Myositis in Critical Care: Recognition, Management, and Outcomes

A Comprehensive Review for the Intensivist

Dr Neeraj Manikath , Claude.ai

Abstract

Myositis represents a heterogeneous group of inflammatory muscle diseases that can present with life-threatening complications requiring intensive care management. This review provides critical care physicians with a systematic approach to recognizing, diagnosing, and managing myositis in the ICU setting. We discuss the spectrum of idiopathic inflammatory myopathies, their systemic manifestations, diagnostic challenges, and evidence-based treatment strategies. Special emphasis is placed on recognizing myositis-associated interstitial lung disease, cardiac involvement, and rhabdomyolysis as critical complications requiring immediate intervention.

Keywords: myositis, polymyositis, dermatomyositis, necrotizing myopathy, critical care, interstitial lung disease

Introduction

Myositis encompasses a diverse group of acquired inflammatory muscle disorders that can rapidly progress to multi-organ failure requiring intensive care support. The idiopathic inflammatory myopathies (IIM) include polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), and antisynthetase syndrome (ASS). While these conditions are relatively rare, with an incidence of 5-10 cases per million population annually, their potential for rapid deterioration and high mortality when complicated by respiratory failure makes recognition and early intervention crucial for intensivists.

Recent advances in myositis-specific antibody (MSA) and myositis-associated antibody (MAA) testing have revolutionized our understanding of these conditions, allowing for more precise phenotyping and prognostication. This review synthesizes current evidence to provide practical guidance for critical care management of myositis patients.

Classification and Clinical Presentation

Dermatomyositis (DM)

Dermatomyositis is characterized by the pathognomonic skin manifestations including heliotrope rash, Gottron's papules, and the shawl sign. In critical care, patients may present with:

Severe muscle weakness progressing to respiratory failure
Rapidly progressive interstitial lung disease (RP-ILD)
Cardiac arrhythmias and heart failure
Severe dysphagia with aspiration risk

Polymyositis (PM)

Pure polymyositis without skin involvement is increasingly recognized as a diagnosis of exclusion. Critical presentations include:

Proximal muscle weakness with elevated CK (often >10,000 IU/L)
Respiratory muscle involvement
Dysphagia and aspiration pneumonia

Immune-Mediated Necrotizing Myopathy (IMNM)

IMNM is associated with anti-HMGCR or anti-SRP antibodies and presents with:

Severe muscle weakness and markedly elevated CK (often >5,000-50,000 IU/L)
Potential for rapid progression
Poor response to corticosteroids alone

Antisynthetase Syndrome (ASS)

This multi-system disorder is defined by the presence of antisynthetase antibodies (most commonly anti-Jo1) and the clinical triad of:

Myositis
Interstitial lung disease (present in 70-90% of cases)
Arthritis

🔹 Pearl: The "mechanic's hands" (hyperkeratotic, cracked skin on palms and fingers) is a subtle but important sign of antisynthetase syndrome that may precede muscle symptoms.

Critical Complications Requiring ICU Management

Myositis-Associated Interstitial Lung Disease (MA-ILD)

MA-ILD is the leading cause of death in myositis patients, occurring in up to 78% of patients with antisynthetase syndrome and 65% with dermatomyositis. Recognition patterns include:

Rapidly Progressive ILD (RP-ILD):

Onset within 3 months of symptom development
Associated with anti-MDA5, anti-Jo1, and anti-PL-7 antibodies
High mortality (up to 50% at 6 months) without aggressive treatment

Chronic ILD:

Gradual onset over months to years
Better prognosis with appropriate treatment
May still require mechanical ventilation during acute exacerbations

🔹 Hack: In any myositis patient, obtain baseline HRCT chest even if asymptomatic - subclinical ILD is present in up to 50% of cases and early detection allows for prophylactic treatment.

Cardiac Involvement

Cardiac manifestations occur in 15-75% of myositis patients and include:

Conduction abnormalities (most common)
Myocarditis with heart failure
Pericarditis
Coronary artery disease (increased risk)

🔹 Oyster: A normal ECG and echocardiogram do not exclude cardiac involvement. Cardiac MRI or PET scan may reveal subclinical myocarditis in up to 75% of patients.

Rhabdomyolysis and Acute Kidney Injury

Severe rhabdomyolysis (CK >50,000 IU/L) can occur, particularly in:

IMNM patients
Statin-induced necrotizing myopathy
Concurrent infections or other triggers

Management principles include aggressive fluid resuscitation, alkalinization of urine, and early renal replacement therapy if indicated.

Diagnostic Approach in the ICU

Laboratory Investigations

Essential Tests:

Complete blood count, comprehensive metabolic panel
Creatine kinase, aldolase, LDH, AST, ALT
Inflammatory markers (ESR, CRP)
Myositis-specific and associated antibodies
Complement levels (C3, C4)

🔹 Pearl: CK levels may be normal in up to 20% of dermatomyositis patients, particularly those with amyopathic dermatomyositis or anti-MDA5 positive rapidly progressive ILD.

Advanced Testing:

Myositis antibody panel including:
- MSAs: Anti-Jo1, Anti-PL-7, Anti-PL-12, Anti-EJ, Anti-OJ, Anti-KS, Anti-Mi-2, Anti-TIF1γ, Anti-MDA5, Anti-NXP2, Anti-SAE, Anti-HMGCR, Anti-SRP
- MAAs: Anti-Ro52, Anti-PM-Scl, Anti-Ku, Anti-U1RNP

Imaging

High-Resolution CT Chest:

Essential in all myositis patients
Patterns include NSIP, UIP, organizing pneumonia, and DAD
Serial monitoring for progression

MRI Muscle:

STIR sequences show muscle edema and inflammation
Useful for biopsy guidance and monitoring treatment response
T1-weighted images reveal fatty replacement in chronic disease

Cardiac Evaluation:

ECG and echocardiogram in all patients
Consider cardiac MRI if clinical suspicion
Holter monitoring for arrhythmia detection

Muscle Biopsy

While often not feasible in critically ill patients, muscle biopsy remains the gold standard for diagnosis when clinical and serological features are inconclusive.

🔹 Hack: If muscle biopsy is being considered, perform MRI first to identify the most appropriate biopsy site and avoid sampling error from end-stage fibrotic muscle.

Treatment Strategies

First-Line Immunosuppression

Corticosteroids:

Prednisolone 1-2 mg/kg/day (maximum 80-100mg daily)
IV methylprednisolone 1g daily x 3 days for severe presentations
Gradual taper over 12-24 months

🔹 Pearl: In anti-MDA5 positive rapidly progressive ILD, early aggressive combination therapy is crucial - don't wait to see steroid response before adding additional agents.

Steroid-Sparing Agents

Methotrexate:

First-line steroid-sparing agent
15-25mg weekly (oral or subcutaneous)
Monitor for hepatotoxicity and pneumonitis
Contraindicated in significant kidney or liver disease

Azathioprine:

Alternative first-line agent
2-3 mg/kg/day
Check TPMT activity before initiation
Monitor CBC and liver function

Second-Line and Rescue Therapies

Mycophenolate Mofetil:

Increasingly used first-line, especially for ILD
2-3 grams daily in divided doses
Better GI tolerability than azathioprine

Calcineurin Inhibitors:

Tacrolimus: particularly effective for anti-MDA5 positive patients
Cyclosporine: alternative option
Require therapeutic drug monitoring

Rituximab:

Anti-CD20 monoclonal antibody
Particularly effective in antisynthetase syndrome
Dosing: 375 mg/m² weekly x 4 or 1g x 2 doses 2 weeks apart

IVIG:

2 g/kg over 2-5 days monthly
Particularly useful in refractory cases or when other agents contraindicated
May provide rapid improvement in severe weakness

Novel Therapies

JAK Inhibitors:

Tofacitinib and baricitinib showing promise
Particularly for anti-MDA5 positive rapidly progressive ILD
Requires careful monitoring for infection risk

🔹 Hack: For anti-MDA5 positive RP-ILD, consider the "triple combination": high-dose steroids + calcineurin inhibitor + mycophenolate, with early addition of rituximab or JAK inhibitor if poor initial response.

ICU-Specific Management Considerations

Mechanical Ventilation

Indications:

Respiratory muscle weakness with impending failure
Severe ILD with hypoxemic respiratory failure
Aspiration pneumonia with compromised airway protection

Ventilatory Strategy:

Lung-protective ventilation (6-8 ml/kg ideal body weight)
PEEP optimization based on recruitability
Consider prone positioning for severe ARDS
Early tracheostomy for prolonged ventilation

🔹 Pearl: Respiratory muscle weakness may persist longer than limb weakness - don't rush extubation based on improving peripheral strength alone.

Infection Prophylaxis and Monitoring

Immunosuppressed myositis patients are at high risk for opportunistic infections:

PCP prophylaxis with trimethoprim-sulfamethoxazole
Consider CMV monitoring and prophylaxis
Fungal prophylaxis in high-risk patients
Regular surveillance cultures

Nutritional Support

Early enteral nutrition when possible
Assess swallowing function before oral intake
Consider PEG tube for prolonged dysphagia
Protein requirements may be increased (1.5-2 g/kg/day)

Rehabilitation

Early mobilization when clinically stable
Physical and occupational therapy
Speech therapy for dysphagia
Gradual activity progression

Monitoring and Assessment of Treatment Response

Clinical Parameters

Manual muscle testing (MMT-8)
Functional assessments (HAQ, patient global assessments)
Respiratory function tests
Swallowing evaluation

Laboratory Monitoring

CK levels (may normalize before clinical improvement)
Inflammatory markers
Myositis antibody titers (some correlate with disease activity)
Drug toxicity monitoring

Imaging Follow-up

Serial HRCT chest for ILD monitoring
MRI muscle for treatment response assessment
Cardiac monitoring as indicated

🔹 Oyster: CK normalization doesn't always correlate with clinical improvement, and CK may remain elevated in IMNM patients despite treatment response. Use clinical assessment as the primary endpoint.

Prognostic Factors and Outcomes

Poor Prognostic Indicators

Rapidly progressive ILD
Anti-MDA5 positive with low/absent CK elevation
Older age at onset (>45 years)
Male gender in dermatomyositis
Cardiac involvement
Malignancy-associated myositis
Delayed treatment initiation

Mortality

Overall 5-year mortality: 20-30%
RP-ILD: up to 50% mortality at 6 months
ICU mortality varies by presentation but can exceed 40%

🔹 Pearl: Early aggressive treatment within the first 3 months of symptom onset significantly improves long-term outcomes, particularly for ILD.

Special Populations

Malignancy-Associated Myositis

Screen all adult dermatomyositis patients for malignancy
Peak risk within 2 years of myositis diagnosis
Age-appropriate screening plus CT chest/abdomen/pelvis
Consider PET scan in high-risk patients

Juvenile Dermatomyositis

Different clinical course with more frequent calcinosis
Higher frequency of severe GI involvement
Generally better prognosis than adult forms

Drug-Induced Myositis

Statins, immune checkpoint inhibitors, D-penicillamine
May require discontinuation of offending agent
Statin-associated IMNM may persist despite drug cessation

Future Directions and Emerging Therapies

Biomarkers

Interferon gene signatures for monitoring disease activity
Novel autoantibodies for phenotype prediction
Muscle-specific biomarkers beyond CK

Targeted Therapies

Type I interferon inhibitors (anifrolumab)
Complement inhibitors
Cell-specific targeting strategies

Precision Medicine

Antibody-guided treatment selection
Pharmacogenomic approaches to drug selection
Personalized monitoring strategies

Key Clinical Pearls and Hacks

Diagnostic Pearls

The "anti-MDA5 paradox": Patients with rapidly progressive ILD often have minimal muscle involvement and normal/low CK levels
Gottron's sign vs. Gottron's papules: The sign (flat erythema over joints) is more specific than papules (raised lesions)
Heliotrope rash mimics: Allergic reactions, angioedema, and dermatomyositis can look similar - check for Gottron's signs
The "shawl sign": V-neck and upper back/shoulder erythema is highly specific for dermatomyositis

Treatment Hacks

The "pulse and taper": Start with IV methylprednisolone pulse, then high-dose oral prednisolone with early steroid-sparing agent
The "triple threat" for RP-ILD: Steroids + mycophenolate + tacrolimus, with early rituximab consideration
The "CK disconnect": Don't rely solely on CK levels for treatment decisions - clinical assessment is paramount
The "infection balance": Aggressive immunosuppression saves lives in severe myositis, but infection surveillance is crucial

Monitoring Oysters

Subclinical ILD: Up to 50% of patients have asymptomatic ILD on HRCT
Cardiac involvement: Often subclinical but can be life-threatening
Cancer screening: All adult DM patients need comprehensive screening
Drug interactions: Many myositis medications have significant drug-drug interactions

Conclusion

Myositis in the critical care setting represents a complex challenge requiring rapid recognition, aggressive treatment, and multidisciplinary care. The key to successful outcomes lies in early identification of high-risk phenotypes, particularly those with rapidly progressive ILD or cardiac involvement, and prompt initiation of appropriate immunosuppressive therapy. Recent advances in antibody testing and targeted therapies offer hope for improved outcomes, but the fundamental principles of intensive care - organ support, infection prevention, and rehabilitation - remain crucial.

The intensivist managing myositis patients must balance aggressive immunosuppression against infection risk, while monitoring for multiple organ system involvement. With proper recognition and management, many patients can achieve significant improvement and return to functional independence.

References

Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76(12):1955-1964.
Aggarwal R, Ringold S, Khanna D, et al. Distinctions between diagnostic and classification criteria? Arthritis Care Res. 2015;67(7):891-897.
Sato S, Hirakata M, Kuwana M, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52(5):1571-1576.
Moghadam-Kia S, Oddis CV, Sato S, et al. Anti-melanoma differentiation-associated gene 5 is associated with rapidly progressive lung disease and poor survival in US patients with amyopathic and myopathic dermatomyositis. Arthritis Care Res. 2016;68(5):689-694.
Marie I, Hatron PY, Dominique S, et al. Short-term and long-term outcomes of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients. Arthritis Rheum. 2011;63(11):3439-3447.
Tymms KE, Webb J. Dermatopolymyositis and other connective tissue diseases: a review of 105 cases. J Rheumatol. 1985;12(6):1140-1148.
Rider LG, Katz JD, Jones OY. Developments in the classification and treatment of the juvenile idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2013;39(4):877-904.
Betteridge Z, Tansley S, Shaddick G, et al. Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. J Autoimmun. 2019;101:48-55.
Aggarwal R, Cassidy E, Fertig N, et al. Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis. 2014;73(1):227-232.
Cavagna L, Trallori G, Felicetti M, et al. Myositis-specific and myositis-associated antibody positive idiopathic inflammatory myopathies: clinical phenotypes, prognosis, and response to therapy. Rheumatology. 2021;60(6):2574-2585.

Declaration of Interests: The authors declare no competing interests.

Friday, August 22, 2025