a severe discomfort, which made him unable to walk. He also
noticed the appearance of red elevated skin lesions over
both legs. He gave a history of a mild, nonspecific epigastric pain. His abdomen was soft and non-distended, and
he had no abdominal pain. A complete blood count was
within normal limits and his blood chemistry revealed
a moderate increase in aspartate aminotransferase levels
(111 U/L) and alanine aminotransferase levels (95 U/L).
Figura 1. Skin lesions at hospital admission.
Painful erythematous nodules at both ankles.
240 Acta Gastroenterol Latinoam 2014;44(3)239-242
María Anders y col
The patient’s amylase and lipase levels were both significantly elevated at hospital admission.
A marked deterioration of renal function was also
observed. At the time of admission, the patient’s immunosuppressive medications included tacrolimus and sodic
mycofenolic acid. Ultrasound of the abdomen ruled out
biliary compromise. Computed tomography scan of the
abdomen showed stranding around the pancreas consistent with acute pancreatitis. The magnetic resonance
cholangiopancreatography was normal. One week after,
some subcutaneous nodules became fluctuant and drained a brown, viscous, sterile fluid (Figure 2). A skin biopsy of a right medial ankle nodule was taken demonstrating
lobular panniculitis with prominent fat necrosis, neutrophilic cell infiltration and the presence of leukocytoclastic granular basophilic debris and numerous ghost cells
(Figure 3). Based on previous studies suggesting that octreotide may have a role in the treatment of pancreatitis, a
single dose of 20 mg of long-acting octreotide was used.7
Since pain was the predominant and disabling symptom
of the patient, pain intensity was assessed daily before and
during the treatment with octreotide. A scale of 0 to 10
was employed in the medical history. Criteria for maximal scoring10 was pain that interfered with sleep, inability
to evaluate the damaged area and need to increase the
amount of analgesics. A full response to treatment was
defined as the complete lack of pain, and a partial response as 50 % reduction in the pain score. This pain scale has
been previously used by our group in patients with primary
biliary cirrhosis and pruritus.8 The onset of beneficial effect
was two days, a partial response was observed between day
three and seven, and the pain disappeared completely after this period. The skin lesions were improved in parallel,
Figura 2. Subcutaneous nodules one week after admission.
Pancreatic pannicultis in a liver transplant patient
Figura 3. Hematoxilin-eosine stained skin biopsy showing anucleated adipocytes (ghost cells) and granulocyte infiltration.
disappearing within the first month after starting specific
treatment. The administration of octreotide was well tolerated and not associated with serious adverse effects.
Discussion
Pancreatic panniculitis is a rare condition occurring
in 0.3% to 3% of patients in the setting of pancreatic
disease, in which fat necrosis occurs in subcutaneous tissue
and elsewhere.1-3 The pancreatic disorders most commonly
associated with pancreatic panniculitis are alcohol-related
acute and chronic pancreatitis. It is also associated with
cancers of the pancreas, usually of acinar cell type.9. Moreover, pancreatic panniculitis can be associated with pancreas divisum, pancreatic pseudocysts, vesiculo-pancreatic
fistula and COX-2 inhibitor intake.10 Our case is relevant
for two reasons: the development of a dermatological complication first described in a patient with liver transplantation as well as the excellent response to treatment with
octreotide, a long-acting analogue of somatostatin.
The exact pathogenic mechanism of pancreatic panniculitis is still unclear, but release of pancreatic enzymes,
such as lipase, phosphorylase, trypsin and amylase, may
be involved. Moreover, the activity of these enzymes may
cause a syndrome called lobular panniculitis with focal
necrosis of lipids and a concomitant inflammatory reaction. In the skin, it is characterized by inflamed-appearing nodules and pustules on an erythematous base.1-3
Because pancreatic panniculitis resembles immunological disorders such as erythema nodosum, immunological
processes have been proposed as the cause of subcutaneous
fat necrosis.11 Moreover, immunosuppressive drugs, such
as tacrolimus or cyclosporine, can cause pancreatitis after
María Anders y col
transplantation.12 In this regard, cases of pancreatic panniculitis in renal transplant alone have been reported in the
literature.4 None of these patients were undergoing acute
renal allograft rejection at the time of the presentation. On
the contrary, the development of pancreatic panniculitis
secondary to allograft pancreatitis in a pancreas-kidney
transplant recipient has been more recently shown.5-6 In
both cases the allograft pancreatitis was associated with
acute pancreas rejection. These findings are important for
clinicians to recognize in these events an expression of dermatological manifestations of pancreas disease including
allograft pancreatitis and acute rejection.
Our patient presented with pancreatic panniculitis
with tender and erythematous nodules. Nodules have also
been reported on the buttocks, trunk, and upper extremities and scalp.1-3 As previously described, in the patient
nodules ulcerate and drain a sterile, oily material.1-3 Despite the high frequency, about 50% of the development of
acute arthritis was not observed in our patient, and neither
serositis (ascites, pleural effusion or pericardial effusion).
At the time of patient admission to hospital the main differential diagnosis to consider at the onset of erythematous
nodules on the lower extremities of an inmmunocompromised patient included erythema nodosum, erythema induratum of Bazin or infectious panniculitis. Therefore, a skin
biopsy was performed immediately. The histopathological
findings were found pathognomic of pancreatic panniculitis. A particularly unique aspect was the foci of anucleated
adipocytes with thickened, shadowy cell membranes known
as “ghost cells” within the affected fat lobules. Surrounding
these groups of clusters was observed a polymorphus inflammatory cell infiltrate consisting of neutrophils, lymphocytes,
macrophages and foreign-body giant cells.
Until now, there is no particular treatment for pancreatic panniculitis other than treatment of the underlying pancreatic disease.1-3 Symptomatic treatment
may include support stockings, leg elevation and bed rest
since the subcutaneous nodules tend to develop on the
lower extremities most commonly.1-3 In our patient, the
evidence for pancreatic enzyme release inducing panniculitis is further reinforced by the beneficial effect of the somatostatin analogue octreotide, a drug that shows mixed
results. In a patient with pancreatic carcinoma a rapid improvement of symptoms after octreotide was observed.13
However, these positive results have not been reproduced
in other patients.14-15 When this treatment was administered, a significant resolution of symptoms was observed in
a few days. Moreover, the clinical picture in our case was
correlated with pancreatic enzyme levels. In this case, resolution of the panniculitis occurred concomitantly with
Acta Gastroenterol Latinoam 2014;44(3)239-242
241
Pancreatic pannicultis in a liver transplant patient
disease regression during the pharmacological treatment,
suggesting that effective management of acute pancreatitis induces regression of panniculitis.
In conclusion, we present a unique case of pancreatic
panniculitis in a liver transplant patient. Although exceptional, the development of panniculitis should alert us of
the presence of some type of pancreatic damage. This case
also illustrates the diagnostic challenges of such cases and
the need for clinical and pathologic correlation in order
to facilitate timely and accurate diagnosis and initiate appropriate treatment.
Disclosure. The authors of this manuscript have no conflicts of interest to disclose and no funding.
References
1.Dahl PR, Su WP, Cullimore KC, Dicken CH. Pancreatic panniculitis. J Am Acad Dermatol 1995;33:413-417.
2.García-Romero D, Vanaclocha F. Pancreatic pannicuitis. Dermatol Clin 2008;26:465-470.
3.Ball NJ, Adams SP, Marx LH, Enta T. Possible origin of pancreatic fat necrosis as a septal panniculitis. J Am Acad Dermatol
1996;34:362-364.
4.Echeverria CM, Fortunato LP, Stengel FM, Laurini J, Diaz C.
Pancreatic panniculitis in a kidney transplant recipient. Int J Dermatol 2001;40:751-753.
242 Acta Gastroenterol Latinoam 2014;44(3)239-242
María Anders y col
5.Pike JL, Rice JC, Sanchez RL, Kelly ED, Kelly BC. Pancreatic panniculitis associated with allograft pancreatitis and rejection in a simultaneous
pancreas-kidney transplant recipient. Am J Transpl 2006;6:2502-2505.
6.Prikis M, Norman D, Rayhill S, Olyaei A, Troxell M, Mittalhenkle A. Preserved endocrine function in a pancreas transplant
recipient with pancreatic panniculitis and antibody-mediated rejection. A J Transplant 2010;10:2717-2722.
7.Narváez J, Bianchi MM, Santo P, de la Fuente D, Ríos-Rodriguez
V, Bolao F, Narváez JA, Nolla JM. Pancreatitis, panniculitis, and
polyarthritis. Semin Arthritis Rheum 2010;39:417-423.
8.Podesta A, Lopez P, Terg R, Villamil F, Flores De, Mastai R.
Treatment of primary biliary cirrhosis with rifamipicin. Dig Dis
Sci 1991;36:216-220.
9.Heykarts B, Anseeuw M, Degreef H. Panniculitis caused by acinous pancreatic carcinoma. Dermatology 1999;198:182-183.
10.Requena L, Yus ES. Panniculitis. Part I. Mostly septal pannicultis.
J Am Acad Dermatol 2001;45:163-183.
11.Preiss JC, Faiss S, Loddenkemper C, Zeitz M, Duchmann R. Pancreatic panniculitis in an 88-year-old man with neuroendocrine
carcinoma. Digestion 2002;66:193-196.
12.Mallory A, Kern F. Drug-induced pancreatitis: a critical review.
Gastroenterology 1980;78:813-820.
13.Hudson-Peacock MJ, Regnard CF, Farr PM. Liquefying panniculitis associated with acinous carcinoma of the pancreas responding
to octreotide. J R Soc Med 1994;87:361-362.
14.Mourad FH, Hannoush HM, Bahlawan M, Uthman I, Uthman
S. Panniculitis and arthritis as the presenting manifestation of
chronic pancreatitis. J Clin Gastroenterol 2001;32:259-261.
15.Durden FM, Variyam E, Chren MM. Fat necrosis with features
of erythema nodosum in a patient with metastatic pancreatic carcinoma. Int J Dermatol 1996;35:39-41.