Dermatomyositis developing in a Duchenne muscular dystrophy carrier

A. N. Bennett, S. R. Sangle, G. R. V. Hughes and D. P. D’Cruz

Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London SE1 7EH, UK

Correspondence to: D. D’Cruz. E-mail: david.d'cruz{at}kcl.ac.uk

SIR, Duchenne muscular dystrophy (DMD) is the commonest muscular dystrophy and its clinical manifestations are well recognized. Less commonly female carriers can become symptomatic, with symptoms ranging from mild generalized weakness to inability to walk. Manifesting carriage of DMD is a rare but important cause of proximal muscle weakness in females, but other diagnoses need to be excluded.

A 42-yr-old lady presented with a lifelong history of fluctuating proximal muscle weakness, fevers, clumsiness and falls. Her brother had died at 19 yr from DMD. Subsequently she gave birth to a boy who has severe DMD. Years later she was referred to neurologists with muscle weakness. Although her history was typical of a manifesting carrier of DMD, her clinical findings were inconsistent and she was discharged. On subsequent referral to the Lupus Unit, muscle weakness, arthralgias, fevers and marked fatigue were noted. Genetic studies confirmed her carrier status but only showed moderately skewed X-inactivation so could not confirm whether she was a manifesting carrier.

Her creatine kinase (CK) was moderately raised [280 IU/l (normal range 0–180)] and ANA, anti-Jo1 and anti-PM-SCL were negative. MRI of the thighs showed atrophy and fatty infiltration (Fig. 1) and shoulder X-rays showed soft tissue calcification. EMG showed motor unit potentials with amplitudes no greater than 2 mV, often with polyphasic waveforms. Muscle biopsy confirmed prominent perivascular inflammation and a tendency for perifascicular atrophy suggestive of dermatomyositis. Dystrophin staining was normal. She responded symptomatically to low-dose prednisolone and methotrexate.



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FIG. 1. MRI of the thighs showing atrophy and fatty infiltration in a symmetrical pattern consistent with myositis.

 
In summary this patient had a chronic history of proximal muscle weakness, arthralgias, fevers, a moderately raised CK, soft tissue calcification on X-ray and an EMG and muscle biopsy suggestive of dermatomyositis. This, in conjunction with inconclusive genetic testing for DMD X-inactivation, led us to conclude that her symptoms were caused by chronic dermatomyositis without evidence of the typical rash.

Dermatomyositis and DMD are important causes of proximal muscle weakness. The incidence of dermatomyositis is 2–10/million per yr [16]. DMD is the most common muscular dystrophy, affecting one in 3500 male infants [7]. It is an X-linked disease, which manifests clinically in affected males. Affected females were thought to be asymptomatic and classified as carriers. It has become apparent that female carriers can become symptomatic and are then classified as manifesting carriers. All carriers of DMD have some cells in which the abnormal X chromosome is active. A compensatory mechanism results in the normal cells producing enough dystrophin to make up for the deficiency, but this is not always the case.

At least 10% of carriers manifest symptoms, ranging from mild generalized weakness to inability to walk. Most manifesting carriers can function normally when well but any mild illness can set them back considerably. There may be a history of weakness and clumsiness in childhood, unexplained abdominal/chest pains, tachycardias, and pseudohypertrophy of the calf muscles caused by atrophic muscle fibres being replaced by fat and connective tissue [7, 8]. Genetic testing easily establishes whether a patient is a carrier, but to establish genetically whether she is a manifesting carrier X-inactivation DNA studies are required to look for preferentially skewed inactivation of the normal X chromosome, hence rendering the affected DMD X chromosome the dominant one. DMD patients will often have a raised CK and EMG studies will show low-amplitude polyphasic units similar to those seen in inflammatory myopathies. Muscle biopsy shows characteristic but non-specific changes of dystrophy. Immunocytochemical studies give quantitative analysis of dystrophin. This is usually normal or near normal in carriers but significantly reduced or absent in DMD patients and, often more subtly, in manifesting carriers. Dermatomyositis can also present with very similar symptoms. Proximal muscle weakness and skin rashes are the most common features, but the presentation may also include fatigue, fevers, arthralgias, interstitial lung disease, oesophageal dysmotility, myocarditis and dysrhythmias. Investigation reveals elevated CK during the active phase of the disease and EMG showing polyphasic action potentials with short duration and low amplitude. The muscle biopsy in dermatomyositis shows chronic inflammatory cell infiltration in the perivascular as well as the perifascicular regions. Perifascicular atrophy is diagnostic of dermatomyositis. MRI of the affected muscles depends on the chronicity and activity of the disease. In acute myositis it shows non-homogeneous increased signal intensities, especially on T2-weighted fat-suppressed sequences. Oedema-like changes on T2 sequences are more typical of acute active disease while replacement with fat is characteristic of chronic, inactive myositis [9] (Fig. 1). X-rays will often show subcutaneous calcification, particularly in the juvenile form of dermatomyositis.

Our patient had several features of both diseases. The presence of fevers, arthralgias, subcutaneous calcification and perivascular inflammation with perifascicular atrophy on muscle biopsy in the presence of normal dystrophin staining and inconclusive X-inactivation studies lead us to conclude that our patient is a carrier for DMD who developed low-grade dermatomyositis that has responded to low-dose immunosuppression.

Informed patient consent was obtained.

The authors have declared no conflicts of interest.

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Accepted 12 November 2003





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