Unusual manifestations in two cases of necrotizing myopathy associated with SRP-antibodies

doi:10.1016/j.clineuro.2011.12.055

Clinical Neurology and Neurosurgery

Volume 114, Issue 7, September 2012, Pages 1104-1106

https://doi.org/10.1016/j.clineuro.2011.12.055 Get rights and content

Abstract

Anti-SRP (signal recognition particle) positive necrotizing myopathy is commonly not associated with neoplasms. We demonstrate two histologically confirmed cases with unusual manifestations of anti-SRP positive necrotizing myopathy.

A 65-year-old man presented with rapidly progressing weakness and mild difficulties in swallowing and speaking. Screening for underlying disorders revealed a moderately differentiated renal adenocarcinoma. The muscular symptoms partially improved after tumor nephrectomy and prednisone treatment. However, the patient developed pulmonary metastases and died of the sequelae of pneumonia 11 months after the diagnosis of renal cancer.

The second patient developed rapidly complete external ophthalmoplegia, severe bulbar dysarthrophonia and dysphagia, bilateral facial palsy, loss of patellar and ankle jerk reflexes, and severe symmetrical tetraparesis of both proximal and distal muscles. CSF showed mildly increased protein levels, neurography axonal impairment of motor nerves. Screening revealed no evidence for infections, ganglioside antibodies, and carcinoma. MRI was normal. The disease course suggested an overlap syndrome of Miller-Fisher-syndrome, axonal Guillain-Barré-syndrome and Bickerstaff brainstem encephalitis.

In conclusion SRP antibodies might be found in necrotizing myopathies associated with autoimmune mediated overlap syndromes and neoplasms. The pathomechanism is not clear. Any otherwise unexplained evidence of necrotizing myopathy should prompt the screening for SRP antibodies.

Introduction

Necrotizing myopathy has been associated with a variety of neoplasms [1]. Large case series have established the association of anti-signal recognition particle (anti-SRP) syndrome and histologically active necrotizing myopathy without inflammatory involvement and an endomysial microangiopathy assessed by membrane attack complexes (C5b-9) deposition and capillary loss [2], [3], [4], [5]. In all of these studies anti-SRP positive necrotizing myopathy was not associated with neoplasm. However, so far there is only one case with anti-SRP positive necrotizing myopathy and cancer (large cell-lung cancer) [6]. We present one case of paraneoplastic anti-SRP positive necrotizing myopathy with renal adenocarcinoma and another case of anti-SRP positive necrotizing myopathy associated with an overlap syndrome of Miller-Fisher-syndrome (MFS), axonal Guillain-Barré-syndrome (GBS) and Bickerstaff brainstem encephalitis (BBE).

Section snippets

Case 1

A 65-year-old man presented with rapidly progressing weakness, mild difficulties in swallowing and speaking, hyperhidrosis, and weight loss by 7 kg over 5 months. The patient became wheelchairbound and needed help to lift from the supine to sitting position. Neurologic examination predominantly showed symmetrical proximal weakness in the arms and legs (3–4 of 5 on the MRC scale), but also axial muscle and mild dysarthria and dysphagia. There were no skin changes. In electromyography

Discussion

The present first case shows the putative association of a malignancies and an anti-SRP positive necrotizing myopathy. In anti-SRP positive necrotizing myopathy as in other paraneoplastic necrotic myopathies, regions of necrotic C5b-9 positive muscle fibres are typical features. However, C5b-9 deposits, which were not seen in case 2, seem to be unspecific and occur inconstantly [5]. In rare cases anti-SRP positive necrotic myopathy was associated with systemic sclerosis and anti-synthetase

Conclusion

In conclusion SRP antibodies might be found in necrotizing myopathies associated with a variant of acute of inflammatory polyneuropathy but also neoplasms. The pathomechanism is not clear. Any otherwise unexplained evidence of necrotizing myopathy should prompt the screening for SRP antibodies.

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Idiopathic inflammatory myopathies
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In a case series, one NM patient harbored antibodies to both Mi-2 and a non–Jo-1 antisynthetase.1 SRP antibodies may be nonspecifically positive in patients with alternative muscle diagnosis or no evidence of muscle involvement.66 The authors routinely obtain Jo-1 antibodies on all IIM cases.
Ascending paresis as presentation of an unusual association between necrotizing autoimmune myopathy and systemic lupus erythematosus
2014, Reumatologia Clinica
El paciente, un hombre de 45 años de edad, ingresó a Emergencias debido a un padecimiento actual que inició 15 días antes de forma insidiosa y curso progresivo. Comenzó con debilidad simétrica y dolor en los pies y los tobillos, que se extendió hacia arriba hasta las rodillas. Más tarde, el dolor progresó a paraparesia, mostrando niveles de creatincinasa de 44.270 U/L e insuficiencia respiratoria que requirió ventilación mecánica. Se llevaron a cabo una electromiografía y un biopsia muscular del cuádriceps. El paciente respondió a la corticoterapia en pulsos y a manejo de soporte. La presentación de parálisis ascendente sugirió el diagnóstico de síndrome de Guillain-Barré; sin embargo, el grado de afectación de los músculos con rabdomiólisis explicó el daño neurológico por sí mismo. La biopsia reveló criterios patológicos para miopatía necrosante autoinmune (MNA), así como otros datos clínicos y de laboratorio. Además, reunió criterios para clasificarse como lupus eritematoso sistémico (LES). De acuerdo con la literatura revisada, este es el primer reporte de la asociación entre MNA y LES.
A 45 year-old man went to the emergency room due to disease duration of 15 days of insidious onset and progressive course. It began with symmetrical weakness and pain in feet and ankles that extends upward to the knees. Later, this progressed to paraparesis with Creatine phosphokinase levels of 44,270 U/L and respiratory failure that required mechanical ventilation. Electromyography and muscle biopsy of quadriceps were made. The patient responded to corticotherapy in pulses and supporting management. The presentation of ascending paresis suggested the diagnosis of Guillain-Barré syndrome. However, the degree of muscle involvement with rhabdomyolysis explains the neurological damage by itself. The biopsy revealed pathological criteria for necrotizing autoimmune miopathy (NAM), as well as other clinical and laboratory evidence. Patient disease continued and reached criteria for systemic lupus erythematosus (SLE). To our best knowledge, this is the first report of the NAM and SLE association.
Necrotizing autoimmune myopathies
2013, Revue Neurologique
Les myopathies nécrosantes auto-immunes (MNA) appartiennent au groupe des myopathies inflammatoires (MI) avec les polymyosites, les dermatomyosites et les myosites à inclusions mais elles sont caractérisées histologiquement par une nécrose musculaire plus sévère généralement sans infiltrat inflammatoire. La présentation clinique est variable, parfois proche des autres myopathies dysimmunes mais les formes graves sont plus fréquentes avec parfois déficit musculaire sévère, atteinte cardiaque, voire une rhabdomyolyse intense. Le taux des enzymes musculaires est habituellement très élevé (créatine kinase autour de 10 000 UI/L). L’électroneuromyogramme (ENMG) retrouve des signes myogènes souvent associés à de nombreuses activités spontanées en relation avec l’importante nécrose musculaire. Le diagnostic repose sur la biopsie musculaire qui révèle une nécrose musculaire sévère sans infiltrats lymphocytaires CD4 ou CD8. Un dépôt de C5b9 est souvent présent alors que l’expression anormale du complexe HLA-I par les fibres musculaires est inconstante ou hétérogène. Des altérations morphologiques évocatrices des capillaires endomysiaux sont souvent décrites. Ces myopathies peuvent être associées à un anticorps anti-SRP ou plus rarement aux autres anticorps décrits dans les autres myopathies auto-immunes. Par ailleurs, des formes paranéoplasiques sont possibles mais restent rares. Enfin, parfois associées à la prise de statines, des observations avec présence d’un nouvel anticorps Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase ont été décrites. Sur le plan thérapeutique, il n’est pas rare d’observer une cortico-résistance et le recours aux immunosuppresseurs ou aux immunoglobulines intraveineuses s’avère souvent indispensable avec des résultats très variables selon les formes cliniques.
Necrotizing autoimmune myopathies are included in the spectrum of inflammatory myopathies, together with polymyosis, dermatopolymyosis and inclusion body myositis, despite the characteristic feature of marked muscular necrosis without inflammatory infiltrates. The clinical presentation is highly variable, often similar to the other inflammatory myopathies. The most common finding is nevertheless the severe form with rhabdomyolysis. The creatine kinase level is elevated (around 10,000 IU/l) and electromyography shows myopathic changes with increased spontaneous activities reflecting the importance of the muscular necrosis. Muscle biopsy is required for diagnosis, revealing active necrosis of the muscle fibers without inflammatory invasion by CDA+ or CD8+ T-cells. Deposition of a microvascular membrane attack complex (C5b9) is often noted, whereas the upregulation of MHC class 1 is rarely detected. Signs of endomysial microangiopathy are frequently reported. Necrotizing autoimmune myopathies can be associated with antisignal recognition particle (SRP) antibodies or more rarely with the usual inflammatory myopathy antibodies. Paraneoplasic forms are described but remain exceptional. Lastly, necrotizing autoimmune myopathies, sometimes associated with statin therapy, have been recently described. They are linked with an antibody directed against 3-hydroxy-3-methyglutaryl-coenzyme A. Treatment is based on corticosteroid therapy, immunosuppressive drugs or intravenous immunoglobulins. Response is variable, depending on the clinical form.
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Necrotizing Autoimmune Myopathy
2022, Acquired Neuromuscular Disorders: Pathogenesis, Diagnosis and Treatment: Second Edition
Secondary cardiac involvement in anti-SRP-antibody-positive myopathy: An 87-year-old woman with heart failure symptoms as the first clinical presentation
2020, BMC Neurology

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Case seriesUnusual manifestations in two cases of necrotizing myopathy associated with SRP-antibodies

Abstract

Introduction

Section snippets

Case 1

Discussion

Conclusion

Neuromuscular Disorders

Paraneoplastic necrotizing myopathy

Neurology

Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy

Ann Rheum Dis

Myopathy with antibodies to the signal recognition particle: clinical and pathological features

J Neurol Neurosurg Psychiatry

Anti-signal recognition particle autoantibodies in patients with and patients without idiopathic inflammatory myopathy

Arthritis Rheum

Myopathy associated with anti-signal recognition peptide antibodies: clinical heterogeneity contrasts with stereotyped histopathology

Muscle Nerve

Clinical and histopathological features of myopathies in Japanese patients with anti-SRP autoantibodies

Mod Rheumatol

Case series
Unusual manifestations in two cases of necrotizing myopathy associated with SRP-antibodies