Brief Review and a Clinical Case of Hemolytic Uremic Syndrome Associated with Interferon β Treatment

Manani, Sabrina Milan; Virzì, Grazia Maria; Gastaldon, Fiorella; Proglio, Marta; Brocca, Alessandra; Ronco, Claudio

doi:10.1159/000454671

Cited by 6 publications

(6 citation statements)

References 34 publications

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“…In this setting, we may hypothesize that eculizumab could express a protective action against both renal and myelin damage, preserving the clinical and radiological course of patient's disease activity after IFNβ therapy discontinuation. The clinical case presented shows the occurrence of aHUS after 18 years of IFNβ-1a-treatment, and to our knowledge, it is the latest onset presented in literature; moreover, this suggests that the effect of IFNβ on the kidney function reflects a cumulative damage according to the most cases reported in literature (Mahe et al, 2013;Manani et al, 2017).…”

Section: Discussionssupporting

confidence: 57%

“…Our search included combination of the keyword "multiple sclerosis" with "interferon beta," "eculizumab," "atypical Haemolytic Uremic Syndrome," and "thrombotic microangiopathy." Sixteen articles were found (Allinovi et al, 2017;Azkune Calle et al, 2016;Broughton et al, 2011;Etemadifar et al, 2018;Hansen et al, 2009;Hunt et al, 2014;Kimura et al, 2011;Larochelle et al, 2014;Mahe et al, 2013;Manani et al, 2017;Nerrant et al, 2013;Olea et al, 2012;Orvain et al, 2014;Rubin et al, 2014;Vosoughi & Marriott, 2014;Yam et al, 2019) and reviewed in full-text form. A descriptive statistic is provided of the identified cases: Summaries of continuous variables have been calculated as medians with interquartile ranges (IQR) or mean and standard deviation (SD); categorical variables have been presented as frequencies (proportions).…”

Section: Me Thodsmentioning

confidence: 99%

“…In the published literature, we identified 24 MS patients who received IFNβ as DMT and then developed thrombotic microangiopathy with kidney injury (Table 1; Allinovi et al, 2017;Azkune Calle et al, 2016;Broughton et al, 2011;Etemadifar et al, 2018;Hansen et al, 2009;Hunt et al, 2014;Kimura et al, 2011;Larochelle et al, 2014;Mahe et al, 2013;Manani et al, 2017;Nerrant et al, 2013;Olea et al, 2012;Orvain et al, 2014;Rubin et al, 2014;Vosoughi & Marriott, 2014;Yam et al, 2019). In 3 of these 24 cases, the kind of INFβ used is not provided; in 4, INFβ-1b has been used.…”

Section: Re Sultsmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionssupporting

confidence: 57%

Section: Me Thodsmentioning

confidence: 99%

Section: Re Sultsmentioning

confidence: 99%

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

et al. 2020

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“…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.…”

Section: Methodsmentioning

confidence: 96%

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

et al. 2021

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(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

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“…However, in this study, no cases of anti-phospholipid antibody syndrome or thrombotic thrombocytopenic purpura were identified. The occurrence of a complement-dependent HUS triggered by IFN-β, revealing underlying genetic abnormalities affecting the complement system, has been reported in only one clinical case [ 21 ]. IFN-β may well be the triggering factor revealing genuine complement-dependent HUS, but such a scenario did not account for any of the cases described here.…”

Section: Discussionmentioning

confidence: 99%

Renal diseases secondary to interferon-β treatment: a multicentre clinico-pathological study and systematic literature review

Dauvergne

Buob

Rafat

et al. 2021

Clinical Kidney Journal

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Background The spectrum of Interferon-beta-associated nephropathy (IFN-β) remains poorly described and the potential features of this uncommon association remain to be determined. Methods In this study, we retrospectively analyzed the clinical, laboratory, histological and therapeutic data of patients with biopsy-proven renal disease in a context of IFN-β treatment administered since at least 6 months. Results Eighteen patients (13 women, median age 48 years) with biopsy-proven renal disease occurring during IFN-β therapy were included. The median exposure to IFN-β (14 patients were treated by IFN-β1a and four patients by IFN-β1b) was 67 months (ranged from 23 to 165 months). The clinical presentation consists in hypertension (HT) (83%), malignant HT (44%), proteinuria >1g/g (94%), reduced renal function (78%), biological hallmark suggesting thrombotic microangiopathy (TMA) (61%), edematous syndrome (17%), or nephritic syndrome (11%). The pathological findings included typical features of isolated TMAs in 11 cases, isolated focal segmental glomerulosclerosis (FSGS) lesions in two cases, and five cases with concomitant TMA and FSGS lesions. An exploration of the alternative complement pathway performed in 10 cases (63%) did not identify mutations in genes that regulate complement system. The statistical analysis highlighted that the occurrence of IFN-β-associated TMA was significantly associated with Rebif®, with a weekly dose >50 µg and with multiple weekly injections. In all cases IFN-β therapy was consequently discontinued. Patients with TMA lesions received other therapies included corticosteroids (44%), eculizumab (13%) or plasmatic exchanges (25%). At the end of a 36-month median follow-up, persistent hypertension and persistent proteinuria were observed in 61% and 22% of patients. Estimated glomerular filtration rate <60 ml/min/1.73m2 was present in 61% of patients. Conclusion IFN-β-associated nephropathy must be sought in the case of hypertension and/or proteinuria onset during treatment. When TMA and/or FSGS are observed on renal biopsy, early discontinuation of IFN-β is essential.

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Brief Review and a Clinical Case of Hemolytic Uremic Syndrome Associated with Interferon β Treatment

Cited by 6 publications

References 34 publications

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

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

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

Renal diseases secondary to interferon-β treatment: a multicentre clinico-pathological study and systematic literature review

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