Real world analysis of paid claims database reveals that disseminated superficial actinic porokeratosis (DSAP) is large orphan disease

Disseminated superficial actinic porokeratosis (DSAP) is a serious chronic, progressive premalignant genodermatosis resulting from mutations in the mevalonate pathway that causes hyperkeratotic, pruritic, red or brown rings on sun-exposed areas such as the arms and legs, that can number in the hundreds, leading to significant discomfort, disfigurement, and psychosocial burden. There are no FDA approved therapies for DSAP and no effective treatment options. We characterized the diagnosed population of DSAP patients in the U.S. We used the Komodo Health real-world claims platform to develop an algorithm to identify patients with probable DSAP using combinations of DSAP-specific diagnosis codes, related codes, and procedures through stepwise claims-based algorithms. Our primary analysis selected patients with at least two occurrences of diagnosis code L56.5 within a defined time window over 8 years (2018–2025), and a shorter window of 3 years (2023-2025) to identify a subpopulation seen in clinic most recently. A subsequent analysis identified a sub-population of patients receiving care with off-label topical therapy such as diclofenac, fluorouracil, imiquimod, ingenol mebutate, tirbanibulin, or destruction therapy such as liquid nitrogen cryotherapy. An additional analysis restricted cases to those diagnosed by dermatology-specialized clinicians (dermatologists, nurse practitioners, or physician assistants). A final analysis assessed potential association between DSAP and actinic keratosis or cutaneous skin cancer diagnoses (melanoma, SCC, BCC, or Merkel cell carcinoma). The number of DSAP patients identified in the primary analysis was 149,600 (2018-2025), with 76,800 seen in the more recent 3-year lookback period (2023-2025). After applying age-specific capture rates, the total US population is estimated to be 154,986 patients. The number of DSAP patients receiving treatment was 89,000 over the 8-year period, and 39,900 over 3 years. Annual counts in the longer time window rose from 36,174 (2018) to a peak of 54,501 (2023), then stabilized in 2024 (51,158) and 2025 (48,319). Age distribution was strongly skewed toward older individuals: ages 65–88 accounted for the vast majority (70% in 2023–2025; 61% in 2018–2025), with very few pediatric cases. Sex distribution: more females affected compared to males (63% vs 36% in 2023–2025; 64% vs 35% in 2018–2025). Among individuals with DSAP who were expert-diagnosed and treated, there was a highly significant association with concomitant diagnosis of actinic keratosis and skin cancer (Chi-square p < 0.0001). In this study, we developed a claims-based model for identifying individuals with probable DSAP using combinations of ICD-10 codes, repeated diagnosis requirements, dermatology encounters, lesion-destruction procedures. e.g. cryotherapy, relevant topical prescriptions, and co-morbidities. This is the first study to characterize the diagnosed prevalence of DSAP in the U.S. Despite the lack of FDA-approved treatments, a large sub-set of individuals (up to 59%) were treated for DSAP with off-label topical immunomodulators or destruction therapy. Hence there is currently a gap in the care of patients with DSAP and need for an FDA- approved treatment option.