Myopathy associated with anti–signal recognition peptide antibodies: Clinical heterogeneity contrasts with stereotyped histopathology

Abstract

We report three patients with anti-signal recognition particle antibodies who had different presenting clinical pictures, mimicking acute polymyositis, limb-girdle muscular dystrophy, and acute rhabdomyolysis. Muscle biopsies typically showed necrotizing myopathy with little or no inflammation and deposits of membrane attack complex (C5b-9) in endomysial capillaries. The clinical course was severe in two patients and mild in one. The combination of corticosteroid with either an immunosuppressive agent or intravenous immunoglobulins was required to improve the condition of these patients.

Anti-Signal Recognition Particle Myopathy in a Geriatric Patient

“…To our knowledge this paper reports the oldest patient yet described with anti-SRP myopathy as symptoms usually present in middle-aged people, more frequently in women [1,3] . Clinically, our patient presented with slow onset disease which was apparent during her previous admissions to the hospital with high CK levels.…”

“…The slow onset of clinical muscle weakness delayed diagnosis as there were no other signs or symptoms to guide the medical investigation towards an immune-mediated myopathy until the patient presented with rapid progression associated with myalgia. Complete or partial resistance to steroids is a common feature of anti-SRP myopathy [3,4] , and for that reason our patient's initial therapy was a combination of steroids and azathioprine [5] . Other options have been proposed, but no combination has proven better than the others in terms of outcome.…”

“…INTRODUCTION Anti-signal recognition particle (anti-SRP) autoantibodies are found in 4-6% of idiopathic inflammatory myopathy (IIM) patients [1][2][3] . SRP is a polypeptide complex, involved in the translocation of recently synthesized proteins into the endoplasmic reticulum membrane [4] .…”

“…Despite the rarity of the disorder, all authors describe it as a severe necrotizing immune-mediated myopathy that usually affects middleaged people and is characterized by rapidly progressive proximal and symmetrical muscle weakness, with severe disability occurring within months (sometimes accompanied by dysphagia), elevated creatine kinase (CK) levels (often extremely elevated), no recognizable seasonal pattern, and poor response to steroids or other traditional immunosuppressive therapies [1,4,5] . Histopathologically, it is defined by a necrotizing myopathy with little or no primary inflammation, weak expression of major histocompatibility complex class I (MHC-I), and the presence of particular patterns of complement C5b-9/membrane attack complex deposition [1,3,4] . Unlike antisynthetase syndrome, anti-SRP patients usually do not present with pulmonary fibrosis, arthritis, skin rash, fever or Raynaud's phenomenon, nor do they have an elevated risk for malignancies [3] .…”

“…Histopathologically, it is defined by a necrotizing myopathy with little or no primary inflammation, weak expression of major histocompatibility complex class I (MHC-I), and the presence of particular patterns of complement C5b-9/membrane attack complex deposition [1,3,4] . Unlike antisynthetase syndrome, anti-SRP patients usually do not present with pulmonary fibrosis, arthritis, skin rash, fever or Raynaud's phenomenon, nor do they have an elevated risk for malignancies [3] . CK level seems to be an excellent indicator of the severity of myolysis in a given patient [4] , useful for the follow-up of individuals, but it is a poor marker of disease activity at the population level.…”