Serum Sickness Following Ocrelizumab Infusion in Two Patients with Multiple Sclerosis

Background: Ocrelizumab is a monoclonal antibody commonly used to treat multiple sclerosis (MS). Serum sickness (SS) is a hypersensitivity reaction that has been reported with several monoclonal antibodies, but only one case has ever been reported with ocrelizumab.

Objective: To describe two patients with MS who developed SS post ocrelizumab infusions.

Case presentations: A 45-year-old man with primary progressive MS developed tingling in his extremities and worsening lower extremity weakness two weeks following his fifth cycle of ocrelizumab. He was initially thought to have a possible MS flare. He later developed arthralgias, myalgias, generalized weakness, and fever. A 59-year-old woman with primary progressive MS developed arthralgias, generalized weakness, abdominal pain, and myalgias two days following her second cycle of ocrelizumab. Brain and spinal cord MRIs revealed no new or enhancing lesions in both cases. They both had elevated inflammatory markers and a negative infectious workup. They were treated for SS with a steroid taper (as well as potent anti-inflammatories, for the second case), and their symptoms improved dramatically after a few days. Their neurological deterioration was determined to represent acute worsening of preexisting MS symptoms in the setting of an inflammatory etiology.

Discussion: Both patients had vague symptoms with concomitant neurological deterioration that rendered diagnosis challenging. SS classically presents with arthralgia, fever, and rash; however, the presence of the complete triad is not required for diagnosis. Infectious etiologies should always be excluded due to similarities in symptomatology and the increased susceptibility to infections with ocrelizumab. It is also crucial to differentiate the symptoms from a possible MS relapse since long-term treatment differs significantly. In the setting of systemic illness, the emergence of older MS symptoms with no new lesions on imaging most likely indicates unmasking of old areas of damage.

Conclusion: SS should be suspected in a patient with new-onset arthralgia, fever, or rash following ocrelizumab infusion, with an otherwise negative workup and rapid response to steroids. Longer experience with ocrelizumab is necessary to characterize the possible rare side effects. In the meantime, it is important to be aware of the possible occurrence of SS to properly address it.