Graves' disease following commencement of alemtuzumab therapy: Case report discussing clinical considerations and possible pathophysiology

Background

Monoclonal antibodies have become a mainstay in treatment of autoimmune and malignant disease. Adverse reactions to antibody therapy are often unpredictable and include endocrinopathies. The monoclonal antibody alemtuzumab, which is licensed for the treatment of MS, induces Graves' disease in 22% of patients with MS receiving the drug. Alemtuzumab targets CD52 which causes depletion of mature lymphocytes. In this case report, clinical considerations and pathophysiology are explored by commentating on a patient who developed Graves' disease following alemtuzumab therapy.

Case description

SK is a 37-year-old woman diagnosed with MS at 25, and also suffers from depression. SK began alemtuzumab treatment at aged 35, subsequently, she was found to have deranged TFTs (TSH <0.01 mU/L and fT4 28 pmol/L). SK experienced regular palpitations, fatigue and disturbed sleep. The patient attributed her fatigue and palpitations to MS and did not seek medical attention. SK reported no other symptoms of hyperthyroidism. Symptoms resolved following administration of carbimazole and propranolol.

Discussion

The exact mechanisms underlying both MS and alemtuzumab-induced Graves' disease are unknown. Lymphocyte depletion and reconstitution is thought to cause autoimmunity by over-repopulation of naïve B-cells, T-lymphocyte modulation and disrupting cytokine signalling (IL-21 and IFNy). The slow regeneration of Treg cells that normally promote tolerance underlies these changes. This report identifies challenges including: identifying adverse reactions to new medications, patients discriminately reporting symptoms and the fragility of quality of life in patients with MS.