AUTOIMMUNE MYOSITIS SUBTYPES AND THEIR CLINICAL MANIFESTATIONS

Distinct clinical phenotypes exist across the autoimmune myositis spectrum

Autoimmune myositis (AIM) encompasses multiple subtypes with distinct clinical, serological, and pathological features. Although progressive muscle weakness is a shared hallmark, patterns of extramuscular involvement, disease progression, and associated autoantibodies can vary substantially between subtypes.1,2

 

Understanding these differences is critical for accurate classification, diagnosis, and management.1

AIM is a rare, chronic, progressive disease with muscular and extramuscular manifestations that can lead to a loss of independence and quality of life2,3

Progressive skeletal muscle weakness remains the hallmark manifestation, most commonly affecting proximal muscle groups. Extramuscular disease is also common and may involve multiple organ systems, including:1

Pulmonary manifestations

Particularly interstitial lung disease (ILD)1,4

Cutaneous

(rashes/calcinosis/itch)1,5

Cardiac

(myocarditis/cardiomyopathy)1,6

Gastrointestinal

(dysphagia)1

Manifestations such as interstitial lung disease, dysphagia and myocarditis are of particular clinical concern due to their impact on morbidity and mortality.7

AIM is comprised of distinct subtypes with diverse presentations

AIM includes several recognized subtypes, classified based on clinical, serological, and pathological features.

Simple cross-section diagram of the skin with 3 hair follicles and inflamed skin tissue.

Dermatomyositis (DM)

Collection of icons representing a muscle, lungs, joints, and skin.

Antisynthetase syndrome (ASyS)

Simplified diagram of a muscle structure.

Immune-mediated necrotizing myopathy (IMNM)

Simplified diagram of a muscle structure with diagnonal line across it, placed next to warning sign over 3 antibody icons.

Inclusion body myositis (IBM)a

Collection of icons representing lungs, stomach, heart, joints, and skin.

Overlap myositis (OM)

Icon of a person walking with wavy lines around the legs.

Polymyositis (PM)b

Differentiating AIM subtypes

The major subtypes of AIM are defined by combinations of clinical manifestations, histopathological findings, imaging features, and autoantibody profiles. Increasing recognition of myositis-specific autoantibodies has refined disease classification and improved understanding of subtype-specific phenotypes.5,8

While overlap exists between subtypes, each demonstrates characteristic patterns of muscle involvement and extramuscular disease.5,8

Clinical Manifestations:

Cutaneous features,c plus: 'Classic (myopathic) DM: symmetric proximal muscle weakness; Amyopathic DM: no muscle involvement; Hypomyopathic DM: no clinical muscle weakness

 

Systemic Manifestations:

Interstitial lung disease (ILD), dysphagia, dysphonia, malignancy

 

Autoantibodies:

TIF1γ, NXP2, MDA5, Mi2, SAE, Sp4, CCAR1

Clinical Manifestations:

Symmetric proximal muscle weakness, prominent muscle atrophy

 

Systemic Manifestations:

Malignancy, connective tissue diseases

 

Autoantibodies:

SRP (severe, progressive weakness); HMGCR (associated with statin exposure)

Clinical Manifestations:

Symmetric proximal muscle weakness, and presence of at least one of the associated conditions

 

Systemic Manifestations:

ILD, mechanic’s hands, arthritis, Raynaud’s syndrome

 

Autoantibodies:

Jo1, PL7, PL12, EJ, OJ, KS, ZO, YRS/HA

Clinical Manifestations:

Symmetric proximal muscle weakness

 

Systemic Manifestations:

ILD, malignancy, myocarditis

 

Autoantibodies:

Seronegative for myositis-specific autoantibodies

Clinical Manifestations:

Symmetric proximal muscle weakness co-exists with features of other autoimmune diseases

 

Systemic Manifestations:

Scleroderma, systemic lupus erythematosus

 

Autoantibodies:

PMScl, Ro52, Ku, U1RNP

Clinical Manifestations:

Proximal as well as distal muscle weakness that is often asymmetric; facial muscles may be involved

 

Systemic Manifestations:

Dysphagia

 

Autoantibodies:

cN1A

Continue exploring AIM

Learn more about AIM.

What is AIM?

AIM is a chronic, progressive autoimmune rheumatic disease comprised of distinct subtypes.1

Take a deeper look at AIM

a The pathogenesis of IBM is debated. While it can be categorized as an idiopathic inflammatory myopathy, it may not fit completely under the term 'autoimmune myositis.'9

b  Polymyositis is increasingly considered a diagnosis of exclusion, as many cases are reclassified into more specific subtypes with advancing diagnostic criteria.2

c Cutaneous features include heliotrope, shawl sign, Gottron’s papules, etc.

Abbreviations:
AIM, autoimmune myositis; ASyS, antisynthetase syndrome; CCAR-1, cell cycle and apoptosis regulator 1; CN1a, cytosolic 5’-nucleotodase 1A; DM, dermatomyositis; EJ, glycyl-tRNA synthetase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IBM, inclusion body myositis; ILD, interstitial lung disease; IMNM, immune-mediated necrotzing myopathy; KS, asparaginyl-tRNA synthetase; MDA5, melanoma differentiation-associated gene 5; NXP2, nuclear matrix protein 2; OJ, isoleucyl-tRNA synthetase; OM, overlap myositis; PL7, threonyl-tRNA-synthetase; PL12, alanyl-tRNA synthetase; PM, polymyositis; PMScl, polymyositis–scleroderma overlap; SAE, small ubiquitin-like modified activating enzyme; Sp4, transcription factor Sp4; SRP, signal recognition particle; TIF1γ, transcription intermediary factor 1-gamma; U1RNP, U1 small nuclear ribonucleoprotein; ZO, phenylalanyl-tRNA synthetase.

 

References:
1. Diomedi M, et al. Clin Exp Rheumatol. 2026;44(2):167–177; 2. Lundberg IE, et al. Nat Rev Dis Primers. 2021;7(1):86; 3. Oldroyd A, et al. BMC Rheumatol. 2020;4:47; 4. Saketkoo LA, et al. Curr Rheumatol Rev. 2010;6(2):108–119; 5. Oldroyd A, et al. Clin Med (Lond). 2017;17(4):322–328; 6. Zhu H, et al. J Inflamm Res. 2025:18:3879–3888; 7. Khoo T, et al. Nat Rev Rheumatol. 2023;19(11):695–712; 8. Paik JJ, et al. Rheumatology. 2025;64:3288–3302; 9. Greenberg SA. Nat Rev Rheumatol. 2019;15(5):257–72.