Development and Validation of the Amyloidosis Area and Severity Index for Primary Cutaneous Amyloidosis

Background Primary cutaneous amyloidosis (PCA) is a chronic, pruritic skin disorder lacking a standardized severity instrument, hindering clinical assessment and research. Objectives To develop and validate a novel clinician-reported outcome measure, the Amyloidosis Area and Severity Index (AASI), for PCA. Methods The AASI was developed via a modified Delphi consensus process informed by surveys of 340 patients and 33 dermatologists. In a prospective validation study involving 50 patients, 10 raters independently assessed PCA patients twice using the AASI. Inter- and intra-rater reliability were determined using intraclass correlation coefficients (ICCs), and construct validity by correlating AASI scores with established outcome measures. Results The Delphi process prioritized four core domains: papule/macule, dryness/scaling, excoriation, and lichenification. The AASI demonstrated moderate inter-rater (ICC = 0.701) and good-to-excellent intra-rater reliability (ICC range: 0.762-0.942). Construct validity was supported by strong correlations with Investigator's Global Assessment (IGA) (ρ = 0.84) and Xerosis Score (ρ = 0.75) (all p < 0.001). Limitations Delphi consensus restricted to Chinese clinicians and patients; single-center validation; treatment responsiveness being evaluated in an ongoing trial. Conclusions The AASI is a new, consensus-derived severity instrument for PCA with moderate-to-good reliability and validity, providing a foundation for future standardized assessment for clinical and trial use.