Immune-mediated necrotizing myopathy (IMNM) calculator
A guide to predict the probability of immune-mediated necrotizing myopathy
The IMNM calculator is a validated clinical prediction tool that combines eight clinical and electrophysiologic features — including electrical myotonia, creatine kinase (CK) elevation greater than 1,000 units per liter (U/L), statin exposure, proximal deltoid and gluteus maximus weakness, and characteristic distal weakness patterns — to estimate the probability of IMNM.
The tool can help identify patients across a range of pretest probabilities who may benefit from testing for autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR-IgG) and signal recognition particle (SRP54-IgG), and help interpret serologic results in the appropriate clinical context. The model demonstrates excellent discrimination (AUC 97.1%) of the most common mimic disorders. When present, electrical myotonia can also be followed during immunotherapy as an adjunctive marker of treatment response.
Advantages
- This tool is aligned with Mayo Clinic research demonstrating that combining eight clinical features, including electrical myotonia, can lead to a higher probability to distinguish IMNM from other myopathies that have overlapping clinical and/or electrophysiological features.
- Electrical myotonia occurred in 56% and 67% of our initial and validation IMNM cohorts, respectively, most commonly with HMGCR-IgG, but also in seronegative and positive SRP54-IgG cases.
- Patients scoring >75% probability on the model should strongly be considered for an IMNM diagnosis, and providers are cautioned to not overinterpret inflammatory infiltrates on muscle biopsies or variants of unclear significance on genetic testing.
- Serological testing facilitates diagnosis in 30% to 58% of patients either by identification of HMGCR-IgG or SRP54-IgG.
Intended use
The IMNM calculator’s ability to model clinical features with electrical myotonia is especially helpful among chronic indolent and seronegative cases. Electrical myotonia favors immune-mediated necrotizing myopathy diagnosis and can serve as an adjuvant immunotherapy biomarker. However, electrical myotonia need not be present to provide accuracy in the model.
NOTE: A thorough understanding of a patient’s history, clinical examination, and laboratory testing are still needed for a clinic-sero-pathological diagnosis of IMNM. As an example, multiple drugs and rare metabolic myopathies might produce transient rapid onset (24–48 hours) rhabdomyolysis with high probability scores, whereas IMNM typically has subacute (over weeks) onset.
Instructions
- Review each clinical feature and mark “Yes” or “No”.
- All eight features must be evaluated to receive a probability result.
- Questions 5 and 6 cannot be the same answer.
- A probability result is calculated automatically based on the marked boxes and includes recommended laboratory testing.
Shahar Shelly, M.D., and Christopher J. Klein, M.D., present:
Data entry for probability calculation of immune-mediated necrotizing myopathy (IMNM)
Results
- A percentage score is given representing the likelihood of the patient having IMNM.
- Patients scoring >75% probability on the model should strongly be considered for an IMNM diagnosis, and physicians should apply caution to not overinterpret inflammatory infiltrates on muscle biopsies or variants of unclear significance on genetic testing.
- Consider serological testing (HMGCR-IgG and SRP54-IgG), muscle biopsy, and temporal course for cases of rapid onset (<48 hours) that is more typical for other forms of rhabdomyolysis.
Resources
References
- Triplett JD, Shelly S, Livne G, et al. Diagnostic modelling and therapeutic monitoring of immune-mediated necrotizing myopathy: role of electrical myotonia. Brain Communications. 2020;2(2):fcaa191. doi:10.1093/braincomms/fcaa191. PMID: 33364599; PMCID: PMC7749792.
- Paganoni S, Amato A. Electrodiagnostic evaluation of myopathies. Phys Med Rehabil Clin N Am. 2013; 24:193–207.