Hemophagocytic syndrome after Kawasaki disease

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Hemophagocytic syndrome (HPS) is a rare and life-threatening disease in which a generalized histiocytic proliferation results in hemophagocytosis and up-regulation of inflammatory cytokines. This syndrome has been associated with infections, malignancy, drugs and immunologic triggers such as Kawasaki disease (KD). We describe the clinical and laboratory features of two children with HPS after KD and review the three previously reported pediatric cases of recrudescence of KD leading to HPS.Hemophagocytic syndrome (HPS) is a nonmalignant disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis and up-regulation of inflammatory cytokines. 1–3 Diagnostic criteria for HPS include fever, splenomegaly, cytopenia in two or more cell lines, hypertriglyceridemia or hypofibrinogenemia and hemophagocytosis in bone marrow, spleen, lymph nodes or other organs. 4 HPS encompasses both primary (familial) and secondary (reactive) disease. Clinical presentations of patients with primary and secondary HPS may be indistinguishable. 1, 4–6Secondary HPS may develop from strong immunologic activation associated with severe bacterial or parasitic infection (infection-associated hemophagocytic syndrome), viral infection, malignancy, drugs (phenytoin) or prolonged administration of fat-soluble lipids in parenteral nutrition (fat overload syndrome). 7, 8 HPS has been reported after conditions associated with significant immunologic stress such as acute lupus erythematosus and Kawasaki disease (KD). 9–12 We report two additional cases of the rare but important occurrence of HPS after Kawasaki disease.Case 1.An 11-year-old previously healthy Asian boy was admitted to Texas Children’s Hospital (TCH) with a 2-week history of fatigue, fever to 103°F and pharyngitis. At the onset of illness he also had nonexudative conjunctival injection and was believed to have a viral illness. Fever persisted despite scheduled antipyretics. Before admission he developed an erythematous, polymorphous, nonpruritic rash on his shoulders, arms and legs that evolved during the ensuing days to affect most of his body. He was evaluated in the outpatient setting where his physician noted a 1.5-cm right posterior cervical lymph node. A white blood cell count at that time was 16 000/mm3. The patient received a steroid injection, and oral prednisone was prescribed. He was afebrile for 1 day, but the rash worsened. He presented to TCH the following day with a fever to 103°F and myalgias.Because the patient had fever above 102°F for >5 days, an enlarged cervical lymph node measuring 1.5 cm, rash, a history of conjunctival injection and red, cracked lips, he fulfilled the diagnostic criteria for Kawasaki disease. Platelet count was 294 000/mm3. The patient was given 2 g/kg intravenous immunoglobulin (IVIG) and high dose (100 mg/kg/day) aspirin. An echocardiogram revealed no coronary artery aneurysms.The patient continued to have fever for 48 h, but the rash slowly improved. Three days after receiving IVIG, the patient was afebrile, but fever to 101°F returned the next day, and he was given a second dose of 2 g/kg IVIG.Two days after the second dose of IVIG, his fever increased to 103–104°F. Serum aspirin concentration was 29.6 mg/dl (therapeutic concentration, 20–30 mg/dl). The rash again worsened, and the posterior cervical lymph node measured 2 by 2 cm. A repeat echocardiogram was normal. An abdominal ultrasound demonstrated splenomegaly, gallbladder wall thickening and bile duct wall thickening or periportal edema. The patient’s hemoglobin decreased from 12.2 g/dl at admission to 10.6 g/dl. A platelet count was 109 000/mm3. His clinical course prompted an evaluation for HPS. The patient’s initial serum ferritin concentration was 4023 μg/l and increased to 11 158 μg/l the following day. Viral, bacterial and other infectious diseases studies did not reveal an infectious cause for HPS.Case 2.

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