Case 2 -

Kawasaki Disease Jan M. Orenstein George Washington University Medical Center Washington, DC

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Clinical History This 4 month old infant was well until one month prior to death, when he developed fever, conjunctival injection, red dry cracked lips, rash and irritability. Lab tests showed a leukocytosis with WBC greater than 30,000, anemia, thrombocytopenia, and markedly elevated CRP. He was initially treated with antibiotics, and then intravenous gammaglobulin (IVIG) and aspirin therapy were administered. An echocardiogram initially showed mild ectasia of the coronary arteries. The patient continued to have fever after IVIG therapy, so additional antibiotics and another dose of IVIG was given. Repeat echocardiogram 5 days later showed diffuse coronary artery dilatation. Fevers persisted and he was treated with pulse doses of steroids and 2 doses of Remicaid. The baby then developed ST segment elevation on EKG and elevated troponin levels. He was placed on a heparin infusion, and EKG changes improved, but further testing (MRI and MRA) showed that he had developed extensive aneurysms of the coronary, brachial, axillary, and iliac arteries. The patient was stable, acting appropriately, and eating well until the morning of his death, when he developed respiratory and cardiac arrest. Stat CT angiography following stabilization showed a ruptured right iliac artery aneurysm. He was emergently taken to the operating room and his right iliac artery was ligated. However, he continued to require blood transfusions and inotropic support for refractory shock and DIC. He again suffered cardiac arrest and could not be resuscitated. Images provided include the gross appearance of the heart and an H&E-stained section of lung. Case 2 - Figure 1 Light microscopic studies of tissues from a patient with Kawasaki Disease. H&E of ciliated bronchial epithelium, demonstrating amphophilic supranuclear RNA-containing cytoplasmic inclusion bodies (arrows). Case 2 - Figure 2 Gross heart specimen from a patient with Kawasaki Disease demonstrating coronary artery aneurysms. Diagnosis: Kawasaki Disease Symptoms A disease of unknown etiology most frequently affecting infants and young children under the age of 5 years (80-85%). Male:Female ratio, 1.3-1.5:1.0; 0.3-0.5% fatality rate; 2-3% recurrence rate; 1-2% proportion of sibling cases. World-wide distribution, highest incidence rate in Japan, seasonal (Winter/Spring), and clusters. Principal Symptoms (suggest infectious agent) Fever persisting for 5 days or more. Changes in peripheral extremities. (Initial stage): Reddening of palms and soles, indurative edema. (Convalescent stage): Membranous desquamation of fingertips. Polymorphous exanthema. Bilateral conjunctival congestion. Changes in lips and oral cavity: Reddening of lips, "strawberry" tongue, diffuse injection of oral and pharyngeal mucosa. Acute non-purulent cervical lymphadenopathy. At least five of items 1-6 should be present to satisfy the diagnosis. However, patients with 4 of the principal symptoms can be diagnosed as having the disease when radiography reveals characteristic cardiac pathology. Other Significant Symptoms or Findings Cardiovascular: Auscultation (heart murmur, gallop rhythm, distant heart sounds); ECG (prolonged PR/QT intervals, abnormal Q wave, low voltage, ST-T changes, arrhythmias); Chest X-ray (cardiomegaly); 2-D echo (pericardial effusion, coronary aneurysms); Aneurysms of peripheral arteries other than coronaries (axillary, inguinal, etc.). Angina pectoris or myocardial infarction. GI tract: Diarrhea, vomiting, abdominal pain, hydrops of gallbladder, paralytic ileus, mild jaundice, slight increase of serum transaminase. Blood: Leukocytosis with left-shift, thrombocytosis, increased ESR, positive CRP, hypoalbuminemia, increased alpha-2 globulin, slight decrease in RBC and Hgb levels. Urine: Proteinuria, increased WBC in urine sediment. Skin: Redness and crust at the site of BCG inoculation, small pustules, transverse furrows of finger nails. Respiratory: Cough, rhinorrhea, abnormal shadow on chest X-ray. Joint: Pain, swelling. Neurological: Pleocytosis of mononuclear cells in CSF, convulsions, unconsciousness, facial palsy, paralysis of the extremities. Principal Pathology Disease of medium size arteries, especially coronaries, also iliacs, axillary, etc. Lymphocytic arteritis Necrosis of smooth muscle cells of media Intimal proliferation, luminal narrowing Aneurysms, can rupture Myocardial ischemia Supranuclear intracytoplasmic inclusions in ciliated cells of medium size bronchi Inclusions stain for RNA Inclusions positive by IHC using artificial IgA antibody prepared from arteritis TEM shows viral-like structures Other Pathology Heart: endocarditis, myocarditis, pericarditis Alimentary tract: inflammation of tongue, salivary gland, small bowel, GALT, liver (especially bile ducts) and pancreas (especially ducts) Respiratory tract: peribronchial inflammation, necrosis and desquamation of bronchial mucosal epithelium, segmental interstitial pneumonia, rarely pleuritis and lung nodules Urinary system: periglomerular interstitial inflammation, prostatitis (mainly ducts), cystitis Nervous system: asceptic leptomeningitis, choriomeningitis, inflammation around ganglia Lymphoreticular system: lymph node enlargement with reactive hyperplasia, congested spleen