Inclusion body myositis evolving in systemic lupus erythrematosus? A case report

G. Massawi, P. Hickling, D. Hilton1 and C. Patterson

Departments of Rheumatology, and
1 Histopathology, Derriford Hospital, Plymouth, UK

SIR, The prevalence of inclusion body myositis (IBM) in the context of an autoimmune connective tissue disorder is not known. There is only one other case report of a patient with systemic lupus erythrematosus (SLE)-associated myositis who went on to develop IBM [1]. We present a second case supporting the hypothesis that at least some cases of IBM are immunologically derived.

In 1981 a 58-yr-old women presented with a 9 month history of malaise, arthralgia and dryness of the eyes. Investigations showed neutropenia (1.49x109/l), positive antinuclear antibodies with speckled pattern (1:640), positive DNA binding >160 IU/ml (0–25), and positive Ro and La antibodies. A diagnosis of SLE and associated Sjogren's syndrome was made. The patient was treated with hydroxychloroquine and oral steroids. In 1988 she developed severe muscle pain and weakness and her creatine phosphokinase (CPK) was high, ranging from 370 to 602 IU/l (24–170). The patient's EMG and an open muscle biopsy from the vastus medialis showed evidence of mild myositis without features of IBM. This was treated with azathioprine and later cyclosporin. The patient showed scant improvement; however, compliance with medication was poor. She had a severe exacerbation of her myositis in 1996 with progressive weakness. A repeat immunological screen showed the presence of the aforementioned autoantibodies. However, the patient's Jo1 antibodies were negative and a repeat muscle biopsy from the vastus medialis showed nercotizing myositis (Fig. 1Go), and this required treatment with intravenous methylpredinsolone. She became progressively weaker in her peripheral muscles, especially the small muscles of her hands, and ran a bearly elevated CPK of 150–190 IU/l. At this stage a further open muscle biopsy from the same muscle demonstrated chronic myopathic changes with prominent fibrosis and presence of rimmed vacuoles, suggesting a diagnosis of IBM. This did not respond to treatment with intramuscular methotrexate 25 mg weekly. In May 2001 a further muscle biopsy confirmed the diagnosis of IBM as evidenced by the classical electron microscopic features of this disorder including the presence of membranous whorls and the tubulo filamentous inclusions (Fig. 2Go).



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FIG. 1. Muscle biopsy showing a patchy myositis with fibre necrosis and a lymphocytic infiltrate, which is surrounding and infiltrating non-necrotic fibres.

 


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FIG. 2. Electron micrograph illustrating 15 nm tubulofilmentous structures, characteristic of IBM.

 
The patient has recently been treated with intravenous immunoglobulins and managed to achieve a reasonable recovery in her muscle strength and functional status.

IBM is defined as an idiopathic inflammatory myopathy [2, 3]. Adams histologically described IBM for the first time in the mid-1960s as a form of myopathy with cellular inclusions [2]. In 1971, IBM was identified as a distinct disorder that could be differentiated from other idiopathic inflammatory myopathies such as polymyositis and dermatomyositis by the presence of fibres containing inclusions that contain amyloid-like deposits [4, 5]. IBM is present in 15–28% of patients with idiopathic inflammatory myositis [6]. It primarily affects men and the age of onset is typically 50 yr or older. The muscle weakness in IBM is classically insidious and slowly progressive, unlike other forms of myositis, often shows prominent involvement of the distal muscles. Myalgias are present in 40% of patients with IBM [7], and muscle atrophy progresses according to disease duration and severity of muscle weakness. Muscle enzymes are typically normal or barely elevated. Muscle biopsy is characterized by the presence of basophilic-rimmed vacuoles and the adjacent eosinophillic inclusions, which are seen within the muscle fibre sarcoplasm. However, the definitive diagnostic feature is the presence of filamentous inclusions and vacuoles on electron microscopy [5].

IBM is very resistant to the conventional immunosuppressive treatment. Muscle weakness continued to progress in patients who were treated with steroid, azathioprine and methotrexate [810]. However, significant improvement of muscle strength and functional status were observed in a recent study using intermittent intravenous immunoglobulins [11].

It is possible that in this patient IBM evolved from autoimmune polymyositis. This assumption is based on the patient's clinical course, the serological findings, which were in keeping with a diagnosis of SLE, and the progressive histological changes that were seen in her sequential muscle biopsies. The observation that the patient's muscle disease became progressively more resistant to the standard immunosuppressive treatment, including azathioprine, methotrexate and cyclosporin, also supports this hypothesis. The later improvement in her muscle strength after treatment with intravenous immunoglobulins is consistent with results of the recent trials, which have focused on this treatment [11].

There are some similarities between this case and the previously reported patient who had developed an IBM on a background of SLE associated myositis. However, in the previous case there was no pathological confirmation that the initial myositis had any of the characteristic features of IBM. In both cases IBM developed several years after the onset of symptoms, once the patient reached the age of 50 yr, lending to support the hypothesis that IBM may occur as a reaction of ‘ageing’ muscle to the same types of immunological stimuli that initiate polymyositis [12]. These findings could argue that muscle biopsy should be undertaken more readily in atypical cases of Lupus-associated myositis. IBM may start to become a more common complication.

Notes

Correspondence to: G. Massawi. E-mail: gmassawi{at}aol.com Back

References

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  10. Leff RL, Miller FW, Hicks J et al. The treatment of inclusion body myositis: a retrospective review and a randomised, prospective trial of immunosuppressive therapy. Medicine 1993;72:225–35.[ISI][Medline]
  11. Dalakas MC, Sonies B, Dambrosia J et al. Treatment of inclusion body myositiswith IVIG: A double-blind, placebo-controlled study. Neurology 1997;48:712–6.[Abstract]
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Accepted 19 December 2002





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Systemic Lupus Erythematosus and Autoimmunity
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