Rheumatology Advance Access originally published online on August 17, 2007
Rheumatology 2007 46(10):1618-1619; doi:10.1093/rheumatology/kem196
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Muscular dystrophy mimicking refractory idiopathic inflammatory myositis: a trio of cases
Centre for Rheumatology, University College London and 1Rheumatology Department, Barnet and Chase Farm Hospitals, London, UK
Correspondence to: Dr Kristine P. Ng, Rheumatology Department, 3rd floor central wing, 250 Euston Road, London NW1 2PQ, UK. E-mail: kristine.ng{at}ucl.ac.uk
SIR, A diagnosis of idiopathic inflammatory myositis (IIM) is usually considered when a patient presents with muscle weakness. Histological diagnosis with a muscle biopsy remains the gold standard test for IIM. The most common diagnostic criteria used for IIM are the Bohan and Peter criteria [1]. We report on three patients who presented with an initial diagnosis of polymyositis (PM), which was subsequently revised on repeat muscle biopsy.
Case 1 is a 23-yr-old female presenting with fatigue and proximal muscle weakness. Anti-nuclear antibodies (ANA) were absent and creatinine kinase (CK) level was 11 297 IU/l. A muscle biopsy showed small basophilic muscle fibres infiltrated with macrophages and lymphocytes, necrotic fibres and increased connective tissue. She was treated for PM with steroids and multiple immunosuppressives (azathioprine, methotrexate, cyclosporine A, cyclophosphamide, plasma exchange) for 7 yrs with limited success. A second muscle biopsy again suggested an IIM. The development of calf hypertrophy led to a third muscle biopsy (Fig. 1) which showed the presence of muscle fibre hypertrophy for the first time and absence of vacuoles on immunohistochemistry, together with the lack of therapeutic response strongly suggesting a diagnosis of muscular dystrophy.
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Case 2 is a 33-yr-old female who presented with muscle weakness and elevated CK of 14 000 IU/l. A muscle biopsy showed intense inflammatory infiltration with numerous necrotic fibres, variation of fibre size and increased fat and fibrous connective tissue. She had ANA (1 : 320) but negative extractable nuclear antigen antibodies. Over the next 7 yrs, she was treated for PM with minimal benefit. Immunosuppressives used included methotrexate, intravenous immunoglobulins (IVIG), tacrolimus, mycophenolate and a trial of rituximab due to ‘refractory’ disease. Another muscle biopsy undertaken showed increased variation in fibre size and no endomysial/perivascular inflammation with no increase of vacuolated fibres. There was a marked increase in utrophin expression on immunohistochemical staining compatible with a dystrophic process. Further, genetic testing for the most common mutation FKRP gene associated with limb girdle muscular dystrophy type 2 I was negative suggesting a sporadic mutation.
Case 3 is a 31-yr-old Asian man who presented with muscle weakness. PM was diagnosed based on elevated CK and myopathic features on electromyogram and magnetic resonance imaging. A muscle biopsy was reported to show histological and immunohistochemistry features of an inflammatory myopathy. Auto-antibody screen was negative. There was no improvement despite IVIG, cyclophosphamide and methotrexate. On further evaluation, he was noted to have calf muscle hypertrophy. A further review of the original muscle biopsy showed abnormal dystrophin glycoprotein complex labelling with severe loss of ß-dystroglycan on immunohistochemistry suggestive of Becker dystrophy. Further, DNA testing confirmed the diagnosis of Becker muscular dystrophy (BMD).
The prevalence of the idiopathic inflammatory myopathies [PM and dermatomyositis (DM)], is estimated at about eight per 100 000 in the general population. It is important to establish a correct diagnosis of IIM to avoid unnecessary exposure of potentially toxic immunosuppressive drugs as highlighted in our cases. The diagnosis of PM may be confused with dystrophinopathies in particular BMD, isolated female carriers of Duchenne muscular dystrophy (DMD) and the recently described dysferlinopathies as the clinical presentation of these disorders can be similar. The late onset presentation of the dysferlinopathies and milder form of the two dystrophinopathies can often be misdiagnosed as PM.
There are pitfalls in the interpretation of a muscle biopsy that could lead to a clinical misdiagnosis. Recent routine molecular diagnostic testing for dystrophies has highlighted the overlap histological features of IIM with some muscular dystrophies [2]. Endomysial lymphocytic infiltrates are considered to be a key pathologic feature of PM but can also occur in DMD, BMD, dysferlinopathies and fascioscapulohumeral dystrophy leading to an initial incorrect diagnosis of PM [3].
Another frequent error in interpreting muscle biopsies is not performing immunocytochemistry to assess for deficiency of sarcolemmal proteins that can cause muscular dystrophies. An assessment of class 1 major histocompatibility complex antigen with immunocytochemistry is important as it is a consistent finding in PM [4]. Although this is helpful, it is not specific and has also been found in patients with dystrophies [5]. Recent advances have led to the availability of genetic testing which can be extremely helpful [6].
The presence of auto-antibodies may help in distinguishing IIM from muscular dystrophies. ANA are present in up to 89% of patients with IIM [7]. Thus, the absence of a positive anti-nuclear antibody should raise doubt about the diagnosis. However, the presence of auto-antibodies does not completely exclude non-inflammatory myopathies as illustrated in the second case.
There was no family history of muscle disease in the three cases presented suggesting the sporadic nature of some forms of muscular dystrophies.
In conclusion, neuromuscular diseases can mimic IIM. In patients thought to have IIM, the absence of ANA and a poor response to immunosuppression should prompt re-consideration of the diagnosis and rebiopsy.
The authors have declared no conflicts of interest.
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