Selective response to rituximab in a young child with MuSK-associated myasthenia gravis

doi:10.1016/j.nmd.2015.03.014

Neuromuscular Disorders

Volume 25, Issue 8, August 2015, Pages 651-652

https://doi.org/10.1016/j.nmd.2015.03.014 Get rights and content

Highlights

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We describe a pediatric case of MuSK myasthenia.
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We highlight the clinical symptoms and diagnostic difficulties with MuSK myasthenia in a pediatric case.
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We also describe the successful treatment of MuSK myasthenia with rituximab.

Abstract

Neuromuscular junction disorders in children are either genetic, such as congenital myasthenic syndrome, or autoimmune with circulating antibodies most commonly against acetylcholine receptors. There is limited experience recognizing and treating children with myasthenia associated with muscle-specific tyrosine kinase antibodies. We report a seven-year-old child with intermittent esotropia since age 3 months, and two years of progressive and severe diplopia, dysarthria, dysphagia, and facial weakness. Acetylcholine receptor antibodies and genetic testing for congenital myasthenic syndrome were negative. Muscle specific tyrosine kinase antibodies were significantly elevated. Ophthalmoplegia and bulbar weakness were refractory to treatment with acetylcholinesterase inhibitors, corticosteroids and IVIg but completely resolved following treatment with rituximab. Her neurologic examination remained normal at the most recent follow-up, 15 months after initiation of rituximab. Children with MuSK myasthenia, like adults, can respond to rituximab despite long standing disease and failure to improve on other immunosuppressant medications.

Introduction

Section snippets

Case report

A seven-year-old girl presented with longstanding abnormal eye movements beginning at three months of age with intermittent bilateral esotropia. At five years of age she developed worsening diplopia, more severe bilateral esotropia with impaired lateral extra ocular movements, and nocturnal dysphagia (cough and gagging). She underwent strabismus surgery (bilateral medial rectus recession) and tonsil and adenoidectomy at age 6 years. Disconjugate gaze, esotropia, and nocturnal dysphagia

Discussion

We describe the successful use of rituximab (a human–mouse chimeric monoclonal CD20 antibody) in a child with longstanding, refractory MuSK antibody associated myasthenia gravis.

Reports of children with MuSK antibody associated myasthenia gravis are scarce [1], [2], [3], [4]. Skjei et al. recently reported 9 children with MuSK-associated myasthenia with age of onset from 2 to 16 years and with predominantly ocular and bulbar symptoms [4]. Our patient also had predominant ocular and bulbar

Conclusion

This case suggests that children with MuSK myasthenia, like adults, can respond to rituximab despite failure to improve on other immunosuppressant medications or pyridostigmine even after several years of symptoms. MuSK antibody testing should be performed in children with signs and symptoms of myasthenia gravis if AChR antibody levels are normal.

References (9)

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K.L. Skjei et al.
Muscle specific kinase autoimmune myasthenia gravis in children: a case series
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M.E. Wylam et al.
Successful treatment of refractory myasthenia gravis using rituximab: a pediatric case report
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Cited by (13)

Rituximab in juvenile myasthenia gravis-an international cohort study and literature review
2022, European Journal of Paediatric Neurology
Citation Excerpt :
Stefano et al. reported 165 patients with AChR positive MG and concluded that significant clinical improvement was seen in 68%, with 36% achieving complete remission. The rituximab experience in children and adolescents with JMG literature is mainly based on case reports or small case series [7–17], consistently reporting a beneficial effect. Here we describe our experience of rituximab in JMG based on the collective experience of a large international multicentre study.
Juvenile myasthenia gravis (JMG) is a rare, antibody-mediated disorder of the neuromuscular junction. Treatment strategies in JMG are largely informed by adult MG treatments as the pathophysiology is similar. Rituximab is increasingly considered as a treatment option in refractory JMG but has not yet been systematically investigated in this patient group We conducted a retrospective study from five international centres with expertise in paediatric myasthenia. 10 JMG patients treated with rituximab were identified. Following rituximab treatment all patients had a reduction in JMG-related hospital admissions. At 24 month follow up, 6 patients (60%) had achieved complete stable remission or pharmacological remission and 7 patients were able to reduce immunomodulatory treatment(s). The main side-effect was infusion-related reactions (30%) which resolved in all patients with symptomatic treatment. We compared our cohort to previously reported JMG cases treated with rituximab and noted similar response rates but a slightly higher side-effect profile. Rituximab is a safe and effective treatment option in moderate to severe JMG and most patients have an improvement in MG symptoms post treatment.
Rituximab as Adjunct Maintenance Therapy for Refractory Juvenile Myasthenia Gravis
2020, Pediatric Neurology
Citation Excerpt :
Autoreactive B cells have demonstrated pathogenicity in the development of autoimmune myasthenia gravis.3 Rituximab has been well-studied for the treatment of adult myasthenia gravis,3-6 but its use has been documented sparsely in JMG.7-9 The objective of our study was to assess the tolerability and efficacy of rituximab use in children with refractory JMG.
Juvenile myasthenia gravis is a pediatric autoimmune disorder of the neuromuscular junction associated with substantial morbidity, for which standard therapies are not always efficacious. The objective of our study was to assess the tolerability and efficacy of rituximab use in children with refractory juvenile myasthenia gravis.
We conduced a retrospective cohort study at a single tertiary care referral center to evaluate children with juvenile myasthenia gravis who were treated with rituximab. The clinical status of these participants before and after initiation of rituximab therapy was measured, focusing on numbers of hospital admissions, numbers of immunomodulatory or immunosuppressive medications needed, and Myasthenia Gravis Foundation of America severity class.
Five children with juvenile myasthenia gravis were ascertained who received rituximab as part of their regimen, four of whom had elevated acetylcholine receptor antibodies and one of whom had elevated muscle-specific kinase antibodies. After initiation of rituximab therapy, all participants experienced reduced numbers of immunomodulatory medications during the follow-up period (mean 11.6 months). Four of the five subjects experienced fewer juvenile myasthenia gravis-related hospital admissions and reduced (improved) Myasthenia Gravis Foundation of America classes, with no subjects having moderate or severe symptoms following treatment with rituximab. No significant adverse events were recorded for any of the participants.
Rituximab was well-tolerated and efficacious in this juvenile myasthenia gravis cohort. The beneficial effect of rituximab was most pronounced in the one participant with muscle-specific kinase antibodies.
AChR myasthenia gravis switching to MuSK or double antibody positive myasthenia gravis in two children and literature review
2020, Neuromuscular Disorders
Citation Excerpt :
Most pediatric MG cases initially manifest extraocular muscle paresis. Muscle tyrosine–specific kinase antibody (MuSK–Ab), discovered in 2001 by Hoch [2], is the second most frequent antibody detected in MG after acetylcholine receptor antibody (AChR–Ab) [3]. AChR–Ab and MuSK–Ab coexistence in the same patient is rare, and only a few double antibody positive MG cases (DP–MG) have been reported [4–9].
Muscle–specific tyrosine kinase antibody (MuSK–Ab) and acetylcholine receptor antibody (AChR–Ab) coexistence in myasthenia gravis (MG) is very rare. In this report, two children with AChR–Ab switching to double antibody positive MG (DP–MG) or MuSK–Ab positive MG (MuSK–MG) are described. Six similar cases were found in the literature via online database search. Therefore, this study describes eight patients in total, six female and two male. The average age of onset was 7.25 ± 5.95 years. Four AChR–MG patients switched to DP–MG with no known precipitating factor and four switched after thymectomy (two to MuSK–MG and two to DP–MG). After the serological switch, the patients transitioned to the phenotype of MuSK–MG and responded poorly to cholinesterase inhibitors and well to corticosteroids and plasma exchange.
Therapeutic target of memory B cells depletion helps to tailor administration frequency of rituximab in myasthenia gravis
2016, Journal of Neuroimmunology
Citation Excerpt :
B lymphocyte recovery CD19 + CD27 + but not total CD19 + was associated with relapse of clinical symptoms in all patients. Similar to previous reports, our 3 patients with MuSK positive myasthenia responded very well to RTX, with ongoing remissions of more than 1 year after therapy (Yi et al., 2013; Govindarajan et al., 2015). Over the 5 years, no case of progressive multifocal leukoencephalopathy or malignancy was observed, and there were no serious adverse events leading to discontinuation of treatment.
Rituximab (RTX) has demonstrated efficacy in limiting relapses in myasthenia gravis (MG). We investigated the interest of CD27 + memory B cell monitoring in patients as a biological marker of clinical relapse. Twenty-four patients have been treated with RTX (375 mg/m²/week-month as an induction treatment). Maintenance treatment consisted with either systematic treatment every 3 months or only when CD27 + memory B cells were detectable. After the induction treatment, the mean infusions were 1.3/year compared with 4/year. We suggest that RTX administration frequency can be decreased safely by monitoring the re-emerging CD27 + memory B cells.
Rituximab treatment in myasthenia gravis
2023, Frontiers in Neurology
Rituximab Therapy in the Treatment of Juvenile Myasthenia Gravis
2022, Neurology

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Case reportSelective response to rituximab in a young child with MuSK-associated myasthenia gravis

Highlights

Abstract

Introduction

Section snippets

Case report

Discussion

Conclusion

J Formos Med Assoc

Pediatr Neurol

Neuromuscul Disord

J Pediatr

Case report
Selective response to rituximab in a young child with MuSK-associated myasthenia gravis