Autoimmune storm following alemtuzumab

Abstract

Alemtuzumab has been associated with the emergence of secondary autoimmune diseases. We report a case of a patient with relapsing-remitting multiple sclerosis who developed a refractory immune thrombocytopaenia associated with vasculitis, myelofibrosis and later Guillain-Barré syndrome following alemtuzumab. The medical community should be aware of unusual and unexpected adverse events that may be associated with alemtuzumab, especially when occurring simultaneously in the same patient.

Keywords: Biological agents; Multiple sclerosis; Neurology (drugs and medicines); Vasculitis.

Figure 1

A focal haemorrhage (arrow) was visualised in the left frontal lobe on the axial susceptibility-weighted imaging (A). It was not visualised on the previous MRI done 6 months earlier. The fluid attenuated inversion recovery sequence (B) showed an increased hypersignal, suggestive of oedema (arrow). It improved 1 month later (not shown). We can also observe many juxtacortical lesions associated with her multiple sclerosis.

Figure 2

On this anteroposterior view of the right carotid territory, a focal narrowing of the proximal right anterior cerebral artery is shown (arrow). The conventional cerebral angiogram also demonstrates discrete narrowing of the right and left internal carotid artery, right M1 and right A1 (not shown).

Figure 3

Two weeks after the left adrenal infarct and 1 week after the brain haemorrhage, the platelets suddenly dropped below 100×10⁹/L over 4 days. She was treated with 65 mg of oral prednisone (P), and the platelets went up within 2 weeks but dropped again. When she started being symptomatic of the thrombocytopaenia (epistaxis), she was treated with intravenous methylprednisolone (M) for 3 consecutive days, simultaneously with a first dose (1000 mg) of rituximab (R). Rituximab led to a minimal and transient rise of the platelet count that dropped again 2 weeks later. She received two doses of IVIg (G) (1 g/kg) 1 week apart, without any effect. While the platelet blood level was undetectable, she developed a severe upper gastrointestinal (GI) bleeding that required massive transfusions. Then, she sequentially received a second 1000 mg of rituximab, 1.3 g of cyclophosphamide (C) and eltrombopag 75 mg/day (E). Within a week, her platelet level rose. Prednisone and eltrombopag are being tapered since. ITP, immune thrombocytopaenia.