Systemic Mastocytosis: A Confounder of Refractory Pruritus in a Liver Disease Patient Creating Management Dilemma

Abstract

Introduction: Systemic mastocytosis (SM) results from a clonal, neoplastic proliferation of abnormal mast cells (MC) in 1 or more organ systems. Patients become susceptible to itching, urticaria, and anaphylactic shock, which occur due to histamine release from mast cells. SM manifestations may co-exist in the presence of other systemic disease, thus confounding the overall clinical presentation. Case Report: A 27-year-old white woman with a history of Crohn’s disease with primary sclerosing cholangitis (PSC) had refractory diarrhea (since Crohn’s diagnosis 15 years ago) and refractory pruritus of 8 years’ duration. She developed intense pruritus in 2005, followed by a diffuse erythematous macular rash, and was seen by dermatology with skin biopsies failing to provide any clear etiology. Concurrently, abnormally elevated liver enzymes (especially alkaline phosphatase) were noted and further work-up with MRCP and liver biopsy suggested a diagnosis of PSC. Her pruritus management consisted of ursodiol, antihistamines, cholestyramine, rifampin, and sertraline, with minimal improvement. The patient was referred for consideration for a liver transplant, in view of her refractory pruritus. She was seen by orthopedics for bilateral knee joint pain and swelling, and orthopedics did a bone scan that revealed increased uptake around the distal right femur, where a bone biopsy was performed and histopathology on the biopsy revealed multifocal aggregates of CD117+/ tryptase+ mast cells (MC) with >25% showing abnormal morphology and co-expression of CD25. Pathology findings were suggestive of indolent systemic mastocytosis. Discussion: SM is diagnosed by 1 major criterion plus 1 minor criterion or 3 minor criteria. The major criterion is defined as multifocal clusters of MC (>15) in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, presence of KITD816V, abnormal MC expression of CD25, and/or CD2. SM classification into indolent (SM), aggressive (ASM), associated with a clonal non-MC lineage disease (SM-AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis. SM treatment is generally palliative. Interferon-α and corticosteroids are used for symptomatic management in ASM patients. Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Treatment of SM-AHNMD is based primarily on a non-MC neoplasm with hydroxyurea having some therapeutic benefit. Through our case, we want the gastroenterologist to remain cognizant of this rare entity and to have a greater suspicion when encountered with patient with refractory pruritus in a setting of biliary disorder (PBC, PSC), for adequate diagnosis and management.