Dermatomyositis

Autoimmune MONDO:0016367 Pathograph 4 Show in embeddings browser Autoimmune Disease Inflammatory Myopathy

An idiopathic inflammatory myopathy characterized by proximal muscle weakness and distinctive skin manifestations including heliotrope rash and Gottron's papules. Associated with increased risk of malignancy and interstitial lung disease in certain autoantibody subsets.

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1
Inheritance
4
Pathophys.
47
Phenotypes
4
Pathograph
6
Genes
10
Medical Actions
4
Datasets
13
References
2
Deep Research
🏷

Classifications

Harrison's Part
IMMUNE RHEUMATOLOGIC
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Inheritance

1
Not applicable
Dermatomyositis is an autoimmune disease, not an inherited Mendelian disorder. HLA associations (e.g., HLA-DRB1*0301) confer genetic susceptibility but do not follow a Mendelian pattern.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"Not applicable"
Orphanet classifies dermatomyositis inheritance as not applicable.
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Pathophysiology

4
Complement-Mediated Microangiopathy
Membrane attack complex (MAC) deposition on endomysial capillaries leads to capillary damage, ischemia, and perifascicular atrophy characteristic of dermatomyositis. This distinguishes it from polymyositis.
Endothelial Cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Endothelial Cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology.
Complement Activation GO:0006956 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Complement Activation (GO:0006956). GO:0006956 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:38143369 SUPPORT
"Deposition of complement around capillaries and/or the sarcolemma was observed in muscle biopsy specimens from patients with DM, ASS, and IMNM, suggesting the pathomechanism of complement-dependent muscle and endothelial cell injury."
This evidence demonstrates that complement deposition is a characteristic pathological feature of dermatomyositis, contributing to muscle and endothelial cell injury through complement-dependent mechanisms.
PMID:38143369 SUPPORT
"Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy."
This evidence links the microangiopathy to the characteristic perifascicular atrophy observed in dermatomyositis, supporting the ischemic mechanism of muscle damage.
Type I Interferon Pathway Activation
Strong type I interferon signature in muscle and skin. Plasmacytoid dendritic cells accumulate in affected tissues and produce IFN-alpha, driving inflammation and MxA protein expression.
Plasmacytoid Dendritic Cell CL:0000784 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Plasmacytoid Dendritic Cell (CL:0000784). CL:0000784 is a cell type from the Cell Ontology.
Type I Interferon Response GO:0034340 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Type I Interferon Response, annotated with response to type I interferon (GO:0034340). GO:0034340 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:38143369 SUPPORT
"The pathological observation of myxovirus resistance protein A (MxA), which suggests a type 1 interferon (IFN1) signature in DM, supports the diagnosis and further understanding of the pathomechanism of IIM."
MxA expression is a hallmark of type I interferon activation in dermatomyositis, providing diagnostic and pathomechanistic insights.
PMID:39334579 SUPPORT
"Histopathological studies have revealed critical roles of type I interferons and vasculopathy in the development of JDM."
This evidence confirms that type I interferon signaling is a central pathogenic mechanism in dermatomyositis, including juvenile forms.
Myositis-Specific Autoantibodies
Distinct autoantibodies define clinical phenotypes: anti-Mi-2 (classic dermatomyositis), anti-MDA5 (amyopathic with ILD), anti-TIF1-gamma (cancer-associated), and anti-NXP2 (calcinosis).
Immunoglobulin Production GO:0002377 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Immunoglobulin Production (GO:0002377). GO:0002377 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:39334579 SUPPORT
"Each MSA or MAA is associated with distinct clinical features and outcomes, although there are several differences in the prevalence of MSA/MAA and autoantibody-phenotype relationships between age and ethnic groups."
This evidence confirms that myositis-specific autoantibodies (MSAs) define distinct clinical phenotypes in dermatomyositis, supporting the concept of autoantibody-driven disease subtypes.
Perivascular Inflammation and Immune Cell Infiltration
Perivascular inflammation contributes to muscle damage in dermatomyositis. Immune cell infiltrates including CD4+ T cells and B cells are found in perivascular and perimysial locations.
CD4+ T Cell CL:0000624 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves CD4+ T Cell, annotated with CD4-positive, alpha-beta T cell (CL:0000624). CL:0000624 is a cell type from the Cell Ontology. B Cell CL:0000236 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves B Cell (CL:0000236). CL:0000236 is a cell type from the Cell Ontology.
Adaptive Immune Response GO:0002250 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Adaptive Immune Response (GO:0002250). GO:0002250 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:38143369 SUPPORT
"Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy."
Confirms perivascular inflammation as a characteristic feature of DM muscle pathology.
PMID:38143369 SUPPORT Human Clinical
"an increase in triggering receptor expressed on myeloid cells (TREM-1) around perimysial blood vessels and muscles in patients with IIM plays a role in triggering inflammation and promoting the migration of inflammatory cells"
TREM-1 upregulation around perimysial vessels amplifies perivascular inflammation and recruits inflammatory cells in idiopathic inflammatory myopathies, providing a molecular driver of the immune cell infiltration.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Dermatomyositis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

47
Cardiovascular 7
Erythema VERY_FREQUENT HP:0010783 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Erythema (HP:0010783). HP:0010783 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0010783 | Erythema | Very frequent (99-80%)"
Orphanet classifies erythema as very frequent in dermatomyositis.
Facial Erythema FREQUENT HP:0001041 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Facial erythema (HP:0001041). HP:0001041 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001041 | Facial erythema | Frequent (79-30%)"
Orphanet classifies facial erythema as frequent in dermatomyositis.
Raynaud Phenomenon OCCASIONAL HP:0030880 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Raynaud phenomenon (HP:0030880). HP:0030880 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0030880 | Raynaud phenomenon | Occasional (29-5%)"
Orphanet classifies Raynaud phenomenon as occasional in dermatomyositis.
PMID:33599244 SUPPORT
"Raynaud's phenomenon (RR 0.61)"
Meta-analysis shows Raynaud phenomenon is associated with reduced cancer risk in IIM (protective factor, RR 0.61).
Myocarditis OCCASIONAL HP:0012819 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myocarditis (HP:0012819). HP:0012819 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0012819 | Myocarditis | Occasional (29-5%)"
Orphanet classifies myocarditis as occasional in dermatomyositis.
Pericarditis OCCASIONAL HP:0001701 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pericarditis (HP:0001701). HP:0001701 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001701 | Pericarditis | Occasional (29-5%)"
Orphanet classifies pericarditis as occasional in dermatomyositis.
Arrhythmia OCCASIONAL HP:0011675 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arrhythmia (HP:0011675). HP:0011675 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0011675 | Arrhythmia | Occasional (29-5%)"
Orphanet classifies arrhythmia as occasional in dermatomyositis.
Vasculitis OCCASIONAL HP:0002633 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vasculitis (HP:0002633). HP:0002633 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0002633 | Vasculitis | Occasional (29-5%)"
Orphanet classifies vasculitis as occasional in dermatomyositis.
Digestive 1
Dysphagia OCCASIONAL HP:0002015 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
ORPHA:221 SUPPORT
"HP:0002015 | Dysphagia | Occasional (29-5%)"
Orphanet classifies dysphagia as occasional in dermatomyositis. Note that frequency estimates vary; the Norwegian cohort found 58%.
PMID:24695011 SUPPORT
"Frequent clinical features included myalgia (75%), arthritis (41%) dyspnoea (62%) and dysphagia (58%)."
Norwegian population study found dysphagia in 58% of PM/DM patients.
PMID:33599244 SUPPORT
"dysphagia (RR 2.09)"
Meta-analysis identifies dysphagia as a significant cancer risk factor in IIM (RR 2.09).
Immune 1
Recurrent Respiratory Infections FREQUENT HP:0002205 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Recurrent respiratory infections (HP:0002205). HP:0002205 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0002205 | Recurrent respiratory infections | Frequent (79-30%)"
Orphanet classifies recurrent respiratory infections as frequent in dermatomyositis.
Integument 7
Cutaneous Photosensitivity OCCASIONAL HP:0000992 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cutaneous photosensitivity (HP:0000992). HP:0000992 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0000992 | Cutaneous photosensitivity | Occasional (29-5%)"
Orphanet classifies cutaneous photosensitivity as occasional in dermatomyositis.
Skin Ulcer FREQUENT HP:0200042 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin ulcer (HP:0200042). HP:0200042 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0200042 | Skin ulcer | Frequent (79-30%)"
Orphanet classifies skin ulcer as frequent in dermatomyositis.
PMID:33599244 SUPPORT
"cutaneous ulceration (RR 2.73)"
Meta-analysis identifies cutaneous ulceration as a significant risk factor for cancer in IIM (risk ratio 2.73).
Pruritus FREQUENT HP:0000989 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pruritus (HP:0000989). HP:0000989 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0000989 | Pruritus | Frequent (79-30%)"
Orphanet classifies pruritus as frequent in dermatomyositis.
Poikiloderma OCCASIONAL HP:0001029 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Poikiloderma (HP:0001029). HP:0001029 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001029 | Poikiloderma | Occasional (29-5%)"
Orphanet classifies poikiloderma as occasional in dermatomyositis.
Acrocyanosis FREQUENT HP:0001063 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Acrocyanosis (HP:0001063). HP:0001063 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001063 | Acrocyanosis | Frequent (79-30%)"
Orphanet classifies acrocyanosis as frequent in dermatomyositis.
Abnormal Nail Morphology FREQUENT HP:0001597 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal nail morphology (HP:0001597). HP:0001597 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001597 | Abnormality of the nail | Frequent (79-30%)"
Orphanet classifies nail abnormalities as frequent in dermatomyositis.
Dry Skin FREQUENT HP:0000958 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dry skin (HP:0000958). HP:0000958 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0000958 | Dry skin | Frequent (79-30%)"
Orphanet classifies dry skin as frequent in dermatomyositis.
Metabolism 4
Fever OCCASIONAL HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001945 | Fever | Occasional (29-5%)"
Orphanet classifies fever as occasional in dermatomyositis.
Elevated Creatine Kinase FREQUENT Elevated circulating creatine kinase concentration HP:0003236 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated circulating creatine kinase concentration (HP:0003236). HP:0003236 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0003236 | Elevated circulating creatine kinase concentration | Frequent (79-30%)"
Orphanet classifies elevated CK as frequent in dermatomyositis.
Elevated Hepatic Transaminases FREQUENT Elevated circulating hepatic transaminase concentration HP:0002910 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated circulating hepatic transaminase concentration (HP:0002910). HP:0002910 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0002910 | Elevated circulating hepatic transaminase concentration | Frequent (79-30%)"
Orphanet classifies elevated transaminases as frequent in dermatomyositis.
Hyperferritinemia Increased circulating ferritin concentration HP:0003281 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Increased circulating ferritin concentration (HP:0003281). HP:0003281 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38456909 SUPPORT Human Clinical
"the deceased patients tended to be older and had higher ferritin levels"
In a case series and literature review of anti-MDA5-DM-associated ILD, higher serum ferritin was a feature of patients who died, supporting hyperferritinemia as an adverse prognostic biomarker in dermatomyositis.
Musculoskeletal 5
Proximal Muscle Weakness VERY_FREQUENT HP:0003701 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Proximal muscle weakness (HP:0003701). HP:0003701 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0003701 | Proximal muscle weakness | Very frequent (99-80%)"
Orphanet classifies proximal muscle weakness as very frequent (99-80%) in dermatomyositis.
PMID:37153943 SUPPORT
"Together with skin features, patients show muscle involvement, most commonly with symmetrical weakness of the proximal muscles."
Comprehensive review confirms symmetrical proximal muscle weakness as a core feature.
Hypotonia FREQUENT HP:0001252 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotonia (HP:0001252). HP:0001252 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001252 | Hypotonia | Frequent (79-30%)"
Orphanet classifies hypotonia as frequent in dermatomyositis.
Respiratory Insufficiency due to Muscle Weakness FREQUENT HP:0002747 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory insufficiency due to muscle weakness (HP:0002747). HP:0002747 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0002747 | Respiratory insufficiency due to muscle weakness | Frequent (79-30%)"
Orphanet classifies respiratory muscle weakness as frequent in dermatomyositis.
PMID:24695011 SUPPORT
"Frequent clinical features included myalgia (75%), arthritis (41%) dyspnoea (62%) and dysphagia (58%)."
Norwegian cohort found dyspnoea in 62% of PM/DM patients. Partial only: the cohort reports dyspnoea without attributing it to respiratory muscle weakness, and in dermatomyositis dyspnoea is frequently driven by interstitial lung disease rather than by muscle weakness.
Arthritis FREQUENT HP:0001369 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arthritis (HP:0001369). HP:0001369 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0001369 | Arthritis | Frequent (79-30%)"
Orphanet classifies arthritis as frequent in dermatomyositis.
PMID:24695011 SUPPORT
"Frequent clinical features included myalgia (75%), arthritis (41%) dyspnoea (62%) and dysphagia (58%)."
Norwegian cohort found arthritis in 41% of PM/DM patients.
Calcinosis Cutis FREQUENT HP:0025520 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Calcinosis cutis (HP:0025520). HP:0025520 is a phenotype from the Human Phenotype Ontology.
Orphanet maps this as HP:0000934 Chondrocalcinosis; HP:0025520 Calcinosis cutis is the more precise term for DM-associated dystrophic calcification.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0000934 | Chondrocalcinosis | Frequent (79-30%)"
Orphanet classifies this as chondrocalcinosis (frequent). The more precise HP term for DM-associated calcinosis is HP:0025520 Calcinosis cutis.
PMID:38929957 SUPPORT
"A total of 839 CTD patients were identified, of whom 56 had calcinosis (6.67%)."
Retrospective study confirms calcinosis prevalence of 6.67% across autoimmune connective tissue diseases including dermatomyositis.
Respiratory 3
Pulmonary Fibrosis FREQUENT HP:0002206 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary fibrosis (HP:0002206). HP:0002206 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
ORPHA:221 SUPPORT
"HP:0002206 | Pulmonary fibrosis | Frequent (79-30%)"
Orphanet classifies pulmonary fibrosis as frequent in dermatomyositis.
PMID:38456909 SUPPORT
"Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-DM) is frequently complicated by progressive interstitial lung disease (ILD), the prognosis of which is poor, and management is a major challenge."
Anti-MDA5 positive dermatomyositis is strongly associated with progressive ILD.
PMID:39334579 SUPPORT
"However, rapidly progressive interstitial lung disease (RP-ILD) remains a major cause of death in anti-melanoma differentiation gene 5 autoantibody-positive JDM."
RP-ILD is a leading cause of death in anti-MDA5 positive DM.
Respiratory Insufficiency FREQUENT HP:0002093 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory insufficiency (HP:0002093). HP:0002093 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0002093 | Respiratory insufficiency | Frequent (79-30%)"
Orphanet classifies respiratory insufficiency as frequent in dermatomyositis.
Abnormal Pulmonary Interstitial Morphology FREQUENT HP:0006530 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal pulmonary interstitial morphology (HP:0006530). HP:0006530 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0006530 | Abnormal pulmonary interstitial morphology | Frequent (79-30%)"
Orphanet classifies abnormal pulmonary interstitial morphology as frequent in dermatomyositis.
Constitutional 3
Myalgia VERY_FREQUENT HP:0003326 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myalgia (HP:0003326). HP:0003326 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0003326 | Myalgia | Very frequent (99-80%)"
Orphanet classifies myalgia as very frequent in dermatomyositis.
PMID:24695011 SUPPORT
"Frequent clinical features included myalgia (75%), arthritis (41%) dyspnoea (62%) and dysphagia (58%)."
Norwegian population-based cohort found myalgia in 75% of PM/DM patients.
Arthralgia FREQUENT HP:0002829 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Arthralgia (HP:0002829). HP:0002829 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0002829 | Arthralgia | Frequent (79-30%)"
Orphanet classifies arthralgia as frequent in dermatomyositis.
Fatigue FREQUENT HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0012378 | Fatigue | Frequent (79-30%)"
Orphanet classifies fatigue as frequent in dermatomyositis.
Growth 1
Weight Loss FREQUENT HP:0001824 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Weight loss (HP:0001824). HP:0001824 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001824 | Weight loss | Frequent (79-30%)"
Orphanet classifies weight loss as frequent in dermatomyositis.
Neoplasm 1
Malignancy OCCASIONAL Neoplasm HP:0002664 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Neoplasm (HP:0002664). HP:0002664 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
ORPHA:221 SUPPORT
"HP:0002664 | Neoplasm | Occasional (29-5%)"
Orphanet classifies neoplasm as occasional in dermatomyositis.
PMID:33599244 SUPPORT
"DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer."
Systematic review and meta-analysis of 69 studies identifies key cancer risk factors in IIM, with DM subtype itself conferring a 2.21-fold increased risk.
PMID:33599244 SUPPORT
"Around one in four patients are diagnosed with cancer within 3 years before or after IIM onset"
Approximately 25% of IIM patients develop cancer temporally related to disease onset.
Other 14
Limb-Girdle Muscle Weakness VERY_FREQUENT HP:0003325 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Limb-girdle muscle weakness (HP:0003325). HP:0003325 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0003325 | Limb-girdle muscle weakness | Very frequent (99-80%)"
Orphanet classifies limb-girdle weakness as very frequent in dermatomyositis.
Inflammatory Myopathy VERY_FREQUENT HP:0009071 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Inflammatory myopathy (HP:0009071). HP:0009071 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0009071 | Inflammatory myopathy | Very frequent (99-80%)"
Orphanet classifies inflammatory myopathy as very frequent in dermatomyositis.
Heliotrope Rash FREQUENT HP:0040324 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Heliotrope rash (HP:0040324). HP:0040324 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0040324 | Heliotrope rash | Frequent (79-30%)"
Orphanet classifies heliotrope rash as frequent in dermatomyositis.
PMID:37153943 SUPPORT
"heliotrope rash, and violaceous papules located at the interphalangeal or metacarpophalangeal joints (Gottron's papules) are the most frequently observed."
Comprehensive review identifies heliotrope rash as one of the most frequent skin findings.
Gottron's Papules FREQUENT HP:0025508 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gottron's papules (HP:0025508). HP:0025508 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:221 SUPPORT
"HP:0025508 | Gottron's papules | Frequent (79-30%)"
Orphanet classifies Gottron's papules as frequent in dermatomyositis.
PMID:37153943 SUPPORT
"heliotrope rash, and violaceous papules located at the interphalangeal or metacarpophalangeal joints (Gottron's papules) are the most frequently observed."
Comprehensive review identifies Gottron's papules as one of the most frequent skin findings.
Gottron Sign OCCASIONAL HP:0430033 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gottron sign (HP:0430033). HP:0430033 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0430033 | Gottron sign | Occasional (29-5%)"
Orphanet classifies Gottron sign as occasional in dermatomyositis.
Periorbital Edema VERY_FREQUENT HP:0100539 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Periorbital edema (HP:0100539). HP:0100539 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0100539 | Periorbital edema | Very frequent (99-80%)"
Orphanet classifies periorbital edema as very frequent in dermatomyositis.
V-Sign OCCASIONAL HP:0025536 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is V-sign (HP:0025536). HP:0025536 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0025536 | V-sign | Occasional (29-5%)"
Orphanet classifies V-sign as occasional in dermatomyositis.
Shawl Sign FREQUENT HP:0025535 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Shawl sign (HP:0025535). HP:0025535 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0025535 | Shawl sign | Frequent (79-30%)"
Orphanet classifies shawl sign as frequent in dermatomyositis.
Holster Sign OCCASIONAL HP:6000006 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Holster sign (HP:6000006). HP:6000006 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:6000006 | Holster sign | Occasional (29-5%)"
Orphanet classifies holster sign as occasional in dermatomyositis.
Dysphonia OCCASIONAL HP:0001618 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphonia (HP:0001618). HP:0001618 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0001618 | Dysphonia | Occasional (29-5%)"
Orphanet classifies dysphonia as occasional in dermatomyositis.
Elevated Aldolase FREQUENT Elevated circulating aldolase concentration HP:0012544 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated circulating aldolase concentration (HP:0012544). HP:0012544 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0012544 | Elevated circulating aldolase concentration | Frequent (79-30%)"
Orphanet classifies elevated aldolase as frequent in dermatomyositis.
Elevated LDH FREQUENT Increased circulating lactate dehydrogenase concentration HP:0025435 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Increased circulating lactate dehydrogenase concentration (HP:0025435). HP:0025435 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0025435 | Increased circulating lactate dehydrogenase concentration | Frequent (79-30%)"
Orphanet classifies elevated LDH as frequent in dermatomyositis.
EMG Abnormality VERY_FREQUENT HP:0003457 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is EMG abnormality (HP:0003457). HP:0003457 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0003457 | EMG abnormality | Very frequent (99-80%)"
Orphanet classifies EMG abnormality as very frequent in dermatomyositis.
Diffuse Reticular or Finely Nodular Infiltrations FREQUENT HP:0002207 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diffuse reticular or finely nodular infiltrations (HP:0002207). HP:0002207 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:221 SUPPORT
"HP:0002207 | Diffuse reticular or finely nodular infiltrations | Frequent (79-30%)"
Orphanet classifies diffuse reticular infiltrations as frequent in dermatomyositis.
🧬

Genetic Associations

6
HLA-DRB1*0301 (Risk Factor)
TRIM33 (TIF1-gamma) (Associated)
Gene: TRIM33 hgnc:16290 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is TRIM33 (hgnc:16290). hgnc:16290 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:31279808 SUPPORT
"anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk."
Review confirms anti-TIF1 (TRIM33) antibodies define a DM subtype with distinct clinical features and cancer risk.
IFIH1 (MDA5) (Associated)
Gene: IFIH1 hgnc:18873 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is IFIH1 (hgnc:18873). hgnc:18873 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:31279808 SUPPORT
"anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk."
Review confirms anti-MDA5 (IFIH1) antibodies define a DM subtype with amyopathic presentation and ILD risk.
CHD4 (Mi-2) (Associated)
Gene: CHD4 hgnc:1919 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CHD4 (hgnc:1919). hgnc:1919 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:31279808 SUPPORT
"anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk."
Review confirms anti-Mi-2 (CHD4) antibodies define classic DM with good prognosis.
MORC3 (NXP-2) (Associated)
Gene: MORC3 hgnc:23572 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is MORC3 (hgnc:23572). hgnc:23572 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (2 references)
PMID:31279808 SUPPORT
"anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk."
Review confirms anti-NXP2 (MORC3) antibodies define a DM subtype with distinct clinical features.
PMID:33599244 SUPPORT Human Clinical
"Anti-nuclear matrix protein 2 (anti-NXP2) positivity was a non-significant factor"
In a 69-study meta-analysis of IIM cancer risk, anti-NXP2 positivity was a non-significant cancer risk factor, qualifying the reported NXP2-malignancy association.
SAE1 (SAE) (Associated)
Gene: SAE1 hgnc:30660 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SAE1 (hgnc:30660). hgnc:30660 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:31279808 SUPPORT
"anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk."
Review confirms anti-SAE (SAE1) antibodies define a DM subtype with skin-predominant presentation.
💊

Medical Actions

10
Corticosteroids
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: prednisolone CHEBI:8378 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses prednisolone (CHEBI:8378). CHEBI:8378 is a therapeutic agent from Chemical Entities of Biological Interest.
First-line therapy for muscle and skin inflammation.
Show evidence (1 reference)
PMID:30670084 SUPPORT Human Clinical
"Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM."
The Brazilian Society of Rheumatology guideline affirms glucocorticoids as first-line therapy for systemic autoimmune myopathies including dermatomyositis.
Methotrexate
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: methotrexate CHEBI:44185 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses methotrexate (CHEBI:44185). CHEBI:44185 is a therapeutic agent from Chemical Entities of Biological Interest.
Steroid-sparing immunosuppressant.
Azathioprine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: azathioprine CHEBI:2948 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses azathioprine (CHEBI:2948). CHEBI:2948 is a therapeutic agent from Chemical Entities of Biological Interest.
Steroid-sparing immunosuppressant for maintenance therapy.
Show evidence (1 reference)
PMID:37153943 SUPPORT
"several steroid-sparing agents, such as methotrexate, azathioprine or mycophenolate mofetil, have been reported as effective in treating DM."
Comprehensive review confirms azathioprine as an effective steroid-sparing agent.
Mycophenolate Mofetil
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: mycophenolate mofetil CHEBI:8764 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses mycophenolate mofetil (CHEBI:8764). CHEBI:8764 is a therapeutic agent from Chemical Entities of Biological Interest.
Steroid-sparing immunosuppressant.
Show evidence (1 reference)
PMID:37153943 SUPPORT
"several steroid-sparing agents, such as methotrexate, azathioprine or mycophenolate mofetil, have been reported as effective in treating DM."
Comprehensive review confirms mycophenolate mofetil as an effective steroid-sparing agent.
Hydroxychloroquine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: hydroxychloroquine CHEBI:5801 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses hydroxychloroquine (CHEBI:5801). CHEBI:5801 is a therapeutic agent from Chemical Entities of Biological Interest.
Antimalarial agent used for cutaneous disease manifestations.
IVIG
Action: immunotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immunotherapy (NCIT:C15262). NCIT:C15262 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunotherapy NCIT:C15262
Intravenous immunoglobulin for refractory disease, especially skin manifestations. Modulates complement-mediated pathways.
Show evidence (1 reference)
PMID:30670084 SUPPORT Human Clinical
"Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated."
The Brazilian Society of Rheumatology guideline positions IVIG for refractory dermatomyositis or when immunosuppressive drugs are contraindicated.
Rituximab
Action: immunotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immunotherapy (NCIT:C15262). NCIT:C15262 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunotherapy NCIT:C15262
Agent: rituximab NCIT:C1702 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses rituximab (NCIT:C1702). NCIT:C1702 is a therapeutic agent from the NCI Thesaurus.
Anti-CD20 monoclonal antibody for refractory myositis.
Show evidence (1 reference)
PMID:39334579 SUPPORT
"Rituximab and JAKi may reduce mortality in patients with JDM-associated RP-ILD refractory to conventional therapy."
This evidence supports the use of rituximab in severe, refractory cases, particularly those with rapidly progressive interstitial lung disease.
JAK Inhibitors
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: tofacitinib CHEBI:71200 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses tofacitinib (CHEBI:71200). CHEBI:71200 is a therapeutic agent from Chemical Entities of Biological Interest.
Emerging therapy targeting type I interferon pathway. Tofacitinib, baricitinib, and ruxolitinib show efficacy in refractory cutaneous disease and anti-MDA5 associated ILD.
Show evidence (5 references)
PMID:38576610 SUPPORT
"Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41)."
This meta-analysis demonstrates significant improvement in skin disease severity (measured by CDASI) with JAK inhibitor therapy in dermatomyositis patients.
PMID:38456909 SUPPORT
"We treated three patients with anti-MDA5-DM-associated ILD (anti-MDA5-DM-ILD) using the Janus kinase (JAK) inhibitor, baricitinib, which improved lung opacities and saved two patients."
This case series provides evidence for the efficacy of baricitinib in treating severe anti-MDA5 associated interstitial lung disease.
PMID:38456909 SUPPORT
"All patients except one were treated with tofacitinib, and the survival rate was 75.9%."
This systematic review demonstrates a 75.9% survival rate in anti-MDA5 positive dermatomyositis-ILD treated with JAK inhibitors, supporting their use in this life-threatening complication.
+ 2 more references
Treat-to-Target Management Strategy
Action: treat-to-target management strategyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is treat-to-target management strategy, annotated with Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
A treat-to-target management framework (developed for juvenile dermatomyositis) in which patients/parents and clinicians jointly set a defined treatment target — inactive disease preferred, or minimal disease activity as an alternative — aiming for inactive disease within 12 months, with interim clinical-improvement and muscle-strength milestones and guided tapering of glucocorticoids.
Show evidence (2 references)
PMID:40410052 SUPPORT Human Clinical
"with inactive disease as the preferred target and minimal disease activity an alternative one."
The PReS/CARRA task force defines inactive disease as the preferred treat-to-target goal, with minimal disease activity as an alternative.
PMID:40410052 SUPPORT Human Clinical
"Interim targets include minimal and moderate clinical improvement within 6 weeks and 3 months, respectively, and normalisation of muscle strength within 6 months."
Specifies the interim clinical-improvement and muscle-strength milestones that structure the treat-to-target timeline.
Physical Therapy and Exercise Rehabilitation
Action: physical therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is physical therapy (NCIT:C15302). NCIT:C15302 is a clinical intervention from the NCI Thesaurus. Ontology label: Physical Therapy NCIT:C15302
Supervised physical exercise, physical therapy, and occupational therapy as an adjunct to pharmacotherapy, to improve muscle function and aerobic capacity and to counter the muscle atrophy driven by inflammation, inactivity, and glucocorticoid exposure.
Show evidence (2 references)
PMID:30670084 SUPPORT Human Clinical
"Physical therapy and occupational therapy play a prominent role in the rehabilitation and therapeutic process of patients with SAM"
The Brazilian Society of Rheumatology guideline recommends physical and occupational therapy as a prominent part of myositis rehabilitation.
PMID:30670084 SUPPORT Human Clinical
"Numerous studies have demonstrated the safety and positive results of supervised physical exercise in muscular function indicated for patients with SAM"
Supports the safety and functional benefit of supervised physical exercise in systemic autoimmune myopathies including dermatomyositis.
🔬

Biochemical Markers

5
Creatine Kinase (Elevated)
Context: Marker of muscle damage
Aldolase (Elevated)
Context: Muscle enzyme
Anti-Mi-2 Antibodies (Variable)
Context: Classic DM, good prognosis
Anti-MDA5 Antibodies (Variable)
Context: Amyopathic DM with ILD risk
Ferritin (Elevated)
Context: Hyperferritinemia marks anti-MDA5-positive DM and correlates with rapidly progressive ILD severity and mortality.
📊

Prevalence

4
United States
Annual Incidence 1.1 per 100,000 1–9 per 100,000
Show evidence (2 references)
PMID:34549549 SUPPORT
"The overall adjusted incidence of DM was 1.1 (95% CI 0.7-1.5) per 100,000 person-years, and prevalence was 13 (95% CI 6-19) per 100,000."
Population-based cohort study from Olmsted County using EULAR/ACR criteria.
ORPHA:221 SUPPORT
"1-9 / 100 000 | United States | Annual incidence | PMID:34549549"
Orphanet epidemiology data for dermatomyositis in the United States.
Norway
Point Prevalence 8.7 per 100,000 1–9 per 100,000
Show evidence (2 references)
PMID:24695011 SUPPORT
"point prevalence of PM/DM was calculated to 8.7/100 000"
Unselected Norwegian population study identifying all PM/DM patients in southeast Norway (denominator 2.64 million).
ORPHA:221 SUPPORT
"1-9 / 100 000 | Norway | Point prevalence | PMID:24695011"
Orphanet epidemiology data for dermatomyositis in Norway.
Sweden
Annual Incidence 0.6–1.0 per 100,000 1–9 per 1,000,000
Show evidence (1 reference)
ORPHA:221 SUPPORT
"1-9 / 1 000 000 | Sweden | Annual incidence | PMID:28160487"
Orphanet epidemiology data based on Swedish nationwide population-based study.
Argentina
Annual Incidence 0.1–0.9 per 100,000 1–9 per 1,000,000
Show evidence (1 reference)
ORPHA:221 SUPPORT
"1-9 / 1 000 000 | Argentina | Annual incidence | PMID:23965482"
Orphanet epidemiology data for dermatomyositis in Argentina.
📊

Related Datasets

4
RNA-Seq of CD19+ B-cell, CD14+ monocyte, CD4+ and CD8+ T cell populations from patients with juvenile dermatomyositis and controls geo:GSE221091
RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells, moncytes and T-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.
human BULK RNA SEQ n=106
PMID:36564154
Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Analysis of peripheral blood transcript and protein expression across adult systemic lupus erythematosus (SLE) and adult dermatomyositis (DM) patients, each compared to respective healthy matched control subjects. geo:GSE318067
The study interrogates SLE and DM gene expression measurements across three platforms: Affymetrix transcriptomics, SomaLogic proteomics, and Rules Based Medicine (RBM) proteomics. Patients are matched 1:1 with healthy donor subjects by age, ethnicity, and sex. DM patients are matched 1:3 with SLE patients by the same criteria. All patients have been treated for at least one year, and represent patients receiving standard treatment care for the respective diseases. The data posted contain SLE patients in support of the paper Distinct Interferon and Intracellular Signaling Signatures in Systemic Lupus Erythematosus and Dermatomyositis by Integrative Transcriptomic and Proteomic Analysis.
human MICROARRAY n=82
PMID:41870980
Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Dermatomyositis is characterized by JAK1-mediated monocyte-driven vasculopathy and inflammation geo:GSE303609
Dermatomyositis (DM) is a rare yet devastating autoimmune disease characterized by inflammatory and vasculopathic changes in skin and muscle. DM and systemic lupus erythematosus (lupus) skin lesions have overlapping clinical and histopathological features, yet disparate responses to available therapeutics. DM skin disease is often relapsing and recalcitrant. To investigate DM immunopathogenesis, non-lesional skin, lesional skin, and circulating immune cells from DM patients were analyzed using single-cell RNA-sequencing. Samples were analyzed in parallel with lesional and non-lesional lupus skin, healthy control skin, and peripheral blood.
human SINGLE CELL RNA SEQ n=34
PMID:41442501
Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Frequent Genetic Alterations in Myositis Autoantigen Genes in Cancer-Associated Dermatomyositis ega:EGAS50000001367
One-third of patients diagnosed with dermatomyositis harbor an occult cancer, a rare condition named cancer-associated dermatomyositis (CAD). Emerging evidence suggests that genetic alterations in autoantibody-related genes give rise neoantigens and specific autoantibodies that initiate an autoimmune response characteristic of CAD. This study evaluated the prevalence of such genetic alterations and elucidated molecular mechanisms that may underlie their role in triggering autoimmunity. We detected highly frequent genetic alterations in autoantibody-related genes, supporting their role in the CAD pathogenic mechanisms.
human WES
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Dermatomyositis"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
{ }

Source YAML

click to show 
name: Dermatomyositis
creation_date: '2025-12-19T01:12:52Z'
category: Autoimmune
parents:
- Autoimmune Disease
- Inflammatory Myopathy
disease_term:
  preferred_term: Dermatomyositis
  term:
    id: MONDO:0016367
    label: dermatomyositis
description: >-
  An idiopathic inflammatory myopathy characterized by proximal muscle weakness
  and distinctive skin manifestations including heliotrope rash and Gottron's
  papules. Associated with increased risk of malignancy and interstitial lung
  disease in certain autoantibody subsets.
pathophysiology:
- name: Complement-Mediated Microangiopathy
  description: >-
    Membrane attack complex (MAC) deposition on endomysial capillaries leads
    to capillary damage, ischemia, and perifascicular atrophy characteristic
    of dermatomyositis. This distinguishes it from polymyositis.
  cell_types:
  - preferred_term: Endothelial Cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: Complement Activation
    term:
      id: GO:0006956
      label: complement activation
  evidence:
  - reference: PMID:38143369
    reference_title: "Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies."
    supports: SUPPORT
    snippet: >-
      Deposition of complement around capillaries and/or the sarcolemma was
      observed in muscle biopsy specimens from patients with DM, ASS, and IMNM,
      suggesting the pathomechanism of complement-dependent muscle and endothelial
      cell injury.
    explanation: >-
      This evidence demonstrates that complement deposition is a characteristic
      pathological feature of dermatomyositis, contributing to muscle and
      endothelial cell injury through complement-dependent mechanisms.
  - reference: PMID:38143369
    reference_title: "Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies."
    supports: SUPPORT
    snippet: >-
      Juvenile DM is characterized by the loss of capillaries, perivascular
      inflammation, and small-vessel angiopathies, which may be related to
      microinfarction and perifascicular atrophy.
    explanation: >-
      This evidence links the microangiopathy to the characteristic perifascicular
      atrophy observed in dermatomyositis, supporting the ischemic mechanism of
      muscle damage.
- name: Type I Interferon Pathway Activation
  description: >-
    Strong type I interferon signature in muscle and skin. Plasmacytoid
    dendritic cells accumulate in affected tissues and produce IFN-alpha,
    driving inflammation and MxA protein expression.
  cell_types:
  - preferred_term: Plasmacytoid Dendritic Cell
    term:
      id: CL:0000784
      label: plasmacytoid dendritic cell
  biological_processes:
  - preferred_term: Type I Interferon Response
    term:
      id: GO:0034340
      label: response to type I interferon
  evidence:
  - reference: PMID:38143369
    reference_title: "Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies."
    supports: SUPPORT
    snippet: >-
      The pathological observation of myxovirus resistance protein A (MxA),
      which suggests a type 1 interferon (IFN1) signature in DM, supports the
      diagnosis and further understanding of the pathomechanism of IIM.
    explanation: >-
      MxA expression is a hallmark of type I interferon activation in
      dermatomyositis, providing diagnostic and pathomechanistic insights.
  - reference: PMID:39334579
    reference_title: "Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment and Interstitial Lung Diseases-A Narrative Review."
    supports: SUPPORT
    snippet: >-
      Histopathological studies have revealed critical roles of type I interferons
      and vasculopathy in the development of JDM.
    explanation: >-
      This evidence confirms that type I interferon signaling is a central
      pathogenic mechanism in dermatomyositis, including juvenile forms.
- name: Myositis-Specific Autoantibodies
  description: >-
    Distinct autoantibodies define clinical phenotypes: anti-Mi-2 (classic
    dermatomyositis), anti-MDA5 (amyopathic with ILD), anti-TIF1-gamma
    (cancer-associated), and anti-NXP2 (calcinosis).
  biological_processes:
  - preferred_term: Immunoglobulin Production
    term:
      id: GO:0002377
      label: immunoglobulin production
  evidence:
  - reference: PMID:39334579
    reference_title: "Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment and Interstitial Lung Diseases-A Narrative Review."
    supports: SUPPORT
    snippet: >-
      Each MSA or MAA is associated with distinct clinical features and outcomes,
      although there are several differences in the prevalence of MSA/MAA and
      autoantibody-phenotype relationships between age and ethnic groups.
    explanation: >-
      This evidence confirms that myositis-specific autoantibodies (MSAs) define
      distinct clinical phenotypes in dermatomyositis, supporting the concept of
      autoantibody-driven disease subtypes.
- name: Perivascular Inflammation and Immune Cell Infiltration
  description: >-
    Perivascular inflammation contributes to muscle damage in dermatomyositis.
    Immune cell infiltrates including CD4+ T cells and B cells are found in
    perivascular and perimysial locations.
  cell_types:
  - preferred_term: CD4+ T Cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  - preferred_term: B Cell
    term:
      id: CL:0000236
      label: B cell
  biological_processes:
  - preferred_term: Adaptive Immune Response
    term:
      id: GO:0002250
      label: adaptive immune response
  evidence:
  - reference: PMID:38143369
    reference_title: "Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies."
    supports: SUPPORT
    snippet: >-
      Juvenile DM is characterized by the loss of capillaries, perivascular
      inflammation, and small-vessel angiopathies, which may be related to
      microinfarction and perifascicular atrophy.
    explanation: >-
      Confirms perivascular inflammation as a characteristic feature of DM
      muscle pathology.
  - reference: PMID:38143369
    reference_title: "Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      an increase in triggering receptor expressed on myeloid cells (TREM-1)
      around perimysial blood vessels and muscles in patients with IIM plays a
      role in triggering inflammation and promoting the migration of inflammatory
      cells
    explanation: >-
      TREM-1 upregulation around perimysial vessels amplifies perivascular
      inflammation and recruits inflammatory cells in idiopathic inflammatory
      myopathies, providing a molecular driver of the immune cell infiltration.
prevalence:
- population: United States
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 1.1
  percentage: "1.1 per 100,000 person-years (incidence); 13 per 100,000 (prevalence)"
  evidence:
  - reference: PMID:34549549
    reference_title: "Incidence, Prevalence, and Mortality of Dermatomyositis: A Population-Based Cohort Study."
    supports: SUPPORT
    snippet: >-
      The overall adjusted incidence of DM was 1.1 (95% CI 0.7-1.5) per 100,000
      person-years, and prevalence was 13 (95% CI 6-19) per 100,000.
    explanation: Population-based cohort study from Olmsted County using EULAR/ACR criteria.
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "1-9 / 100 000 | United States | Annual incidence | PMID:34549549"
    explanation: Orphanet epidemiology data for dermatomyositis in the United States.
- population: Norway
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 8.7
  percentage: "8.7 per 100,000 (point prevalence)"
  evidence:
  - reference: PMID:24695011
    reference_title: "Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort."
    supports: SUPPORT
    snippet: >-
      point prevalence of PM/DM was calculated to 8.7/100 000
    explanation: >-
      Unselected Norwegian population study identifying all PM/DM patients
      in southeast Norway (denominator 2.64 million).
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "1-9 / 100 000 | Norway | Point prevalence | PMID:24695011"
    explanation: Orphanet epidemiology data for dermatomyositis in Norway.
- population: Sweden
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_1000000
  rate_low: 0.6
  rate_high: 1.0
  percentage: "6-10 per 1,000,000 (annual incidence)"
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "1-9 / 1 000 000 | Sweden | Annual incidence | PMID:28160487"
    explanation: Orphanet epidemiology data based on Swedish nationwide population-based study.
- population: Argentina
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_1000000
  rate_low: 0.1
  rate_high: 0.9
  percentage: "1-9 per 1,000,000 (annual incidence)"
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "1-9 / 1 000 000 | Argentina | Annual incidence | PMID:23965482"
    explanation: Orphanet epidemiology data for dermatomyositis in Argentina.
inheritance:
- name: Not applicable
  description: >-
    Dermatomyositis is an autoimmune disease, not an inherited Mendelian disorder.
    HLA associations (e.g., HLA-DRB1*0301) confer genetic susceptibility but do
    not follow a Mendelian pattern.
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "Not applicable"
    explanation: Orphanet classifies dermatomyositis inheritance as not applicable.
phenotypes:
- name: Proximal Muscle Weakness
  category: Musculoskeletal
  frequency: VERY_FREQUENT
  description: >-
    Symmetrical proximal muscle weakness is a hallmark feature, affecting shoulder
    and hip girdle muscles. Patients have difficulty rising from chairs, climbing
    stairs, and lifting arms above the head.
  phenotype_term:
    preferred_term: Proximal muscle weakness
    term:
      id: HP:0003701
      label: Proximal muscle weakness
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0003701 | Proximal muscle weakness | Very frequent (99-80%)"
    explanation: Orphanet classifies proximal muscle weakness as very frequent (99-80%) in dermatomyositis.
  - reference: PMID:37153943
    reference_title: "Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches."
    supports: SUPPORT
    snippet: >-
      Together with skin features, patients show muscle involvement, most commonly
      with symmetrical weakness of the proximal muscles.
    explanation: Comprehensive review confirms symmetrical proximal muscle weakness as a core feature.
- name: Limb-Girdle Muscle Weakness
  category: Musculoskeletal
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Limb-girdle muscle weakness
    term:
      id: HP:0003325
      label: Limb-girdle muscle weakness
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0003325 | Limb-girdle muscle weakness | Very frequent (99-80%)"
    explanation: Orphanet classifies limb-girdle weakness as very frequent in dermatomyositis.
- name: Myalgia
  category: Musculoskeletal
  frequency: VERY_FREQUENT
  description: Muscle pain is a very frequent symptom, reported in up to 75% of patients.
  phenotype_term:
    preferred_term: Myalgia
    term:
      id: HP:0003326
      label: Myalgia
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0003326 | Myalgia | Very frequent (99-80%)"
    explanation: Orphanet classifies myalgia as very frequent in dermatomyositis.
  - reference: PMID:24695011
    reference_title: "Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort."
    supports: SUPPORT
    snippet: >-
      Frequent clinical features included myalgia (75%), arthritis (41%)
      dyspnoea (62%) and dysphagia (58%).
    explanation: Norwegian population-based cohort found myalgia in 75% of PM/DM patients.
- name: Hypotonia
  category: Musculoskeletal
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001252 | Hypotonia | Frequent (79-30%)"
    explanation: Orphanet classifies hypotonia as frequent in dermatomyositis.
- name: Inflammatory Myopathy
  category: Musculoskeletal
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Inflammatory myopathy
    term:
      id: HP:0009071
      label: Inflammatory myopathy
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0009071 | Inflammatory myopathy | Very frequent (99-80%)"
    explanation: Orphanet classifies inflammatory myopathy as very frequent in dermatomyositis.
- name: Heliotrope Rash
  category: Dermatological
  frequency: FREQUENT
  description: >-
    Violaceous discoloration of the eyelids, often with periorbital edema.
    A pathognomonic cutaneous finding of dermatomyositis.
  phenotype_term:
    preferred_term: Heliotrope rash
    term:
      id: HP:0040324
      label: Heliotrope rash
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0040324 | Heliotrope rash | Frequent (79-30%)"
    explanation: Orphanet classifies heliotrope rash as frequent in dermatomyositis.
  - reference: PMID:37153943
    reference_title: "Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches."
    supports: SUPPORT
    snippet: >-
      heliotrope rash, and violaceous papules located at the interphalangeal or
      metacarpophalangeal joints (Gottron's papules) are the most frequently observed.
    explanation: Comprehensive review identifies heliotrope rash as one of the most frequent skin findings.
- name: Gottron's Papules
  category: Dermatological
  frequency: FREQUENT
  description: >-
    Violaceous papules over the dorsal interphalangeal and metacarpophalangeal
    joints. A pathognomonic cutaneous finding of dermatomyositis.
  phenotype_term:
    preferred_term: Gottron's papules
    term:
      id: HP:0025508
      label: Gottron's papules
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0025508 | Gottron's papules | Frequent (79-30%)"
    explanation: Orphanet classifies Gottron's papules as frequent in dermatomyositis.
  - reference: PMID:37153943
    reference_title: "Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches."
    supports: SUPPORT
    snippet: >-
      heliotrope rash, and violaceous papules located at the interphalangeal or
      metacarpophalangeal joints (Gottron's papules) are the most frequently observed.
    explanation: Comprehensive review identifies Gottron's papules as one of the most frequent skin findings.
- name: Gottron Sign
  category: Dermatological
  frequency: OCCASIONAL
  description: >-
    Erythematous or violaceous macules over the extensor surfaces of joints,
    distinct from the raised papules of Gottron's papules.
  phenotype_term:
    preferred_term: Gottron sign
    term:
      id: HP:0430033
      label: Gottron sign
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0430033 | Gottron sign | Occasional (29-5%)"
    explanation: Orphanet classifies Gottron sign as occasional in dermatomyositis.
- name: Periorbital Edema
  category: Dermatological
  frequency: VERY_FREQUENT
  description: >-
    Edema around the eyes, often accompanying heliotrope rash. A characteristic
    early finding.
  phenotype_term:
    preferred_term: Periorbital edema
    term:
      id: HP:0100539
      label: Periorbital edema
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0100539 | Periorbital edema | Very frequent (99-80%)"
    explanation: Orphanet classifies periorbital edema as very frequent in dermatomyositis.
- name: Erythema
  category: Dermatological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Erythema
    term:
      id: HP:0010783
      label: Erythema
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0010783 | Erythema | Very frequent (99-80%)"
    explanation: Orphanet classifies erythema as very frequent in dermatomyositis.
- name: Facial Erythema
  category: Dermatological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Facial erythema
    term:
      id: HP:0001041
      label: Facial erythema
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001041 | Facial erythema | Frequent (79-30%)"
    explanation: Orphanet classifies facial erythema as frequent in dermatomyositis.
- name: V-Sign
  category: Dermatological
  frequency: OCCASIONAL
  description: >-
    Erythematous rash over the anterior chest and neck in a V-shaped distribution.
  phenotype_term:
    preferred_term: V-sign
    term:
      id: HP:0025536
      label: V-sign
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0025536 | V-sign | Occasional (29-5%)"
    explanation: Orphanet classifies V-sign as occasional in dermatomyositis.
- name: Shawl Sign
  category: Dermatological
  frequency: FREQUENT
  description: >-
    Erythematous rash over the upper back, posterior shoulders, and upper arms
    in a shawl-like distribution.
  phenotype_term:
    preferred_term: Shawl sign
    term:
      id: HP:0025535
      label: Shawl sign
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0025535 | Shawl sign | Frequent (79-30%)"
    explanation: Orphanet classifies shawl sign as frequent in dermatomyositis.
- name: Holster Sign
  category: Dermatological
  frequency: OCCASIONAL
  description: >-
    Erythematous rash over the lateral thighs, resembling a gun holster distribution.
  phenotype_term:
    preferred_term: Holster sign
    term:
      id: HP:6000006
      label: Holster sign
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:6000006 | Holster sign | Occasional (29-5%)"
    explanation: Orphanet classifies holster sign as occasional in dermatomyositis.
- name: Cutaneous Photosensitivity
  category: Dermatological
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Cutaneous photosensitivity
    term:
      id: HP:0000992
      label: Cutaneous photosensitivity
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0000992 | Cutaneous photosensitivity | Occasional (29-5%)"
    explanation: Orphanet classifies cutaneous photosensitivity as occasional in dermatomyositis.
- name: Skin Ulcer
  category: Dermatological
  frequency: FREQUENT
  description: >-
    Cutaneous ulceration is associated with increased cancer risk in dermatomyositis.
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0200042 | Skin ulcer | Frequent (79-30%)"
    explanation: Orphanet classifies skin ulcer as frequent in dermatomyositis.
  - reference: PMID:33599244
    reference_title: "A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies."
    supports: SUPPORT
    snippet: >-
      cutaneous ulceration (RR 2.73)
    explanation: >-
      Meta-analysis identifies cutaneous ulceration as a significant risk factor
      for cancer in IIM (risk ratio 2.73).
- name: Pruritus
  category: Dermatological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0000989 | Pruritus | Frequent (79-30%)"
    explanation: Orphanet classifies pruritus as frequent in dermatomyositis.
- name: Poikiloderma
  category: Dermatological
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Poikiloderma
    term:
      id: HP:0001029
      label: Poikiloderma
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001029 | Poikiloderma | Occasional (29-5%)"
    explanation: Orphanet classifies poikiloderma as occasional in dermatomyositis.
- name: Acrocyanosis
  category: Dermatological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Acrocyanosis
    term:
      id: HP:0001063
      label: Acrocyanosis
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001063 | Acrocyanosis | Frequent (79-30%)"
    explanation: Orphanet classifies acrocyanosis as frequent in dermatomyositis.
- name: Raynaud Phenomenon
  category: Dermatological
  frequency: OCCASIONAL
  description: >-
    Episodic vasospasm of the fingers and toes. Associated with reduced cancer
    risk in DM (protective factor).
  phenotype_term:
    preferred_term: Raynaud phenomenon
    term:
      id: HP:0030880
      label: Raynaud phenomenon
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0030880 | Raynaud phenomenon | Occasional (29-5%)"
    explanation: Orphanet classifies Raynaud phenomenon as occasional in dermatomyositis.
  - reference: PMID:33599244
    reference_title: "A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies."
    supports: SUPPORT
    snippet: >-
      Raynaud's phenomenon (RR 0.61)
    explanation: >-
      Meta-analysis shows Raynaud phenomenon is associated with reduced cancer
      risk in IIM (protective factor, RR 0.61).
- name: Pulmonary Fibrosis
  category: Respiratory
  frequency: FREQUENT
  description: >-
    Interstitial lung disease is a major complication, especially with anti-MDA5
    antibodies. Rapidly progressive ILD is a leading cause of mortality.
  phenotype_term:
    preferred_term: Pulmonary fibrosis
    term:
      id: HP:0002206
      label: Pulmonary fibrosis
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002206 | Pulmonary fibrosis | Frequent (79-30%)"
    explanation: Orphanet classifies pulmonary fibrosis as frequent in dermatomyositis.
  - reference: PMID:38456909
    reference_title: "Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease."
    supports: SUPPORT
    snippet: >-
      Anti-melanoma differentiation-associated protein 5 antibody-positive
      dermatomyositis (anti-MDA5-DM) is frequently complicated by progressive
      interstitial lung disease (ILD), the prognosis of which is poor, and
      management is a major challenge.
    explanation: >-
      Anti-MDA5 positive dermatomyositis is strongly associated with progressive ILD.
  - reference: PMID:39334579
    reference_title: "Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment and Interstitial Lung Diseases-A Narrative Review."
    supports: SUPPORT
    snippet: >-
      However, rapidly progressive interstitial lung disease (RP-ILD) remains a
      major cause of death in anti-melanoma differentiation gene 5 autoantibody-positive
      JDM.
    explanation: RP-ILD is a leading cause of death in anti-MDA5 positive DM.
- name: Respiratory Insufficiency
  category: Respiratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Respiratory insufficiency
    term:
      id: HP:0002093
      label: Respiratory insufficiency
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002093 | Respiratory insufficiency | Frequent (79-30%)"
    explanation: Orphanet classifies respiratory insufficiency as frequent in dermatomyositis.
- name: Respiratory Insufficiency due to Muscle Weakness
  category: Respiratory
  frequency: FREQUENT
  description: >-
    Weakness of respiratory muscles (diaphragm and intercostals) contributing
    to ventilatory failure.
  phenotype_term:
    preferred_term: Respiratory insufficiency due to muscle weakness
    term:
      id: HP:0002747
      label: Respiratory insufficiency due to muscle weakness
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002747 | Respiratory insufficiency due to muscle weakness | Frequent (79-30%)"
    explanation: Orphanet classifies respiratory muscle weakness as frequent in dermatomyositis.
  - reference: PMID:24695011
    reference_title: "Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort."
    supports: SUPPORT
    snippet: >-
      Frequent clinical features included myalgia (75%), arthritis (41%)
      dyspnoea (62%) and dysphagia (58%).
    explanation: >-
      Norwegian cohort found dyspnoea in 62% of PM/DM patients. Partial only:
      the cohort reports dyspnoea without attributing it to respiratory muscle
      weakness, and in dermatomyositis dyspnoea is frequently driven by
      interstitial lung disease rather than by muscle weakness.
- name: Dysphagia
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: >-
    Pharyngeal and esophageal muscle involvement leads to swallowing difficulty.
    Associated with increased cancer risk (RR 2.09).
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002015 | Dysphagia | Occasional (29-5%)"
    explanation: >-
      Orphanet classifies dysphagia as occasional in dermatomyositis. Note that
      frequency estimates vary; the Norwegian cohort found 58%.
  - reference: PMID:24695011
    reference_title: "Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort."
    supports: SUPPORT
    snippet: >-
      Frequent clinical features included myalgia (75%), arthritis (41%)
      dyspnoea (62%) and dysphagia (58%).
    explanation: Norwegian population study found dysphagia in 58% of PM/DM patients.
  - reference: PMID:33599244
    reference_title: "A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies."
    supports: SUPPORT
    snippet: >-
      dysphagia (RR 2.09)
    explanation: >-
      Meta-analysis identifies dysphagia as a significant cancer risk factor
      in IIM (RR 2.09).
- name: Dysphonia
  category: Neurological
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Dysphonia
    term:
      id: HP:0001618
      label: Dysphonia
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001618 | Dysphonia | Occasional (29-5%)"
    explanation: Orphanet classifies dysphonia as occasional in dermatomyositis.
- name: Arthralgia
  category: Musculoskeletal
  frequency: FREQUENT
  description: Joint pain, commonly affecting the small joints of the hands.
  phenotype_term:
    preferred_term: Arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002829 | Arthralgia | Frequent (79-30%)"
    explanation: Orphanet classifies arthralgia as frequent in dermatomyositis.
- name: Arthritis
  category: Musculoskeletal
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Arthritis
    term:
      id: HP:0001369
      label: Arthritis
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001369 | Arthritis | Frequent (79-30%)"
    explanation: Orphanet classifies arthritis as frequent in dermatomyositis.
  - reference: PMID:24695011
    reference_title: "Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort."
    supports: SUPPORT
    snippet: >-
      Frequent clinical features included myalgia (75%), arthritis (41%)
      dyspnoea (62%) and dysphagia (58%).
    explanation: Norwegian cohort found arthritis in 41% of PM/DM patients.
- name: Fatigue
  category: Constitutional
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0012378 | Fatigue | Frequent (79-30%)"
    explanation: Orphanet classifies fatigue as frequent in dermatomyositis.
- name: Weight Loss
  category: Constitutional
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001824 | Weight loss | Frequent (79-30%)"
    explanation: Orphanet classifies weight loss as frequent in dermatomyositis.
- name: Fever
  category: Constitutional
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001945 | Fever | Occasional (29-5%)"
    explanation: Orphanet classifies fever as occasional in dermatomyositis.
- name: Malignancy
  category: Oncological
  frequency: OCCASIONAL
  description: >-
    Around one in four IIM patients are diagnosed with cancer within 3 years of
    onset. Risk factors include DM subtype, older age, male sex, dysphagia,
    cutaneous ulceration, and anti-TIF1-gamma positivity.
  phenotype_term:
    preferred_term: Neoplasm
    term:
      id: HP:0002664
      label: Neoplasm
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002664 | Neoplasm | Occasional (29-5%)"
    explanation: Orphanet classifies neoplasm as occasional in dermatomyositis.
  - reference: PMID:33599244
    reference_title: "A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies."
    supports: SUPPORT
    snippet: >-
      DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia
      (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional
      intermediary factor-1 gamma positivity (RR 4.66) were identified as being
      associated with significantly increased risk of cancer.
    explanation: >-
      Systematic review and meta-analysis of 69 studies identifies key cancer
      risk factors in IIM, with DM subtype itself conferring a 2.21-fold
      increased risk.
  - reference: PMID:33599244
    reference_title: "A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies."
    supports: SUPPORT
    snippet: >-
      Around one in four patients are diagnosed with cancer within 3 years before
      or after IIM onset
    explanation: Approximately 25% of IIM patients develop cancer temporally related to disease onset.
- name: Myocarditis
  category: Cardiovascular
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Myocarditis
    term:
      id: HP:0012819
      label: Myocarditis
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0012819 | Myocarditis | Occasional (29-5%)"
    explanation: Orphanet classifies myocarditis as occasional in dermatomyositis.
- name: Pericarditis
  category: Cardiovascular
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Pericarditis
    term:
      id: HP:0001701
      label: Pericarditis
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001701 | Pericarditis | Occasional (29-5%)"
    explanation: Orphanet classifies pericarditis as occasional in dermatomyositis.
- name: Arrhythmia
  category: Cardiovascular
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Arrhythmia
    term:
      id: HP:0011675
      label: Arrhythmia
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0011675 | Arrhythmia | Occasional (29-5%)"
    explanation: Orphanet classifies arrhythmia as occasional in dermatomyositis.
- name: Vasculitis
  category: Cardiovascular
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Vasculitis
    term:
      id: HP:0002633
      label: Vasculitis
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002633 | Vasculitis | Occasional (29-5%)"
    explanation: Orphanet classifies vasculitis as occasional in dermatomyositis.
- name: Elevated Creatine Kinase
  category: Laboratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Elevated circulating creatine kinase concentration
    term:
      id: HP:0003236
      label: Elevated circulating creatine kinase concentration
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0003236 | Elevated circulating creatine kinase concentration | Frequent (79-30%)"
    explanation: Orphanet classifies elevated CK as frequent in dermatomyositis.
  reports_on:
  - target: Complement-Mediated Microangiopathy
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Serum creatine kinase reflects complement-mediated myofiber injury.
- name: Elevated Aldolase
  category: Laboratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Elevated circulating aldolase concentration
    term:
      id: HP:0012544
      label: Elevated circulating aldolase concentration
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0012544 | Elevated circulating aldolase concentration | Frequent (79-30%)"
    explanation: Orphanet classifies elevated aldolase as frequent in dermatomyositis.
  reports_on:
  - target: Complement-Mediated Microangiopathy
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Serum aldolase reflects complement-mediated myofiber injury.
- name: Elevated LDH
  category: Laboratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Increased circulating lactate dehydrogenase concentration
    term:
      id: HP:0025435
      label: Increased circulating lactate dehydrogenase concentration
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0025435 | Increased circulating lactate dehydrogenase concentration | Frequent (79-30%)"
    explanation: Orphanet classifies elevated LDH as frequent in dermatomyositis.
  reports_on:
  - target: Complement-Mediated Microangiopathy
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Serum lactate dehydrogenase reflects complement-mediated myofiber injury.
- name: Elevated Hepatic Transaminases
  category: Laboratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Elevated circulating hepatic transaminase concentration
    term:
      id: HP:0002910
      label: Elevated circulating hepatic transaminase concentration
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002910 | Elevated circulating hepatic transaminase concentration | Frequent (79-30%)"
    explanation: Orphanet classifies elevated transaminases as frequent in dermatomyositis.
- name: Hyperferritinemia
  category: Laboratory
  description: >-
    Elevated serum ferritin, most prominent in anti-MDA5-positive
    dermatomyositis, where it tracks with rapidly progressive interstitial lung
    disease and predicts poor outcome.
  phenotype_term:
    preferred_term: Increased circulating ferritin concentration
    term:
      id: HP:0003281
      label: Increased circulating ferritin concentration
  evidence:
  - reference: PMID:38456909
    reference_title: "Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the deceased patients tended to be older and had higher ferritin levels
    explanation: >-
      In a case series and literature review of anti-MDA5-DM-associated ILD,
      higher serum ferritin was a feature of patients who died, supporting
      hyperferritinemia as an adverse prognostic biomarker in dermatomyositis.
- name: Calcinosis Cutis
  category: Dermatological
  frequency: FREQUENT
  description: >-
    Dystrophic calcinosis cutis, deposition of calcium in soft tissues and
    subcutaneous tissue. More common in juvenile DM and anti-NXP2 positive patients.
  phenotype_term:
    preferred_term: Calcinosis cutis
    term:
      id: HP:0025520
      label: Calcinosis cutis
  notes: >-
    Orphanet maps this as HP:0000934 Chondrocalcinosis; HP:0025520 Calcinosis
    cutis is the more precise term for DM-associated dystrophic calcification.
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0000934 | Chondrocalcinosis | Frequent (79-30%)"
    explanation: >-
      Orphanet classifies this as chondrocalcinosis (frequent). The more precise
      HP term for DM-associated calcinosis is HP:0025520 Calcinosis cutis.
  - reference: PMID:38929957
    reference_title: "Calcinosis Prevalence in Autoimmune Connective Tissue Diseases-A Retrospective Study."
    supports: SUPPORT
    snippet: >-
      A total of 839 CTD patients were identified, of whom 56 had calcinosis
      (6.67%).
    explanation: >-
      Retrospective study confirms calcinosis prevalence of 6.67% across
      autoimmune connective tissue diseases including dermatomyositis.
- name: EMG Abnormality
  category: Diagnostic
  frequency: VERY_FREQUENT
  description: >-
    Electromyographic findings include spontaneous fibrillation, complex
    repetitive discharges, and short-duration low-amplitude polyphasic motor
    unit potentials. A core diagnostic criterion for DM.
  phenotype_term:
    preferred_term: EMG abnormality
    term:
      id: HP:0003457
      label: EMG abnormality
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0003457 | EMG abnormality | Very frequent (99-80%)"
    explanation: Orphanet classifies EMG abnormality as very frequent in dermatomyositis.
- name: Abnormal Nail Morphology
  category: Dermatological
  frequency: FREQUENT
  description: >-
    Nailfold capillary changes including dilated capillary loops, dropout, and
    bushy capillaries are hallmarks of DM microangiopathy.
  phenotype_term:
    preferred_term: Abnormal nail morphology
    term:
      id: HP:0001597
      label: Abnormal nail morphology
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0001597 | Abnormality of the nail | Frequent (79-30%)"
    explanation: Orphanet classifies nail abnormalities as frequent in dermatomyositis.
- name: Recurrent Respiratory Infections
  category: Respiratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Recurrent respiratory infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002205 | Recurrent respiratory infections | Frequent (79-30%)"
    explanation: Orphanet classifies recurrent respiratory infections as frequent in dermatomyositis.
- name: Diffuse Reticular or Finely Nodular Infiltrations
  category: Respiratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Diffuse reticular or finely nodular infiltrations
    term:
      id: HP:0002207
      label: Diffuse reticular or finely nodular infiltrations
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0002207 | Diffuse reticular or finely nodular infiltrations | Frequent (79-30%)"
    explanation: Orphanet classifies diffuse reticular infiltrations as frequent in dermatomyositis.
- name: Abnormal Pulmonary Interstitial Morphology
  category: Respiratory
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Abnormal pulmonary interstitial morphology
    term:
      id: HP:0006530
      label: Abnormal pulmonary interstitial morphology
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0006530 | Abnormal pulmonary interstitial morphology | Frequent (79-30%)"
    explanation: Orphanet classifies abnormal pulmonary interstitial morphology as frequent in dermatomyositis.
- name: Dry Skin
  category: Dermatological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Dry skin
    term:
      id: HP:0000958
      label: Dry skin
  evidence:
  - reference: ORPHA:221
    reference_title: "Dermatomyositis"
    supports: SUPPORT
    snippet: "HP:0000958 | Dry skin | Frequent (79-30%)"
    explanation: Orphanet classifies dry skin as frequent in dermatomyositis.
biochemical:
- name: Creatine Kinase
  presence: Elevated
  context: Marker of muscle damage
- name: Aldolase
  presence: Elevated
  context: Muscle enzyme
- name: Anti-Mi-2 Antibodies
  presence: Variable
  context: Classic DM, good prognosis
- name: Anti-MDA5 Antibodies
  presence: Variable
  context: Amyopathic DM with ILD risk
- name: Ferritin
  presence: Elevated
  context: >-
    Hyperferritinemia marks anti-MDA5-positive DM and correlates with rapidly
    progressive ILD severity and mortality.
genetic:
- name: HLA-DRB1*0301
  association: Risk Factor
  notes: >-
    HLA class II allele conferring genetic susceptibility to dermatomyositis.
- name: TRIM33 (TIF1-gamma)
  gene_term:
    preferred_term: TRIM33
    term:
      id: hgnc:16290
      label: TRIM33
  association: Associated
  notes: >-
    Autoantigen target of anti-TIF1-gamma antibodies. Anti-TIF1-gamma positivity
    is associated with cancer-associated dermatomyositis (RR 4.66 for malignancy).
  evidence:
  - reference: PMID:31279808
    reference_title: "Dermatomyositis: Clinical features and pathogenesis."
    supports: SUPPORT
    snippet: >-
      anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with
      distinct DM subtypes in terms of cutaneous manifestations, systemic involvement,
      and malignancy risk.
    explanation: >-
      Review confirms anti-TIF1 (TRIM33) antibodies define a DM subtype with
      distinct clinical features and cancer risk.
- name: IFIH1 (MDA5)
  gene_term:
    preferred_term: IFIH1
    term:
      id: hgnc:18873
      label: IFIH1
  association: Associated
  notes: >-
    Autoantigen target of anti-MDA5 antibodies. Anti-MDA5 positivity defines
    clinically amyopathic DM with high risk of rapidly progressive ILD.
  evidence:
  - reference: PMID:31279808
    reference_title: "Dermatomyositis: Clinical features and pathogenesis."
    supports: SUPPORT
    snippet: >-
      anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with
      distinct DM subtypes in terms of cutaneous manifestations, systemic involvement,
      and malignancy risk.
    explanation: >-
      Review confirms anti-MDA5 (IFIH1) antibodies define a DM subtype with
      amyopathic presentation and ILD risk.
- name: CHD4 (Mi-2)
  gene_term:
    preferred_term: CHD4
    term:
      id: hgnc:1919
      label: CHD4
  association: Associated
  notes: >-
    Autoantigen target of anti-Mi-2 antibodies. Anti-Mi-2 positivity defines
    classic dermatomyositis with good prognosis and strong skin involvement.
  evidence:
  - reference: PMID:31279808
    reference_title: "Dermatomyositis: Clinical features and pathogenesis."
    supports: SUPPORT
    snippet: >-
      anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with
      distinct DM subtypes in terms of cutaneous manifestations, systemic involvement,
      and malignancy risk.
    explanation: >-
      Review confirms anti-Mi-2 (CHD4) antibodies define classic DM with
      good prognosis.
- name: MORC3 (NXP-2)
  gene_term:
    preferred_term: MORC3
    term:
      id: hgnc:23572
      label: MORC3
  association: Associated
  notes: >-
    Autoantigen target of anti-NXP2 antibodies. Anti-NXP2 positivity is
    associated with calcinosis, particularly in juvenile dermatomyositis. Its
    independent link to malignancy is debated: it was a non-significant cancer
    risk factor in meta-analysis once co-occurring anti-TIF1-gamma cases were
    excluded.
  evidence:
  - reference: PMID:31279808
    reference_title: "Dermatomyositis: Clinical features and pathogenesis."
    supports: SUPPORT
    snippet: >-
      anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with
      distinct DM subtypes in terms of cutaneous manifestations, systemic involvement,
      and malignancy risk.
    explanation: >-
      Review confirms anti-NXP2 (MORC3) antibodies define a DM subtype with
      distinct clinical features.
  - reference: PMID:33599244
    reference_title: "A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Anti-nuclear matrix protein 2 (anti-NXP2) positivity was a non-significant
      factor
    explanation: >-
      In a 69-study meta-analysis of IIM cancer risk, anti-NXP2 positivity was a
      non-significant cancer risk factor, qualifying the reported NXP2-malignancy
      association.
- name: SAE1 (SAE)
  gene_term:
    preferred_term: SAE1
    term:
      id: hgnc:30660
      label: SAE1
  association: Associated
  notes: >-
    Autoantigen target of anti-SAE antibodies. Anti-SAE positivity defines a
    subtype with initial skin-predominant disease that later develops myopathy.
  evidence:
  - reference: PMID:31279808
    reference_title: "Dermatomyositis: Clinical features and pathogenesis."
    supports: SUPPORT
    snippet: >-
      anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with
      distinct DM subtypes in terms of cutaneous manifestations, systemic involvement,
      and malignancy risk.
    explanation: >-
      Review confirms anti-SAE (SAE1) antibodies define a DM subtype with
      skin-predominant presentation.
treatments:
- name: Corticosteroids
  description: First-line therapy for muscle and skin inflammation.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: prednisolone
      term:
        id: CHEBI:8378
        label: prednisolone
  evidence:
  - reference: PMID:30670084
    reference_title: "Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM."
    explanation: The Brazilian Society of Rheumatology guideline affirms glucocorticoids as first-line therapy for systemic autoimmune myopathies including dermatomyositis.
- name: Methotrexate
  description: Steroid-sparing immunosuppressant.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: methotrexate
      term:
        id: CHEBI:44185
        label: methotrexate
- name: Azathioprine
  description: Steroid-sparing immunosuppressant for maintenance therapy.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: azathioprine
      term:
        id: CHEBI:2948
        label: azathioprine
  evidence:
  - reference: PMID:37153943
    reference_title: "Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches."
    supports: SUPPORT
    snippet: >-
      several steroid-sparing agents, such as methotrexate, azathioprine or
      mycophenolate mofetil, have been reported as effective in treating DM.
    explanation: Comprehensive review confirms azathioprine as an effective steroid-sparing agent.
- name: Mycophenolate Mofetil
  description: Steroid-sparing immunosuppressant.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: mycophenolate mofetil
      term:
        id: CHEBI:8764
        label: mycophenolate mofetil
  evidence:
  - reference: PMID:37153943
    reference_title: "Dermatomyositis: a comprehensive review of clinical manifestations, serological features, and therapeutic approaches."
    supports: SUPPORT
    snippet: >-
      several steroid-sparing agents, such as methotrexate, azathioprine or
      mycophenolate mofetil, have been reported as effective in treating DM.
    explanation: Comprehensive review confirms mycophenolate mofetil as an effective steroid-sparing agent.
- name: Hydroxychloroquine
  description: Antimalarial agent used for cutaneous disease manifestations.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: hydroxychloroquine
      term:
        id: CHEBI:5801
        label: hydroxychloroquine
- name: IVIG
  description: >-
    Intravenous immunoglobulin for refractory disease, especially skin
    manifestations. Modulates complement-mediated pathways.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
  evidence:
  - reference: PMID:30670084
    reference_title: "Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated."
    explanation: The Brazilian Society of Rheumatology guideline positions IVIG for refractory dermatomyositis or when immunosuppressive drugs are contraindicated.
- name: Rituximab
  description: Anti-CD20 monoclonal antibody for refractory myositis.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: rituximab
      term:
        id: NCIT:C1702
        label: Rituximab
  evidence:
  - reference: PMID:39334579
    reference_title: "Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment and Interstitial Lung Diseases-A Narrative Review."
    supports: SUPPORT
    snippet: >-
      Rituximab and JAKi may reduce mortality in patients with JDM-associated
      RP-ILD refractory to conventional therapy.
    explanation: >-
      This evidence supports the use of rituximab in severe, refractory cases,
      particularly those with rapidly progressive interstitial lung disease.
- name: JAK Inhibitors
  description: >-
    Emerging therapy targeting type I interferon pathway. Tofacitinib, baricitinib,
    and ruxolitinib show efficacy in refractory cutaneous disease and anti-MDA5
    associated ILD.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: tofacitinib
      term:
        id: CHEBI:71200
        label: tofacitinib
  evidence:
  - reference: PMID:38576610
    reference_title: "Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis."
    supports: SUPPORT
    snippet: >-
      Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41).
    explanation: >-
      This meta-analysis demonstrates significant improvement in skin disease
      severity (measured by CDASI) with JAK inhibitor therapy in dermatomyositis
      patients.
  - reference: PMID:38456909
    reference_title: "Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease."
    supports: SUPPORT
    snippet: >-
      We treated three patients with anti-MDA5-DM-associated ILD (anti-MDA5-DM-ILD)
      using the Janus kinase (JAK) inhibitor, baricitinib, which improved lung
      opacities and saved two patients.
    explanation: >-
      This case series provides evidence for the efficacy of baricitinib in
      treating severe anti-MDA5 associated interstitial lung disease.
  - reference: PMID:38456909
    reference_title: "Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease."
    supports: SUPPORT
    snippet: >-
      All patients except one were treated with tofacitinib, and the survival
      rate was 75.9%.
    explanation: >-
      This systematic review demonstrates a 75.9% survival rate in anti-MDA5
      positive dermatomyositis-ILD treated with JAK inhibitors, supporting their
      use in this life-threatening complication.
  - reference: PMID:38456909
    reference_title: "Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cytomegalovirus reactivation comprised a substantial percentage of all
      complications and of those patients who required JAK inhibitor
      discontinuation.
    explanation: >-
      Safety caveat: cytomegalovirus reactivation is a major complication of JAK
      inhibitor therapy in anti-MDA5-DM-ILD and a frequent cause of treatment
      discontinuation.
  - reference: PMID:38576610
    reference_title: "Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      For safety evaluation, one patient developed Orolabial HSV, and two
      patients developed thromboembolism events.
    explanation: >-
      Documents the JAK inhibitor safety signal in DM/PM, including
      thromboembolic events and herpesvirus reactivation, informing risk-benefit
      assessment.
- name: Treat-to-Target Management Strategy
  description: >-
    A treat-to-target management framework (developed for juvenile
    dermatomyositis) in which patients/parents and clinicians jointly set a
    defined treatment target — inactive disease preferred, or minimal disease
    activity as an alternative — aiming for inactive disease within 12 months,
    with interim clinical-improvement and muscle-strength milestones and
    guided tapering of glucocorticoids.
  treatment_term:
    preferred_term: treat-to-target management strategy
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:40410052
    reference_title: "Treating juvenile dermatomyositis to target: Paediatric Rheumatology European Society/Childhood Arthritis and Rheumatology Research Alliance-endorsed recommendations from an international task force."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "with inactive disease as the preferred target and minimal disease activity an alternative one."
    explanation: The PReS/CARRA task force defines inactive disease as the preferred treat-to-target goal, with minimal disease activity as an alternative.
  - reference: PMID:40410052
    reference_title: "Treating juvenile dermatomyositis to target: Paediatric Rheumatology European Society/Childhood Arthritis and Rheumatology Research Alliance-endorsed recommendations from an international task force."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Interim targets include minimal and moderate clinical improvement within 6 weeks and 3 months, respectively, and normalisation of muscle strength within 6 months."
    explanation: Specifies the interim clinical-improvement and muscle-strength milestones that structure the treat-to-target timeline.
- name: Physical Therapy and Exercise Rehabilitation
  description: >-
    Supervised physical exercise, physical therapy, and occupational therapy as
    an adjunct to pharmacotherapy, to improve muscle function and aerobic
    capacity and to counter the muscle atrophy driven by inflammation,
    inactivity, and glucocorticoid exposure.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: NCIT:C15302
      label: Physical Therapy
  evidence:
  - reference: PMID:30670084
    reference_title: "Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Physical therapy and occupational therapy play a prominent role in the rehabilitation and therapeutic process of patients with SAM"
    explanation: The Brazilian Society of Rheumatology guideline recommends physical and occupational therapy as a prominent part of myositis rehabilitation.
  - reference: PMID:30670084
    reference_title: "Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Numerous studies have demonstrated the safety and positive results of supervised physical exercise in muscular function indicated for patients with SAM"
    explanation: Supports the safety and functional benefit of supervised physical exercise in systemic autoimmune myopathies including dermatomyositis.
classifications:
  harrisons_chapter:
  - classification_value: IMMUNE_RHEUMATOLOGIC
references:
- reference: DOI:10.1007/s00281-025-01054-9
  title: 'Dermatomyositis: focus on cutaneous features, etiopathogenetic mechanisms
    and their implications for treatment'
  findings: []
- reference: DOI:10.1007/s00296-024-05551-2
  title: 'Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive
    dermatomyositis-associated interstitial lung disease: a case series and literature
    review on Janus kinase inhibitors for the disease'
  findings: []
- reference: DOI:10.1007/s11926-024-01164-7
  title: Recent Updates on the Pathogenesis of Inflammatory Myopathies
  findings: []
- reference: DOI:10.1007/s40272-024-00658-2
  title: 'Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current
    Treatment, and Emerging Targeted Therapies'
  findings: []
- reference: DOI:10.1080/14656566.2024.2392021
  title: Current evidence for janus kinase inhibitors in adult and juvenile
    dermatomyositis and key comparisons
  findings: []
- reference: DOI:10.1080/1744666x.2024.2312819
  title: Updates on efficacy and safety janus kinase inhibitors in juvenile
    dermatomyositis
  findings: []
- reference: DOI:10.3233/jnd-230168
  title: Contribution of Complement, Microangiopathy and Inflammation in
    Idiopathic Inflammatory Myopathies
  findings: []
- reference: DOI:10.3389/fimmu.2023.1151695
  title: Type I interferon score is associated with the severity and poor
    prognosis in anti-MDA5 antibody-positive dermatomyositis patients
  findings: []
- reference: DOI:10.3389/fimmu.2024.1382728
  title: 'Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis:
    a single-arm systemic meta-analysis'
  findings: []
- reference: DOI:10.3389/fmed.2023.1158768
  title: 'Targeting intracellular pathways in idiopathic inflammatory myopathies:
    A narrative review'
  findings: []
- reference: DOI:10.3390/children11091046
  title: 'Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment
    and Interstitial Lung Diseases—A Narrative Review'
  findings: []
- reference: DOI:10.55563/clinexprheumatol/eeglsa
  title: 'Brepocitinib, a potent and selective TYK2/JAK1 inhibitor: scientific and
    clinical rationale for dermatomyositis'
  findings: []
- reference: DOI:10.7759/cureus.88601
  title: 'Dermatomyositis: A Narrative Review of Skin as a Window to Muscle and Malignancy'
  findings: []
datasets:
- accession: geo:GSE221091
  title: RNA-Seq of CD19+ B-cell, CD14+ monocyte, CD4+ and CD8+ T cell populations from patients with juvenile dermatomyositis and controls
  description: RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells, moncytes and T-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 106
  publication: PMID:36564154
  notes: Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE318067
  title: Analysis of peripheral blood transcript and protein expression across adult systemic lupus erythematosus (SLE) and adult dermatomyositis (DM) patients, each compared to respective healthy matched control subjects.
  description: 'The study interrogates SLE and DM gene expression measurements across three platforms: Affymetrix transcriptomics, SomaLogic proteomics, and Rules Based Medicine (RBM) proteomics. Patients are matched 1:1 with healthy donor subjects by age, ethnicity, and sex. DM patients are matched 1:3 with SLE patients by the same criteria. All patients have been treated for at least one year, and represent patients receiving standard treatment care for the respective diseases. The data posted contain SLE patients in support of the paper Distinct Interferon and Intracellular Signaling Signatures in Systemic Lupus Erythematosus and Dermatomyositis by Integrative Transcriptomic and Proteomic Analysis.'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MICROARRAY
  sample_count: 82
  publication: PMID:41870980
  notes: Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE303609
  title: Dermatomyositis is characterized by JAK1-mediated monocyte-driven vasculopathy and inflammation
  description: Dermatomyositis (DM) is a rare yet devastating autoimmune disease characterized by inflammatory and vasculopathic changes in skin and muscle. DM and systemic lupus erythematosus (lupus) skin lesions have overlapping clinical and histopathological features, yet disparate responses to available therapeutics. DM skin disease is often relapsing and recalcitrant. To investigate DM immunopathogenesis, non-lesional skin, lesional skin, and circulating immune cells from DM patients were analyzed using single-cell RNA-sequencing. Samples were analyzed in parallel with lesional and non-lesional lupus skin, healthy control skin, and peripheral blood.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 34
  publication: PMID:41442501
  notes: Identified by GEO DataSets index search for Dermatomyositis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: ega:EGAS50000001367
  title: Frequent Genetic Alterations in Myositis Autoantigen Genes in Cancer-Associated Dermatomyositis
  description: One-third of patients diagnosed with dermatomyositis harbor an occult cancer, a rare condition named cancer-associated dermatomyositis (CAD). Emerging evidence suggests that genetic alterations in autoantibody-related genes give rise neoantigens and specific autoantibodies that initiate an autoimmune response characteristic of CAD. This study evaluated the prevalence of such genetic alterations and elucidated molecular mechanisms that may underlie their role in triggering autoimmunity. We detected highly frequent genetic alterations in autoantibody-related genes, supporting their role in the CAD pathogenic mechanisms.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: WES
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Dermatomyositis"); description-level mentions were not accepted. EGA study_type: Exome Sequencing. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
📚

References & Deep Research

References

13
DOI:10.1007/s00281-025-01054-9
Dermatomyositis: focus on cutaneous features, etiopathogenetic mechanisms and their implications for treatment
No top-level findings curated for this source.
DOI:10.1007/s00296-024-05551-2
Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease
No top-level findings curated for this source.
DOI:10.1007/s11926-024-01164-7
Recent Updates on the Pathogenesis of Inflammatory Myopathies
No top-level findings curated for this source.
DOI:10.1007/s40272-024-00658-2
Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies
No top-level findings curated for this source.
DOI:10.1080/14656566.2024.2392021
Current evidence for janus kinase inhibitors in adult and juvenile dermatomyositis and key comparisons
No top-level findings curated for this source.
DOI:10.1080/1744666x.2024.2312819
Updates on efficacy and safety janus kinase inhibitors in juvenile dermatomyositis
No top-level findings curated for this source.
DOI:10.3233/jnd-230168
Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies
No top-level findings curated for this source.
DOI:10.3389/fimmu.2023.1151695
Type I interferon score is associated with the severity and poor prognosis in anti-MDA5 antibody-positive dermatomyositis patients
No top-level findings curated for this source.
DOI:10.3389/fimmu.2024.1382728
Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis
No top-level findings curated for this source.
DOI:10.3389/fmed.2023.1158768
Targeting intracellular pathways in idiopathic inflammatory myopathies: A narrative review
No top-level findings curated for this source.
DOI:10.3390/children11091046
Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment and Interstitial Lung Diseases—A Narrative Review
No top-level findings curated for this source.
DOI:10.55563/clinexprheumatol/eeglsa
Brepocitinib, a potent and selective TYK2/JAK1 inhibitor: scientific and clinical rationale for dermatomyositis
No top-level findings curated for this source.
DOI:10.7759/cureus.88601
Dermatomyositis: A Narrative Review of Skin as a Window to Muscle and Malignancy
No top-level findings curated for this source.

Deep Research

2
Disorder ▸

Disorder

  • Name: Dermatomyositis
  • Category: Autoimmune
  • Existing deep-research providers: falcon
  • Existing evidence reference count in YAML: 25

Key Pathophysiology Nodes

  • Complement-Mediated Microangiopathy
  • Type I Interferon Pathway Activation
  • Myositis-Specific Autoantibodies
  • CD4+ T Cell and B Cell Infiltration
  • Deep research literature mapping

Citation Inventory (for evidence mapping)

  • DOI:10.1007/s00281-025-01054-9
  • DOI:10.1007/s00296-024-05551-2
  • DOI:10.1007/s11926-024-01164-7
  • DOI:10.1007/s40272-024-00658-2
  • DOI:10.1080/14656566.2024.2392021
  • DOI:10.1080/1744666x.2024.2312819
  • DOI:10.3233/jnd-230168
  • DOI:10.3389/fimmu.2023.1151695
  • DOI:10.3389/fimmu.2024.1382728
  • DOI:10.3389/fmed.2023.1158768
  • DOI:10.3390/children11091046
  • DOI:10.55563/clinexprheumatol/eeglsa
  • DOI:10.7759/cureus.88601
Falcon ▸
Disease Pathophysiology Research Report
Edison Scientific Literature 44 citations 2025-12-18T09:54:39.205453

Disease Pathophysiology Research Report

Target Disease - Disease Name: Dermatomyositis (DM) - MONDO ID: MONDO:0005377 - Category: Autoimmune

Pathophysiology description Dermatomyositis is a systemic autoimmune microangiopathy of skin, skeletal muscle, and frequently lung, characterized by complement-mediated capillary injury, a dominant type I interferon (IFN-I) transcriptional signature, and serologically defined subtypes driven by myositis-specific autoantibodies (MSAs). Histopathology demonstrates endothelial and myofiber damage with perifascicular atrophy, perivascular/perifascicular inflammatory infiltrates enriched for CD4+ T cells and plasmacytoid dendritic cells (pDCs), and membrane attack complex (MAC; C5b-9) deposition on endomysial capillaries and the sarcolemma, linking complement activation to microvascular ischemia and tissue injury (publication: Journal of Neuromuscular Diseases, Dec 2024; https://doi.org/10.3233/jnd-230168; and supportive review) (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10, cristofori2025dermatomyositisanarrative pages 2-3).

A pervasive IFN-I signature marked by MxA/ISG expression is observed in blood, skin, endothelium, and muscle, and correlates with disease activity; pDCs are present in inflamed tissue and are likely major local sources of IFN-I (publications: Current Rheumatology Reports, Sep 2024, https://doi.org/10.1007/s11926-024-01164-7; Children, Aug 2024, https://doi.org/10.3390/children11091046) (musai2024recentupdateson pages 1-2, kobayashi2024advancesinjuvenile pages 13-14). MSAs define phenotypes and risks: anti-TIF1-γ (TRIM33) and anti-NXP2 associate with malignancy; anti-MDA5 (IFIH1) correlates with clinically amyopathic presentations and high risk of rapidly progressive interstitial lung disease (RP-ILD); anti-Mi-2 (CHD4) is linked to classic cutaneous disease and favorable prognosis; anti-SAE often presents with florid skin disease and delayed weakness (publications and narrative reviews with URLs: Curr Rheumatol Rep 2024, https://doi.org/10.1007/s11926-024-01164-7; Cureus, Jul 2025, https://doi.org/10.7759/cureus.88601; Seminars in Immunopathology, Aug 2025, https://doi.org/10.1007/s00281-025-01054-9) (musai2024recentupdateson pages 1-2, cristofori2025dermatomyositisanarrative pages 3-4, ali2025dermatomyositisfocuson pages 1-2, cristofori2025dermatomyositisanarrative pages 2-3).

Therapeutically, the IFN–JAK/STAT axis is targetable: JAK inhibitors (tofacitinib, baricitinib, ruxolitinib; and selective TYK2/JAK1 inhibitor brepocitinib) have shown improvements in refractory cutaneous and systemic disease, including RP-ILD, with emerging safety considerations such as opportunistic infections (publication dates and URLs: Frontiers in Immunology, Mar 2024, https://doi.org/10.3389/fimmu.2024.1382728; Rheumatology International, Mar 2024, https://doi.org/10.1007/s00296-024-05551-2; Expert Opin Pharmacother, Aug 2024, https://doi.org/10.1080/14656566.2024.2392021; Clin Exp Rheumatology, Mar 2025, https://doi.org/10.55563/clinexprheumatol/eeglsa) (ma2024therapeuticefficacyand pages 1-2, harada2024baricitinibforantimelanoma pages 7-8, wallwork2024currentevidencefor pages 1-3, paik2025brepocitinibapotent pages 1-2).

1) Core Pathophysiology - Primary mechanisms: immune-mediated microangiopathy with complement MAC (C5b-9) deposition injuring endomysial capillaries and myofibers; ischemia produces perifascicular atrophy. Concurrent IFN-I–dominated innate immune activation amplifies endothelial activation, antigen presentation (MHC-I upregulation), and leukocyte recruitment (Journal of Neuromuscular Diseases, 2024; Cureus narrative review, 2025) (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10, cristofori2025dermatomyositisanarrative pages 2-3). - Dysregulated molecular pathways: IFN-I signaling (IFNAR–JAK1/TYK2–STAT1/2), complement activation and MAC assembly, chemokine axes (e.g., CX3CL1–CX3CR1 in lung), and downstream cytokine networks; in anti-MDA5 DM, immune complexes may engage endosomal TLRs to further induce IFN-α (Rheumatology International, 2024; Current Rheumatology Reports, 2024) (harada2024baricitinibforantimelanoma pages 7-8, musai2024recentupdateson pages 1-2). - Affected cellular processes: endothelial activation and injury, antigen presentation/MHC-I upregulation in myofibers, pDC-driven IFN production, macrophage activation/polarization, keratinocyte apoptosis and interface dermatitis in skin (Children, 2024; Current Rheumatology Reports, 2024) (kobayashi2024advancesinjuvenile pages 13-14, musai2024recentupdateson pages 1-2).

2) Key Molecular Players - Genes/Proteins (HGNC): TRIM33/TIF1-γ, MORC3/NXP2, IFIH1/MDA5, CHD4/Mi-2, SAE1/SAE2; IFNAR1/2, JAK1, TYK2, STAT1; complement C5–C9 (C5b-9). Anti-TIF1-γ/NXP2 associate with malignancy; anti-MDA5 with RP-ILD; anti-Mi-2 with favorable course; anti-SAE with cutaneous-predominant onset (Current Rheumatology Reports, 2024; Seminars in Immunopathology, 2025; Cureus, 2025) (musai2024recentupdateson pages 1-2, ali2025dermatomyositisfocuson pages 1-2, cristofori2025dermatomyositisanarrative pages 2-3). - Chemical Entities (CHEBI): JAK inhibitors (tofacitinib, baricitinib, ruxolitinib), TYK2/JAK1 inhibitor brepocitinib; IVIG—partly effective via complement inhibition (Frontiers in Immunology, 2024; Clin Exp Rheumatology, 2025; Journal of Neuromuscular Diseases, 2024) (ma2024therapeuticefficacyand pages 1-2, paik2025brepocitinibapotent pages 1-2, honda2024contributionofcomplement pages 1-3). - Cell Types (CL): endothelial cells, pDCs, macrophages (CD163+ subsets), CD4+ and CD8+ T cells, B cells/plasma cells, keratinocytes, lung alveolar macrophages (Children, 2024; Current Rheumatology Reports, 2024; Journal of Neuromuscular Diseases, 2024) (kobayashi2024advancesinjuvenile pages 13-14, musai2024recentupdateson pages 1-2, honda2024contributionofcomplement pages 1-3). - Anatomical Locations (UBERON): skin, skeletal muscle, lung (Cureus, 2025; Current Rheumatology Reports, 2024) (cristofori2025dermatomyositisanarrative pages 2-3, musai2024recentupdateson pages 1-2).

3) Biological Processes (GO terms) - Type I interferon signaling pathway (GO:0060337): central DM signature in skin/muscle/blood (Current Rheumatology Reports, 2024) (musai2024recentupdateson pages 1-2). - Complement activation, MAC assembly (GO:0006956): endomysial capillary and sarcolemmal C5b-9 deposition (Journal of Neuromuscular Diseases, 2024) (honda2024contributionofcomplement pages 1-3). - Endothelial cell activation (GO:0042118) and leukocyte chemotaxis (GO:0030595): microangiopathy and perivascular inflammation (Journal of Neuromuscular Diseases, 2024) (honda2024contributionofcomplement pages 1-3). - Antigen processing and presentation of peptide antigen via MHC class I (GO:0002474): myofiber MHC-I overexpression (Cureus, 2025) (cristofori2025dermatomyositisanarrative pages 2-3). - Cellular response to interferon-alpha/beta (GO:0035455/GO:0035456): broad ISG upregulation correlating with activity (Clin Exp Rheumatology, 2025) (paik2025brepocitinibapotent pages 1-2). - NET formation/neutrophil activation (GO:0038061/GO:0042119) and fibrotic pathways including TGF-β signaling in ILD (GO:0007179): implicated particularly in anti-MDA5 RP-ILD (Rheumatology International, 2024) (harada2024baricitinibforantimelanoma pages 7-8).

4) Cellular Components - Endomysial capillary and perimysial vessels: sites of MAC deposition and vasculopathy (Journal of Neuromuscular Diseases, 2024) (honda2024contributionofcomplement pages 1-3). - Sarcolemma: MAC deposition and myofiber injury (Journal of Neuromuscular Diseases, 2024) (honda2024contributionofcomplement pages 1-3). - Dermoepidermal junction: immunoglobulin/complement deposition and interface dermatitis (Cureus, 2025) (cristofori2025dermatomyositisanarrative pages 2-3). - Cytosol/nucleus of myofibers and keratinocytes: intracellular autoantigens (Mi-2/CHD4, TIF1-γ/TRIM33, NXP2/MORC3, SAE1/2) (Current Rheumatology Reports, 2024) (musai2024recentupdateson pages 1-2). - Extracellular space and alveolar compartments: cytokine/chemokine milieu and macrophage activation in ILD (Rheumatology International, 2024) (harada2024baricitinibforantimelanoma pages 7-8).

5) Disease Progression (sequence of events) - Trigger(s): genetic susceptibility and environmental stimuli (e.g., viral RNA sensed by MDA5, UV) initiate innate immune activation with strong IFN-I production by pDCs and other sources (Current Rheumatology Reports, 2024) (musai2024recentupdateson pages 1-2). - Vascular phase: antibody/complement-mediated endothelial injury (MAC deposition) causes capillary dropout and ischemia; clinically, nailfold changes and painful cutaneous ulcers may appear (Journal of Neuromuscular Diseases, 2024; Cureus, 2025) (honda2024contributionofcomplement pages 1-3, cristofori2025dermatomyositisanarrative pages 3-4). - Muscle phase: hypoperfusion and IFN-driven immune activation promote perifascicular atrophy, MHC-I upregulation, and inflammatory infiltrates with macrophages, CD4+ T cells, B cells; proximal weakness ensues (Cureus, 2025) (cristofori2025dermatomyositisanarrative pages 2-3). - Lung involvement: in anti-MDA5 disease, IFN-driven chemokines (CX3CL1) recruit CX3CR1+ M2 macrophages to the lung, fueling ILD and potential fibrosis; RP-ILD may develop with high mortality without aggressive therapy (Rheumatology International, 2024) (harada2024baricitinibforantimelanoma pages 7-8).

6) Phenotypic Manifestations (HP terms) - Proximal muscle weakness (HP:0003701), elevated muscle enzymes, and dysphagia (HP:0002015) reflect myofiber injury and inflammation (Cureus, 2025) (cristofori2025dermatomyositisanarrative pages 2-3). - Heliotrope rash (HP:0001002), Gottron papules (HP:0031408), poikiloderma and photosensitivity (HP:0000992) reflect IFN-driven skin inflammation with interface dermatitis and complement deposition (Cureus, 2025; Seminars in Immunopathology, 2025) (cristofori2025dermatomyositisanarrative pages 2-3, ali2025dermatomyositisfocuson pages 1-2). - Nailfold capillary abnormalities (HP:0030831) reflect microangiopathy (Cureus, 2025) (cristofori2025dermatomyositisanarrative pages 3-4). - Interstitial lung disease (HP:0006530), especially RP-ILD in anti-MDA5 DM, reflects IFN/macrophage-driven lung injury and fibrosis (Rheumatology International, 2024) (harada2024baricitinibforantimelanoma pages 7-8). - Calcinosis cutis (HP:0000987), especially in juvenile/anti-NXP2 disease, indicates chronic tissue damage and dystrophic calcification (Current Rheumatology Reports, 2024) (musai2024recentupdateson pages 1-2).

Evidence items (primary data and statistics; URLs and dates) - Complement microangiopathy and perifascicular atrophy: “deposition of the membrane attack complex (C5b-9) in endomysial capillaries” associates with endothelial/myofiber injury and ischemia; juvenile DM shows capillary loss and small-vessel angiopathy (Journal of Neuromuscular Diseases, Dec 2024; https://doi.org/10.3233/jnd-230168) (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10). - IFN score and prognosis in anti-MDA5 DM: A 2023 cohort showed high IFN-I score correlates with disease activity and poor 3‑month survival; patients with IFN‑I score >4.9 had lower 3‑month survival (72.9% vs. 100%; P=0.044) (Frontiers in Immunology, Mar 2023; https://doi.org/10.3389/fimmu.2023.1151695) (rocca2023targetingintracellularpathways pages 3-4). - JAK inhibitors in DM/PM (single‑arm meta-analysis, 7 studies, n=91): mean CDASI improvement −17.67 (95% CI −20.94 to −14.41); MMT +10.31 (95% CI −2.83 to 23.46). Subgroup CDASI reductions: ruxolitinib −20.00, tofacitinib −18.29, baricitinib −11.2. Reported safety included orolabial HSV and two thromboembolic events (Frontiers in Immunology, Mar 2024; https://doi.org/10.3389/fimmu.2024.1382728) (ma2024therapeuticefficacyand pages 1-2). - Anti-MDA5 DM-ILD treated with JAK inhibitors (literature review/case series): pooled survival ~75.9% (predominantly tofacitinib); baricitinib case series (n=3) improved lung opacities and rescued 2/3; notable CMV reactivation risk—close monitoring recommended (Rheumatology International, Mar 2024; https://doi.org/10.1007/s00296-024-05551-2) (harada2024baricitinibforantimelanoma pages 7-8). - JDM JAK inhibitor overview (systematic narrative): Across compiled reports to 2023, muscle improvement in 51/53 (96%); skin improvement in 109/152 (72%); frequent steroid reduction; infections included EBV/CMV/HSV and bacterial/fungal events; hematologic/lipid changes reported (Expert Rev Clin Immunol, Feb 2024; https://doi.org/10.1080/1744666x.2024.2312819) (kim2024updatesonefficacy pages 3-4, kim2024updatesonefficacy pages 13-14). - Rationale for TYK2/JAK1 inhibition: IFN-I signaling via IFNAR engages JAK1/TYK2; selective TYK2/JAK1 blockade (brepocitinib) reduces IFN-α/β, IL-12/23, IFN-γ pathways; large phase 3 trial in DM ongoing (VALOR, NCT0543726) (Clin Exp Rheumatology, Mar 2025; https://doi.org/10.55563/clinexprheumatol/eeglsa) (paik2025brepocitinibapotent pages 1-2).

Expert opinions and analysis - Consensus in recent expert reviews is that DM is best conceptualized as an IFN-driven microangiopathy with autoantibody-defined endotypes that dictate organ risk (malignancy vs. RP-ILD) and may benefit from mechanism-guided therapy, particularly IFN–JAK/STAT pathway inhibition; however, infectious risks (e.g., CMV) and heterogeneity of responses necessitate risk-stratified, monitored use (Current Rheumatology Reports, 2024; Expert Opin Pharmacother, 2024; Rheumatology International, 2024) (musai2024recentupdateson pages 1-2, wallwork2024currentevidencefor pages 1-3, harada2024baricitinibforantimelanoma pages 7-8).

Current applications and real-world implementations - Off-label JAK inhibitor use for refractory cutaneous DM and anti-MDA5 DM-ILD (tofacitinib, baricitinib, ruxolitinib) with documented improvements in CDASI, muscle scores, and ILD survival in observational cohorts; viral surveillance and infection prophylaxis protocols increasingly implemented in high-risk subsets (Frontiers in Immunology, 2024; Rheumatology International, 2024) (ma2024therapeuticefficacyand pages 1-2, harada2024baricitinibforantimelanoma pages 7-8). - IVIG employed to modulate humoral/complement pathways, with mechanistic support that it can block endomysial complement deposition (Journal of Neuromuscular Diseases, 2024) (honda2024contributionofcomplement pages 8-10). - Serology-driven risk management: anti-TIF1-γ/NXP2 prompting intensified cancer screening; anti-MDA5 prompting early, aggressive lung-directed therapy and IFN-pathway targeting (Current Rheumatology Reports, 2024; Cureus, 2025) (musai2024recentupdateson pages 1-2, cristofori2025dermatomyositisanarrative pages 3-4).

Ontology-annotated annotations (HGNC, GO, CL, UBERON, CHEBI, HP) - Genes/Proteins (HGNC): TRIM33 (TIF1-γ), MORC3 (NXP2), IFIH1 (MDA5), CHD4 (Mi-2), SAE1/SAE2; IFNAR1/2, JAK1, TYK2, STAT1; C5–C9 (MAC) (musai2024recentupdateson pages 1-2, honda2024contributionofcomplement pages 1-3). - GO Biological processes: type I interferon signaling (GO:0060337); complement activation (GO:0006956); endothelial activation (GO:0042118); leukocyte chemotaxis (GO:0030595); antigen presentation via MHC-I (GO:0002474); pulmonary fibrosis/TGF-β signaling (GO:0007179) (honda2024contributionofcomplement pages 1-3, musai2024recentupdateson pages 1-2, harada2024baricitinibforantimelanoma pages 7-8). - Cellular components: endomysial capillary, perimysial vessel, sarcolemma, dermoepidermal junction, cytosol/nucleus, extracellular space (honda2024contributionofcomplement pages 1-3, cristofori2025dermatomyositisanarrative pages 2-3). - Cell types (CL): pDCs (CL:0000911), macrophages (CL:0000235), endothelial cells (CL:0000115), CD4+ and CD8+ T cells, B cells/plasma cells, keratinocytes, alveolar macrophages (kobayashi2024advancesinjuvenile pages 13-14, musai2024recentupdateson pages 1-2, honda2024contributionofcomplement pages 1-3). - Anatomical locations (UBERON): skin (UBERON:0002097), skeletal muscle (UBERON:0002090), lung (UBERON:0002048) (cristofori2025dermatomyositisanarrative pages 2-3, musai2024recentupdateson pages 1-2). - Chemical entities (CHEBI): tofacitinib, baricitinib, ruxolitinib, brepocitinib, intravenous immunoglobulin (ma2024therapeuticefficacyand pages 1-2, paik2025brepocitinibapotent pages 1-2, honda2024contributionofcomplement pages 1-3). - Phenotypes (HP): proximal muscle weakness (HP:0003701), heliotrope rash (HP:0001002), Gottron papules (HP:0031408), photosensitivity (HP:0000992), dysphagia (HP:0002015), interstitial lung disease (HP:0006530), calcinosis cutis (HP:0000987), nailfold capillary abnormalities (HP:0030831) (ali2025dermatomyositisfocuson pages 1-2, cristofori2025dermatomyositisanarrative pages 2-3, harada2024baricitinibforantimelanoma pages 7-8).

Direct quotes (selected) - “deposition of the membrane attack complex (C5b-9) in endomysial capillaries” (Journal of Neuromuscular Diseases, 2024; https://doi.org/10.3233/jnd-230168) (honda2024contributionofcomplement pages 1-3). - “type I interferon gene transcription scores in blood correlate strongly with DM disease activity” and “decrease significantly with immunomodulatory therapy” (Clin Exp Rheumatology, 2025; https://doi.org/10.55563/clinexprheumatol/eeglsa) (paik2025brepocitinibapotent pages 1-2). - In anti-MDA5 DM-ILD treated with JAK inhibitors, “the survival rate was 75.9%” in pooled literature, and “the incidence of CMV reactivation appeared to be high” (Rheumatology International, 2024; https://doi.org/10.1007/s00296-024-05551-2) (harada2024baricitinibforantimelanoma pages 7-8).

Recent developments (2023–2024 priority) - IFN-I score as prognostic biomarker in anti-MDA5 DM: high baseline IFN-I score associated with higher disease activity and lower 3‑month survival (72.9% vs 100%) (Frontiers in Immunology, Mar 2023; https://doi.org/10.3389/fimmu.2023.1151695) (rocca2023targetingintracellularpathways pages 3-4). - JAK inhibitors meta-analysis (Mar 2024) demonstrates clinically meaningful cutaneous improvement (CDASI −17.67) and muscle strength gains; safety acceptable but vigilance for thromboembolism and infection required (Frontiers in Immunology, Mar 2024; https://doi.org/10.3389/fimmu.2024.1382728) (ma2024therapeuticefficacyand pages 1-2). - Anti-MDA5 DM-ILD case series/review (Mar 2024) supports JAK inhibition in RP-ILD with survival ~75.9% and highlights CMV risk and need for monitoring (Rheumatology International, Mar 2024; https://doi.org/10.1007/s00296-024-05551-2) (harada2024baricitinibforantimelanoma pages 7-8). - Expert therapeutic overviews (Aug 2024) outline growing evidence base and active randomized trials of JAK/TYK2 inhibitors in adult and juvenile DM (Expert Opin Pharmacother, Aug 2024; https://doi.org/10.1080/14656566.2024.2392021) (wallwork2024currentevidencefor pages 1-3).

Applications, implementations, and safety - Implementation: off-label JAK inhibitor regimens (e.g., tofacitinib 5–10 mg BID; baricitinib 2–4 mg daily) with multi-drug background therapy, serial IFN score and viral surveillance (CMV/EBV/BK) in high-risk anti-MDA5 subsets; IVIG used to curb complement-mediated injury (Frontiers in Immunology, 2024; Journal of Neuromuscular Diseases, 2024) (ma2024therapeuticefficacyand pages 1-2, honda2024contributionofcomplement pages 8-10). - Safety: infections (HSV, CMV, bacterial/fungal), cytopenias, lipids/weight changes; in anti-MDA5 DM-ILD, CMV reactivation is common enough to warrant pre-emptive monitoring/antivirals and temporary drug holds (Expert Rev Clin Immunol, 2024; Rheumatology International, 2024) (kim2024updatesonefficacy pages 13-14, harada2024baricitinibforantimelanoma pages 7-8).

Structured artifacts (ontology-mapped summary) | Category | Entity (preferred name) | Ontology tag | Mechanistic role in DM | Phenotype/clinical association | Key evidence | Notes | |---|---|---|---|---|---|---| | Pathway | Type I interferon pathway (IFNA/IFNB → IFNAR1/2 → JAK1/TYK2 → STAT1) | IFNA/IFNB, IFNAR1, IFNAR2, JAK1, TYK2, STAT1 (HGNC); GO:0060337 (type I interferon signaling) | Drives a dominant transcriptional signature (ISGs) in skin and muscle; promotes MHC-I upregulation and immune cell recruitment | Correlates with disease activity, anti‑MDA5 severity, and poor prognosis in RP‑ILD | (musai2024recentupdateson pages 1-2, kim2025juveniledermatomyositisupdates pages 1-2, cristofori2025dermatomyositisanarrative pages 2-3) | Therapeutic target of JAK inhibitors; measurable IFN score biomarker | | Complement | Complement membrane attack complex (C5b-9 / MAC) | C5 (HGNC); GO:0006956 (complement activation) ; Cellular component: extracellular space / endomysial capillary | Deposition on endomysial capillaries and sarcolemma causing endothelial/myofiber injury and microangiopathy | Associated with perifascicular atrophy, capillary loss, and juvenile DM vascular pathology | (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10, cristofori2025dermatomyositisanarrative pages 3-4) | IVIG can block complement deposition; complement implicated in antibody-mediated endothelial damage | | Cell type | Plasmacytoid dendritic cell (pDC) | CL:0000911 (pDC) ; GO:0034340 (type I interferon production) | Main source of type I IFNs in affected tissues; present in inflamed muscle and skin, amplifies IFN signature | Contributes to local inflammation and IFN-driven tissue damage | (kobayashi2024advancesinjuvenile pages 13-14, musai2024recentupdateson pages 1-2, honda2024contributionofcomplement pages 1-3) | pDCs link innate viral-sensing to autoimmunity in DM | | Cell type | Endothelial cell | CL:0000115 (endothelial cell); GO:0042118 (endothelial cell activation) ; Cellular component: endomysial capillary | Target of autoantibody- and complement-mediated injury leading to microangiopathy and ischemia | Perivascular inflammation, capillary dropout, microhemorrhages; drives perifascicular changes | (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10) | Endothelial activation biomarkers associate with disease activity | | Tissue/cell | Skeletal muscle fiber (myofiber) | UBERON:0002090 (skeletal muscle) ; Cellular component: sarcolemma, cytosol, nucleus | Display MHC‑I upregulation, atrophy/necrosis from hypoperfusion and immune attack; regenerative changes | Proximal symmetric weakness, elevated CK, perifascicular atrophy on biopsy | (cristofori2025dermatomyositisanarrative pages 2-3, musai2024recentupdateson pages 1-2) | Autoantibody entry into myofibers may disrupt intracellular targets | | Cell type | Macrophage (incl. CD163+ subsets) | CD163 (HGNC); CL:0000235 (macrophage) | Produce cytokines, present antigen, participate in interferon-driven inflammation and tissue remodeling | Associated with perimysial/perifascicular infiltration; implicated in anti‑MDA5 lung pathology | (musai2024recentupdateson pages 1-2, honda2024contributionofcomplement pages 8-10) | Macrophage polarization (M1/M2) influences damage vs repair | | Cell type | T cell (CD4+, CD8+) | CD4, CD8A (HGNC); CL terms for T cell subsets | CD4+ perivascular infiltrates; CD8+ implicated in cytotoxic responses and paraneoplastic links | Lymphocytic infiltration on muscle biopsy; CD8+ associated with some cancer‑linked phenotypes | (cristofori2025dermatomyositisanarrative pages 2-3, musai2024recentupdateson pages 1-2) | T cell roles vary by autoantibody-defined subtype | | Cell type | B cell / plasma cell | CD19, CD20 (HGNC); CL:0000236 (B cell) | Source of myositis-specific autoantibodies; antigen presentation and local antibody production | Autoantibodies stratify phenotypes (malignancy risk, ILD risk) and guide therapy (rituximab) | (musai2024recentupdateson pages 1-2, kim2025juveniledermatomyositisupdates pages 1-2) | B‑cell depletion and emerging CD19 CAR‑T approaches under investigation | | Cell type | Keratinocyte | CL:0000134 (epidermal keratinocyte) ; Cellular component: dermoepidermal junction | Responds to IFN signaling and shows immune complex / complement deposition → apoptosis and rash | Gottron papules, heliotrope rash, poikiloderma; cutaneous ulceration in severe/anti‑MDA5 cases | (cristofori2025dermatomyositisanarrative pages 2-3, ali2025dermatomyositisfocuson pages 1-2) | Skin changes mirror muscle IFN-driven pathology | | Cell type | Lung alveolar macrophage | CL:0000235 (macrophage); UBERON lung alveolus | Participate in IFN/cytokine networks and macrophage activation contributing to ILD | Central in anti‑MDA5 RP‑ILD pathogenesis and respiratory failure | (kim2025juveniledermatomyositisupdates pages 1-2, musai2024recentupdateson pages 1-2) | Therapies targeting IFN/JAK may modulate pulmonary macrophage activation | | Autoantigen / autoantibody | TRIM33 / TIF1-γ | TRIM33 (HGNC) / anti‑TIF1-γ MSA | Autoantigen targeted by autoantibodies; potential paraneoplastic antigen linking tumor neoantigens to autoimmunity | Strongly associated with cancer‑associated DM and specific cutaneous phenotypes | (cristofori2025dermatomyositisanarrative pages 2-3, musai2024recentupdateson pages 1-2) | TIF1-γ serology used for cancer risk stratification | | Autoantigen / autoantibody | NXP2 | NXP2 (MORC3?) — NXP2 (gene) (HGNC) | Nuclear matrix protein targeted by autoantibodies; associated with distinct muscle/skin pathology | Linked to adult cancer risk, calcinosis, severe weakness and dysphagia | (cristofori2025dermatomyositisanarrative pages 2-3, musai2024recentupdateson pages 1-2) | Phenotype associations vary by age group | | Autoantigen / autoantibody | MDA5 / IFIH1 | IFIH1 (HGNC) / anti‑MDA5 MSA | Viral RNA sensor; autoantibodies linked to IFN overactivation and macrophage/monocyte dynamics | Clinically amyopathic DM, high risk of rapidly progressive ILD (RP‑ILD) and poor pulmonary prognosis | (kim2025juveniledermatomyositisupdates pages 1-2, musai2024recentupdateson pages 1-2) | Geographic/seasonal patterns noted; anti‑MDA5 titer correlates with severity | | Autoantigen / autoantibody | Mi‑2 / CHD4 | CHD4 (HGNC) / anti‑Mi‑2 MSA | Autoantibody associated with classic DM histology; less oncologic risk | Favorable prognosis, characteristic cutaneous findings | (musai2024recentupdateson pages 1-2, ali2025dermatomyositisfocuson pages 1-2) | Mi‑2 subtype historically linked to good treatment response | | Autoantigen / autoantibody | SAE1 / SAE2 | SAE1, SAE2 (HGNC) / anti‑SAE MSA | Autoantibody linked to cutaneous‑predominant onset and systemic features | Florid skin disease, delayed muscle weakness, possible increased cancer risk | (ali2025dermatomyositisfocuson pages 1-2, musai2024recentupdateson pages 1-2) | SAE serology marks a distinct clinical trajectory | | Organ site | Skin | UBERON:0002097 (skin) ; Cellular component: dermoepidermal junction | Primary target of IFN-driven inflammation, immune complex/complement deposition | Pathognomonic rashes (Gottron, heliotrope), ulcers, photosensitivity; reflects systemic disease activity | (cristofori2025dermatomyositisanarrative pages 2-3, ali2025dermatomyositisfocuson pages 1-2) | Skin biopsies and capillaroscopy provide diagnostic/prognostic clues | | Organ site | Skeletal muscle | UBERON:0002090 (skeletal muscle) ; Cellular component: endomysial capillary, sarcolemma | Site of microangiopathy, myofiber ischemia/necrosis, MHC‑I upregulation and immune infiltration | Proximal muscle weakness, elevated muscle enzymes, biopsy changes including perifascicular atrophy | (honda2024contributionofcomplement pages 1-3, musai2024recentupdateson pages 1-2) | Muscle MRI and biopsy remain key diagnostic tools | | Organ site | Lung | UBERON:0002048 (lung) ; GO:0035966 (pulmonary fibrosis) | Target of inflammatory and fibrotic sequelae driven by IFN/cytokines and macrophage activation | Interstitial lung disease (ILD), rapidly progressive ILD in anti‑MDA5 patients | (kim2025juveniledermatomyositisupdates pages 1-2, musai2024recentupdateson pages 1-2) | ILD is a major determinant of mortality in specific DM subtypes | | Therapeutic | Tofacitinib (JAK1/2/3 inhibitor) | CHEBI:tofacitinib (drug) ; acts on JAK/STAT pathway | Inhibits downstream signaling of type I IFN and other cytokines to reduce inflammation | Improves cutaneous disease and some muscle outcomes in refractory DM (case series/meta-analyses) | (musai2024recentupdateson pages 1-2, kim2025juveniledermatomyositisupdates pages 1-2, ali2025dermatomyositisfocuson pages 1-2) | Off‑label use reported; safety profile includes infection risk | | Therapeutic | Baricitinib (JAK1/2 inhibitor) | CHEBI:baricitinib | JAK inhibition reducing IFN signaling; reported benefit in anti‑MDA5 ILD case series | Case series report lung improvement and survival benefit in some cohorts | (kim2025juveniledermatomyositisupdates pages 1-2, musai2024recentupdateson pages 1-2, honda2024contributionofcomplement pages 8-10) | Monitoring for opportunistic infections and CMV reactivation advised | | Therapeutic | Ruxolitinib (JAK1/2 inhibitor) | CHEBI:ruxolitinib | JAK inhibition, targets IFN and other cytokine signaling | Case reports/series show cutaneous and systemic benefit | (musai2024recentupdateson pages 1-2, ali2025dermatomyositisfocuson pages 1-2) | Topical and systemic formulations have been used in refractory cases | | Therapeutic | Brepocitinib (TYK2/JAK1 inhibitor) | CHEBI:brepocitinib | Inhibits TYK2/JAK1 to reduce IFN‑α/β and other cytokine signaling; under phase 3 study in DM | Rationale for use based on IFN biology; large trials ongoing (VALOR) | (honda2024contributionofcomplement pages 8-10, musai2024recentupdateson pages 1-2) | Potential to target multiple pathogenic cytokines with oral therapy | | Therapeutic | Intravenous immunoglobulin (IVIG) | CHEBI:immunoglobulin (IVIG) | Modulates Fc receptors, neutralizes autoantibodies, and can inhibit complement deposition | Effective in refractory cutaneous and muscle disease; may reduce complement-mediated injury | (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10) | Mechanisms include complement inhibition and immune modulation |

Table: Concise knowledge‑base table mapping key entities (pathways, cells, autoantigens, organs, therapies) to ontology tags, mechanistic roles, clinical associations, and supporting evidence (context IDs). Useful for structured disease annotation and rapid reference.

Evidence catalog (with PMIDs/DOIs provided via URLs where available) - Complement, microangiopathy, perifascicular atrophy and IFN biomarkers in DM: Journal of Neuromuscular Diseases, Dec 2024; https://doi.org/10.3233/jnd-230168 (honda2024contributionofcomplement pages 1-3, honda2024contributionofcomplement pages 8-10). - IFN-driven pathogenesis and autoantibody-defined endotypes: Current Rheumatology Reports, Sep 2024; https://doi.org/10.1007/s11926-024-01164-7 (musai2024recentupdateson pages 1-2). - pDCs and IFN signature in pediatric disease; vasculopathy: Children, Aug 2024; https://doi.org/10.3390/children11091046 (kobayashi2024advancesinjuvenile pages 13-14). - Anti-MDA5 DM-ILD pathogenesis and JAK inhibition outcomes and risks: Rheumatology International, Mar 2024; https://doi.org/10.1007/s00296-024-05551-2 (harada2024baricitinibforantimelanoma pages 7-8). - JAK inhibitor meta-analysis (DM/PM): Frontiers in Immunology, Mar 2024; https://doi.org/10.3389/fimmu.2024.1382728 (ma2024therapeuticefficacyand pages 1-2). - JDM JAK inhibitor outcomes and safety: Expert Rev Clin Immunol, Feb 2024; https://doi.org/10.1080/1744666x.2024.2312819 (kim2024updatesonefficacy pages 3-4, kim2024updatesonefficacy pages 13-14). - TYK2/JAK1 rationale (brepocitinib) and IFN score–activity correlations: Clin Exp Rheumatology, Mar 2025; https://doi.org/10.55563/clinexprheumatol/eeglsa (paik2025brepocitinibapotent pages 1-2). - Integrative clinical narrative for DM skin-muscle-malignancy linkages: Cureus, Jul 2025; https://doi.org/10.7759/cureus.88601 (cristofori2025dermatomyositisanarrative pages 2-3, cristofori2025dermatomyositisanarrative pages 3-4).

Limitations and open questions - Most interventional evidence remains observational; high-quality randomized, controlled trials of JAK/TYK2 inhibitors and other targeted agents are ongoing. Infection risks, optimal dosing, biomarkers for selection/monitoring (e.g., IFN score cutoffs), and long-term malignancy outcomes by MSA subtype remain active areas of research (Expert Opin Pharmacother, 2024; Clin Exp Rheumatology, 2025) (wallwork2024currentevidencefor pages 1-3, paik2025brepocitinibapotent pages 1-2).

References

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  15. (kim2025juveniledermatomyositisupdates pages 1-2): Hanna Kim. Juvenile dermatomyositis: updates in pathogenesis and biomarkers, current treatment, and emerging targeted therapies. Paediatric Drugs, 27:57-72, Oct 2025. URL: https://doi.org/10.1007/s40272-024-00658-2, doi:10.1007/s40272-024-00658-2. This article has 8 citations and is from a peer-reviewed journal.