A case report of late‐onset atypical Hemolytic Uremic Syndrome during interferon beta in multiple sclerosis: Open issues in literature review

Abstract

Background and aims Interferon beta (IFNβ) is a well‐established first‐line therapy for relapsing–remitting multiple sclerosis (RRMS) patients and remains the most widely prescribed agent. Atypical hemolytic uremic syndrome (aHUS) represents a rare but severe adverse effect (AE) that could occur even after many years from the beginning of IFNβ therapy. Eculizumab is currently approved for treatment of aHUS and recently for neuromyelitis optica spectrum disorder (NMOSD) with aquaporin‐4 antibodies (AQP4‐IgG). In this article, we report the case of the latest onset of IFNβ‐related aHUS experienced by an MS patient and we briefly review the literature on this topic. Methods We performed a systematic review of the literature using PubMed, and we performed a retrospective analysis of RRMS patients that received IFNβ‐1a in our center and developed thrombotic microangiopathy (TMA). From this search, we identified only one patient. Results In the published literature, we identified 24 MS patients who received IFNβ as disease‐modifying treatment (DMT) and then developed thrombotic microangiopathy with kidney injury. The aHUS has been diagnosed in 6, all received IFNβ‐1a and the latest onset was after 15 years. We report a case of a 39‐year‐old man affected by RRMS who assumed IFNβ‐1a since 1999. In July 2018, he developed an IFNβ‐related aHUS. After the failure of plasma exchange, he underwent eculizumab, with an improvement of glomerular filtration rate and without new signs of MS activity. Conclusion To our knowledge, this case represents the latest onset of IFNβ‐related aHUS in MS patients. Up to now, there are not literary reports about the possibility to reintroduce a DMT as add‐on therapy to eculizumab.

Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series

“…Six out of the nine cases have been described in previous articles from a nephrological [13,14,25] or a neurological [26] point of view, not analyzing the potential role of eculizumab in MS, and with a much shorter follow-up.…”

Interferon-β1a-Induced Thrombotic Microangiopathy: Possible Implication of the Alternative Pathway of the Complement

“…IFN β-1a mediated TMA was first described in 1998 (7) and about thirty cases have been reported since then. Based on limited case reports and case series in literature, IFN β-1a mediated TMA occurs after several years of a well-tolerated treatment (mean duration of 11 years) as in our patient (3). It is also more frequent in women and occurs mostly in young adults (mean age of 39 years old).…”

“…Withdrawal of the drug is key. Plasma exchange and corticosteroids are often used with poor renal outcome (3,8). About 20% of patients will recover normal renal function, about one third will experience CKD and about 40%, end-stage renal disease (8).…”

“…Despite the absence of proven mutation for regulators of the ACP, eculizumab was associated with a significant improvement of renal function, with persistence of CKD stage 2 to 4. HD was stopped five months after the initiation of eculizumab in the most severe case (3,8). These data suggest a potential efficacy of eculizumab but are not a proof for a causal relationship.…”

“…CFHR1/3 is known to be associated with anti-factor H antibodies, but that was not the case in this patient. Genetic workup was negative in three patients and missing in one case report (3). Interestingly, among these 6 patients, 4 were treated with eculizumab, an anti-complement C5 monoclonal antibody.…”