Secondary hemophagocytic lymphohistiocytosis in a patient with rheumatoid arthritis and vasculitis: a case report and review of the literature

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by excessive systemic inflammation, caused by uncontrolled activation of lymphocytes and macrophages, which secrete increased amounts of cytokines. HLH may be caused by gene mutations (primary HLH) or associated with malignancy, immunodeficiency, infection or autoimmune disease (secondary HLH). A 58-year-old woman with seropositive rheumatoid arthritis (RA) presented with fever, ulcers on the left foot and in the intergluteal cleft and increased inflammation markers. Clinical and laboratory evaluation, combined with findings from intra-arterial digital subtraction angiography of the lower limbs, pointed towards the diagnosis of vasculitis. Intravenous administration of low-dose cyclophosphamide resulted in recession of fever and decrease of inflammation markers. However, the patient later developed pancytopenia, hepatomegaly, hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia, while bone marrow aspiration demonstrated hemophagocytosis. The diagnosis of HLH was established. An extensive workup excluded malignancies, systemic infections and immunodeficiencies. HLH in our patient was attributed to activation of RA and presentation of vasculitis. Treatment with corticosteroids and intravenous immunoglobulin led to resolution of fever, correction of pancytopenia and complete healing of the ulcers. Timely diagnosis and treatment of HLH is highly important for a favorable outcome for the patients. Treatment of secondary HLH associated with autoimmune diseases involves corticosteroids and/or other immunomodulatory agents, such as intravenous immunoglobulin.