Exacerbation of myasthenia gravis in a patient after interferon-β treatment for chronic active hepatitis C

doi:10.1016/S0022-510X(99)00082-9

Journal of the Neurological Sciences

Volume 165, Issue 2, 1 June 1999, Pages 182-183

https://doi.org/10.1016/S0022-510X(99)00082-9 Get rights and content

Abstract

We report the case of a 53-year-old female patient, who developed bilateral blepharoptosis, limb weakness, dysphagia, and dyspnea several days after human natural interferon-β (IFN-β) treatment for chronic active hepatitis C. A positive edrophonium test, an elevated anti-acetylcholine receptor antibody titer, and decrements in the amplitude of muscle action potentials evoked by repetitive stimulation confirmed the diagnosis of myasthenia gravis (MG). Since she had been suffering from drooping of her right eyelid, fluctuating diplopia and easy fatiguability of limbs before receiving IFN-β, her symptoms of MG were considered to be exacerbated by IFN-β. It is recommended that IFN-β should be used with particular care in patients with known MG or its compatible symptoms.

Introduction

Interferon (IFN)-β is used frequently to treat patients with glioblastoma, medulloblastoma, astrocytoma, and melanoma as an antimitogenic agent [1], [2], [3] as well as with chronic active hepatitis B or C as an antiviral agent. In addition, it is now approved for the treatment of relapsing multiple sclerosis in several countries in Europe and North America. However, as one of its side effects myasthenia gravis (MG) was reported in a single patient to have been precipitated by IFN-β (recombinant IFN-β1b) [4].

We treated a patient with MG who showed exacerbation after treatment with IFN-β (human natural IFN-β) for chronic active hepatitis C, reinforcing the impression that IFN-β, like IFN-α [5] may induce or exacerbate MG.

Section snippets

Case report

A 53-year-old Japanese woman noted drooping of her right eyelid. Several months later she began to experience fluctuating diplopia and easy fatiguability of limbs. Previously, she had been in good health except for requiring surgery with a blood transfusion because of ileus following appendicitis at age 25. She sought treatment for her neuromuscular symptoms at age 54; laboratory tests demonstrated elevated serum transaminases and anti-HCV seropositivity. A liver biopsy specimen showed

Discussion

IFNs are potent immunomodulating cytokines (lymphokines) which are produced during an immune response as part of a ‘cascade’ of lymphokine chemical messages, and exert positive and negative influences on such immune responses. If exogenous IFNs are added into experimental immune response both in vivo and in vitro profound changes are seen. Among various effects of IFNs on immune reactions, they inhibit antibody response and delayed type hypersensitivity if given before sensitization, and

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Current and future immunotherapy targets in autoimmune neurology
2016, Handbook of Clinical Neurology
Citation Excerpt :
While it has been effective in the treatment of relapsing-remitting MS (The IFNB Multiple Sclerosis Study Group, 1993), its use in other autoimmune diseases is not well established. A few studies have suggested its efficacy in refractory CIDP (Choudhary et al., 1995; Vallat et al., 2003); however, interferon treatment has also been reported to exacerbate symptoms in a number of other diseases, including NMO and MG (Harada et al., 1999; Palace et al., 2010; Shimizu et al., 2010). Consequently, interferon use in antibody-mediated autoimmune disease might be contraindicated.
Randomized controlled treatment trials of autoimmune neurologic disorders are generally lacking and data pertaining to treatment are mostly derived from expert opinion, large case series, and anecdotal reports. The treatment of autoimmune neurologic disorders comprises oncologic therapy (where appropriate) and immunotherapy. In this chapter, we first describe the standard acute and chronic immunotherapies and provide a practical overview of their use in the clinic (mechanisms of action, dosing, monitoring, and side effects). Novel approaches to treatment of autoimmune neurologic disorders, through new drug discovery or repurposing, are dependent on improved mechanistic understanding of immunopathology. Such approaches, with emphasis on monoclonal antibodies, are discussed using the paradigm of three autoimmune neurologic disorders whose immunopathogenesis is better understood, specifically myasthenia gravis, neuromyelitis optica, and chronic inflammatory demyelinating polyradiculoneuropathy. It is important to realize that the treatment strategy and management plan must be individualized for each patient. In general these are influenced by the following: clinical severity, antibody type, presence or absence of cancer, and prior treatment response, if known.
Myasthenia, from the internist's point of view
2014, Revue de Medecine Interne
La myasthénie, ou « myasthenia gravis », est une maladie auto-immune due à des auto-anticorps spécifiques responsables d’un dysfonctionnement de la transmission neuromusculaire induisant une fatigabilité musculaire. Survenant à tout âge, elle affecte surtout des adultes de moins de 40 ans, en majorité des femmes. Les caractéristiques de l’affection sont les suivantes : début fréquemment oculaire (ptosis ou diplopie), extension à d’autres muscles dans 80 % des cas, variabilité, aggravation par l’effort, évolution par poussées, sévérité fonction de l’atteinte des muscles respiratoires et des troubles de déglutition (dont la majoration rapide signe la crise myasthénique), association à un thymome dans 20 % des cas et à une grande variété de maladies auto-immunes, au premier rang desquelles une dysthyroïdie. Le diagnostic repose sur le tableau clinique, la réponse aux anticholinestérasiques, la détection d’anticorps spécifiques (anti-RACh ou anti-MuSK) et la présence d’un décrément à l’EMG. Les aspects concernant plus particulièrement l’interniste ont été développés : pièges diagnostiques, maladies associées dont les myopathies inflammatoires qui peuvent mimer la myasthénie, effets indésirables de thérapeutiques utilisées en médecine interne dont certaines peuvent induire un syndrome myasthénique. Le traitement est bien codifié : (1) respect des contre-indications médicamenteuses, recours systématique aux anticholinestérasiques et thymectomie si thymome, complétée par radiothérapie si malignité, (2) thymectomie dans la forme généralisée du sujet jeune, sans anticorps anti-MuSK, (3) corticothérapie ou immunosuppresseurs dans les formes sévères ou invalidantes, (4) mesures de réanimation, échanges plasmatiques ou immunoglobulines intraveineuses en cas de crise myasthénique.
Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a neuromuscular transmission defect causing muscle fatigability. If onset of the disease may be at any age, myasthenia gravis concerns mostly young adults, in majority females. The disease characteristic features are the following: ocular symptoms (ptosis or diplopia) as main initial manifestation, extension to other muscles in 80 % of the cases, variability of the deficit, effort induced worsening, successive periods of exacerbation during the disease course, severity depending on respiratory and swallowing impairment (if rapid worsening, a myasthenic crisis is to be suspected), association with thymoma in 20 % of patients and with other various autoimmune diseases, most commonly hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical features, improvement with cholinesterase inhibitors, detection of specific autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by electrophysiological tests. The points concerning specifically the internist have been highlighted in this article: diagnostic traps, associated autoimmune diseases, including inflammatory myopathies that may mimic myasthenia gravis, adverse effects of medications commonly used in internal medicine, some of them inducing myasthenic syndromes. The treatment is well codified: the treatment is well codified: (1) respect of adverse drugs contra-indications, systematically use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or intravenous immunoglobulins for patients with myasthenic crisis.
Recombinant interferon-beta therapy and neuromuscular disorders
2009, Journal of Neuroimmunology
Interferon-beta (IFNβ) is an extra-cellular protein mediator of host defense and homeostasis. IFNβ has well-established direct antiviral, antiproliferative and immunomodulatory properties. Recombinant IFNβ is approved for the treatment of relapsing–remitting multiple sclerosis. The immunomodulatory effects of IFNβ administration failed to demonstrate consistent benefit during treatment of various autoimmune neuromuscular diseases. Existing studies were flawed due to the often uncontrolled and unblinded nature of protocols, small patient numbers per study, the undetermined optimum dose and schedule of IFNβ therapy, and the relatively brief periods of IFNβ administration and clinical follow-up for mostly chronic inflammatory disorders. Additional, controlled, prospective studies are needed to definitely establish the full potential of this cytokine for this group of diseases. IFNβ therapy may trigger autoantibody production, but only rarely clinically overt autoimmune disease. Anecdotal reports hint at the exceptional association between IFNβ treatment and the induction or exacerbation of a variety of immune-mediated neuromuscular diseases, likely in genetically predisposed individuals. Thus, recombinant IFNβ has the theoretical potential to either treat or cause autoimmune neuromuscular disorders by altering the complicated and delicate balances within the immune system networks.
Development of a myasthenia crisis during interferon treatment for chronic C hepatitis
2007, Gastroenterologie Clinique et Biologique
Si la myasthénie n’est pas une complication habituelle du traitement par interféron, plusieurs observations ont cependant été décrites depuis l’utilisation de ce médicament dans le traitement de l’hépatite C, des néoplasies ou de la sclérose en plaques. Nous rapportons une nouvelle observation de myasthénie sévère survenue au cours du traitement combiné d’une hépatite C par interféron-α et ribavirine.
If myasthenia gravis is not a usual complication of interferon therapy, several cases have been described with the use of theses molecules in the treatment of hepatitis C, cancer or multiple sclerosis. We report a new case of serious myasthenia gravis during interferon alpha and ribavirin therapy for hepatitis C.
Diseases of the Neuromuscular Junction
2005, Peripheral Neuropathy: 2-Volume Set with Expert Consult Basic
Diseases of the Neuromuscular Junction
2005, Peripheral Neuropathy

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Exacerbation of myasthenia gravis in a patient after interferon-β treatment for chronic active hepatitis C

Abstract

Introduction

Section snippets

Case report

Discussion

Clinical trial of intrathecal injection of interferon-β (MR-21) for glioblastoma

Biotherapy

Clinical trials of interferon-β (MR-21) on malignant brain tumors

J Jpn Soc Cancer Ther

Clinical trials of interferon-β (MR-21) in the treatment of malignant tumors of the skin

J Jpn Soc Cancer Ther

Onset of myasthenia gravis in a patient with multiple sclerosis during interferon-1b treatment

Neurology

Myasthenia gravis during interferon alfa therapy

Neurology

Interferons: from molecular biology to man. Part 2. Interferons and cell function

Microbiol Sci