Musculoskeletal

Inflammatory myopathies: dermatomyositis and polymyositis

Clinical Overview and When to Suspect Inflammatory Myopathy

— Dermatomyositis (DM): perimysial/perivascular inflammation, complement-mediated microangiopathy, skin findings (Gottron, heliotrope), strong malignancy association

— Polymyositis (PM): endomysial CD8+ T-cell infiltrate invading non-necrotic fibers; diagnosis of exclusion, less skin, weaker cancer link

— Immune-mediated necrotizing myopathy (IMNM): anti-HMGCR (statin-triggered) or anti-SRP, very high CK, scant inflammation

— Inclusion body myositis (IBM): older men, asymmetric distal + proximal weakness (finger flexors, quads), refractory to steroids

— Interstitial lung disease (ILD) — anti-synthetase syndrome (anti-Jo-1), antiMDA5 (rapidly progressive ILD, amyopathic DM)

— Cardiac involvement — myocarditis, conduction disease

— Raynaud, mechanic's hands, arthritis, fever — antisynthetase phenotype

— Proximal weakness + ↑CK without statin or trauma

— Rash + weakness in middle-aged adult

— New-onset DM in an older adult → search for occult malignancy

Board pearl: Pain is not the dominant feature — patients describe weakness, not soreness. If pain dominates with normal strength, think polymyalgia rheumatica or fibromyalgia, not PM/DM.

Step 3 management: First ambulatory move when suspicion is high — order CK, aldolase, AST/ALT, LDH, TSH, ANA, myositis-specific antibody panel, and refer to rheumatology; do not start empiric steroids before establishing baseline labs and ruling out mimics like hypothyroid myopathy or statin myopathy.

Inflammatory myopathies (IIM) are autoimmune disorders producing symmetric, proximal muscle weakness with elevated CK and characteristic autoantibodies

Core subtypes tested on Step 3:

Typical patient: woman 40–60 with weeks-to-months of trouble climbing stairs, rising from chairs, lifting arms overhead, brushing hair

Spares ocular muscles (vs myasthenia) and usually facial muscles; dysphagia (pharyngeal/esophageal striated muscle) in up to 30% and is a red flag for aspiration

Systemic features that change management:

When to suspect on a Step 3 stem:

Presentation Patterns and Key History

— Difficulty rising from low chair/toilet, climbing stairs (hip girdle)

— Trouble washing hair, reaching overhead shelves (shoulder girdle)

— Neck flexor weakness — "head feels heavy" lifting off pillow

— Dysphagia to solids then liquids; nasal regurgitation suggests palatal weakness

— Dyspnea on exertion → screen for ILD and respiratory muscle weakness

— Heliotrope rash — violaceous periorbital with edema

— Gottron papules — scaly violaceous plaques over MCPs, PIPs, elbows, knees

— Shawl sign / V-sign — photodistributed erythema on upper back, anterior chest

— Holster sign — lateral thighs

— Mechanic's hands — fissured hyperkeratotic lateral fingers (antisynthetase)

— Cuticular overgrowth, periungual telangiectasias

— Statins — myopathy (resolves) vs anti-HMGCR IMNM (persists, worsens off statin)

— Glucocorticoids — steroid myopathy (normal CK, type II atrophy)

— Colchicine, hydroxychloroquine, alcohol, cocaine, zidovudine

— Checkpoint inhibitors (pembrolizumab, nivolumab) — irAE myositis ± myocarditis

— Age >45, rapid onset, refractory disease, dysphagia, cutaneous necrosis, anti-TIF1-γ or anti-NXP2 antibodies

Key distinction: IBM stems describe an older man with falls from buckling knees and dropping objects from finger-flexor weakness — asymmetric, distal-predominant, normal-to-mildly elevated CK. Steroids won't help, so the right answer is often supportive care + PT, not immunosuppression.

Board pearl: Always ask about photosensitivity and inspect sun-exposed areas — DM rash is photodistributed and often mistaken for SLE or rosacea.

Tempo: subacute over weeks to months — distinguishes from rhabdomyolysis (hours-days) and muscular dystrophy (years)

Cardinal symptoms to elicit:

Skin history (DM-specific):

Drug and exposure history is mandatory:

Red flags for malignancy in DM:

Family history — exclude muscular dystrophies (Becker, LGMD), metabolic myopathies (exercise-triggered cramps)

Physical Exam Findings

— Symmetric, proximal weakness 5/5 distally, 3–4/5 proximally is classic PM/DM

— Asymmetric, finger flexor + quadriceps weakness → IBM

— Facial/ocular weakness → think myasthenia gravis, not IIM

— Gower sign — uses hands to climb up thighs to stand

— Cannot rise from chair without arms, cannot squat-and-stand

— Trendelenburg gait from hip girdle weakness

— Heliotrope, Gottron papules/sign, shawl/V-sign, holster sign

— Calcinosis cutis — especially juvenile DM

— Cutaneous ulceration over Gottron areas → anti-MDA5 (high ILD risk)

— Palmar papules ("inverse Gottron") also anti-MDA5

— Bibasilar Velcro crackles → ILD; order PFTs and HRCT

— Weak cough, paradoxical breathing → diaphragmatic weakness, impending respiratory failure

— Tachycardia, S3, JVD, new conduction abnormality → myocarditis

— Pericardial rub uncommon

— Non-erosive arthritis of small joints (antisynthetase)

— Muscle tenderness mild; severe tenderness suggests pyomyositis or rhabdo, not IIM

— Bedside water swallow; if cough/wet voice → NPO, speech/swallow consult, video fluoroscopy

Step 3 management: On admission for severe IIM flare, the CCS-style order set is NPO until swallow eval, IV methylprednisolone, telemetry (myocarditis risk), CK/troponin/BNP, CXR, SpO₂ with incentive spirometry, DVT prophylaxis, PT/OT consult.

Board pearl: If the stem describes proximal weakness + ptosis or diplopia, the answer is myasthenia gravis, not myositis — IIM spares extraocular muscles.

Strength testing — MRC grading (0–5): document hip flexion, shoulder abduction, neck flexion at baseline; these are the longitudinal monitoring metrics

Functional maneuvers:

Skin exam (DM):

Pulmonary:

Cardiac:

Musculoskeletal:

Swallowing assessment:

Diagnostic Workup — Initial Labs and Imaging

— CK — most sensitive; often 10–50× ULN in PM/DM, >50× in IMNM, only mildly ↑ or normal in IBM and amyopathic DM

— Aldolase — may be elevated when CK is normal (esp. DM)

— AST/ALT — muscle origin; do not assume hepatic without GGT

— LDH — nonspecific but supportive

— Anti-Jo-1 (anti-histidyl-tRNA synthetase) → antisynthetase syndrome (ILD, mechanic's hands, arthritis, Raynaud, fever)

— Anti-Mi-2 → classic DM rash, good prognosis, steroid-responsive

— Anti-MDA5 → amyopathic DM, rapidly progressive ILD, cutaneous ulcers — high mortality

— Anti-TIF1-γ, anti-NXP2 → adult malignancy-associated DM

— Anti-SRP, anti-HMGCR → IMNM (HMGCR after statin exposure)

— Anti-cN1A → IBM

— Mammogram, Pap/HPV, colonoscopy, PSA per guideline; CT chest/abdomen/pelvis; pelvic US in women (ovarian); consider PET-CT if high-risk antibody (TIF1-γ)

Key distinction: Troponin I is muscle-specific (cardiac); troponin T can rise from skeletal muscle in IIM and falsely suggest myocarditis — order troponin I to confirm cardiac involvement.

Board pearl: A new DM diagnosis in a 60-year-old without recent cancer screening = occult malignancy hunt is the next best step, not just immunosuppression.

Muscle enzymes (order all four — sensitivity varies):

Inflammatory markers: ESR/CRP often only mildly elevated — markedly high ESR should prompt reconsideration (vasculitis, infection, malignancy)

Autoantibody panel — high-yield pairings:

TSH — rule out hypothyroid myopathy (mimics with ↑CK and proximal weakness)

HIV, HCV — viral myopathies and IIM mimics

ECG — screen for conduction disease, ischemia; baseline before starting steroids/IS

CXR — ILD screen; if abnormal or dyspnea → HRCT chest + PFTs (DLCO, FVC)

Age-appropriate cancer screening for any new adult DM:

Diagnostic Workup — Advanced and Confirmatory Studies

— Detects muscle edema (active inflammation), fatty replacement (chronicity), fascial edema

— Guides biopsy site to avoid sampling error

— Useful when CK normal but suspicion high (amyopathic DM, IBM)

— Myopathic pattern — short-duration, low-amplitude, polyphasic motor units

— Spontaneous activity — fibrillations, positive sharp waves, complex repetitive discharges

— Normal nerve conduction (excludes neuropathy/ALS)

— Perform on contralateral side to planned biopsy (needle artifact)

— DM: perifascicular atrophy, perimysial/perivascular CD4+ infiltrate, complement (MAC) on capillaries, reduced capillary density

— PM: endomysial CD8+ T cells invading non-necrotic MHC-I-upregulated fibers

— IMNM: scattered necrotic and regenerating fibers, sparse inflammation, MAC on sarcolemma

— IBM: endomysial inflammation + rimmed vacuoles, congophilic inclusions, p62/TDP-43 aggregates

— HRCT — NSIP most common, OP, UIP possible; ground-glass + traction bronchiectasis

— PFTs — restrictive pattern, ↓DLCO; serial FVC monitoring

— BAL/lung biopsy if infection or alternative diagnosis suspected

Step 3 management: Don't biopsy a muscle that has been recently EMG'd or injected — artifact mimics myositis. Choose clinically weak but not end-stage muscle (deltoid or quadriceps) identified by MRI.

Board pearl: Perifascicular atrophy on biopsy = dermatomyositis, pathognomonic enough to start treatment even without rash (amyopathic-equivalent muscle disease).

MRI of thighs (or symptomatic muscle group) with STIR/T2:

EMG/NCS:

Muscle biopsy — gold standard when diagnosis unclear:

Skin biopsy (DM): interface dermatitis with vacuolar change, dermal mucin — similar to SLE; correlate clinically

Pulmonary workup if any respiratory feature:

Cardiac workup if symptoms or ECG changes: echo, cardiac MRI (LGE = myocarditis), Holter

Swallow evaluation: video fluoroscopic swallow study if dysphagia

Risk Stratification and First-Line Management Logic

— Mild: weakness without dysphagia, no ILD, no myocarditis, ambulatory

— Moderate: functional impairment limiting ADLs, mild ILD, mild dysphagia

— Severe/organ-threatening: rapidly progressive ILD (esp. anti-MDA5), myocarditis, severe dysphagia with aspiration, profound weakness, vasculopathy/ulceration

— Methotrexate or azathioprine — standard first-line sparing agents

— Mycophenolate mofetil — preferred with ILD or hepatic concern (avoid MTX in ILD)

— IVIG — first-line add-on for refractory disease, severe dysphagia, IMNM, and when infection risk precludes more IS

— Rituximab — refractory PM/DM, antisynthetase ILD

— Calcineurin inhibitors (tacrolimus, cyclosporine) — anti-MDA5 ILD (combination therapy)

— TB screen (IGRA), HBV/HCV serologies, HIV, varicella immunity

— Baseline DEXA, glucose/HbA1c, lipid panel, BP

— Vaccinations before immunosuppression: inactivated influenza, COVID, pneumococcal (PCV20 or PCV15→PPSV23), shingrix, Tdap, HBV as indicated

— PJP prophylaxis (TMP-SMX) when on prednisone ≥20 mg/day for >4 weeks plus another IS

— Calcium 1200 mg + vitamin D 800 IU + bisphosphonate consideration for steroid-induced osteoporosis prevention

CCS pearl: In a CCS case of new DM with anti-MDA5 and ground-glass HRCT, advance the clock only after ordering pulse methylpred + tacrolimus + cyclophosphamide/MMF; delaying is the wrong action — anti-MDA5 ILD kills in weeks.

Stratify severity at diagnosis to choose induction intensity:

First-line backbone: oral prednisone 1 mg/kg/day (max ~80 mg) for 4–6 weeks, then taper over 9–12 months guided by strength + CK

Pulse IV methylprednisolone 1 g × 3 days for severe disease, dysphagia, myocarditis, rapidly progressive ILD

Start a steroid-sparing agent at the same time as steroids in most patients (CK and weakness alone aren't enough — long taper guarantees steroid toxicity):

Pre-treatment checklist (CCS-style):

Pharmacotherapy — First-Line Drug Regimen

— Prednisone 1 mg/kg/day PO (typical 60–80 mg) for 4–6 weeks until CK normalizes and strength improves, then taper ~10 mg/month to 20 mg, then slower

— Methylprednisolone 1 g IV daily × 3 days for severe/organ-threatening disease

— Counsel on weight, glucose, mood, sleep, infection risk

— Methotrexate 15–25 mg PO/SC weekly + folic acid 1 mg daily

— Avoid in significant ILD, hepatic disease, heavy alcohol use, pregnancy

— Monitor CBC, LFTs, Cr every 2–4 weeks initially

— Azathioprine 1.5–2.5 mg/kg/day

— Check TPMT/NUDT15 activity before starting; deficiency → severe myelosuppression

— Avoid concurrent allopurinol (use 25% dose or switch)

— Mycophenolate mofetil 1–1.5 g BID

— Preferred in ILD; teratogenic — REMS, contraception required

— IVIG 2 g/kg over 2–5 days monthly

— First-line for dermatomyositis (FDA-approved octagam 10%), IMNM, severe dysphagia

— Watch for aseptic meningitis, thrombosis, volume overload, IgA deficiency anaphylaxis

— Rituximab 1 g IV × 2 (days 0, 14) — refractory disease, antisynthetase ILD

— Tacrolimus/cyclosporine — anti-MDA5 ILD combination therapy

— Cyclophosphamide — severe rapidly progressive ILD, vasculopathy

— JAK inhibitors (tofacitinib) — emerging for refractory DM, anti-MDA5

— Hydroxychloroquine 5 mg/kg/day (baseline eye exam, annual screen after 5 years)

— Strict photoprotection (SPF 50+, hats)

— Topical steroids/tacrolimus for Gottron areas

— Don't stop a statin and call it "statin myopathy" if symptoms persist or CK rises off drug → think anti-HMGCR IMNM → treat with steroids + IVIG ± MTX

Board pearl: IVIG is first-line, not rescue, for dermatomyositis per current evidence — favored when infection, diabetes, or pregnancy limits other immunosuppression.

Glucocorticoids — induction:

Steroid-sparing/disease-modifying agents:

Skin-directed therapy for DM:

What NOT to do:

Procedures and Expanded Pharmacology

— Muscle biopsy (diagnostic, open or needle)

— Skin biopsy for DM rash confirmation

— PEG tube for refractory dysphagia/aspiration

— Cricopharyngeal myotomy or dilation for fixed upper esophageal sphincter dysfunction (selected cases)

— Excision of symptomatic calcinosis (juvenile DM)

— Inadequate response at 3 months → escalate sparing agent or switch class

— Add IVIG if not already on it

— Rituximab for B-cell-mediated phenotypes (antisynthetase, refractory DM)

— Combination IS for anti-MDA5 RP-ILD: pulse steroids + tacrolimus + IV cyclophosphamide or MMF + IVIG ± plasma exchange ± tofacitinib

— Mortality 30–50%; triple therapy from day 1 improves survival

— Serial ferritin (>1500 portends poor prognosis), KL-6, HRCT

— Consider ECMO bridge to lung transplant in select centers

— Stop statin permanently

— Steroids + IVIG + MTX or rituximab; IMNM is often steroid-refractory and IVIG-responsive

— No proven immunosuppressive therapy works

— PT/OT, fall prevention, swallow therapy, assistive devices; AVOID prolonged steroids

— Aspiration prevention: thickened liquids, head positioning, swallow therapy

— Calcinosis: diltiazem, bisphosphonates, sodium thiosulfate (anecdotal)

— Raynaud: amlodipine, hand-warming

Step 3 management: When a stem describes a patient with DM + cancer screening turning up ovarian mass — treat the malignancy; paraneoplastic DM often remits with cancer resection/chemo. Don't escalate IS without oncologic control.

Board pearl: The single most cost-effective intervention you can add at every visit is physical therapy — preserves function during the long steroid taper.

IIM is non-procedural — management is pharmacologic plus supportive procedures:

Refractory disease algorithm:

Anti-MDA5 ILD specifically:

IMNM (anti-HMGCR / anti-SRP):

IBM:

Symptom-directed:

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher rate of malignancy-associated DM — aggressive age-appropriate screening at diagnosis and re-screen at 1 and 2 years (highest risk first 3 years)

— Steroid toxicity amplified: osteoporosis, hyperglycemia, delirium, infection, cataracts, skin fragility

— Lower steroid threshold: target taper to ≤10 mg by 6 months when possible

— Polypharmacy review — interactions with azathioprine/allopurinol, MTX/TMP-SMX (additive myelosuppression), warfarin

— Fall risk compounded by proximal weakness — home safety eval, PT, gait aids

— Consider denosumab or zoledronate if oral bisphosphonate adherence/esophageal concerns

— Methotrexate — contraindicated if CrCl <30; reduce dose 50% for CrCl 30–60; monitor closely

— Mycophenolate — generally safe; dose unchanged but increased GI/heme toxicity

— Cyclophosphamide — reduce dose, ensure hydration and mesna for IV; monitor for hemorrhagic cystitis

— IVIG — risk of acute kidney injury (sucrose-containing products worst, avoid); use non-sucrose, slower infusion, hydrate

— Hydroxychloroquine — accumulates in CKD; reduce dose

— Bisphosphonates — avoid if eGFR <30; use denosumab (monitor calcium)

— Methotrexate, azathioprine — hepatotoxic; avoid or dose-reduce, monitor LFTs

— MMF — preferred in hepatic disease

— Screen and treat HBV before any IS; HBV reactivation with rituximab/cyclophosphamide is high-risk

Key distinction: A statin-using 70-year-old with rising CK off statin = anti-HMGCR IMNM until proven otherwise — order anti-HMGCR antibody and do not rechallenge with statin. Use PCSK9 inhibitor or ezetimibe for ongoing CV risk management.

Board pearl: In elderly DM, the answer to "next best step" is often CT chest/abdomen/pelvis before immunosuppressive escalation.

Elderly (>65):

Renal impairment:

Hepatic impairment:

CK interpretation in CKD: baseline CK may be mildly elevated; trend rather than single value

Special Populations — Pregnancy and Pediatrics

— Disease activity at conception predicts outcome — plan pregnancy during remission for ≥6 months

— Active IIM increases preterm birth, IUGR, fetal loss, preeclampsia

— Pre-conception drug review:

— Safe(r): prednisone (lowest effective dose, <20 mg ideal), hydroxychloroquine, azathioprine, IVIG, tacrolimus, cyclosporine

— Contraindicated: methotrexate (teratogen, stop ≥3 months pre-conception), mycophenolate (REMS, stop ≥6 weeks pre-conception), cyclophosphamide, leflunomide

— Steroid flare-management; pulse if needed

— Monitor for neonatal complications if maternal anti-Ro/SSA (congenital heart block — overlap syndromes)

— Delivery planning with high-risk OB; epidural fine

— Breastfeeding-compatible: prednisone, hydroxychloroquine, azathioprine, IVIG

— Peak age 5–10; girls > boys

— Calcinosis cutis much more common than in adults

— Vasculopathy with GI ulceration/perforation, retinal involvement

— No malignancy association (unlike adult DM)

— Treatment: steroids + methotrexate first-line; IVIG for refractory

— Aggressive PT/OT, school accommodations, growth monitoring

— Long-term complications: lipodystrophy, calcinosis, growth failure (steroid-related)

— Counsel on contraception with teratogenic agents (MTX, MMF)

— Mental health screening — chronic illness + steroid mood effects

— Transition-of-care planning from pediatric to adult rheumatology

Step 3 management: A 32-year-old woman on MTX for DM asks about pregnancy — stop MTX, switch to azathioprine or maintain on prednisone + hydroxychloroquine, supplement folate, confirm disease control × 6 months, then attempt conception. Document teratogenicity counseling.

Board pearl: JDM presenting with abdominal pain is a surgical emergency — GI vasculopathy with perforation is the dreaded complication.

Pregnancy:

Juvenile dermatomyositis (JDM):

Adolescents/young adults:

Complications and Adverse Outcomes

— Interstitial lung disease — leading cause of death; NSIP, OP, UIP patterns; rapidly progressive in anti-MDA5

— Aspiration pneumonia from oropharyngeal dysphagia

— Respiratory muscle weakness — hypoventilation, atelectasis

— Myocarditis — heart failure, arrhythmia, sudden death

— Malignancy — especially adult DM; ovarian, lung, pancreatic, gastric, colorectal, NHL, nasopharyngeal (Asian populations)

— Calcinosis cutis — pain, ulceration, infection (mainly juvenile DM)

— Cutaneous ulceration / vasculopathy — anti-MDA5

— Dysphagia → malnutrition, weight loss, dehydration

— Disability — chronic weakness, contractures, falls

— Pulmonary hypertension secondary to ILD

— Glucocorticoid toxicity: osteoporosis, fragility fracture, hyperglycemia/steroid-induced DM, hypertension, weight gain, cataracts, glaucoma, AVN of femoral head, mood/psychosis, adrenal insufficiency on taper, infection

— Opportunistic infections: PJP, CMV, TB reactivation, HBV reactivation, fungal, VZV

— MTX: hepatotoxicity, pneumonitis, cytopenias, mucositis

— Azathioprine: myelosuppression (TPMT-dependent), hepatitis, pancreatitis, squamous cell skin cancer, lymphoma

— MMF: GI intolerance, leukopenia, infection, teratogenicity

— IVIG: headache, aseptic meningitis, thromboembolism, AKI, hemolysis, anaphylaxis (IgA deficiency)

— Rituximab: infusion reaction, HBV reactivation, PML, hypogammaglobulinemia

— Cyclophosphamide: hemorrhagic cystitis, infertility, bladder cancer, secondary leukemia

Key distinction: Worsening weakness on prednisone with rising CK = disease flare → escalate; normal/falling CK with weakness = steroid myopathy → reduce dose.

Board pearl: Adult-onset DM has ~25% lifetime malignancy risk, highest in first 3 years — re-screen annually.

Disease-related complications:

Treatment-related complications:

Steroid myopathy — paradoxical worsening on high-dose steroids; CK normal, type II fiber atrophy on biopsy; treat by reducing steroid dose, not increasing it

When to Escalate Care — ICU, Consult, Inpatient Triage

— Mild-moderate weakness, no dysphagia, no ILD, normal cardiac assessment

— Reliable follow-up, can take PO, social support adequate

— Moderate-severe weakness limiting ADLs/safety

— Dysphagia requiring NPO and swallow workup

— New ILD requiring HRCT, PFTs, pulm consult, possible pulse steroids

— Starting pulse methylprednisolone or IV cyclophosphamide

— Suspected myocarditis with stable hemodynamics → telemetry, cardiology

— Diagnostic uncertainty requiring biopsy and multi-specialty input

— Respiratory failure — diaphragm weakness, severe ILD with hypoxemia, aspiration pneumonia with sepsis; FVC <15 mL/kg or NIF worse than −20 cmH₂O = intubate

— Rapidly progressive anti-MDA5 ILD — even before overt failure

— Myocarditis with hemodynamic instability, arrhythmia, complete heart block

— GI vasculopathy with perforation (juvenile DM)

— Severe rhabdomyolysis-like CK elevation with AKI

— Rheumatology — diagnosis and immunosuppression decisions

— Pulmonology — any ILD or PFT abnormality

— Dermatology — biopsy, skin-directed therapy

— Cardiology — abnormal ECG/troponin/echo

— Oncology / age-appropriate screening clinic — adult new DM

— Speech/Swallow (SLP) — dysphagia

— PT/OT — every patient at diagnosis

— Ophthalmology — baseline before hydroxychloroquine

CCS pearl: In a CCS case of new dyspnea + Gottron papules + anti-MDA5 positive, the correct sequence is: admit → ICU bed → HRCT → IV methylprednisolone 1 g → tacrolimus + IV cyclophosphamide → pulmonology and rheumatology consults. Advancing the clock without escalation in this scenario will fail the case.

Board pearl: A negative initial FVC doesn't reassure — trend FVC q6h in respiratory muscle weakness; the drop can be precipitous.

Outpatient management is appropriate when:

Admit to floor when:

ICU admission for:

Consults to obtain:

Key Differentials — Same-Category (Muscle) Causes

— Older men, asymmetric, distal + proximal (finger flexors, quadriceps)

— CK mildly elevated, rimmed vacuoles on biopsy

— Steroid-refractory — answer is PT, not immunosuppression

— Very high CK, scant inflammation on biopsy, MAC on sarcolemma

— Anti-HMGCR (statin-associated) or anti-SRP

— Treat with steroids + IVIG + MTX/rituximab

— Statins — myalgia/mild CK ↑, resolves with discontinuation

— Glucocorticoid myopathy — normal CK, type II atrophy

— Colchicine, hydroxychloroquine — vacuolar myopathy

— Zidovudine — mitochondrial myopathy

— Checkpoint inhibitor myositis — irAE, can overlap with myocarditis + myasthenia (triad)

— Alcohol, cocaine — acute necrotizing myopathy

— Viral — influenza, HIV, coxsackie, enterovirus; usually self-limited

— Bacterial pyomyositis — S. aureus, focal, fever, painful

— Parasitic — trichinosis (periorbital edema, eosinophilia, raw pork)

— McArdle disease (myophosphorylase deficiency) — exercise-induced cramps, second wind phenomenon

— CPT II deficiency — prolonged exercise/fasting triggers rhabdo

— Mitochondrial myopathies — ragged red fibers, multisystem

— Duchenne/Becker — boys, childhood onset, Gowers sign, calf pseudohypertrophy, dilated cardiomyopathy

— LGMD, FSHD — family history, slow progression

— Hypothyroid myopathy — ↑CK, slow reflexes, normal strength often; treat with levothyroxine

— Hyperthyroidism, Cushing, Addison

Key distinction: Second-wind phenomenon + post-exercise myoglobinuria = McArdle (glycogen storage), not inflammatory myopathy — don't immunosuppress.

Board pearl: Always check TSH in any patient with elevated CK and weakness before labeling it PM.

Inclusion body myositis (IBM):

Immune-mediated necrotizing myopathy (IMNM):

Toxic / drug-induced myopathies:

Infectious myositis:

Metabolic myopathies:

Muscular dystrophies:

Endocrine myopathies:

Rhabdomyolysis: acute, CK often >10,000, myoglobinuria, AKI

Key Differentials — Other-Category Causes

— Myasthenia gravis — fluctuating, fatigable weakness, ptosis, diplopia, bulbar symptoms, normal CK, anti-AChR/MuSK; ice pack test, edrophonium (rarely used), SFEMG

— Lambert-Eaton myasthenic syndrome — proximal weakness that improves with repeated contraction, autonomic features, paraneoplastic (SCLC), anti-VGCC

— ALS — UMN + LMN signs, fasciculations, asymmetric, no sensory loss; CK can be modestly elevated

— CIDP — proximal + distal weakness, sensory loss, areflexia, ↑CSF protein

— GBS — ascending weakness, areflexia, post-infectious, ↑CSF protein

— Stroke (acute, asymmetric, sensory/cognitive features)

— Spinal cord compression (sensory level, bladder/bowel)

— Polymyalgia rheumatica (PMR) — age >50, stiffness > weakness, shoulder/hip girdle pain, ↑ESR/CRP, normal CK, dramatic response to prednisone 15–20 mg; screen for GCA

— SLE, MCTD, scleroderma overlap — myositis is one feature; ANA, dsDNA, Smith, RNP

— Vasculitis with myalgia

— Fibromyalgia — diffuse pain, tender points, normal labs, normal strength

— Sarcoidosis — granulomatous myopathy, often with pulmonary, lymph, skin findings

— Amyloidosis — macroglossia, cardiomyopathy, nephrotic syndrome

— Eosinophilic myositis — eosinophilia, parasites, drug-related

— Hypokalemia, hypocalcemia, hypomagnesemia, hypophosphatemia

— Adrenal insufficiency, Cushing, hyper/hypothyroidism

Key distinction: PMR vs PM — PMR has stiffness and pain with preserved strength and normal CK; PM has weakness with normal-to-mild pain and high CK. PMR responds to 15 mg prednisone; PM needs 60 mg.

Board pearl: Fluctuating weakness worse at end of day + ptosis = MG; sustained progressive weakness over weeks + Gottron = DM. They almost never confuse on the exam if you anchor to rash, fatigability, and CK.

Neuromuscular junction disorders:

Motor neuron disease:

Peripheral neuropathies:

CNS causes:

Rheumatologic mimics:

Systemic illness:

Electrolyte/endocrine:

Secondary Prevention, Discharge Meds, Long-Term Plan

— Prednisone with written taper schedule (taper by ~10 mg/month from 60 → 20, then 2.5 mg/month)

— Steroid-sparing agent (MTX, AZA, MMF, or IVIG schedule)

— Hydroxychloroquine for DM skin disease

— TMP-SMX 80/400 daily or 160/800 thrice weekly for PJP prophylaxis while on prednisone ≥20 mg + another IS

— Calcium 1200 mg + vitamin D 800–1000 IU daily

— Bisphosphonate (alendronate 70 mg weekly) or denosumab if high FRAX or anticipated steroid ≥3 months

— PPI if steroid + NSAID overlap or GERD

— Folic acid 1 mg daily if on MTX

— Statin or alternative lipid agent only if non-HMGCR cause confirmed

— Insulin or oral hypoglycemic if steroid-induced hyperglycemia

— Annual influenza, COVID-19, pneumococcal (PCV20 or PCV15→PPSV23), Shingrix, Tdap

— Avoid live vaccines (MMR, varicella, yellow fever) on significant IS

— Age-appropriate screening at diagnosis

— CT chest/abdomen/pelvis, mammogram, pelvic US, Pap, colonoscopy, PSA

— Repeat malignancy screen annually for 3 years, longer with anti-TIF1-γ

— Steroid + chronic inflammation = atherosclerosis acceleration

— BP <130/80, lipid management, smoking cessation, weight, exercise

Step 3 management: A patient discharged on prednisone 60 mg + MTX must leave with TMP-SMX, vitamin D/calcium, bisphosphonate consideration, glucose monitoring plan, folic acid, written steroid taper, follow-up in 2–4 weeks with labs. Missing any of these is a common Step 3 wrong-answer trap.

Board pearl: Stopping steroids abruptly after >3 weeks of high dose = adrenal crisis risk — always taper.

Discharge medication bundle (typical post-induction DM/PM):

Vaccinations (inactivated preferred during IS):

Cancer surveillance for adult DM:

Cardiovascular risk modification:

Bone health: DEXA at baseline and q1–2 years on chronic steroids

Reproductive planning: contraception with teratogens; pre-conception counseling

Follow-Up, Monitoring, Rehab, Counseling

— First 1–3 months: visits q2–4 weeks with strength exam (MMT-8), CK, CBC, CMP

— Months 3–6: q4–8 weeks

— Stable maintenance: q3 months

— PFTs (FVC, DLCO) q3–6 months if ILD; HRCT for new symptoms or worsening PFTs

— ECG/echo if cardiac involvement at baseline or symptoms

— DEXA baseline, then q1–2 years on chronic steroids

— Ophthalmology baseline before HCQ, screen at 5 years then annually

— Drug-specific:

— MTX: CBC, LFTs, Cr q4–8 weeks

— AZA: CBC q2 weeks initially, LFTs

— MMF: CBC q2–4 weeks initially

— IVIG: pre-infusion Cr, IgA level once

— Trend CK + manual muscle testing (MMT-8) + patient global together — CK alone is misleading

— Persistent weakness with normal CK → consider steroid myopathy or fixed damage

— PT early and ongoing — strength, endurance, aerobic conditioning; not contraindicated even in active disease (low-intensity preserves function)

— OT for ADLs, energy conservation

— Speech/swallow therapy for dysphagia

— Cardiopulmonary rehab if ILD

— Sun protection (DM photosensitivity, HCQ-associated)

— Infection awareness — fever on IS = urgent eval

— Vaccination plan

— Sick-day steroid stress-dose rules (double or triple for moderate illness, IV hydrocortisone for surgery/sepsis)

— Fertility, contraception, pregnancy planning

— Mental health — depression, body-image with rash/calcinosis

— Smoking cessation (ILD progression)

CCS pearl: On a CCS follow-up visit, ordering CK and MMT-8 together is more valuable than either alone — exam pattern rewards combined functional + biochemical monitoring.

Board pearl: Exercise is therapy, not contraindicated — modern guidance favors graded aerobic + resistance training even during active myositis.

Monitoring cadence:

Disease activity measures:

Rehab:

Counseling:

Patient education resources: Myositis Association, Arthritis Foundation; MedicAlert bracelet for steroid dependence

Ethical, Legal, and Patient Safety Considerations

— Discuss infection risk, malignancy risk (esp. AZA/cyclophosphamide), infertility (cyclophosphamide — offer sperm/oocyte cryopreservation before treatment), teratogenicity

— Document REMS programs for mycophenolate (mandatory pregnancy testing, two contraception methods)

— Hospital discharge to outpatient: ensure prednisone taper schedule is written, not verbal; reconcile PJP prophylaxis, bisphosphonate, calcium/vitamin D, folic acid; schedule labs and rheum follow-up within 2 weeks — missed handoff is a top patient-safety failure mode

— Sick-day rules and stress-dose steroids before surgery/dental procedures/intercurrent illness — failure = adrenal crisis

— Pediatric-to-adult rheumatology transition for JDM patients

— Medication reconciliation when adding new drugs (e.g., TMP-SMX + MTX = severe pancytopenia; allopurinol + azathioprine = fatal myelosuppression)

— Driving safety — proximal weakness affecting pedal control or dysphagia with cognitive steroid effects; counsel and document; some states require physician reporting of impairment

— Occupational disclosure — patients in physically demanding jobs; FMLA paperwork; reasonable accommodations under ADA

— Household contacts should be immunized (especially against influenza, COVID, varicella) to protect the immunosuppressed patient — discuss with family

— In refractory anti-MDA5 RP-ILD with poor prognosis, early palliative care consultation alongside aggressive immunosuppression; discuss code status, lung transplant candidacy

— Many agents (rituximab, JAKi, IVIG for PM) are off-label/expensive — document medical necessity, anticipate insurance prior authorization

— Document teratogenicity counseling; verify negative pregnancy test before starting MTX/MMF/CYC; provide contraception

Step 3 management: A patient on chronic prednisone presenting for elective surgery requires stress-dose hydrocortisone (e.g., 50–100 mg IV at induction, then taper) — failure to provide this is a sentinel safety event.

Board pearl: Allopurinol + azathioprine without dose reduction is a classic Step 3 medication-error scenario causing fatal pancytopenia.

Informed consent for immunosuppression:

Transition-of-care risks (high-yield Step 3):

Mandatory and recommended reporting / disclosure:

Vaccination ethics:

Goals of care:

Off-label and cost issues:

Pregnancy:

High-Yield Associations and Rapid-Fire Facts

— Anti-Jo-1 → antisynthetase syndrome (ILD, mechanic's hands, arthritis, Raynaud, fever)

— Anti-Mi-2 → classic DM, steroid-responsive, good prognosis

— Anti-MDA5 → amyopathic DM, rapidly progressive ILD, cutaneous ulcers

— Anti-TIF1-γ → adult malignancy-associated DM

— Anti-NXP2 → calcinosis (juvenile), malignancy (adult)

— Anti-SAE → DM with dysphagia

— Anti-SRP → severe IMNM, cardiac involvement

— Anti-HMGCR → statin-associated IMNM

— Anti-cN1A → IBM

— DM: perifascicular atrophy, complement on capillaries

— PM: endomysial CD8+ invading non-necrotic fibers, MHC-I upregulation

— IMNM: necrotic fibers, scant inflammation

— IBM: rimmed vacuoles, endomysial inflammation

— Induction: prednisone 1 mg/kg ± pulse steroids

— First-line sparing: MTX or AZA (MMF if ILD)

— DM-specific: IVIG (FDA-approved), HCQ for rash

— Anti-MDA5 RP-ILD: triple therapy (steroids + tacro + CYC/MMF)

— IMNM: steroids + IVIG + MTX/rituximab

— IBM: PT only

Board pearl: The single most discriminating exam finding for adult DM = Gottron papules; the single most prognostically devastating antibody = anti-MDA5.

DM rash buzzwords: heliotrope, Gottron papules, shawl sign, V-sign, holster sign, mechanic's hands, periungual telangiectasia, cuticular overgrowth

Autoantibody → phenotype:

Biopsy patterns:

Treatment quick reference:

Cancer screening at DM diagnosis (adult): mammogram, Pap, colonoscopy, PSA, CT C/A/P, pelvic US, consider PET if anti-TIF1-γ

Spares: ocular and (usually) facial muscles

Troponin T elevated in IIM from skeletal muscle — order troponin I for cardiac

Second-wind = McArdle, not PM

PMR vs PM: stiffness + pain + normal CK vs weakness + high CK

Steroid myopathy: normal CK + worsening weakness on high-dose steroids → reduce, don't increase

Board Question Stem Patterns

Board pearl: When the stem combines rash + weakness + age >45, the highest-yield next test is the one you'd usually skip: CT chest/abdomen/pelvis for occult cancer.

Pattern 1 — Classic DM: 52-year-old woman with 3 months of difficulty climbing stairs, violaceous rash over knuckles and eyelids, CK 3,500. Best next step? → confirm with antibodies/EMG/MRI/biopsy + age-appropriate malignancy screening including CT C/A/P; treat with prednisone 1 mg/kg + MTX or IVIG.

Pattern 2 — Anti-MDA5 RP-ILD: Amyopathic DM with palmar papules, cutaneous ulcers, rapidly worsening dyspnea, HRCT ground-glass, ferritin 3,000. Answer: ICU, pulse steroids + tacrolimus + cyclophosphamide/MMF — combination therapy from day 1.

Pattern 3 — IBM disguised as PM: 70-year-old man, 2-year history of falls, asymmetric finger flexor + quadriceps weakness, CK 800, biopsy with rimmed vacuoles. Answer: PT and supportive care, not high-dose prednisone.

Pattern 4 — Anti-HMGCR IMNM: Patient on atorvastatin develops proximal weakness; statin stopped but CK keeps rising to 12,000. Answer: anti-HMGCR antibody, treat with steroids + IVIG, do not restart statin; use PCSK9i or ezetimibe.

Pattern 5 — Malignancy-associated DM: New DM in 65-year-old, anti-TIF1-γ positive. Answer: comprehensive cancer workup; treating malignancy can remit DM.

Pattern 6 — Antisynthetase: Arthritis + Raynaud + mechanic's hands + ILD + mild myositis, anti-Jo-1 positive. Answer: glucocorticoids + MMF or rituximab + pulmonary follow-up.

Pattern 7 — Mimic trap (PMR): 70-year-old with shoulder/hip stiffness, ESR 80, normal CK, dramatic improvement on prednisone 15 mg. Answer: PMR, screen for GCA — not PM.

Pattern 8 — Mimic trap (hypothyroidism): ↑CK, weakness, fatigue, weight gain, constipation. Answer: check TSH before muscle workup.

Pattern 9 — Steroid myopathy: Patient on prednisone for DM × 6 months, worsening weakness, normal CK. Answer: taper steroids, do not escalate.

Pattern 10 — Drug interaction safety: DM patient on azathioprine started on allopurinol for gout, presents with pancytopenia. Answer: stop allopurinol, reduce AZA, recognize TPMT/xanthine oxidase interaction.

Pattern 11 — Pregnancy: Woman with DM on MTX wants pregnancy. Answer: stop MTX ≥3 months pre-conception, switch to AZA/HCQ/low-dose pred, confirm remission.

One-Line Recap

Inflammatory myopathies are subacute autoimmune diseases of symmetric proximal weakness whose subtype-specific antibodies, skin findings, and organ involvement (ILD, dysphagia, myocarditis, malignancy) dictate a regimen built on glucocorticoids plus an early steroid-sparing agent — IVIG and combination immunosuppression for severe disease — alongside cancer screening, PJP prophylaxis, bone protection, vaccination, and structured rehabilitation.

Board pearl: If you remember nothing else: Gottron + proximal weakness in a middle-aged adult = DM until proven otherwise → cancer hunt + steroids + sparing agent + IVIG; anti-MDA5 = ICU; IBM = PT; anti-HMGCR = stop the statin forever.

Step 3 management: The exam rewards the candidate who orders the boring but life-saving bundle — TMP-SMX, calcium/vitamin D, bisphosphonate, vaccinations, taper schedule, and 2-week follow-up — alongside the glamorous immunosuppression.

Diagnose with CK + aldolase + myositis antibody panel + EMG + MRI-guided muscle biopsy; rule out hypothyroidism, statin myopathy, IBM, MG, and PMR before committing to immunosuppression

Treat with prednisone 1 mg/kg + MTX/AZA/MMF (MMF if ILD); add IVIG early in DM, severe dysphagia, IMNM, or pregnancy; use triple therapy day-one for anti-MDA5 rapidly progressive ILD; PT/OT for everyone; IBM gets rehab, not steroids

Screen every adult with new DM for occult malignancy (CT C/A/P, age-appropriate screens, repeat annually × 3 years); anti-TIF1-γ raises that risk further

Prevent harm with PJP prophylaxis, bone protection, vaccination before IS, written steroid tapers, stress-dose steroids for surgery/illness, teratogen counseling, and vigilance for drug interactions (allopurinol+AZA, TMP-SMX+MTX)