Sporadic inclusion body myositis (sIBM) is a slowly progressive acquired inflammatory muscle disease that develops in adults aged 50 years and older. It is considered the most common inflammatory muscle disease in individuals over 50 years of age5).
The prevalence is estimated at 4.9 to 10.7 per million people, with a high misdiagnosis rate and an average of 5.2 years to confirm the diagnosis. A pooled analysis of prevalence reports 46 per million people 5). Onset before age 60 occurs in 18–20% of cases, and the male-to-female ratio is approximately 3:1, with a male predominance. The number of patients in Japan is estimated at 1,000 to 1,500 4).
The etiology remains unknown, and a major characteristic of this disease is its resistance to immunosuppressive therapy. Genetic associations with HLA-DRB1*03:01 and HLA-B*08:01 have been reported.
It is more common in adults aged 50 and older, with a male-to-female ratio of approximately 3:1, showing male predominance. The prevalence is estimated at 4.9 to 10.7 per million people, and it is the most frequent inflammatory muscle disease in individuals over 50 5).
Asymmetric and distal-predominant muscle weakness is characteristic. Onset is often insidious, and by the time of diagnosis, several years of progression have usually passed.
Upper Limb Findings
Weakness of finger flexors and wrist flexors: A characteristic finding observed from early stages. Often more prominently affected than the deltoid muscle.
Atrophy of finger flexors and wrist flexors: Occurs in parallel with muscle weakness.
Decreased grip strength: Affects daily activities such as opening bottle caps or turning keys.
Ophthalmic Findings
Weakness of the orbicularis oculi muscle: Causes lagophthalmos. Usually remains mild.
Ptosis: Mild ptosis has been reported.
Dry eye: Can occur due to corneal exposure from lagophthalmos.
Retinal vasculitis: The first reported case of bilateral occlusive retinal vasculitis associated with IBM has been described1).
In the lower limbs, weakness and atrophy of the quadriceps femoris muscle are predominant, and it is affected earlier than the hip flexors.
Lagophthalmos due to weakness of the orbicularis oculi muscle and mild ptosis have been reported. Dry eye may occur secondarily. Rare cases of retinal vasculitis (bilateral occlusive) have also been reported1), and regular ophthalmologic evaluation is recommended.
The underlying etiology is unknown. Multiple mechanisms have been suggested, including autoimmune, inflammatory, degenerative, viral infection, and prion-like mechanisms.
The main risk factors and associated factors are as follows:
The pathological mechanism is thought to involve a dual inflammatory and degenerative process progressing in parallel5). Both endomysial infiltration by CD8-positive T cells and macrophages, and loss of TDP-43 from muscle nuclei with cytoplasmic aggregation are observed.
Diagnosis is often delayed, taking an average of 5.2 years. Differentiation from polymyositis and amyotrophic lateral sclerosis (ALS) is important.
In 20–30% of muscle biopsies, rimmed vacuoles are not observed, and only 43% show all three major findings (endomysial inflammation, rimmed vacuoles, mononuclear invasion)2). Additional immunostaining for TDP-43 and p62, as well as mitochondrial DNA analysis, is recommended2).
The performance comparison of major diagnostic criteria is shown.
| Diagnostic Criteria | Sensitivity | Specificity |
|---|---|---|
| ENMC 2013 probable | 84% | ≥97% |
| Griggs criteria | ~60% | High |
Requirements for Griggs criteria: disease duration >6 months, age at onset >30 years, weakness of finger flexors and quadriceps, CK level <12 times the upper limit of normal 5).
The main differential diagnoses are as follows.
The finding of a cricopharyngeal bar (CPB) on videofluoroscopy (VF) has a specificity of 96% for IBM 4).
IBM is resistant to conventional immunosuppressive therapy. There is moderate-quality evidence that IFN-β-1a and methotrexate do not affect IBM progression. Some promising results have been reported with anti-T-lymphocyte immunoglobulin plus methotrexate, but no established standard drug therapy exists.
Dysphagia is an important complication of IBM, and appropriate management affects life prognosis. The 1-year mortality rate for IM patients with dysphagia is reported to be 31% 6).
The characteristics of each treatment are shown below.
| Treatment | Duration of effect | Notes |
|---|---|---|
| Diet modification and speech therapy | Ongoing | First-line conservative treatment |
| Botulinum toxin injection | Less than 1 year | Requires repeated administration |
| Balloon dilation | Short to medium term | Improvement rate less than 33% |
| Cricopharyngeal myotomy (CPM) | Long-term | Improvement in about 60% of patients |
Ramirez Ramirez et al. (2023) reported a 57-year-old female IBM patient with cricopharyngeal dysfunction who underwent endoscopic cricopharyngeal myotomy and had no aspiration for 2 years postoperatively3). The incidence of dysphagia in IBM patients is reported to be 33–50%.
Aerobic exercise and low-load resistance exercise play an important role in treatment.
D’Alton et al. (2022) reported the safety and efficacy of 16 weeks of supervised resistance training in a 71-year-old man with advanced IBM 7). CK levels remained stable (188→181 IU/L), confirming a muscle-strengthening effect. Improvements in subjective fatigue, sleep quality, and balance were also observed.
Treatment is selected stepwise, starting with dietary adjustments and speech therapy, followed by botulinum toxin injection (effect lasts less than 1 year), balloon dilation (improvement rate less than 33%), and cricopharyngeal myotomy (improvement in about 60% of patients)3). Surgery is contraindicated if hiatal hernia is present.
Even in advanced stages, supervised resistance training is safe and has been shown to maintain muscle strength7). No elevation in CK levels has been observed, so it can be performed without concern for muscle damage. Improvements in subjective fatigue and sleep quality have also been reported.
IBM is characterized by the parallel progression of inflammatory and degenerative mechanisms5).
Law et al. (2021) reported coexistence of TDP-43 and C5b-9 in a muscle biopsy of a 77-year-old male IBM patient5). They argued that simultaneous staining of C5b-9 and TDP-43 indicates parallel inflammatory and degenerative dual mechanisms, which may contribute to the development of staged therapeutic strategies.
Chronic inflammation of the pharyngeal constrictor muscles and cricopharyngeus muscle leads to fibrosis and thickening, resulting in impaired opening of the upper esophageal sphincter (UES)4). Histologically, atrophic fibers, immune cell infiltration, endomysial fibrosis, and fatty replacement are observed.
The involvement of highly differentiated cytotoxic T cells has been suggested. These cells function as memory T cells and effector T cells, and are a population that current immunosuppressive therapies cannot target.
Monoclonal antibody against type II activin receptor.
In clinical trials, thigh muscle volume increased after 8 weeks, but at 52 weeks, the 6-minute walk distance was not significantly different from the control group. This suggests that increased muscle mass may not directly translate to improved functional walking ability.
Stenzel et al. and authors (2023) reported that RNA analysis of muscle biopsies enables diagnosis of IBM with high sensitivity and specificity 2). Overexpression of cadherin 1 and detection of missplicing due to TDP-43 loss of function are promising biomarkers.
Shigeyama et al. (2023) performed endoscopic CPM using a new technique with a curved rigid laryngoscope in 4 patients with sIBM, with a mean operative time of 104 minutes, and confirmed improvement or maintenance of swallowing function in all cases 4). A Hyodo score of 6 or higher has been proposed as an indication for surgery.
