2518 Transitory Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in a Child With Very Early Onset (VEO) of Ulcerative Colitis (UC) Complicated With Primary Sclerosing Cholangitis (PSC)

Abstract

INTRODUCTION: VEO - Inflammatory bowel disease (IBD), in children younger than 6 years of age, is frequently associated with a more severe course and distinct genetic profile compared with later onset IBD. We report the case of a child with VEO - UC complicated with PSC and HLH/MAS. CASE DESCRIPTION/METHODS: A 10-year-old male, presented with bloody diarrhea, hepatomegaly and elevated transaminases when he was 30 months old. He had moderate pancolitis associated with C difficile (Cdiff) infection. He improved after metronidazole and sulfasalazine (SFZ) treatment. Two months later, he had hematochezia and endoscopic worsening of his colitis, which improved after discontinuing SFZ and receiving steroids and 6-MP. MRCP was consistent with PSC (Figure 1) and he was started on ursodiol. At ∼ 7 years of age, while receiving treatment with 6MP and Infliximab, he was hospitalized due to fever, hepatomegaly, diarrhea and pancytopenia. Blood and stool cultures, and tests for Cdiff, EBV, CMV, rota and parvovirus were negative. Triglyceride and ferritin levels were normal. He improved clinically and his pancytopenia resolved after 5 days of empirical antibiotic treatment (AbTx). Bone marrow biopsy (BMBx) was deferred. Metabolites of 6MP were normal but 6MP was held temporarily. Six months later, he had fever and diarrhea associated with pancytopenia and high levels of ESR, CRP, ferritin, triglyceride and interleukin 2 receptor. Number and function of NK cells were decreased. Stools and blood cultures, and tests for EBV, HSV and CMV were negative. Cdiff stool antigen was positive but PCR was negative. BMBx showed histiocytosis and erythophagocytosis (Figure 2). Lymphocyte flow cytometry was negative for lymphoproliferative disorder. After AbTx he improved and pancytopenia and ferritin level corrected within one week. Routine immunodeficiency tests were normal. Gene mutations associated with familial HLH: PRF1, Rab27A, SH2D1A, STX11, STXBP2, UNC 13D and XIAP were negative. 6MP was held. Infliximab initially, and subsequently Adalimubab, were discontinued because of high antibodies and allergic reactions. Five months later 6MP was restarted. He has been in remission of UC for 16 months. DISCUSSION: HLH/MAS is a very rare, potentially fatal complication in IBD patients. Our patient has a history of VEO - UC, PSC and two episodes of pancytopenia not associated with EBV or CMV - one of which fulfilled criteria for HLH/MAS. Remarkably, he recovered within one week after empirical AbTx without steroids or other treatment for HLH/MAS.