Site-level cutaneous phenotyping framework for anti-MDA5-positive dermatomyositis: exploratory associations with...

Area of Science:

• Rheumatology
• Dermatology
• Immunology
• Medical Informatics

Background:

• Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) exhibits significant clinical heterogeneity.
• Conventional skin assessments in DM may lack the granularity to capture this heterogeneity.
• A detailed, site-by-lesion cutaneous phenotyping approach could offer deeper insights into disease manifestations.

Purpose of the Study:

• To develop and validate a medical-record-based, site-by-lesion cutaneous phenotyping framework for anti-MDA5-positive DM.
• To assess if this framework provides enhanced phenotypic resolution compared to traditional binary skin assessments.
• To explore associations between detailed skin phenotypes and established systemic/immunological markers.

Main Methods:

• A retrospective cross-sectional study of 339 anti-MDA5-positive DM patients.
• Cutaneous involvement coded by lesion type (ulceration, itch, scale) across seven anatomical regions.
• Framework informed by the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) but without formal scores.
• Systemic and immunological markers (e.g., pulmonary arterial hypertension [PAH], IgG, IgM, CD8+ T-cell counts) used as reference anchors.
• Statistical analyses included univariate screening, multivariable models, and cross-correlation singular value decomposition (CC-SVD).

Main Results:

• The framework identified complementary skin-systemic associations.
• Spatial extent of ulceration refined signals related to CD8+ T-cell depletion.
• Facial ulceration showed a stronger association with PAH than overall ulcer burden.
• Specific lesion types correlated with distinct immunological profiles: ulceration with CD8+/IgG, and itch with IgM.
• CC-SVD delineated dimensions like facial involvement-PAH/infection and acral ulcer-CD8+/IgG.

Conclusions:

• Site-by-lesion cutaneous phenotyping offers a valuable framework for dissecting phenotypic heterogeneity in anti-MDA5-positive DM.
• The observed associations suggest a more nuanced understanding of disease subtypes.
• Prospective validation with standardized assessments and clinical outcome data is warranted.