Case reportMuscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency
Introduction
The idiopathic inflammatory myopathies—polymyositis, dermatomyositis and inclusion body myositis—are a group of acquired, heterogeneous, systemic diseases that are characterized by progressive symmetric muscle weakness, elevated serum levels of muscle enzymes, electromyographic abnormalities and inflammatory infiltrates on muscle [1]. These processes are commonly regarded as autoimmune disorders. Differential diagnosis of the inflammatory myopathies includes muscular dystrophies, specially the dysferlin-deficiency myopathy. Limb girdle muscular dystrophy type 2B (LGMD2B) is an autosomal recessive disease caused by the diminution or absence of dysferlin, a sarcolemmal protein which is thought to play a role in the fusion and repair of cellular membranes. It is known that patients with LGMD2B can present clinically in early adulthood with a significant perivascular and endomysial inflammatory infiltrate on muscle biopsy, leading to a confusing diagnosis of polymyositis [2]. Herein, we report a case of a patient diagnosed with polymyositis and with associated autoimmune diseases (sarcoidosis and Addison's disease) that finally resulted to be a dysferlin deficiency.
Section snippets
Case report
A 34-year-old man with a history of progressive proximal muscle weakness and atrophy was admitted for evaluation. Ten years ago, the patient was diagnosed with Addison's disease. Serum value of ACTH, cortisol and a dynamic test with ACTH stimulation confirmed the diagnosis of primary adrenocortical insufficiency. Circulating adrenal antibodies were highly positive and hormone replacement therapy with cortisone was administered. Six months later, he presented with proximal muscle weakness
Discussion
In contrast to dermatomyositis or sporadic inclusion body myositis which have definite criteria, polymyositis is considered an exclusion diagnosis by some authors, being necessary to exclude other diseases that can mimic it, such as metabolic and dystrophic myopathies. The case reported is a good example of this issue. It has been suggested that patients with dysferlin-deficiency may worsen after receiving steroid treatment [4], as could be, at some extent, the case herein described. Although
Acknowledgements
Supported in part by Grant Fis 040464.
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Cited by (26)
Dysferlinopathy masquerading as a refractory polymyositis
2015, Medicina ClinicaMyositis or dystrophy? Traps and pitfalls
2011, Presse MedicaleCitation Excerpt :Clinical factors that can compound the difficult in distinguishing between dysferlinopathy and myositis include the age of onset (22–23 years) [7,8], that can vary from 12 to 59 years [8], the occasional rapidity of disease progression, and the lack of cardiac, respiratory and facial impairment in dysferlinopathy. In general, cases of dysferlinopathy misdiagnosed as polymyositis and treated with immunosuppressants have been reported [13–15] to show no clear evidence of improvement, as for our patient. Nevertheless, it has to be noted that Lerario et al. reported recently two cases of dysferlinopathy in whom rituximab (anti-CD20 monoclonal antibody depleting B cells) seemed to ameliorate limb girdle and grip strength [16].
Autoantibody profiles in two patients with non-autoimmune muscle disease implicate a role for gliadin autoreactivity
2010, Neuromuscular DisordersCitation Excerpt :This finding is consistent with other data indicating that subclinical CD may be more common than previously thought; the prevalence might be as high as 1% [10]. Autoimmune disease in the setting of LGMD2B has been reported previously in a patient who had autoimmune adrenal insufficiency and sarcoidosis along with dysferlin deficiency [11]. Of further interest is the observation that dysferlin-deficient monocytes show enhanced phagocytic properties [12] and that altered vesicular trafficking in muscles of these patients creates a local inflammatory environment [13].
Dexamethasone induces dysferlin in myoblasts and enhances their myogenic differentiation
2010, Neuromuscular DisordersCitation Excerpt :Studies in DMD patients indicated that glucocorticoid therapy reduced muscle inflammation and muscle proteolysis, while increasing myogenic repair and myoblast proliferation [22,23]. Surprisingly, even though there is significant muscle inflammation in LGMD2B/MM, glucocorticoid treatment is not effective in reducing myopathy and in some cases may have resulted in non-recoverable loss of strength [4–10]. Consistent with effects in DMD patients, prednisolone or deflazacort treatment increased muscle strength in mdx mice, a dystrophin-null mouse model for DMD [24,25].
Inflammatory myopathies. Dermatomyositis, polymyositis, and inclusion body myositis
2008, Reumatologia ClinicaChapter 9 Adrenal Involvement in Systemic Autoimmune Diseases
2008, Handbook of Systemic Autoimmune Diseases