Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders—including polymyositis, dermatomyositis, and inclusion body myositis—characterized by chronic skeletal muscle inflammation leading to progressive, predominantly proximal muscle weakness.

Idiopathic Inflammatory Myopathies (IIM)

3. Anatomy and Function: Skeletal Muscle Basics

To understand why IIM presents the way it does, you need to understand muscle architecture:

4. Aetiology and Associations

Association	Proportion	Key Details
Malignancy	~1/3	Lung, breast, gastric, NPC (Hong Kong!), ovarian, cervical, pancreatic, bladder
Connective tissue disease	~1/3	SLE, systemic sclerosis, Sjögren's, RA, MCTD
Idiopathic	~1/3	No identifiable cause

5. Pathophysiology

Feature	DM	PM	IBM	IMNM
Immune mechanism	Humoral (B-cell, complement)	Cellular (CD8+ T-cell)	T-cell + degenerative	Antibody-mediated necrosis
Infiltrate location	Perimysial/perivascular	Endomysial	Endomysial	Minimal/absent
Key biopsy finding	Perifascicular atrophy	Endomysial CD8+ T-cells	Rimmed vacuoles, inclusion bodies	Necrosis and regeneration
MHC-I upregulation	++	+++	+++	±
Complement deposition	On capillaries (C5b-9)	Absent	Absent	Absent

6. Classification

This is increasingly how IIM is understood and classified. Each antibody defines a distinct clinical phenotype:

Antibody	Associated Subtype	Key Clinical Features
Anti-Jo-1 (and other anti-synthetases: anti-PL-7, PL-12, EJ, OJ, KS)	Anti-synthetase syndrome	ILD, mechanic's hands, Raynaud's, arthritis, fever — "FIRMA"
Anti-Mi-2	Classic DM	Classic cutaneous DM, good prognosis, good treatment response
Anti-MDA5 (anti-CADM-140)	CADM / DM	Very aggressive ILD (rapidly progressive), skin ulceration, minimal/no myositis, high mortality
Anti-TIF1-γ (anti-p155/140)	DM	Strongest association with malignancy (especially adult DM)
Anti-NXP2 (anti-MJ)	DM	Calcinosis (especially juvenile DM), malignancy in adults
Anti-SRP	IMNM	Severe necrotizing myopathy, very high CK, poor prognosis
Anti-HMGCR	IMNM	Statin-associated necrotizing myopathy (but can occur without statin exposure)
Anti-SAE	DM	Skin-predominant initially, then develops muscle weakness
Anti-cN1A	IBM	Supports diagnosis of inclusion body myositis

Anti-synthetase Syndrome — 'FIRMA' Mnemonic

F — Fever I — Interstitial lung disease R — Raynaud's phenomenon M — Mechanic's hands A — Arthritis (non-erosive) (+ myositis, of course!)

Anti-Jo-1 is the most common anti-synthetase antibody. The synthetases are aminoacyl-tRNA synthetases — enzymes that attach amino acids to tRNA during translation. Why the immune system targets these is not fully understood, but the antibodies define this very distinct clinical syndrome.

High Yield — Anti-MDA5 and Rapidly Progressive ILD

↑ risk of ILD in anti-synthetase and anti-MDA5 (very aggressive ILD) ^[4]. Anti-MDA5 positive patients can present with minimal or no myositis but develop rapidly progressive ILD that can be fatal within weeks to months. MDA5 = melanoma differentiation-associated gene 5, a cytoplasmic RNA sensor in the innate immune system. This is extremely high yield for exams — if a patient has DM rash + rapidly progressive respiratory failure + minimal muscle weakness, think anti-MDA5.

7. Clinical Features

7.1 Symptoms

Symptom	Pathophysiological Basis
Difficulty climbing stairs, rising from chair, squatting	Proximal weakness of hip flexors and quadriceps — these muscles are needed for antigravity movements of the lower limbs
Difficulty combing hair, reaching overhead, carrying heavy groceries	Proximal weakness of shoulder girdle (deltoid) — needed for overhead arm movements
Difficulty holding head up	Neck flexor weakness — a hallmark of IIM; the neck flexors are considered a "proximal" muscle group
Dysphagia	Bulbar muscle weakness — pharyngeal and upper oesophageal striated muscle involvement → oropharyngeal dysphagia (difficulty initiating swallow). Indicates poor prognosis ^[2]
Dysphonia / hoarse voice	Laryngeal muscle weakness — vocal cord dysfunction
Mild myalgia / muscle tenderness	Pain if acute, usually mild ^[4]; inflammatory mediators (cytokines, prostaglandins) stimulate muscle nociceptors; muscle tenderness in 25-50% ^[2]

Onset Pattern

DM: More severe and acute onset ^[4] — can present over days to weeks PM: Subacute/chronic onset, progressive ^[4] — typically over weeks to months IBM: Insidious onset over months to years, often misdiagnosed as PM initially

Key point: Distal muscles may be present but usually mild with little functional impairment ^[2] — except in IBM, where distal involvement (especially finger flexors, quadriceps) is characteristic and early. If an "inflammatory myopathy" has prominent distal weakness, think IBM.

Skin manifestations usually appear before myopathy ^[3] — this is important clinically because the rash may precede weakness by weeks to months.

Dermatomyositides are a heterogeneous group of inflammatory myopathies ^[1].

Cutaneous Feature	Description & Pathophysiological Basis
Heliotrope rash	Violaceous discolouration of upper eyelid associated with periorbital oedema ^[2]. "Heliotrope" refers to the purple colour of the heliotrope flower. Caused by complement-mediated vasculopathy of the periorbital capillaries → oedema and purple discolouration.
Gottron's papules	Scaly purplish erythema at extensor aspect of joints ^[4] — especially dorsal MCP, PIP, DIP joints (and also elbows, knees). Pathognomonic for DM ^[3]. Caused by immune-mediated vasculopathy of dermal vessels over bony prominences (mechanical shear stress may localise the lesions).
V sign	Erythematous rash over anterior neck and upper chest in a "V" distribution (matching the neckline of a shirt). Photodistributed poikiloderma.
Shawl sign	Erythematous rash over upper back and posterior shoulders — as if wearing a shawl.
Holster sign	Poikiloderma in lateral aspects of thigh ^[3] — like where a holster would sit.
Mechanic's hands	Hyperkeratosis and scaling with fissures on digits ^[3] — looks like the rough, cracked hands of a mechanic. Strongly associated with anti-synthetase syndrome.
Facial/malar erythema	Midfacial erythema → can mimic lupus malar rash, but often involves the nasolabial fold ^[2] (lupus classically spares the nasolabial fold).
Calcinosis cutis	Calcium deposits in skin/subcutaneous tissue. Common in juvenile DM but less so in adult DM ^[2]. Caused by chronic inflammation → dystrophic calcification.
Dilated nailfold capillaries / periungual erythema	Periungual erythema ^[1]. Capillaroscopy shows dilated, tortuous capillary loops and dropout — reflects the underlying microangiopathy. Also seen in systemic sclerosis.
Poikiloderma	Telangiectasia, epidermal atrophy with violaceous hue, hyper/hypopigmentation ^[2]. Reflects chronic skin vasculopathy.

Gottron's Papules vs. Lupus Hand Rash

A common exam trap: both DM and SLE can cause hand rashes. Gottron's papules are over the dorsal surface of joints (knuckles). Lupus hand rash spares the knuckles and affects the skin between joints. Also, DM facial rash involves the nasolabial fold; SLE malar rash spares it.

Symptom	Pathophysiological Basis
Interstitial lung disease (ILD)	Autoimmune inflammation of lung parenchyma. Presents as progressive dyspnoea and dry cough. Especially with anti-synthetase and anti-MDA5 antibodies ^[4]. Can be the presenting feature and the leading cause of mortality.
Arthralgia / polyarthritis	ILD, polyarthritis are features of DM ^[1]. Non-erosive, symmetric, small joint — part of anti-synthetase syndrome or overlap with CTD.
Raynaud's phenomenon	Vasospasm of digital arteries due to autoimmune vasculopathy. Common in anti-synthetase syndrome and overlap with systemic sclerosis.
Constitutional symptoms	Fever, fatigue, weight loss — systemic inflammatory response with elevated cytokines (IL-1, TNF-α, IL-6).
Cardiac symptoms	Myocarditis, conduction defects, heart failure — autoimmune inflammation can affect cardiac muscle.
GI involvement	GI involvement in juvenile cases ^[1] — vasculopathy of GI tract vessels → ulceration, perforation (rare but serious).

7.2 Signs

Sign	Description & Pathophysiological Basis
Symmetric proximal weakness	Commonly shoulder (deltoid), pelvic girdles (hip flexor), neck (neck flexor) ^[2]. Tested by: asking patient to rise from chair without using arms, squat and rise, hold arms above head, resist neck flexion. MRC grading should be documented.
Waddling gait	Hip abductor weakness → pelvis drops on the unsupported side during walking (positive Trendelenburg sign). The trunk compensates by lurching toward the weight-bearing side.
Lordotic posture	Trunk and hip extensor weakness → compensatory exaggerated lumbar lordosis to keep centre of gravity over the base of support.
Gower's sign	Patient uses hands to "climb up" their own thighs when rising from the floor — compensating for proximal lower limb weakness. Classic in children (DMD and juvenile DM).
Retained/normal reflexes	Retained reflexes ^[2]^[4]. Unlike neuropathies (where reflexes are lost because the reflex arc is interrupted), in myopathy the peripheral nerve and reflex arc are intact — only the muscle effector is weak. Reflexes may be reduced in very advanced/severe disease when muscle bulk is severely depleted.
No sensory loss	The disease affects muscle, not nerve. Sensory pathways are completely spared.
No fatigability	Unlike myasthenia gravis (where the NMJ is the problem and weakness worsens with repeated use), IIM weakness is constant.
Muscle wasting/contractures	Only if chronic ^[4]. In acute/subacute disease, muscles may be swollen and oedematous rather than atrophied. Chronic ongoing inflammation → fibrosis → contractures (especially in juvenile DM: muscle contractures with tip-toe gait ^[4]).

Sign	Details
Fine bibasal crackles	ILD — fibrotic/inflammatory lung parenchymal disease
Joint swelling/tenderness	Non-erosive polyarthritis (anti-synthetase syndrome)
Raynaud's	Colour changes in fingers with cold exposure
Skin tightening	Telangiectasia and skin tightening ^[4] — may overlap with scleroderma features
Lymphadenopathy / masses	May indicate underlying malignancy
Signs of underlying malignancy	Any suspicious mass, hepatomegaly, supraclavicular lymphadenopathy, etc.

7.3 Special Subtypes — Clinical Feature Highlights

Feature	Details
Demographics	Older males (> 50 years)
Weakness pattern	Proximal + distal muscle weakness ^[3] — particularly quadriceps (knee extension weakness → falls) and finger flexors (weak grip)
Onset	Insidious, over months to years
Asymmetry	Can be asymmetric (unlike PM/DM)
Treatment response	Failed response to treatment ^[3] — this is the clinical clue
Dysphagia	Common (~40%)

Feature	Details
Onset	Subacute, can be severe
CK	Very high (often > 10,000 IU/L)
Weakness	Severe proximal
Association	Anti-SRP or anti-HMGCR (statin exposure)
Biopsy	Necrosis and regeneration with minimal/no inflammation

Feature	Details
Definition	Cutaneous manifestations but no muscle weakness for ≥ 6 months ^[3]
Prevalence	10-30% of DM ^[2]
Key risk	Anti-MDA5 → rapidly progressive ILD

Feature	Polymyositis	Dermatomyositis
Course	Subacute/chronic onset, progressive	More severe and acute onset
Pathology	Endomysial infiltration; predominantly T-cell mediated	Perimysial infiltration; predominantly B-cell or complement-mediated microangiopathy
Muscle features	Painful/tender muscles; proximal weakness (may be asymmetrical initially); ± spreading to distal; dysphagia and dysphonia; ± respiratory failure; retained reflexes	Muscle weakness similar to PM
Skin	None	Heliotrope rash, Gottron's papules, telangiectasia and skin tightening, photodistributed poikiloderma (V sign, shawl sign), periungual erythema
Childhood form	Rare	May have calcification — muscle contractures (tip-toe gait), scarring and calcinosis
Malignancy association	2× risk	Adult form associated with malignancy in 60% ^[4] (lecture slides say 6-45% ^[1])

High Yield — Malignancy Risk Discrepancy

Ryan Ho's notes state "60%" malignancy association for adult DM ^[4], while the GC lecture slide states "6-45%" ^[1]. For exam purposes, use the GC lecture slide figure (6-45%) as the primary answer, but know that the risk is substantially elevated, especially in adults with anti-TIF1-γ antibodies.

High Yield Summary

Definition: Autoimmune diseases with inflammatory infiltration/necrosis of skeletal muscle → limb-girdle weakness ± extra-muscular manifestations.

Classification (5 main types): PM, DM, Overlap myositis, IBM, IMNM. Additional: CADM, CAM.

Epidemiology: Incidence ~5/100,000/year. F > M (2:1). Peak 40-50 years.

Aetiology: 1/3 malignancy (especially NPC in HK), 1/3 CTD, 1/3 idiopathic.

Pathophysiology:

DM = complement-mediated microangiopathy (B-cell/humoral) → perimysial/perivascular → perifascicular atrophy
PM = CD8+ T-cell mediated → endomysial infiltration → direct muscle fibre killing
IBM = T-cell + degenerative (rimmed vacuoles) → proximal + distal weakness → treatment-resistant
IMNM = antibody-mediated necrosis (anti-SRP/anti-HMGCR) → minimal inflammation

Clinical Features:

Symmetric proximal weakness (shoulder, hip, neck flexors), retained reflexes, no sensory loss
DM skin: heliotrope rash, Gottron's papules (pathognomonic), V sign, shawl sign, holster sign, mechanic's hands, calcinosis
Systemic: ILD (anti-synthetase, anti-MDA5), arthritis, Raynaud's, dysphagia, cardiac
IBM: older males, distal + proximal, treatment-resistant

MSA: Anti-Jo-1 (anti-synthetase syndrome), anti-MDA5 (rapidly progressive ILD), anti-TIF1-γ (malignancy), anti-SRP/anti-HMGCR (IMNM), anti-Mi-2 (classic DM, good prognosis)

Always screen for malignancy and ILD in every IIM patient.

Active Recall - Idiopathic Inflammatory Myopathies (Definition to Clinical Features)

Differential Diagnosis of Idiopathic Inflammatory Myopathies

Before you can diagnose IIM, you must rule out other causes of weakness that mimic myopathy. The key clinical features that help you localise are: distribution of weakness, reflexes, sensory involvement, fatigability, and wasting pattern.

Localisation	Weakness Pattern	Reflexes	Sensory Loss	Fatigability	Other Clues
UMN lesion (cortical, spinal cord)	Pyramidal distribution (extensors in arms, flexors in legs)	Hyperreflexia, upgoing plantar	May be present (if spinal cord — sensory level)	No	Spasticity, Babinski sign
Anterior horn cell (MND/ALS)	Mixed proximal/distal, asymmetric, wasting	May be brisk (UMN + LMN)	No	No	Fasciculations, tongue fasciculation, mixed UMN/LMN signs
Peripheral nerve (polyneuropathy)	Distal > proximal, glove-and-stocking	Hyporeflexia/areflexia	Yes (glove-and-stocking)	No	Sensory symptoms first, length-dependent
NMJ (myasthenia gravis)	Ocular, bulbar, proximal; fluctuating	Normal	No	Yes — fatigability	Ptosis, diplopia worsen through the day
Muscle (myopathy)	Proximal, symmetrical	Normal/retained reflexes ^[4]	No sensory loss	No fatigability ^[3]	CK elevated, no fasciculations

High Yield — The 3 Negatives of Myopathy

A myopathy is characterised by what it does NOT have:

No sensory loss (nerve is intact)
No fatigability (NMJ is intact — DDx myasthenia gravis) ^[3]
Normal reflexes (reflex arc is intact — both afferent nerve and efferent nerve work; only the muscle effector is weakened) ^[3]^[4]

If any of these three are present, reconsider your localisation.

Key Mimics at Level 1

A. Myasthenia Gravis (MG) — The Most Important DDx to Distinguish from IIM

Feature	IIM	MG
Weakness pattern	Proximal limb-girdle, neck flexors	Ocular (ptosis, diplopia) → bulbar → proximal limbs
Fatigability	No ^[3]	Yes — weakness worsens with repeated use, improves with rest
Reflexes	Normal	Normal
CK	Elevated (often > 10× ULN)	Normal
EMG	Myopathic (short duration, polyphasic)	Decremental response on repetitive nerve stimulation
Antibodies	MSA (anti-Jo-1, anti-MDA5, etc.)	Anti-AChR, anti-MuSK

Why does MG cause fatigability but IIM does not? In MG, the problem is at the NMJ — autoantibodies destroy acetylcholine receptors. With repeated nerve stimulation, less and less ACh successfully binds, so the muscle gets progressively weaker. In IIM, the muscle fibres themselves are damaged/inflamed — they are weak at baseline but don't get progressively worse with repeated contraction (they're already damaged, not running out of signal).

B. Motor Neuron Disease (MND/ALS)

Feature	IIM	MND
UMN signs	Absent	Present (hyperreflexia, spasticity, Babinski)
LMN signs	Absent	Present (fasciculations, wasting)
Mixed UMN + LMN	No	YES — hallmark
Sensory	No	No
CK	Very elevated	Mildly elevated (usually < 5× ULN)
Distribution	Symmetric proximal	Asymmetric, can be focal initially

C. Guillain-Barré Syndrome (GBS) / Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Feature	IIM	GBS/CIDP
Distribution	Proximal	Distal → proximal (ascending)
Reflexes	Normal	Areflexia
Sensory	No	Yes (paraesthesia, sensory ataxia in CIDP)
CSF	Normal	Albuminocytological dissociation
NCS	Normal	Demyelinating pattern

Level 2: It IS a Myopathy — But Is It Inflammatory?

Once you've confirmed the lesion is in the muscle, you must distinguish IIM from the many other causes of myopathy. The differential of myopathy is broad ^[3]^[4]:

Endocrine Cause	Why It Causes Myopathy	Key Distinguishing Features
Hypothyroidism	Low T3/T4 → impaired muscle energy metabolism, reduced Na/K-ATPase activity → myofibre oedema and reduced contractility	Slow relaxation phase of reflexes ("hung-up reflexes"), fatigue, cold intolerance, constipation, weight gain. CK can be mildly elevated. TFT diagnostic. ^[3]^[4]
Hyperthyroidism	Excess thyroid hormone → accelerated protein catabolism, increased metabolic rate → net muscle protein breakdown	Weight loss, tremor, tachycardia, heat intolerance, exophthalmos. CK usually normal. Often affects proximal muscles (thyrotoxic myopathy).
Cushing's syndrome	Proximal myopathy from excess cortisol ^[5]: glucocorticoids promote protein catabolism → type II (fast-twitch) muscle fibre atrophy	Moon face, buffalo hump, thin skin, striae, bruising ^[5]. CK is usually NORMAL (this is a key distinguishing point — cortisol doesn't cause muscle necrosis, just atrophy).
Addison's disease	Adrenal insufficiency → electrolyte derangements (hyperK, hypoNa) + direct effect of cortisol deficiency	Hyperpigmentation, hypotension, fatigue.
Acromegaly	GH excess → initial muscle hypertrophy then progressive myopathy from myofibre degeneration	Coarsened facial features, enlarged hands/feet, prognathism.

CK: The Key Differentiator

In endocrine myopathies, CK is usually normal or only mildly elevated (except hypothyroidism, where it can be moderately raised). In IIM, CK is typically >10× ULN ^[2], and in severe cases can be >50–100× ULN ^[2]. If a patient has proximal weakness with a normal CK, think endocrine, drug-induced (steroid), or NMJ disease before IIM.

This is extremely common and must always be excluded (ask the drug history!):

Drug	Mechanism	Key Features
Statins	HMG-CoA reductase inhibition → impaired cholesterol synthesis in muscle membranes → membrane instability; can trigger immune-mediated necrotizing myopathy (anti-HMGCR)	Most common cause of drug-induced myopathy. CK elevated. Usually reversible on withdrawal. If IMNM develops (anti-HMGCR), myopathy persists despite drug cessation → needs immunosuppression.
Steroids (glucocorticoids)	Catabolic effect on type II muscle fibres → atrophy without necrosis	CK is normal (no necrosis!). This is a critical DDx when a patient on steroids for IIM develops worsening weakness — is it disease flare (CK ↑) or steroid myopathy (CK normal)?
Colchicine	Disrupts microtubules → impaired intracellular transport	Vacuolar myopathy. Often co-existing neuropathy (neuromyopathy).
Alcohol	Direct toxic effect on myofibres; also associated with nutritional deficiency	Acute alcoholic myopathy (rhabdomyolysis), chronic alcoholic myopathy (insidious proximal weakness).
Antimalarials (hydroxychloroquine, chloroquine)	Lysosomal dysfunction → vacuolar myopathy	Prolonged use. Also causes cardiomyopathy and retinal toxicity.
Cocaine, heroin	Direct myotoxicity, vasoconstriction → ischaemia	Rhabdomyolysis.

Steroid Myopathy vs. IIM Flare — A Classic Exam Trap

A patient with IIM on prednisolone develops worsening proximal weakness. Is it:

Steroid myopathy? → CK will be normal, EMG shows type II fibre atrophy but no active myopathic changes.
Disease flare? → CK will be elevated, EMG shows active myopathic/irritative changes.

Check CK — it's the simplest way to distinguish.

Electrolyte	Mechanism	Clinical Clues
Hypokalaemia	K+ is essential for muscle membrane potential. Low K+ → hyperpolarisation → muscle cannot depolarise properly → weakness/paralysis	Diuretic use, vomiting/diarrhoea, RTA. ECG changes (U waves, flattened T waves). Can be severe (periodic paralysis).
Hypercalcaemia	Impaired neuromuscular excitability (Ca2+ raises threshold for depolarisation)	Polyuria, constipation, confusion ("bones, stones, groans, moans").
Hypophosphataemia	ATP depletion (phosphate is needed for ATP synthesis) → impaired muscle contraction	Refeeding syndrome, alcoholism.
Hypo/hypernatraemia	Osmotic shifts across cell membranes → cellular swelling or dehydration	Usually other neurological features predominate.

Infection	Mechanism	Distinguishing Features
Viral (influenza, Coxsackie, HIV)	Direct viral invasion of myocytes + immune-mediated damage	Acute myalgia, often in children (benign acute childhood myositis). Self-limiting. CK elevated transiently. Recent viral illness.
Bacterial pyomyositis	Haematogenous seeding (usually Staph aureus) → intramuscular abscess	Focal, not diffuse. Swelling, warmth, fever. MRI shows abscess.
Parasitic (trichinosis, toxoplasmosis, cysticercosis)	Encystation/direct invasion of muscle	Travel history, eosinophilia. Calcified cysts on imaging.

Type	Key Distinguishing Features
Muscular dystrophy (DMD/BMD)	Young males (X-linked recessive). Calf pseudohypertrophy, Gower's sign, tip-toe gait. Genetic testing (dystrophin gene Xp21.2). CK very elevated (> 10,000). Progressive, no response to immunosuppression.
Limb-girdle muscular dystrophy	AD/AR. Proximal weakness similar to IIM but progressive from childhood/adolescence. Genetic testing confirms. No skin rash, no response to steroids.
Facioscapulohumeral dystrophy (FSHD)	AD. Facial weakness + scapular winging + humeral weakness. Cannot whistle, weak eye closure. Asymmetric.
Myotonic dystrophy	Distal muscle weakness ^[3] (unlike IIM which is proximal). Myotonia (delayed relaxation after grip) ^[3]. Myopathic facies, frontal balding, cataracts, cardiomyopathy. CTG repeat in DMPK gene.
Metabolic myopathy (glycogen storage, lipid metabolism, mitochondrial)	Exercise intolerance, cramps, second-wind phenomenon. Fatiguability indicates NMJ diseases or mitochondrial disorders ^[4]. Specific enzyme assays, genetic testing.

How to Tell Hereditary from Inflammatory Myopathy

Think hereditary if:

Family history positive
Onset in childhood/adolescence
Very slow progression (years to decades)
No response to immunosuppression
CK pattern is stable (not fluctuating with disease activity)
Specific phenotypic clues (pseudohypertrophy, myotonia, facial weakness pattern)
No skin rash, no systemic inflammatory features

Condition	Key Features
Critical illness myopathy	ICU patients on prolonged steroids ± neuromuscular blocking agents. Diffuse weakness, CK may be elevated. Biopsy shows thick filament (myosin) loss.
Rhabdomyolysis	Acute muscle necrosis → very high CK (> 10,000), myoglobinuria (dark "cola-coloured" urine), AKI. Many causes: crush injury, drugs, extreme exercise, infections, metabolic.

This is both a classification and a DDx problem. The key distinguishing features:

Feature	PM	DM	IBM	IMNM	Overlap Myositis
Age	Adults	Adults (or children)	>50 years, M > F	Adults	Adults
Onset	Subacute/chronic	Acute/subacute	Insidious (months–years)	Subacute, can be severe	Variable
Distribution	Symmetric proximal	Symmetric proximal	Proximal + distal (quad + finger flexors) ^[3]	Severe proximal	Proximal
Skin rash	No	Yes (pathognomonic features)	No	No	± (if overlap with DM)
CK	↑↑↑ (> 10× ULN)	↑↑ (> 10× ULN)	Normal to mildly ↑ (< 10×)	↑↑↑↑ (often > 50× ULN)	↑↑
Biopsy	Endomysial CD8+ T-cells	Perifascicular atrophy, perimysial B-cells/complement	Rimmed vacuoles, inclusion bodies	Necrosis + regeneration, minimal inflammation	Variable
Treatment response	Good (steroids)	Good (steroids)	Poor ^[3]	Moderate (aggressive immunosuppression)	Good
Malignancy risk	2×	5×	Not increased	Increased (anti-HMGCR less; anti-SRP not)	Not typically
Key MSA	None specific (diagnosis of exclusion)	Anti-Mi-2, anti-MDA5, anti-TIF1-γ, anti-NXP2	Anti-cN1A	Anti-SRP, anti-HMGCR	Anti-synthetase (Jo-1), anti-PM-Scl

High Yield — PM as a Diagnosis of Exclusion

"Symmetric proximal myositis and the absence of histopathological signs of other myopathies or typical rash of DM" ^[1]. Actually a heterogeneous group of disorders; many PM cases in fact sIBM or OM ^[1]. True idiopathic PM rare (or even a controversial entity) ^[1]. Similarities with other AIM, hence "diagnosis of exclusion" ^[1].

Translation: Before you diagnose PM, you must rule out:

DM (look for subtle skin signs — even mechanic's hands or nailfold changes)
IBM (check for distal weakness, especially finger flexor and quadriceps; biopsy for rimmed vacuoles)
Overlap myositis (check for features of other CTDs — Raynaud's, sclerodactyly, anti-synthetase features)
IMNM (biopsy: necrosis without significant inflammation)
Non-inflammatory myopathies (muscular dystrophies, endocrine, drug-induced)

Specific Mimics to Highlight

This is a common clinical and exam trap. Both present with "proximal muscle" complaints in older adults, but the pathology is fundamentally different:

Feature	PMR	IIM
What hurts	Joints/bursae/periarticular structures (shoulders, hips) — NOT muscle itself	Muscles themselves
True weakness	No — pain limits movement, but power is normal if pain is overcome	Yes — genuine proximal weakness on formal testing
CK	Normal	Elevated (usually > 10× ULN)
ESR/CRP	Markedly elevated (ESR often > 50)	Elevated but less markedly
EMG	Normal	Myopathic changes
Response to low-dose steroids	Dramatic (15–20 mg prednisolone)	Requires high-dose steroids (1 mg/kg)
Association	Giant cell arteritis (15–20%)	Malignancy, ILD, CTDs

Why the confusion? PMR causes stiffness and pain around the shoulder and hip girdles, making patients unable to raise their arms or climb stairs — which superficially mimics proximal weakness. But careful motor examination (testing power while controlling for pain) reveals normal strength in PMR and reduced strength in IIM.

DDx	Distribution	CK	Reflexes	Sensory	Fatigability	Key Distinguishing Feature
IIM	Proximal, symmetric	↑↑↑	Normal	No	No	Skin rash (DM), MSA, muscle biopsy
MG	Ocular → bulbar → proximal	Normal	Normal	No	Yes	Anti-AChR, decremental on RNS
MND	Asymmetric, mixed	Mild ↑	Mixed UMN/LMN	No	No	Fasciculations, UMN + LMN signs
GBS	Ascending, distal → proximal	Normal/mild ↑	Areflexia	Yes	No	CSF albuminocytological dissociation
PMR	Shoulder/hip girdle (stiffness, not true weakness)	Normal	Normal	No	No	ESR ↑↑, dramatic response to low-dose steroid
Hypothyroid	Proximal	Mild–moderate ↑	Slow relaxation	No	No	TFT diagnostic, "hung-up" reflexes
Cushing's/steroid	Proximal	Normal	Normal	No	No	Cushingoid features, normal CK
Statin myopathy	Proximal	↑ (variable)	Normal	No	No	Drug history, resolves on withdrawal (unless IMNM)
Muscular dystrophy	Proximal (some distal)	↑↑↑	Normal	No	No	Family history, childhood onset, pseudohypertrophy, genetic testing
IBM	Proximal + distal	Normal–mild ↑	Normal	No	No	> 50y, male, treatment-resistant, rimmed vacuoles

High Yield Summary — Differential Diagnosis of IIM

Level 1 — Is it a myopathy? Rule out: MG (fatigability), MND (UMN + LMN signs), GBS/CIDP (areflexia, sensory loss), UMN lesions (hyperreflexia). Key: myopathy = proximal weakness, normal reflexes, no sensory loss, no fatigability.

Level 2 — Is the myopathy inflammatory? Rule out:

Endocrine: hypothyroidism (TFT), Cushing's/steroid myopathy (CK normal), hyperthyroidism
Drug-induced: statins (most common), steroids, alcohol, colchicine
Electrolyte: hypoK, hyperCa, hypophosphataemia
Infectious: viral myositis (self-limiting), pyomyositis (focal)
Hereditary: muscular dystrophy (family Hx, childhood onset), metabolic, mitochondrial
PMR (no true weakness, normal CK, responds to low-dose steroid)

Level 3 — Which IIM subtype? PM (diagnosis of exclusion), DM (skin rash), IBM (older male, distal weakness, treatment-resistant), IMNM (necrosis on biopsy, anti-SRP/HMGCR), OM (CTD features).

Key investigations to narrow DDx: CK, TFT, drug history, NCS/EMG, MSA panel, muscle biopsy.

Active Recall - Differential Diagnosis of IIM

References

^[1] Lecture slides: GC 056. Generalized muscle weakness.pdf (pages 27–35) ^[2] Senior notes: Ryan Ho Rheumatology.pdf (pages 90–92) ^[3] Senior notes: Maksim Medicine Notes.pdf (pages 274, 318) ^[4] Senior notes: Ryan Ho Neurology.pdf (pages 191, 194–195) ^[5] Senior notes: Ryan Ho Endocrine.pdf (page 61) ^[6] Senior notes: Ryan Ho Rheumatology.pdf (pages 83, 87)

Diagnostic Criteria, Algorithm and Investigations for Idiopathic Inflammatory Myopathies

1. Diagnostic Criteria

There are two major sets of diagnostic criteria to know: the classic Bohan & Peter criteria (1975) and the modern 2017 EULAR/ACR classification criteria. Both are examinable, but the Bohan & Peter criteria remain the most commonly tested because they are simpler and more intuitive.

These are the classic criteria that defined IIM for decades ^[1]^[3].

Bohan and Peter (1975) classified IIM into: Polymyositis, Dermatomyositis, DM (PM) associated with neoplasia, Childhood DM (PM), PM/DM overlap with collagen-vascular disease ^[1].

The criteria use 5 domains:

#	Criterion	Explanation
1	Symmetrical weakness of limb-girdle muscles and anterior neck flexors	Clinical assessment — proximal weakness in shoulder girdle, hip girdle, and neck flexors. Why neck flexors specifically? They are a "proximal" group anatomically (supplied by C1–C4), and their early involvement distinguishes IIM from many other myopathies.
2	Muscle biopsy: typical of myositis	Histological confirmation showing inflammatory infiltrate ± necrosis ± regeneration.
3	Muscle enzyme elevation (esp. CK)	CK is the most sensitive and specific muscle enzyme. Elevated because damaged sarcolemma releases intracellular CK into blood.
4	EMG: typical of myositis (spontaneous fibrillation; polyphasic low-amplitude motor unit potential)	Electrophysiological evidence of active myopathy with irritability.
5	Cutaneous manifestations of DM: e.g. heliotrope rash, Gottron's papules	Skin findings specific to dermatomyositis.

Application rules ^[3]:

Diagnosis	Criteria Required
Definite PM	All 4 of criteria 1–4
Probable PM	Any 3 of criteria 1–4
Possible PM	Any 2 of criteria 1–4
Definite DM	Any 3 of criteria 1–4 PLUS criterion 5
Probable DM	Any 2 of criteria 1–4 plus criterion 5
Possible DM	Any 1 of criteria 1–4 plus criterion 5

High Yield — Bohan & Peter in One Sentence

PM needs all 4 clinical/lab/EMG/biopsy criteria (no skin). DM needs any 3 of those 4 PLUS the characteristic skin rash.

The logic: DM has skin findings that are virtually pathognomonic (especially Gottron's papules), so you need slightly less "proof" of the myositis component because the skin rash already points strongly to the diagnosis.

Limitations of Bohan & Peter criteria:

Does not include IBM, IMNM, or overlap myositis as separate entities
Does not incorporate autoantibodies (MSAs were not yet discovered in 1975)
Does not account for amyopathic DM
Low specificity — can misclassify muscular dystrophies or IBM as PM

2017 EULAR/ACR classification criteria for IIM: include age of onset, antibodies (only anti-Jo1 now), different scoring with/without muscle biopsy ^[3].

IMCCP (2017) — International Myositis Classification Criteria Project ^[1].

This is a probability-based scoring system rather than a checklist. It assigns weighted scores to clinical, laboratory, and biopsy variables and calculates a probability of IIM.

Variable	Without Biopsy (Score)	With Biopsy (Score)
Age of onset	18–40 years: 1.3; ≥ 40 years: 2.1	1.5 / 2.2
Muscle weakness
- Objective symmetric proximal UL weakness	0.7	0.7
- Objective symmetric proximal LL weakness	0.8	0.5
- Neck flexor weakness > neck extensor	1.9	1.6
Skin manifestations
- Heliotrope rash	3.1	3.2
- Gottron's papules	2.1	2.7
- Gottron's sign	3.3	3.7
Dysphagia	0.7	0.6
Anti-Jo-1 antibody	3.9	3.8
Elevated CK or LDH or AST or ALT	1.3	1.4
Muscle biopsy features	N/A	Endomysial infiltration: 1.7; Perifascicular atrophy: 1.9; Rimmed vacuoles: 3.1

Scoring:

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"
Sensitivity 93%, Specificity 88% (higher than Bohan & Peter)

Once classified as IIM, a classification tree further subclassifies into DM, PM, IBM, amyopathic DM, and juvenile DM based on skin findings, age, and biopsy features.

Key Difference from Bohan & Peter

The 2017 criteria incorporate anti-Jo-1 as the only MSA (it was the most validated at the time). They also give very high weight to skin manifestations (heliotrope: 3.1 points; Gottron's sign: 3.3) and neck flexor > extensor weakness (1.9 points) — reflecting their high specificity for IIM.

2. Investigation Modalities — Detailed

The investigations for IIM serve four purposes:

Confirm the myopathy (CK, EMG)
Characterise the type (autoantibodies, biopsy)
Rule out mimics (TFT, drug history, NCS)
Screen for complications and associations (ILD: HRCT/PFT; malignancy: comprehensive screen)

Test	Expected Findings	Interpretation / Why
ESR/CRP	↑↑ ^[2]	Non-specific markers of systemic inflammation. CRP reflects IL-6-driven hepatic acute-phase response. In the GC tutorial case, CRP is 6.7 mg/dL (N < 0.5) ^[7] — markedly elevated, supporting active inflammation.
CBC	Usually normal; may show mild anaemia of chronic disease	Rule out haematological malignancy; baseline before immunosuppression.
L/RFT	Usually normal; check renal function for myoglobinuria risk	Baseline; AKI from myoglobinuria in severe rhabdomyolysis component.
TFT	Should be normal in IIM	TFT to rule out thyroid myopathy ^[2]^[4]. Hypothyroidism can mimic IIM with proximal weakness + elevated CK. A simple test that avoids unnecessary biopsy.

Muscle enzymes: CK, LDH, AST, ALT ^[1]^[2]^[3]

Enzyme	Details
CK (creatine kinase)	The single most important blood test. CK is an intracellular enzyme in skeletal (and cardiac) muscle. When the sarcolemma is damaged by inflammation/necrosis, CK leaks into the blood. CK values: rarely normal (~5%), usually > 10× ULN, may even be > 50–100× ULN in severe cases ^[2]. In the GC tutorial case, serum CK 1570 U/L (NR 22–198) ^[7] — approximately 8× ULN.
LDH	Less specific than CK (also found in liver, RBCs, etc.), but rises in parallel with CK in active myositis.
AST and ALT	These are also found in muscle (not just liver!). A common trap: elevated AST/ALT in IIM is from muscle damage, not hepatitis. Always check CK alongside transaminases.
Aldolase	Another muscle enzyme; sometimes used but less commonly than CK. More sensitive for DM where CK may be less elevated.

CK Ranges in Different Myopathies

CK 200–1000 IU/L: most myopathies (endocrine, drug-induced, metabolic) ^[3]^[4] CK 1000–10,000 IU/L: inflammatory myopathies, acute rhabdomyolysis, DMD/BMD ^[4] CK > 10,000 IU/L: severe rhabdomyolysis, IMNM (anti-SRP), DMD

A normal CK does NOT exclude IIM entirely (~5% of cases have normal CK ^[2]), but it would be unusual and should prompt reconsideration of the diagnosis.

CK as a Disease Activity Marker

CK is not just diagnostic — it is used to monitor disease activity and treatment response. A falling CK with treatment suggests the inflammation is being controlled. A rising CK during steroid taper suggests disease flare (as opposed to steroid myopathy, where CK remains normal).

Autoantibodies panel ^[2]^[3]:

A. Myositis-Specific Antibodies (MSA)

Myositis-specific (only in myositis) ^[2] — these are found exclusively in IIM and define clinical subsets:

Antibody	Subtype	Clinical Significance
Anti-Jo-1 (and other anti-synthetases: PL-7, PL-12, EJ, OJ, KS)	Anti-synthetase syndrome	ILD, mechanic's hands, Raynaud's, arthritis, fever ^[3]. Anti-Jo-1 is the most common MSA overall (~20–30% of IIM). In the GC tutorial case, the myositis specific antibody test is reported as positive for anti-Jo1 antibody ^[7].
Anti-Mi-2	DM, good response to treatment ^[3]	Classic DM with prominent skin features (V sign, shawl sign). Best prognosis among DM subtypes.
Anti-MDA5	CADM with rapidly progressive ILD, skin rash, poor prognosis ^[3]	Minimal/no myositis but devastating ILD. Skin ulceration, oral ulcers, palmar papules. High mortality without aggressive treatment.
Anti-TIF1-γ (anti-p155/140)	DM, strongly associated with malignancy (50%), severe skin rash, less ILD, poor prognosis ^[3]	The "malignancy antibody." Any adult with DM + anti-TIF1-γ needs thorough cancer screen.
Anti-HMGCR	Association with statin-induced IMNM ^[3]	HMGCR = HMG-CoA reductase (the enzyme statins inhibit). Myopathy persists despite statin cessation → needs immunosuppression.
Anti-NXP2 (anti-MJ)	Severe weakness and rash, calcinosis ^[3]	Especially in juvenile DM (calcinosis). In adults, associated with malignancy.
Anti-SRP	IMNM, no rash ^[3]	Severe myopathy with muscle fibre necrosis / endomysial fibrosis with minimal inflammatory infiltrates on histology ^[2]. Aggressive disease refractory to high-dose steroids and immunosuppressants ^[2].
Anti-SAE	DM, dark skin discolouration ^[3]	Initially skin-dominant, then progresses to involve muscle.

B. Myositis-Associated Antibodies (MAA)

Myositis-associated (suggestive of other CTDs) ^[2]:

Anti-PM/Scl, anti-Ku: overlap with scleroderma ^[3]
Anti-U1RNP, anti-U3RNP ^[3]
Anti-Sm, anti-Ro, anti-La ^[3]^[2]

These antibodies are also found in SLE, Sjögren's, MCTD, etc. — their presence in a myositis patient suggests overlap syndrome.

C. ANA

Positive in ~80% of IIM patients (non-specific but supportive)
In the GC tutorial case: anti-nuclear antibodies test is reported as positive with a titre of 1/160 ^[7]
ANA staining pattern can give clues: speckled pattern common in IIM (anti-Jo-1, anti-Mi-2 give speckled/cytoplasmic patterns)

High Yield — The Significance of a Positive ANA in IIM

Per the GC interactive tutorial learning objectives: "The significance of a positive anti-nuclear antibodies test" and "Diagnostic role of the various autoantibodies in autoimmune rheumatic disease" ^[7].

A positive ANA is sensitive but NOT specific for autoimmune disease. An ANA titre of 1:160 is considered significant. However, ANA alone doesn't tell you which disease — you need the specific autoantibody profile (anti-Jo-1, anti-MDA5, anti-TIF1-γ, etc.) to define the IIM subtype and guide management.

EMG: to rule out neuropathic disorders ^[2] — this is a critical investigation because it helps localise the pathology to the muscle (myogenic vs. neurogenic).

EMG triad of findings in myositis ^[2]:

Spontaneous fibrillation potentials at rest — why? Active denervation/necrosis of individual muscle fibres causes unstable membranes that fire spontaneously. In IIM, inflammation damages individual fibres, making them electrically irritable.
Polyphasic or short duration potentials on voluntary contraction — why? In a normal motor unit, all muscle fibres fire synchronously, producing a clean triphasic potential. In myopathy, some fibres within the motor unit are destroyed/damaged, so fewer fibres contribute to the potential → smaller amplitude, shorter duration. The remaining fibres fire slightly asynchronously → polyphasic morphology. Polyphasic low-amplitude motor unit potential ^[3].
Salvos of repetitive potentials on mechanical stimulation of nerve — complex repetitive discharges reflecting membrane instability.

In the GC tutorial case: Electromyography shows low amplitude motor-unit potentials with occasional fibrillation potentials, compatible with inflammatory myopathy ^[7].

Feature	Myopathic (IIM)	Neurogenic (e.g. MND, neuropathy)
Motor unit potential amplitude	Low (few fibres per unit)	High (collateral reinnervation, more fibres per unit)
Motor unit potential duration	Short	Long
Recruitment	Early (many small units fire early to compensate)	Reduced (fewer units available)
Fibrillation potentials	Present (active muscle damage)	Present (denervation)
Fasciculation potentials	Absent	Present (MND)

Why do we do EMG before biopsy?

Confirms the pathology is myopathic (not neuropathic)
Can guide biopsy site by identifying which muscles are actively involved
Important: biopsy should be done on the OPPOSITE side to the EMG, because the needle itself causes minor trauma that can create artefactual inflammatory changes on biopsy

This is the gold standard for definitive diagnosis and subtype classification ^[2]^[4].

Site selection:

Done on weak but not atrophied muscle ^[2] — why? A severely atrophied muscle will show end-stage fibrosis/fat replacement, which is non-specific. You want a muscle that is actively involved (weak) but still has enough viable tissue to show the diagnostic inflammatory pattern.
Guided by P/E, EMG ± MRI ^[2]
Usually sample deltoid, biceps or vastus medialis ^[4]
May be guided by MRI esp in myositis → choose those with signal changes ^[4]
Biopsy the contralateral side from EMG to avoid needle artefact

Biopsy findings by subtype:

Subtype	Histological Findings	Why
PM	Endomysial lymphocytic infiltrates ^[2]; CD8+ T-cells surrounding and invading non-necrotic muscle fibres expressing MHC class I	T-cell mediated: cytotoxic T-cells directly recognise MHC-I on muscle fibres and kill them via perforin/granzyme
DM	Perimysial infiltrates ^[2]; perifascicular atrophy (atrophy of fibres at periphery of fascicles); CD4+ T-cells, B-cells, plasmacytoid dendritic cells; complement C5b-9 on capillaries	Humoral/complement-mediated microangiopathy: antibodies + complement destroy endomysial capillaries → ischaemia → peripheral fibres (watershed) atrophy first
IBM	Endomysial CD8+ infiltrate (like PM) PLUS rimmed vacuoles and intracellular inclusions (amyloid-β, p-tau, TDP-43)	Combined inflammatory + degenerative process; the vacuoles and inclusions distinguish it from PM
IMNM	Muscle fibre necrosis with minimal inflammatory infiltrates ^[2]; prominent regeneration; macrophage-predominant	Antibody-mediated direct myofibre necrosis (anti-SRP or anti-HMGCR) without significant T-cell infiltration

Skin Biopsy in DM

Skin biopsy can also support the diagnosis of DM ^[2]: Interface dermatitis: perivascular lymphocyte infiltrate in dermis with vacuolar changes in basal keratinocyte layer ^[2]. This finding is similar to lupus skin biopsy, so clinical context is essential.

ILD is a major cause of morbidity and mortality in IIM, particularly with anti-synthetase and anti-MDA5 antibodies. Every IIM patient needs pulmonary evaluation.

Investigations of interstitial lung disease ^[7]:

Investigation	Expected Findings	Interpretation
CXR	Faint reticulation over bilateral lower zones ^[7]	Early/subtle ILD; may be normal in early disease.
HRCT thorax	Ground glass opacities predominantly over the lower lobes. No honeycombing ^[7]	GGO suggests active inflammation (potentially reversible with treatment). Honeycombing = established fibrosis (irreversible). NSIP pattern is most common in IIM-associated ILD.
PFT (Pulmonary Function Test)	Reduced FVC of 70% predicted and DLCO of 64% predicted ^[7]	Restrictive pattern (reduced FVC) + impaired gas exchange (reduced DLCO). DLCO may be disproportionately reduced relative to FVC in early ILD (gas exchange impaired before volumes drop significantly).
ABG	May show type 1 respiratory failure (hypoxia, normal/low CO2)	Exercise-induced desaturation may be the earliest sign
6MWT	Desaturation with exertion	Functional assessment of exercise capacity

High Yield — ILD Patterns in IIM

The most common ILD pattern in IIM is NSIP (non-specific interstitial pneumonia) — characterised by bibasal GGO, sparing subpleural region, with volume loss and traction bronchiectasis but rare honeycombing (unlike UIP/IPF). NSIP has a much better prognosis than UIP because it responds to immunosuppression. The GC tutorial case shows this classic pattern: GGO predominantly over lower lobes, no honeycombing ^[7].

Potential association between cancer and dermatomyositis and the rationale of cancer screening ^[7].

Thorough malignancy screen in elderly ^[2]. Investigations to rule out malignancy ^[3]:

Investigation	Target
Refer ENT	NPC (especially in Hong Kong) ^[3] — nasopharyngoscopy, EBV serology
Refer Gynae	CA cervix ^[3] — Pap smear; also ovarian cancer screen (pelvic USS/CT)
Refer GI	Upper and lower endoscopy ^[3] — gastric, colonic malignancy
CXR / CT thorax	Lung cancer
Mammography	Breast cancer
FOBT	Occult GI malignancy
Urinalysis	Bladder cancer
Testicular exam	Testicular cancer (males)
PET-CT	Consider in high-risk cases (anti-TIF1-γ positive, older adults) — whole-body screen
Tumour markers	AFP, CEA, CA125, CA19-9, PSA — low sensitivity/specificity but adjunctive

When to Screen for Malignancy

Cancer can occur before, with, or after onset of IIM ^[4]^[7]. Screen at diagnosis AND repeat screening periodically for at least 3 years after diagnosis ^[1]. The risk is highest in the first year but persists for up to 3 years after ^[1]. In Hong Kong, NPC screening is especially important.

Test	Purpose
ECG / Echocardiography	Detect cardiac muscle involvement ^[4] — myocarditis, conduction defects, cardiomyopathy. IIM can affect cardiac muscle (autoimmune myocarditis).
Swallowing assessment (by speech therapist)	Mild to moderate dysphagia upon speech therapist assessment ^[7] — evaluates oropharyngeal dysphagia from pharyngeal/upper oesophageal striated muscle weakness.
Video fluoroscopy / barium swallow	Objective assessment of swallow mechanism if dysphagia present
Nailfold capillaroscopy	Dilated, irregular capillary loops and dropout — supports DM diagnosis and helps differentiate from SLE

This exemplifies the classic diagnostic workup ^[7]:

Step	Finding	Interpretation
History	Dyspnoea, proximal weakness	Suggests myopathy + ILD
Examination	Cold hands, blue finger pulps (Raynaud's), nailbed erythema (periungual), faint erythematous patch over knuckles (Gottron's), bibasal fine inspiratory crackles (ILD), proximal weakness grade 5−/5	Skin + muscle + lung = DM with ILD
Bloods	CK 1570 U/L (NR 22–198) (~8× ULN), CRP 6.7 mg/dL (N < 0.5)	Active myositis + systemic inflammation
ANA	Positive 1/160	Supports autoimmune aetiology
MSA	Anti-Jo1 positive	Defines as anti-synthetase syndrome
CXR	Faint reticulation bilateral lower zones	Early ILD
PFT	FVC 70% predicted, DLCO 64% predicted	Restrictive defect + impaired gas exchange → ILD
EMG	Low amplitude MUPs with fibrillation potentials	Inflammatory myopathy
HRCT	GGO predominantly lower lobes, no honeycombing	NSIP pattern ILD (potentially reversible)
Speech therapy	Mild to moderate dysphagia	Bulbar muscle involvement

Diagnosis: Dermatomyositis (anti-synthetase syndrome / anti-Jo1 positive) with interstitial lung disease ^[7].

Category	Investigations
Confirm myopathy	CK (+LDH, AST, ALT), EMG/NCS
Characterise subtype	MSA panel, MAA panel, ANA, muscle biopsy (± MRI-guided), skin biopsy (DM)
Rule out mimics	TFT, drug history (statins!), electrolytes (K, Ca, PO4), genetic testing if hereditary suspected
Screen for ILD	CXR, HRCT thorax, PFT (FVC, DLCO), ABG, 6MWT
Screen for malignancy	ENT (NPC), Gynae (cervix), GI (endoscopy), CXR/CT, mammography, FOBT, urinalysis, PET-CT
Screen for cardiac	ECG, echocardiography
Assess functional impact	Swallowing assessment, respiratory muscle strength, functional testing
Baseline before treatment	CBC, L/RFT, HBV/HCV serology (before immunosuppression), bone density (before steroids)

High Yield Summary — Diagnosis of IIM

Diagnostic Criteria:

Bohan & Peter (1975): 5 criteria — PM needs all 4 of (weakness + biopsy + CK + EMG); DM needs any 3 of those 4 + skin rash
Practical rule: Myositis = 2 out of 3 of ↑CK, EMG abnormalities, positive muscle biopsy
2017 EULAR/ACR: Probability-based scoring system; includes anti-Jo-1 as only antibody; heliotrope and Gottron's score highest

Key Investigations:

CK: Most important blood test. Usually > 10× ULN. Also monitors disease activity. ~5% may be normal.
EMG: Myopathic triad — fibrillation at rest, polyphasic short-duration MUPs, complex repetitive discharges. Rules out neuropathy.
Muscle biopsy: Gold standard. Endomysial (PM) vs perimysial + perifascicular atrophy (DM) vs rimmed vacuoles (IBM) vs necrosis (IMNM). Site: weak but not atrophied muscle, contralateral to EMG.
MSA panel: Defines subtype and prognosis. Anti-Jo-1 (synthetase syndrome/ILD), anti-MDA5 (aggressive ILD), anti-TIF1-γ (malignancy), anti-SRP/HMGCR (IMNM).
ILD screen: HRCT (GGO, NSIP pattern), PFT (↓FVC, ↓DLCO) — do on ALL patients.
Malignancy screen: Comprehensive — ENT (NPC in HK!), Gynae, GI, imaging. Repeat for 3 years.

Active Recall - Diagnostic Criteria and Investigations for IIM

References

^[1] Lecture slides: GC 056. Generalized muscle weakness.pdf (pages 27–35) ^[2] Senior notes: Ryan Ho Rheumatology.pdf (pages 90–92) ^[3] Senior notes: Maksim Medicine Notes.pdf (pages 318–321) ^[4] Senior notes: Ryan Ho Neurology.pdf (pages 44, 191–195) ^[5] Senior notes: Ryan Ho Endocrine.pdf (page 61) ^[7] Lecture slides: GC Interactive tutorial (Rheum case 2) student copy.pdf (pages 1, 4, 6)

Management of Idiopathic Inflammatory Myopathies

Non-pharmacological: bed rest in acute attacks, sun protection, physiotherapy to prevent contracture, IV fluids (rhabdomyolysis prophylaxis), stop statins ^[3].

Measure	Rationale / Explanation
Bed rest in acute attacks	During active severe myositis, exercising inflamed muscles can worsen damage. Relative rest reduces metabolic demand on damaged fibres. However, prolonged immobility itself causes deconditioning — so rest is for the acute phase only.
Sun protection	DM skin manifestations are photosensitive — UV radiation exacerbates the skin rash (photoexacerbation triggers complement-mediated vasculopathy in skin). Use broad-spectrum sunscreen, protective clothing, and avoid peak sun hours.
Physiotherapy to prevent contracture	Supportive (for late bulbar S/S): PT, speech therapy, PEG tube ^[2]. During the chronic/recovery phase, regular physiotherapy maintains range of motion and prevents contractures (which develop from chronic inflammation → fibrosis → shortening of muscle-tendon units). In juvenile DM, muscle contractures (tip-toe gait) are a particular concern ^[4]. Active assisted exercises in the subacute phase, progressing to strengthening exercises once inflammation is controlled (CK normalising).
IV fluids (rhabdomyolysis prophylaxis)	Severe myositis with very high CK ( > 10,000) can cause myoglobinuria → acute kidney injury from myoglobin cast nephropathy. Aggressive hydration with IV normal saline dilutes myoglobin and maintains renal perfusion. Target urine output > 200 mL/hour initially.
Stop statins	If the patient is on statins, stop immediately. Statins can trigger both toxic myopathy AND immune-mediated necrotizing myopathy (anti-HMGCR). Even if the myopathy is not statin-related, statins may worsen ongoing muscle damage. Association with statin-induced IMNM ^[3].
Speech therapy / swallowing assessment	For patients with bulbar involvement (dysphagia). Modified diet textures, swallowing exercises. If severe, consider PEG tube (percutaneous endoscopic gastrostomy) for enteral nutrition to prevent aspiration pneumonia.
Vaccination	Before starting immunosuppression: influenza, pneumococcal, COVID-19, hepatitis B (if non-immune). Avoid live vaccines once on immunosuppression.
Bone protection	All patients starting long-term steroids need calcium + vitamin D supplementation ± bisphosphonate (for osteoporosis prevention).
Infection screening	Before immunosuppression: screen for hepatitis B (risk of reactivation on rituximab/steroids), hepatitis C, TB (quantiferon/IGRA), HIV. Treat latent TB before starting immunosuppression.

4. Pharmacological Management — Detailed

High-dose steroid (PO prednisolone 1 mg/kg/day) ^[3] — this is the cornerstone of initial treatment for PM, DM, and most IIM subtypes.

Aspect	Details
Drug	Prednisolone 1 mg/kg/day (typically 60–80 mg/day in adults) ^[3]^[2]^[4]
Route	Oral for most cases
IV pulse steroids	For severe/life-threatening disease (e.g., rapidly progressive ILD, severe bulbar involvement, respiratory failure): IV methylprednisolone 500 mg–1 g/day for 3–5 days, then switch to oral prednisolone
Mechanism	Glucocorticoids suppress virtually all arms of the immune system: ↓ T-cell and B-cell activation, ↓ pro-inflammatory cytokine production (IL-1, IL-6, TNF-α), ↓ NF-κB transcription, ↓ complement activation, ↓ adhesion molecule expression → reduced inflammatory cell migration into muscle
Duration	Prolonged therapy until active disease controlled for 1 year ^[3]. Maintain high dose for 4–6 weeks (or until CK normalises and strength improves), then begin gradual taper.
Taper	Slow taper: typically reduce by 10 mg every 2–4 weeks down to 20 mg, then by 2.5–5 mg every 2–4 weeks. Guided by CK and clinical strength. Total treatment duration often 12–24 months.

Why start high and taper slowly?

Starting high ensures adequate suppression of the active autoimmune process (under-dosing leads to smouldering disease and progressive muscle damage)
Tapering too fast risks disease flare (the autoimmune process is not fully extinguished)
CK is your guide: a rising CK during taper = too fast, disease still active

High Yield — Steroid Myopathy vs. Disease Flare During Taper

This is the most important clinical conundrum in IIM management. If a patient on steroids develops worsening weakness:

Disease flare: CK rises, EMG shows active irritative changes → increase steroid dose
Steroid myopathy: CK stays normal, EMG shows type II fibre atrophy without fibrillation → reduce steroid dose

The solution is simple: check CK. If CK is normal and the patient is getting weaker, you are likely causing steroid myopathy and need to reduce the dose.

Side effects of long-term steroids (why we need steroid-sparing agents):

Osteoporosis, avascular necrosis
Cushing's syndrome, weight gain, hyperglycaemia/DM
Hypertension, hyperlipidaemia
Immunosuppression → infections
Cataracts, glaucoma
Peptic ulcer disease
Psychiatric disturbance (mood changes, insomnia)
Skin thinning, poor wound healing
Adrenal suppression (cannot stop abruptly → need to taper)

Steroid-sparing agents: initiated with steroids to decrease steroid dose and side effects ^[3].

These are started concurrently with steroids (or within the first few weeks) because they take 2–3 months to reach full effect. Starting them early allows earlier steroid taper.

Drug	Mechanism	Key Details	Indications	Major Side Effects / Contraindications
Azathioprine	Purine analogue → inhibits DNA synthesis → suppresses T and B-cell proliferation	First-line steroid-sparing agent. Dose: 2–3 mg/kg/day. Takes 2–3 months to work.	Myositis ^[2]^[3]. Often preferred as first choice due to long safety track record.	Check TPMT (thiopurine methyltransferase) level before starting — low TPMT activity → high risk of life-threatening myelosuppression. Monitor FBC regularly. S/E: bone marrow suppression, hepatotoxicity, GI upset, increased infection risk.
Methotrexate	Folate antagonist → inhibits dihydrofolate reductase → impairs DNA synthesis and T-cell function; also anti-inflammatory via adenosine pathway	Dose: 7.5–25 mg/week (oral or SC). Co-prescribe folic acid 5 mg weekly (not on same day as MTX) to reduce mucosal side effects.	Myositis ^[2]^[3]. Good alternative to azathioprine, particularly for joint involvement.	Contraindicated in significant ILD — MTX itself can cause pneumonitis (drug-induced ILD), making it risky in patients who already have IIM-associated ILD. Also contraindicated in pregnancy (teratogenic), significant liver disease, renal impairment. S/E: hepatotoxicity, bone marrow suppression, oral ulcers, pneumonitis.
Mycophenolate mofetil (MMF)	Inhibits inosine monophosphate dehydrogenase → blocks de novo purine synthesis → preferentially suppresses lymphocyte proliferation (lymphocytes uniquely depend on de novo pathway, unlike other cells which use salvage pathways)	Dose: 2–3 g/day in divided doses. Increasingly used first-line.	Myositis and ILD. Good choice when ILD is present (unlike MTX).	S/E: GI upset (diarrhoea, nausea), bone marrow suppression, teratogenic.
Cyclophosphamide	Alkylating agent → cross-links DNA → potent immunosuppression of both T and B cells	IV pulse preferred (reduces cumulative toxicity vs. daily oral). Dose: 500 mg–1 g/m² IV monthly for 3–6 months.	Severe ILD, refractory myositis ^[2]. Reserved for life-threatening disease due to toxicity profile.	S/E: bone marrow suppression, haemorrhagic cystitis (co-administer MESNA), gonadal toxicity (infertility), increased malignancy risk (bladder cancer, lymphoma). C/I: pregnancy, active infection.
Hydroxychloroquine (HCQ)	Inhibits TLR signalling, reduces antigen presentation, anti-inflammatory	Dose: 200–400 mg/day.	Only effective for skin disease ^[3]. Does NOT treat myositis component. Used for DM cutaneous manifestations.	Topical or systemic ^[3]. S/E: retinal toxicity (bull's eye maculopathy — annual ophthalmology screening after 5 years), QTc prolongation, skin hyperpigmentation. Max dose < 5 mg/kg/day to minimise retinal risk.
Calcineurin inhibitors (tacrolimus, ciclosporin)	Inhibit calcineurin → block IL-2 transcription → suppress T-cell activation	Tacrolimus often preferred.	Refractory myositis, ILD (especially anti-MDA5 ILD where combination therapy is needed).	S/E: nephrotoxicity, hypertension, hyperglycaemia, tremor, gingival hyperplasia (ciclosporin). Monitor trough drug levels.

MTX and ILD — A Critical Contraindication

Methotrexate can itself cause drug-induced pneumonitis/ILD. In a patient who already has IIM-associated ILD (e.g., anti-synthetase syndrome or anti-MDA5), using MTX is dangerous because:

You cannot distinguish drug-induced from disease-related ILD worsening
You may exacerbate the lung disease

Use MMF or azathioprine instead when significant ILD is present. Cyclophosphamide is reserved for rapidly progressive ILD.

IVIG for severe or refractory disease ^[2]^[3].

Therapy	Mechanism	Indication	Details
IVIg (Intravenous Immunoglobulin)	Multiple mechanisms: neutralises pathogenic autoantibodies, modulates Fc receptor function, inhibits complement activation (C3b/C4b), saturates neonatal Fc receptor (FcRn) → accelerates catabolism of pathogenic IgG, modulates cytokine production	Severe or refractory disease ^[3]. Particularly useful in DM (where humoral/complement pathway is dominant — IVIg directly counters this). Also used when rapid response needed (e.g., severe dysphagia, respiratory failure).	Dose: 2 g/kg total, divided over 2–5 days. Can be repeated monthly as maintenance. Onset: faster than steroid-sparing agents (days to weeks). S/E: headache, aseptic meningitis, anaphylaxis (IgA-deficient patients), thromboembolic events, renal impairment. C/I: IgA deficiency (risk of anaphylaxis), renal failure.
Rituximab (anti-CD20)	Monoclonal antibody targeting CD20 on B cells → depletes circulating B cells → reduces autoantibody production and B-cell mediated antigen presentation	Anti-CD20 (still experimental) ^[2] — however, now increasingly mainstream for refractory IIM. Evidence from RIM trial and open-label studies.	Dose: 1 g IV × 2 doses, 2 weeks apart. Repeated every 6 months as needed. Particularly effective in DM (B-cell driven), anti-synthetase syndrome, and anti-SRP IMNM. Screen for hepatitis B before (risk of reactivation), monitor immunoglobulin levels. S/E: infusion reactions, hypogammaglobulinaemia, progressive multifocal leukoencephalopathy (PML — rare), hepatitis B reactivation.
Plasmapheresis	Physically removes circulating autoantibodies, complement factors, and immune complexes from the plasma	Acute severe disease (severe bulbar weakness, respiratory failure), particularly antibody-mediated subtypes (DM, IMNM).	Short-term bridge to allow time for steroids/immunosuppressants to work. Usually 5 exchanges over 2 weeks. Effect is temporary (antibodies are re-synthesised unless concurrent immunosuppression is given).
JAK inhibitors (tofacitinib, ruxolitinib)	Inhibit Janus kinase → block intracellular signalling downstream of multiple cytokine receptors (IFN, IL-6, IL-12, IL-23)	Emerging therapy for refractory DM, particularly skin-predominant disease and anti-MDA5 CADM	Growing evidence but not yet standard of care. Particularly relevant because type I interferon pathway is strongly implicated in DM pathogenesis, and JAK inhibitors effectively block IFN signalling. S/E: infections (herpes zoster), VTE risk, cardiovascular risk (boxed warning in RA).

This is where understanding the antibody profile directly changes management:

Subtype	Key Treatment Considerations
Classic DM (anti-Mi-2)	Good response to treatment ^[3]. Standard approach: prednisolone + azathioprine/MTX. Usually achieves remission. HCQ for skin.
Anti-synthetase syndrome (anti-Jo-1)	Focus on ILD management. Avoid MTX (risk of pneumonitis). Prefer azathioprine, MMF, or tacrolimus as steroid-sparing agent. If ILD progressive: cyclophosphamide or rituximab. Typically not associated with malignancy ^[3].
Anti-MDA5 DM (CADM with RP-ILD)	Most aggressive subtype — medical emergency. CADM with rapidly progressive ILD, skin rash, poor prognosis ^[3]. Standard triple combination from the outset: high-dose steroids + calcineurin inhibitor (tacrolimus) + cyclophosphamide (the "Japanese triple therapy"). IVIg and plasmapheresis as rescue. JAK inhibitors emerging. Mortality 30–50% without aggressive treatment.
Anti-TIF1-γ DM	Strongly associated with malignancy (50%) ^[3]. Search for and treat any malignancy ^[2] — the myositis may improve or resolve with successful cancer treatment. Standard immunosuppression if no malignancy found.
IMNM (anti-SRP or anti-HMGCR)	Aggressive disease refractory to high-dose steroids ^[2] (particularly anti-SRP). Often requires combination of steroids + IVIg + rituximab from the outset. Anti-HMGCR: stop statins first, but immunosuppression usually still needed because the autoimmune process becomes self-sustaining.
IBM	Failed response to treatment ^[3]. Immunosuppression is generally ineffective. IVIg may provide modest temporary benefit for dysphagia. Management is primarily supportive: physiotherapy, occupational therapy, falls prevention, assistive devices, swallowing rehabilitation. Consider dysphagia-specific interventions (cricopharyngeal myotomy or botulinum toxin for cricopharyngeal dysfunction).
Cancer-associated myositis (CAM)	Search for and treat any malignancy ^[2]. The myositis may improve/resolve with successful treatment of the underlying cancer (paraneoplastic mechanism). Standard immunosuppression used concurrently as a bridge. If myositis persists after cancer treatment, manage as idiopathic IIM.
Overlap myositis	Response to steroid: overlap myositis > DM > PM ^[2]. Treat both the myositis and the associated CTD. Management of the CTD component follows disease-specific guidelines (e.g., SLE, SSc).

5. Organ-Specific Management

Lung fibrosis: high dose steroids + immunosuppressants ^[2].

Severity	Treatment
Mild/stable ILD	Prednisolone + azathioprine or MMF. Monitor with serial PFTs (FVC, DLCO) and HRCT.
Moderate ILD	Prednisolone + MMF or tacrolimus. Consider adding rituximab if progressive.
Rapidly progressive ILD (especially anti-MDA5)	IV pulse methylprednisolone + tacrolimus + IV cyclophosphamide ("triple therapy"). IVIg, plasmapheresis, JAK inhibitors as rescue.
Chronic fibrotic ILD (established honeycombing)	Antifibrotics (nintedanib — now approved for progressive fibrosing ILD of any cause, including CTD-ILD). Immunosuppression less effective once fibrosis is established.
End-stage ILD	Lung transplant: high mortality for ILD → consider early referral ^[8]. Long-term O2 if PaO2 < 55 mmHg. Palliative care if not transplant candidate.

Parameter	Frequency	Purpose
CK	Every 2–4 weeks during induction, then monthly	Disease activity marker. Should normalise with effective treatment. Rising CK = flare or inadequate suppression.
Muscle strength (MRC grading, functional testing)	Every visit	Objective clinical improvement lags behind CK normalisation by weeks.
PFT (FVC, DLCO)	Every 3–6 months (more frequently if active ILD)	Monitor ILD progression/response.
HRCT	Annually or if PFTs deteriorate	Structural assessment of ILD.
FBC, L/RFT	Regularly (frequency depends on agent)	Monitor for drug toxicity (myelosuppression, hepatotoxicity, nephrotoxicity).
Malignancy screening	At diagnosis, then annually for 3–5 years	Cancer can present years after IIM diagnosis.
Bone density (DEXA)	Baseline, then every 1–2 years on steroids	Steroid-induced osteoporosis prevention.
Ophthalmology	Annually after 5 years of HCQ use	HCQ retinal toxicity screening.
Blood glucose / HbA1c	Regularly on steroids	Steroid-induced diabetes.

Prognosis: variable depending on type of myositis, severity, delay in diagnosis and autoantibody profile ^[2].

Factor	Better Prognosis	Worse Prognosis
Subtype	Overlap myositis, anti-Mi-2 DM	Anti-MDA5 CADM, anti-SRP IMNM, IBM
Antibody	Anti-Mi-2 (excellent steroid response)	Anti-MDA5 (RP-ILD, 30–50% mortality), anti-SRP (refractory)
Organ involvement	Isolated myositis ± skin	ILD (major cause of mortality), cardiac involvement, severe bulbar
Malignancy	No malignancy	Cancer-associated (prognosis depends on cancer stage)
Treatment response	Overlap myositis > DM > PM ^[2]	IBM (does not respond to immunosuppression)
Delay in diagnosis	Early diagnosis and treatment	Delayed treatment → chronic damage, fibrosis, contractures

Domain	First-Line	Second-Line / Refractory	Supportive
Myositis	Prednisolone 1 mg/kg/d + AZA or MTX	IVIg, rituximab, cyclophosphamide	PT, bed rest (acute), PEG tube (bulbar)
Skin (DM)	Topical steroids + HCQ + sun protection	Moderate-dose systemic steroids, MMF, MTX	Photoprotection
ILD	Prednisolone + MMF or AZA	CYC, rituximab, tacrolimus, JAK inhibitor	O2, pulmonary rehab, transplant referral
RP-ILD (anti-MDA5)	Triple therapy: steroids + tacrolimus + CYC	IVIg, plasmapheresis, JAK inhibitor	ICU if respiratory failure
IMNM	Prednisolone + IVIg ± rituximab	Combination immunosuppression	Stop statins (if HMGCR)
IBM	None reliably effective	IVIg trial (modest dysphagia benefit)	PT, OT, falls prevention, assistive devices
CAM	Treat underlying malignancy + steroids	Standard immunosuppression if myositis persists	Cancer-directed therapy
Arthritis	NSAIDs	HCQ, low-dose steroids, MTX
Raynaud's	CCB (nifedipine)	PDE5 inhibitor (sildenafil), iloprost	Hand warming, smoking cessation

High Yield Summary — Management of IIM

Principles: Suppress inflammation (steroids), spare steroids (immunosuppressants), treat each organ, screen/treat malignancy, supportive care.

Non-pharmacological: Bed rest (acute), sun protection (DM), physiotherapy, IV fluids (rhabdomyolysis prophylaxis), stop statins, speech therapy for dysphagia, vaccination before immunosuppression, bone protection.

Induction: Prednisolone 1 mg/kg/day. IV methylprednisolone pulses for severe disease. Maintain until disease controlled, then slow taper guided by CK.

Steroid-sparing (start early):

First-line: Azathioprine (check TPMT), Methotrexate (AVOID if ILD), MMF
Second-line: Cyclophosphamide (severe ILD/refractory), calcineurin inhibitors (tacrolimus)
HCQ: skin disease ONLY

Refractory: IVIg (especially DM, dysphagia), Rituximab (B-cell depletion), plasmapheresis (acute bridge).

Subtype-specific:

Anti-Mi-2: Good prognosis, responds well to steroids
Anti-MDA5 RP-ILD: Triple therapy (steroids + tacrolimus + CYC) upfront — medical emergency
Anti-SRP IMNM: Aggressive combination (steroids + IVIg + rituximab)
IBM: Does NOT respond to immunosuppression → supportive only
CAM: Treat the cancer — myositis may resolve

Monitoring: CK (activity), muscle strength (function), PFT/HRCT (ILD), FBC/LFT/RFT (drug toxicity), malignancy screen (annually × 3–5 years), DEXA (steroids), ophthalmology (HCQ).

Steroid myopathy vs. flare: Check CK — normal = steroid myopathy (reduce dose); elevated = flare (increase dose).

Active Recall - Management of IIM

References

^[1] Lecture slides: GC 056. Generalized muscle weakness.pdf (pages 27–35) ^[2] Senior notes: Ryan Ho Rheumatology.pdf (pages 85, 92) ^[3] Senior notes: Maksim Medicine Notes.pdf (pages 318–321) ^[4] Senior notes: Ryan Ho Neurology.pdf (pages 191, 194–195) ^[8] Senior notes: Ryan Ho Respiratory.pdf (pages 121–122)

Complications of Idiopathic Inflammatory Myopathies

1. Pulmonary Complications

ILD: note correlation with anti-synthetase syndrome and anti-MDA5 syndrome ^[8].

ILD, polyarthritis are features of DM ^[1].

↑ risk of ILD in anti-synthetase and anti-MDA5 (very aggressive ILD) ^[4].

Aspect	Details
Prevalence	20–65% of IIM patients overall; up to 80% in anti-synthetase syndrome
Pathophysiology	The same autoimmune process that attacks muscle also attacks the pulmonary interstitium. Anti-synthetase antibodies (e.g., anti-Jo-1) target aminoacyl-tRNA synthetases, which are expressed in lung tissue. Immune complex deposition and T-cell mediated inflammation → alveolar damage → fibrosis. Anti-MDA5 drives a particularly aggressive type I interferon-mediated alveolitis.
ILD patterns	Most commonly NSIP (non-specific interstitial pneumonia): bibasal GGO, rare honeycombing, responds to immunosuppression ^[8]. Also: organizing pneumonia (OP), UIP (usual interstitial pneumonia — worst prognosis), diffuse alveolar damage (DAD — acute, devastating).
Clinical presentation	Progressive dyspnoea, dry cough, bibasal fine inspiratory crackles. May be the presenting feature (before muscle weakness).
Prognosis	NSIP: 5-year mortality < 15% ^[8]. RP-ILD (anti-MDA5): 30–50% mortality without aggressive treatment. UIP pattern: poorest prognosis, similar to IPF.
Management	Immunosuppression (steroids + MMF/AZA for moderate; triple therapy with steroids + tacrolimus + cyclophosphamide for RP-ILD). Antifibrotics (nintedanib) for progressive fibrosing phenotype. Lung transplant: high mortality for ILD → consider early referral ^[8].

High Yield — ILD is the Leading Cause of Death in IIM

More patients with IIM die from ILD than from the myositis itself. Always screen every IIM patient with PFTs (FVC, DLCO) and HRCT at diagnosis, and monitor serially. Anti-MDA5 positive RP-ILD is a medical emergency — can be fatal within weeks if untreated.

Aspect	Details
Pathophysiology	The diaphragm and intercostal muscles are skeletal muscles. In severe IIM, inflammatory damage to these respiratory muscles → reduced tidal volume → type 2 respiratory failure (hypercapnia). This is a different mechanism from ILD (which causes type 1 respiratory failure — hypoxia with normal/low CO2).
Clinical presentation	± respiratory failure ^[4]. Orthopnoea (diaphragm works less efficiently when supine), tachypnoea, reduced chest expansion, paradoxical abdominal movement (diaphragm moves upward instead of downward during inspiration).
Monitoring	Serial FVC (forced vital capacity) — a falling FVC indicates worsening respiratory muscle weakness. An FVC < 1L or < 15 mL/kg is a red flag for impending respiratory failure. Supine-to-upright FVC drop > 20% suggests diaphragmatic weakness.
Management	Aggressive immunosuppression to treat the underlying myositis. Non-invasive ventilation (NIV/BiPAP) as a bridge. Mechanical ventilation if severe.

Two Types of Respiratory Failure in IIM

Do not confuse these — they have different mechanisms and treatments:

ILD → Type 1 RF (hypoxia, normal/low CO2) → treat with immunosuppression + O2
Respiratory muscle weakness → Type 2 RF (hypercapnia + hypoxia) → treat with immunosuppression + ventilatory support

Both can coexist. Check ABG to distinguish.

Aspect	Details
Pathophysiology	Bulbar muscle weakness (pharyngeal + upper oesophageal striated muscle) → oropharyngeal dysphagia → failure to protect the airway → aspiration of food/saliva into the tracheobronchial tree → chemical + infective pneumonitis
Risk factors	Dysphagia and dysphonia ^[4]. Late-stage disease with bulbar involvement. Oesophageal involvement: dysphagia, nasal regurgitation, aspiration, aspiration pneumonia ^[2].
Clinical features	Recurrent lower respiratory tract infections, especially right lower lobe (aspiration preferentially goes to the right main bronchus because it is wider and more vertical). Cough with meals, wet/gurgling voice after swallowing.
Prevention	Speech therapy assessment, modified diet (thickened fluids), head-of-bed elevation, PEG tube if severe. Treat the myositis aggressively to improve swallowing function.

Complication	Pathophysiology	Clinical Features
Oropharyngeal dysphagia	Dysphagia and dysphonia ^[4] — pharyngeal striated muscle weakness → difficulty initiating swallow, nasal regurgitation, coughing/choking during meals. The upper 1/3 of the oesophagus is striated muscle and is affected; the lower 2/3 (smooth muscle) is typically spared.	Presents as difficulty swallowing solids AND liquids (because the problem is muscle weakness, not obstruction). Associated with poor prognosis ^[2].
Nasal regurgitation	Palatal muscle weakness → failure to close off the nasopharynx during swallowing → food/liquid regurgitates through the nose	Liquids come out through the nose during attempted swallowing
GI involvement in juvenile cases ^[1]	Calcinosis and GI involvement in juvenile cases ^[1]. In juvenile DM, complement-mediated vasculopathy affects GI tract vessels → mucosal ischaemia → ulceration, haemorrhage, perforation	Abdominal pain, GI bleeding, perforation (surgical emergency). This is specific to juvenile DM and is rare in adults.

Myocardial involvement, e.g. HF, arrhythmia, MI ^[2].

Complication	Pathophysiology	Clinical Features
Myocarditis	The autoimmune process can target cardiac muscle (which is also striated muscle, though structurally different from skeletal muscle). Inflammatory infiltrate in myocardium → impaired contractility.	Heart failure symptoms: dyspnoea, orthopnoea, peripheral oedema. Elevated troponin/BNP. Echo: reduced ejection fraction, wall motion abnormalities.
Conduction defects / Arrhythmias	Inflammation of the cardiac conduction system → bundle branch block, AV block, atrial/ventricular arrhythmias	Palpitations, syncope, sudden cardiac death (rare but recognised). ECG monitoring is essential.
Heart failure	End result of chronic/severe myocarditis → dilated cardiomyopathy	Progressive cardiac dysfunction despite treatment. Management of complications: heart failure, arrhythmia, respiratory failure ^[3].
Pericarditis	Serositis (autoimmune inflammation of serous membranes) — less common than in SLE	Pleuritic chest pain, pericardial rub, pericardial effusion on echo

Why does IIM affect the heart? Cardiac myocytes express MHC class I under inflammatory conditions (just like skeletal muscle), making them targets for the same autoimmune process. Additionally, complement-mediated microangiopathy (in DM) can affect the coronary microvasculature, contributing to myocardial ischaemia.

Complication	Pathophysiology	Clinical Features
Muscle wasting and contractures	Wasting/contractures ONLY if chronic ^[4]. Chronic inflammation → progressive destruction of muscle fibres → fibrosis and fatty replacement → loss of muscle mass (wasting) and shortening of muscle-tendon units (contractures). Fibrosis is irreversible — this is why early, aggressive treatment is critical.	Fixed joint deformity, inability to fully extend/flex joints. Childhood form may have muscle contractures (tip-toe gait) ^[4] — tight Achilles tendons from gastrocnemius/soleus fibrosis.
Calcinosis cutis	Scarring and calcinosis ^[4]. Dystrophic calcification: calcium deposits in damaged/inflamed tissues. The chronic inflammatory process creates areas of tissue necrosis where calcium salts precipitate. Particularly common in juvenile DM ^[2] but less so in adult DM.	Hard, palpable subcutaneous nodules. Can ulcerate through skin, become infected, or cause pain. May occur over bony prominences, pressure points, or within muscle. Difficult to treat — usually does not respond to immunosuppression.
Falls and fractures	Proximal weakness (especially quadriceps and hip flexors) → impaired balance → falls. Compounded by steroid-induced osteoporosis.	Recurrent falls, hip fractures (a major cause of morbidity, especially in elderly IBM patients).

Associated with neoplasia in 6–45% of cases ^[1].

Adult form associated with malignancy in 60% ^[4] (note: GC lecture slides state 6–45% ^[1]; use lecture slide figure for exams).

Aspect	Details
Mechanism	IIM can be a paraneoplastic phenomenon: the immune system mounts an anti-tumour response, but anti-tumour antibodies cross-react with muscle antigens (molecular mimicry). The tumour itself may express muscle-like antigens that trigger the autoimmune response.
Risk by subtype	5× risk in dermatomyositis, 2× risk in polymyositis ^[4]. Highest risk: anti-TIF1-γ positive DM (up to 50%). IBM: not associated with increased malignancy risk.
Cancer types	Adenocarcinoma of cervix, lung, ovaries, pancreas, bladder, stomach, NPC (this locality) ^[4]. Breast, lung, pancreas, colon, cervix, NPC ^[1]. In Hong Kong, always consider NPC (EBV-driven, endemic in Southern Chinese).
Temporal relationship	2 years before to 3 years after diagnosis of IIM ^[1]. Can be diagnosed before, with or after diagnosis of inflammatory myopathy ^[4]. Usually within 1 year ^[3].
Screening	Systemic malignancy screen: CBC, LFT, urinalysis, CXR, FOBT, Pap test, mammography, testicular self-exam, colonoscopy ± PET-CT ^[4]. In HK: refer ENT (NPC), Gynae (CA cervix), GI (upper and lower endoscopy) ^[3].
Management	Search for and treat any malignancy ^[2]. The myositis may improve or resolve completely with successful cancer treatment (supporting the paraneoplastic hypothesis).

High Yield — Cancer Screening Is Mandatory

Every adult with newly diagnosed DM (and to a lesser extent PM) MUST undergo comprehensive malignancy screening at diagnosis and annually for at least 3–5 years. The highest risk period is the first year, but cancer can present up to 3 years after IIM diagnosis. Anti-TIF1-γ positive patients warrant the most intensive screening, including consideration of PET-CT.

Complication	Pathophysiology	Clinical Features
Myoglobin-induced AKI (rhabdomyolysis)	Severe muscle necrosis (especially in acute PM or IMNM with CK > 10,000) → massive release of myoglobin into the blood → myoglobin precipitates in renal tubules (especially in acidic urine) → tubular obstruction + direct nephrotoxicity → acute tubular necrosis → AKI	Dark "cola-coloured" urine (myoglobinuria), oliguria, rising creatinine. IV fluids (rhabdomyolysis prophylaxis) ^[3] — aggressive hydration is the key preventive measure.
Drug-induced nephrotoxicity	Calcineurin inhibitors (tacrolimus, ciclosporin) → afferent arteriolar vasoconstriction → reduced GFR. IVIg (sucrose-containing formulations) → osmotic nephrosis.	Rising creatinine during treatment. Monitor renal function and drug levels.

These are critically important and often cause more day-to-day morbidity than the disease itself.

Long-term prednisolone at high doses causes a constellation of side effects:

System	Complication	Pathophysiology
Metabolic	Steroid-induced diabetes, weight gain, hyperlipidaemia	Glucocorticoids → hepatic gluconeogenesis ↑, peripheral insulin resistance ↑, lipogenesis ↑
Bone	Osteoporosis, avascular necrosis (especially femoral head)	Osteoblast suppression, osteoclast activation, calcium malabsorption, sex hormone suppression → rapid bone loss. AVN: multifactorial — fat embolism in intraosseous microcirculation.
Infection	Opportunistic infections (PJP, TB reactivation, fungal, viral)	Broad immunosuppression — impaired T-cell function, neutrophil migration, cytokine production
Muscle	Steroid myopathy	Type II fibre atrophy from catabolic protein effect. CK is NORMAL (no necrosis). The most important DDx during IIM management.
Eye	Posterior subcapsular cataracts, glaucoma	Cataracts: altered lens protein metabolism. Glaucoma: increased aqueous humour production and reduced outflow.
Skin	Thin skin, easy bruising, poor wound healing, striae	Collagen and extracellular matrix breakdown from chronic glucocorticoid exposure.
Adrenal	Adrenal suppression	Exogenous steroids suppress ACTH → adrenal cortex atrophies. Abrupt cessation → adrenal crisis (hypotension, shock). Must taper gradually.
Psychiatric	Mood disturbance, insomnia, psychosis	Direct CNS effects of glucocorticoids on hippocampal and limbic neurotransmission.
GI	Peptic ulcer disease	Glucocorticoids reduce prostaglandin-mediated gastric mucosal protection. Consider PPI co-prescription.

Drug	Key Complications	Monitoring
Azathioprine	Myelosuppression (especially if TPMT-deficient), hepatotoxicity, infections, lymphoma risk (long-term)	FBC fortnightly for first 2 months, then monthly. LFTs. Check TPMT before starting.
Methotrexate	Hepatotoxicity (fibrosis/cirrhosis), myelosuppression, pneumonitis (drug-induced ILD!), mucositis, teratogenicity	FBC, LFTs every 4–8 weeks. CXR if new respiratory symptoms. Contraception mandatory.
MMF	GI upset (diarrhoea), myelosuppression, teratogenicity, infections (especially CMV)	FBC, LFTs. Pregnancy test before starting.
Cyclophosphamide	Haemorrhagic cystitis (acrolein metabolite → bladder urothelial toxicity), gonadal toxicity (infertility), bladder carcinoma (long-term), myelosuppression, infections	Co-administer MESNA (2-mercaptoethane sulfonate — neutralises acrolein in bladder). Hydration. FBC. Fertility counselling.
Rituximab	Hypogammaglobulinaemia, hepatitis B reactivation, PML (JC virus), infusion reactions	Immunoglobulin levels, hepatitis B serology pre-treatment, JC virus monitoring.
Calcineurin inhibitors	Nephrotoxicity, hypertension, hyperglycaemia, neurotoxicity (tremor, headache)	Drug trough levels, renal function, blood pressure, glucose.
HCQ	Retinal toxicity (bull's eye maculopathy — irreversible)	Annual ophthalmology screening after 5 years of use. Dose < 5 mg/kg/day.

Steroid Myopathy — The Critical Iatrogenic Complication

This bears repeating because it is commonly tested: a patient on steroids for IIM who develops worsening weakness could have steroid myopathy (CK normal — reduce steroid) or disease flare (CK elevated — increase steroid/add immunosuppressant). Getting this wrong has opposite management implications. Always check CK.

Complication	Pathophysiology
Chronic poikiloderma	Long-standing DM skin disease → permanent skin atrophy, dyspigmentation, telangiectasia. Cosmetically distressing.
Skin ulceration	Particularly in anti-MDA5 DM. Vasculopathy-driven ischaemic ulceration over Gottron's papules, digital pulps, nailfolds. Can become infected.
Calcinosis cutis	As above — dystrophic calcification. Calcinosis and GI involvement in juvenile cases ^[1]. Can ulcerate, discharge chalky material, become secondarily infected. Very difficult to treat (surgical excision, diltiazem, colchicine, sodium thiosulfate — all have limited evidence).
Photoexacerbation	UV exposure worsens DM skin disease. Patients must use rigorous sun protection lifelong.

Because IIM frequently overlaps with other CTDs:

Complication	Context
Raynaud's phenomenon → digital ischaemia → ulceration/gangrene	Vasospasm + microangiopathy. Particularly in anti-synthetase syndrome and overlap with SSc.
Polyarthritis	Non-erosive, small joint. Polyarthritis ^[2]. Managed with NSAIDs, HCQ.
Sicca symptoms	Overlap with Sjögren's syndrome (anti-Ro/anti-La positive).
Scleroderma features	Anti-PM-Scl antibody → overlap PM/SSc. Skin thickening, oesophageal dysmotility, pulmonary fibrosis, pulmonary hypertension.

Juvenile DM has a distinct complication profile compared to adult IIM:

Complication	Details
Calcinosis	Childhood form may have calcification — scarring and calcinosis ^[4]. More common and more severe than in adults. Can be extensive, debilitating, and functionally limiting.
Muscle contractures	Muscle contractures (tip-toe gait) ^[4]. Chronic inflammation → fibrosis of gastrocnemius/soleus → fixed equinus deformity. Physiotherapy is critical to prevent this.
GI vasculopathy	GI involvement in juvenile cases ^[1]. Vasculitis of mesenteric vessels → intestinal ischaemia, ulceration, perforation, haemorrhage. Potentially life-threatening.
Lipodystrophy	Generalised or partial loss of subcutaneous fat. Mechanism unclear — possibly autoimmune destruction of adipocytes. Associated with insulin resistance, metabolic syndrome.
Growth retardation	From chronic disease + long-term steroid use → impaired linear growth.

Complication	Frequency	Severity / Impact	Key MSA Association
ILD	20–65%	Leading cause of death	Anti-Jo-1, anti-MDA5
Malignancy	6–45% (DM)	Major cause of mortality	Anti-TIF1-γ
Dysphagia / aspiration	30–40%	Risk of aspiration pneumonia, malnutrition	Late-stage disease
Cardiac	10–30% (subclinical)	HF, arrhythmia, sudden death	Non-specific
Calcinosis	Common in jDM, rare in adult	Chronic morbidity, functional limitation	Anti-NXP2
Muscle contractures	Chronic disease	Disability	Juvenile DM
Rhabdomyolysis / AKI	Severe acute disease	Life-threatening	Anti-SRP (IMNM)
Steroid myopathy	Very common on treatment	Diagnostic confusion, disability	Treatment-related
Infections (opportunistic)	Depends on treatment intensity	Sepsis, PJP, TB reactivation	Treatment-related
Osteoporosis / AVN	Long-term steroids	Fractures, disability	Treatment-related

High Yield Summary — Complications of IIM

Disease-related complications:

ILD (leading cause of death; anti-Jo-1, anti-MDA5): NSIP most common pattern, RP-ILD in anti-MDA5 is a medical emergency
Respiratory muscle weakness → Type 2 respiratory failure (different from ILD which causes Type 1)
Aspiration pneumonia from dysphagia/bulbar weakness
Cardiac: myocarditis, conduction defects, HF, arrhythmia
Oesophageal dysphagia → malnutrition, aspiration
GI vasculopathy (juvenile DM): ulceration, perforation
Malignancy: 5× in DM, 2× in PM; screen at diagnosis and for 3–5 years; NPC in HK
Calcinosis (juvenile DM > adult DM): dystrophic calcification, difficult to treat
Contractures (chronic/juvenile DM): fibrosis → fixed deformity
Rhabdomyolysis → AKI (severe acute disease)

Treatment-related complications:

Steroid myopathy (CK normal — reduce dose; DDx from disease flare where CK elevated)
Infections (opportunistic — PJP, TB, fungal)
Osteoporosis / AVN (long-term steroids)
Drug-specific: AZA myelosuppression (check TPMT), MTX pneumonitis (avoid if ILD), CYC haemorrhagic cystitis (use MESNA), rituximab HBV reactivation, HCQ retinal toxicity

Active Recall - Complications of IIM

References

^[1] Lecture slides: GC 056. Generalized muscle weakness.pdf (pages 27, 33) ^[2] Senior notes: Ryan Ho Rheumatology.pdf (pages 90–92) ^[3] Senior notes: Maksim Medicine Notes.pdf (pages 318–321) ^[4] Senior notes: Ryan Ho Neurology.pdf (pages 194–195) ^[8] Senior notes: Ryan Ho Respiratory.pdf (pages 121–124, 127)

High Yield Summary

Definition: Autoimmune diseases with inflammatory infiltration/necrosis of skeletal muscle → limb-girdle weakness ± extra-muscular manifestations.

Classification (5 main types): PM, DM, Overlap myositis, IBM, IMNM. Additional: CADM, CAM.

Epidemiology: Incidence ~5/100,000/year. F > M (2:1). Peak 40-50 years.

Aetiology: 1/3 malignancy (especially NPC in HK), 1/3 CTD, 1/3 idiopathic.

Pathophysiology:

DM = complement-mediated microangiopathy (B-cell/humoral) → perimysial/perivascular → perifascicular atrophy
PM = CD8+ T-cell mediated → endomysial infiltration → direct muscle fibre killing
IBM = T-cell + degenerative (rimmed vacuoles) → proximal + distal weakness → treatment-resistant
IMNM = antibody-mediated necrosis (anti-SRP/anti-HMGCR) → minimal inflammation

Clinical Features:

Symmetric proximal weakness (shoulder, hip, neck flexors), retained reflexes, no sensory loss
DM skin: heliotrope rash, Gottron's papules (pathognomonic), V sign, shawl sign, holster sign, mechanic's hands, calcinosis
Systemic: ILD (anti-synthetase, anti-MDA5), arthritis, Raynaud's, dysphagia, cardiac
IBM: older males, distal + proximal, treatment-resistant

MSA: Anti-Jo-1 (anti-synthetase syndrome), anti-MDA5 (rapidly progressive ILD), anti-TIF1-γ (malignancy), anti-SRP/anti-HMGCR (IMNM), anti-Mi-2 (classic DM, good prognosis)

Always screen for malignancy and ILD in every IIM patient.

High Yield Summary — Differential Diagnosis of IIM

Level 2 — Is the myopathy inflammatory? Rule out:

Endocrine: hypothyroidism (TFT), Cushing's/steroid myopathy (CK normal), hyperthyroidism
Drug-induced: statins (most common), steroids, alcohol, colchicine
Electrolyte: hypoK, hyperCa, hypophosphataemia
Infectious: viral myositis (self-limiting), pyomyositis (focal)
Hereditary: muscular dystrophy (family Hx, childhood onset), metabolic, mitochondrial
PMR (no true weakness, normal CK, responds to low-dose steroid)

Level 3 — Which IIM subtype? PM (diagnosis of exclusion), DM (skin rash), IBM (older male, distal weakness, treatment-resistant), IMNM (necrosis on biopsy, anti-SRP/HMGCR), OM (CTD features).

Key investigations to narrow DDx: CK, TFT, drug history, NCS/EMG, MSA panel, muscle biopsy.

High Yield Summary — Diagnosis of IIM

Diagnostic Criteria:

Bohan & Peter (1975): 5 criteria — PM needs all 4 of (weakness + biopsy + CK + EMG); DM needs any 3 of those 4 + skin rash
Practical rule: Myositis = 2 out of 3 of ↑CK, EMG abnormalities, positive muscle biopsy
2017 EULAR/ACR: Probability-based scoring system; includes anti-Jo-1 as only antibody; heliotrope and Gottron's score highest

Key Investigations:

CK: Most important blood test. Usually > 10× ULN. Also monitors disease activity. ~5% may be normal.
EMG: Myopathic triad — fibrillation at rest, polyphasic short-duration MUPs, complex repetitive discharges. Rules out neuropathy.
Muscle biopsy: Gold standard. Endomysial (PM) vs perimysial + perifascicular atrophy (DM) vs rimmed vacuoles (IBM) vs necrosis (IMNM). Site: weak but not atrophied muscle, contralateral to EMG.
MSA panel: Defines subtype and prognosis. Anti-Jo-1 (synthetase syndrome/ILD), anti-MDA5 (aggressive ILD), anti-TIF1-γ (malignancy), anti-SRP/HMGCR (IMNM).
ILD screen: HRCT (GGO, NSIP pattern), PFT (↓FVC, ↓DLCO) — do on ALL patients.
Malignancy screen: Comprehensive — ENT (NPC in HK!), Gynae, GI, imaging. Repeat for 3 years.

High Yield Summary — Management of IIM

Principles: Suppress inflammation (steroids), spare steroids (immunosuppressants), treat each organ, screen/treat malignancy, supportive care.

Induction: Prednisolone 1 mg/kg/day. IV methylprednisolone pulses for severe disease. Maintain until disease controlled, then slow taper guided by CK.

Steroid-sparing (start early):

First-line: Azathioprine (check TPMT), Methotrexate (AVOID if ILD), MMF
Second-line: Cyclophosphamide (severe ILD/refractory), calcineurin inhibitors (tacrolimus)
HCQ: skin disease ONLY

Refractory: IVIg (especially DM, dysphagia), Rituximab (B-cell depletion), plasmapheresis (acute bridge).

Subtype-specific:

Anti-Mi-2: Good prognosis, responds well to steroids
Anti-MDA5 RP-ILD: Triple therapy (steroids + tacrolimus + CYC) upfront — medical emergency
Anti-SRP IMNM: Aggressive combination (steroids + IVIg + rituximab)
IBM: Does NOT respond to immunosuppression → supportive only
CAM: Treat the cancer — myositis may resolve

Monitoring: CK (activity), muscle strength (function), PFT/HRCT (ILD), FBC/LFT/RFT (drug toxicity), malignancy screen (annually × 3–5 years), DEXA (steroids), ophthalmology (HCQ).

Steroid myopathy vs. flare: Check CK — normal = steroid myopathy (reduce dose); elevated = flare (increase dose).

High Yield Summary — Complications of IIM

Disease-related complications:

ILD (leading cause of death; anti-Jo-1, anti-MDA5): NSIP most common pattern, RP-ILD in anti-MDA5 is a medical emergency
Respiratory muscle weakness → Type 2 respiratory failure (different from ILD which causes Type 1)
Aspiration pneumonia from dysphagia/bulbar weakness
Cardiac: myocarditis, conduction defects, HF, arrhythmia
Oesophageal dysphagia → malnutrition, aspiration
GI vasculopathy (juvenile DM): ulceration, perforation
Malignancy: 5× in DM, 2× in PM; screen at diagnosis and for 3–5 years; NPC in HK
Calcinosis (juvenile DM > adult DM): dystrophic calcification, difficult to treat
Contractures (chronic/juvenile DM): fibrosis → fixed deformity
Rhabdomyolysis → AKI (severe acute disease)

Treatment-related complications:

Steroid myopathy (CK normal — reduce dose; DDx from disease flare where CK elevated)
Infections (opportunistic — PJP, TB, fungal)
Osteoporosis / AVN (long-term steroids)
Drug-specific: AZA myelosuppression (check TPMT), MTX pneumonitis (avoid if ILD), CYC haemorrhagic cystitis (use MESNA), rituximab HBV reactivation, HCQ retinal toxicity

Idiopathic Inflammatory Myopathies

1. Definition

2. Epidemiology

3. Anatomy and Function: Skeletal Muscle Basics

3.1 Structural Organisation

3.2 Proximal vs. Distal Muscles

3.3 Bulbar Muscles

4. Aetiology and Associations

4.1 The "Rule of Thirds" (Traditional Teaching) [3]

4.2 Malignancy Association (Cancer-Associated Myositis, CAM)

4.3 Connective Tissue Disease Association (Overlap Myositis)

4.4 Drug-Induced Myositis

4.5 Infection-Related

5. Pathophysiology

5.1 Dermatomyositis (DM) — Complement-Mediated Microangiopathy (Humoral/B-cell)

5.2 Polymyositis (PM) — T-cell Mediated

5.3 Inclusion Body Myositis (IBM) — Degenerative + Inflammatory

5.4 Immune-Mediated Necrotizing Myopathy (IMNM) / Necrotizing Autoimmune Myopathy (NAM)

5.5 Summary Table of Pathophysiology

6. Classification

6.1 Traditional Classification — Bohan and Peter (1975) [1][3]

6.2 Dalakas (1991) [1]

6.3 Troyanov (2005) [1]

6.4 ENMC (2003) [1]

6.5 Modern Classification (Currently Used) [1][3]

6.6 Myositis-Specific Antibodies (MSA) — The Modern Serological Classification

7. Clinical Features

7.1 Symptoms

A. Muscle Symptoms

B. Cutaneous Symptoms (Dermatomyositis)

C. Extra-Muscular/Systemic Symptoms

7.2 Signs

A. Musculoskeletal Signs

B. Cutaneous Signs (Dermatomyositis)

C. Systemic Signs

7.3 Special Subtypes — Clinical Feature Highlights

Inclusion Body Myositis (IBM)

Immune-Mediated Necrotizing Myopathy (IMNM)

Clinically Amyopathic Dermatomyositis (CADM)

7.4 Comparison: Polymyositis vs. Dermatomyositis

8. Myositis-Specific vs. Myositis-Associated Antibodies

9. General Approach to a Patient with Suspected IIM

Active Recall - Idiopathic Inflammatory Myopathies (Definition to Clinical Features)

References

Framing the Differential

Level 1: Localising the Lesion — Is This a Myopathy?

Level 2: It IS a Myopathy — But Is It Inflammatory?

A. Endocrine Myopathies

B. Drug-Induced Myopathy [3][4]

C. Electrolyte Imbalances [3][4]

D. Infectious Myositis [4]

E. Hereditary Myopathies [3][4]

F. Other Acquired Myopathies

Level 3: Distinguishing Within IIM Subtypes

Specific Mimics to Highlight

Polymyalgia Rheumatica (PMR) vs. IIM

SLE Myopathy vs. IIM

Systemic Sclerosis with Myopathy vs. IIM

Hypothyroid Myopathy vs. IIM

The Diagnostic Decision Algorithm — Putting It All Together

Summary Table: Key Differentiating Features

Active Recall - Differential Diagnosis of IIM

1. Diagnostic Criteria

1.1 Bohan and Peter Criteria (1975)

1.2 Practical "2 out of 3" Rule

1.3 2017 EULAR/ACR Classification Criteria for IIM (IMCCP)

1.4 Anti-Synthetase Syndrome Diagnostic Criteria

2. Investigation Modalities — Detailed

2.1 Bloods — General

2.2 Muscle Enzymes

2.3 Autoantibodies

2.4 Electromyography (EMG)

2.5 Nerve Conduction Studies (NCS)

2.6 Muscle Biopsy

2.7 MRI (Magnetic Resonance Imaging)

2.8 Pulmonary Investigations (ILD Screening)

2.9 Malignancy Screening

2.10 Other Investigations

3. Diagnostic Algorithm

4. Putting It All Together — The GC Tutorial Case