Systemic Mastocytosis as an Unconventional Cause of Variceal Bleeding: Think Outside the Box

Abstract

Systemic mastocytosis is a rare infiltrative disease caused by excessive mast cell proliferation and accumulation in various organs including skin, bone marrow, digestive system, liver and spleen. Common gastrointestinal symptoms include abdominal pain, diarrhea, nausea and vomiting. Gastrointestinal bleeding is seldom reported in mastocytosis and is predominantly caused by peptic ulcer disease secondary to excessive histamine secretion by mast cells resulting in hyperacidemia. Though exceptionally rare, non cirrhotic portal hypertension is peculiar in mastocytosis and is caused by perisinusoidal mast cell infiltration and fibrosis. Those patients typically present with variceal bleeding in the setting of preserved liver function. Herein we report a rare case of systemic mastocytosis that was disclosed after a massive variceal bleeding. 59 year old male with atrial fibrillation on coumadin, congestive heart failure and smoldering multiple myeloma presents with hematemesis and melena of 1 day duration. At presentation, he was hemodynamically unstable with severe blood loss (Hb:5.2g/dl) and supratherapeutic INR of >15. His liver profile was unremarkable except for albumin of 2.3. After resuscitation and reversal of anticoagulation, EGD reveals large gastroesophageal varices (Fig 1) with red whale signs. Band ligation was performed and control of bleeding achieved. He denied any history of liver diseases, hepatitis or alcohol abuse. Abdominal sonogram revealed normal liver parenchyma and patent hepatic and portal veins without any evidence of cirrhosis. Serologic tests for hepatitis A, B, C, HIV, markers of autoimmune hepatitis (AMA, ASMA, LKM antibodies), ceruloplasmin, iron indices and tumor markers were all unrevealing. Liver biopsy revealed severe perisinusoidal fibrosis with focal nodule formation (Fig 2). CD117 (c-kit) immunostain disclosed abundant mast cells in portal tracts (Fig 3). Serum tryptase level was elevated: 104 ng/ml (reference: 2 to 10) and bone marrow biopsy revealed hypercellular marrow infiltrated predominantly by mast cells, establishing the diagnosis of systemic mastocytosis.Figure 1Figure 2Figure 3This unique report highlights an out of the ordinary reason of variceal bleeding due to non cirrhotic portal hypertension in a patient with systemic mastocytosis. In this rare myeloproliferative disease, mast cell derived factors (tryptase, TNF α, PDGF and chymase) induce excessive collagen formation and fibrosis deposition in the hepatic sinusoids which lead to compression of portal veins and increased portal pressures. Typically liver function is preserved, which serves as an important clue for the diagnosis. Bone marrow biopsy is essential for diagnosis. Heightened awareness of this unique and rare presentation of mastocytosis is advised, to improve early recognition and avoid unnecessary investigation.