Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature

Abstract

Background: Anti-Signal Recognition Particle associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis, which is under-recognised in children and fails to respond to conventional first line therapies. We present three cases where remission was successfully induced using combination therapy with intensive rehabilitation.

Case presentations: Three new patients are reported. All 3 cases presented with profound, rapid-onset, proximal myopathy and markedly raised CK, but no rash. Histology revealed a destructive myopathy characterized by scattered atrophic and necrotic fibres with little or no inflammatory infiltrate. All 3 patients responded to induction with cyclophosphamide, IVIG and rituximab, in conjunction with intensive physiotherapy and methotrexate as the maintenance agent. Our patients regained near-normal strength (MMT > 70/80), in contrast with the current literature where >50% of cases reported severe residual weakness. A literature search on paediatric anti-SRP myositis was performed to June 2016; PubMed was screened using a combination of the following terms: signal recognition particle, autoantibodies, antibodies, myositis, muscular diseases, skeletal muscle, childhood, paediatric, juvenile. Articles in a foreign language were excluded. Nine case studies were found.

Conclusion: This paper supports the hypothesis that anti-SRP myositis is distinct from other JIIM. It is an important differential to JDM and should be considered where there is severe weakness without rash or if highly elevated muscle enzymes (CK > 10,000 U/l) are found. Early identification is essential to initiate aggressive medical and physical therapy. Greater international collaboration and long-term follow-up data is needed to establish the most effective treatment strategy for this rare group of patients.

Conflict of interest statement

Ethics approval and consent to participate

All patients were included following full, informed parental consent and age appropriate assent. The study was approved by the North Yorkshire Multi Centre Research Ethics Committee, Ref: MREC/1/3/22.

Consent for publication

Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Muscle histology of all 3 SRP cases: a-f haematoxylin and eosin (H&E) stain showing scattered necrotic fibres (arrows) and atrophic fibres (open arrows) across the biopsies. c and f Numerous regenerating fibres (open arrow heads) could also be seen in case 3. g-i there was very little staining for CD3 in case 1 (arrow) and none in case 2 h. Moderate levels of CD3 were seen in case 3 in the endomysial compartment (i, arrows). j-l there was diffuse MHC class 1 up regulation in all 3 cases, but case 3 had higher levels at the sarcolemma and within fibres. m-o MAC C5b9 stained necrotic fibres in all cases (arrows) and also some endomysial capillaries (not shown). p-r there was scattered expression of neonatal myosin in the muscle fibres of case 1 and 2 (p & q, arrows) and expression in numerous fibres in case 3 r. Scale bars: a, b, f, m-o, q and r – 100 μm. c, g-l, p - 250 μm. d and e - 50 μm

Fig. 2

Summary of treatment and clinical course for Case 1 (a), Case 2 (b) and Case 3 (c). Line chart of muscle strength (dotted line with circles, Manual muscle testing, MMT, range 0–80, low numbers indicate weakness) and creatine kinase (CK, intermittent line) from diagnosis. Bold arrows indicate treatment with Rituximab. Duration of treatment is represented by horizontal lines above chart. Short vertical lines indicate treatment with high dose intravenous methylprednisolone (IVMP). Narrowing of the top horizontal line represents tailing of the oral corticosteroid dose (PO prednisolone)