Methods
Adalimumab, a human anti-TNF monoclonal antibody, is effective for inducing and maintaining remission in patients with Crohn disease who are naive to infliximab (8–10).A 73-year-old male was diagnosed with CD in 2016. Colonoscopy at that time revealed a mild chronic inflammation of his sigmoid for which he was initially treated with mesalazine. No comorbidities were present. Infliximab was started one year later, but after 14 weeks of treatment the patient developed polyarthralgia, myalgia and weight loss after which the infliximab was stopped. Analysis revealed a lupus-like disease with positive antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA), although these antibodies were also detectable prior to infliximab treatment. Seven months later, a colonoscopy showed significant chronic, active colitis of the distal sigmoid with ulcerations. Due to the formation of antibodies against infliximab, adalimumab was started. Adalimumab treatment was started with 160mg subcutaneously at week 0, followed by 80mg at week 1 and was then maintained on 40mg every 2 weeks. His polyarthralgia and myalgia resolved and his weight stabilized. After three injections of adalimumab, routine laboratory tests revealed a deep thrombocytopenia (thrombocytes 24x109/l) after which adalimumab was discontinued. His other medication at this time was mesalazine only. Bleeding symptoms included cutaneous hematomashematomas hematomas and mild epistaxis. There were no bleeding symptoms requiring immediate intervention. He denied any drug and alcohol abuse. Physical examination revealed no fever, hepatosplenomegaly or lymphadenopathy.
Besides the thrombocytopenia, the complete blood count showed a mild and stable normocytic anemia (hemoglobin 13.05 g/dL [normal 13.5-17.5] with unremarkable leukocyte count and differentiation, and low C-reactive protein. Thrombocyte counts in citrate anticoagulated blood excluded EDTA-induced pseudo thrombocytopenia. Levels of folic acid, vitamin B12, iron, liver enzymes and renal function were all within normal ranges. Protein electrophoresis showed no monoclonal protein. Peripheral blood smear revealed rouleaux formation and macrothrombocytes. A bone marrow aspirate and biopsy showed hypercellularity with an increased number of megakaryocytes with normal morphology, consistent with intact megakaryopoiesis. Erythropoiesis and myelopoiesis were unremarkable. Direct monoclonal antibody-specific immobilization of platelet antigens (MAIPA assay) revealed autoantibodies specific to glycoprotein IIb/IIIa (GPIIb/IIIa) and glycoprotein V (GPV) platelet receptors. The thrombopoietin level was normal (10 E/ml, normal 4-32).
Platelet count improved 6 days after cessation of adalimumab (platelet count 71×109/L) without further intervention and increased to 139×109/L in two weeks. A fully normalized platelet count (platelet count 203×109/L) was observed 4 weeks after the last dose of adalimumab. Therapy for CD was continued with methotrexate combined with mesalazine. There has been no recurrence of the thrombocytopenia during further treatment. His CD remained in clinical remission during treatment with methotrexate.