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.