Immune‐mediated necrotizing myopathy: Unusual presentations of a treatable disease

Abstract

Introduction/Aims: Immune-mediated necrotizing myopathy (IMNM) is an immunemediated myopathy typically presenting with progressive subacute weakness and characteristic, but nonspecific, myopathological findings. Atypical cases however can mimic other inherited or acquired myopathies, depriving patients of treatment. We describe a cohort of such patients.Methods: We retrospectively identified IMNM patients who either previously carried a diagnosis of an inherited myopathy established on clinicopathological grounds or whose muscle biopsies displayed atypical features suggestive of a different myopathy.Results: Among 131 IMNM patients, seven previously unreported patients (5%) met one of the above criteria. Three patients were diagnosed with limb-girdle muscular dystrophy on the basis of a chronic progressive course of weakness and family history of myopathy or cardiomyopathy. The other four patients displayed atypical histological features (two prominent mitochondrial abnormalities, one myofibrillar pathology, and one granulomatous inflammation). Immunostaining of biopsies from 12 additional IMNM patients did not identify myofibrillar pathology. The patient with granulomatous inflammation was known to have pulmonary sarcoidosis. Genetic testing for inherited myopathies was unrevealing. Antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle were identified in 5 and 1 patients, respectively. Four patients presented with slowly progressive weakness over 3-13 y, while weakness was subacute over ≤6 mo in three patients. All patients responded to immunomodulatory therapy. Discussion: Atypical clinical and histological features can occur in IMNM patients, causing delays in diagnosis and treatment. Clinicians should, therefore, consider IMNM in the differential diagnosis of unexplained proximal myopathies in spite of atypical clinical and myopathological findings.

Reply to: Atypical presentations of immune‐mediated necrotizing myopathy: Clues and caveats

“…4 These autoantibodies represent an easily accessible means of detecting previously unsuspected cases of IMNM, especially in patients with a young age of onset, chronic course of disease, positive family history without genetically identified etiology, or atypical myopathological findings. 5,6 We found that these atypical presentations represented approximately 5% of IMNM cases in our cohort. It should be noted that the true incidence could be higher, as additional cases may have gone undetected in the absence of serological testing.…”

“…There are several reports demonstrating that a SARS-CoV-2 infection can be complicated by hypophysitis. 6 Furthermore, patients with a pre-existing pituitary micro-or macroadenoma have an increased risk of pituitary apoplexy during SARS-CoV-2 infection. 7 Accordingly, the hypophysial-pituitary-adrenergic axis can be impaired, 8 thus leading to autonomic dysfunction.…”

Incidence and prevalence of immune‐mediated necrotizing myopathy in adults in Olmsted County, Minnesota

“…Patients' clinical characteristics are shown in Table 1. Two patients (patients 4 and 5) were described in detail in a previous study 15 . Six patients (patients 1‐6) were tested for IMNM antibodies (four anti‐HMGCR IgG positive, one anti‐SRP IgG positive, and one double seronegative).…”

“…Two patients (patients 4 and 5) were described in detail in a previous study. 15 Six patients (patients 1-6) were tested for IMNM antibodies (four anti-HMGCR IgG positive, one anti-SRP IgG positive, and one double seronegative). Two (patients 1 and 6) of the three patients, who were diagnosed with IMNM before IMNM antibody testing became commercially available, were tested on serum…”

Atypical presentations of immune‐mediated necrotizing myopathy: Clues and caveats

“…We read with interest the clinical research report by Nicolau et al 1 Although we found their article to be stimulating and informative, we believe that the authors' conclusions need to be read with certain caveats, to avoid misinterpretation.…”