Inflammatory Myopathies
Inflammatory Myopathies
What You'll Learn
- Four major types: Dermatomyositis (DM), Polymyositis (PM), Immune-Mediated Necrotizing Myopathy (IMNM), and Inclusion Body Myositis (IBM) — PM is now rare/diagnosis of exclusion; many previously labeled PM are actually IMNM
- IBM is the most common inflammatory myopathy in patients >50: Insidious, asymmetric, targets finger flexors (FDP) + quadriceps; DOES NOT respond to immunosuppression
- DM = skin + proximal weakness + cancer risk: Heliotrope rash, Gottron papules; 10–15% malignancy in adults >40; TIF1-γ antibody has strongest cancer association
- IMNM = very high CK + necrosis without inflammation: Anti-SRP (severe, cardiac) and anti-HMGCR (statin-associated); requires aggressive immunosuppression
- Biopsy is diagnostic: Perifascicular atrophy = highly characteristic of DM (also seen rarely in antisynthetase syndrome with perifascicular pattern); rimmed vacuoles = IBM; necrosis/regeneration with MAC = IMNM; endomysial CD8+ T cells = PM
- Antisynthetase syndrome: Myositis + ILD + arthritis + Raynaud + mechanic's hands + fever; Jo-1 most common antibody; ILD may dominate
- Treatment: DM/PM/IMNM → steroids + steroid-sparing agent ± IVIg/rituximab; IBM → no proven effective therapy (exercise + supportive care)
HighYield Pearls
- DM hallmark: proximal symmetric weakness + skin (heliotrope, Gottron papules, shawl/V sign, mechanic’s hands) + perifascicular atrophy on biopsy + MAC on capillaries (humoral/complement-mediated microangiopathy)
- IBM = older adult (>50, M>F), insidious, ASYMMETRIC distal + proximal weakness with preferential finger flexor + quadriceps involvement, dysphagia, mild CK; steroid-unresponsive — never call it PM
- IBM biopsy: endomysial inflammation + rimmed vacuoles + 15–18 nm filamentous inclusions on EM + TDP-43/p62 aggregates; anti-cN1A supportive but not sensitive
- IMNM: severe proximal weakness + CK often >10,000 + necrotic/regenerating fibers with minimal inflammation; anti-HMGCR (statin-associated, persists after withdrawal — distinct from self-limited toxic statin myopathy) or anti-SRP; treat steroids + IVIG + immunosuppression
- Antisynthetase syndrome: myositis + ILD + arthritis + Raynaud + mechanic’s hands + fever; anti-Jo-1 most common (also PL-7, PL-12, OJ, EJ, KS); ILD often dominates
- Anti-MDA5: amyopathic DM + rapidly progressive ILD + skin ulcers/digital ischemia — high mortality, needs aggressive immunosuppression
- Cancer-associated DM: anti-TIF1γ and anti-NXP2 — screen with age-appropriate malignancy workup (CT chest/abd/pelvis, ovarian/lung, PET-CT)
- PM is a diagnosis of exclusion — most historical “PM” cases are IBM, IMNM, antisynthetase, or muscular dystrophy mimics; biopsy required (endomysial CD8+ T cells invading non-necrotic fibers + MHC-I upregulation)
- Juvenile DM → calcinosis cutis (especially NXP-2); anti-Mi-2 → classic DM with good prognosis
- MRI muscle STIR/T2 shows edema in active myositis — useful for biopsy targeting; ICI-associated myositis often overlaps with myasthenia/myocarditis with high mortality
🔍 Quick ReferenceClinical · EMG / labs / imaging · Biopsy / antibody / pathology
Clinical phenotype
- Heliotrope rash + Gottron papules + shawl/V sign → Dermatomyositis
- Mechanic’s hands + arthritis + ILD + Raynaud + fever → Antisynthetase syndrome
- Finger flexor + quadriceps weakness + dysphagia + falls in older adult → Inclusion body myositis (IBM)
- Markedly elevated CK + recent statin use + ongoing weakness despite withdrawal → Anti-HMGCR IMNM
- Rapidly progressive ILD + skin ulcers + amyopathic DM → Anti-MDA5 DM
- Juvenile DM + calcinosis cutis → Anti-NXP2 (juvenile DM)
- Cancer-associated DM in middle-aged adult → Anti-TIF1γ / anti-NXP2
EMG / labs / imaging
- Myopathic motor units (small polyphasic) + fibrillations/PSWs → Active inflammatory myopathy
- CK >10,000 → IMNM (typical); 1,000–10,000 → DM/PM; <2,000 with mild elevation → IBM
- MRI muscle STIR/T2 edema → Active myositis (useful for biopsy targeting)
- MRI muscle fatty replacement of anterior thigh sparing rectus + medial gastroc/forearm flexors → IBM pattern
- Elevated aldolase + LDH → Myositis (supportive); ESR/CRP variable
Biopsy / antibody / pathology
- Perifascicular atrophy + MAC on capillaries + perivascular B-cell/CD4 inflammation → Dermatomyositis
- Rimmed vacuoles + 15–18 nm filaments + TDP-43/p62 inclusions → IBM
- Necrotic + regenerating fibers with minimal inflammation → IMNM
- Endomysial CD8 invading non-necrotic fibers + MHC-I overexpression → Polymyositis
- Anti-Jo-1 / PL-7 / PL-12 / OJ / EJ / KS → Antisynthetase syndrome
- Anti-Mi-2 → Classic DM, good prognosis
- Anti-TIF1γ / anti-NXP2 → Cancer-associated DM
- Anti-MDA5 → Amyopathic DM + rapidly progressive ILD
- Anti-HMGCR / anti-SRP → IMNM
- Anti-cN1A → IBM (supportive)
Classification
Four Major Types of Inflammatory Myopathy
| Type | Key Distinction |
|---|---|
| Dermatomyositis (DM) | Skin rash + proximal weakness; complement-mediated microangiopathy; perifascicular atrophy on biopsy |
| Polymyositis (PM) | Proximal weakness without skin rash; CD8+ T cell-mediated; now rare — diagnosis of exclusion after ruling out IBM, IMNM, and dystrophy |
| Immune-Mediated Necrotizing Myopathy (IMNM) | Severe proximal weakness + very high CK; necrosis/regeneration with minimal inflammation; anti-SRP or anti-HMGCR antibodies |
| Inclusion Body Myositis (IBM) | Insidious asymmetric weakness (finger flexors + quadriceps); rimmed vacuoles on biopsy; refractory to immunosuppression |
💎 Board Pearl
- PM is now considered a diagnosis of exclusion — many historical PM cases were actually IMNM or IBM; always check for IMNM antibodies and consider biopsy before labeling PM
- If a “PM” patient does not respond to steroids, reconsider the diagnosis — think IBM (if older + distal weakness) or IMNM (if very high CK)
DM vs PM vs IBM vs IMNM — Master Comparison
| Feature | DM | PM | IMNM | IBM |
|---|---|---|---|---|
| Age of onset | Any age (adults + children) | >18 years | Any age | >50 years |
| Sex | F > M (2:1) | F > M | F > M | M > F (3:1) |
| Onset | Subacute (weeks–months) | Subacute | Acute/subacute | Insidious (years) |
| Weakness pattern | Proximal, symmetric | Proximal, symmetric | Proximal, symmetric, severe | Proximal + distal, asymmetric (finger flexors + quadriceps) |
| Skin involvement | Yes (hallmark) | No | No | No |
| CK level | Elevated (5–50×) | Elevated (10–50×) | Very high (often >10,000) | Mild (1–10×) |
| Pathology | Perifascicular atrophy; perimysial inflammation; complement (MAC) on capillaries | Endomysial CD8+ T cells invading non-necrotic fibers | Necrosis/regeneration; minimal/absent inflammation; MAC on capillaries | Rimmed vacuoles; intracellular inclusions (amyloid, TDP-43, p62); endomysial CD8+ T cells |
| Key antibodies | Mi-2, MDA5, TIF1-γ, NXP-2, SAE | No specific MSA; antisynthetases (Jo-1, etc.) may occur but define antisynthetase syndrome rather than pure PM | Anti-SRP, anti-HMGCR | Anti-cN1A (~33–50%, up to 60% in some series) |
| Cancer risk | 10–15% (highest with TIF1-γ) | Low | Moderate (especially anti-HMGCR) | None |
| Treatment response | Good | Good | Variable (often aggressive Rx needed) | Poor/none |
| Dysphagia | 20–30% | Uncommon | Uncommon | ~60% |
💎 Board Pearl
- Older man + slow progressive weakness + finger flexors + quadriceps + rimmed vacuoles = IBM — the most tested inflammatory myopathy on boards
- Very high CK (>10,000) + minimal biopsy inflammation = IMNM, not PM
- Skin rash precedes or accompanies weakness = DM — if only skin and no weakness, it is amyopathic DM (check MDA5)
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