September 12th, 2011 Good Morning

Incomplete (atypical) Kawasaki

Incomplete Kawasaki Infants are more likely to present with incomplete KD, even presenting only with fever and no other clinical features Infants are also at increased risk of CA aneurysms, because of delay in treatment due to their lack of complete diagnostic criteria Thus, infants six months of age or less with unexplained fever ≥ 7 days should be evaluated for KD regardless of whether they have signs of mucocutaneous inflammation

Incomplete Kawasaki Continued consideration of alternative diagnoses in “atypical cases” is essential despite initial response to IVIG This is particularly important in children who fail to respond or respond only incompletely to IVIG

HLH Hemophagocytic lymphohistiocytosis Proliferation of cells of the mononuclear phagocyte system Familial – underlying genetic disorder Secondary- caused by acquired conditions, including viral, neoplastic, and rheumatologic diseases

Familial HLH Autosomal recessive Mutation in the perforin gene accounts for 20-40% Incidence 1.2 per million Presents in infancy (birth to 18 months) Negative family history does not exclude Hyperactiviation of T cells and macrophages = cytokine storm TNF-alpha, IL1, IL6, and interferon gamma

Clinical Features Prolonged fever and hepatosplenomegaly LAD, rash, and jaundice May mimic viral infections, leukemia, multiorgan failure due to sepsis, and encephalitis CNS involvement Develops later in course Nonspecific Irritability, neck stiffness, hypo- or hypertonia, convulsions, ↑ICP, 6th or 7th cranial nerve palsy, atxia, bulging fontanelle

Lab abnormalities The pathologic findings result from the aggressive proliferation of normal histiocytes and T-lymphocytes in various tissues Cytopenias, hypertriglyceridemia, coagulopathy, elevated ferritin and transaminases CSF typically shows hyperproteinemia and pleocytosis

Bone Marrow Biopsy Reactive histiocytes show phagocytosis of nucleated red blood cells (red arrows) and platelets (black arrows). *In nearly 20 percent of cases, documenting hemophagocytosis on the first bone marrow specimen is difficult or impossible

Histiocyte Society *5 of 8 criteria must be fullfilled to diagnose Diagnostic Criteria 1. Fever 2. Splenomegaly 3. Cytopenias affecting at least 2 or 3 cell lines in peripheral blood 4. Hypertriglyceridemia or hypofibrinogenemia 5. Hemophagocytosis in BM, spleen, or lymph node biopsy 6. Low or absent natural killer cell activity 7. Serum ferritin concentration greater than 500 mcg/L 8. High concentrations of soluble IL-2 *5 of 8 criteria must be fullfilled to diagnose *Unless there is a gene mutation

Treatment Treat any underlying conditions Chemotherapy Etoposide, corticosteroids, cyclosporine, and IT MTX Stem cell transplant Best overall cure rates

Prognosis Familial HLH is fatal Median survival is less than 2 months if untreated

Take Home Message If an infant presents with fever, hepatosplenomegaly, and cytopenia, HLH should be high in the differential Early diagnosis of HLH is crucial because prognosis depends on prompt treatment

Noon Conference Jaundice/Anemia in the Newborn, Dr. Wetzel