To elucidate whether anti‐SRP autoantibodies are associated with a specific form of myositis, we analysed the clinical and histological data of the largest group of anti‐SRP‐positive patients to date. Several interesting conclusions can be made, keeping the retrospective nature of the study in mind.
Clinically, the disease had a rapidly progressive course and caused severe disability within months, with most patients barely able to stand, let alone walk. Dysphagia was a prominent symptom and serum creatine kinase levels were highly elevated. The disease was responsive to immunosuppression and immunomodulation, and patients in general had a moderate to good recovery. Treatment seemed to be needed for a long time (years) because most patients studied were not drug free and the relapse rate was high, although not significantly different from polymyositis and dermatomyositis in general.10
None of the patients studied was diagnosed with any other inflammatory connective tissue disorder. ILD was present in almost one quarter of the patients, thus not differing from polymyositis and dermatomyositis in general.11
The type and frequency of abnormalities on the electrocardiogram was comparable to that found in a large series of patients with polymyositis and dermatomyositis.12
Muscle biopsy showed the presence of a necrotising myopathy. The typical histological features of myositis (presence of inflammatory infiltrates and positive HLA‐ABC staining of the sarcolemma) were absent.13,14
Necrotising myopathies occur most often as a paraneoplastic phenomenon or as secondary to myotoxic drugs or toxins.15
Several muscle biopsy specimens in our study showed diffuse staining of the necrotic muscle fibres with antibodies to MAC as has been described for paraneoplastic necrotising myopathy.16
In our study, only two patients had a neoplastic disease and only one patient had used drugs associated with a myopathy (in this particular patient cessation of the drug did not stop the progression of the disease, thus making the diagnosis of a drug‐induced myopathy unlikely).
A few cases have been published of patients with a necrotising myopathy who responded more or less favourably to immunosuppressive drugs.17
Inflammatory infiltrates were not found in the muscle biopsy specimens of these patients, and in some of these cases signs and symptoms suggestive of an inflammatory connective tissue disorder were present.17
The disease was named “necrotising myopathy with pipe stem capillaries” because the capillaries had thick walls with accumulation of periodic acid Schiff‐positive material and a small lumen. Furthermore, microvascular deposits of MAC were present. None of our patients with anti‐SRP autoantibodies had capillary abnormalities suggestive of pipe stem capillaries, and none of the muscle biopsies showed capillary deposition of MAC. Therefore, the necrotising myopathy seen in our patients with anti‐SRP autoantibodies seems to be a distinct disease entity. The clinical syndrome of the described patients with necrotising myopathy with pipe stem capillaries also differs from that seen in our anti‐SRP‐positive patients with a relatively mild myopathy, and marked extramuscular involvement in the few patients who have been described in the literature so far.17,18
Three anti‐SRP‐positive patients were diagnosed with dermatomyositis. The observation of anti‐SRP autoantibodies in dermatomyositis and the presence of these autoantibodies in systemic sclerosis have been reported before. 1,5,7,9
Whether this implies that anti‐SRP autoantibodies can be formed in several distinct disorders resulting in muscle fibre necrosis is unknown. However, it does illustrate that anti‐SRP autoantibodies are not solely seen in polymyositis‐like disorders.
The presence of a disease‐specific autoantibody and a favourable response to immunosuppressive and immunomodulating agents suggest an immune‐mediated pathogenic mechanism underlying the anti‐SRP myopathy despite the absence of clear inflammation. On the basis of the findings of deposition of MAC in capillaries, a reduction in the capillary density and an increase in endomysial connective tissue, it has been suggested that the myopathy is secondary to multifocal ischaemia.8
We were unable to confirm these observations, with the exception of the presence of swollen capillaries.
The major shortcoming of our study is the large amount of missing data, caused by the retrospective design. Diagnostic investigation of extramuscular manifestations was not routinely performed but was guided by clinical judgement. Hence, subclinical extramuscular involvement could have remained unnoticed. Histological data were available only for two thirds of the included patients although no other selection bias had occurred other than availability. Furthermore, treatment responses could not be defined using quantifiable outcome measures such as standard muscle strength measurements because this was not the routine in daily practice in all participating centres. Nevertheless, the study does provide a useful descriptive view of a rare disorder that differs strongly from regular myositis. The pathogenesis of this disorder, which probably should be placed in the spectrum of immune‐mediated myopathies, is unclear. Further, preferably prospective studies are needed to fully define the disease and to elucidate the pathogenesis, including the role of the anti‐SRP autoantibodies.