September 12th, 2011
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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
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Continued consideration of alternative diagnoses
in “atypical cases” is essential despite initial
response to IVIG
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This is particularly important in children who fail
to respond or respond only incompletely to IVIG
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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
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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
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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
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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
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
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
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Treat any underlying conditions
Chemotherapy
 Etoposide, corticosteroids, cyclosporine, and IT MTX
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Stem cell transplant
 Best overall cure rates
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Familial HLH is fatal
 Median survival is less than 2 months if untreated
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If an infant presents with fever,
hepatosplenomegaly, and cytopenia, HLH should
be high in the differential
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Early diagnosis of HLH is crucial because
prognosis depends on prompt treatment
Jaundice/Anemia in the Newborn, Dr. Wetzel