1. September 12th, 2011
Good Morning

2. Incomplete (atypical) Kawasaki

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

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

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

13. 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

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