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The three major categories of the idiopathic inflammatory myopathies are dermatomyositis, polymyositis, and inclusion body myositis.1 The most important clinical feature distinguishing inclusion body myositis from dermatomyositis and polymyositis is the lack of responsiveness to immunosuppressive treatment.1 2 Yet, it is the experience of many clinicians that a small subgroup of patients with inclusion body myositis show at least a partial response to immunosuppressive treatment. There are no specific characteristics which can identify this subgroup. In this report we present an anti-Jo-1 positive patient with inclusion body myositis who showed a marked and sustained clinical improvement after treatment with oral prednisone.
A 74 year old man, with no relevant medical history, presented with a slowly progressive proximal muscle weakness of the lower limbs. On presentation there were no complaints of muscle weakness of the upper limbs, dysphagia, myalgia, arthralgia, or feelings of general malaise. He denied any sensory symptoms. His family history was negative for neuromuscular or rheumatic disorders and he did not use any myotoxic drugs.
Physical examination showed asymmetric proximal and distal muscle weakness (muscle strength in MRC grades: neck flexors 3, right and left triceps 4, right and left iliopsoas 4, right and left gluteus maximus 4, right quadriceps 4, left quadriceps 2.5, right and left hamstrings 4, right and left anterior tibial 2, left gastrocnemius 4, all other muscles 5), marked atrophy of the quadriceps muscles and low symmetric tendon reflexes. The muscles were not painful to palpation. All other aspects of the general and neurological examination were normal.
Laboratory investigations showed slightly increased concentrations of serum creatine kinase (260 U/l; normal<200 U/l). All other aspects of the routine laboratory investigation including erythrocyte sedimentation rate, lactate dehydrogenase, vitamins, thyroid function tests, and antinuclear factor were normal or negative. Serum was screened for the presence of myositis specific autoantibodies (MSAs) using immunoblotting, enzyme- linked immunosorbent assay (ELISA), and immunoprecipitation as previously described.3 Assays were positive for the anti-Jo-1 autoantibody.
Electromyography demonstrated fibrillation potentials with positive sharp waves, polyphasia, short duration small amplitude motor unit potentials, and several high amplitude motor unit potentials in proximal and distal muscles. Nerve conduction studies were normal.
Muscle biopsy of the right quadriceps muscle showed the presence of small endomysial inflammatory infiltrates, invasion of non-necrotic muscle fibres, basophilic rimmed vacuoles, increased number of muscle fibres containing internal nuclei, ragged-red fibres, atrophic muscle fibres, and positive staining of the sarcolemma for HLA-ABC. Electron microscopy demonstrated the presence of 15–18 nm tubulofilaments in the cytoplasm. The diagnosis of definite inclusion body myositis was made.2
Because the patient was in good general health and the degree of inflammation on muscle biopsy was rather extensive, the decision was made to start treatment with oral prednisone (60 mg once daily). Three months after the initiation of treatment a marked improvement of muscle strength was found (fig 1), serum creatine kinase had normalised (62 U/l), the anti-Jo-1 autoantibody was no longer detectable, and EMG demonstrated a significant improvement with less spontaneous activity and fewer short duration small amplitude motor unit potentials. Prednisone was slowly tapered and stopped 1 year after the initiation of treatment. Muscle strength remained stable (muscle strength in MRC grades 18 months after treatment initiation: right and left triceps 4, right and left quadriceps 4, right and left hamstrings 4, right and left anterior tibial 2, all other muscles 5).
What makes this particular case of great interest are the presence of the anti-Jo-1 autoantibody and the marked and sustained clinical improvement after treatment with oral prednisone. Although a few studies have reported mild improvement in inclusion body myositis with various immunomodulating agents, significant and sustained improvement remains extremely rare in inclusion body myositis.1 2
The anti-Jo-1 autoantibody is the most prevalent MSA and is found in 25% of patients with dermatomyositis and patients with polymyositis.4 In patients with inclusion body myositis the antibody is hardly ever detected.4 5 Until now, only three patients with inclusion body myositis have been reported in whom the antibody was found.5 Unfortunately, the clinical picture of these patients was not described. The relative absence of Jo-1 in inclusion body myositis is seen as support for the hypothesis that the immune response in this disease differs from that in dermatomyositis and polymyositis.4 It has therefore been suggested that the anti-Jo-1 autoantibody can aid in the differential diagnosis between the three entities by virtually excluding inclusion body myositis in cases of anti-Jo-1 positivity and therefore providing an additional argument for the start of immunosuppressive therapy.4
The clinical and electrophysiological improvement after immunosuppressive therapy in the presented patient, together with the presence of a disease specific autoantibody, suggests a prominent role of the inflammatory response. Although it is only based on one case history, this report raises the question whether the presence of an MSA can aid in the identification of patients with inclusion body myositis who might show a response to immunosuppressive therapy. It is not known how MSAs are generated and whether they represent an epiphenomenon or whether they are somehow involved in the pathogenesis of idiopathic inflammatory myopathies. Based on their specificity for myositis it does seem likely that they are the result of a yet unidentified immunological mechanism which is specific for idiopathic inflammatory myopathies and which is, directly or indirectly, linked to the occurrence of clinical myopathy. It can be hypothesised that the presence of an MSA in inclusion body myositis is the result of an identical immunological mechanism as in MSA positive patients with dermatomyositis or polymyositis and that thus immunosuppressive treatment would be of benefit, as in this patient. Additional studies are required to consider these questions.
In conclusion, the present data suggest that in a patient with an idiopathic inflammatory myopathy, even inclusion body myositis, and the presence of an MSA, immunosuppressive treatment should be started and continued for at least 3 months.
We thank WTM Vree Egberts, BAW de Jong, and E Nuy-Terwindt for their expert technical assistance. This work was supported by grant 93–1112 of the Prinses Beatrix Fonds and grant 940–37–009 of MW-NWO.