Endocrine Abstracts

Introduction

Alemtuzumab is an anti-CD52 antibody, leading to lysis and transient depletion of T and B lymphocytes. Its therapeutic effect is mediated by the alteration in immune repertoire that accompanies subsequent lymphocyte reconstitution. It is mainly used for the treatment of relapsing–remitting multiple sclerosis (RRMS). Common side effects are autoimmune diseases, including thyroid disease (>40%), immune thrombocytopenia (ITP, 1–3%) and nephropathy ( <1%). Concurrent Graves’ disease with other alemtuzumab-related autoimmune disorders have not been described so far.

Case-report

A 27-year-old female with oculocutaneous albinism and RRMS diagnosed in 2009, received three cycles of alemtuzumab between 2016 and 2018. Twenty-one months later, she presented to the emergency department with petechiae, purpura and tachycardia. Laboratory tests revealed severe thrombocytopenia, autoimmune hemolytic anemia, leukopenia and mildly elevated liver enzymes. Immunological and virological tests were negative. Thyroid function tests revealed hyperthyroidism with positive anti-Tg, anti-TPO and TSHR antibodies. Increased uptake in thyroid scan confirmed the diagnosis of Graves’ disease. Of note, her family history is significant for thyroid dysfunction and rheumatoid arthritis. She was treated with low dose thiamazole and propranolol, as well as methylprednisolone and gamma globulin. Interestingly, a fluctuating course with alternating phases of hypo- and hyperthyroidism followed and ITP relapse was observed following treatment initiation. Currently, she is on concomitant treatment with thiamazole and thyroxine, and remains euthyroid with normal hematological and biochemical laboratory tests. Methylprednisolone was discontinued 2 months ago.

Discussion

Hyperthyroidism associated with ITP is rare, and only 160 cases have been reported so far. To our knowledge our case with Graves’ disease and concurrent ITP after alemtuzumab is the first described in the literature. The exact mechanism of autoimmunity in alemtuzumab-treated patients with RRMS is poorly understood. It has been proposed that the quick/complete recovery of B lymphocyte numbers (6–12 months), versus the slower/partial recovery of T lymphocytes, during the reconstitution phase, is responsible for the enhanced production of autoantibodies. In addition, lymphocytes escaped from cytolysis undergo homeostatic proliferation, potentially setting up an exaggerated and self-oriented response behind adverse autoimmune events. In our case the production of both platelet‑associated IgG, and antithyroid antibodies, may be responsible for the coexistence of both diseases. Another contributory factor may be the increased reticuloendothelial phagocytic activity induced by hyperthyroidism, which may shorten the platelet survival. Genetic predisposition as well as smoking, family history of autoimmunity, female gender, younger age, and early brainstem involvement may also have played a role to this unusual case.