Clinical characteristics of hemophagocytic lymphohistiocytosis following Kawasaki disease: differentiation from recurrent Kawasaki disease

Abstract

BackgroundOur aim was to investigate the clinical pattern of hemophagocytic lymphohistiocytosis following Kawasaki disease (HLH-KD), to enable differentiation of HLH from recurrent or refractory KD and facilitate early diagnosis.MethodsWe performed a nationwide retrospective survey and reviewed the clinical characteristics of patients with HLH-KD, including the interval between KD and HLH, clinical and laboratory findings, treatment responses, and outcomes, and compared them with historical data for both diseases.ResultsTwelve patients with HLH-KD, including 5 previously reported cases, were recruited. The median age was 6.5 years (range, 9 months-14.7 years). Eight patients were male and 4 were female. The median interval between the first episode of KD and the second visit with recurrent fever was 12 days (3-22 days). Of the 12 children, 2 were initially treated with intravenous IgG (IVIG) for recurrent KD when they presented at the hospital with recurrent fever. Eventually, 10 children received chemotherapy under an HLH protocol and 2 received supportive treatment. Two patients died of combined infections during chemotherapy, 1 was lost to follow up, and 9 remain alive. The overall survival rate at 4 years was 81.1% with a median follow up of 45.1 months.ConclusionA diagnosis of HLH-KD should be considered when symptoms similar to recurrent KD develop within 1 month of the first episode of KD. Our findings will help physicians differentiate between HLH and the recurrent form of KD.

Differentiation between incomplete Kawasaki disease and secondary hemophagocytic lymphohistiocytosis following Kawasaki disease using N-terminal pro-brain natriuretic peptide

“… 1) Eight secondary HLH patients who had previously been diagnosed with incomplete KD were compared with the 247 incomplete KD patients without HLH. 2) …”

“…The diagnostic criteria of HLH is met when at least 5 of the 8 following criteria were fulfilled: (1) fever; (2) splenomegaly; (3) cytopenia affecting at least 2 of the 3 lineages in the peripheral blood ( hemoglobin <9 g/dL, in infants <4 weeks: hemoglobin <10 g/dL, platelets <100×10 3 /mL, neutrophils <1×10 3 /mL); (4) hypertriglyceridemia (fasting, 265 mg/dL) and/or hypofibrinogenemia (<150 mg/dL); (5) hemophagocytosis in bone marrow, spleen, lymph nodes, or liver; (6) low or absent natural killer-cell activity; (7) ferritin >500 ng/mL; (8) elevated sCD25 (soluble IL-2 receptor≥2,400/mL). 2) …”

“…KD includes many associated complications such as cardiac, neurological, hematological, renal and gastrointestinal manifestations. Hematologic complications of KD include hemophagocytic syndrome (HLH) 2) and macrophage activation syndrome (MAS). 3)…”

Severe Recurrent Fever Episodes With Clinical Diagnosis of Hemophagocytic Lymphohistiocytosis, Incomplete Kawasaki Disease and Systemic-Onset Juvenile Idiopathic Arthritis: A Case Report and Literature Review

“…Accordingly, the common involvement of IL-6 might explain the overlapping clinical parameters observed in HLH, IKD, SoJIA and PFAPA. KD had been described as a precursor of secondary HLH, particularly IKD or IVIG-nonresponsive KD (9)(10)(11)(45)(46)(47)(48), but HLH was also observed before the diagnosis of KD (49). MAS complicated with KD was observed in some cases (50)(51)(52).…”

Kawasaki disease: guidelines of Italian Society of Pediatrics, part II - treatment of resistant forms and cardiovascular complications, follow-up, lifestyle and prevention of cardiovascular risks

“…The occurrence of macrophage activation syndrome (MAS) has also been reported in KD, heralded by non-remitting fever, impaired liver function, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, pancytopenia and frequently hemophagocytosis, that can be observed in bone marrow fine needle aspiration [ 22 , 23 ]. Some authors have reported the presence of clinical symptoms and laboratory abnormalities compatible with MAS in 1.1% of KD patients if using the Ravelli’s diagnostic criteria and in 0.42% if using the 2009 hemophagocytic lymphohistiocytosis diagnostic criteria [ 24 , 25 ]. Another complication is KD shock syndrome (KDSS), with similar symptoms to MAS, but with higher incidence, which was described by Kanegaye et al in 2009 [ 26 ]: this disorder is associated with severely increased inflammatory markers, platelet consumption and increased risk of CAA, mitral regurgitation and prolonged myocardial dysfunction.…”