Polymyositis
Polymyositis is a chronic idiopathic inflammatory myopathy characterized by symmetric proximal muscle weakness due to endomysial T-cell–mediated skeletal muscle inflammation.
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References
[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (Polymyositis/Dermatomyositis) [2] Senior notes: Ryan Ho Rheumatology.pdf (pp. 90–92); Ryan Ho Neurology.pdf (Inflammatory Myopathies, pp. 194–195) [3] Lecture slides: GC 056. Generalized muscle weakness.pdf (Polymyositis as diagnosis of exclusion)
Polymyositis (PM) — from Greek: "poly" = many, "myo" = muscle, "itis" = inflammation — is a chronic autoimmune inflammatory myopathy characterised by symmetric proximal skeletal muscle weakness due to endomysial inflammatory infiltration predominantly mediated by CD8+ cytotoxic T-cells [1][2][3].
"A member of the connective tissue disease family as evidenced by autoimmune disease associations and other immunologic features. Characterised by chronic inflammation of striated muscles (polymyositis) and sometimes the skin (dermatomyositis). Autoantibody associations (e.g. anti-Jo-1, anti-Mi-2) define homogeneous clinical subsets of disease." [4]
PM belongs to the broader group of idiopathic inflammatory myopathies (IIMs), which include [2][3][5]:
| IIM Subtype | Key Distinguishing Feature |
|---|---|
| Polymyositis (PM) | Muscle manifestation only |
| Dermatomyositis (DM) | Skin + muscle manifestations |
| Amyopathic DM (ADM/CADM) | Cutaneous manifestations, but no muscle weakness for ≥ 6 months |
| Inclusion body myositis (IBM) | Very rare in HK; proximal + distal muscle weakness; failed response to treatment; diagnosed by inclusion bodies on muscle biopsy |
| Immune-mediated necrotising myopathy (IMNM) | Prominent muscle necrosis with minimal inflammatory infiltrate; may be statin-associated |
| Cancer-associated myositis (CAM) | Temporal association with malignancy |
| Overlap myositis | When associated with another connective tissue disease (CTD) |
Why is PM classified separately from DM?
Although PM and DM share proximal weakness, their immunopathogenesis is fundamentally different. PM is a T-cell-mediated endomysial process targeting individual muscle fibres, while DM is a B-cell/complement-mediated perimysial microangiopathy targeting the intramuscular vasculature. This distinction has therapeutic and prognostic implications — for example, DM in adults carries a much higher malignancy risk than PM.
- Combined incidence of PM/DM: approximately 2/100,000 per year; prevalence 5–22/100,000 [3]
- Demographics: Female > Male = 2:1; peak age of onset 40–50 years (but can occur at any age) [3]
- PM is exceedingly rare in children (juvenile inflammatory myositis is almost always DM)
- PM is the least common of the major IIM subtypes when strict histopathological criteria are applied — many cases historically labelled "PM" are now reclassified as IMNM or overlap myositis using modern autoantibody panels and biopsy criteria [6]
- In Hong Kong/Southern China, nasopharyngeal carcinoma (NPC) is an important malignancy associated with IIM, particularly DM [3]
Risk Factors
| Category | Detail |
|---|---|
| Sex | Female predominance (2:1) |
| Age | Peak 40–50 years; bimodal in DM (childhood 5–15y and adult 40–60y) |
| Genetic susceptibility | HLA-DRB103:01 is the strongest genetic risk factor across multiple IIM subtypes; HLA-B08:01 also associated |
| Ethnicity | Higher prevalence in African Americans vs Caucasians |
| Environmental triggers | Viral infections (e.g. Coxsackie B, influenza, HIV, HTLV-1); UV exposure (more for DM) |
| Drug-induced myositis | Statins (more often IMNM), D-penicillamine, hydroxyurea, TNF inhibitors — these are mimics rather than true PM but important differentials |
| Association with other CTDs | SLE, systemic sclerosis, Sjögren syndrome, MCTD, RA |
| Association with malignancy | 1/3 malignancy (lung, breast, gastric, NPC in this locality); usually diagnosed within 1 year of DM/PM — the malignancy risk is ≈2× in PM and ≈5× in DM [3][2] |
High Yield — The Rule of Thirds for IIM Associations
1/3 malignancy (lung, breast, gastric, NPC) — usually diagnosed within 1 year of DM/PM; 1/3 autoimmune (connective tissue disease); 1/3 idiopathic [2]
Anatomy and Functional Considerations
To understand why PM preferentially affects proximal muscles, you need to appreciate the concept of muscle fibre type distribution and functional loading:
- Proximal muscles (shoulder girdle: deltoid, supraspinatus; hip girdle: iliopsoas, glutei, quadriceps) are rich in Type I (slow-twitch, oxidative) fibres. These fibres have abundant mitochondria and are metabolically active.
- The autoimmune process in PM involves CD8+ T-cells directly invading and destroying non-necrotic muscle fibres expressing MHC class I on their sarcolemma. Type I fibres in proximal muscles appear particularly susceptible, possibly because their high metabolic activity and MHC I upregulation make them preferential targets.
- Distal muscles are relatively spared early on but may be involved in advanced disease.
| Muscle Group | Clinical Consequence |
|---|---|
| Shoulder girdle (deltoid, infraspinatus) | Cannot raise arms above head (e.g., combing hair, reaching overhead shelves) |
| Hip girdle (iliopsoas, glutei, quadriceps) | Cannot squat, climb stairs, rise from a chair |
| Neck flexors | Cannot lift head off pillow (head drop); anterior neck flexors are among the earliest and most sensitive indicators |
| Pharyngeal/oesophageal muscles (striated portion of upper oesophagus) | Dysphagia (for solids > liquids initially), aspiration risk |
| Laryngeal muscles | Dysphonia (nasal, breathy voice), hoarseness of voice (HOV) |
| Intercostal and diaphragm | Respiratory failure (a late, ominous sign) — hypoventilation rather than parenchymal lung disease |
Important Distinction
PM does NOT affect:
- Extraocular muscles (unlike mitochondrial myopathy)
- Facial muscles (unlike facioscapulohumeral dystrophy or myasthenia gravis)
- Cardiac muscle (though cardiac involvement can occur as cardiomyopathy/conduction defects, it is not the primary target)
- Smooth muscle (though oesophageal dysmotility can occur from inflammation of the striated upper oesophageal muscle)
Etiology and Pathophysiology
PM is an autoimmune condition. The exact trigger remains unknown, but the pathogenesis involves a combination of:
- Genetic predisposition — HLA associations (HLA-DRB103:01, HLA-B08:01)
- Environmental triggers — Viral infections (molecular mimicry), UV light (more DM), drugs
- Immune dysregulation — Loss of self-tolerance → autoreactive T-cells targeting skeletal muscle
PM: Endomysial infiltration, predominantly T-cell mediated [1][2][3]
Key Pathophysiological Points
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MHC Class I Upregulation: Normal skeletal muscle fibres do not express MHC class I on their surface. In PM, an unknown trigger (possibly viral or cytokine-driven) causes aberrant MHC class I expression on the sarcolemma. This is the critical initiating event — it allows CD8+ T-cells to "see" the muscle fibre as a target.
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CD8+ T-cell-Mediated Cytotoxicity: CD8+ T-cells infiltrate the endomysium (the connective tissue sheath surrounding individual muscle fibres) and directly invade non-necrotic muscle fibres. They release perforin (punches holes in the sarcolemma) and granzyme B (enters through perforin pores and activates apoptosis). This is a classic MHC class I–restricted, antigen-specific cytotoxic response.
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Why Endomysial, Not Perimysial?: This is the key histological distinction from DM. In PM, the T-cells home to individual fibres (endomysium). In DM, complement-mediated damage targets the perimysial blood vessels (perifascicular microangiopathy). Different immune mechanisms → different anatomical compartments targeted.
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Muscle Enzyme Release: As muscle fibres undergo necrosis, intracellular enzymes leak into the bloodstream:
- Creatine kinase (CK): the most sensitive and specific muscle enzyme, markedly elevated with CK > 10× upper limit of normal (ULN) [1][3]
- LDH, AST, ALT: also released from damaged muscle (remember AST/ALT are not liver-specific!)
- Aldolase: another muscle enzyme, elevated but less commonly measured
- Myoglobin: released from necrotic fibres → can cause myoglobinuria → risk of acute kidney injury (AKI)
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Systemic Autoimmune Features: PM does not exist in isolation. The autoimmune milieu can drive:
- Interstitial lung disease (ILD) — especially with anti-synthetase antibodies (e.g., anti-Jo-1) or anti-MDA5
- Arthritis — non-erosive polyarthritis
- Raynaud phenomenon — vasospasm from immune-mediated vascular dysfunction
- Cardiac involvement — myocarditis, conduction defects
- Association with other CTDs — SLE, SSc, Sjögren syndrome, MCTD
Autoantibody associations (e.g. anti-Jo-1, anti-Mi-2) define homogeneous clinical subsets of disease [4]
| Autoantibody | Type | Target | Clinical Significance |
|---|---|---|---|
| Anti-Jo-1 | Myositis-specific (anti-synthetase) | Histidyl-tRNA synthetase | Anti-synthetase syndrome: myositis + ILD + mechanic's hands + arthritis + Raynaud + fever. ↑ risk of ILD [1][3] |
| Anti-PL-7, anti-PL-12, anti-EJ, anti-OJ | Myositis-specific (anti-synthetase) | Other aminoacyl-tRNA synthetases | Similar anti-synthetase syndrome phenotype; ILD risk |
| Anti-SRP | Myositis-specific | Signal recognition particle | Severe necrotising myopathy, cardiac involvement, poor response to treatment |
| Anti-Mi-2 | Myositis-specific | Nuclear helicase | Classic DM with good prognosis; typical skin rashes; good treatment response |
| Anti-MDA5 | Myositis-specific | Melanoma differentiation-associated gene 5 | Clinically amyopathic DM (CADM); very aggressive rapidly progressive ILD; skin ulceration; poor prognosis [1][3] |
| Anti-TIF1-γ (anti-p155/140) | Myositis-specific | Transcription intermediary factor 1-gamma | Strongly associated with cancer-associated DM in adults |
| Anti-NXP-2 (anti-MJ) | Myositis-specific | Nuclear matrix protein 2 | Associated with calcinosis in juvenile DM; cancer risk in adults |
| Anti-SAE | Myositis-specific | Small ubiquitin-like modifier activating enzyme | DM with dysphagia; may initially present as amyopathic DM |
| Anti-HMGCR | Myositis-specific | HMG-CoA reductase | Statin-associated IMNM; may persist even after statin cessation |
| Anti-Ro (SSA), anti-La (SSB), anti-Sm, anti-RNP | Myositis-associated | Various nuclear antigens | Also found in association with other rheumatic diseases (SLE, Sjögren, MCTD) [1][3] |
High Yield — Myositis-Specific vs Myositis-Associated Antibodies
Classification
The classic approach groups IIM into five categories based on clinical features:
- Primary idiopathic polymyositis
- Primary idiopathic dermatomyositis
- Dermatomyositis/polymyositis associated with malignancy
- Childhood (juvenile) dermatomyositis/polymyositis
- Dermatomyositis/polymyositis associated with other CTDs (overlap)
Current rheumatology practice increasingly classifies IIM based on autoantibody profile, which better predicts clinical phenotype, complications, and prognosis:
| Autoantibody-Defined Subset | Clinical Phenotype |
|---|---|
| Anti-synthetase syndrome | Myositis + ILD + mechanic's hands + arthritis + Raynaud + fever |
| Anti-Mi-2 DM | Classic DM with prominent skin features; good prognosis |
| Anti-MDA5 CADM | Rapidly progressive ILD with minimal myositis |
| Anti-TIF1-γ/anti-NXP-2 DM | Cancer-associated DM |
| Anti-SRP myopathy | Severe necrotising myopathy, cardiac involvement |
| Anti-HMGCR IMNM | Statin-associated necrotising myopathy |
| Feature | Polymyositis | Dermatomyositis |
|---|---|---|
| Pathology | Endomysial infiltration; predominantly T-cell mediated | Perimysial infiltration; predominantly B-cell or complement-mediated microangiopathy |
| Course | Subacute/chronic onset, progressive | More severe and acute onset |
| Skin | No skin involvement | Heliotrope rash, Gottron's papules, V sign, shawl sign, Holster sign, mechanic's hands, calcinosis cutis, dilated nailfold capillaries |
| Malignancy risk | 2× risk | 5× risk; adult form associated with malignancy in up to 60% |
| Biopsy | CD8+ T-cells surrounding and invading individual fibres; endomysial inflammation | Perifascicular atrophy (pathognomonic); perimysial/perivascular B-cells, CD4+ T-cells, complement (MAC) deposits on capillaries |
| Age | Adults only (rarely children) | Adults and children |
| Prognosis | 5–10% mortality | Better with treatment if no malignancy or ILD |
Clinical Features
A. Symptoms
Presents as painless proximal weakness with retained reflexes [3]
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Onset: Subacute/chronic progressive (weeks to months); insidious — patients often cannot pinpoint exactly when it started [1][3]
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Distribution: Classically symmetric proximal — shoulder girdle and hip girdle [3]
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Functional complaints — this is how patients describe the weakness:
- Early: inability to squat, climb stairs, getting up from a chair, carrying heavy groceries [3]
- Late: dysphonia, dysphagia, muscle wasting (generally only in severe, long-standing cases) [3]
- Difficulty combing hair, reaching overhead shelves (shoulder girdle)
- Difficulty rising from toilet, getting out of a car, climbing a bus (hip girdle)
- Head drop — cannot hold head upright against gravity (neck flexor weakness)
Why proximal? As explained above, proximal muscles with high Type I fibre content and high metabolic activity appear to be preferentially targeted by the autoimmune T-cell response. Distal muscles (e.g. hand intrinsics, foot dorsiflexors) are relatively spared early on, which helps distinguish PM from inclusion body myositis (IBM), where distal weakness — especially finger flexors and knee extensors — is a hallmark.
- Painful/tender muscles — present in 25–50% of patients [1][3]
- ± pain (if acute, usually mild) [3]
- Pain is NOT the dominant symptom (unlike fibromyalgia or viral myositis where pain is the chief complaint). If pain is more prominent than weakness, reconsider the diagnosis.
Why pain? Inflammatory mediators (IL-1, TNF-α, IL-6) released during T-cell-mediated muscle fibre destruction sensitise nociceptors in the endomysium and perimysium.
- Dysphagia and dysphonia — result from involvement of pharyngeal and upper oesophageal striated muscles [1][2]
- Dysphagia is for solids more than liquids initially (because it is a mechanical/muscular problem, not a mucosal one)
- Choking episodes may occur due to pharyngeal weakness and impaired epiglottic closure → aspiration risk
- Dysphonia manifests as a nasal, breathy, or weak voice (hoarseness of voice, HOV) [2]
Why dysphagia? The upper one-third of the oesophagus is composed of striated muscle (voluntary), which is targeted by the same autoimmune process. The lower two-thirds is smooth muscle and is typically spared in PM (unlike scleroderma, which affects the smooth muscle portion).
- Dyspnoea on exertion → can progress to respiratory failure [1]
- Two mechanisms:
- Respiratory muscle weakness (diaphragm, intercostals) → restrictive ventilatory defect → hypoventilation
- Interstitial lung disease (ILD) — especially with anti-synthetase antibodies (anti-Jo-1) or overlap with other CTDs
- Fatigue, malaise, low-grade fever, weight loss
- These reflect the systemic inflammatory state (elevated IL-6, TNF-α)
- Non-erosive, non-deforming polyarthralgia or polyarthritis (especially in anti-synthetase syndrome)
- Symmetric small joint involvement similar to RA but non-erosive
- Cold-triggered digital vasospasm → white (ischaemia) → blue (cyanosis) → red (reactive hyperaemia)
- More common in overlap syndromes and anti-synthetase syndrome
- Palpitations, exertional dyspnoea, chest pain — suggest myocarditis, conduction abnormalities, or pericarditis
- Often subclinical; screening ECG is important
B. Signs
| Sign | Detail | Pathophysiological Basis |
|---|---|---|
| Proximal muscle weakness | Symmetric; shoulder girdle + hip girdle + neck flexors | CD8+ T-cell-mediated destruction of proximal muscle fibres |
| Retained reflexes | Deep tendon reflexes are preserved (unlike neuropathy) | The reflex arc (sensory neuron → spinal cord → motor neuron → muscle) is intact; the problem is the muscle end-organ, not the nerve [1][2] |
| Muscle wasting | Only if chronic/long-standing | Chronic fibre destruction with inadequate regeneration → replaced by fibrosis and fatty infiltration |
| Muscle contractures | Only if chronic | Fibrosis of damaged muscle → shortening → fixed contracture |
| No fasciculations | Fasciculations are a sign of lower motor neuron (anterior horn cell) disease, not myopathy | PM is a muscle disease, not a nerve disease |
| Gower's sign | Rising from the floor using hands to "walk up" own thighs — indicates hip girdle weakness | Proximal (hip girdle) muscle weakness requires the patient to use upper limbs as mechanical leverage to extend the trunk |
How to distinguish myopathy from neuropathy at the bedside
- Myopathy (e.g. PM): Proximal weakness, retained reflexes, no fasciculations, no sensory loss, CK markedly elevated
- Neuropathy (e.g. CIDP): Distal > proximal weakness, absent/diminished reflexes, fasciculations (if LMN), sensory loss may be present
- NMJ disorder (e.g. MG): Fatigable weakness (worse with repetition), fluctuating, ptosis/diplopia common, CK usually normal
| System | Sign | Pathophysiological Basis |
|---|---|---|
| Respiratory | Reduced chest expansion, bibasal crackles (if ILD), paradoxical abdominal breathing (diaphragm weakness) | Respiratory muscle weakness (restrictive defect) or ILD (parenchymal inflammation/fibrosis) |
| Cardiac | Irregular pulse, displaced apex, murmurs (rare) | Myocarditis, conduction block, cardiomyopathy |
| Joints | Swollen, tender small joints (non-deforming) | Synovial inflammation in overlap/anti-synthetase syndrome |
| Skin | No skin signs in pure PM (if present → consider DM) | — |
| Hands | Mechanic's hands (hyperkeratosis, fissuring of lateral/palmar surfaces of fingers) — more anti-synthetase syndrome | Chronic inflammation → hyperkeratotic reaction |
| Nailfold | Dilated nailfold capillaries (seen with dermoscopy/ophthalmoscope) | Autoimmune microangiopathy affecting capillary loops |
- No skin rash in pure PM (if rash is present, it is DM, not PM)
- No sensory deficit (sensory system is completely normal — this is a pure motor/muscle disease)
- No cranial nerve involvement (extraocular muscles and facial muscles are spared)
- No fasciculations (this is not a denervation process)
| System | Feature | Mechanism |
|---|---|---|
| Muscle | Symmetric proximal weakness; painless or mildly painful; subacute onset | T-cell-mediated endomysial muscle destruction |
| Pharynx/Larynx | Dysphagia, dysphonia, aspiration | Striated muscle involvement of pharynx/upper oesophagus |
| Respiratory | Dyspnoea, respiratory failure, ILD | Respiratory muscle weakness + autoimmune ILD (anti-Jo-1, anti-MDA5) |
| Joint | Polyarthralgia/arthritis (non-erosive) | Systemic autoimmune inflammation |
| Cardiac | Palpitations, conduction defects, cardiomyopathy | Myocardial inflammation |
| Vascular | Raynaud phenomenon | Vasospasm from immune-mediated endothelial dysfunction |
| Constitutional | Fatigue, fever, weight loss | Systemic cytokine release (IL-6, TNF-α) |
This deserves special mention because it is commonly examined and cuts across PM/DM boundaries:
Anti-synthetase syndrome = myositis (PM or DM) + any combination of:
- Interstitial lung disease (ILD) — the most important prognostic determinant
- Mechanic's hands — hyperkeratosis and fissuring of fingers
- Non-erosive arthritis — symmetric small joints
- Raynaud phenomenon
- Fever
- Anti-synthetase antibodies (anti-Jo-1 is the most common; others: anti-PL-7, anti-PL-12, anti-EJ, anti-OJ)
High Yield — Anti-synthetase Syndrome
The name comes from the target antigen: aminoacyl-tRNA synthetases — enzymes that attach amino acids to their corresponding tRNA during protein translation. Anti-Jo-1 targets histidyl-tRNA synthetase. Why these particular enzymes become autoantigenic is unclear, but there is a hypothesis that viral infections may expose these intracellular enzymes, triggering molecular mimicry.
Cancer types associated with IIM in this locality: lung, breast, gastric, NPC [2][3]
- Nasopharyngeal carcinoma (NPC) is particularly important in the Hong Kong/Southern Chinese population due to the high endemic rate of EBV-associated NPC
- Adult form of DM is associated with malignancy in up to 60% [1] — while PM carries a lower but still significant cancer risk (2× risk in PM vs 5× risk in DM) [3]
- Temporal relationship: malignancy can be diagnosed before, with, or after diagnosis of inflammatory myopathy [3]
- Always perform a comprehensive malignancy screen at diagnosis and at regular intervals
High Yield Summary
Definition: PM = chronic autoimmune inflammatory myopathy with symmetric proximal muscle weakness; endomysial T-cell-mediated destruction.
Epidemiology: Incidence ~2/100k/year; F:M = 2:1; peak 40–50 years.
Rule of Thirds: 1/3 malignancy, 1/3 CTD-associated, 1/3 idiopathic.
Pathophysiology: Aberrant MHC class I upregulation on sarcolemma → CD8+ T-cell recognition → endomysial invasion → perforin/granzyme-mediated fibre destruction → CK release → proximal weakness.
PM vs DM: PM = endomysial/T-cell; DM = perimysial/B-cell+complement microangiopathy.
Clinical Features:
- Symmetric proximal weakness (shoulder girdle, hip girdle, neck flexors)
- Retained reflexes, no sensory loss, no fasciculations
- Dysphagia/dysphonia (bulbar striated muscle involvement)
- ± Respiratory failure (muscle weakness or ILD)
- ± Raynaud, arthritis, cardiac involvement
Key Autoantibodies: Anti-Jo-1 (anti-synthetase syndrome, ILD risk); Anti-SRP (severe myopathy); Anti-MDA5 (rapidly progressive ILD); Anti-Mi-2 (classic DM, good prognosis).
Cancer Association: PM 2× risk; DM 5× risk. In HK: lung, breast, gastric, NPC. Screen at diagnosis.
Labs: CK > 10× ULN; ESR/CRP elevated; EMG shows myopathic potentials with fibrillations.
Active Recall - Polymyositis (Definition, Epidemiology, Etiology, Pathophysiology, Classification, Clinical Features)
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p146, Polymyositis/Dermatomyositis section) [2] Senior notes: Maksim Medicine Notes.pdf (p318–320, Idiopathic inflammatory myopathies) [3] Senior notes: Ryan Ho Rheumatology.pdf (p86–90, Polymyositis and Dermatomyositis; MCTD) [4] Lecture slides: GC 053. Fingers turn white and blue.pdf (p41, Dermato- and poly-myositis) [5] Senior notes: Ryan Ho Neurology.pdf (p194–195, Inflammatory Myopathies) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p706, Differential diagnosis of myopathies)
Differential Diagnosis of Polymyositis
When a patient presents with symmetric proximal muscle weakness, you are essentially asking: "What is destroying or impairing the function of proximal skeletal muscle?" The differential diagnosis is broad and spans multiple organ systems. The key is to systematically work through the anatomical localisation and aetiological categories.
"Symmetric proximal myositis and the absence of histopathological signs of other myopathies or typical rash of DM" — PM is actually considered a "diagnosis of exclusion." True idiopathic PM is rare (or even a controversial entity). Previously considered relatively prevalent, but actually a heterogeneous group of disorders; many PM cases in fact sIBM [sporadic inclusion body myositis] or OM [overlap myositis]." [7]
High Yield — PM as a Diagnosis of Exclusion
This is a critical modern concept from the GC lecture slides. Many cases historically labelled "PM" have been reclassified with modern autoantibody panels and biopsy techniques as inclusion body myositis, immune-mediated necrotising myopathy, or overlap myositis. Therefore, when you diagnose PM, you must actively exclude these mimics. In clinical practice and exams, always demonstrate that you have considered and ruled out the alternatives.
Before diving into specific diseases, the first clinical step is to confirm that the weakness is truly myopathic (i.e., the problem is in the muscle itself) rather than at another level of the neuraxis. This is a fundamental neurology principle.
| Feature | UMN Lesion | LMN Lesion | Neuropathy | NMJ Disorder | Myopathy (PM) |
|---|---|---|---|---|---|
| Distribution | Pyramidal pattern | Segmental/root | Distal > proximal | Ocular, bulbar, proximal | Proximal > distal |
| Tone | ↑ (spastic) | ↓ (flaccid) | ↓ | Normal | Normal or ↓ |
| Reflexes | ↑, Babinski +ve | ↓/absent | ↓/absent | Preserved | Preserved |
| Fasciculations | No | Yes | ± | No | No |
| Sensory loss | ± (depends on level) | ± (dermatomal) | Yes (glove-stocking) | No | No |
| Fatiguability | No | No | No | Yes (hallmark) | No |
| CK | Normal | Normal/mildly ↑ | Normal | Normal | Markedly ↑ (> 10× ULN) |
| Wasting | Late (disuse) | Early, prominent | Yes (distal) | No | Only if chronic |
Once you have localised the lesion to the muscle, you must differentiate PM from other causes of myopathy. The following is the comprehensive differential, drawn from multiple sources [6][8][9]:
| Category | Differential Diagnosis | Key Distinguishing Features from PM |
|---|---|---|
| Inflammatory (autoimmune) | Dermatomyositis (DM) | Characteristic skin findings: heliotrope rash, Gottron's papules, V sign, shawl sign, Holster sign. Perimysial infiltration with B-cell/complement-mediated microangiopathy on biopsy. Adult form associated with malignancy in up to 60% [1][5] |
| Inclusion body myositis (IBM) | Very rare in HK. Proximal + distal muscle weakness (especially finger flexors, wrist flexors, quadriceps). Failed response to treatment (steroids and immunosuppressants don't work). Diagnosed by inclusion bodies (rimmed vacuoles) on muscle biopsy. Age > 50, M > F [2][5] | |
| Immune-mediated necrotising myopathy (IMNM) | Prominent muscle fibre necrosis with minimal inflammatory infiltrate on biopsy (unlike PM where there is endomysial lymphocytic infiltration). Often associated with anti-SRP or anti-HMGCR antibodies. May be statin-triggered [2][5] | |
| Overlap myositis (OM) | Myositis occurring in the context of another CTD (SLE, SSc, Sjögren, MCTD, RA). Myositis-associated antibodies (anti-Ro, anti-La, anti-RNP, anti-Sm) rather than myositis-specific antibodies [2][3] | |
| Anti-synthetase syndrome | Myositis + ILD + mechanic's hands + arthritis + Raynaud + fever. Anti-Jo-1 or other anti-synthetase antibodies. Can overlap with PM or DM phenotype [3][5] | |
| Infective | Viral myositis (HIV, CMV, EBV, influenza A/B, parainfluenza, adenovirus, echovirus) [6][8][9] | Acute onset, often self-limiting, associated with viraemia/prodrome. CK may be elevated. Viral serology positive. |
| Bacterial pyomyositis [6][8] | Localised muscle abscess (NOT symmetric proximal weakness). Fever, leukocytosis. Common in tropics/immunocompromised (e.g. HIV). | |
| Parasitic (toxoplasmosis, trichinosis) [6][8] | Exposure history (undercooked meat), eosinophilia, specific serology. | |
| Endocrine | Hypothyroidism [6][8][9] | Proximal myopathy + fatigue, weight gain, cold intolerance, constipation. ↑TSH, ↓fT4. CK may be mildly elevated. Always check TFT to rule this out! |
| Hyperthyroidism (thyrotoxic myopathy) [6][8] | Proximal weakness + weight loss, tremor, tachycardia, heat intolerance. ↓TSH, ↑fT4. | |
| Cushing's syndrome (steroid myopathy) [6][8][9] | Proximal weakness from excess glucocorticoids (endogenous or exogenous). Cushingoid features: moon face, central obesity, striae, buffalo hump. CK is normal (this is a key distinguishing feature — steroids cause myopathy through muscle protein catabolism, not inflammation). | |
| Electrolyte disturbances [6][8] | Hypokalemia: muscle weakness, paralysis (proximal), cardiac arrhythmia, ECG changes (large U wave, loss of T wave). Hypocalcemia, hyponatremia, hypophosphatemia also cause myopathy [10] | |
| Drug-induced | Statins (HMG-CoA reductase inhibitors) [6][8][9] | Most common drug-induced myopathy. Ranges from myalgia → myopathy → rhabdomyolysis. CK elevated. Usually improves on drug withdrawal. Can trigger true IMNM via anti-HMGCR antibodies (persists after cessation). |
| Corticosteroids [6][8][9] | Proximal myopathy, CK is normal (non-inflammatory, catabolic mechanism). Dose-dependent. Consider in any patient on chronic steroids who develops worsening weakness — steroid myopathy vs disease flare is a critical clinical dilemma! | |
| Other drugs: colchicine, chloroquine/HCQ, zidovudine (AZT), amiodarone, fibrates | Drug history is essential. | |
| Congenital / Hereditary | Duchenne muscular dystrophy (DMD) [6][8] | X-linked recessive. Boys, onset < 5 years. Pseudohypertrophy of calves. Very high CK. Dystrophin absent on biopsy. |
| Becker muscular dystrophy (BMD) [6][8] | Milder form of DMD. Later onset, slower progression. Reduced dystrophin. | |
| Limb-girdle muscular dystrophy [6][8] | Proximal weakness mimicking PM. Genetic testing for LGMD subtypes. No inflammatory infiltrate on biopsy. | |
| Facioscapulohumeral muscular dystrophy (FSHMD) [6][8] | Facial + shoulder girdle weakness (asymmetric). Genetic testing. | |
| Myotonic dystrophy [1][6][8] | Distal weakness + myotonia (delayed relaxation after contraction). Characteristic facies (hatchet face). Multisystem involvement (cataracts, cardiac conduction defects, DM2, testicular atrophy). CTG repeat expansion in DMPK gene. | |
| Metabolic | Glycogen storage diseases (e.g. McArdle disease, Pompe disease) [6][8] | Exercise intolerance, myoglobinuria with exertion. Specific enzyme deficiencies. |
| Lipid storage myopathies (e.g. carnitine deficiency) | Lipid droplets in muscle fibres on biopsy. | |
| Mitochondrial myopathies | Ptosis, ophthalmoplegia (extraocular muscle involvement — unlike PM), lactic acidosis, ragged red fibres on biopsy. | |
| Channelopathy | Periodic paralysis (thyrotoxic, hypokalaemic, hyperkalaemic) [6][8] | Episodic attacks of paralysis (not chronic progressive weakness). Associated with electrolyte shifts or thyrotoxicosis. |
| Neuromuscular junction | Myasthenia gravis (MG) | Fatigable weakness (worse with repetition, better with rest). Ptosis, diplopia common. Anti-AChR or anti-MuSK antibodies. Tensilon test +ve. CK usually normal. |
| Lambert-Eaton myasthenic syndrome (LEMS) | Proximal weakness that improves with repeated use (opposite of MG). Associated with SCLC. Anti-VGCC antibodies. Autonomic dysfunction. | |
| Motor neuron disease | Amyotrophic lateral sclerosis (ALS) [8] | Combined UMN + LMN signs. Fasciculations (absent in PM). Progressive, no sensory loss. |
| Other | Polymyalgia rheumatica (PMR) | Proximal pain and stiffness (NOT weakness). Age > 50. Very high ESR (often > 50). CK is normal. Associated with giant cell arteritis. Dramatic response to low-dose prednisone (15–20 mg/d). |
| Fibromyalgia | Widespread pain, fatigue, tender points. No objective weakness. CK normal. Normal inflammatory markers. | |
| Rhabdomyolysis [6][8][9] | Acute muscle necrosis (crush injury, seizures, drugs, malignant hyperthermia). Markedly elevated CK (> 10,000). Myoglobinuria → AKI. Not chronic/progressive. | |
| Paraneoplastic myopathy | Proximal weakness as a paraneoplastic phenomenon. Must screen for underlying malignancy. |
Step 3: Key Differentials Explained in Detail
This is the most commonly tested comparison:
| Feature | PM | DM |
|---|---|---|
| Skin involvement | Absent | Heliotrope rash, Gottron's papules (pathognomonic), V sign, shawl sign, Holster sign, mechanic's hands, calcinosis cutis, dilated nailfold capillaries [2][3] |
| Pathology | Endomysial infiltration; CD8+ T-cell mediated | Perimysial infiltration; B-cell/complement-mediated microangiopathy; perifascicular atrophy (pathognomonic on biopsy) [1][5] |
| Course | Subacute/chronic, progressive | More severe and acute onset |
| Malignancy risk | 2× risk | 5× risk; adult form associated with malignancy in up to 60% [1][5] |
| Childhood form | Very rare | Common (juvenile DM) |
Why is this distinction important? Because DM has a much higher malignancy association (especially NPC in HK), and the treatment response and prognosis differ. DM also has a distinct amyopathic variant (CADM) that can present with devastating ILD without any muscle weakness.
IBM: very rare in HK, proximal + distal muscle weakness, failed response to treatment; diagnosed by inclusion bodies (rimmed vacuoles) on muscle biopsy [2]
| Feature | PM | IBM |
|---|---|---|
| Age/Sex | 40–50y, F > M | > 50y, M > F |
| Distribution | Symmetric proximal | Asymmetric, proximal AND distal (finger flexors, wrist flexors, quadriceps) |
| Onset | Subacute (weeks–months) | Very insidious (months–years) |
| CK | > 10× ULN | Mildly elevated (usually < 10× ULN) |
| Biopsy | Endomysial CD8+ T-cells | Rimmed vacuoles, endomysial inflammation, congophilic (amyloid) inclusions |
| Treatment response | Responds to steroids | Failed response to treatment — this is the hallmark |
| Dysphagia | Late feature | Common and early |
Why does IBM not respond to immunosuppression? Because IBM has both an inflammatory and a degenerative component (amyloid deposition, mitochondrial dysfunction). The degenerative component is not immune-mediated and therefore does not respond to steroids or immunosuppressants. Many patients initially diagnosed with "treatment-resistant PM" actually have IBM — repeat biopsy reveals rimmed vacuoles.
| Feature | PM | IMNM |
|---|---|---|
| Biopsy | Endomysial lymphocytic infiltrate | Prominent myofibre necrosis with minimal/no inflammatory infiltrate |
| Autoantibodies | Anti-Jo-1, anti-SRP, anti-Mi-2 | Anti-SRP or anti-HMGCR |
| Statin association | No | Yes (anti-HMGCR) — but persists after statin cessation |
| CK | > 10× ULN | Often very high (> 50× ULN) |
| Severity | Moderate | Often severe and aggressive |
| Treatment | Steroids + steroid-sparing | Steroids + IVIG ± rituximab (often needs aggressive immunosuppression) |
A crucial differential because both MG and PM cause proximal weakness without sensory loss:
| Feature | PM | MG |
|---|---|---|
| Nature of weakness | Constant (not fatigable) | Fatigable (worse with repetition, better with rest) |
| Distribution | Proximal limbs, neck flexors | Ocular (ptosis, diplopia), bulbar, proximal limbs |
| Diurnal variation | No | Yes — worse in evening, better in morning |
| CK | Markedly elevated | Normal |
| Reflexes | Preserved | Preserved |
| Antibodies | Anti-Jo-1, anti-SRP | Anti-AChR (85%), anti-MuSK (5–8%) |
| EMG | Myopathic potentials | Decremental response on repetitive nerve stimulation |
| Edrophonium test | Negative | Positive (transient improvement) |
| Treatment | Steroids + immunosuppression | Cholinesterase inhibitors (pyridostigmine) ± immunosuppression |
Why does MG cause fatigable weakness? Because the problem is at the NMJ — antibodies block or destroy acetylcholine receptors. With repeated stimulation, the available ACh is depleted and fewer functional receptors are available → progressive transmission failure → worsening weakness. Rest allows ACh to accumulate again → temporary improvement.
Always Check TFT and Electrolytes Before Diagnosing PM
TFT (to rule out thyroid myopathy) is listed as a mandatory investigation in the workup of suspected inflammatory myopathy [1][3]. Hypothyroid myopathy can perfectly mimic PM with proximal weakness and elevated CK. It is easily reversible with thyroid hormone replacement — don't miss it!
Similarly, hypokalemia (from any cause) can present with profound proximal weakness. Always check electrolytes. Hypokalemia complications: muscle weakness/paralysis (proximal myopathy), cardiac arrhythmia, ECG changes (large U wave, loss of T wave, prolonged QT), ileus, rhabdomyolysis, polyuria [10].
| Feature | Hypothyroid myopathy | Steroid myopathy | PM |
|---|---|---|---|
| CK | Mildly ↑ (rarely > 10× ULN) | Normal | Markedly ↑ (> 10× ULN) |
| Other features | Weight gain, cold intolerance, constipation, bradycardia | Cushingoid features | Subacute onset, ± systemic autoimmune features |
| TFT | ↑TSH, ↓fT4 | Normal | Normal |
| EMG | Normal or mildly myopathic | Normal | Myopathic with fibrillations |
| Treatment | Levothyroxine | Reduce steroid dose | Immunosuppression |
PMR and PM sound similar but are fundamentally different diseases:
| Feature | PMR | PM |
|---|---|---|
| Primary symptom | Pain and stiffness (NO true weakness) | Weakness (± mild pain) |
| Age | > 50 (usually > 65) | 40–50 |
| CK | Normal | Markedly ↑ |
| ESR | Very high (often > 50 mm/hr) | Moderately elevated |
| Association | Giant cell arteritis (temporal arteritis) | Malignancy, ILD, CTDs |
| Biopsy | Synovitis/bursitis (NOT myositis) | Endomysial T-cell infiltration |
| Treatment | Low-dose prednisone (15–20 mg) → dramatic response | High-dose prednisone (1 mg/kg) + steroid-sparing agents |
Why is CK normal in PMR? Because PMR is NOT a muscle disease — it is a periarticular/synovial inflammatory condition affecting the shoulder and hip girdle bursae and synovium. There is no actual muscle fibre destruction, hence no CK leak. The "proximal pain" mimics weakness because patients are reluctant to move due to pain, but on careful examination, power is preserved against resistance.
| Investigation | PM | DM | IBM | IMNM | Hypothyroid myopathy | Steroid myopathy | PMR |
|---|---|---|---|---|---|---|---|
| CK | > 10× ULN | > 10× ULN | Mildly ↑ | Very high | Mildly ↑ | Normal | Normal |
| EMG | Myopathic + fibrillations | Myopathic + fibrillations | Mixed myopathic + neuropathic | Myopathic | Normal/mildly myopathic | Normal | Normal |
| Biopsy | Endomysial CD8+ T-cells | Perimysial, perifascicular atrophy | Rimmed vacuoles | Necrosis, minimal inflammation | Type II fibre atrophy | Type II fibre atrophy | No myositis |
| Autoantibodies | Anti-Jo-1, anti-SRP | Anti-Mi-2, anti-MDA5, anti-TIF1-γ | None specific | Anti-SRP, anti-HMGCR | None | None | None |
| Skin | Normal | Heliotrope, Gottron | Normal | Normal | Dry, coarse | Thin, striae | Normal |
| Treatment response | Responds | Responds | Does NOT respond | Responds (aggressive Rx needed) | Levothyroxine | Reduce dose | Low-dose pred |
Connective tissue disease patients often present with multi-system complaints [11]
Myositis can be associated with: [3][5][11]
- SLE — more overt proximal muscle weakness distinguishes myositis overlap from SLE-related myalgia [8]
- Systemic sclerosis (SSc) — coexistence of Raynaud phenomenon and GERD typically observed [8]
- MCTD — myositis histologically and clinically identical to polymyositis; defined by anti-U1 RNP [3]
- Sjögren syndrome
- Rheumatoid arthritis (rare)
When myositis occurs with another CTD, it is classified as "overlap myositis" rather than "pure PM" [2][5]
Since PM can present with dysphagia (striated muscle of pharynx/upper oesophagus), it features in the DDx of oropharyngeal dysphagia [12]:
| Neuromuscular Cause of Oropharyngeal Dysphagia | Distinguishing Feature from PM |
|---|---|
| Stroke | UMN signs, acute onset, other focal neurological deficits |
| Parkinson's disease | Rigidity, tremor, bradykinesia |
| ALS/MND | UMN + LMN signs, fasciculations |
| MG | Fatigable weakness, ptosis/diplopia |
| Myotonic dystrophy | Distal weakness, myotonia, characteristic facies |
| Polymyositis/Dermatomyositis | Proximal weakness, CK elevated, autoantibodies |
High Yield Summary — DDx of Polymyositis
-
PM is a diagnosis of exclusion — many historical "PM" cases are actually IBM, IMNM, or overlap myositis.
-
First confirm myopathy (proximal weakness, retained reflexes, no sensory loss, elevated CK) then exclude:
- Endocrine: hypothyroidism (TFT), Cushing's (steroid use)
- Drugs: statins, corticosteroids, colchicine
- Electrolytes: hypokalemia, hypocalcemia
- Other IIMs: DM (skin rash), IBM (distal weakness, treatment-resistant, rimmed vacuoles), IMNM (necrosis without inflammation, anti-HMGCR/anti-SRP)
-
Key exam traps:
- PMR vs PM: PMR = pain without true weakness, CK normal, ESR very high, dramatic response to low-dose pred
- MG vs PM: MG = fatigable weakness, ptosis/diplopia, CK normal, decremental response on RNS
- Steroid myopathy vs PM flare: CK normal in steroid myopathy, elevated in PM flare
- Hypothyroid myopathy: Always check TFT — easily reversible!
-
In HK: always consider NPC and other malignancies (lung, breast, gastric) in the cancer screen.
Active Recall - Differential Diagnosis of Polymyositis
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p145–146, Inflammatory Myopathies / PM / DM) [2] Senior notes: Maksim Medicine Notes.pdf (p318–320, Idiopathic inflammatory myopathies) [3] Senior notes: Ryan Ho Rheumatology.pdf (p86–92, Polymyositis and Dermatomyositis; MCTD) [4] Lecture slides: GC 053. Fingers turn white and blue.pdf (p41, Dermato- and poly-myositis) [5] Senior notes: Ryan Ho Neurology.pdf (p194–195, Inflammatory Myopathies) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p706, Differential diagnosis of myopathies) [7] Lecture slides: GC 056. Generalized muscle weakness.pdf (p35, Polymyositis) [8] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1116–1118, Differential diagnosis of myopathy; p1718–1720, DDx of SLE including DM/PM) [9] Lecture slides: Neurology- Two cases of lower limb weakness.pdf (p38, Differential Diagnosis of Myopathy) [10] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (p27, Hypokalemia) [11] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p1, Learning objectives for IIM) [12] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p324–326, DDx of oropharyngeal and esophageal dysphagia)
Diagnostic Criteria
Polymyositis is a clinical diagnosis supported by investigations. Because PM is now recognised as a "diagnosis of exclusion" [7], formal criteria serve two purposes: (1) standardising the diagnosis for research and clinical trials, and (2) reminding clinicians to systematically confirm the key features and exclude mimics. Two main sets of criteria are used.
These are the traditional and most widely cited criteria, still commonly examined in HKUMed assessments [2][8].
Bohan and Peter criteria (1975): PM requires all of 1–4; DM requires any 3 in 1–4 + 5 [2]
| Criterion | Description | Why this criterion matters |
|---|---|---|
| 1. Symmetrical weakness of limb-girdle muscles and anterior neck flexors | Progressive, proximal, symmetric | Confirms the clinical phenotype — the cardinal feature of PM |
| 2. Muscle biopsy: typical of myositis | Endomysial mononuclear inflammatory infiltrates for PM; perimysial infiltrates with perifascicular atrophy for DM | Confirms the pathological substrate — rules out dystrophy, IBM, IMNM |
| 3. Muscle enzyme elevation (especially CK) | CK markedly elevated, usually > 10× ULN | Evidence of ongoing muscle fibre destruction — CK leaks from necrotic sarcolemma |
| 4. EMG: typical of myositis | Spontaneous fibrillation; polyphasic low-amplitude motor unit potential | Confirms the process is myopathic (not neuropathic) and active (fibrillations = ongoing damage) |
| 5. Cutaneous manifestations of DM | e.g. heliotrope rash, Gottron's papules | Only needed for DM classification — by definition absent in PM |
High Yield — How to Apply Bohan & Peter for PM vs DM
- PM = ALL of criteria 1–4 (no skin involvement; if you cannot fulfil all four, you cannot confidently call it PM under these criteria)
- DM = ANY 3 of criteria 1–4 PLUS criterion 5 (skin manifestations)
This means a patient with classic DM skin rash + elevated CK + EMG changes can be diagnosed even WITHOUT biopsy. But for PM, the biopsy is required (all four criteria needed).
Limitations of Bohan & Peter
These criteria were developed in 1975 — before the discovery of most myositis-specific antibodies and before MRI became available. They do not account for:
- Autoantibody subgroups (anti-Jo-1, anti-MDA5, anti-SRP, etc.)
- IBM (which would fulfil PM criteria but is a completely different disease)
- IMNM (prominent necrosis but minimal inflammation — may not meet biopsy criterion)
- Amyopathic DM (no muscle weakness → does not meet criterion 1)
Therefore, modern practice supplements Bohan & Peter with autoantibody panels and careful biopsy interpretation.
2017 EULAR/ACR classification criteria for IIM: include age of onset, antibodies (only anti-Jo-1 now), different scoring with/without muscle biopsy [2]
This is the current international standard. It uses a probability-based scoring system rather than a simple checklist.
Key Features of the 2017 Criteria
| Variable | Score without biopsy | Score with biopsy |
|---|---|---|
| Age of onset ≥ 18 years | 1.3 | 1.5 |
| Age of onset ≥ 40 years | 2.1 | 2.2 |
| Muscle weakness — proximal upper extremity | 0.7 | 0.7 |
| Muscle weakness — proximal lower extremity | 0.5 | 0.8 |
| Neck flexor weakness | 1.9 | 1.6 |
| Objective symmetric weakness | 0.2 | 0.5 |
| Dysphagia or oesophageal dysmotility | 0.7 | 0.6 |
| Anti-Jo-1 antibody positive | 3.9 | 3.8 |
| Elevated CK or LDH or AST or ALT | 1.3 | 1.4 |
| Heliotrope rash | 3.1 | 3.2 |
| Gottron's papules | 2.1 | 2.7 |
| Gottron's sign | 3.3 | 3.5 |
| Endomysial infiltration (biopsy) | — | 1.7 |
| Perimysial/perivascular infiltration (biopsy) | — | 1.2 |
| Perifascicular atrophy (biopsy) | — | 1.9 |
| Rimmed vacuoles (biopsy) | — | 3.1 (subtracts — towards IBM) |
- Total score ≥ 5.5 (without biopsy) or ≥ 6.7 (with biopsy) = probable IIM
- Total score ≥ 7.5 (without biopsy) or ≥ 8.7 (with biopsy) = definite IIM
- Once classified as IIM, a classification tree further subclassifies into PM, DM, IBM, juvenile DM/PM, or amyopathic DM
Key Differences from Bohan & Peter
- Anti-Jo-1 carries the highest score (3.8–3.9) — a single positive anti-Jo-1 antibody significantly pushes the diagnosis toward IIM
- Age of onset is factored in (older age = higher score)
- Biopsy improves specificity but is not absolutely required
- Rimmed vacuoles (IBM marker) subtract from the IIM classification
- Other myositis-specific antibodies (anti-MDA5, anti-SRP, anti-Mi-2, anti-TIF1-γ) are not yet included in the scoring (only anti-Jo-1 is) — this is a limitation of the 2017 criteria that will likely be updated in future revisions
Anti-synthetase syndrome diagnostic criteria: Presence of anti-synthetase antibodies (Jo-1, PL-7, PL-12, EJ, OJ) + 2 major OR 1 major + 1 minor [2][8]
| Category | Criteria |
|---|---|
| Required | Positive anti-synthetase antibody (anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ) |
| Major criteria | ILD, Dermatomyositis, Polymyositis |
| Minor criteria ("ARM") | Arthritis, Raynaud's phenomenon, Mechanic's hands |
The mnemonic "ARM" helps remember the minor criteria [2].
The following algorithm represents the systematic approach to a patient with suspected polymyositis, integrating history, examination, blood tests, EMG, imaging, biopsy, and malignancy screening.
Investigation Modalities — Detailed Breakdown
General: CBC, L/RFT, TFT (r/o thyroid myopathy), ESR/CRP (↑↑) [1][3]
| Investigation | Expected Finding in PM | Why? |
|---|---|---|
| CBC | Mild normocytic anaemia (anaemia of chronic disease); WCC usually normal | Chronic inflammatory state suppresses erythropoiesis via IL-6/hepcidin axis |
| ESR / CRP | ↑↑ (elevated) | Systemic inflammatory response — IL-6 drives hepatic acute-phase protein synthesis (CRP, fibrinogen → ↑ESR) |
| Liver function tests | AST, ALT may be elevated | Not from liver damage — AST/ALT are also released from damaged skeletal muscle. This is a classic exam trap! Always check CK alongside to confirm the source |
| Renal function tests | Usually normal unless myoglobinuria → AKI | Massive muscle necrosis → myoglobin release → precipitates in renal tubules → acute tubular necrosis |
| TFT | Should be normal (to exclude hypothyroid myopathy) | Always check TFT — hypothyroidism can perfectly mimic PM with proximal weakness and elevated CK [1][3] |
| Electrolytes | Should be normal (to exclude electrolyte myopathy) | Hypokalaemia, hypocalcaemia, hypophosphataemia can all cause proximal weakness |
| Urinalysis | Check for myoglobinuria (dark urine, dipstick +ve for "blood" but no RBCs on microscopy) | Myoglobin is haem-containing → cross-reacts with dipstick haemoglobin reagent |
Exam Trap — Elevated AST/ALT in PM
Do NOT mistake elevated AST/ALT in PM for liver disease! Skeletal muscle contains both AST and ALT. When muscle fibres are destroyed, these enzymes leak into blood alongside CK. If you see elevated transaminases in a patient with proximal weakness, always check CK first — if CK is massively elevated, the transaminase elevation is likely from muscle, not liver.
Muscle enzymes (CK, LDH, AST): markedly elevated with CK > 10× ULN [1][3]
| Enzyme | Details |
|---|---|
| Creatine kinase (CK) | Most sensitive and specific marker of muscle injury. In active PM, usually > 10× ULN (can be up to 50–100× ULN in severe cases). Rarely normal (~5% of cases) [3]. CK levels correlate roughly with disease activity and can be used to monitor treatment response |
| LDH | Less specific than CK (also found in liver, RBCs, heart). Elevated in PM |
| AST / ALT | Present in both muscle and liver — see above |
| Aldolase | Another muscle enzyme; elevated but less commonly measured in clinical practice |
| Myoglobin | Released from necrotic muscle → can cause myoglobinuria and AKI if massive |
Why is CK the best marker? CK (creatine kinase) catalyses the transfer of a phosphate group from phosphocreatine to ADP → regenerates ATP in muscle. It is highly concentrated in skeletal muscle (CK-MM isoform). When the sarcolemma is disrupted by T-cell-mediated cytotoxicity, CK leaks into the bloodstream. Because skeletal muscle CK concentration is orders of magnitude higher than in other tissues, even modest muscle damage produces a large serum CK rise.
CK as a monitoring tool: CK levels typically fall with successful immunosuppressive treatment. A rising CK may indicate disease flare — but remember, CK is normal in steroid myopathy, so a patient with worsening weakness on treatment who has a normal CK likely has steroid myopathy rather than a PM flare.
Auto-Ab: myositis-specific and myositis-associated antibodies [1][3][4] "Autoantibody associations (e.g. anti-Jo-1, anti-Mi-2) define homogeneous clinical subsets of disease" [4] The significance of a positive anti-nuclear antibodies test; Diagnostic role of the various autoantibodies in autoimmune rheumatic disease [11]
| Antibody Category | Antibody | Target | Clinical Subset / Significance |
|---|---|---|---|
| ANA | Anti-nuclear antibody | Various nuclear antigens | Positive in > 80% of IIM. Non-specific — also positive in SLE, SSc, Sjögren. A negative ANA does NOT exclude PM |
| Myositis-specific | Anti-Jo-1 | Histidyl-tRNA synthetase | Anti-synthetase syndrome (myositis + ILD + mechanic's hands + arthritis + Raynaud + fever). ↑ risk of ILD. Included in 2017 EULAR/ACR criteria [2][6] |
| Anti-SRP | Signal recognition particle | Severe necrotising myopathy with muscle fibre necrosis / endomysial fibrosis with minimal inflammatory infiltrates. Aggressive disease refractory to high-dose steroids [3] | |
| Anti-Mi-2 | Nuclear helicase | Classic DM with good prognosis. Responds well to therapy [3] | |
| Anti-MDA5 | Melanoma differentiation-associated gene 5 | Clinically amyopathic DM (CADM); very aggressive rapidly progressive ILD; cutaneous ulceration; poor prognosis [1][3] | |
| Anti-TIF1-γ (anti-p155/140) | Transcription intermediary factor 1-gamma | Strongly associated with cancer-associated DM in adults | |
| Anti-NXP-2 (anti-MJ) | Nuclear matrix protein 2 | Confers a higher risk of malignancy in patients with DM and PM; calcinosis in juvenile DM [6] | |
| Anti-HMGCR | HMG-CoA reductase | Statin-associated IMNM | |
| Anti-SAE | Small ubiquitin-like modifier activating enzyme | DM with dysphagia | |
| Myositis-associated | Anti-Ro (SSA), anti-La (SSB) | Ro/La ribonucleoproteins | Also found in Sjögren syndrome and SLE [1][3] |
| Anti-Sm, anti-RNP | Smith antigen, U1-RNP | Also found in SLE and MCTD respectively [1][3] | |
| Anti-PM/Scl | PM/Scl complex | Overlap myositis (PM-SSc overlap); ILD and cardiac involvement [6] |
High Yield — Interpreting Autoantibodies
Myositis-specific antibodies: only found in inflammatory myositis; may have prognostic implications [1][3]
Myositis-associated antibodies: also found in association with other rheumatic diseases [1][3]
↑ risk of ILD in anti-synthetase and anti-MDA5 (very aggressive ILD) [1][3]
The autoantibody profile does not just confirm the diagnosis — it predicts the phenotype and prognosis. For example:
- Anti-Jo-1 → screen aggressively for ILD
- Anti-TIF1-γ or anti-NXP-2 → screen aggressively for malignancy
- Anti-MDA5 → expect minimal myopathy but potentially fatal rapidly progressive ILD
- Anti-SRP → expect aggressive necrotising myopathy refractory to standard treatment
EMG is the electrodiagnostic study that differentiates myopathic from neuropathic causes of weakness. It involves inserting a needle electrode into the muscle and recording electrical activity at rest and during voluntary contraction.
The Classic Triad of EMG Findings in Inflammatory Myopathy [2][6][8]
| Finding | Description | What It Means |
|---|---|---|
| Spontaneous fibrillation potentials at rest | Small, brief, regular discharges from individual denervated/damaged muscle fibres | Indicates active muscle fibre damage — the sarcolemma of damaged fibres becomes unstable and generates spontaneous electrical activity. This tells you the disease is active |
| Polyphasic, short-duration, low-amplitude motor unit potentials on voluntary contraction | The motor unit action potential (MUAP) is smaller and more fragmented than normal | In myopathy, individual muscle fibres within a motor unit are destroyed → fewer fibres contribute to the MUAP → the potential is smaller (low amplitude), shorter (short duration), and more fragmented (polyphasic) |
| High-frequency repetitive discharges (complex repetitive discharges) | Bursts of repetitive potentials on mechanical stimulation | Reflects muscle membrane irritability and instability — a sign of ongoing inflammatory/metabolic perturbation [6] |
"EMG is most useful in distinguishing myopathic causes of weakness from neuropathic causes" [8]
Why does PM show fibrillation potentials? Fibrillations are classically associated with denervation (e.g., after nerve injury), but they also occur in inflammatory myopathy. This is because T-cell-mediated muscle fibre destruction segments muscle fibres — the surviving portions of damaged fibres lose their connection to the motor end plate and behave like denervated fibres, generating spontaneous discharges.
Why are MUAPs small, short, and polyphasic in myopathy? A motor unit normally consists of one motor neuron innervating hundreds of muscle fibres. In myopathy, many of these fibres are destroyed or non-functional. The surviving fibres fire asynchronously (polyphasic), and because fewer fibres contribute, the overall potential is smaller (low amplitude) and shorter (short duration). This is the opposite of the neuropathic pattern, where reinnervation produces large, long-duration, high-amplitude MUAPs.
| Feature | Myopathic Pattern (PM) | Neuropathic Pattern (MND, neuropathy) |
|---|---|---|
| MUAP amplitude | Low | High (due to reinnervation) |
| MUAP duration | Short | Long |
| Polyphasic | Yes | Yes (also, from reinnervation) |
| Fibrillations | Yes (active disease) | Yes (denervation) |
| Fasciculations | No | Yes |
| Recruitment | Early recruitment (many small MUAPs needed to generate force) | Reduced recruitment (fewer motor units available) |
Nerve conduction studies (NCS): Typically normal unless severe muscle necrosis and atrophy are present [6]. This is important — normal NCS helps exclude neuropathy as the cause of weakness.
5. Muscle Biopsy
Muscle biopsy: characteristic changes — endomysial infiltration, predominantly T-cell mediated (PM); perimysial infiltration, predominantly B-cell or complement-mediated microangiopathy (DM) [1][5]
Muscle biopsy is the gold standard for confirming the diagnosis and subclassifying the type of inflammatory myopathy.
- "Open or closed-needle biopsy should be taken from muscle that is weak but not atrophied, and the usual targets are quadriceps and deltoid" [8]
- Why weak but not atrophied? A severely atrophied muscle will show only end-stage fibrosis and fatty replacement — you will miss the active inflammatory process. Conversely, biopsying a clinically normal muscle may miss the patchy disease.
- Guided by P/E, EMG ± MRI [3] — MRI or EMG helps identify areas of active inflammation to improve biopsy yield and avoid sampling error
- Biopsy should be taken from the opposite side to the EMG — needle EMG can cause focal artefactual inflammation that confounds biopsy interpretation
| Subtype | Key Histological Features | Immune Mechanism |
|---|---|---|
| PM | Cellular infiltrate is predominantly within the fascicle (endomysial) with inflammatory cells invading individual muscle fibres. ↑ Cytotoxic CD8+ T lymphocytes. NO signs of vasculopathy or immune complex deposition [8] | MHC class I–restricted CD8+ T-cell cytotoxicity → direct muscle fibre invasion and destruction |
| DM | Cellular infiltrate is predominantly perifascicular and perivascular. ↑ B lymphocytes and plasmacytoid dendritic cells. Signs of vasculopathy or immune complex deposition. Perifascicular atrophy (pathognomonic) [8] | Complement-mediated (MAC C5b-9) microangiopathy → ischaemic damage to perifascicular fibres |
| IBM | Endomysial inflammation (similar to PM) + rimmed vacuoles + congophilic (amyloid) inclusions + mitochondrial abnormalities (COX-negative fibres) | Mixed immune + degenerative process |
| IMNM | Prominent myofibre necrosis with minimal/no inflammatory infiltrate; macrophage-predominant clean-up | Antibody-mediated (anti-SRP or anti-HMGCR) targeting muscle fibre surface |
- Muscle fibre necrosis, degeneration and regeneration
- Chronic mononuclear inflammatory infiltrate
- ± Perifascicular atrophy (pathognomonic for DM but can occur in PM overlap)
± MRI: muscle inflammation, oedema, fibrosis, calcification [1][3] "Detects areas of muscle inflammation and oedema with active myositis, fibrosis and calcification. Assess large areas of muscle and thus avoid problems with sampling error in muscle biopsy" [8]
| Sequence | Finding in Active PM | Interpretation |
|---|---|---|
| T2-weighted / STIR | Patchy ↑ T2 signal indicating inflammation, oedema [3] | Increased water content in inflamed muscle → bright on T2/STIR |
| T1-weighted | Fatty replacement (in chronic disease) | Normal muscle is intermediate signal on T1; fatty infiltration appears bright |
| Post-contrast (Gadolinium) | Enhancement in active myositis | Vascular leakiness from active inflammation |
Clinical utility of MRI:
- Guides biopsy: identifies areas of active inflammation → improves biopsy yield, avoids sampling error
- Assessment of disease extent: shows distribution and symmetry of involvement
- Monitoring treatment response: serial MRI can track resolution of oedema
- Sensitive but non-specific: D/dx: muscular dystrophy, metabolic myopathy, rhabdomyolysis [3] — MRI cannot distinguish PM from other causes of muscle oedema on imaging alone
Why is MRI increasingly used over EMG?
MRI is non-invasive (no needles), can assess the entire musculature bilaterally (unlike EMG which samples individual muscles), and can guide biopsy to the most inflamed area. However, it is less specific than EMG for distinguishing myopathic from neuropathic processes. In modern practice, MRI is often used first to guide where to biopsy, while EMG is reserved for cases where the diagnosis remains uncertain.
7. Assessment for Systemic Complications
Connective tissue disease patients often present with multi-system complaints [11]
Investigations of interstitial lung disease [11]
| Investigation | Finding | Interpretation |
|---|---|---|
| CXR | Should be performed in all patients with findings suggestive of DM or PM to detect presence of ILD [8] | Bilateral basal reticular/reticulonodular opacities; may be normal in early ILD |
| HRCT chest | Ground-glass opacification (GGO), reticular changes, traction bronchiectasis; ± honeycombing | NSIP pattern most common in PM/DM-associated ILD; UIP pattern less common [13] |
| Pulmonary function tests (PFTs) | ↓ FVC, ↓ TLC (restrictive pattern); ↓ DLCO (often earliest abnormality) | Restrictive defect from: (1) parenchymal fibrosis (ILD), or (2) respiratory muscle weakness, or both |
| 6-minute walk test | Desaturation on exertion | Functional assessment of gas exchange impairment |
| Investigation | Rationale |
|---|---|
| ECG | Screen for conduction defects (AV block, bundle branch block), arrhythmias |
| Echocardiography | Screen for myocarditis (↓ LVEF), pericardial effusion, pulmonary hypertension (↑ RVSP) |
| Investigation | Rationale |
|---|---|
| Barium swallow / videofluoroscopy | Assess pharyngeal and upper oesophageal striated muscle function; detect aspiration |
| Bedside swallowing assessment | Screen for aspiration risk |
Thorough search for malignancies is mandatory especially in the elderly [4] Potential association between cancer and dermatomyositis and the rationale of cancer screening [11] Systemic malignancy screen: CBC, LFT, urinalysis, CXR, FOBT, Pap test, mammography, testicular self-exam, colonoscopy ± PET-CT [1][3]
| Investigation | Target Malignancy |
|---|---|
| CBC + blood film | Haematological malignancy (leukaemia, lymphoma) |
| LFT | Hepatic metastases |
| Urinalysis | Bladder/renal malignancy |
| CXR | Lung cancer |
| FOBT | Colorectal cancer |
| Pap test (females) | Cervical cancer |
| Mammography (females) | Breast cancer |
| Testicular self-exam (males) | Testicular cancer |
| Colonoscopy | Colorectal cancer (especially in > 50 years) |
| PET-CT | Whole-body screen for occult malignancy — especially in NPC (this locality) [5] |
| NPC screen (HK-specific) | EBV serology (VCA IgA, EA IgA), nasopharyngoscopy |
High Yield — When to Screen and How Often
- Screen at diagnosis of PM/DM
- Repeat screening annually for at least 3 years (malignancy can present before, with, or after myositis onset)
- Risk is highest in the first year after IIM diagnosis
- Adult form associated with malignancy: 5× risk in DM, 2× risk in PM [1][5]
- Types: adenocarcinoma of cervix, lung, ovaries, pancreas, bladder, breast, stomach, NPC (this locality) [5]
- Higher suspicion if: anti-TIF1-γ +ve, anti-NXP-2 +ve, older age, male, severe/refractory disease, rapid onset
Myositis: defined as 2 out of 3 of: ↑ muscle enzymes, EMG abnormalities, +ve muscle biopsy [1][3][4]
| Investigation | Primary Purpose | Key Finding in PM |
|---|---|---|
| CK | Confirm muscle damage | > 10× ULN, rarely normal |
| LDH, AST, ALT | Ancillary muscle enzymes | Elevated (from muscle, not liver) |
| ESR/CRP | Systemic inflammation | ↑↑ |
| TFT | Exclude thyroid myopathy | Normal |
| Electrolytes | Exclude metabolic myopathy | Normal |
| ANA | Screening autoantibody | +ve in > 80% (non-specific) |
| Myositis-specific Ab | Subtype classification and prognostication | Anti-Jo-1 (ILD), anti-SRP (severe), anti-Mi-2 (classic DM), anti-MDA5 (RP-ILD) |
| Myositis-associated Ab | Overlap CTD screen | Anti-Ro, anti-La, anti-Sm, anti-RNP |
| EMG | Confirm myopathy; exclude neuropathy | Spontaneous fibrillations; polyphasic, low-amplitude, short-duration MUAPs |
| NCS | Exclude neuropathy | Normal |
| MRI muscles | Guide biopsy; assess extent | Patchy ↑ T2 signal (oedema/inflammation) |
| Muscle biopsy | Gold standard — subtype classification | Endomysial CD8+ T-cell infiltrate; NO vasculopathy |
| Skin biopsy (DM) | Confirm DM | Interface dermatitis |
| CXR / HRCT / PFT | Screen for ILD | Bibasal GGO, reticular changes; restrictive PFT |
| ECG / Echo | Screen for cardiac involvement | Conduction defects; ↓ LVEF; pHTN |
| Malignancy screen | Mandatory, especially in elderly | Age/sex-appropriate + PET-CT |
High Yield Summary — Diagnosis of Polymyositis
Bohan & Peter (1975): PM requires ALL of (1) symmetric proximal weakness, (2) +ve muscle biopsy, (3) ↑ CK, (4) myopathic EMG. DM = any 3 of 1–4 + skin rash.
2017 EULAR/ACR: Probability-based scoring; anti-Jo-1 carries highest score (3.9); classifies into PM, DM, IBM, juvenile forms.
Simplified diagnostic rule: Myositis = 2 out of 3 of: ↑ CK, EMG abnormalities, +ve muscle biopsy.
Must-do investigations: CK (most sensitive), EMG (myopathic vs neuropathic), muscle biopsy (gold standard, guided by MRI), autoantibodies (prognostic subtyping), TFT (exclude thyroid myopathy), malignancy screen (mandatory in elderly).
PM is a diagnosis of exclusion — actively exclude DM (no skin rash), IBM (no rimmed vacuoles, does respond to treatment), IMNM (endomysial CD8+ infiltrate present, not pure necrosis), and endocrine/drug-induced causes.
Active Recall - Diagnostic Criteria, Algorithm and Investigations for Polymyositis
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p145–146, Inflammatory Myopathies / PM / DM) [2] Senior notes: Maksim Medicine Notes.pdf (p318–320, Idiopathic inflammatory myopathies, Diagnostic criteria, Anti-synthetase syndrome) [3] Senior notes: Ryan Ho Rheumatology.pdf (p90–92, PM and DM Diagnosis and Management) [4] Lecture slides: GC 053. Fingers turn white and blue.pdf (p47, DM Investigations) [5] Senior notes: Ryan Ho Neurology.pdf (p191–195, Diseases of Muscles, Inflammatory Myopathies) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p706–712, JDM/JPM, Serum autoantibodies, EMG findings) [7] Lecture slides: GC 056. Generalized muscle weakness.pdf (p35, Polymyositis) [8] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1754–1762, DM and PM - Clinical manifestation, Investigations, Biopsy, EMG, MRI) [11] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p1, Learning objectives for IIM) [13] Senior notes: Ryan Ho Respiratory.pdf (p121–124, ILD including NSIP and UIP associated with PM-DM)
Management of Polymyositis
Before diving into the specifics, there are several overarching management principles for PM:
- PM is a treatable disease — unlike IBM (which is refractory to immunosuppression), PM generally responds to immunosuppressive therapy. Early, aggressive treatment improves outcomes.
- The backbone of treatment is systemic glucocorticoids — but long-term steroid use causes serious toxicity, so a steroid-sparing agent is introduced early.
- Management is multi-pronged — addressing (a) myositis itself, (b) extra-muscular complications (ILD, cardiac, dysphagia), (c) underlying malignancy if present, and (d) supportive/rehabilitative care.
- Response to steroids differs by subtype: In general, overlap myositis > DM > PM [3]. Anti-SRP-associated myopathy is notoriously refractory.
- Prognosis: 5–10% mortality [1].
Treatment Modalities — Detailed Breakdown
Systemic glucocorticoids: typically start prednisolone 1 mg/kg/d [1][3][5]
| Aspect | Detail |
|---|---|
| Drug | Oral prednisolone (or IV methylprednisolone for severe/acute presentations) |
| Induction dose | 1 mg/kg/day (usually 60–80 mg/day, maximum 100 mg) |
| IV pulse | IV methylprednisolone 500–1000 mg/day for 3 days — used for severe myositis, respiratory failure, rapidly progressive ILD, or life-threatening involvement |
| Onset of action | CK starts to fall within 2–4 weeks; clinical strength improvement lags behind (6–12 weeks) |
| Tapering | Once CK normalises and strength improves (usually 4–6 weeks), begin slow taper: reduce by ~10 mg every 2–4 weeks until reaching ~20 mg, then reduce by 2.5–5 mg every 2–4 weeks. Target maintenance of ≤ 7.5 mg/day or off steroids if possible |
| Duration | Typically maintained for 6–12 months minimum; some patients need low-dose long-term |
Why glucocorticoids work: Glucocorticoids broadly suppress both innate and adaptive immunity by:
- Inhibiting NF-κB → ↓ pro-inflammatory cytokines (IL-1, IL-6, TNF-α)
- Inducing lymphocyte apoptosis → ↓ autoreactive T-cells
- Stabilising lysosomal membranes → ↓ tissue damage
- Inhibiting MHC class II expression on antigen-presenting cells → ↓ T-cell activation
In PM, this dampens the CD8+ T-cell-mediated endomysial attack on muscle fibres, allowing regeneration.
Why we must taper and add steroid-sparing agents: Chronic high-dose steroids cause devastating side effects:
| System | Steroid Adverse Effect | Prevention |
|---|---|---|
| Metabolic | Hyperglycaemia, diabetes | Monitor BSL; diabetic diet |
| Bone | Osteoporosis → fractures | Bisphosphonates (alendronate/zoledronic acid) + calcium + vitamin D [14] |
| GI | Peptic ulcer, GI bleeding | PPI prophylaxis (if on concurrent NSAIDs or anticoagulants) |
| Infection | Immunosuppression → opportunistic infections (PCP, TB, fungal) | Consider PCP prophylaxis (co-trimoxazole) if prednisolone ≥ 20 mg for > 4 weeks; screen for hepatitis B/TB before starting |
| CVS | Hypertension, dyslipidaemia, ↑ CV risk | Monitor BP, lipids [14] |
| Ophthalmologic | Posterior subcapsular cataract, glaucoma | Regular eye screening |
| MSK | Steroid myopathy — proximal weakness with normal CK | Minimise dose; distinguish from PM flare by checking CK |
| Skin | Thin skin, easy bruising, striae | — |
| Psychiatric | Insomnia, mood disturbance, psychosis | Warn patients; short courses of anxiolytics if needed |
| Adrenal | Adrenal suppression → crisis on abrupt withdrawal | Never stop abruptly — always taper gradually |
Steroid Myopathy vs PM Flare — A Critical Clinical Dilemma
When a patient on steroids for PM develops worsening weakness, you must distinguish between:
- PM flare: CK will be elevated → increase steroids / add immunosuppressant
- Steroid myopathy: CK will be normal → reduce steroid dose
Getting this wrong is dangerous: increasing steroids for steroid myopathy will worsen the patient; reducing steroids for a PM flare will worsen the disease.
2. Steroid-Sparing Immunosuppressive Agents (Added Early)
Steroid-sparing agents: methotrexate, azathioprine to allow tapering steroids [1][3][5]
These are introduced early (often simultaneously with steroids or within the first 2–4 weeks) to:
- Enable steroid dose reduction (steroid-sparing effect)
- Provide sustained long-term immunosuppression
- Reduce steroid-related morbidity
| Aspect | Detail |
|---|---|
| Mechanism | Folate antagonist → inhibits dihydrofolate reductase → ↓ purine and pyrimidine synthesis → ↓ lymphocyte proliferation. At low immunosuppressive doses, also has anti-inflammatory effects via ↑ adenosine release |
| Dose | 7.5–25 mg once weekly (oral or subcutaneous) |
| Onset | 4–8 weeks (slow onset — steroids bridge this gap) |
| Indications | First-line steroid-sparing agent for PM (and most autoimmune diseases) |
| Contraindications | Pregnancy (teratogenic — category X), significant renal impairment (MTX is renally cleared → accumulation → toxicity), significant hepatic impairment, active infection, pre-existing ILD (can rarely cause MTX pneumonitis — a difficult clinical scenario when the patient already has ILD from PM) |
| Side effects | Hepatotoxicity (monitor LFT), bone marrow suppression (monitor CBC), mucositis, nausea, MTX pneumonitis (rare but important — must distinguish from PM-associated ILD), teratogenicity |
| Monitoring | CBC, LFT, RFT every 1–2 months; CXR if respiratory symptoms |
| Key point | Always co-prescribe folic acid 5 mg weekly (taken on a different day from MTX) to reduce side effects without compromising efficacy |
MTX and ILD — A Clinical Conundrum
MTX can rarely cause drug-induced pneumonitis (MTX pneumonitis). In a PM patient who already has anti-synthetase-associated ILD, new respiratory deterioration could be from (1) ILD progression, (2) MTX pneumonitis, or (3) infection from immunosuppression. This is why some clinicians prefer azathioprine or MMF over MTX in PM patients with pre-existing ILD.
| Aspect | Detail |
|---|---|
| Mechanism | Pro-drug → metabolised to 6-mercaptopurine (6-MP) → inhibits purine synthesis → ↓ lymphocyte proliferation |
| Dose | 1–3 mg/kg/day |
| Onset | Delayed onset ~3 months [15] — hence steroids must be maintained during this period |
| Indications | First-line steroid-sparing agent (interchangeable with MTX); preferred in patients with ILD (no risk of drug-induced pneumonitis unlike MTX) |
| Contraindications | TPMT or NUDT15 deficiency (see below), concurrent xanthine oxidase inhibitors (allopurinol, febuxostat) |
| Side effects | Bone marrow suppression, allergy, hepatotoxicity, pancreatitis [15]; ↑ risk of lymphoma with long-term use |
| Monitoring | CBC, LFT regularly |
Always measure TPMT and NUDT15 enzyme activity before starting azathioprine [15]
Why check TPMT and NUDT15? Azathioprine is metabolised via three pathways. One of these produces the active but potentially toxic metabolite 6-thioguanine triphosphate (6-TGTP). TPMT and NUDT15 are enzymes that divert azathioprine metabolism away from 6-TGTP accumulation:
- TPMT converts 6-MP → inactive 6-MMP (methylated metabolite)
- NUDT15 helps prevent excessive accumulation of the toxic 6-TGTP
- Xanthine oxidase (XO) converts 6-MP → inactive 6-thiouric acid (6-TU)
If any of these pathways is deficient:
- TPMT deficiency → shunting of metabolism toward 6-TGTP → toxic accumulation → severe bone marrow suppression / neutropenic fever
- NUDT15 deficiency → same principle; more common in HK / East Asian population [15]
- Concurrent allopurinol/febuxostat (XO inhibitors) → block the XO pathway → more 6-MP is shunted to 6-TGTP → bone marrow suppression
High Yield — Three Things to Check Before Starting Azathioprine
1. TPMT enzyme activity, 2. NUDT15 enzyme activity (especially important in HK population), 3. Is the patient taking any xanthine oxidase inhibitors (allopurinol, febuxostat)? [15]
3. Second-Line / Refractory Disease Options
Other strategies: IVIG, plasmapheresis, rituximab, MMF, calcineurin inhibitor [5]
When PM is refractory to steroids + first-line steroid-sparing agent, or when there are specific indications, second-line agents are used.
| Aspect | Detail |
|---|---|
| Mechanism | Multiple mechanisms: Fc receptor blockade → ↓ macrophage activation; anti-idiotype antibodies neutralise pathogenic autoantibodies; modulation of complement; ↓ cytokine production. In practice, IVIG broadly dampens the immune response without the severe immunosuppression of cytotoxic agents |
| Dose | 0.4 g/kg/day for 5 days (total 2 g/kg per cycle); repeated every 4–6 weeks as maintenance |
| Indications | Refractory PM/DM [1][3]; severe disease; patients who cannot tolerate or have contraindications to conventional immunosuppressants; dysphagia/life-threatening disease requiring rapid response |
| Advantages | Relatively rapid onset (days to weeks); can be used in pregnancy; does not increase infection risk as much as other immunosuppressants |
| Contraindications | IgA deficiency (risk of anaphylaxis); severe renal impairment (osmotic nephropathy); uncontrolled heart failure (volume overload) |
| Side effects | Headache, fever, nausea (infusion-related); aseptic meningitis; thrombosis (due to hyperviscosity); renal injury; haemolytic anaemia (if blood group incompatibility) |
| Aspect | Detail |
|---|---|
| Mechanism | Chimeric monoclonal antibody targeting CD20 on B-cells → B-cell depletion via complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and direct apoptosis. By depleting B-cells, it reduces autoantibody production and B-cell antigen presentation to T-cells |
| Dose | Typically 1000 mg IV on day 1 and day 15 (or 375 mg/m² weekly × 4) |
| Indications | Refractory IIM (especially anti-synthetase syndrome, DM); growing evidence base; used in many HKU/HKHA rheumatology centres for refractory myositis |
| Contraindications | Active severe infection; hepatitis B (risk of reactivation — screen for HBV before starting and give antiviral prophylaxis if HBsAg +ve or anti-HBc +ve); hypersensitivity |
| Side effects | Infusion reactions; ↑ infection risk (especially after repeated cycles); progressive multifocal leukoencephalopathy (PML — extremely rare); late-onset neutropenia; hypogammaglobulinaemia |
| Monitoring | Hepatitis B serology before treatment; immunoglobulin levels; CBC; vaccination status (no live vaccines) |
Why does rituximab work in PM if it is a T-cell-mediated disease? Although PM is primarily T-cell driven, B-cells play an important supportive role as antigen-presenting cells (APCs) to T-cells and as producers of pro-inflammatory cytokines. B-cell depletion disrupts this T–B cell cross-talk and reduces the overall autoimmune drive.
| Aspect | Detail |
|---|---|
| Mechanism | Inhibits inosine monophosphate dehydrogenase (IMPDH) → blocks de novo purine synthesis in lymphocytes (which are uniquely dependent on this pathway, unlike most other cells which can use the salvage pathway) → selective anti-lymphocyte effect |
| Dose | 1–3 g/day in divided doses |
| Indications | Steroid-sparing agent; particularly useful for PM-associated ILD (NSIP pattern) [13]; alternative to MTX/AZA |
| Contraindications | Pregnancy (teratogenic); active GI disease (GI side effects) |
| Side effects | GI upset (nausea, diarrhoea — most common), bone marrow suppression, ↑ infection risk |
| Aspect | Detail |
|---|---|
| Mechanism | Alkylating agent → cross-links DNA → cytotoxic to rapidly dividing cells including lymphocytes. The most potent conventional immunosuppressant |
| Dose | IV pulse 0.5–1 g/m² monthly for 6 months (induction); or oral 1–2 mg/kg/day |
| Indications | Severe PM-associated ILD (especially rapidly progressive ILD); life-threatening visceral involvement; refractory to other agents |
| Contraindications | Pregnancy; active infection; bone marrow failure |
| Side effects | Haemorrhagic cystitis (prevent with MESNA and hydration), bone marrow suppression, infection, infertility (gonadal toxicity), ↑ bladder cancer risk (long-term), nausea/vomiting |
| Monitoring | CBC, urinalysis; encourage adequate hydration |
| Aspect | Detail |
|---|---|
| Mechanism | Inhibit calcineurin → block IL-2 transcription in T-cells → ↓ T-cell activation and proliferation. Tacrolimus ("tacroli-mus" → FK-506 binding protein → calcineurin inhibition) |
| Indications | Refractory PM; particularly favoured in Japan for anti-synthetase syndrome with ILD (tacrolimus); alternative steroid-sparing agent |
| Side effects | Nephrotoxicity (monitor RFT), hypertension, tremor, hyperglycaemia, hyperkalaemia, gingival hyperplasia (ciclosporin), hypertrichosis (ciclosporin) |
| Monitoring | Drug trough levels, RFT, BP, BSL, electrolytes |
| Aspect | Detail |
|---|---|
| Mechanism | Physical removal of circulating pathogenic autoantibodies, immune complexes, and inflammatory mediators from plasma |
| Dose | 50 mL/kg per session; 5 exchanges over 2 weeks [5] |
| Indications | Severe, life-threatening myositis (acute respiratory failure from muscle weakness, severe dysphagia with aspiration); as a bridge therapy while waiting for other immunosuppressants to take effect |
| Limitations | Effect is temporary (antibodies regenerate unless immunosuppressive therapy is given concurrently); invasive (large-bore vascular access required); expensive |
4. Organ-Specific Management
ILD management: high-dose steroids + immunosuppressants [3][13]
| Severity | Approach |
|---|---|
| Mild, stable ILD | Monitor with serial PFTs (FVC, DLCO) and HRCT; may not need escalation if stable |
| Moderate–severe ILD | Initial therapy: oral steroid or IV pulse steroid ± azathioprine, MMF [13] |
| Rapidly progressive ILD | 2nd line: cyclophosphamide, rituximab, calcineurin inhibitor [13]; consider antifibrotic agents (nintedanib — now approved for progressive pulmonary fibrosis including CTD-ILD) |
| End-stage ILD | Lung transplant referral; palliative care if not a candidate |
| General | Long-term O2 if PaO2 < 55 mmHg or SaO2 < 88% [13]; vaccination (influenza, pneumococcal); pulmonary rehabilitation |
High Yield — Anti-MDA5 Rapidly Progressive ILD
Anti-MDA5-associated ILD is a medical emergency. It can progress to respiratory failure within weeks. Aggressive combination immunosuppression (IV methylprednisolone + cyclophosphamide + calcineurin inhibitor) is required. Even so, mortality is high (up to 50%).
Supportive (for late bulbar symptoms): physiotherapy, speech therapy, PEG tube [3]
| Approach | Rationale |
|---|---|
| Speech and language therapy | Swallowing rehabilitation, modified diet texture, postural techniques to reduce aspiration |
| Thickened fluids / soft diet | Reduce aspiration risk |
| PEG tube (percutaneous endoscopic gastrostomy) | For severe dysphagia with recurrent aspiration or inadequate oral intake |
| IVIG | May produce rapid improvement in pharyngeal muscle strength — consider early |
| Approach | Detail |
|---|---|
| Non-pharmacological | Keep warm, avoid cold exposure, stop smoking, avoid vasoconstrictors |
| Pharmacological | CCB (nifedipine), PDE-5 inhibitors (sildenafil), prostacyclin analogues (iloprost) for severe cases |
Polyarthritis: NSAIDs [3]
| Approach | Detail |
|---|---|
| NSAIDs | Symptomatic relief for joint pain/swelling |
| Hydroxychloroquine (HCQ) | May help arthritis and skin features in DM |
| Approach | Detail |
|---|---|
| Myocarditis | High-dose steroids + immunosuppressants (treat aggressively like severe myositis) |
| Conduction defects | Cardiology input; antiarrhythmic drugs; pacemaker if needed |
| Heart failure | Standard HF management (ACEI/ARB, beta-blockers, diuretics) |
Search for and treat any malignancy [3]
- If malignancy is identified, treating the underlying cancer may lead to remission of the myositis (paraneoplastic mechanism)
- Cancer treatment takes priority; immunosuppression for myositis must be carefully balanced against cancer therapy
- Even if no malignancy is found at initial screening, continue surveillance annually for ≥ 3 years
| Domain | Intervention | Rationale |
|---|---|---|
| Physiotherapy | Graded exercise programme (passive ROM initially → active strengthening as inflammation controlled) | Prevents contractures and disuse atrophy; improves functional recovery. Exercise does NOT exacerbate myositis (a former misconception) — supervised exercise is beneficial and safe once inflammation is controlled |
| Occupational therapy | ADL modifications, assistive devices, home adaptations | Maximise functional independence |
| Speech therapy | Swallowing rehabilitation, voice exercises | For dysphonia and dysphagia |
| Nutritional support | PEG tube if severe dysphagia | Ensure adequate caloric intake; prevent aspiration pneumonia |
| Steroid side-effect prophylaxis | Calcium + vitamin D + bisphosphonate (for osteoporosis); PPI (if concurrent NSAID use); PCP prophylaxis (co-trimoxazole) if on high-dose immunosuppression; HBV/TB screening before immunosuppression; annual influenza + pneumococcal vaccination | Critical — steroid complications are a major source of morbidity |
| Psychological support | Counselling, support groups | Chronic disease with functional limitation → ↑ depression and anxiety |
| Screen | Why? |
|---|---|
| Hepatitis B serology (HBsAg, anti-HBc, anti-HBs) | Immunosuppression (especially rituximab, steroids) can cause HBV reactivation → fulminant hepatitis. If HBsAg +ve or anti-HBc +ve, start antiviral prophylaxis (entecavir or tenofovir) |
| TB screening (CXR ± IGRA/TST) | Latent TB can reactivate with immunosuppression. If latent TB detected, treat with isoniazid before or concurrently with immunosuppression |
| Baseline bloods | CBC (for bone marrow reserve), LFT (for hepatotoxicity baseline), RFT (for drug dosing), BSL (steroid-induced DM) |
| TPMT/NUDT15 (if starting AZA) | Prevent life-threatening bone marrow suppression [15] |
| Pregnancy test | MTX, MMF, CYC are teratogenic — must exclude pregnancy |
| Vaccination status | No live vaccines during immunosuppression; ensure influenza + pneumococcal + HBV vaccines are up to date before starting |
| Parameter | Frequency | Interpretation |
|---|---|---|
| CK level | Every 2–4 weeks during induction; every 1–3 months during maintenance | CK falls before clinical strength improves; normalisation = biochemical remission. Rising CK → flare or non-compliance |
| Muscle strength (manual muscle testing, MMT) | Every visit | Objective documentation of power; validated scores (e.g., MMT-8) track treatment response |
| Inflammatory markers (ESR/CRP) | Every visit | Should normalise with treatment |
| PFTs (FVC, DLCO) | Every 3–6 months if ILD present | ↓ FVC or ↓ DLCO suggests ILD progression |
| Drug-specific monitoring | Variable | CBC, LFT, RFT for MTX/AZA/MMF; drug levels for tacrolimus/ciclosporin; urinalysis for CYC |
| Step | Treatment | Key Points |
|---|---|---|
| 1st line | High-dose prednisolone 1 mg/kg/d | Backbone of therapy; bridge to steroid-sparing agent |
| 1st line (steroid-sparing) | Methotrexate OR azathioprine | Added early; allows steroid taper; check TPMT/NUDT15 for AZA |
| 2nd line (refractory) | IVIG, rituximab, MMF, calcineurin inhibitors | For steroid-resistant or relapsing disease |
| 3rd line (severe/life-threatening) | Cyclophosphamide, plasmapheresis | Reserved for rapidly progressive ILD, respiratory failure, severe refractory myositis |
| Supportive | PT, OT, speech therapy, PEG, steroid prophylaxis | Essential throughout — do not neglect rehabilitation |
| Malignancy | Screen and treat underlying cancer | May cause remission of paraneoplastic myositis |
High Yield Summary — Management of Polymyositis
First-line: Prednisolone 1 mg/kg/d (or IV methylprednisolone pulses for severe disease) + early steroid-sparing agent (MTX or AZA).
Steroid taper: Begin once CK normalising and strength improving (4–6 weeks); slow taper over months; target ≤ 7.5 mg/d or off.
Refractory: IVIG, rituximab, MMF, calcineurin inhibitors, cyclophosphamide, plasmapheresis.
ILD: High-dose steroids + immunosuppressants (AZA, MMF, CYC); nintedanib for progressive pulmonary fibrosis.
Steroid myopathy vs PM flare: CK elevated = flare (↑ steroids); CK normal = steroid myopathy (↓ steroids).
Before starting AZA: Check TPMT, NUDT15, concurrent allopurinol.
Before immunosuppression: Screen HBV, TB, pregnancy; update vaccines.
Supportive: PT, OT, speech therapy, PEG, steroid prophylaxis (Ca/VitD/bisphosphonate, PPI, PCP prophylaxis).
Prognosis: 5–10% mortality; response to steroids: overlap myositis > DM > PM.
Always: Screen for malignancy at diagnosis and annually for ≥ 3 years.
Active Recall - Management of Polymyositis
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p145–146, Inflammatory Myopathies — PM/DM Management) [3] Senior notes: Ryan Ho Rheumatology.pdf (p85–92, PM and DM Management; SSc management of myopathy) [5] Senior notes: Ryan Ho Neurology.pdf (p183–195, Inflammatory Myopathies Management, GBS management principles) [13] Senior notes: Ryan Ho Respiratory.pdf (p121–124, ILD management including NSIP) [14] Senior notes: Block A - Rheumatology Interactive Tutorial.pdf (p2, Steroid side-effect management — bisphosphonates, osteoporosis, DM control) [15] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p45, Azathioprine — TPMT/NUDT15 screening, drug interactions, side effects)
Complications of Polymyositis
Complications of PM arise from three sources: (1) the disease process itself (autoimmune inflammation damaging muscle and other organs), (2) consequences of muscle weakness (functional disability, aspiration, respiratory failure), and (3) treatment-related side effects (long-term immunosuppression). Understanding complications from first principles requires tracing each one back to the underlying pathophysiology.
| Category | Complications |
|---|---|
| Pulmonary | Interstitial lung disease (ILD); respiratory failure (from respiratory muscle weakness); aspiration pneumonia |
| Oropharyngeal/GI | Dysphagia; aspiration; malnutrition |
| Cardiac | Myocarditis; conduction defects; cardiomyopathy; heart failure |
| Musculoskeletal | Muscle atrophy/contractures; calcinosis; disability |
| Malignancy | Cancer-associated myositis |
| Renal | Myoglobinuria → AKI |
| Vascular | Raynaud phenomenon; venous thromboembolism |
| Treatment-related | Steroid toxicity; immunosuppression-related infections; drug-specific adverse effects |
1. Interstitial Lung Disease (ILD) — The Most Important Prognostic Complication
↑ risk of ILD in anti-synthetase and anti-MDA5 (very aggressive ILD) [1][3] Clinical presentations including systemic manifestations of idiopathic inflammatory myopathy (IIM); Investigations of interstitial lung disease [11][16]
ILD in PM is an autoimmune-driven parenchymal lung disease where the same immune dysregulation that targets skeletal muscle also targets the pulmonary interstitium. The most common histological pattern is non-specific interstitial pneumonia (NSIP) [13], characterised by diffuse alveolar wall inflammation and fibrosis, rather than the honeycombing pattern of UIP/IPF.
- Why anti-synthetase antibodies predispose to ILD: Anti-aminoacyl-tRNA synthetase antibodies (e.g. anti-Jo-1) target enzymes involved in protein synthesis. There is a hypothesis that these enzymes, when exposed on the surface of damaged alveolar epithelial cells or released into the extracellular space during lung injury, trigger an autoimmune response specifically directed at the lung parenchyma. Additionally, cleaved fragments of synthetases can act as chemokines, recruiting T-cells and monocytes into the lung.
- Anti-MDA5: MDA5 is a cytoplasmic RNA helicase involved in innate antiviral immunity. Anti-MDA5 antibodies are associated with clinically amyopathic DM (CADM) with very aggressive, rapidly progressive ILD [1][8] — this can progress to respiratory failure within weeks and has mortality rates of up to 50%.
- Dry cough, progressive dyspnoea on exertion
- Bibasal fine inspiratory crackles ("velcro" crackles) on auscultation
- Reduced FVC (restrictive pattern) and reduced DLCO on pulmonary function testing [16]
- HRCT: ground-glass opacities predominantly over the lower lobes; no honeycombing (consistent with NSIP pattern) [13][16]
Pulmonary function test shows a reduced forced vital capacity of 70% predicted and diffusion capacity of the lungs for carbon monoxide of 64% predicted. High-resolution computer tomography scan of the thorax reveals ground glass opacities predominantly over the lower lobes. There was no honeycombing. [16]
| Autoantibody | ILD Risk | ILD Pattern | Prognosis |
|---|---|---|---|
| Anti-Jo-1 (anti-synthetase) | High (~70%) | NSIP or organising pneumonia | Moderately good if treated; responsive to immunosuppression |
| Anti-MDA5 | Very high (> 80%) | Rapidly progressive ILD | Poor — up to 50% mortality |
| Anti-SRP | Low–moderate | Variable | Severe myopathy is the main problem, not ILD |
| Anti-Mi-2 | Low | Uncommon | Good prognosis overall |
| No myositis-specific Ab | ≈10% | Variable | Variable |
- Initial therapy: oral steroid or IV pulse steroid ± azathioprine, MMF [13]
- 2nd line: cyclophosphamide, rituximab, calcineurin inhibitor [13]
- Nintedanib (antifibrotic) for progressive pulmonary fibrosis
- Long-term O2 if PaO2 < 55 mmHg or SaO2 < 88% [13]
- Lung transplant referral for end-stage disease
High Yield — ILD is the Leading Cause of Morbidity and Mortality in PM
ILD, not the myositis itself, is the major driver of poor prognosis in PM. All PM patients should be screened for ILD at diagnosis (CXR, PFTs, consider HRCT) and monitored longitudinally with serial FVC and DLCO measurements. The autoantibody profile (anti-Jo-1, anti-MDA5) predicts ILD risk and guides screening intensity and treatment urgency.
PM can cause respiratory failure through two distinct mechanisms, and it is critical to distinguish between them because the management differs:
| Mechanism | Pathophysiology | Clinical Clues | PFT Pattern | Management |
|---|---|---|---|---|
| Respiratory muscle weakness | CD8+ T-cell-mediated inflammation/destruction of the diaphragm and intercostal muscles → mechanical ventilatory failure → hypoventilation → Type II respiratory failure (↑CO₂, ↓O₂) | Late-stage myositis; reduced FVC out of proportion to DLCO reduction; paradoxical abdominal breathing; weak cough; orthopnoea from diaphragm weakness | ↓ FVC, ↓ TLC; DLCO may be relatively preserved (or reduced proportionally); FVC < 15 mL/kg BW suggests need for mechanical ventilation [5] | Immunosuppression for the myositis + supportive ventilation (NIV or intubation) |
| Interstitial lung disease | Autoimmune alveolitis → fibrosis → impaired gas exchange → Type I respiratory failure (↓O₂, normal/↓CO₂) | Subacute dyspnoea, dry cough, bibasal crackles, clubbing (rare); HRCT shows GGO / reticular changes | ↓ FVC, ↓ TLC, ↓↓ DLCO (disproportionately reduced) | Immunosuppression ± antifibrotics |
± respiratory failure [1]
Why is the distinction important? Because respiratory muscle weakness responds to myositis treatment (steroids/immunosuppression to restore muscle strength), while ILD requires specific lung-directed immunosuppression (and may need antifibrotics). A falling FVC with preserved DLCO suggests muscle weakness; a falling DLCO with GGO on HRCT suggests ILD progression.
3. Dysphagia, Aspiration, and Related Complications
Dysphagia and dysphonia [1] May progress to bulbar muscle weakness in late stages → associated with poor prognosis [3]
The upper one-third of the oesophagus and the entire pharynx are composed of striated muscle, which is the same muscle type targeted by the autoimmune process in PM. When these muscles are weakened:
- Impaired pharyngeal contraction → food bolus is not propelled efficiently through the pharynx → pooling in piriform sinuses
- Impaired epiglottic closure → food/liquid enters the airway → aspiration
- Impaired upper oesophageal sphincter opening → food sticks in the upper oesophagus → regurgitation
| Complication | Mechanism | Management |
|---|---|---|
| Aspiration pneumonia | Aspiration of food, secretions, or gastric contents into the lower respiratory tract → bacterial superinfection | Antibiotics; speech therapy; modified diet texture; PEG tube for severe cases |
| Malnutrition / weight loss | Inability to eat adequate calories due to dysphagia | Nutritional support; enteral feeding (NG or PEG tube) |
| Choking / acute airway obstruction | Food bolus lodged in pharynx or larynx | Emergency airway management; Heimlich manoeuvre |
| Dysphonia | Laryngeal muscle weakness → weak, breathy, or nasal voice | Speech therapy |
She has mild to moderate dysphagia upon speech therapist assessment [16]
Aspiration Pneumonia — A Leading Cause of Death in PM
Aspiration pneumonia is a major contributor to mortality in PM, especially in patients with bulbar weakness. Always assess swallowing function early (bedside swallow test → videofluoroscopy). A patient with PM who develops fever and new pulmonary infiltrate should be assumed to have aspiration pneumonia until proven otherwise, not just ILD progression.
Pathophysiology
Although PM primarily targets skeletal muscle, cardiac muscle (myocardium) can also be affected by the autoimmune process. The myocardium shares some antigenic similarity with skeletal muscle, and inflammatory infiltrates can extend to the heart.
| Cardiac Complication | Mechanism | Clinical Presentation |
|---|---|---|
| Myocarditis | Autoimmune inflammatory infiltration of the myocardium → myocyte damage → impaired contractility | Dyspnoea, fatigue, chest pain, ↓ LVEF on echo |
| Conduction defects | Inflammation of the cardiac conduction system (SA node, AV node, bundle branches) → block or arrhythmia | Syncope, palpitations; ECG shows AV block, bundle branch block, or arrhythmias |
| Cardiomyopathy | Chronic myocardial inflammation → fibrosis → dilated cardiomyopathy | Heart failure symptoms (SOBOE, peripheral oedema, raised JVP) |
| Heart failure | End result of myocarditis or cardiomyopathy | Reduced exercise tolerance; biventricular failure |
| Pericarditis | Serosal inflammation (part of the systemic autoimmune process) | Pleuritic chest pain, pericardial rub, pericardial effusion |
Myocardial involvement, e.g. HF, arrhythmia, MI [3]
Screening: All PM patients should have a baseline ECG (to detect conduction defects) and echocardiography (to assess LV function and screen for pHTN). Cardiac involvement is often subclinical — up to 70% of patients may have ECG abnormalities on monitoring, even when asymptomatic.
5. Malignancy — Cancer-Associated Myositis
Adult form associated with malignancy: 5× risk in dermatomyositis, 2× risk in polymyositis [1][3][5] Types: adenocarcinoma of cervix, lung, ovaries, pancreas, bladder, breast, stomach, NPC (this locality) [5] Potential association between cancer and dermatomyositis and the rationale of cancer screening [11]
The exact mechanism linking IIM and malignancy is incompletely understood, but the leading hypothesis is a paraneoplastic mechanism:
- Tumour cells express muscle antigens (or antigens that cross-react with muscle proteins) on their surface
- The immune system mounts a response against the tumour antigens
- Due to molecular mimicry, the immune response cross-reacts with normal skeletal muscle → myositis
- This explains why treating the underlying malignancy can sometimes lead to remission of the myositis
- Temporal relationship: malignancy can be diagnosed before, with, or after diagnosis of inflammatory myopathy [5]
- Risk is highest in the first 1–3 years after IIM diagnosis, but cancer can present years later
- Cancer risk: DM > PM (5× vs 2× general population) [3]
- Cancer-associated autoantibodies: anti-TIF1-γ (anti-p155/140) and anti-NXP-2 (confers a higher risk of malignancy in patients with DM and PM) [6][8]
- Higher risk with: older age at onset, male sex, refractory myositis, absence of myositis-specific antibodies, anti-TIF1-γ or anti-NXP-2 positivity
In Hong Kong / Southern China, NPC is an important associated malignancy because of the high endemic rate of EBV-associated NPC. Always include NPC screening (EBV VCA IgA, EA IgA, nasopharyngoscopy) in the malignancy workup for PM/DM patients in this population [5].
| Complication | Pathophysiology | Clinical Significance |
|---|---|---|
| Muscle atrophy | Chronic inflammation → irreversible fibre destruction → replaced by fibrosis and fatty infiltration; generally only seen in severe, long-standing disease [3] | Loss of functional capacity; visible wasting; MRI shows fatty replacement |
| Muscle contractures | Fibrosis within damaged muscle → shortening of muscle length → fixed joint deformity; only if chronic [5] | Reduced ROM; in childhood DM: tip-toe gait (ankle contractures) [1] |
| Calcinosis cutis | Dystrophic calcification within damaged muscle or subcutaneous tissue; calcium hydroxyapatite deposited at sites of chronic inflammation. Common in juvenile DM but less so in adult DM/PM [3] | Hard subcutaneous nodules; may ulcerate through skin; cosmetically disfiguring; painful; can limit joint movement |
| Functional disability | Cumulative weakness → inability to perform ADLs (dressing, bathing, transfers) | Need for OT assessment, assistive devices, home modifications |
7. Renal Complications — Myoglobinuria and Acute Kidney Injury
When extensive muscle fibre necrosis occurs (whether from severe active PM, rhabdomyolysis, or a disease flare), myoglobin is released from destroyed muscle fibres into the bloodstream:
- Myoglobin is freely filtered by the glomerulus (small molecular weight, ~17 kDa)
- In the renal tubules, myoglobin precipitates — especially in acidic urine — forming myoglobin casts that obstruct tubular flow
- Myoglobin is also directly nephrotoxic: it releases free iron (Fe²⁺), which generates reactive oxygen species (ROS) via the Fenton reaction → oxidative damage to tubular epithelial cells
- Result: acute tubular necrosis (ATN) → oliguric AKI
- Dark brown/cola-coloured urine
- Urine dipstick positive for "blood" but no RBCs on microscopy (because the dipstick reagent detects haem, and myoglobin contains haem)
- Massively elevated CK (usually > 10,000 U/L, sometimes > 100,000 U/L)
- Rising creatinine, hyperkalaemia (from both AKI and muscle necrosis)
- Aggressive IV hydration (normal saline) to maintain renal perfusion and urine output
- Urine alkalinisation (IV sodium bicarbonate) — raising urine pH reduces myoglobin precipitation
- Correct hyperkalaemia (cardiac monitoring, insulin-dextrose, calcium gluconate for cardioprotection)
- Renal replacement therapy (dialysis) if refractory AKI
- Treat the underlying PM flare aggressively
Myoglobinuria-Related AKI
This complication is more common in acute severe flares or in IMNM (anti-SRP associated) than in typical chronic PM. However, any PM patient with CK > 10,000 and dark urine should be assessed for renal function and managed proactively to prevent AKI.
8. Venous Thromboembolism (VTE)
PM patients have an increased risk of DVT and PE due to:
- Immobility — severe proximal weakness → bedbound → venous stasis (Virchow's triad)
- Chronic inflammation — systemic inflammatory state activates the coagulation cascade (elevated fibrinogen, Factor VIII, von Willebrand factor) → hypercoagulability
- Malignancy association — cancers are independent risk factors for VTE (Trousseau syndrome)
- Endothelial dysfunction — autoimmune vasculopathy
- Thromboprophylaxis for hospitalised, immobile PM patients (LMWH, compression stockings)
- Therapeutic anticoagulation if DVT/PE diagnosed
- Maintain mobility with physiotherapy
9. Treatment-Related Complications
These are iatrogenic complications from the immunosuppressive therapy needed to treat PM.
| System | Complication | Mechanism |
|---|---|---|
| Metabolic | Hyperglycaemia / steroid-induced DM | Glucocorticoids ↑ hepatic gluconeogenesis + ↑ insulin resistance |
| Bone | Osteoporosis → fractures | ↓ osteoblast activity, ↑ osteoclast activity, ↓ Ca²⁺ absorption, ↑ renal Ca²⁺ loss |
| Infection | Opportunistic infections (PCP, TB reactivation, fungal, herpes zoster) | Broad immunosuppression → ↓ T-cell and macrophage function |
| MSK | Steroid myopathy (proximal weakness with normal CK) | Glucocorticoid-induced muscle protein catabolism → Type II fibre atrophy |
| Eye | Posterior subcapsular cataract, glaucoma | Lens protein aggregation; ↑ aqueous humour resistance to outflow |
| CVS | Hypertension, dyslipidaemia | Mineralocorticoid effect (Na/water retention); ↑ hepatic lipid synthesis |
| GI | Peptic ulcer (especially with concurrent NSAIDs) | ↓ mucosal prostaglandin production |
| Adrenal | HPA axis suppression → adrenal crisis on abrupt withdrawal | Exogenous steroid suppresses ACTH → adrenal atrophy |
| Psychiatric | Insomnia, mood disturbance, psychosis | Direct CNS effects |
Any patient on chronic immunosuppression (steroids, MTX, AZA, MMF, rituximab, cyclophosphamide) is at increased risk of:
| Infection Type | Examples |
|---|---|
| Bacterial | Pneumonia, urinary tract infections, skin/soft tissue infections |
| Viral | Herpes zoster reactivation, CMV reactivation (especially rituximab/CYC), HBV reactivation |
| Fungal | Pneumocystis jirovecii pneumonia (PCP) — prophylaxis with co-trimoxazole if on high-dose steroids (≥ 20 mg prednisolone) for > 4 weeks; invasive aspergillosis |
| Mycobacterial | TB reactivation — screen before starting immunosuppression |
| Drug | Major Adverse Effects |
|---|---|
| Methotrexate | Hepatotoxicity, bone marrow suppression, MTX pneumonitis, teratogenicity |
| Azathioprine | Bone marrow suppression (TPMT/NUDT15 dependent), hepatotoxicity, pancreatitis, lymphoma |
| MMF | GI upset (nausea, diarrhoea), bone marrow suppression, teratogenicity |
| Cyclophosphamide | Haemorrhagic cystitis (MESNA for prevention), gonadal toxicity/infertility, bladder cancer, bone marrow suppression |
| Rituximab | Infusion reactions, HBV reactivation, PML (extremely rare), hypogammaglobulinaemia, late-onset neutropenia |
| IVIG | Infusion reactions, aseptic meningitis, thrombosis, renal injury, haemolytic anaemia |
| Calcineurin inhibitors | Nephrotoxicity, hypertension, tremor, hyperglycaemia, hyperkalaemia |
Prognosis: 5–10% mortality [1] Response to steroid: in general, overlap myositis > DM > PM [3]
| Factor | Better Prognosis | Worse Prognosis |
|---|---|---|
| Autoantibody | Anti-Mi-2 (responds well) | Anti-SRP (refractory); anti-MDA5 (RP-ILD) |
| ILD | Absent or mild/stable | Present, especially rapidly progressive |
| Bulbar involvement | Absent | Present (dysphagia → aspiration → pneumonia) |
| Malignancy | Absent | Present |
| Treatment response | Early CK normalisation; steroid-responsive | Refractory to steroids; delayed treatment |
| Age | Younger | Older age at onset |
| Severity at presentation | Mild proximal weakness | Severe weakness, respiratory failure at onset |
Variable prognosis depending on type of myositis, severity, delay in diagnosis, and autoantibody profile [3].
| Complication | Frequency | Mechanism | Screening / Prevention |
|---|---|---|---|
| ILD | 10–70% (depends on autoAb) | Autoimmune alveolitis → NSIP/UIP | CXR, HRCT, PFTs at diagnosis; serial FVC/DLCO |
| Respiratory failure | Late complication | Respiratory muscle weakness ± ILD | Serial FVC; monitor for orthopnoea, paradoxical breathing |
| Aspiration pneumonia | Common if dysphagia | Pharyngeal muscle weakness → aspiration | Swallowing assessment; modified diet; PEG if severe |
| Cardiac | Subclinical in up to 70% | Myocardial inflammation, conduction system damage | ECG, echo at diagnosis |
| Malignancy | 2× risk in PM; 5× in DM | Paraneoplastic (molecular mimicry) | Age/sex-appropriate cancer screen at diagnosis + annually × 3y |
| Muscle atrophy/contractures | Chronic, untreated disease | Irreversible fibre destruction → fibrosis | Early treatment; physiotherapy |
| Calcinosis | More juvenile DM | Dystrophic calcification | No reliable prevention; treat active disease |
| AKI from myoglobinuria | Severe flares | Myoglobin → tubular obstruction + direct nephrotoxicity | Hydration; monitor CK and renal function |
| VTE | Increased risk | Immobility + inflammation + malignancy | Thromboprophylaxis if immobile |
| Steroid toxicity | Universal with chronic use | Multiple mechanisms (see above) | Ca/VitD/bisphosphonate; PPI; PCP prophylaxis; monitor BSL/BP |
| Infections | Increased with immunosuppression | Iatrogenic immunodeficiency | Screen HBV/TB; vaccinate; PCP prophylaxis |
High Yield Summary — Complications of Polymyositis
#1 Cause of morbidity/mortality: ILD (especially anti-Jo-1 and anti-MDA5). Screen all patients; monitor with serial PFTs.
#2 Cause of death: Aspiration pneumonia (from bulbar weakness). Always assess swallowing; speech therapy; PEG if needed.
Cardiac: Often subclinical; ECG + echo at baseline. Can cause conduction defects, myocarditis, cardiomyopathy.
Malignancy: PM = 2× risk; DM = 5× risk. Screen at diagnosis + annually × 3 years. In HK: include NPC screening.
Renal: Myoglobinuria → AKI in severe flares. Monitor CK and urine; hydrate aggressively.
Musculoskeletal: Chronic disease → atrophy, contractures, calcinosis. Early treatment + physiotherapy prevents this.
Treatment-related: Steroid myopathy (CK normal — distinguish from flare!), infections (PCP, TB, HBV reactivation), drug-specific toxicities. Pre-treatment screening essential.
Prognosis: 5–10% mortality overall. Worse with ILD, malignancy, anti-SRP/anti-MDA5, bulbar involvement, delayed treatment.
Active Recall - Complications of Polymyositis
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (p146, PM/DM — Clinical features, prognosis) [3] Senior notes: Ryan Ho Rheumatology.pdf (p90–92, PM and DM — Complications, malignancy association, prognosis) [5] Senior notes: Ryan Ho Neurology.pdf (p194–195, Inflammatory Myopathies — Malignancy association, types, temporal relationship) [6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p709, Cancer-associated antibodies — anti-NXP-2) [8] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1759, Autoantibodies — anti-MDA5, anti-TIF1-gamma, anti-NXP-2) [11] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p1, Learning objectives — systemic manifestations, ILD investigations, cancer screening rationale) [13] Senior notes: Ryan Ho Respiratory.pdf (p121–124, ILD management, NSIP, UIP associated with PM-DM) [16] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p6, Case scenario — dysphagia, anti-Jo-1, PFT results, HRCT findings, complications)
High Yield Summary
Definition: PM = chronic autoimmune inflammatory myopathy with symmetric proximal muscle weakness; endomysial T-cell-mediated destruction.
Epidemiology: Incidence ~2/100k/year; F:M = 2:1; peak 40–50 years.
Rule of Thirds: 1/3 malignancy, 1/3 CTD-associated, 1/3 idiopathic.
Pathophysiology: Aberrant MHC class I upregulation on sarcolemma → CD8+ T-cell recognition → endomysial invasion → perforin/granzyme-mediated fibre destruction → CK release → proximal weakness.
PM vs DM: PM = endomysial/T-cell; DM = perimysial/B-cell+complement microangiopathy.
Clinical Features:
- Symmetric proximal weakness (shoulder girdle, hip girdle, neck flexors)
- Retained reflexes, no sensory loss, no fasciculations
- Dysphagia/dysphonia (bulbar striated muscle involvement)
- ± Respiratory failure (muscle weakness or ILD)
- ± Raynaud, arthritis, cardiac involvement
Key Autoantibodies: Anti-Jo-1 (anti-synthetase syndrome, ILD risk); Anti-SRP (severe myopathy); Anti-MDA5 (rapidly progressive ILD); Anti-Mi-2 (classic DM, good prognosis).
Cancer Association: PM 2× risk; DM 5× risk. In HK: lung, breast, gastric, NPC. Screen at diagnosis.
Labs: CK > 10× ULN; ESR/CRP elevated; EMG shows myopathic potentials with fibrillations.
High Yield Summary — DDx of Polymyositis
-
PM is a diagnosis of exclusion — many historical "PM" cases are actually IBM, IMNM, or overlap myositis.
-
First confirm myopathy (proximal weakness, retained reflexes, no sensory loss, elevated CK) then exclude:
- Endocrine: hypothyroidism (TFT), Cushing's (steroid use)
- Drugs: statins, corticosteroids, colchicine
- Electrolytes: hypokalemia, hypocalcemia
- Other IIMs: DM (skin rash), IBM (distal weakness, treatment-resistant, rimmed vacuoles), IMNM (necrosis without inflammation, anti-HMGCR/anti-SRP)
-
Key exam traps:
- PMR vs PM: PMR = pain without true weakness, CK normal, ESR very high, dramatic response to low-dose pred
- MG vs PM: MG = fatigable weakness, ptosis/diplopia, CK normal, decremental response on RNS
- Steroid myopathy vs PM flare: CK normal in steroid myopathy, elevated in PM flare
- Hypothyroid myopathy: Always check TFT — easily reversible!
-
In HK: always consider NPC and other malignancies (lung, breast, gastric) in the cancer screen.
High Yield Summary — Diagnosis of Polymyositis
Bohan & Peter (1975): PM requires ALL of (1) symmetric proximal weakness, (2) +ve muscle biopsy, (3) ↑ CK, (4) myopathic EMG. DM = any 3 of 1–4 + skin rash.
2017 EULAR/ACR: Probability-based scoring; anti-Jo-1 carries highest score (3.9); classifies into PM, DM, IBM, juvenile forms.
Simplified diagnostic rule: Myositis = 2 out of 3 of: ↑ CK, EMG abnormalities, +ve muscle biopsy.
Must-do investigations: CK (most sensitive), EMG (myopathic vs neuropathic), muscle biopsy (gold standard, guided by MRI), autoantibodies (prognostic subtyping), TFT (exclude thyroid myopathy), malignancy screen (mandatory in elderly).
PM is a diagnosis of exclusion — actively exclude DM (no skin rash), IBM (no rimmed vacuoles, does respond to treatment), IMNM (endomysial CD8+ infiltrate present, not pure necrosis), and endocrine/drug-induced causes.
High Yield Summary — Management of Polymyositis
First-line: Prednisolone 1 mg/kg/d (or IV methylprednisolone pulses for severe disease) + early steroid-sparing agent (MTX or AZA).
Steroid taper: Begin once CK normalising and strength improving (4–6 weeks); slow taper over months; target ≤ 7.5 mg/d or off.
Refractory: IVIG, rituximab, MMF, calcineurin inhibitors, cyclophosphamide, plasmapheresis.
ILD: High-dose steroids + immunosuppressants (AZA, MMF, CYC); nintedanib for progressive pulmonary fibrosis.
Steroid myopathy vs PM flare: CK elevated = flare (↑ steroids); CK normal = steroid myopathy (↓ steroids).
Before starting AZA: Check TPMT, NUDT15, concurrent allopurinol.
Before immunosuppression: Screen HBV, TB, pregnancy; update vaccines.
Supportive: PT, OT, speech therapy, PEG, steroid prophylaxis (Ca/VitD/bisphosphonate, PPI, PCP prophylaxis).
Prognosis: 5–10% mortality; response to steroids: overlap myositis > DM > PM.
Always: Screen for malignancy at diagnosis and annually for ≥ 3 years.
High Yield Summary — Complications of Polymyositis
#1 Cause of morbidity/mortality: ILD (especially anti-Jo-1 and anti-MDA5). Screen all patients; monitor with serial PFTs.
#2 Cause of death: Aspiration pneumonia (from bulbar weakness). Always assess swallowing; speech therapy; PEG if needed.
Cardiac: Often subclinical; ECG + echo at baseline. Can cause conduction defects, myocarditis, cardiomyopathy.
Malignancy: PM = 2× risk; DM = 5× risk. Screen at diagnosis + annually × 3 years. In HK: include NPC screening.
Renal: Myoglobinuria → AKI in severe flares. Monitor CK and urine; hydrate aggressively.
Musculoskeletal: Chronic disease → atrophy, contractures, calcinosis. Early treatment + physiotherapy prevents this.
Treatment-related: Steroid myopathy (CK normal — distinguish from flare!), infections (PCP, TB, HBV reactivation), drug-specific toxicities. Pre-treatment screening essential.
Prognosis: 5–10% mortality overall. Worse with ILD, malignancy, anti-SRP/anti-MDA5, bulbar involvement, delayed treatment.
Dermatomyositis
Dermatomyositis is an idiopathic inflammatory myopathy characterized by progressive proximal muscle weakness and distinctive skin manifestations, including a heliotrope rash and Gottron papules.
Inclusion Body Myositis
Inclusion body myositis is a chronic inflammatory myopathy characterized by slowly progressive asymmetric weakness, particularly of the finger flexors and quadriceps, with rimmed vacuoles and protein aggregates on muscle biopsy.