The Perfect (Cytokine) Storm: Autoimmune Hepatitis as a Catalyst for Macrophage Activation Syndrome: 1950 : Official journal of the American College of Gastroenterology | ACG

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The Perfect (Cytokine) Storm: Autoimmune Hepatitis as a Catalyst for Macrophage Activation Syndrome


Mbachu, Jean MD1; Bul, Vadim MD2; Koppe, Sean W.P. MD2

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American Journal of Gastroenterology 111():p S930, October 2016.
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A 74-year-old male presented to an outside hospital with dyspnea on exertion, weight loss, and generalized fatigue for two months. His physical exam was notable for temporal wasting, conjunctival icterus and splenomegaly. ALT of 455 U/L and AST of 593 U/L as well as a leukocyte count of 1.3 thous/uL, Hgb 12.3 mg/dL, and platelets 83 thous/uL were noted. Hepatitis viral serologies were unremarkable; however, serum autoimmune markers were elevated: ANA titer was 1:1280, Anti-Smooth muscle was 42 units, and serum IgG was 2639 mg/dL. A liver biopsy demonstrated autoimmune hepatitis (AIH) with Batts-Ludwig stage three fibrosis while a bone marrow biopsy was without malignancy. The bone marrow biopsy was complicated by persistent hematomas. He was started on 60 mg of prednisone. After two weeks of treatment the patient began spiking fevers and was clinically worsening so he was transferred to our facility. Despite the fevers, all cultures and tests for atypical organisms were negative. A repeat liver biopsy showed decreased inflammation while a repeat bone marrow biopsy showed evidence of hemophagocytosis. The patient was diagnosed with macrophage activation syndrome (MAS) and he was started on high dose IV methylprednisolone and transitioned to cyclosporine and prednisone. Despite immunosuppressant medications and supportive care with total parenteral nutrition, the patient developed multi-organ failure and died on day 30 of his hospitalization. MAS is the uncontrolled regulation of T and natural killer cells resulting in cytokine-mediated uncontrolled macrophage activation. While primary MAS is an X-linked recessive disease, type 2 MAS occurs in the setting of an underlying autoimmune disease or infection. Given the rarity of the disease, no accepted diagnostic guidelines exist for MAS. The only proposed diagnostic algorithm is based on a publication of 74 cases of MAS in the setting of various autoimmune diseases. Diagnosis relies on at least 2 of the following: leukopenia, thrombocytopenia, hypofibrinogenemia, elevated AST, CNS dysfunction, hemorrhages and hepatomegaly. Our patient fit six of the seven criteria. Patients with hepatic involvement tend to have poor outcomes with mortality rates has approaching 75%. We report a case of AIH leading to MAS, a rare etiology of an even rarer disease. MAS should be considered in patients with severe refractory AIH as early treatment with high dose steroids and immunosuppression may lead to improved outcomes.

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