Dermatomyositis is an idiopathic inflammatory myopathy characterized by progressive proximal muscle weakness and distinctive skin manifestations, including a heliotrope rash and Gottron papules.

Exam domain	One-glance essentials
Definition / diagnosis	*Dermatomyositis = inflammatory myopathy with characteristic skin disease* ^[1] Complement-mediated microangiopathy of muscle/skin capillaries causes perifascicular atrophy ^[1]^[2]
Epidemiology / risks	Bimodal onset (juvenile and 40–60 years), female predominance ^[2] Adult DM has important malignancy association; NPC is a key Hong Kong screen, with anti-TIF1γ/anti-NXP2 highest risk ^[1]^[3]
Core mechanism	B-cell/complement activation → C5b-9 on capillary endothelium → capillary dropout → perifascicular ischaemia ^[1]^[2] This vascular mechanism explains both proximal myopathy and photodistributed skin disease
Clinical picture	Symmetric proximal weakness with preserved sensation/reflexes; dysphagia/dysphonia indicates severe bulbar disease ^[1]^[2] *Heliotrope rash and Gottron papules*; V/shawl/holster signs, nailfold changes and mechanic hands may occur ^[1] CADM has skin disease without weakness for ≥6 months
Investigations	CK/aldolase, myopathic EMG and MRI-STIR; biopsy shows perifascicular atrophy + perivascular/perimysial inflammation ^[2] Antibodies direct action: MDA5 → urgent ILD screen; TIF1γ/NXP2 → cancer screen; Jo-1 → antisynthetase/ILD ^[2]^[3]
Management	Prednisolone ~1 mg/kg/day (IV pulse if severe) + early MTX/AZA/MMF steroid-sparing therapy ^[2] Anti-MDA5 RP-ILD requires urgent multidrug induction; refractory DM may need IVIG/rituximab ^[2] Photoprotection and topical therapy for skin; treat associated cancer
Complications	Aspiration pneumonia, ILD and myocarditis/arrhythmia are major fatal complications ^[2] Anti-MDA5 → rapidly progressive ILD; JDM → calcinosis, GI vasculopathy and contractures ^[2]
Prevention / follow-up	Baseline/serial PFT-HRCT, ECG/echo and swallowing assessment; ongoing age-appropriate cancer surveillance including NPC ^[2]^[3] Vaccinate and screen HBV/TB before immunosuppression; protect bone and prevent PJP when indicated
Exam traps	DM rash involves nasolabial folds/knuckles; SLE malar rash spares nasolabial folds and affects skin between joints ^[1] CADM can have normal CK yet fatal ILD ^[2] Weakness on steroids: normal CK suggests steroid myopathy; rising CK/active rash suggests relapse

References

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (Dermatomyositis) ^[2] Senior notes: Ryan Ho Neurology.pdf (Inflammatory Myopathies, pp. 194–195); Maksim Medicine Notes.pdf (Rheumatology, pp. 318–320) ^[3] Senior notes: Block A - Dermatology PBL 2.pdf (anti-TIF1γ/anti-NXP2 and malignancy)

Dermatomyositis

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) — the name itself tells you the condition:

"Dermato" (Greek: derma = skin) → skin involvement
"myo" (Greek: mys = muscle) → muscle involvement
"itis" (Greek: -itis = inflammation) → inflammatory process

"A member of the connective tissue disease family as evidenced by autoimmune disease associations and other immunologic features. Characterised by chronic inflammation of striated muscles (polymyositis) and sometimes the skin (dermatomyositis). Autoantibody associations (e.g. anti-Jo-1, anti-Mi-2) define homogeneous clinical subsets of disease." ^[1]

In practical terms, DM is a systemic autoimmune disease targeting skeletal muscle and skin, characterised by:

Symmetric proximal muscle weakness (myopathy)
Pathognomonic cutaneous manifestations (heliotrope rash, Gottron's papules)
Distinctive autoantibody profiles that predict clinical phenotype, organ involvement, and prognosis

An important variant to understand upfront:

Clinically amyopathic dermatomyositis (CADM): cutaneous manifestations of DM are present, but no clinically significant muscle weakness for ≥6 months ^[2]. This is NOT a benign entity — CADM with anti-MDA5 antibody carries extremely high risk of rapidly progressive interstitial lung disease (RP-ILD) with high mortality.

Key Conceptual Point

DM is fundamentally different from polymyositis (PM) at the pathological level. PM is a T-cell–mediated attack on muscle fibres themselves (endomysial infiltration), while DM is a B-cell/complement-mediated microangiopathy targeting intramuscular blood vessels (perimysial infiltration). This vascular mechanism explains the skin findings in DM — the skin vasculature is also targeted.

2. Epidemiology

Combined incidence of PM + DM: ~2 per 100,000/year in the general population ^[3]
Prevalence: 5–22 per 100,000 ^[3]
DM is rarer than PM overall, but DM is the more common inflammatory myopathy in children (juvenile DM)

Sex: Female > Male = 2:1 ^[3]
Age: Bimodal distribution
- Juvenile DM: peak at 5–15 years (most common inflammatory myopathy in children)
- Adult DM: peak at 40–60 years
Ethnicity: DM occurs worldwide; in Hong Kong, the association with nasopharyngeal carcinoma (NPC) as the paraneoplastic malignancy is particularly important ^[1]^[4]

Overall 5–10% mortality ^[5]
Mortality is driven by:
- Rapidly progressive ILD (especially anti-MDA5 CADM)
- Malignancy (cancer-associated myositis)
- Cardiac involvement (myocarditis, arrhythmia)
- Aspiration pneumonia (from dysphagia)
- Infection (from immunosuppressive therapy)

Category	Details
Genetic	HLA-DRB10301, HLA-B08 associations; familial clustering reported in monozygotic twins and first-degree relatives ^[6]
Environmental triggers	UV light exposure (photosensitive rash), viral infections (Coxsackievirus B, parvovirus B19, HTLV-1)
Drugs	Statins (HMG-CoA reductase inhibitors — can trigger immune-mediated necrotizing myopathy with anti-HMGCR antibodies; distinct from DM but in the differential), checkpoint inhibitors, hydroxyurea, penicillamine
Malignancy	Strong paraneoplastic association in adult DM — see below
Other autoimmune diseases	Overlap with other connective tissue diseases (SLE, scleroderma, Sjögren's, MCTD)

Hong Kong–Specific High Yield

In Hong Kong, nasopharyngeal carcinoma (NPC) is a key malignancy associated with dermatomyositis, reflecting the high local prevalence of EBV-driven NPC. Other common associated malignancies include carcinoma of the bronchus, breast, stomach, ovary, cervix, and prostate ^[1]^[4]. Always think of NPC when you see DM in a Hong Kong patient.

4. Anatomy and Function (Relevant Structures)

Understanding why DM causes proximal weakness requires knowing normal muscle anatomy:

Muscle fascicle = bundle of muscle fibres wrapped by perimysium (connective tissue sheath)
Muscle fibre (individual cell) is wrapped by endomysium
Blood vessels travel in the perimysium to supply the fascicle

In DM, the autoimmune attack is directed against the intramuscular vasculature within the perimysium → complement-mediated microangiopathy → perifascicular atrophy (fibres at the periphery of fascicles are ischaemic and atrophy first because they are farthest from the surviving central vessels). This is the pathological hallmark of DM.

Why proximal muscles? Proximal muscles (deltoid, hip flexors, quadriceps) have higher metabolic demand and are more susceptible to ischaemic injury from microangiopathy. Additionally, proximal muscles rely on type I (slow-twitch) fibres that are more vulnerable to inflammatory damage.

The cutaneous vasculature is similarly targeted by the complement-mediated microangiopathy → explains the characteristic photodistributed rash
Poikiloderma (telangiectasia + atrophy + dyspigmentation) reflects chronic vascular damage and epidermal thinning

Organ	Relevance
Lungs	Interstitial lung disease (ILD) — major cause of morbidity/mortality
Heart	Myocarditis, conduction defects
Oesophagus/Pharynx	Striated muscle of upper oesophagus/pharynx → dysphagia, aspiration risk
Joints	Non-erosive polyarthritis
GI tract	Vasculopathy (especially in juvenile DM) → ulceration, perforation

5. Etiology and Pathophysiology

1/3 malignancy (lung, breast, gastric, NPC), 1/3 autoimmune (connective tissue disease), 1/3 idiopathic ^[2]

This is a useful clinical heuristic — every patient with DM needs screening for malignancy and overlap CTD.

Immunopathogenesis of Dermatomyositis

DM and PM are fundamentally different diseases at the immunological level:

Trigger (unknown in most cases; possible viral, UV, or paraneoplastic antigen)
B-cell activation → production of autoantibodies (myositis-specific antibodies)
Complement activation via classical pathway
C5b-9 membrane attack complex (MAC) deposits on endomysial capillary endothelium
Capillary necrosis and dropout → reduced capillary density in muscle
Ischaemia of perifascicular muscle fibres → perifascicular atrophy (pathognomonic finding on biopsy)
Perimysial infiltration by B-cells, CD4+ T-helper cells, plasmacytoid dendritic cells, and macrophages
Type I interferon signature is upregulated (this is why anti-MDA5, an interferon-pathway protein, is such a key antibody)

DM: Perimysial infiltration, predominantly B-cell or complement-mediated microangiopathy ^[5]^[7]

PM: Endomysial infiltration, predominantly T-cell mediated ^[5]^[7]

Because DM is a vasculopathy — the complement-mediated attack targets blood vessels, and the skin has abundant vasculature. The dermal capillaries undergo similar MAC deposition → capillary damage → the characteristic rash. PM, being a direct T-cell attack on muscle fibres, does not affect skin vessels.

Tumour antigens may share molecular mimicry with muscle/endothelial antigens
The immune response against the tumour cross-reacts with muscle/skin
Probable association with malignancy in elderly population ^[1]
Associated malignancies in HK: carcinoma of the nasopharynx (HK), bronchus, breast, stomach, ovary, cervix, prostate ^[1]
Specific antibodies predict malignancy risk:
- Anti-TIF1-γ (p155/140): highest association with malignancy (~60–80% in adults) ^[8]
- Anti-NXP-2 (p140): also high association with malignancy ^[8]
- Anti-Mi-2: low malignancy risk (good prognosis)
- Anti-MDA5: associated with CADM + RP-ILD, not strongly associated with malignancy

High Yield Antibody–Phenotype Correlation

Antibody	Clinical Phenotype	Malignancy Risk	ILD Risk
Anti-Mi-2	Classic DM (good skin response to Tx)	Low	Low
Anti-TIF1-γ	Cancer-associated DM	Very High (~60–80%)	Low
Anti-NXP-2	Calcinosis, cancer-associated	High	Moderate
Anti-MDA5	CADM, mechanic's hands, ulcers	Low	Very High (RP-ILD)
Anti-Jo-1 (antisynthetase)	Antisynthetase syndrome	Moderate	High (86%)
Anti-SRP	Immune-mediated necrotizing myopathy	Low-Moderate	Low

6. Classification

Polymyositis (PM)
Dermatomyositis (DM)
Inclusion body myositis (IBM) — very rare in HK; proximal + distal weakness; rimmed vacuoles on biopsy; refractory to treatment
Cancer-associated myositis (CAM)
Myositis associated with other CTD (overlap myositis)

Clinically amyopathic dermatomyositis (CADM): cutaneous manifestations, but no muscle weakness for ≥6 months
Immune-mediated necrotizing myopathy (IMNM): associated with anti-SRP or anti-HMGCR (statin-associated); prominent necrosis with minimal inflammation on biopsy

Subtype	Key Feature
Childhood (juvenile) DM	More vasculopathy, calcinosis, GI vasculitis, muscle contractures, tip-toe gait; better prognosis overall but calcinosis is disabling ^[5]
Adult idiopathic DM	Classic presentation
DM associated with CTD	Overlap with SLE, SSc, Sjögren's, MCTD
Cancer-associated DM	Must screen all adults; especially if > 40 years, anti-TIF1-γ positive
Amyopathic DM (CADM)	Skin only, no weakness ≥6 months; beware anti-MDA5 + RP-ILD

Uses a probability-based scoring system
Variables include: age of onset, pattern of weakness, skin manifestations, anti-Jo-1 antibody, CK elevation, muscle biopsy features
Score ≥55% (without biopsy) or ≥90% (with biopsy) classifies as "probable" or "definite" IIM
Subclassified into PM, DM, ADM, juvenile DM, juvenile PM using a classification tree

7. Clinical Features

A. Symptoms (What the Patient Tells You)

Onset: occurs in > 90% PM and 50–60% DM at onset ^[3]

Mode: generally subacute/chronic progressive in PM vs acute severe in DM at onset ^[3]

Symptom	Pathophysiological Basis	Clinical Detail
Difficulty climbing stairs, rising from chair, squatting	Proximal hip girdle weakness (hip flexors, quadriceps) due to ischaemic perifascicular muscle damage	Early: inability to squat, climb stairs, getting up from chair, carrying heavy groceries ^[3]
Difficulty lifting arms overhead, combing hair	Proximal shoulder girdle weakness (deltoid, supraspinatus) from same mechanism	Patients may report inability to hang laundry or reach overhead shelves
Difficulty holding head up	Neck flexor weakness — suggests more advanced disease	Neck flexors are classically affected; neck extensors less so
Dysphagia	Involvement of striated muscle of the pharynx and upper oesophagus → impaired swallowing initiation	Late: dysphonia, dysphagia ^[3]; implies bulbar involvement → poor prognosis
Dysphonia (hoarse/nasal voice)	Laryngeal/pharyngeal muscle weakness	Often accompanies dysphagia
Myalgia / muscle tenderness	Inflammatory mediators (cytokines, complement) irritate pain-sensing nerve endings in muscle	Present in 25–50% — notably, many patients have painless weakness ^[3]

Clinical Pearl

A classic exam question distinguishes myopathy from neuropathy. In inflammatory myopathy:

Weakness is proximal > distal
Reflexes are preserved (until very late, severe wasting)
Sensation is intact
No fasciculations (fasciculations suggest LMN denervation, not myopathy)

If you see distal weakness + reduced reflexes + sensory loss → think neuropathy, not myopathy.

Symptom	Description
Facial rash	Patients notice a purplish discoloration around the eyes, sometimes mistaken for allergy or fatigue
Rash on hands	Red/purple bumps over knuckles
Photosensitivity	Rash worsened by sun exposure → photodistributed pattern ^[9]
Rash on neck/chest/back	V-neck and shawl distribution
Nail changes	Painful, ragged cuticles; visible dilated capillaries at nail fold
Itching	The rash of DM is often intensely pruritic — an underappreciated symptom that can be debilitating
Cracked, fissured hands	"Mechanic's hands" — especially in antisynthetase syndrome

Symptom	Pathophysiological Basis
Fatigue, malaise	Systemic inflammation (elevated IL-6, TNF-α, type I interferons)
Weight loss	Chronic inflammation + dysphagia reducing oral intake; also think malignancy
Fever	Inflammatory cytokines; also consider infection (immunosuppression) or malignancy
Arthralgia	Polyarthritis — non-erosive, symmetric, small joint involvement ^[1]
Dyspnoea, dry cough	Interstitial lung disease (ILD); lung fibrosis — association with anti-Jo1 antibody ^[1]
Raynaud's phenomenon	Vasospasm of digital arteries — seen in overlap with SSc or MCTD

B. Signs (What You Find on Examination)

Sign	Description	Pathophysiology
Heliotrope rash	Periorbital oedema with violaceous (heliotropic) discolouration of upper eyelids ^[2]^[3]^[5] — "heliotrope" refers to the purple-blue flower of the Heliotropium genus	Complement-mediated microangiopathy of periorbital dermal vasculature → capillary leak (oedema) + haemoglobin degradation products (violaceous hue)
Gottron's papules	Scaly purplish erythema / pink papules on dorsal surface of IP joints (MCP, PIP, DIP) and extensor surfaces ^[2]^[3]^[5] — pathognomonic for DM	Microangiopathy at extensor surfaces where skin is taut and subjected to mechanical stress; similar mechanism to heliotrope rash
Gottron's sign	Flat, violaceous erythema over extensor surfaces (elbows, knees, malleoli) — similar distribution to Gottron's papules but macular rather than papular	Same vascular mechanism; distinguished from papules by being flat
V sign	Poikilodermatous erythematous rash over anterior neck and upper chest in a V-shaped distribution ^[2]^[3]	Photodistributed — UV triggers/exacerbates the microangiopathy in sun-exposed skin
Shawl sign	Poikilodermatous rash over upper back, posterior shoulders, and posterior neck — resembling a shawl ^[2]^[3]	Photodistributed poikiloderma; same mechanism
Holster sign	Poikiloderma in lateral aspects of thighs ^[2]^[3]	Named because the distribution resembles where a gun holster sits; lateral thigh is often UV-exposed
Mechanic's hands	Hyperkeratosis and scaling with fissures on digits — resembles hands of a manual labourer ^[2]	Associated with antisynthetase syndrome (anti-Jo-1, anti-PL-7, anti-PL-12); reflects chronic dermal inflammation
Calcinosis cutis	Calcium deposits in skin and subcutaneous tissue	Common in juvenile DM ^[3]^[5]; dystrophic calcification from chronic tissue damage; can cause skin breakdown and functional impairment
Dilated nailfold capillaries	Visible dilated, tortuous capillary loops at the proximal nail fold; may see capillary dropout	Direct visualization of the microangiopathy — capillary dilatation is a compensatory response to capillary dropout
Periungual erythema and ragged cuticles	Red, inflamed cuticles with irregular edges	Same nailfold capillary microangiopathy
Photodistributed poikiloderma	Telangiectasia, epidermal atrophy with violaceous hue, hyper/hypopigmentation ^[3] in sun-exposed areas	Chronic vascular damage + melanocyte dysfunction from inflammation

Poikiloderma = hypo/hyperpigmentation + telangiectasias + skin atrophy ^[2]

DM vs Lupus Rash — Exam Favourite

Both DM and SLE can cause a facial erythema. Key distinguishing features:

DM: Involves the nasolabial folds and eyelids (heliotrope rash); Gottron's papules affect dorsal IP joints
SLE (malar rash): Spares the nasolabial folds; does NOT cause Gottron's papules

Also: Gottron's papules (DM) affect the dorsal surface of joints (extensor surfaces), while lupus causes erythema on the skin between joints (metacarpal phalanges), sparing the knuckles. This is a classic clinical distinction.

DM Rash vs Psoriasis at IP Joints

Both Gottron's papules (DM) and psoriasis can cause scaly erythematous lesions on extensor surfaces. However, psoriasis plaques are typically silvery-white, well-demarcated, and much thicker, whereas Gottron's papules are violaceous/pink, flatter, and associated with periungual changes and proximal weakness.

Sign	Description	Pathophysiology
Symmetric proximal weakness	Distribution: classically symmetric proximal — commonly shoulder (deltoid), pelvic girdles (hip flexor), neck (neck flexor) ^[3]	Ischaemic perifascicular atrophy from complement-mediated capillary damage
Preserved deep tendon reflexes	Retained reflexes ^[5]^[7] — unlike neuropathy where reflexes are reduced	The reflex arc is intact — the sensory nerve, spinal cord synapse, and motor nerve are all normal; the problem is the muscle itself
No sensory loss	Normal sensation throughout	Myopathy does NOT affect sensory neurons
Muscle tenderness	Present in 25–50% of cases	Inflammatory mediators in muscle tissue activate nociceptors
Muscle wasting	Late finding; generally only in severe, long-standing cases ^[3]	Chronic ischaemia and inflammation → fibrosis and fatty replacement of muscle
Muscle contractures (tip-toe gait)	Childhood form may have calcification, muscle contractures ^[5]	Fibrosis of gastrocnemius/soleus → fixed equinus contracture → child walks on tiptoes
Gower's sign	Child uses hands to "climb up" their own legs to stand from sitting	Non-specific sign of proximal (hip girdle) weakness; also seen in Duchenne muscular dystrophy

Sign	Pathophysiology
Fine bibasal inspiratory crackles	ILD — fibrotic change in lung parenchyma causes "Velcro-like" crackles
Reduced chest expansion	Restrictive pattern from ILD and/or respiratory muscle weakness
Tachypnoea	Compensatory for reduced lung volumes

Lung fibrosis — association with anti-Jo1 antibody ^[1] ↑risk of ILD in anti-synthetase and anti-MDA5 (very aggressive ILD) ^[5]^[7]

Sign	Pathophysiology
Non-erosive polyarthritis	Polyarthritis ^[1] — symmetric, small joints; synovial inflammation without bony erosion
Raynaud's phenomenon	Digital vasospasm — associated with overlap CTD
Cardiac findings (rare)	Myocarditis → tachycardia, heart failure signs; conduction defects → irregular pulse
Subcutaneous calcinosis	Dystrophic calcification; palpable hard nodules

DM associated with ovarian cancer ^[8] Adult form is associated with malignancy in 60% ^[5] (Note: this figure from the paediatrics notes likely refers to cancer-associated DM subset specifically; overall adult DM-malignancy association is ~15–30%, with much higher rates in anti-TIF1-γ positive patients)

Red Flag	Implication
Age > 40 at DM onset	Higher malignancy risk
Anti-TIF1-γ or anti-NXP-2 positive	Strong malignancy association ^[8]
Refractory to immunosuppressive therapy	May indicate underlying malignancy driving the immune response
Unexplained weight loss, lymphadenopathy	Systemic malignancy signs
Abnormal screening tests (FOBT, Pap, mammogram)	Direct evidence of neoplasm

Feature	Juvenile DM	Adult DM
Vasculopathy	More prominent — GI vasculitis (ulceration, perforation, haemorrhage)	Less prominent GI involvement
Calcinosis	Very common — can be disabling, affecting function	Less common
Muscle contractures	Tip-toe gait from gastrocnemius contracture ^[5]	Rare
Malignancy risk	Very low	Significant (~15–30%, higher with anti-TIF1-γ)
Lipodystrophy	Can occur — loss of subcutaneous fat	Rare
Prognosis	Generally better with treatment; calcinosis is main long-term morbidity	Depends on malignancy and ILD

Feature	Polymyositis	Dermatomyositis
Pathology	Endomysial infiltration; predominantly T-cell mediated	Perimysial infiltration; predominantly B-cell or complement-mediated microangiopathy
Course	Subacute/chronic onset, progressive	More severe and acute onset
Muscle weakness	Proximal, symmetric; may be asymmetric initially; ± distal spread	Similar to PM
Skin	None	Heliotrope rash, Gottron's papules, poikiloderma (V sign, shawl sign, holster sign), calcinosis, mechanic's hands, nailfold changes
Malignancy	Lower association	Strong association, especially in adults
Biopsy	CD8+ T-cell endomysial infiltrate; no perifascicular atrophy	Perifascicular atrophy; complement MAC on capillaries; perimysial B-cell/CD4+ infiltrate

[Adapted from 5, 7]

8. Special Considerations

A distinct clinical syndrome defined by anti-aminoacyl-tRNA synthetase antibodies (most commonly anti-Jo-1, also anti-PL-7, anti-PL-12, anti-EJ, anti-OJ). The classic pentad:

Myositis (often mild)
ILD (present in up to 86% with anti-Jo-1) ^[5]^[7]
Mechanic's hands
Non-erosive arthritis
Raynaud's phenomenon
Fever

Anti-MDA5 = very aggressive ILD ^[5]^[7]
Often presents as CADM (minimal or no muscle disease)
Characteristic skin features: skin ulceration (especially over Gottron's papules and digital pulps), palmar papules, mechanic's hands
Rapidly progressive ILD can be fatal within weeks-months despite aggressive immunosuppression
MDA5 = melanoma differentiation-associated gene 5, a cytoplasmic RNA helicase involved in innate antiviral immunity — its upregulation in DM points to the type I interferon pathway being central to pathogenesis

Exam-Critical Antibody Alert

Anti-TIF1-γ dermatomyositis → high association with malignancy ^[8] Anti-NXP-2 also high association with malignancy ^[8] Anti-MDA5 → rapidly progressive ILD, often amyopathic ^[5]^[7] Anti-Jo-1 → ILD (86%), antisynthetase syndrome ^[5]^[7]

These antibody–phenotype links are extremely high yield for exams.

High Yield Summary

Definition: DM is an autoimmune inflammatory myopathy with characteristic skin involvement, driven by complement-mediated microangiopathy (B-cell/complement) targeting intramuscular and cutaneous vasculature → perifascicular atrophy on biopsy.
Epidemiology: F:M = 2:1, bimodal (juvenile 5–15y, adult 40–60y), incidence ~2/100k/year.
Aetiology rule of thirds: 1/3 malignancy, 1/3 autoimmune/CTD overlap, 1/3 idiopathic.
Key HK malignancy: Nasopharyngeal carcinoma (NPC), plus lung, breast, gastric, ovarian, cervical, prostate.
Pathophysiology: B-cell/complement → MAC on capillary endothelium → capillary dropout → perifascicular atrophy (muscle) + poikiloderma/heliotrope/Gottron's (skin). PM is different: CD8+ T-cell → endomysial attack.
Skin findings (usually precede weakness): Heliotrope rash, Gottron's papules (pathognomonic), V sign, shawl sign, holster sign, mechanic's hands, calcinosis cutis, nailfold capillary changes.
Muscle findings: Symmetric proximal weakness (shoulder/hip girdle, neck flexors), retained reflexes, no sensory loss; dysphagia/dysphonia = poor prognostic sign.
Key antibodies: Anti-Mi-2 (classic DM, good prognosis), anti-TIF1-γ (malignancy), anti-NXP-2 (malignancy + calcinosis), anti-MDA5 (CADM + RP-ILD), anti-Jo-1 (antisynthetase syndrome + ILD), anti-SRP (necrotizing myopathy).
CADM: Skin features without weakness ≥6 months; anti-MDA5 variant carries highest mortality from RP-ILD.
Juvenile DM: More calcinosis, GI vasculitis, contractures (tip-toe gait); very low malignancy risk.

Active Recall - Dermatomyositis (Definition to Clinical Features)

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (Dermatomyositis slides, pp.41–46) ^[2] Senior notes: Maksim Medicine Notes.pdf (Rheumatology, p.318–320) ^[3] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.5, p.90) ^[4] Lecture slides: GC 053. Fingers turn white and blue.pdf (Malignancy associations, p.46) ^[5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.146) ^[6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p.706) ^[7] Senior notes: Ryan Ho Neurology.pdf (p.195) ^[8] Senior notes: Block A - Dermatology PBL 2.pdf (pp.6–7) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p.414)

Differential Diagnosis of Dermatomyositis

When a patient presents with features suggestive of dermatomyositis — proximal muscle weakness, characteristic rash, or both — you need to systematically work through two overlapping diagnostic questions:

Is this really an inflammatory myopathy, or is the weakness from something else? (i.e., differential diagnosis of myopathy broadly)
If it IS an inflammatory myopathy, which subtype is it? (i.e., DM vs PM vs IBM vs IMNM vs overlap myositis)
If the rash is the dominant feature, could this be another dermatological or autoimmune condition mimicking DM skin findings?

The clinical approach therefore branches at two levels: the myopathy differential and the skin rash differential, converging on the diagnosis of DM when both are present with the right pattern.

Differential Diagnosis of Myopathy: Infective (viral — HIV, CMV, EBV; pyomyositis), Neoplastic (paraneoplastic), Inflammatory (RA, Sjögren's), Congenital (muscular dystrophy), Autoimmune (dermatomyositis, necrotising autoimmune myositis), Trauma/toxin (crush injuries/seizures causing rhabdomyolysis, glucocorticoids, colchicine, statins), Endocrine (hypothyroidism, Cushing's syndrome, hypokalemia) ^[10]

This is best organised using a mnemonic and aetiological approach. The paediatric notes provide a comprehensive table ^[6]:

Category	Differential Diagnoses	Key Distinguishing Features from DM
Infectious	Viral myositis (Influenza A/B, Parainfluenza, Adenovirus, EBV, CMV, HIV) ^[6]^[10]; Bacterial pyomyositis; Parasitic (toxoplasmosis, trichinosis)	Usually acute onset with preceding viral prodrome; self-limiting (days–weeks); associated fever, lymphadenopathy; CK mildly elevated; NO characteristic DM rash
Other inflammatory myopathies	Polymyositis, Inclusion body myositis, Immune-mediated necrotizing myopathy (IMNM), Overlap myositis ^[2]^[6]	See Section C below for detailed differentiation
Congenital / Hereditary	Duchenne muscular dystrophy (DMD), Becker MD (BMD), Facioscapulohumeral MD, Limb-girdle MD ^[6]	Onset in childhood (DMD by age 5); family history; progressive course without remission; specific genetic mutations; NO rash; CK markedly elevated in dystrophinopathies
Endocrine	Cushing's syndrome, Hyperthyroidism, Hypothyroidism ^[6]^[10]	Proximal weakness but accompanied by other endocrine stigmata (moon face/striae in Cushing's; tremor/tachycardia/weight loss in hyperthyroidism; bradycardia/cold intolerance in hypothyroidism); CK usually normal or mildly elevated; NO rash
Electrolyte disturbance	Hypokalemia, Hypocalcemia, Hypophosphatemia, Hypo/hypernatremia ^[6]	Acute onset often in context of diuretic use, renal failure, or critical illness; corrects with electrolyte replacement; NO rash; check serum electrolytes
Drug-induced	Corticosteroids (proximal), Statins (HMG-CoA reductase inhibitors) ^[6]^[10], colchicine, hydroxychloroquine, zidovudine, checkpoint inhibitors	Temporal relationship with drug initiation; resolves on drug cessation (steroid myopathy is painless and has NORMAL CK; statin myopathy has elevated CK); statins can also trigger true IMNM with anti-HMGCR antibodies
Metabolic	Glycogen storage diseases (McArdle's, Pompe's), lipid storage myopathies, mitochondrial myopathies	Typically onset in childhood; exercise intolerance; second-wind phenomenon (McArdle's); lactic acidosis (mitochondrial); specific enzyme deficiencies on biopsy
Channelopathy	Myotonic dystrophy, Periodic paralysis (thyrotoxic, hypokalemic, hyperkalemic) ^[6]	Myotonia (delayed relaxation) is pathognomonic for myotonic dystrophy — NOT seen in DM; periodic paralysis has episodic weakness, not progressive
Neuromuscular junction	Myasthenia gravis (MG)	Fatigable weakness (worsens with repeated use, improves with rest) — DM weakness is constant; ptosis and diplopia prominent in MG; anti-AChR/anti-MuSK antibodies; NO rash; normal CK
Motor neuron disease	Amyotrophic lateral sclerosis (ALS)	Mixed UMN + LMN signs (fasciculations, hyperreflexia, Babinski); NO rash; normal CK or mildly elevated; EMG shows denervation not myopathic changes
Neuropathy	Chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré syndrome (GBS)	Distal > proximal weakness (or ascending in GBS); areflexia; sensory loss; NCS shows demyelination; NO rash
Rhabdomyolysis	Crush injury, malignant hyperthermia ^[6]	Acute, severe; dark urine (myoglobinuria); massively elevated CK (often > 10,000); specific trigger (trauma, anaesthesia)

The Big Three Distinguishing Features of DM from Non-Inflammatory Myopathies

Characteristic skin rash (heliotrope, Gottron's papules, V/shawl/holster sign) — no other myopathy causes these
Inflammatory markers (elevated ESR/CRP) and autoantibodies (myositis-specific antibodies)
Muscle biopsy showing perifascicular atrophy with complement deposition — pathognomonic for DM

If a patient has proximal weakness + normal CK + no rash → think endocrine, steroid myopathy, or early IBM. If a patient has proximal weakness + elevated CK + no rash → think PM, IMNM, or muscular dystrophy. If a patient has proximal weakness + elevated CK + characteristic DM rash → DM until proven otherwise.

This is the critical step once you've established that the patient has an inflammatory myopathy. The GC interactive tutorial lists the subtypes explicitly:

Brief introduction on the subtypes of IIM — Dermatomyositis, Polymyositis, Anti-synthetase syndrome, Immune mediated necrotizing myopathy ^[11]

Feature	Dermatomyositis	Polymyositis	Inclusion Body Myositis (IBM)	IMNM	Antisynthetase Syndrome
Age/Sex	Bimodal (child + adult); F > M	Adult; F > M	> 50y; M > F	Any adult; F > M	Adult; F > M
Onset	Acute/subacute	Subacute/chronic	Insidious (months–years)	Subacute/acute	Acute with constitutional symptoms
Weakness pattern	Proximal, symmetric	Proximal, symmetric; may be asymmetric initially	Proximal + distal (quadriceps + finger flexors — unique!) ^[2]	Proximal, symmetric, severe	Proximal, symmetric
Skin	Yes — heliotrope, Gottron's, V/shawl/holster	No	No	No	Mechanic's hands, Raynaud's
CK	Elevated (5–50× ULN)	Elevated (5–50× ULN)	Normal or mildly elevated	Very elevated (often > 50× ULN)	Elevated
Key antibody	Anti-Mi-2, anti-TIF1-γ, anti-NXP-2, anti-MDA5	Anti-Jo-1, anti-SRP	Anti-cN1A (cytosolic 5'-nucleotidase 1A)	Anti-SRP, anti-HMGCR	Anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ
Biopsy	Perifascicular atrophy, perimysial B-cell/CD4+, complement MAC on capillaries	Endomysial CD8+ T-cell infiltrate invading muscle fibres	Rimmed vacuoles, endomysial CD8+ infiltrate, inclusion bodies	Necrotic fibres with minimal inflammation, macrophage predominant	Variable — may overlap PM or DM patterns
ILD risk	Moderate (higher with anti-Jo-1, anti-MDA5)	Moderate (anti-Jo-1)	Very low	Low	Very high (up to 86% with anti-Jo-1)
Malignancy risk	High (5× risk) ^[7]^[5]	Moderate (2× risk) ^[7]^[5]	Low	Moderate (anti-HMGCR)	Low
Treatment response	Good (except anti-MDA5 RP-ILD)	Good	Poor — refractory to immunosuppression ^[2]	Variable; anti-HMGCR responds to IVIg	Good

IBM — The Great Mimicker in Elderly Men

IBM is the most commonly misdiagnosed inflammatory myopathy because:

It is often initially labelled as "treatment-resistant PM"
Clues: elderly male, insidious onset, distal involvement (finger flexors — can't grip), quadriceps wasting (falls and difficulty with stairs), poor response to steroids, rimmed vacuoles on biopsy
IBM is very rare in HK ^[2] but must be considered in treatment-refractory "PM"

When the rash is the presenting feature (especially in amyopathic DM / CADM), you need to differentiate from:

Condition	Mimicked DM Feature	How to Distinguish
Systemic lupus erythematosus (SLE)	Facial erythema can resemble DM facial rash	SLE malar rash SPARES the nasolabial folds; DM facial rash INVOLVES nasolabial folds and eyelids ^[12]; SLE does NOT cause Gottron's papules; SLE has anti-dsDNA, anti-Sm; DM has myositis-specific antibodies
Contact dermatitis / Eczema	Hand dermatitis can mimic mechanic's hands	Contact dermatitis is pruritic, vesicular, follows allergen distribution; mechanic's hands have fissuring of lateral/palmar fingers specifically and are associated with systemic features
Psoriasis	Scaly erythema on extensor surfaces can mimic Gottron's	Psoriasis plaques are silvery-white, thicker, well-demarcated; Gottron's papules are violaceous/pink and thinner; psoriasis has nail pitting, not nailfold capillary changes
Seborrhoeic dermatitis	Facial erythema	Involves scalp, nasolabial folds, eyebrows — greasy yellowish scale; no periorbital violaceous hue; no proximal weakness
Allergic/periorbital dermatitis	Periorbital oedema	Usually bilateral, itchy, acute; no violaceous hue; no muscle weakness; resolves with allergen avoidance
Systemic sclerosis (SSc)	Raynaud's, skin tightening, nailfold capillary changes	SSc has skin THICKENING (sclerodactyly); DM has skin ATROPHY (poikiloderma) ^[12]; SSc has GERD, anti-Scl-70 or anti-centromere
Drug eruption / Photosensitivity	Photodistributed rash	Drug history crucial; no Gottron's papules; no weakness; resolves on drug withdrawal
Cutaneous T-cell lymphoma (mycosis fungoides)	Poikilodermatous patches	Very slow progression; patches → plaques → tumours; biopsy shows atypical T-cell epidermotropism, not interface dermatitis

Patients with dermatomyositis have characteristic skin findings including Gottron's papules, heliotrope eruption and photodistributed poikiloderma — these distinguish DM from SLE and other CTDs presenting with joint pain and rash ^[12]

DM-related dysphagia occurs because the striated muscle of the pharynx and upper oesophagus is affected by the same inflammatory process. This produces oropharyngeal dysphagia (difficulty initiating a swallow, nasal regurgitation, cough/aspiration during swallowing).

The differential for oropharyngeal dysphagia includes ^[13]:

Neurological: Stroke, brainstem tumour, Parkinson's disease, ALS, multiple sclerosis
Neuromuscular junction: Myasthenia gravis
Other myopathies: Myotonic dystrophy, polymyositis ^[13]
Structural: Oropharyngeal tumours, Zenker's diverticulum

Why this matters: Bulbar muscle involvement has poor prognosis ^[4] — it indicates severe disease and raises the risk of aspiration pneumonia.

The GC lecture slides and interactive tutorial emphasise several differential considerations that are high-yield for the in-house exam:

Connective tissue disease patients often present with multi-system complaints ^[11]

Conditions that are associated with Raynaud's phenomenon — Raynaud's can be seen in DM (especially overlap syndromes) but is more characteristic of SSc, MCTD, and SLE ^[11]

Potential association between cancer and dermatomyositis and the rationale of cancer screening ^[11] — when you diagnose DM, the differential must always include paraneoplastic DM driven by an occult malignancy. This is not just "another diagnosis" — it is a subtype of DM itself.

Probable association with malignancy in elderly population — Carcinoma of the nasopharynx (HK), bronchus, breast, stomach, ovary, cervix, prostate ^[1]

Must-Screen Malignancies in DM — Hong Kong Context

Every adult patient diagnosed with DM must undergo a systematic malignancy screen:

CBC, LFT, urinalysis (haematuria → renal/bladder)
CXR (lung mass)
FOBT (GI malignancy)
Pap smear (cervical cancer)
Mammography (breast cancer)
Testicular examination (testicular cancer)
Colonoscopy (colorectal cancer)
NPC screen: EBV DNA / nasopharyngoscopy (particularly in HK)
Consider PET-CT if high suspicion (anti-TIF1-γ positive, refractory disease, elderly)

Feature	Myopathy (including DM)	Neuropathy
Distribution	Proximal > distal	Distal > proximal (glove-and-stocking)
Reflexes	Preserved (retained reflexes) ^[5]^[7]	Reduced or absent
Sensation	Normal	Impaired (numbness, tingling)
Fasciculations	Absent	Present (LMN neuropathy)
Wasting	Late, proximal	Early, distal
CK	Elevated	Normal (unless secondary denervation)
EMG	Myopathic: low amplitude, short duration, polyphasic motor unit potentials; spontaneous fibrillation	Neuropathic: high amplitude, long duration; fibrillation/positive sharp waves in denervation
NCS	Normal	Abnormal (reduced velocities in demyelinating; reduced amplitudes in axonal)

High Yield Summary — Differential Diagnosis of Dermatomyositis

Two-level differential: First distinguish inflammatory myopathy from non-inflammatory causes of proximal weakness (endocrine, drug-induced, hereditary, NMJ, neuropathy, MND); then distinguish DM from other IIM subtypes (PM, IBM, IMNM, antisynthetase syndrome).
Characteristic DM rash is the key discriminator: Heliotrope rash and Gottron's papules are not seen in any other myopathy. If both weakness + rash are present, DM is the diagnosis.
DM vs SLE: DM involves nasolabial folds, SLE spares them. DM has Gottron's on knuckles, lupus affects skin between joints. Both are photosensitive.
DM vs PM: DM = skin + muscle, B-cell/complement, perifascicular atrophy. PM = muscle only, CD8+ T-cell, endomysial infiltration.
DM vs IBM: IBM is insidious, affects distal (finger flexors) + proximal (quads), elderly male, refractory to treatment, rimmed vacuoles on biopsy.
Myopathy vs neuropathy: Myopathy = proximal weakness, preserved reflexes, no sensory loss, elevated CK, myopathic EMG. Neuropathy = distal weakness, reduced reflexes, sensory loss, normal CK, neuropathic EMG/NCS.
Always screen for malignancy: 5× risk in DM. In HK, think NPC. Anti-TIF1-γ and anti-NXP-2 carry highest malignancy risk.
Drug-induced myopathy: Steroids cause painless proximal weakness with NORMAL CK. Statins cause myalgia ± elevated CK; can trigger true IMNM (anti-HMGCR).

Active Recall - Differential Diagnosis of Dermatomyositis

References

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (pp.41–46) ^[2] Senior notes: Maksim Medicine Notes.pdf (Rheumatology, p.318–320) ^[4] Lecture slides: GC 053. Fingers turn white and blue.pdf (Malignancy associations, p.46) ^[5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.145–146) ^[6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p.706) ^[7] Senior notes: Ryan Ho Neurology.pdf (p.194–195) ^[8] Senior notes: Block A - Dermatology PBL 2.pdf (pp.6–7) ^[10] Lecture slides: Neurology- Two cases of lower limb weakness.pdf (pp.38–39) ^[11] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p.1) ^[12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.1718–1720) ^[13] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.324–326)

Diagnostic Criteria, Algorithm and Investigations for Dermatomyositis

A. Diagnostic Criteria

There are two major criteria systems you need to know — the older Bohan and Peter criteria (1975) that is still widely referenced in teaching, and the newer 2017 EULAR/ACR classification criteria that is increasingly used in clinical practice and research.

Bohan and Peter criteria (1975): PM requires all of 1–4, DM requires any 3 in 1–4 + criterion 5 ^[2]

Criterion	Description	Why This Is Included
1. Symmetrical weakness of limb-girdle muscles and anterior neck flexors	Clinical hallmark; assessed on history and physical examination	This is the defining functional deficit — proximal muscle groups are preferentially affected by the complement-mediated microangiopathy (DM) or CD8+ T-cell infiltration (PM)
2. Muscle biopsy: typical of myositis	Histological confirmation of inflammatory infiltrate ± perifascicular atrophy	Biopsy is the gold standard; DM shows perimysial B-cell/complement changes with perifascicular atrophy, PM shows endomysial CD8+ T-cell invasion
3. Muscle enzyme elevation (esp. CK)	Serum creatine kinase is the most sensitive muscle enzyme	CK leaks from damaged/necrotic muscle fibres into the bloodstream — degree of elevation correlates roughly with disease activity
4. EMG: typical of myositis	Spontaneous fibrillation; polyphasic low-amplitude motor unit potential ^[2]	EMG distinguishes myopathic from neuropathic processes and confirms active muscle membrane instability
5. Cutaneous manifestations of DM	e.g. heliotrope rash, Gottron's papules ^[2]	The skin findings are what distinguish DM from PM; pathognomonic features make clinical diagnosis possible

Interpretation:

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
Definite PM = all 4 of criteria 1–4 (no skin findings)

Exam Shortcut

The senior notes provide an even more concise rule: Dx: 2 out of 3 of ↑CK, EMG abnormalities and +ve muscle biopsy ^[5]^[7] — this is a simplified practical approach. For DM, add characteristic skin findings to clinch the diagnosis. This simplified "2 out of 3" rule is commonly tested.

2017 EULAR/ACR classification criteria for IIM: include age of onset, antibodies (only anti-Jo1 now), different scoring with / without muscle biopsy ^[2]

This is a probability-based scoring system rather than a simple checklist. Key points:

Variable	Points (without biopsy)	Points (with biopsy)
Age of onset ≥ 18y	1.3	1.5
Age of onset ≥ 40y	2.1	2.2
Muscle weakness
— Objective symmetric weakness of proximal UL	0.7	0.7
— Objective symmetric weakness of proximal LL	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 positive	3.9	2.7
Elevated CK / LDH / AST / ALT	1.3	1.4
Muscle biopsy features (if done)	N/A	Variable

Interpretation:

Score ≥ 55% probability (without biopsy) or ≥ 90% (with biopsy) → classified as probable/definite IIM
Once classified as IIM, a classification tree further subclassifies into DM, PM, ADM (amyopathic DM), juvenile DM, or juvenile PM based on skin findings and age

Why the 2017 criteria are better than Bohan and Peter:

They are validated with sensitivity 87% / specificity 82% (without biopsy) and 93% / 88% (with biopsy)
They incorporate anti-Jo-1 as a criterion — reflecting the importance of autoantibodies
They allow classification without biopsy — important because many patients, especially children, do not undergo biopsy
They explicitly address amyopathic DM — which Bohan and Peter could not classify

High Yield for Exams

The Bohan and Peter criteria are more commonly tested in MCQ/SAQ because they are simpler to recall. The 2017 EULAR/ACR criteria are more relevant clinically but are harder to memorise in full. Know both — but for quick recall in exams, fall back on Bohan and Peter + the "2 out of 3" simplified rule.

Since antisynthetase syndrome is a major clinical subset of IIM that overlaps heavily with DM, its diagnostic criteria are worth knowing:

Diagnostic criteria: Presence of anti-synthetase antibodies (Jo-1, PL7, PL12, EJ, OJ) + 2 major / 1 major 1 minor ^[2]

Major criteria: ILD, DM, PM ^[2]^[12]

Minor criteria ("ARM"): Arthritis, Raynaud's phenomenon, Mechanic's hands ^[2]^[12]

The approach to diagnosing DM follows a logical sequence: clinical suspicion → biochemical confirmation → autoantibody profiling → electrophysiology → imaging → biopsy (if needed) → malignancy screening.

Investigations of interstitial lung disease and the rationale of cancer screening are explicitly listed as learning objectives ^[11]

C. Investigation Modalities — Detailed Breakdown

Investigation	Expected Findings in DM	Interpretation / Why
CBC	Usually normal; may show anaemia of chronic disease or leucocytosis	Anaemia can also result from GI vasculopathy bleeding (juvenile DM) ^[6]; leucocytosis may indicate infection or steroid use
ESR / CRP	↑↑ ^[5]^[7]	Non-specific markers of systemic inflammation; elevated due to circulating cytokines (IL-6, TNF-α). Note: ESR/CRP do NOT correlate well with disease activity and are NOT useful for monitoring ^[6]
LFT (AST, ALT)	May be elevated	Pitfall: AST and ALT are present in skeletal muscle, not just liver. In DM, elevated "transaminases" may be entirely from muscle damage, not hepatitis. Always check CK simultaneously — if CK is markedly elevated, the AST/ALT is likely of muscle origin
RFT	Usually normal unless myoglobin-induced AKI	Rhabdomyolysis from severe muscle necrosis can cause myoglobinuria → AKI
TFT	To exclude thyroid myopathy	TFT (r/o thyroid myopathy) ^[5]^[7] — both hypothyroidism and hyperthyroidism cause proximal myopathy; this must be excluded

Elevation of serum muscle enzymes, most notably creatine kinase ^[4]

Enzyme	Specificity for Muscle	Typical Elevation in DM	Notes
Creatine Kinase (CK)	Most specific for skeletal muscle (CK-MM isoform)	Markedly elevated with CK > 10× ULN ^[5]^[7]; range 5–50× ULN	Most sensitive and specific single marker; correlates with disease activity; used for monitoring treatment response
LDH	Present in many tissues	Mildly–moderately elevated	Less specific; useful as adjunct
AST	Muscle + liver	Elevated	See LFT pitfall above
ALT	Primarily liver but also in muscle	May be elevated	Less reliable for muscle damage monitoring
Aldolase	Muscle + liver	Elevated	Useful in patients with normal CK but clinical suspicion of myositis (rare) ^[6]

CK Interpretation Nuances

CK can be NORMAL in: amyopathic DM (CADM), burnt-out disease with fibrosis/atrophy, early disease, IBM (often mildly elevated only), steroid myopathy
CK is NOT specific for DM: also elevated in other myopathies, rhabdomyolysis, MI (CK-MB), hypothyroidism, strenuous exercise, intramuscular injections, and in individuals of African descent at baseline
Serial CK measurements are used to monitor treatment response — a falling CK suggests response to immunosuppression

Diagnostic role of the various autoantibodies in autoimmune rheumatic disease ^[11]

The significance of a positive anti-nuclear antibodies test ^[11]

ANA (anti-nuclear antibodies):

Present in up to > 80% of patients with JDM and JPM ^[6]
ANA is sensitive but NOT specific — positive in many autoimmune conditions (SLE, SSc, Sjögren's, drug-induced lupus, healthy individuals)
A positive ANA raises clinical suspicion for CTD but does NOT confirm DM; must proceed to specific antibodies

Myositis-Specific Antibodies (MSAs):

Autoantibodies: Anti-Mi2, anti-NXP2, anti-TIF1, anti-Jo1 (associated with interstitial lung disease) ^[10]

MSA	Target Antigen	Clinical Association	Exam Significance
Anti-Jo-1	Histidyl-tRNA synthetase	Antisynthetase syndrome; ILD (up to 86%); mechanic's hands; Raynaud's; arthritis; fever ^[1]^[2]^[5]^[7]	Anti-Jo1 antibodies is included in the diagnostic criteria in EULAR/ACR classification (2017) ^[6]; most common antisynthetase antibody (~20–30% of IIM)
Anti-Mi-2	Nuclear helicase	Classic DM with prominent skin findings; relatively acute onset; good response to therapy	Low malignancy risk; best prognosis among DM subtypes
Anti-TIF1-γ (p155/140)	Transcription intermediary factor 1-gamma	Cancer-associated DM; highest malignancy risk (~60–80% in adults) ^[8]	Must trigger intensive malignancy screening
Anti-NXP-2 (p140)	Nuclear matrix protein 2	Also high association with malignancy ^[8]; calcinosis (especially in juveniles)	Confers a higher risk of malignancy in patients with dermatomyositis and polymyositis ^[6]
Anti-MDA5	Melanoma differentiation-associated gene 5	CADM + rapidly progressive ILD ^[5]^[7]; skin ulceration, palmar papules, oral ulcers	Low malignancy risk but highest mortality from RP-ILD
Anti-SRP	Signal recognition particle	Severe necrotizing myopathy (IMNM); minimal inflammation on biopsy; aggressive, refractory disease	Typically classified as IMNM, not DM
Anti-HMGCR	HMG-CoA reductase	Statin-associated IMNM	Not a DM antibody — indicates IMNM

Myositis-Associated Antibodies (MAAs):

Anti-Ro (SSA), anti-La (SSB), anti-Sm, anti-RNP ^[5]^[7]
Found in overlap between DM and other CTDs (SLE, Sjögren's, MCTD)
Not specific for myositis but indicate CTD association
Anti-PM/Scl: identifies a small, distinct subgroup of myopathies with a protracted disease course often complicated by pulmonary interstitial fibrosis and/or cardiac involvement ^[6]

Antibody → Action Pairs (High Yield)

If You Find...	You Must Do...
Anti-TIF1-γ or Anti-NXP-2	Intensive malignancy screen including PET-CT
Anti-MDA5	Urgent HRCT chest + PFTs for RP-ILD; may need ICU-level monitoring
Anti-Jo-1 or other antisynthetase	ILD screening (HRCT + PFTs); assess for antisynthetase syndrome features
Anti-SRP or Anti-HMGCR	Reclassify as IMNM, not DM; check statin history for anti-HMGCR

Electromyography: myopathic pattern ^[10]

EMG is an electrodiagnostic study that records the electrical activity of muscle at rest and during contraction. It serves two purposes in DM:

Confirms myopathic process (distinguishes from neuropathy)
Guides biopsy site selection (biopsy the contralateral side of the EMG-tested muscle to avoid needle artefact)

Classic EMG findings in inflammatory myopathy (the "triad"):

Short, polyphasic, small motor unit potentials; Insertional irritability, spontaneous fibrillations, positive sharp waves; High-frequency repetitive discharges ^[6]

EMG Finding	What It Means	Why It Occurs
Spontaneous fibrillation and positive sharp waves	Muscle fibre membrane is irritable and firing spontaneously at rest	Inflammation/necrosis destabilises the sarcolemmal membrane; denervated or necrotic fibres fire independently
Low-amplitude, short-duration, polyphasic motor unit potentials (MUPs)	Each motor unit recruits fewer functional muscle fibres	Many fibres within each motor unit are damaged/destroyed → the remaining fibres generate a smaller, shorter, more complex electrical signal
Increased insertional activity	Needle insertion triggers excessive electrical discharge	Hyperexcitable membranes from inflammation
Complex repetitive discharges	Rhythmic, machine-like repetitive potentials	Ephaptic (direct electrical) transmission between adjacent hyperexcitable fibres

Key distinction from neuropathic EMG:

Neuropathy: high-amplitude, long-duration MUPs (surviving motor neurons re-innervate orphaned fibres → larger motor units)
Myopathy: low-amplitude, short-duration MUPs (motor unit is intact but fewer fibres respond)

Nerve conduction study (NCS): typically normal unless severe muscle necrosis and atrophy are present ^[6] — this is because NCS tests the nerve, which is unaffected in myopathy

EMG Is Supportive, Not Definitive

EMG findings are suggestive of inflammatory myopathy but not specific to DM or PM ^[12]. EMG cannot distinguish DM from PM from IMNM — it can only confirm a myopathic process. The specific IIM subtype requires autoantibody profiling and/or muscle biopsy.

Muscle biopsy ^[10] — the definitive investigation for histological confirmation

Practical points:

Open or closed-needle biopsy should be taken from muscle that is weak but not atrophied ^[12] — atrophied muscle may show only end-stage fibrosis, losing diagnostic information
Usual targets are quadriceps and deltoid ^[12]
Biopsy should be taken from the contralateral side to EMG testing (needle EMG can cause artefactual inflammation)
MRI can guide biopsy to areas of active inflammation (STIR hyperintensity)

Histopathological findings specific to DM:

Finding	Description	Significance
Perifascicular atrophy	Atrophy of muscle fibres at the periphery of fascicles, typically 2–4 layers deep	Pathognomonic for DM; reflects ischaemia from complement-mediated capillary dropout — peripheral fibres are furthest from surviving central vasculature
Perimysial and perivascular B-cell/CD4+ T-cell infiltrate	Inflammatory cells concentrated around blood vessels and in perimysium, NOT within fascicles	Reflects the humoral/complement-mediated microangiopathy targeting vasculature
Complement C5b-9 MAC deposition on capillary endothelium	Immunohistochemistry shows complement membrane attack complex on intramuscular capillaries	Signs of vasculopathy or immune complex deposition ^[12]; directly demonstrates the complement-mediated pathomechanism
Capillary dropout	Reduced capillary density on immunostaining	Consequence of complement-mediated capillary necrosis
Muscle fibre necrosis, degeneration and regeneration	Non-specific finding shared with PM and IMNM	Common histopathological features of DM and PM ^[12]

Comparison with PM biopsy:

Feature	DM	PM
Infiltrate location	Perifascicular and perivascular ^[12]	Within the fascicle, invading individual muscle fibres ^[12]
Predominant cells	B lymphocytes and plasmacytoid dendritic cells ^[12]	Cytotoxic CD8+ T lymphocytes ^[12]
Perifascicular atrophy	Present (pathognomonic)	Absent
Vasculopathy / immune complex	Yes ^[12]	No ^[12]

When Is Biopsy NOT Needed?

In clinical practice, biopsy may be deferred if:

Classic DM skin findings (heliotrope + Gottron's) + proximal weakness + elevated CK + positive MSA → clinical diagnosis is secure
Muscle biopsy is NOT commonly performed in children ^[6] — JDM is usually diagnosed clinically + supported by MRI

Biopsy is essential when:

Diagnosis is uncertain (atypical features, possible IBM, possible IMNM)
Treatment-refractory disease (need to re-evaluate histology)
Medicolegal/insurance requirements

4 mm punch biopsy is obtained for histological examination under light microscopy with H&E staining ^[12]

Finding	Description
Mild atrophy of epidermis with vacuolar changes in the basal keratinocyte layer ^[12]	Interface dermatitis — lymphocytes attack the dermoepidermal junction
Perivascular lymphocytic infiltrate in the dermis ^[12]	Reflects the same microangiopathic process seen in muscle vasculature
Mucin deposition in the dermis	Distinguishes DM from lupus dermatitis (both can show interface dermatitis, but mucin deposition is more prominent in DM)

MRI: muscle inflammation / necrosis ^[10]

T2W MRI scan (either full body or the thigh and shoulder muscles) ^[6]

Sequence	Findings	Significance
T2-weighted / STIR	Increased signal in affected muscles (appears bright/white)	Detects muscle oedema from active inflammation — the STIR sequence suppresses fat signal, making inflammatory oedema stand out
T1-weighted	Fatty replacement (chronic), muscle atrophy	Indicates chronic damage — irreversible fibrosis and fatty infiltration
Post-gadolinium T1	Enhancement in actively inflamed areas	Active inflammation with increased vascular permeability

Why MRI is valuable:

Detects areas of muscle inflammation and edema with active myositis, fibrosis and calcification ^[12]
Assesses large areas of muscle and thus avoids problems with sampling error in muscle biopsy ^[12] — biopsy samples only a tiny piece of muscle; MRI can survey the entire body to find the most affected area
Guides biopsy site selection to areas of active inflammation (STIR-bright) rather than chronic fibrosis (which would be non-diagnostic)
Can monitor treatment response non-invasively

Investigations of interstitial lung disease ^[11]

Every DM patient needs ILD assessment because ILD is a major driver of morbidity and mortality:

Investigation	Findings in DM-ILD	Interpretation
CXR	Bibasal reticular opacities, reduced lung volumes	Should be performed in all patients with findings suggestive of DM or PM to detect presence of interstitial lung disease ^[12]; screening tool — low sensitivity for early ILD
HRCT chest	Ground-glass opacities (active inflammation), reticular pattern (fibrosis), traction bronchiectasis, honeycombing (end-stage)	Most sensitive imaging for ILD; pattern often NSIP (bibasal GGO sparing subpleural) or organising pneumonia
Pulmonary function tests (PFTs)	Restrictive pattern: ↓FVC, ↓TLC, preserved or ↑FEV1/FVC ratio; ↓DLCO	DLCO is often the earliest abnormality — it decreases before volumes drop because the alveolar-capillary membrane is damaged (reduced gas transfer) even before lung volumes shrink
6-minute walk test	Desaturation with exercise	Functional assessment of gas exchange capacity

Anti-MDA5 + ILD = Emergency

If anti-MDA5 is positive, pursue urgent HRCT regardless of respiratory symptoms. RP-ILD can progress from mild GGO to respiratory failure within weeks. Serial PFTs and HRCT monitoring are essential. Some centres monitor ferritin (markedly elevated in anti-MDA5 RP-ILD) as a surrogate activity marker.

Investigation	Purpose
ECG	Screen for conduction defects, arrhythmias (AV block, bundle branch block)
Echocardiography	Assess for myocarditis (reduced EF, wall motion abnormalities), pericardial effusion
Cardiac MRI	If clinical suspicion of myocarditis — detects oedema and late gadolinium enhancement
Troponin	May be elevated in myocarditis; but note CK-MB can be elevated from skeletal muscle alone

Investigation	Findings
Barium swallow / videofluoroscopic swallowing study (VFSS)	Pharyngeal muscle dysfunction, aspiration, nasal regurgitation
Manometry	Reduced upper oesophageal sphincter pressure, reduced pharyngeal contraction amplitude

Why this matters: dysphagia in DM reflects involvement of pharyngeal/upper oesophageal striated muscle and is a poor prognostic sign indicating severe disease.

Potential association between cancer and dermatomyositis and the rationale of cancer screening ^[11]

Malignancy screen: tumour markers, PET-CT, ENT review ^[10]

Investigation	Target Malignancy
CBC + blood film	Haematological malignancy
LFT	Hepatic metastases
Urinalysis	Renal/bladder cancer (haematuria)
CXR	Lung cancer
FOBT / Colonoscopy	GI malignancy (colorectal, gastric)
Mammography	Breast cancer
Pap smear	Cervical cancer
Testicular examination	Testicular cancer
NPC screen: EBV DNA / nasopharyngoscopy / ENT review	NPC (HK) ^[10]^[5]
CT abdomen/pelvis	Ovarian, pancreatic, bladder cancer
PET-CT	Whole-body screen for occult malignancy; especially if anti-TIF1-γ/anti-NXP-2 positive ^[10]
Tumour markers (CEA, CA-125, CA 19-9, AFP, PSA)	Adjunctive — low sensitivity/specificity but may support suspicion

When and How Often to Screen for Malignancy

Screen at initial diagnosis and repeat annually for at least 3–5 years (malignancy can present before, with, or after DM onset — can be diagnosed before, with or after diagnosis of inflammatory myopathy ^[5]^[7])
Higher intensity screening if: age > 40, male, anti-TIF1-γ or anti-NXP-2 positive, refractory to treatment, new or unexplained symptoms
In HK: always include NPC screening given the high local prevalence of EBV-driven NPC

The diagnostic workup for DM can be summarised in a systematic stepwise approach:

Step	Investigation	Purpose
1. Baseline bloods	CBC, ESR/CRP, L/RFT, TFT	Exclude mimics (thyroid, electrolytes); assess inflammation
2. Muscle enzymes	CK, LDH, AST, ALT, Aldolase	Confirm muscle damage; CK most specific
3. Autoantibodies	ANA, then MSAs (anti-Mi-2, anti-TIF1-γ, anti-NXP-2, anti-MDA5, anti-Jo-1), MAAs	Subtype classification; predict organ involvement and prognosis
4. EMG	Myopathic vs neuropathic pattern	Confirm myopathic process; guide biopsy site
5. MRI muscles	STIR / T2W for active inflammation	Guide biopsy; monitor response; non-invasive
6. Muscle biopsy	Histological confirmation	Gold standard; perifascicular atrophy = DM
7. Skin biopsy	If rash atypical or diagnosis uncertain	Interface dermatitis with perivascular infiltrate
8. ILD screen	CXR, HRCT, PFTs	Major complication; especially if anti-Jo-1 / anti-MDA5
9. Cardiac screen	ECG, Echo ± cardiac MRI	Myocarditis, arrhythmia
10. Swallowing	Barium swallow / VFSS	Aspiration risk assessment
11. Malignancy screen	Age/sex-appropriate + NPC screening	Cancer-associated DM in adults

High Yield Summary — Diagnosis of Dermatomyositis

Bohan and Peter criteria (1975): DM = any 3 of (weakness, biopsy, elevated CK, abnormal EMG) + characteristic skin findings. PM = all 4 without skin. Simplified: "2 out of 3 of ↑CK, EMG abnormalities, +ve biopsy."
2017 EULAR/ACR criteria: probability-based scoring; includes anti-Jo-1; allows classification without biopsy; better for amyopathic DM.
CK is the single most useful blood test: most sensitive/specific muscle enzyme; > 10× ULN typical; correlates with disease activity; used for monitoring. But can be NORMAL in CADM, burnt-out disease, steroid myopathy.
MSAs define clinical subsets: Anti-Mi-2 (classic DM, good prognosis), anti-TIF1-γ/anti-NXP-2 (cancer), anti-MDA5 (CADM + RP-ILD), anti-Jo-1 (antisynthetase + ILD).
EMG: myopathic pattern (low amplitude, short duration, polyphasic MUPs + fibrillation). Distinguishes myopathy from neuropathy but cannot distinguish DM from PM.
Muscle biopsy: perifascicular atrophy + complement MAC on capillaries + perimysial B-cell infiltrate = pathognomonic for DM. PM shows endomysial CD8+ invasion.
MRI muscles: STIR/T2W hyperintensity in active disease; guides biopsy; avoids sampling error.
Every DM patient needs: ILD screen (HRCT + PFTs), cardiac screen (ECG + Echo), swallowing assessment, and age-appropriate malignancy screen including NPC in HK.
Malignancy screen is ongoing: repeat annually for ≥3–5 years. Malignancy can precede, coincide with, or follow DM diagnosis.

Active Recall - Diagnostic Criteria, Algorithm and Investigations for DM

References

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (pp.41–46) ^[2] Senior notes: Maksim Medicine Notes.pdf (Rheumatology, p.318–320) ^[4] Lecture slides: GC 053. Fingers turn white and blue.pdf (clinical features, p.44) ^[5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.145–146) ^[6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (pp.706–709) ^[7] Senior notes: Ryan Ho Neurology.pdf (pp.194–195) ^[8] Senior notes: Block A - Dermatology PBL 2.pdf (pp.6–7) ^[10] Lecture slides: Neurology- Two cases of lower limb weakness.pdf (p.40) ^[11] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p.1) ^[12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp.1754–1762)

Management of Dermatomyositis

The management of DM rests on four pillars, and it is critical to understand why each is necessary:

Suppress the autoimmune inflammation → immunosuppressive therapy (the core of treatment)
Prevent and manage complications → ILD, malignancy, dysphagia/aspiration, cardiac involvement
Mitigate treatment side effects → steroids cause osteoporosis, DM, cataracts, infections, CVD risk
Rehabilitation and supportive care → physiotherapy, sun protection, patient education

The overarching strategy follows a pattern shared across many autoimmune diseases: Start high-dose steroid, then taper and give steroid-sparing agent ^[14]. The reason for this is that glucocorticoids work fast (within days–weeks) but have devastating long-term side effects, so you use them as a "bridge" while waiting for slower-acting steroid-sparing immunosuppressants (which take weeks–months to reach full efficacy) to take over.

C. Pharmacological Treatment — Detailed Breakdown

Systemic glucocorticoids: typically start prednisone 1 mg/kg/d ^[5]^[7]

Aspect	Detail
Drug	Oral prednisolone (or prednisone)
Dose	1 mg/kg/day (typically 40–60 mg/day for adults) ^[5]^[7]
Mechanism	Glucocorticoids suppress the immune system at multiple levels: (1) inhibit NF-κB → reduce pro-inflammatory cytokine transcription (IL-1, IL-6, TNF-α); (2) suppress B-cell antibody production; (3) reduce complement activation; (4) inhibit leukocyte migration into inflamed tissues. In DM specifically, this damps down the complement-mediated microangiopathy driving muscle and skin damage
Onset	Days to weeks — this is why steroids are the initial "bridge" therapy
Response monitoring	Clinical: improving muscle strength (quantified by manual muscle testing or functional tests such as ability to rise from chair). Biochemical: falling CK towards normal. Expect CK to start declining within 2–4 weeks
Tapering	Begin taper once CK normalises and strength improves (usually 4–8 weeks). Taper slowly — typically reduce by ~10 mg every 2–4 weeks, then by 2.5 mg once below 20 mg, aiming for ≤7.5 mg/day or off steroids by 6–12 months
IV pulse	IV methylprednisolone 0.5–1 g/day for 3 days — used for severe/fulminant disease (e.g., RP-ILD, severe dysphagia, respiratory failure) ^[14]

Why NOT stay on high-dose steroids long-term?

The side effects of chronic glucocorticoids are extensive and themselves cause morbidity that can rival the underlying disease:

Side Effect	Mechanism	Relevance to DM
Steroid myopathy	Type II (fast-twitch) muscle fibre atrophy from catabolic glucocorticoid effects	Critical pitfall: worsening weakness on steroids may be steroid myopathy, NOT disease flare. CK is NORMAL in steroid myopathy (no inflammation/necrosis). Reducing the steroid dose improves steroid myopathy
Osteoporosis	Inhibit osteoblast function, promote osteoclast activity, reduce calcium absorption	Osteoporosis prophylaxis essential ^[14] — calcium, vitamin D, bisphosphonates if indicated
Diabetes mellitus	Hepatic gluconeogenesis, peripheral insulin resistance	DM control must be monitored ^[14]; steroids can worsen glycaemic control in pre-existing diabetes or cause new-onset steroid-induced DM
Cushing's features	Exogenous hypercortisolism	Moon face, central obesity, striae, thin skin, easy bruising
Infection risk	Immunosuppression	Opportunistic infections (PJP, TB reactivation, fungal); consider PJP prophylaxis with cotrimoxazole if high-dose steroids for > 4 weeks
CVD risk	Hypertension, dyslipidaemia, diabetes, fluid retention	Steroid → increased CV risk ^[14]
Cataracts, glaucoma	Posterior subcapsular cataract from lens protein changes	Regular ophthalmological screening
AVN	Ischaemic necrosis of femoral head	Especially with high cumulative doses
Adrenal suppression	HPA axis suppression from exogenous steroids	Must taper gradually; do not stop abruptly

The Steroid Myopathy Trap

One of the most common clinical dilemmas in DM management: the patient is on high-dose steroids, weakness is not improving (or is worsening). Is it disease flare or steroid myopathy?

Disease flare: CK elevated, ESR/CRP elevated, active rash, MRI shows oedema
Steroid myopathy: CK normal, no active rash, MRI may show fatty atrophy but no oedema
Management is opposite: flare → increase steroids; steroid myopathy → reduce steroids

ii. Steroid-Sparing Immunosuppressants (Maintenance — Second Essential Component)

Steroid-sparing agents: methotrexate, azathioprine to allow tapering steroids ^[5]^[7]

These agents are started early (often simultaneously with steroids) because they take weeks to months to reach full therapeutic effect. The goal is to maintain remission while steroids are tapered off.

Aspect	Detail
Mechanism	MTX = "metho" + "trex" + "ate" → originally a folate antagonist. Inhibits dihydrofolate reductase → blocks purine and pyrimidine synthesis → suppresses rapidly dividing immune cells (T-cells, B-cells). At low doses used in autoimmune disease, the primary anti-inflammatory effect is via adenosine accumulation (inhibiting AICAR transformylase), which reduces neutrophil and macrophage activation
Dose	Typically 7.5–25 mg once weekly (oral or subcutaneous) — NOT daily (daily dosing causes fatal bone marrow suppression)
Onset	4–8 weeks
Monitoring	FBC (bone marrow suppression), LFT (hepatotoxicity), RFT (renal clearance affects drug levels)
Key side effects	Bone marrow suppression (pancytopenia), hepatotoxicity/fibrosis, pneumonitis (rare but important — must distinguish from DM-ILD!), teratogenicity, oral mucositis, nausea
Supplement	Folic acid 5 mg once weekly (given on a different day from MTX) — reduces side effects without diminishing efficacy
Contraindications	Pregnancy/breastfeeding (teratogenic — category X), significant renal impairment (reduced clearance → toxicity), active hepatitis, severe bone marrow suppression, active infection
Advantage for DM	First-line steroid-sparing agent for DM in many centres; good evidence for muscle disease

MTX Pneumonitis vs DM-ILD

MTX can cause drug-induced pneumonitis (acute onset dyspnoea, fever, dry cough, bilateral infiltrates on CXR). This mimics DM-associated ILD. Key differences: MTX pneumonitis usually develops within 1–2 years of starting MTX, is associated with acute onset and fever, and improves with MTX cessation + steroids. DM-ILD tends to have a more insidious onset and is associated with anti-Jo-1/anti-MDA5 positivity. Biopsy (if needed) shows hypersensitivity pneumonitis pattern in MTX pneumonitis.

Aspect	Detail
Mechanism	AZA is a prodrug → metabolised to 6-mercaptopurine (6-MP) → converted to 6-thioguanine nucleotides (6-TGN) → incorporated into DNA of dividing lymphocytes → apoptosis. This preferentially targets rapidly dividing immune cells
Dose	1–3 mg/kg/day orally
Onset	Slow — delayed onset 3 months ^[15]; this is why you cannot rely on AZA alone for induction
Monitoring	FBC (bone marrow suppression), LFT (hepatotoxicity)
Key side effects	Bone marrow suppression, allergy, hepatotoxicity, pancreatitis ^[15]

Critical pre-treatment pharmacogenomic testing:

Always measure TPMT and NUDT15 enzyme activity before starting azathioprine ^[15]

Enzyme	Role	Clinical Relevance
TPMT (thiopurine S-methyltransferase)	Converts active 6-MP into inactive 6-MMP ^[15]	Deficiency (1 in 300 homozygous) → all AZA shunted to active/toxic 6-TGN → severe bone marrow suppression
NUDT15	Prevents excessive accumulation of toxic 6-TGTP ^[15]	More common in HK population ^[15] — East Asian populations have higher rates of NUDT15 variants
Drug interactions	Xanthine oxidase (XO) inhibitors (allopurinol, febuxostat) block XO-mediated breakdown of 6-MP → accumulation → toxicity ^[15]	Must reduce AZA dose by 75% if co-prescribed with allopurinol; ideally avoid the combination

Aspect	Detail
Mechanism	MMF → mycophenolic acid → inhibits inosine monophosphate dehydrogenase (IMPDH) → blocks de novo purine synthesis. Lymphocytes uniquely depend on the de novo pathway (other cells can use the salvage pathway), so MMF is relatively lymphocyte-selective
Dose	1–3 g/day in divided doses
Advantage	Good for ILD component of DM (used as first-line for DM-ILD in many centres); fewer hepatotoxicity concerns than MTX
Side effects	GI upset (diarrhoea, nausea), bone marrow suppression, increased infection risk, teratogenic
Contraindications	Pregnancy (teratogenic), hypersensitivity

Aspect	Detail
Mechanism	Inhibit calcineurin → block NFAT (nuclear factor of activated T-cells) → suppress T-cell activation and IL-2 production. Tacrolimus binds FKBP12; cyclosporine binds cyclophilin — different binding proteins but same downstream target
Key indication in DM	Anti-MDA5 CADM with RP-ILD — increasingly used as first-line combination therapy (tacrolimus + steroids + cyclophosphamide); also used for refractory DM
Side effects	Nephrotoxicity (dose-dependent vasoconstriction of afferent arteriole → ↓GFR), hypertension, hyperglycaemia, tremor, hyperkalaemia, gingival hyperplasia (cyclosporine)
Monitoring	Drug trough levels, RFT, BP, glucose, K+

iii. Rescue / Refractory Disease Therapies

Other strategies: IVIg, plasmapheresis, rituximab, MMF, calcineurin inhibitor ^[7]

Aspect	Detail
Mechanism	Pooled human IgG from thousands of donors. Mechanism is multifactorial: (1) saturates FcRn receptors → accelerates catabolism of pathogenic autoantibodies; (2) blocks Fc receptors on macrophages → reduces antibody-dependent phagocytosis; (3) modulates complement activation; (4) provides anti-idiotypic antibodies that neutralise autoantibodies
Dose	2 g/kg over 2–5 days, repeated every 4 weeks
Indication	Refractory DM (especially skin-predominant or dysphagia); severe disease unresponsive to steroids + conventional agents; preferred when infection risk prohibits further immunosuppression
Evidence	The ProDERM trial (2022) demonstrated significant efficacy of IVIg in DM — IVIg has gained an FDA-approved indication for DM (Octagam 10%)
Side effects	Headache, fever, chills, nausea (infusion-related); rarely: aseptic meningitis, thromboembolic events (especially in elderly, immobilised patients), renal failure (sucrose-containing preparations), anaphylaxis (IgA-deficient patients receiving IgA-containing IVIg)
Contraindications	Complete IgA deficiency with anti-IgA antibodies (risk of anaphylaxis); caution in renal impairment, thrombotic risk

Aspect	Detail
Mechanism	Rituximab = "ri" (chimeric) + "tu" (tumour-directed) + "xi" (chimeric) + "mab" (monoclonal antibody). Targets CD20 on B-cell surface → B-cell depletion via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptosis. Since DM is a B-cell/complement-mediated disease, depleting B-cells is logically sound
Dose	1 g IV × 2 doses (Day 0 and Day 14); repeat cycle every 6 months if needed
Indication	Refractory DM/PM; increasingly used for anti-MDA5 RP-ILD; effective for DM-associated ILD
Side effects	Infusion reactions, increased infection risk (hypogammaglobulinaemia with repeated cycles), hepatitis B reactivation (MUST screen HBsAg and anti-HBc before starting), progressive multifocal leukoencephalopathy (PML — extremely rare), late-onset neutropenia
Monitoring	Immunoglobulin levels, B-cell counts, HBV serology

Aspect	Detail
Mechanism	Alkylating agent → cross-links DNA strands → prevents DNA replication → cytotoxic to rapidly dividing cells including lymphocytes. "Cyclo" (cyclic) + "phosph" (phosphorus-containing) + "amide" (nitrogen-containing). It is a prodrug activated by hepatic cytochrome P450
Dose	IV pulse cyclophosphamide (typically 0.5–1 g/m² every 2–4 weeks for 6 months) or oral daily (less commonly used now due to higher cumulative toxicity)
Indication	Severe, life-threatening DM: RP-ILD (especially anti-MDA5), severe systemic vasculitis, refractory disease
Side effects	Bone marrow suppression (nadir at 10–14 days), haemorrhagic cystitis (toxic metabolite acrolein damages bladder epithelium → prevent with MESNA [2-mercaptoethane sulfonate sodium] and aggressive hydration), gonadal toxicity (infertility — counsel and offer gamete preservation), increased malignancy risk (bladder cancer, haematological malignancies with cumulative dose > 36 g), infections, nausea
Monitoring	FBC before each pulse (ensure WCC recovery), urinalysis, cumulative dose tracking

Aspect	Detail
Mechanism	Physically removes circulating pathogenic autoantibodies, immune complexes, and complement components from the blood. In DM, this directly removes the anti-endothelial antibodies and complement driving the microangiopathy
Indication	Adjunctive in severe/refractory DM; useful for acute crises while waiting for immunosuppressants to take effect
Limitations	Temporary effect (antibodies are re-synthesised unless combined with immunosuppression); vascular access complications; infection risk; electrolyte disturbance

iv. Management of Specific Organ Involvement

Severity	Approach
Mild, stable ILD	Steroids + steroid-sparing agent (MMF or azathioprine preferred for ILD)
Moderate ILD	Higher-dose steroids + MMF or azathioprine; consider rituximab if refractory
RP-ILD (anti-MDA5)	EMERGENCY: IV methylprednisolone pulse + calcineurin inhibitor (tacrolimus) + cyclophosphamide ± IVIg/rituximab; consider plasmapheresis; may need ICU with mechanical ventilation. Some centres use JAK inhibitors (tofacitinib) as salvage therapy based on emerging evidence
End-stage fibrotic ILD	Lung transplantation referral; long-term oxygen therapy; antifibrotics (nintedanib) may be considered

Issue	Approach
Mild dysphagia	Speech and language therapy (SLT) assessment; modified diet texture; head-of-bed elevation
Severe dysphagia / aspiration risk	Nasogastric tube feeding or PEG; aggressive immunosuppression (dysphagia indicates severe disease); IVIg can be particularly effective for DM-related dysphagia

Dermatomyositis associated with ovarian cancer ^[8] — treat the cancer first; DM may remit with successful oncological treatment

Principle	Detail
Treat the underlying malignancy	Surgery, chemotherapy, radiotherapy as per tumour type; DM often improves or remits when tumour is treated
Immunosuppression for DM	Concurrent steroids ± steroid-sparing agents; but be cautious about aggressive immunosuppression in the setting of active malignancy (may worsen cancer outcomes)
Recurrence	DM relapse may herald cancer recurrence → repeat malignancy screen

Approach	Detail
Aggressive early immunosuppression	Best prevention — calcinosis is less common when inflammation is well-controlled early
Established calcinosis	Difficult to treat; options include diltiazem (calcium channel blocker — may reduce calcium deposition), colchicine (anti-inflammatory), surgical excision for functionally limiting deposits

Modality	Detail
Photoprotection	Essential — DM rash is photosensitive; broad-spectrum UVA/UVB sunscreen (SPF ≥ 50), protective clothing, sun avoidance during peak hours
Topical corticosteroids	Low-to-mid potency for face; mid-to-high potency for trunk/limbs; useful for localised skin disease
Topical calcineurin inhibitors	Tacrolimus 0.1% ointment or pimecrolimus cream — steroid-sparing for facial/periorbital rash; avoids skin atrophy from prolonged topical steroids
Hydroxychloroquine (HCQ)	Can help DM skin disease; however, some DM patients paradoxically develop drug rash from HCQ (more common than in SLE) — use with caution and monitor
Systemic therapy	For refractory skin disease: MTX, MMF, IVIg, rituximab

Hepatitis, Osteoporosis, DM [diabetes mellitus] — must be monitored and managed ^[14]

Side Effect	Prophylaxis / Monitoring
Osteoporosis	Calcium (1000–1200 mg/day) + Vitamin D (800–1000 IU/day); DEXA scan at baseline and annually; bisphosphonates, or more potent ones ^[14] if high fracture risk or established osteoporosis
Diabetes	Monitor fasting glucose / HbA1c regularly; lifestyle modification; hypoglycaemic agents if needed
Hepatitis B reactivation	Check HBV serology (HBsAg, anti-HBc, anti-HBs) before starting immunosuppression ^[14]; prophylactic antivirals (entecavir/tenofovir) if HBsAg+ or if anti-HBc+ and receiving rituximab or high-dose steroids
PJP prophylaxis	Cotrimoxazole (TMP-SMX) 480 mg daily or 960 mg 3×/week if prednisolone ≥ 20 mg/day for > 4 weeks
TB screening	CXR + IGRA (QuantiFERON) before immunosuppression; isoniazid prophylaxis if latent TB
Vaccination	Influenza (annual), pneumococcal; avoid live vaccines during immunosuppression
CVD risk	Steroid → increased CV risk ^[14]; monitor BP, lipids, glucose; lifestyle modification
Eye screening	Annual ophthalmology review for cataracts and glaucoma if on chronic steroids

Modality	Detail
Physiotherapy	Critical for functional recovery; gentle range-of-motion exercises during active disease (avoid vigorous exercise which may worsen inflammation); progressive strengthening once inflammation controlled; focus on proximal muscle groups
Occupational therapy	Adaptive devices for functional limitations (raised toilet seats, grab rails, dressing aids)
Speech and language therapy	For patients with dysphagia — swallowing exercises, diet modification, aspiration prevention strategies
Psychological support	Chronic autoimmune disease with visible skin changes, functional disability, and cancer anxiety → significant psychological burden; address depression, anxiety, body image
Patient education	Sun avoidance and photoprotection; medication compliance; recognising flare symptoms; importance of follow-up; fertility counselling (many immunosuppressants are teratogenic)

Parameter	Frequency	Purpose
Muscle strength	Every visit	Assess disease activity; standardised tools (MMT-8, CMAS for children)
CK	Every visit during active disease; less frequent in remission	Biochemical correlate of muscle damage; falling CK = response
FBC, LFT, RFT	Every 1–3 months	Monitor drug toxicity (bone marrow, liver, kidney)
Inflammatory markers	Every visit	ESR/CRP for general activity (though poor correlation in DM)
PFTs	Every 3–6 months if ILD present	Monitor ILD progression/response
HRCT chest	As clinically indicated; baseline at diagnosis	ILD assessment
Malignancy screen	At diagnosis; annually for ≥3–5 years	Cancer-associated DM surveillance
DEXA scan	Baseline; annually on chronic steroids	Osteoporosis monitoring
Eye check	Annual if on HCQ or chronic steroids	HCQ maculopathy, steroid cataracts

5–10% mortality ^[5]

Prognostic Factor	Good Prognosis	Poor Prognosis
Antibody	Anti-Mi-2	Anti-MDA5 (RP-ILD), Anti-SRP (refractory myositis)
Age	Juvenile DM (lower malignancy risk)	Older adult (higher malignancy risk)
Organ involvement	Skin + mild muscle only	Bulbar involvement (dysphagia), ILD, cardiac
Malignancy	Absent	Present — depends on tumour prognosis
Treatment response	Rapid CK normalisation, strength recovery	Refractory to steroids + steroid-sparing agents
Calcinosis	Absent	Extensive (functional disability, especially in JDM)

High Yield Summary — Management of Dermatomyositis

Induction: Prednisolone 1 mg/kg/day (or IV methylprednisolone pulse 0.5–1 g/day × 3 days for severe disease).
Steroid-sparing agents (started early, take weeks–months to work): First-line = methotrexate or azathioprine. MMF is preferred when ILD is present. Calcineurin inhibitors (tacrolimus) especially for anti-MDA5 RP-ILD.
Rescue therapies: IVIg (ProDERM trial — FDA-approved for DM), rituximab (B-cell depletion — logical given DM is B-cell/complement-mediated), cyclophosphamide (severe/life-threatening), plasmapheresis.
Before starting AZA: Check TPMT + NUDT15 (especially important in HK/East Asian population). Check for XO inhibitor co-prescription (allopurinol).
Before starting any immunosuppression: Screen for HBV (reactivation risk), TB (IGRA + CXR), baseline blood tests.
Steroid side effect prophylaxis: Ca + Vit D + bisphosphonates (osteoporosis), glucose monitoring (diabetes), PJP prophylaxis (cotrimoxazole), HBV prophylaxis, vaccination, CVD risk management.
Cancer-associated DM: Treat the underlying malignancy — DM may remit; DM relapse may signal cancer recurrence.
Anti-MDA5 RP-ILD: Medical emergency — triple therapy (high-dose steroids + calcineurin inhibitor + cyclophosphamide/rituximab ± IVIg); may need ICU.
Non-pharmacological: Physiotherapy (gentle during flare, progressive strengthening in remission), photoprotection, OT, SLT, psychological support.
Prognosis: Overall 5–10% mortality, driven by RP-ILD, malignancy, cardiac involvement, aspiration, and infection.

Active Recall - Management of Dermatomyositis

References

^[2] Senior notes: Maksim Medicine Notes.pdf (Rheumatology, p.318–320) ^[5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.145–146) ^[7] Senior notes: Ryan Ho Neurology.pdf (pp.194–195) ^[8] Senior notes: Block A - Dermatology PBL 2.pdf (pp.6–7) ^[14] Senior notes: Block A - Rheumatology Interactive Tutorial.pdf (p.2) ^[15] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p.45 — azathioprine pharmacogenomics)

Complications of Dermatomyositis

The complications of DM arise from three sources: (1) the disease itself (autoimmune damage to muscle, skin, lungs, heart, GI tract), (2) the treatment (immunosuppression and steroid side effects), and (3) the associated malignancy (paraneoplastic DM). Understanding the pathophysiological basis of each complication makes them easy to predict and remember.

Lung fibrosis — association with anti-Jo1 antibody ^[1] ↑risk of ILD in anti-synthetase and anti-MDA5 (very aggressive ILD) ^[5]

Aspect	Detail
Prevalence	≥10% of all DM patients; much higher in specific antibody subsets (up to 86% with anti-Jo-1 ^[5]; nearly universal with anti-MDA5)
Pathophysiology	The same autoimmune process that attacks intramuscular vasculature can target pulmonary vasculature and alveolar epithelium. Type I interferon–driven inflammation damages the alveolar-capillary membrane → inflammatory infiltrate → fibroblast activation → progressive fibrosis. In anti-MDA5 disease, the mechanism is particularly aggressive with innate immune overactivation (MDA5 is a cytoplasmic RNA sensor in the interferon pathway)
Clinical patterns	NSIP (most common — bibasal GGO sparing subpleural region ^[16]), organising pneumonia, UIP pattern (less common), or rapidly progressive ILD (RP-ILD)
RP-ILD	Strongly associated with anti-MDA5; rapidly progressive course and poor overall survival related to pulmonary complications ^[12]; can progress from mild GGO to respiratory failure within weeks. This is the single most feared complication of DM
Clinical features	Progressive dyspnoea, dry cough, bibasal fine inspiratory crackles ("Velcro crackles"), tachypnoea, desaturation on exertion
Detection	HRCT chest (sensitive), PFTs (restrictive pattern with ↓DLCO as earliest abnormality), CXR (screening)
Impact	ILD is one of the MOST common fatal complications ^[12]

Why does DLCO decrease first? DLCO (diffusing capacity for carbon monoxide) measures the ability of gas to transfer across the alveolar-capillary membrane. In early ILD, the membrane is inflamed and thickened — gas transfer is impaired even before lung volumes shrink. So DLCO falls before FVC or TLC decline.

High Yield — ILD Antibody Correlation

Antibody	ILD Pattern	Prognosis
Anti-Jo-1 (antisynthetase)	Chronic ILD, often NSIP	Moderate — responds to immunosuppression
Anti-MDA5	RP-ILD — fulminant	Very poor — can be fatal within weeks despite aggressive therapy
Anti-Mi-2	ILD uncommon	Good
Anti-TIF1-γ	ILD uncommon	Cancer, not ILD, is the main risk

MOST common fatal complications: Aspiration pneumonia due to dysphagia ^[12]

Aspect	Detail
Pathophysiology	DM affects the striated muscle of the pharynx and upper one-third of the oesophagus (the same muscle type as skeletal muscle). Weakness of these muscles → inability to protect the airway during swallowing → food/secretions enter the trachea and lungs → aspiration pneumonia
Why it is so dangerous	(1) DM patients are already on immunosuppressive therapy → impaired immune defence against aspirated bacteria; (2) respiratory muscle weakness may impair cough reflex → cannot clear aspirated material effectively; (3) if concurrent ILD is present, the lung has less reserve to tolerate additional insult
Clinical features	Recurrent episodes of cough/choking with meals, nasal regurgitation, wet/gurgly voice after swallowing, fever, new pulmonary infiltrate on CXR
Risk assessment	Videofluoroscopic swallowing study (VFSS) or fibreoptic endoscopic evaluation of swallowing (FEES); clinical bedside swallowing assessment
Prevention	Early recognition and treatment of dysphagia; SLT-guided swallowing therapy; dietary modification (thickened fluids, pureed food); upright positioning during meals; nasogastric tube or PEG insertion if severe; aggressive immunosuppressive treatment to improve pharyngeal muscle strength; IVIg can be particularly effective for DM dysphagia

Bulbar muscle involvement has poor prognosis ^[1]^[4] — this is because bulbar weakness leads to aspiration, which is the most common directly fatal complication.

Clinical Pearl

In the GC interactive tutorial case, the patient has new onset difficulty in swallowing food with 2 episodes of choking ^[14] — this illustrates bulbar involvement in DM and is an indicator of severe disease requiring urgent escalation of immunosuppressive therapy.

Myocarditis — leads to conduction abnormalities and fatal arrhythmia ^[12]

Complication	Pathophysiology	Clinical Significance
Myocarditis	The same complement-mediated microangiopathy and/or lymphocytic infiltration that targets skeletal muscle can involve cardiac myocytes → myocardial inflammation and necrosis	Can cause heart failure (reduced EF, dilated cardiomyopathy), conduction defects (AV block, bundle branch block), and fatal arrhythmias (VT, VF)
Pericarditis / pericardial effusion	Serosal inflammation (similar to pleuritis in SLE)	Usually subclinical; occasionally causes tamponade
Accelerated atherosclerosis	Chronic systemic inflammation + long-term steroid use → endothelial dysfunction, dyslipidaemia, hypertension, insulin resistance	Increased risk of MI and stroke — this is a long-term complication particularly relevant for patients on chronic steroids

Why is cardiac involvement often missed? Skeletal muscle CK-MM elevation dominates the picture. Cardiac-specific troponin (troponin I is more specific than troponin T for cardiac injury in the setting of myositis; troponin T can be released from regenerating skeletal muscle) and ECG/Echo should be performed routinely. Cardiac MRI with late gadolinium enhancement is the most sensitive test for subclinical myocarditis.

Probable association with malignancy in elderly population ^[1] Thorough search for an underlying malignancy and treat as appropriate ^[1] Potential association between cancer and dermatomyositis and the rationale of cancer screening ^[11]

Aspect	Detail
Risk	5× risk in dermatomyositis, 2× risk in polymyositis ^[3]^[7] compared to general population
Temporal relationship	Can be diagnosed before, with or after diagnosis of inflammatory myopathy ^[7]; most cancers are diagnosed within 1 year of DM onset (before or after) ^[2], but screening should continue for ≥3–5 years
Associated malignancies (HK)	Carcinoma of the nasopharynx (HK), bronchus, breast, stomach, ovary, cervix, prostate ^[1]
Specific case	Dermatomyositis associated with ovarian cancer ^[8] — this was illustrated in the dermatology PBL
Antibody predictors	Anti-TIF1-γ: highest malignancy risk (~60–80% in adults); anti-NXP-2: also high malignancy risk ^[8]
Pathophysiology	Likely molecular mimicry — tumour antigens share epitopes with muscle/endothelial antigens, so the immune response against the tumour cross-reacts with self-tissues. This explains why DM may improve with successful tumour treatment and relapse with cancer recurrence
Screening	Age/sex-appropriate screening at diagnosis; repeated annually for ≥3–5 years; intensified if anti-TIF1-γ/anti-NXP-2+; always include NPC screening (EBV DNA, nasopharyngoscopy) in HK

The Cancer–DM Bidirectional Relationship

This is a subtle but important concept: in cancer-associated DM, treating the cancer may cause DM to remit. Conversely, DM relapse should prompt a repeat malignancy screen — it may herald cancer recurrence or a new primary malignancy. This bidirectional relationship is a hallmark of paraneoplastic syndromes.

Aspect	Detail
Pathophysiology	The diaphragm and intercostal muscles are skeletal muscles → susceptible to the same inflammatory myopathy process. Severe weakness of these muscles → respiratory failure ^[5]
Distinct from ILD	Respiratory muscle weakness causes a restrictive ventilatory defect (reduced FVC and maximal inspiratory/expiratory pressures) BUT with normal DLCO (the alveolar-capillary membrane is intact). In ILD, DLCO is reduced
Clinical significance	Patients may present with progressive dyspnoea, orthopnoea (diaphragmatic weakness is worse when supine), morning headache (CO₂ retention overnight), and eventually hypercapnic respiratory failure
Detection	Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) are the specific tests; also upright vs supine FVC (> 20% drop supine suggests diaphragmatic weakness)

Childhood form may have calcification — muscle contractures (tip-toe gait), scarring and calcinosis ^[5]

Aspect	Detail
Prevalence	Occurs in ~40% of JDM ^[6]; much less common in adult DM
Pathophysiology	Dystrophic calcification — calcium phosphate and hydroxyapatite crystals deposit in chronically damaged, necrotic, or inflamed tissue. This is NOT metabolic hypercalcaemia (serum calcium is normal); it is deposition in tissue that has been injured by the autoimmune process
Clinical features	Dystrophic deposits of calcium phosphate/hydroxyapatite crystals in subcutaneous plaques or nodules resulting in painful ulceration of skin with extrusion of crystite or calcite liquid ^[6]; can affect muscles, fascia, and skin
Functional impact	Can be severely disabling — restricts joint movement, causes chronic pain, skin breakdown with secondary infection, and cosmetic disfigurement
Prevention	Best strategy: early aggressive immunosuppression to control inflammation before dystrophic calcification develops
Treatment	Very difficult once established; options include diltiazem, colchicine, sodium thiosulphate, surgical excision of large deposits

Aspect	Detail
Pathophysiology	Chronic inflammation → muscle fibre necrosis → replacement by fibrosis and fatty infiltration → fixed shortening of muscle. In JDM, the tip-toe gait results from contracture of the gastrocnemius/soleus complex ^[5]
Clinical significance	Fixed contractures are irreversible — prevention through early treatment and physiotherapy is key
Detection	Reduced passive range of motion at affected joints; MRI shows fatty replacement (T1 hyperintensity)

Gastrointestinal vasculopathy leads to cramping abdominal pain, GI bleeding, infarction or perforation ^[6]

Aspect	Detail
Pathophysiology	The complement-mediated microangiopathy in JDM can be particularly severe and affect mesenteric vessels → ischaemia of GI tract wall → ulceration, haemorrhage, perforation
Clinical significance	Rare but potentially fatal; presents with abdominal pain, bloody stools, or acute abdomen
Relevance	More common in JDM than adult DM; a red flag for severe vasculopathic disease

Aspect	Detail
Pathophysiology	Pharyngeal and upper oesophageal striated muscle weakness → dysphagia + nasal regurgitation → reduced oral intake → malnutrition and weight loss
Additional risk	Aspiration pneumonia (see above); patients may develop secondary malnutrition from chronic inability to eat adequately
Management	SLT assessment; modified diet; NG/PEG feeding if severe; aggressive immunosuppressive treatment of underlying DM

These complications arise from the immunosuppressive medications used to treat DM. Understanding these is essential because they can mimic disease flare or cause independent morbidity.

Complication	Cause	Pathophysiology and Clinical Detail
Steroid myopathy	Chronic high-dose glucocorticoids	Type II (fast-twitch) fibre atrophy from catabolic steroid effects; causes proximal weakness with NORMAL CK — critical to distinguish from disease flare (where CK is elevated). The most common diagnostic dilemma in DM management
Opportunistic infections	Immunosuppression (steroids, MTX, AZA, rituximab, CYC)	PJP (Pneumocystis jirovecii pneumonia), TB reactivation, herpes zoster, CMV reactivation, invasive fungal infections. PJP presents with progressive dyspnoea and bilateral GGO on HRCT — can mimic ILD flare
Osteoporosis and fractures	Chronic steroids	Inhibit osteoblasts, promote osteoclasts, reduce Ca absorption → bone loss → vertebral compression fractures, hip fractures
Steroid-induced diabetes	Chronic steroids	Hepatic gluconeogenesis ↑, peripheral insulin resistance ↑ → hyperglycaemia
HBV reactivation	Rituximab, high-dose steroids	B-cell depletion or suppression allows latent HBV to reactivate → fulminant hepatitis. Must screen HBV serology before immunosuppression
Bone marrow suppression	MTX, AZA, CYC	Direct cytotoxic effect on rapidly dividing haematopoietic cells → pancytopenia → infection, bleeding, anaemia. AZA toxicity especially with TPMT/NUDT15 deficiency ^[15]
Hepatotoxicity	MTX, AZA	MTX causes hepatic fibrosis with cumulative dosing; AZA causes hepatocellular injury
MTX pneumonitis	Methotrexate	Drug-induced hypersensitivity pneumonitis — acute dyspnoea, fever, bilateral infiltrates; mimics DM-ILD; improves with MTX cessation
Haemorrhagic cystitis	Cyclophosphamide	Toxic metabolite acrolein damages bladder urothelium; prevent with MESNA and hydration
Gonadal toxicity	Cyclophosphamide	Toxic to gonadal tissue → premature ovarian failure, azoospermia; counsel about fertility preservation
Infection from IVIg	IVIg	Rarely: blood-borne infection transmission (theoretical with modern screening); anaphylaxis in IgA-deficient patients
Thromboembolic events	IVIg, chronic inflammation, immobility	IVIg increases serum viscosity; DM inflammation is prothrombotic; immobility from weakness → VTE risk
Avascular necrosis	Chronic high-dose steroids	Ischaemic necrosis of femoral head — presents with hip/groin pain; MRI is the most sensitive investigation
Cataracts and glaucoma	Chronic steroids	Posterior subcapsular cataract; open-angle glaucoma from increased aqueous outflow resistance
Cardiovascular disease	Steroid → increased CV risk ^[14]	Hypertension, dyslipidaemia, diabetes, atherosclerosis acceleration

PJP vs DM-ILD vs MTX Pneumonitis — A Diagnostic Minefield

Three conditions that can all present with progressive dyspnoea + bilateral infiltrates in a DM patient on immunosuppression:

Feature	DM-ILD Flare	PJP	MTX Pneumonitis
Context	Active DM, anti-Jo-1/MDA5+	High-dose steroids, CD4 < 200	On MTX, usually within 1–2 years
Onset	Subacute (weeks) or acute (RP-ILD)	Subacute (days–weeks)	Acute (days)
CXR/HRCT	Bibasal GGO/reticulation	Bilateral diffuse GGO, often perihilar	Bilateral GGO ± consolidation
Key test	MSAs, PFTs, serial HRCT	BAL with PJP staining/PCR; β-D-glucan	Biopsy: granulomatous inflammation; improve with MTX cessation
Fever	Variable	Prominent	Prominent
LDH	Normal/mildly ↑	Markedly ↑	Variable
Treatment	Increase immunosuppression	Cotrimoxazole + reduce immunosuppression	Stop MTX + steroids

Getting this wrong can be fatal — increasing immunosuppression for PJP kills the patient; reducing immunosuppression for DM-ILD flare also kills the patient. BAL and microbiological workup are essential when in doubt.

x. Lipodystrophy (Juvenile DM)

Aspect	Detail
Prevalence	10–40% of JDM patients ^[6]
Pathophysiology	Progressive loss of subcutaneous and visceral fat, typically over face and upper body; mechanism unclear but likely related to chronic inflammation and cytokine effects on adipocytes
Metabolic consequences	Associated with insulin resistance, acanthosis nigricans, dyslipidaemia, hypertension and menstrual irregularities ^[6] — essentially a metabolic syndrome phenotype

Organ System	Complication	Mechanism	Key Antibody Association
Lungs	ILD (NSIP, OP, RP-ILD)	Alveolar-capillary membrane inflammation/fibrosis	Anti-Jo-1, anti-MDA5 ^[5]
Lungs	Aspiration pneumonia	Pharyngeal muscle weakness + immunosuppression	Bulbar involvement
Lungs	Respiratory failure (muscle)	Diaphragm/intercostal weakness	Severe myositis
Heart	Myocarditis, conduction defects, arrhythmia ^[12]	Cardiac myocyte microangiopathy/inflammation	Non-specific
GI tract	Dysphagia, aspiration	Pharyngeal/oesophageal striated muscle weakness	Severe myositis
GI tract	GI vasculopathy (JDM)	Mesenteric microangiopathy	JDM
Skin/soft tissue	Calcinosis cutis	Dystrophic calcification in damaged tissue	JDM ^[5]; anti-NXP-2
MSK	Muscle contractures	Fibrosis replacing damaged muscle	Chronic/undertreated
Metabolic	Lipodystrophy (JDM)	Adipocyte inflammation/destruction	JDM
Malignancy	Cancer-associated DM	Molecular mimicry; paraneoplastic	Anti-TIF1-γ, anti-NXP-2 ^[8]
Iatrogenic	Steroid myopathy, infections, osteoporosis, DM, CVD	Treatment side effects	N/A

High Yield Summary — Complications of Dermatomyositis

Three most common FATAL complications: (1) Aspiration pneumonia from dysphagia, (2) Interstitial lung disease (especially RP-ILD with anti-MDA5), (3) Myocarditis with fatal arrhythmia.
ILD: Present in ≥10% of DM; most commonly NSIP pattern; anti-Jo-1 associated with chronic ILD (86%), anti-MDA5 with RP-ILD (can be fatal within weeks). DLCO decreases first because alveolar-capillary membrane damage impairs gas transfer before volumes shrink.
Aspiration pneumonia: Leading direct cause of death. Pharyngeal striated muscle weakness → cannot protect airway → aspiration. Worsened by concurrent immunosuppression and respiratory muscle weakness. Bulbar involvement = poor prognosis.
Malignancy: 5× risk in DM. HK: think NPC. Anti-TIF1-γ / anti-NXP-2 = highest risk. Screen at diagnosis and annually for ≥3–5 years. DM relapse may herald cancer recurrence.
Cardiac: Myocarditis → HF, conduction defects, arrhythmia. Often subclinical. Screen with ECG + Echo. Use troponin I (more cardiac-specific than troponin T in myositis setting).
JDM-specific: Calcinosis (40%), GI vasculopathy (ulceration/perforation/haemorrhage), lipodystrophy (10–40%), muscle contractures (tip-toe gait).
Treatment complications: Steroid myopathy (normal CK — distinguish from flare!), opportunistic infections (PJP, TB, HBV reactivation), osteoporosis, diabetes, CVD, bone marrow suppression (AZA/MTX/CYC), MTX pneumonitis, CYC haemorrhagic cystitis/gonadal toxicity, AVN.
Diagnostic pitfall: PJP vs DM-ILD flare vs MTX pneumonitis — all present with bilateral infiltrates and dyspnoea. BAL and microbiological workup are essential. Getting this wrong is potentially fatal.

Active Recall - Complications of Dermatomyositis

References

^[1] Lecture slides: GC 053. Fingers turn white and blue.pdf (pp.44, 46, 51) ^[2] Senior notes: Maksim Medicine Notes.pdf (Rheumatology, p.318–320) ^[3] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.5, pp.90–91) ^[4] Lecture slides: GC 053. Fingers turn white and blue.pdf (clinical features, p.44) ^[5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.146) ^[6] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (pp.708–709) ^[7] Senior notes: Ryan Ho Neurology.pdf (pp.194–195) ^[8] Senior notes: Block A - Dermatology PBL 2.pdf (pp.6–7) ^[11] Lecture slides: GC_Interactive tutorial (Rheum case 2) student copy.pdf (p.1) ^[12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp.1762–1764) ^[14] Senior notes: Block A - Rheumatology Interactive Tutorial.pdf (p.2–3) ^[15] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p.45) ^[16] Senior notes: Ryan Ho Respiratory.pdf (pp.123–128)

High Yield Summary

Definition: DM is an autoimmune inflammatory myopathy with characteristic skin involvement, driven by complement-mediated microangiopathy (B-cell/complement) targeting intramuscular and cutaneous vasculature → perifascicular atrophy on biopsy.
Epidemiology: F:M = 2:1, bimodal (juvenile 5–15y, adult 40–60y), incidence ~2/100k/year.
Aetiology rule of thirds: 1/3 malignancy, 1/3 autoimmune/CTD overlap, 1/3 idiopathic.
Key HK malignancy: Nasopharyngeal carcinoma (NPC), plus lung, breast, gastric, ovarian, cervical, prostate.
Pathophysiology: B-cell/complement → MAC on capillary endothelium → capillary dropout → perifascicular atrophy (muscle) + poikiloderma/heliotrope/Gottron's (skin). PM is different: CD8+ T-cell → endomysial attack.
Skin findings (usually precede weakness): Heliotrope rash, Gottron's papules (pathognomonic), V sign, shawl sign, holster sign, mechanic's hands, calcinosis cutis, nailfold capillary changes.
Muscle findings: Symmetric proximal weakness (shoulder/hip girdle, neck flexors), retained reflexes, no sensory loss; dysphagia/dysphonia = poor prognostic sign.
Key antibodies: Anti-Mi-2 (classic DM, good prognosis), anti-TIF1-γ (malignancy), anti-NXP-2 (malignancy + calcinosis), anti-MDA5 (CADM + RP-ILD), anti-Jo-1 (antisynthetase syndrome + ILD), anti-SRP (necrotizing myopathy).
CADM: Skin features without weakness ≥6 months; anti-MDA5 variant carries highest mortality from RP-ILD.
Juvenile DM: More calcinosis, GI vasculitis, contractures (tip-toe gait); very low malignancy risk.

High Yield Summary — Differential Diagnosis of Dermatomyositis

Two-level differential: First distinguish inflammatory myopathy from non-inflammatory causes of proximal weakness (endocrine, drug-induced, hereditary, NMJ, neuropathy, MND); then distinguish DM from other IIM subtypes (PM, IBM, IMNM, antisynthetase syndrome).
Characteristic DM rash is the key discriminator: Heliotrope rash and Gottron's papules are not seen in any other myopathy. If both weakness + rash are present, DM is the diagnosis.
DM vs SLE: DM involves nasolabial folds, SLE spares them. DM has Gottron's on knuckles, lupus affects skin between joints. Both are photosensitive.
DM vs PM: DM = skin + muscle, B-cell/complement, perifascicular atrophy. PM = muscle only, CD8+ T-cell, endomysial infiltration.
DM vs IBM: IBM is insidious, affects distal (finger flexors) + proximal (quads), elderly male, refractory to treatment, rimmed vacuoles on biopsy.
Myopathy vs neuropathy: Myopathy = proximal weakness, preserved reflexes, no sensory loss, elevated CK, myopathic EMG. Neuropathy = distal weakness, reduced reflexes, sensory loss, normal CK, neuropathic EMG/NCS.
Always screen for malignancy: 5× risk in DM. In HK, think NPC. Anti-TIF1-γ and anti-NXP-2 carry highest malignancy risk.
Drug-induced myopathy: Steroids cause painless proximal weakness with NORMAL CK. Statins cause myalgia ± elevated CK; can trigger true IMNM (anti-HMGCR).

High Yield Summary — Diagnosis of Dermatomyositis

Bohan and Peter criteria (1975): DM = any 3 of (weakness, biopsy, elevated CK, abnormal EMG) + characteristic skin findings. PM = all 4 without skin. Simplified: "2 out of 3 of ↑CK, EMG abnormalities, +ve biopsy."
2017 EULAR/ACR criteria: probability-based scoring; includes anti-Jo-1; allows classification without biopsy; better for amyopathic DM.
CK is the single most useful blood test: most sensitive/specific muscle enzyme; > 10× ULN typical; correlates with disease activity; used for monitoring. But can be NORMAL in CADM, burnt-out disease, steroid myopathy.
MSAs define clinical subsets: Anti-Mi-2 (classic DM, good prognosis), anti-TIF1-γ/anti-NXP-2 (cancer), anti-MDA5 (CADM + RP-ILD), anti-Jo-1 (antisynthetase + ILD).
EMG: myopathic pattern (low amplitude, short duration, polyphasic MUPs + fibrillation). Distinguishes myopathy from neuropathy but cannot distinguish DM from PM.
Muscle biopsy: perifascicular atrophy + complement MAC on capillaries + perimysial B-cell infiltrate = pathognomonic for DM. PM shows endomysial CD8+ invasion.
MRI muscles: STIR/T2W hyperintensity in active disease; guides biopsy; avoids sampling error.
Every DM patient needs: ILD screen (HRCT + PFTs), cardiac screen (ECG + Echo), swallowing assessment, and age-appropriate malignancy screen including NPC in HK.
Malignancy screen is ongoing: repeat annually for ≥3–5 years. Malignancy can precede, coincide with, or follow DM diagnosis.

High Yield Summary — Management of Dermatomyositis

Induction: Prednisolone 1 mg/kg/day (or IV methylprednisolone pulse 0.5–1 g/day × 3 days for severe disease).
Steroid-sparing agents (started early, take weeks–months to work): First-line = methotrexate or azathioprine. MMF is preferred when ILD is present. Calcineurin inhibitors (tacrolimus) especially for anti-MDA5 RP-ILD.
Rescue therapies: IVIg (ProDERM trial — FDA-approved for DM), rituximab (B-cell depletion — logical given DM is B-cell/complement-mediated), cyclophosphamide (severe/life-threatening), plasmapheresis.
Before starting AZA: Check TPMT + NUDT15 (especially important in HK/East Asian population). Check for XO inhibitor co-prescription (allopurinol).
Before starting any immunosuppression: Screen for HBV (reactivation risk), TB (IGRA + CXR), baseline blood tests.
Steroid side effect prophylaxis: Ca + Vit D + bisphosphonates (osteoporosis), glucose monitoring (diabetes), PJP prophylaxis (cotrimoxazole), HBV prophylaxis, vaccination, CVD risk management.
Cancer-associated DM: Treat the underlying malignancy — DM may remit; DM relapse may signal cancer recurrence.
Anti-MDA5 RP-ILD: Medical emergency — triple therapy (high-dose steroids + calcineurin inhibitor + cyclophosphamide/rituximab ± IVIg); may need ICU.
Non-pharmacological: Physiotherapy (gentle during flare, progressive strengthening in remission), photoprotection, OT, SLT, psychological support.
Prognosis: Overall 5–10% mortality, driven by RP-ILD, malignancy, cardiac involvement, aspiration, and infection.

High Yield Summary — Complications of Dermatomyositis

Three most common FATAL complications: (1) Aspiration pneumonia from dysphagia, (2) Interstitial lung disease (especially RP-ILD with anti-MDA5), (3) Myocarditis with fatal arrhythmia.
ILD: Present in ≥10% of DM; most commonly NSIP pattern; anti-Jo-1 associated with chronic ILD (86%), anti-MDA5 with RP-ILD (can be fatal within weeks). DLCO decreases first because alveolar-capillary membrane damage impairs gas transfer before volumes shrink.
Aspiration pneumonia: Leading direct cause of death. Pharyngeal striated muscle weakness → cannot protect airway → aspiration. Worsened by concurrent immunosuppression and respiratory muscle weakness. Bulbar involvement = poor prognosis.
Malignancy: 5× risk in DM. HK: think NPC. Anti-TIF1-γ / anti-NXP-2 = highest risk. Screen at diagnosis and annually for ≥3–5 years. DM relapse may herald cancer recurrence.
Cardiac: Myocarditis → HF, conduction defects, arrhythmia. Often subclinical. Screen with ECG + Echo. Use troponin I (more cardiac-specific than troponin T in myositis setting).
JDM-specific: Calcinosis (40%), GI vasculopathy (ulceration/perforation/haemorrhage), lipodystrophy (10–40%), muscle contractures (tip-toe gait).
Treatment complications: Steroid myopathy (normal CK — distinguish from flare!), opportunistic infections (PJP, TB, HBV reactivation), osteoporosis, diabetes, CVD, bone marrow suppression (AZA/MTX/CYC), MTX pneumonitis, CYC haemorrhagic cystitis/gonadal toxicity, AVN.
Diagnostic pitfall: PJP vs DM-ILD flare vs MTX pneumonitis — all present with bilateral infiltrates and dyspnoea. BAL and microbiological workup are essential. Getting this wrong is potentially fatal.

Dermatomyositis

1. Definition

2. Epidemiology

Incidence and Prevalence

Demographics

Mortality

3. Risk Factors

4. Anatomy and Function (Relevant Structures)

Skeletal Muscle Architecture

Skin

Other Relevant Organs

5. Etiology and Pathophysiology

The "Rule of Thirds" for Aetiology (Practical Framework) [2]

Immunopathogenesis of Dermatomyositis

Step-by-step DM Pathophysiology:

Why Does the Skin Get Involved in DM but Not PM?

Cancer-Associated Myositis (Paraneoplastic Mechanism)

6. Classification

Traditional Classification of Idiopathic Inflammatory Myopathies (IIM) [2]

Newer Entities [2]

DM-Specific Subclassification by Clinical Context [3]

2017 EULAR/ACR Classification Criteria for IIM [2]

7. Clinical Features

A. Symptoms (What the Patient Tells You)

i. Muscle Symptoms

ii. Skin Symptoms (Usually PRECEDE Muscle Symptoms)

iii. Systemic Symptoms

B. Signs (What You Find on Examination)

i. Cutaneous Signs (Pathognomonic and Characteristic)

ii. Musculoskeletal Signs

iii. Respiratory Signs

iv. Other Systemic Signs

v. Signs Suggesting Underlying Malignancy

C. Juvenile Dermatomyositis (JDM) — Key Differences from Adult DM

D. Summary Table: PM vs DM

8. Special Considerations

Antisynthetase Syndrome

Anti-MDA5 Dermatomyositis

Active Recall - Dermatomyositis (Definition to Clinical Features)

References

A. Conceptual Framework: What Are You Actually Differentiating?

B. Systematic Differential Diagnosis of Myopathy

C. Differentiating Among the Idiopathic Inflammatory Myopathies (IIM)

D. Differentiating the Skin Rash of DM from Other Conditions

E. Differentiating DM-Related Dysphagia from Other Causes

F. Approach Algorithm: Differential Diagnosis of a Patient Presenting with Proximal Weakness ± Rash

G. Key Differentials Highlighted on GC Lecture Slides

H. Summary: Distinguishing Myopathy from Neuropathy (A Fundamental Exam Distinction)

Active Recall - Differential Diagnosis of Dermatomyositis

A. Diagnostic Criteria

i. Bohan and Peter Criteria (1975) — Classic, Still Commonly Examined

ii. 2017 EULAR/ACR Classification Criteria for IIM

iii. Antisynthetase Syndrome Diagnostic Criteria

B. Diagnostic Algorithm

C. Investigation Modalities — Detailed Breakdown

i. Blood Tests — Baseline and Screening

ii. Muscle Enzymes

iii. Autoantibodies

iv. Electromyography (EMG)

v. Muscle Biopsy

vi. Skin Biopsy

vii. MRI of Skeletal Muscles

viii. Chest Investigations (ILD Screening)

ix. Cardiac Assessment

x. Swallowing Assessment

xi. Malignancy Screening

D. Summary: Putting It All Together

Active Recall - Diagnostic Criteria, Algorithm and Investigations for DM

A. Principles of Management

B. Management Algorithm

C. Pharmacological Treatment — Detailed Breakdown

i. Glucocorticoids (Induction — First Line)

ii. Steroid-Sparing Immunosuppressants (Maintenance — Second Essential Component)

Methotrexate (MTX)

Azathioprine (AZA)

Mycophenolate Mofetil (MMF)

Calcineurin Inhibitors (Tacrolimus, Cyclosporine A)

iii. Rescue / Refractory Disease Therapies

Intravenous Immunoglobulin (IVIg)

Rituximab (Anti-CD20)