Download Pulmonary hypertension

七院聯合病例討論會
三軍總醫院
R2 李宗翰 / Vs. 喩永生主任
History
• This 12-year-old boy was suffered
from fever, cough, and abdominal
pain for 3 days.
• He is a victim of acute rheumatic
fever, including arthritis and carditis
and received regular Penicillin-G
treatment monthly for 1 year.
History
• He got an insert bite in his right
lower leg with a small infected
wound; the wound was treated at
home and improved.
History
• However, about 1 week later, the
symptoms of low-grade fever, cough
and abdominal pain with fullness
sensation were noted.
• 3 days later, progressive dyspnea
during exertion was noted and then
he was sent to our hospital for help.
Physical examination
• The physical examination showed
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respiratory distress, bilateral coarse
breathing sounds, grade Ⅰ-Ⅱ/Ⅳ systolic
murmurs over LSB, distended abdomen,
dilated jugular and superficial veins,
hepatosplenomegaly and pitting edema of
bilateral lower legs.
A small healed insert bite wound over
right lower leg.
Image
• The CXR showed minimal right side
pleural effusion with normal heart
size.
Laboratory data
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WBC:14100
Neutrophil:67% (40-74)
Lymphocyte:20% (19-48)
Monocyte:11% (3.4-9)
CRP:8.4 mg/dl (0-0.5)
Albumin:3.0 g/dl (3.4-4.8)
BUN:8 mg/dl (7-20) Creatinine:0.5 (0.5-1)
AST:126 U/L (-37) ALT:107 U/L (-41)
Total bilirubin: 1.2 mg/dl
Na:135 mmol/L (136-145) K:3.4 mmol/L
(3.5-5.1) Cl:98 mmol/L
Admission course
• Echocardiography:
• Tricuspid valve regurgitation
• Mitral valve regurgitation
• Pulmonary valve regurgitation
Admission course
• Abdominal sonography
• Hepatosplenomegaly
• Patent hepatic artery and portal vein
• Mild to moderate ascites
Subjective findings
• Fever
• Cough
• Abdominal pain with fullness
• Exertional dyspnea
• Insert bite
Objective findings
• Coarse breathing sounds
• Systolic heart murmurs over LLSB
• Pitting edema over bilateral lower
legs.
• Hepatosplenomegaly
• Wound of insert bite
Objective findings
• Liver function impairment
• Hypoalbuminemia
• Hyponatremia
• Elevated CRP level
• Elevated WBC count
• Pleural effusion
• MR, TR, PR.
Problems
• R/O Heart failure
• Fever
• Insert bite
• Hepatosplenomegaly
• Impaired liver functions
• Pleural effusion
• Ascites
Question
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Patient traveling history
EKG finding (arrhythmia, ST or T wave change)
Echocardiography findings (compared with previous)
Arterial blood gas (hypoxia, hypercapnea)
Bacterial culture (blood,pleural effusion)
Virus isolation and identification
Pleural effusion study (transudate or exudate, AFB stain)
Heart rate, blood pressure (arrhythmia, hypertension)
Anemia or thrombocytopenia (hematologic abnormalities)
Urine routine (Proteinuria ,hematuria)
Indirect fluorescent antibody assay serology
Causes of splenomegaly
• Infection
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Bacterial: Typhoid fever, endocarditis, septicemia, abscess
Viral:E-B virus, CMV, and others
Protozoal: Malaria, toxoplasmosis
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Hemolytic anemia: Congenital, acquired
Extramedullary hematopoiesis: thalassemia, osteopetrosis, myelofibrosis
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Malignant: Leukemia, lymphoma, histiocytoses, metastatic tumors
Benign: Hemagioma, hamartoma
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Lipidosis: Niemann-Pick, Gaucher disease
Mucopolysaccharidosis infiltration: Histiocytosis
• Hematologic processes
• Neoplasms
• Metabolic diseases
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Congestion
Cirrhosis
Cysts
Miscellaneous
Causes of ascites
• Hepatic (cirrhosis, fibrosis, obstruction)
• Renal (nephrotic syndrome, obstrutive, PD)
• Cardiac (heart failure, constrictive pericarditis)
• Infectious (abscess,TB, Chlamydia, schistosomia)
• Gastraointestinal (infarcted bowel perforation)
• Neoplastic (lymphoma, neuroblastoma)
• Pancreatic (pancreatitis, ruptured pancreatic duct)
• GYN (ovarian tumor, torsion, rupture)
• Miscellaneous (SLE, VP shunt, chylous,
hypothyroidism)
Heart failure
• Symptoms
– Fatigue, effort intolerance, anorexia,
abdominal pain, dyspnea, cough
• Sign
– Engorged jugular vein, hepatomegaly, basilar
rales, edema, cardiomegaly, gallop rhythm,
holosystolic murmur of mitral or tricuspid valve
regurgitation may be heard when ventricular
dilatation is advanced.
Heart failure
• Sign
– Pitting edema occurred usually in the legs.
– Pitting edema of the arms and face occurs
rarely and then only in the late course of HF.
– Ascites occurred most frequently in patients
with tricuspid valve disease or constrictive
pericarditis
Heart failure
• Chest X ray
• Exaggeration of the pulmonary arterial
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vessels to the periphery of the lung fields.
(Patients with cardiomyopathy may have a
relatively normal pulmonary vascular bed
early in the course of disease)
Cardiomegaly is invariable noted.
Pleural effusion was more frequent in the
right side than in the left side.
Heart failure
• EKG
• Left or right ventricular ischemic changes
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may correlate well with clinical and other
non invasive parameters of ventricular
function.
Low voltage QRS morphologic
characteristic with ST-T wave
abnormaluties may also suggest
myocardial inflammatory disease but can
be seen with pericarditis
Rhythm disease is also a potential cause
of heart failure.
Diagnosis of congestive heart
failure
(Framingham criteria)
• Major criteria (at least 1)
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Paroxysmal nocturnal dyspnea
Neck vein distention
Rales
Cardiomegaly
Acute pulmonary edema
S3 gallop
Increased venous pressure (>16 cm H2O)
Positive hepatojugular reflux
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Extremity edema
Night cough
Dyspnea on exertion
Hepatomegaly
Pleural effusion
Vital capacity reduced by 1/3 from normal
Tachycardia (>120 bpm)
• Minor criteria (at least 2)
Acute versus Chronic
• Acute: Sudden development of
myocardial infection or rupture of a
cardiac valve, no cardiomegaly, no
peripheral edema.
• Chronic: Dilated cardiomyopathy,
multiple valvular heart disease,
cardiomegaly, peripheral edema.
Right sided versus left sided
• Left: Dyspnea or orthorpnea as the
result of pulmonary congestion.
• Right: Edema, congestive
hepatomegaly, systemic venous
distention.
Carditis in rheumatic fever
• Rheumatic carditis is characterized by
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pancarditis, with active inflammation of
myocardium, pericardium, and endocardium.
Endocarditis, which is manifest by one or more
cardiac murmurs, is a universal finding in
rheumatic carditis.
Most case consist of mitral valvular disease or
combined aortic and mitral valvular disease.
Isolated aortic or right side valvular involvement
is uncommon.
Rheumatic heart disease
• Mitral valve: MR will result in increased atrium pressure and
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pulmoary congestion and symptoms of left side heart failure.
Spontaneous improvement usually occurs with time even in sever
cases. In chronic MR, pulmonary arterial pressure elevated and
right ventricle and atrium become enlarged and right side heart
failure develops.
MS will result in increased pressure and enlargement and
hypertrophy of the left atrium, pulmonary venous hypertension,
increased vascular resistance and pulmonary hypertension.
Aortic valve: AR will lead to volume overload with dilatation of LV.
Right-sided heart manifestations are rare.
Tricuspid valve: Primary tricuspid involvement is rare after
rheumatic fever. TR is more common secondary to right
ventricular dilatation resulting from unrepaired left side lesion.
Pulmonary valve: PR usually occurs on a functional basis
secondary to pulmonary hypertension and is a late finding with
severe mitral valve stenosis.
Pulmonary regurgitation
• Isolated congenital pulmonary
regurgitation is rare.
• Pulmoary valvular insufficiency most
often accompanies other
cardiovascular disease or may be
secondary to severe pulmonary
hypertension.
Tricuspid regurgitation
• Tricuspid regurgitation usually functional.
• Secondary to marked RV dilatation of any
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cause and often associated with
pulmonary hypertension.
When volume overload or intrinsic
myocardial disease -> dilated right
ventricle.
Tricuspid regurgitation often accompanies
with right ventricular dysfunction.
Pulmonary regurgitation &
Tricuspid regurgitation
• Pulmonary hypertension
• Cardiovascular disease -> RV
dysfunction
Causes of pulmonary hypertension
Conditions directly affecting pulmonary arteries
Primary pulmonary hypertension
Toxin-induced (ie, anorexic agents)
Vasculitis
Granulomatoses, collagen-vascular disorders, arteritis
Hepatic cirrhosis/portal disease
Congenital heart disease (Eisenmenger syndrome [ASD, VSD, PDA])
Infection
Human immunodeficiency virus
Causes of pulmonary hypertension
Conditions affecting pulmonary parenchyma
Chronic obstructive lung disease
Infiltrative/granulomatous diseases
Sarcoidosis, pneumoconiosis, radiation, fibrosis, neoplasm,
pneumonia, collagen-vascular diseases
Cystic fibrosis
Upper airway obstruction
High-altitude disease
Arteriovenous fistulas within the lung
Restrictive lung diseases
Causes of pulmonary hypertension
Conditions affecting the thoracic cage and
neuromuscular system
Obesity-hypoventilation/sleep apnea
Pharyngeal-tracheal obstruction
Kyphoscoliosis
Pleural fibrosis
Neuromuscular disorders
Myasthenia gravis, poliomyelitis, central respiratory disorders
Causes of pulmonary hypertension
• Conditions causing left atrial/or pulmonary
venous hypertension
Elevated left ventricular diastolic pressure
Systolic failure, diastolic dysfunction, constrictive
pericarditis
Aortic valve disease
Mitral valve disease
Cor triatriatum
Left atrial masses
Myxoma or neoplasm, thrombus
Fibrosing mediastinitis
Congenital pulmonary vein stenosis
Anomalous pulmonary venous connection
Pulmonary venoocclusive disease
Causes of pulmonary hypertension
• Nonvasculitis conditions that result in pulmonary
artery obstruction
Acute and chronic thromboembolism
Hemoglobinopathies (eg, sickle cell disease)
Primary or metastatic malignancies
Peripheral pulmonic stenosis
• Congenital pulmonary hypoplasia
Vasculitis syndrome
• Goodpasture disease
• Pulmonary hemorrhage and
glomerulonephritis.
• Symptoms & signs
• Hemoptysis, hematuria, proteinuria
and hypertension.
Vasculitis syndrome
• Wegener Granulomatosis
• Fever, myalgia, cough, nasal
discharge, hematuria proteinuria.
• Hemoptysis and dyspnea from lung
lesion.
• Uveitis, conjuctivitis.
• Peripheral granuloma.
• Palpalbe purpuric nodules and ulcers
Vasculitis syndrome
• Polyarteritis Nodosa
• Associated with infection of group A
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streptococcus, hepatitis B, CMV,
parvovirus , TB, E-B virus.
Symptoms & signs.
Fever
Abdominal pain (mesenteric arterial inflammation)
Hypertension, hematuria, proteinuria (renal vessels)
Purpura, edema, painful nodule (skin involvement)
Heart failure (myocarditis, myocardial ischemia)
Elevated liver function (hepatitis B infection more common in
adults)
Elevated ESR, anemia and leukocytosis
An algorithm for the workup of a patient with unexplained pulmonary hypertension
Pulmonary embolism
• Precipitating factor
• CVP insertion, immobility, heart disease, oral contraceptives,
ventriculoatrial shunt, trauma, infection, dehydration,
collagen vascular disease, shock , obesity, hematologic
disorder.
• Symptoms
• Chest pain, dyspnea, cough, fever, hemoptysis.
• Signs
• Rales, heart murmurs, tachycardia, fever, diaphoresis,
phlebitis, wheezing.
Pulmonary embolism
• Lab
• ABG: Respiratory alkalosis, arterial hypoxemia
• Elevated WBC count, D-dimer, fibrinogen, protein C, protein
S.
• Chest: Often normal in patient with PE.
• EKG: Nonspecific ST segment change and signs of cor
pulmonale
• Ventilation-perfusion image: Regional blood flow
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and ventilation defects . But normal V-P scan cant exclude
a PE and are interpreted as high probability, intermediate
probability, low probability, very low probability and normal.
Lung disease can limit the utility of this study.
Pulmonary angiography is the gold standard
diagnostic test for pulmonary embolism.
Cause of heart failure in
child
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Rheumatic fever
Acute hypertension
Thyrotoxicosis
Hemochromatosis-hemosiderosis
Cancer therapy (radiation, doxorubincin)
Sickle cell anemia
Endocarditis
Cardiomyopathy (Viral myocarditis, nonviral)
Myocarditis, hypertrophic, dilated.)
Cor pulmoale (cystic fibrosis)
Pulmonary regurgitation &
Tricuspid regurgitation
• Pulmonary hypertension
• Infection
• Pulmonary embolism
• Cardiovascular disease -> RV
dysfunction
• Rheumatic fever
• Endocarditis
• Cardiomyopathy (carditis, dilated,
hypertrophic )
Acute rheumatic fever
• Major: (least 2 major or 1+2
minor)
• Carditis, polyarthritis, erythema marginatum,
subcutaneous nodules
• Minor:
• Fever, arthralgia, elevated ESR or CRP, prolonged
PR interval
• Supported evidence of GAS infection:
• Positive throat culture or streptococcal antigen
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test
Elevated or increased streptococcal antibody titer
Infectious endocarditis
• Etiology: Viridans-type streptococci and staphylococcus
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aureus are the leading causative agents responsible for
endocarditis in pediatric patients.
Infective endocarditis is often a complication of congenital
or rheumatic heart disease
Prolonged fever without other manifestation.
Low grade fever, fatigue, myalgia, arthralgia, headache,
and at times, chills, nausea, and vomiting.
Splenomegaly and petechiae are relative common.
Osler nodes (tender, pea-sized intradermal nodules in the
pads of the fingers and toes), Janeway lesion (painless
small erythematous or hemorrhagic lesion on the palms
and soles), splinter hemorrhages (linear lesions beneath
the nails)
Embolic strokes, cerebral abscess, mycotic aneurysm, and
hemorrhage in staphylococcus disease.
Infectious endocarditis
• History
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Congenital or rheumatic heart disease
Preceding dental, urinary tract or intestinal procedure
Intravenous drugs abuse
Central venous catheter
Prosthetic heart valve
• Symptoms
• Fever, chills, chest and abdominal pain, arthralgia, myalgia,
dyspnea, malaise, night sweats, weight loss, CNS
manifestations
Infectious endocarditis
• Signs
• Elevated temperature, tachycardia, embolic phenomena (Roth
spots, petechia, splinter nail bed hemorrahge, Osler nodes, CNS
or ocular lesions), Janeway lesions, New or changing murmur,
splenomegaly, arthritis, heart failure, arrythmias, Metastatic
infection (arthritis, meningitis, mycotic arterial aneurysm,
pericarditis, abscesses, septic pulmonary emboli), clubbing
• Labs
• Blood culture (+), ESR ↑, CRP↑, anemia, leukocytosis, immune
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complexes, hypergammaglobulinemia, hypocomplementemia,
rheumatoid factor, hematuria, renal failure
Chest X ray: bilateral infiltration, nodules, pleural effusions
Echocardiography: valve vegetations, prosthetic valve dysfunction
or leak, myocardial abscess, new-onset valve insufficiency.
Infectious endocarditis
• Duke criteria
• Major: 1.Blood culture (+) 2.Evidence of endocarditis on
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echocardiography (intracardiac mass on a valve or other
site, regurgitation flow near a prosthesis, abscess, partial
dehiscence of prosthetic valves or new valve regurgitation
flow)
Minor:fever, embolic-vascular signs, immune complex
phenomena (GN, arthritis, rheumatoid factor, Osler nodes,
Roth spots),
2 major + 1 minor
1 major + 3 minors
5 minors
Infectious endocarditis
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• Etiology
Common: Native valve or other cardiac lesions
Viridans group streptococcus (dental procedure)
Staphylococcus aureus (drugs abuse)
Group D streptococcus (GU or GI tract procedures)
Uncommon: Native valve or other cardiac lesions
Streptococcus pneumoniae
Haemophilus influenzae
Coagulase-negative staphylococci
Coxiella burnetii (tick borne)
Neisseria gonorrhoeae (in human, sexual , intimate contact)
Brucella (zoonotic disease, contact with infected animals)
Chlamydia psittacli, Chlamydia trachomatis, Chlamydia pneumoniae (human,
sexual,respira)
Legionella (fresh water or aerosols containing bacteria)
Bartonella (cat scratch)
HACEK group (H: respiratory;A:trauma, aspiration to lung, )
Streptobacillus moniliformis
Pasteurella multocida (chesse, milk )
Campylobacter fetus
Culture negative (6% of cases)
Myocarditis
• Symptoms:
• Fever, severe heart failure, respiratory distress.
• Incubation time:1-7 days of the onset of
symptoms.
• Signs:
• Cyanosis, distant heart sounds, weak pulses,
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tachycardia, Gallop rhythm, acidosis, and shock.
Evidence of hepatitis, aseptic meningitis,
associated rash may be present.
Myocarditis
• Lab:
• Elevated CK, LDH
• EKG: Sinus tachycardia, reduced QRS voltage,
ST-segment and T-wave abnormalities,
arrhythmia.
• Echo: poor ventricular function, pericardial
effusion, mitral valve regurgitation, absence of
congenital heart lesion or coronary artery
Etiology of myocardial
disease
• Familial-Hereditary (myopathy, cardiomyopathy)
• Infection (Virus, Richettsiae,
Bacteria,parasite,fungus)
• Metabolic, nutritional, endocarine
• Connective tissue-Granulomatous diseaseinfiltrative
(SLE, vasculitis, Scleroderma, sarcoidosis,
dermatomyositis, leukemia)
• Drugs-Toxins (chemo, alcohol,irradiation.)
• Coronary arteries (Kawasaki disease, meidal necrosis,
anomalous left coronary artery)
• Other (anemia, ischemia)
Etiology of myocardial
disease
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• Infection:
Virus:
Coxsackievirus A and B
Adenovirus
HIV
Echovirus
Rubella
Varicella
Influenza
Mumps
Epstein-Barr
Measles
Poliomyelitis.
Etiology of myocardial
disease
• Richettsiae:
• Infection:
• Psittacosis
• Q fever, Coxiella burnetii(Ticks)
• Rocky Moutain spotted fever. (Tick bites)
• Bacterial
• Diphtheria (respiratory, cutaneous)
• Mycoplasma (airborne, human to human)
• Meningococcus (respiratory)
• Leptospirosis (water or soil contaminated with rat urine)
• Lyme disease (tick bites)
• Typhoid fever (foods or water contaminate with human
feces)
• Tuberculosis (airborne, human to human)
• Streptococcus (respiratory, dental procedure)
• Listeriosis (food(cheese, milk) contaminate with feces of
Etiology of myocardial
disease
• Parasites:
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• Infection:
Chagas disease (kissing bugs)
Toxoplasmosis (food or water comtaminated by cat feces)
Loa loa (biting flies)
Toxocara canis (dog feces)
Schistosomiasis (contact water contaminated with cercaria)
Cysticercosis
Echinococcus
Trichinosis. (meat with larvae of trichinella)
• Fungi:
• Histoplasmosis.
• Coccidiomyocosis.
• Actiomycosis.
Differential problems
• R/O Pulmonary hypertension
• R/O Pulmonary embolism
• R/O Cardiomyopathy
• Hepatosplenomegaly
• Insert bite transmitted disease
Transmission
Heart
Pul. hypertentsion
Pul. embolism
Hepatomegal
y
Splenomegaly
Malaria
Mosquitoes
Yellow
Fever
Mosquitoes
Dengue
Fever
Mosquitoes
J.
encephaliti
s
Mosquitoes
(-)
(-)
(-)
(-)
(-)
(-)
(-)
(-)
(+)
(-)
(-)
(-)
Filariasis
Mosquitoes
(-)
(-)
(-)
Colorado
tick fever
Tick
Tick born
Encephaliti
s
Tick
(-)
(-)
(-)
(-)
(-)
(-)
Disease
Transmission
Heart
Pul. hypertentsion
Pul. embolism
Hepatomegal
y
Splenomegaly
Leishmanias
is
Sandflies
Chagas
Disease
Tick
Sleeping
sickness
Tsetse fly
Loa loa
biting flies
(-)
(+)
(-)
(+)
(-)
(-)
(-)
(-)
(+)
(+)
(-)
(-)
Disease
Disease
Transmission
Heart
Relapsing fever
Tick,louse
Myocarditis
Lyme disease
Tick bite
Myocarditis
RMSF
Tick bite
Myocarditis
MSF
Tick bite
(-)
Scrub typhus
Chigger bite
Myocarditis
Murine typhus
Flea feces
(-)
Epidemic typhus Louse feces
(-)
HME, HE
Tick bite
(-)
Q fever
Tick borne
Myocarditis
Endocariditis
Chagas disease
Kissing bug
Myocarditis
Loa Loa
Biting flies
Cardiomyopathy
Hepatomegaly Pul. E.
Splenomegaly Pul. H.
(+)
(-)
(+) 33%
(-)
(-)
(-)
(-)
(-)
(-)
(+) P.E.
(-)
(-)
(-)
(-)
(+)
(+)
(-)
(+)P.E.
(+)
(-)
(-)
(-)
Richettsial infection
• Spotted fever group
• Typhus
• Scrub typhus
• Ehrlichioses and Anaplasmosis
• Q fever
Richettsial infection
• Spotted fever group
• Rocky Mountain spotted feverr
• Mediterranean Spotted fever
• African tick-bite fever
• Rickettsialpox
• Murine typhus-like
Spotted fever group
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Rocky mountain spotted fever
Tick bite transmission disease (Host:Dogs, rodents)
United states, southwestern, Canada, Mexico, Central America, South America
The incubation period: 2-14 days (median 7 days)
Headache, fever, anorexia, myalgia, restlessness.
GI symptoms(39-63%): Nausea, vomiting, diarrhea, abdominal pain.
Skin rash: Maculopapules onset after the 3rd day of illness -> petechia or purpura
after several days. (49~74%) (1st day: 14%, 3rd day:49%)
Hepatosplenomegaly (33%)
Clinical triad: Headache, fever, rash
Lab data: Low leukocyte count with left shift; low platelet count; low serum sodium
are clues for RMSF, impaired liver function (38%)
Severe case may present: myocarditis, facial edema, DIC, non cardiogenic
pulmonary edema, respiratory distress.
Diagnosis: Immunohistologic demonstration of specific rickettsial antigen (IFA, DFA,
IH; sensitivity 70%) (single IFA tilter>1:64 or 4 fold increased between acute and
convalescent sera (2-4 wk apart))
Treatment: Doxycycline (2.2mg/Kg/dose q12h->2.2mg/Kg/D divided q12h)
Tetracycline (25-50mg/Kg/D q6h po); Chloramphenicol (50-100mg/Kg/D q6h iv) at
least 5 days until afebrile 2-4 days.
Spotted fever group
• Mediterranean Spotted fever
• Tick bite transmission disease (Host: Dogs, rodents)
• Pathogen: R. conorii
• India, Pakistan, Russia, Ukraine, Georgia, Israel, Ethiopia, Kenya, South
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Africa, Morocco, and Southern Europe.
Fever, headache, myalgias, maculopapular rash which appears 3-5 days
after onset of symptoms.
70% of patient have eschar, tache noire, regional lymphadenopathy.
6% of cases: Purpuric skin lesion, neurologic signs,myocarditis,
respiratory distress, acute renal failure, thrombocytopenia.
Diagnosis: Immunohistologic demonstration of specific rickettsial antigen
Treatment: tetracycline, doxycycline, chloramphenichol
Azithromycin (10mg/Kg/D once daily po) and clarithromycin (15mg/Kg/D
bid po)
Spotted fever group
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• Rickettsialpox
Mite bite transmission disease (Host: Mouse, rodents)
Pathogen: R. akari
United States, Europe, and Asia.
90% papular or ulcerative lesion at the initial site of inoculation.
Varicelliform rash (maculopapular rash may become vesicular),
fever, headache, chills
The infection resolves spontaneously even without therapy.
Scrub typhus
• Scrub typhus
• Chigger bite transmission disease (Host: Rats, )
• Pathogen: Orientia tsutsugamushi
• Southern Asia, Japan, Indonesia, Australia, Korea, Asiatic Russia, India,
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China
Incubation period:6-21 days.
<50% of cases necrotic eschar with an erythematous rim
Fever, headache, myalgia, cough and GI symptoms.
Regional or generalized lymphadenopathy is common.
<50% of patients presents maculopapular rash.
Complications: Meningoencephalitis, myocarditis, interstitial pneumonitis.
Diagnosis:indirect fluorescent antibody assay or immunoperoxidase
serologic tests of O. tsutsugamushi antigen
Treatment: Doxycycline ; tetracycline; chloramphenicol at least 5 days
until afebrile 2-4 days.
Typhus Group Rickettsioses
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• Murine Typhus
Rat flea or cat flea feces transmission disease (Host: Rats )
Pathogen: Richesttsia typhi (mouse flea); R. felis(cat flea)
Distribution: Worldwide.
Incubation period: 1 to 2 weeks
Fever, rash (48-80%), myalgias (29-57%), vomiting (29-45%), cough
(15-40%), headache (19-77%), and diarrhea or abdominal pain(10-40%)
Usually maculopapule rashs distributed on the trunk and extremities.
Neurologic involvement(photophobia, confusion, stupor, coma, seizures,
meningismus and ataxia) may be a frequent finding in adults; 17% of
hospitalized and 6% of outpatients of infected children.
Lab data: Leukopenia with left shift(36-40%); thrombocytopenia(43-60%);
Hyponatremia(20-66%); Hypoalbuminemia (46-87%); elevated AST and
ALT
Diagnosis:Indirect fluorescent antibody assay serology
Treatmet: Doxycycline, tetracycline, chloramphenicol at least 5 days until
afebrile 2-4 days.
Typhus Group Rickettsioses
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• Epidemic typhus
Louse feces (via wound or conjunctiva) disease (Host: Human )
Pathogen: Richesttsia prowazekii
Distribution: Africa, South Amercia. Central America. Mexico, Asia.
Incubation period:<14 days.
Fever, severe headache, abdominal pain, rash in most people
Chills(82%); myalgias(70%); arthralgia(70%); anorexia (48%),
nonproductive cough (38%), dizziness (35%), photophobia (33%),
nausea (32%), abdominal pain (30%), tinnitus (23%);
meningismus (17%), visual disturbances (15%), vomiting (10%)
Treatment: Doxycycline; tetracycline; Chloraphenicol at least 5
days until afebrile 2-4 days.
Ehrlichioses and
Anaplasmosis
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• Ehrlichiosis and anaplasmosis
Tick bite disease (Host: Deer, dogs(HME) ; deer rodents, ruminants (HGE))
Pathogen: E. chaffeensis (Human monocytic ehrlichiosis (HME));
Anaplasma phagocytophilum (Hauman anaplasmosis; Human granulocytic ehrlichiosis
(HGE))
Distribution: United states, Europe, Africa
Incubation period:2 days to 3 weeks.
Fever(97%), headache (81%), myalgias(68%), malaise (84%) anorexia, and nausea
or vomiting, maculopapular rash(2/3 of children with HME), conjunctivitis,
pharyngitis and lymphadenopathy (minority),
Hepatomegaly and splenomegaly (frequent), systolic ejection murmur (often)
Lab data: leuopenia (58-72%); lymphopenia (75-78%); thrombocytopenia(80-92%);
Granulomas and granulomatous inflammation in 75% in bone marrow examinations
of HME; Elevated transaminase levels; Hyponatremia; prolonged PT/PTT; Morulae in
peripheral blood monocyte or neutrophil.
Diagnosis: The demonstration of morulae, single high tilter (>=1:128) of A.
phargocytophilum antibodies or seroconversion (>=1:64)
Treatment: Doxycycline, Tetracycline at least 5 days until afebrile 2-4 days.
Q fever
• Acute Q fever
• Inhalation of infectious aerosols, ingestion of contaminated dairy products,
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ticks disease (Host: Cattle, sheep, goats, cats, rabbits )
Pathogen: Coxiella burnetii
Distribution: Worldwide
Incubation day: 3-30 days.
Fever, sever headache, arthralgia, myalgia, cough, fatigue, vomiting,
abdominal pain.
Hepatomegaly and splenomegaly may be detected in some patients.
Fever (91%), respiratory involvement (34%); rash (11%), neurologic
findings (4%)
Lab data: Leukopenia with left shift (50%), thrombocytopenia (9-48%),
reative thrombocytosis in recovery state results in DVT, Elevated
transaminase levels (62%), elevated ESR (50%)
Hepatitis (40%), Myocarditis, pericarditis.
Right side endocarditis results in pulmonary embolism is reported.
Self-limited illness that last for 2-36 weeks.
Q fever
• Chronic Q fever
• Chronic Q fever occurred months to years after acute Q fever or even in
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the absence of any history of acute Q fever.
Presents with endocarditis, hepatitis, myocarditis, FUO, pneumonia,
osteomyelitis.
Q fever endocarditis: Fever may be absent in up to 15% of cases. More
than 75% of all identified have congestive heart failure.
Data: ESR > 20 mm/hr (80%), hypergammaglobulinemia (54%),
hyperfibrinogenemia (67%). Rheumatoid factor (>50%) , antiplatelet
antibodies, anti-smooth muscle antibodies, antimitochondrial antibodies,
positive direct Coombs test.
Diagnosis: (children with fever of unknown origin, atypical pneumonia,
culture negative endocarditis) 4-fold increase in indirect fluorescent
antibody tilters to phase 1 and phase 2 antigens in acute and convalescent
(2-4 weeks) sera
Treatment: Acute:Treated within 3 days of onset of symptoms with
tetracycline or doxycycline.
Chronic:Tetracycline or doxycycline + rifampin, ofloxacin or pefloxacin.
(18months until phase 1 tilters of <1:200 for IgG and negative IgA tilters)
Relapsing fever (Borrelia)
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Human louse, tick disease (Host: Human )
Pathogen: Borrelia. Recurrentis
Distribution: Worldwide
Incubation time: 5-15 days(median 8 days)
Fever lasting 2-9 days then a febrile periods of 2-7 days.
Symptoms: High fever, delirium, lethaygy, headache, myalgia, arthralgia,
photophobis,nausea, vomiting, abdominal pain, productive cough, mild
respiratory distress, bleeding tendency(epistaxis, hemoptysis, hematuria,
hematemesis), skin rash
Sings: lymphadenopathy, splenomegaly, hepatic tenderness with
hepatomegaly is a common sign, jaundice (50%)
Severe complication: CNS, mycocarditis, hepatic failure, DIC.
Diagnosis: spirochete in Giemsa or Wright’s stain
Treatment: Doxycycline (500mg po q6h), erythromycin (50mg/Kg/D) for
<12 years old children.
Lyme disease
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• Lyme disease
Tick bite disease (Host: Deer, Rodent)
Pathogen: Borrelia burdorferi
Distribution:Worldwide
Early localized disease: typical annular rash, erythema migrans(90%)
occurs in 7-14 days after the bite, it appear as a target lesion with central
clearing and may be associated with systemic features including fever,
myalgia, headache, malaise. Without treatment, the rash will expands to
an average diameter of 15cm and remains present at least 1-2 wks.
Early disseminated disease: Multiple skin lesion, accompanied by fever,
myalgia, headache, malaise; conjunctivitis and lymphadenopathy may
develop.; Aseptic meningitis, uveitis, focal neurologic findings, especially
cranioneuropathies, carditis with varying degrees of heart block, palalysis
of the facial nerve is relatively common in children.
Late disease: Arthritis, especially the large joints (> 90% in knees) with
swollen and tender joints, chronic demyelinating encephalitis, polyneuritis,
impairment of memories
Lyme disease
• Diagnosis: The presence of EM rashes > 5cm in diameter or serologic
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confirmation of infection with evidence of at least one manifestation of
musculo skeletal, neurological or cardiovascular disease .
The culture of B. burgdorferi in Barbour-Stoenner-Kelly medium from the
specimen of plasma, biopsy samples of erythema migrans lesions,
occasionally from cerebrospinal fluid samples in patients with meningitis
can permit a definitive diagnosis.
Serologic tests was used as diagnostic method in public health surveillance
and in clinical diagnosis. This Western Blot detects the presence or
absence of antibodies and is not quantitative. Antibody can still be
detected with Western blot even after a successful. It was used to confirm
equivocal and positive serology results obtained by ELISA or IFA.
Treatment:doxycycline (100mg bid for 14-21 days) in children older than 8
yr of age; Amoxicillin (50 mg /Kg/D tid po 14-21 days); cefuroxime
(30mg/kg/D bid po for 14-21 days ); erythromycin (30-50mg/Kg/D qid for
14-21 days.)
Meningitis: Ceftriaxone 50-80 mg/Kg/D iv qd for 14-28 days.
Carditis: Mild to moderate as EM; Severe as meningitis
Late disease: the same as for EM except for 28 days->recurrence choose
second dose or meningitis.
Chagas disease
• Acute Chagas disease
• Kissing bugs bite transmission disease
• Pathogen: Trypanosoma cruzi
• Distribution: Western hemisphere (Mixeco, south America, Brazil,
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Argentina)
Acute chagas disease: mild fever, malaise, facial edema, lymphadenopathy,
local sign of inflammation at the site entry(chagomas) .
50% with Romana sign (Unilateral, painless eye swelling), conjunctivitis,
preauricular lymphadenitis
Lymphadenopathy, hepatosplenomegaly, meningoencephalitis can occur
in children younger than 2 years old.
The heart is the primarily target organ, 4 chamber dilatation, diffuse
myocarditis and inflammation of the conduction system lead to the
development of fibrosis.
Chagas disease
• Chronic Chagas disease
• Chronic Chagas disease: Cardiomyopathy included congestive
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heart failure, arrhythmia and thrombocytopenia events. EKG will
showed complete A-V block, RBBB, LBBB, left ventricular apical
aneurysm.
Diagnosis: Giemsa-stain smear will demonstrate motile
trypanosomes.
These are only seen in the peripheral blood in the first 6-12 week
of the illness.
Specific IgM antibodies in ELISA or IFA in acute Chagas disease.
Complement fixation is considered the most reliable
immunodiagnostic method for chronic Chagas disease.
Treatment: Nifurtimox (15-20mg/kg/D qid po(1-10 y/o); 12.515mg/KG/D (11-16 y/o), 8-10mg/Kg/D(>16 y/o)) for 90 days and
benznidazole (10mg/Kg/D bid po(<12y/o); 5-7 mg/kg/D(>12y/o))
for 60 days
Disease
Transmission
Heart
Relapsing fever
Tick,louse
Myocarditis
Lyme disease
Tick bite
Myocarditis
RMSF
Tick bite
Myocarditis
MSF
Tick bite
(-)
Scrub typhus
Chigger bite
Myocarditis
Murine typhus
Flea feces
(-)
Epidemic typhus Louse feces
(-)
HME, HE
Tick bite
(-)
Q fever
Tick borne
Myocarditis
Endocariditis
Chagas disease
Kissing bug
Myocarditis
Loa Loa
Biting flies
Cardiomyopathy
Hepatomegaly Pul. E.
Splenomegaly Pul. H.
(+)
(-)
(+) 33%
(-)
(-)
(-)
(-)
(-)
(-)
(+) P.E.
(-)
(-)
(-)
(-)
(+)
(+)
(-)
(+)P.E.
(+)
(-)
(-)
(-)
Impression
• Q fever
• Rocky mountain spotted fever
Laboratory Diagnosis and Treatment of Selected Rickettsial Diseases
Disease
Laboratory Diagnosis
Treatment
Mediterranean
spotted fever,
Japanese spotted
fever, Queensland
tick typhus, Flinders
Island spotted fever,
African tick-bite
fever
Isolation of rickettsiae by
shell-vial culture; serology,
IFA (IgM, ≥1:64; or IgG,
≥1:128); skin biopsy
immunohistochemical
detection of rickettsiae;
PCR amplification of DNA
from tissue specimens
Doxycycline (100 mg bid
PO for 1-5 days) or
Ciprofloxacin (750 mg bid
PO for 5 days) or
Chloramphenicol (500 mg
qid PO for 7-10 days)
or (in pregnancy)
Josamycina (3 g/d PO for 5
days)
Rickettsialpox
IFA: seroconversion to a
titer of ≥1:64 or a single
titer of ≥1:128; crossadsorption to eliminate
antibodies to shared
antigens necessary for a
specific diagnosis of the
spotted fever rickettsial
species; skin biopsy
immunohistochemistry
Doxycycline (100 mg bid
PO for 1-5 days) or
Ciprofloxacin (750 mg bid
PO for 5 days) or
Chloramphenicol (500 mg
qid PO for 7-10 days)
or (in pregnancy)
Josamycina (3 g/d PO for 5
days)
Endemic (murine)
typhus
IFA: fourfold rise to a titer
of ≥1:64 or a single titer of
≥1:128; immunohistology:
skin biopsy; PCR
amplification of R. typhi or
R. felis DNA from blood;
dot ELISA and
immunoperoxidase
methods also available
Doxycycline (100 mg bid
PO for 7-15 days) or
Chloramphenicol (500 mg
qid PO for 7-15 days)
Epidemic typhus
IFA: titer of ≥1:128;
necessary to use clinical
and epidemiologic data to
distinguish among louseborne epidemic typhus,
flying-squirrel typhus, and
Brill-Zinsser disease
Doxycycline (200 mg PO as
a single dose or until
patient is afebrile for 24 h)
Scrub typhus
IFA: titer of ≥1:200; PCR
amplification of O.
tsutsugamushi DNA from
blood of febrile patients
Doxycyclineb (100 mg bid
PO for 7-15 days) or
Chloramphenicol (500 mg
qid PO for 7-15 days or (for
children)
Chloramphenicol (150
mg/kg per day for 5 days)
Diagnosis of Q fever
• Q fever results from infection with C.
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burnetii.
This small gram-negative microorganism
(0.2 um by 0.7 um) exists in two antigenic
forms: phase I and phase II.
The phase I form is extremely infectious
and exists in humans and other animals.
Passage in cell culture or embryonated
eggs results in a shift to the phase II form,
which is avirulent.
Diagnosis of Q fever
• C. burnetii can be isolated from buffy-coat blood samples or
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tissue specimens by a shell-vial technique; C. burnetii since it
is considered highly infectious.
PCR can be used to amplify C. burnetii DNA from tissue or
biopsy specimens. This technique can also be used on paraffinembedded tissues.
Serology is the most commonly used diagnostic tool. Three
techniques are available: complement fixation, indirect
immunofluorescence, and enzyme-linked immunosorbent
assay.
Indirect immunofluorescence is sensitive and specific and is
the method of choice.
Rheumatoid factor should be adsorbed from the specimen
before testing.
Diagnosis of Q fever
• 4-fold increased in IFA titers to phase I and phase II antigens
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between acute and convalescent sera(2-4wks)
An IgG titer of ≥1:800 to phase I antigen is suggestive of
chronic Q fever.
In almost all instances of chronic Q fever, the antibody titer to
phase I antigen is much higher than that to phase II antigen.
The reverse is true in acute Q fever. In addition, in acute Q fever,
it is usually possible to demonstrate a fourfold rise in titer
between acute- and convalescent-phase serum samples.
Elevated phase I IgA antibody are diagnostic for Q fever
endocariditis.
Diagnosis of RMSF
• The most common serologic test for confirmation of the
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diagnosis is the indirect immunofluorescence assay.
Between 7 and 10 days after onset, a diagnostic titer of ≥1:64
is usually detectable.
The sensitivity and specificity of the indirect
immunofluorescence assay are 94 to 100% and 100%
The only diagnostic test that is useful during the acute illness
is immunohistologic examination (immunofluorescence or
immunoenzyme staining) of a cutaneous biopsy of a rash
lesion for R. rickettsii.
Examination of a 3-mm punch biopsy of such a lesion is 70%
sensitive and 100% specific.