inclusion body myositis

**Epidemiology/Presentation** - Most common inflammatory myopathy in those >50 yr; male > female (unlike polymyositis/dermatomyositis, which are female-predominant). - Insidious onset over years. Characteristic pattern: **quadriceps weakness** (frequent falls, difficulty climbing stairs/rising from chair) and **finger flexor/wrist flexor weakness** (poor grip, trouble with buttons/keys). Often asymmetric. Distal involvement is a clue, since PM/DM are typically proximal and symmetric. - Dysphagia in ~40-60% (cricopharyngeus involvement). Facial weakness may occur; extraocular muscles are spared. Sensation is normal. Mild late atrophy of quadriceps and forearm flexors. - No skin rash (vs dermatomyositis); no strong association with malignancy (vs DM).

**Pathophysiology** - Mixed inflammatory and degenerative process. Autoimmune component: clonal CD8+ cytotoxic T cells and macrophages surround and invade non-necrotic muscle fibers expressing MHC class I (endomysial infiltrate). Degenerative component: protein misfolding/aggregation (β-amyloid, tau, TDP-43, p62, ubiquitin), impaired autophagy, mitochondrial abnormalities (COX-negative fibers). - Autoantibody: **anti-cN1A (anti-NT5C1A)** in ~50-70%; fairly specific, not required for diagnosis. - Associated with HLA-DR3/8.17 ancestral haplotype; some associations with T-cell large granular lymphocytic leukemia, HCV, HIV.

**Diagnosis** - CK normal to mildly elevated (usually <10× ULN, much lower than PM). - EMG: myopathic, often mixed with short-duration, small, polyphasic motor units; may also show chronic neurogenic features (large units), which can mimic ALS. - **Muscle biopsy (gold standard):** endomysial mononuclear infiltrate (CD8+ T cells invading non-necrotic fibers), **rimmed vacuoles** (basophilic granular material on H&E/Gomori trichrome), eosinophilic cytoplasmic inclusions, Congo red-positive amyloid deposits, ubiquitin/p62/TDP-43-positive aggregates, COX-negative fibers. Electron microscopy: 15-18 nm tubulofilamentous inclusions in cytoplasm/nucleus. - MRI: fatty replacement of the flexor digitorum profundus and quadriceps (relative sparing of rectus femoris is sometimes noted).

**Treatment/Prognosis** - **Poor response to corticosteroids, IVIG, and other immunosuppressants** (key board point; a patient with "polymyositis" not responding to steroids should prompt consideration of IBM). - Management is supportive: PT/OT, fall prevention, dysphagia management (swallow evaluation, cricopharyngeal myotomy/dilation, IVIG may help in select cases). Clinical trials of agents like arimoclomol and sirolimus have not established clear benefit. - Slowly progressive; most patients eventually need assistive devices; life expectancy is near normal, though aspiration risk is notable.

**High-yield comparison** | | IBM | Polymyositis | Dermatomyositis | |---|---|---|---| | Age | >50 | Adult | Bimodal (juvenile and adult) | | Sex | M > F | F > M | F > M | | Distribution | Distal finger flexors and quadriceps, asymmetric | Proximal, symmetric | Proximal, symmetric | | CK | Normal/mildly ↑ | Markedly ↑ | ↑ | | Biopsy | CD8+ endomysial, rimmed vacuoles | CD8+ endomysial | CD4+ perimysial/perivascular, perifascicular atrophy | | Steroid response | Poor | Good | Good | | Skin/Malignancy | No | No | Heliotrope/Gottron; ↑ malignancy |

**Exam pearl:** An older man with slowly progressive weakness of the quadriceps and finger flexors, dysphagia, mildly elevated CK, and no response to steroids, with rimmed vacuoles on biopsy = inclusion body myositis.