Delayed diagnosis of immune-mediated necrotizing myopathy leads to increased morbidity. Patients with the chronic course without 3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG or signal recognition particle-IgG are often challenging to diagnose.
Immunotherapy response can also be difficult to assess. We created a statistical model to assist immune-mediated necrotizing myopathy diagnosis. Electrical myotonia versus fibrillations were reviewed as biomarkers for immunotherapy treatment response.
Identified were 119 immune-mediated necrotizing myopathy cases and 938 other myopathy patients. Inclusion criteria included all
having electrophysiological evaluations, muscle biopsies showing inflammatory/necrotizing myopathies, comprehensively recorded
neurological examinations, and creatine kinase values. Electrical myotonia was recorded in 56% (67/119) of retrospective and
67% (20/30) of our validation immune-mediated necrotizing myopathy cohorts, and significantly (P < 0.001) favoured immunemediated necrotizing myopathy over other myopathies: sporadic inclusion body myositis (odds ratio ¼ 4.78); dermatomyositis
(odds ratio ¼ 10.61); non-specific inflammatory myopathies (odds ratio ¼ 8.46); limb-girdle muscular dystrophies (odds
ratio ¼ 5.34) or mitochondrial myopathies (odds ratio ¼ 14.17). Electrical myotonia occurred in immune-mediated necrotizing myopathy seropositive (3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG 70%, 37/53; signal recognition particle-IgG 29%, 5/
17) and seronegative (51%, 25/49). Multivariate regression analysis of 20 variables identified 8 (including electrical myotonia) in
combination accurately predicted immune-mediated necrotizing myopathy (97.1% area-under-curve). The model was validated in
a separate cohort of 30 immune-mediated necrotizing myopathy cases. Delayed diagnosis of cases with electrical myotonia
occurred in 24% (16/67, mean 8 months; range 0–194). Half (8/19) had a chronic course and were seronegative, with high model
prediction (>86%) at the first visit. Inherited myopathies were commonly first suspected in them. Follow-up evaluation in patients
with electrical myotonia on immunotherapy was available in 19 (median 21 months, range 2–124) which reduced from 36% (58/
162) of muscles to 7% (8/121; P < 0.001). Reduced myotonia correlated with immunotherapy response in 64% (9/14) as well as
with median creatine kinase reduction of 1779 U/l (range 401–9238, P < 0.001). Modelling clinical features with electrical myotonia is especially helpful in immune-mediated necrotizing myopathy diagnostic suspicion among chronic indolent and seronegative
cases. Electrical myotonia favours immune-mediated necrotizing myopathy diagnosis and can serve as an adjuvant immunotherapy
biomarker.