Abstract
This study aims to evaluate treatments for actinic prurigo, a chronic, photosensitive dermatosis disproportionately affecting Indigenous populations. We present the case of a 49-year-old Indigenous woman with refractory actinic prurigo successfully managed with upadacitinib, a Janus kinase inhibitor. After inadequate responses to photoprotection and topical corticosteroids, the patient demonstrated substantial clinical improvement with systemic upadacitinib therapy, achieving marked symptom reduction and improved quality of life. A systematic review including 334 actinic prurigo patients from 38 studies found the highest complete resolution rates with Janus kinase inhibitors (100%), hydroxychloroquine (100%), and topical tacrolimus (100%). Treatment recurrence was common with thalidomide (34%), highlighting limitations of traditional therapies. Janus kinase inhibitors, targeting cytokine-driven inflammation, appear particularly promising. Although further large-scale studies are needed, our findings suggest Janus kinase inhibitors such as upadacitinib offer effective and safe treatment alternatives for refractory actinic prurigo, significantly enhancing patient outcomes and quality of life.
Keywords
Introduction
Actinic prurigo (AP) is a rare, chronic, idiopathic photodermatosis characterized by intensely pruritic papules, nodules, and plaques predominantly affecting sun-exposed areas, including the malar cheeks, nose, lips, forehead, and extensor forearms. 1 The etiology of AP is unproven; however, its strong genetic association, particularly with HLA-DR4 and the DRB1*0407 subtype in up to 60% of cases, supports an autoimmune pathogenesis. 2 Cheilitis and conjunctivitis are frequently observed, with some patients exhibiting lip involvement as the sole manifestation of disease. 3 Symptoms substantially impact quality of life, typically beginning in childhood and disproportionately affect Indigenous populations in the Americas, with a strong female predominance. 1 Despite first-line management with sun avoidance and topical corticosteroids, many patients experience limited relief. Historically, thalidomide is effective but limited by teratogenicity, while anti-malarials have limited efficacy. 1 As our understanding of immune-mediated skin diseases evolves, biologics and small-molecule therapies offer new potential for managing refractory AP.3,4 Following CARE guidelines (Supplemental Table 1), and with written consent for publication of clinical details and images, we report successful management of AP with upadacitinib together with a systematic review of prior treatment outcomes.
Case
A 49-year-old Indigenous female from a remote Northern Canadian community presented with a longstanding history of photosensitive skin eruptions since age 23, characterized by intensely pruritic rashes predominantly on sun-exposed areas of the face and arms, recurring annually from March to September. Her medical history was notable for latent tuberculosis infection, fully treated 3 years prior, and symptomatic iron-deficiency anemia due to severe menorrhagia. Family history included a niece experiencing episodes of photosensitivity. At the initial consultation 4 years prior, physical examination revealed eroded papules with some lichenification on the arms and exophytic plaques with erosions on the face (Figure 1). A clinical diagnosis of AP was established. Initial management emphasized rigorous photoprotection, sun avoidance strategies, and application of high Sun Protection Factor (SPF) sunscreen. However, adherence to photoprotection proved challenging, resulting in persistent lesions throughout the summer months, which resolved completely during winter.
Symmetric erythematous plaques and lichenification on the malar cheeks, nasal bridge, and forehead, with relative sparing of the perioral region and eyelids.
In March 2024, topical therapy was optimized with 0.1% tacrolimus ointment for facial lesions and mometasone cream for body lesions, along with reinforced photoprotection counseling and high-SPF sunscreen use. Biologic therapy was considered; however, initiation was delayed pending resolution of symptomatic anemia and confirmation of previous tuberculosis treatment. After 1 month of topical treatment, the patient achieved partial improvement, yet continued to experience discomfort upon sun exposure. In May 2024, systemic therapy was commenced with upadacitinib 15 mg daily. At the 3-month follow-up, the patient demonstrated partial clinical improvement with a body surface area (BSA) involvement of 10%, Eczema Area and Severity Index of 16, Dermatology Life Quality Index score of 20/30, and Numerical Rating Scale (NRS) for pruritus at 9/10. By 6-month follow-up, significant improvement was noted (BSA <1%, NRS 4/10).
Due to persistent sun-triggered symptoms, the upadacitinib dose was increased to 30 mg daily in March 2025, while continuing topical mometasone and tacrolimus. At the 3-month follow-up post-dose escalation, the patient reported ongoing xerosis and mild pruritus triggered by sun exposure but maintained significant symptomatic and clinical improvement compared to baseline. During a brief interview, the patient remarked that she felt fortunate to have access to upadacitinib while frustrated that others from her community with her community lacked access to major dermatologic centers or advanced therapeutics.
Discussion
Our case represents the fourth reported use of a Janus kinase inhibitor (JAKi), and the second involving upadacitinib, for AP, all in Indigenous patients, with no reported adverse events (AEs) and complete clinical resolution, supporting its potential as an effective therapeutic option.5–7 Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Embase and MEDLINE databases were searched using the keywords (actinic prurigo OR Hutchinson* prurigo OR hydroa aestivale; Supplementary Table 2) to explore treatment outcomes associated with AP. The search, conducted to March 2025 with no start date limit, included observational or experimental studies (case reports, case series, retrospective studies) reporting treatment outcomes in patients with confirmed AP; abstracts and reviews were excluded. This systematic review was registered on PROSPERO (ID: CRD420251016109). After two independent screenings by two reviewers, 38 studies were included, representing a total of 334 patients (Figure 2 and Supplementary Table 3). Risk of bias was evaluated using a modified Joanna Briggs Institute framework: 84% (31/37) were rated moderate risk, 11% (4/37) low risk, and 5% (2/37) high risk. 8 The mean age was 24.9 years (range: 6–87 years), with 29.4% (98/334) males, 70.6% (236/334) females, and 66.7% (76/114) of patients of Indigenous ancestry. Cheilitis was reported in 80.2% (182/227) of cases. A family history of AP was present in 14.7% (49/334) of patients, while 5.1% (17/334) had a family history of atopy. A biopsy was performed in 56.3% (188/334) of cases, revealing a positive HLA-DR4 serotype in 89.7% (35/39) of patients tested. Ultraviolet A (UVA) photo testing confirmed the diagnosis in 80.6% (25/31) of patients with a mean minimal erythema dose (MED) of 105.2 J/cm², while UVB phototesting confirmed the diagnosis in 45.5% (10/22) with a mean MED of 0.30 J/cm². The most frequently reported failed treatments were topical corticosteroids (31.3%, 21/67), sunscreens or sunblocks (29.9%, 20/67), hydroxychloroquine (11.9%, 8/67), and antihistamines (11.9%, 8/67).
Flow diagram of literature screening using the PRISMA guidelines. Figure adapted from http://prisma-statement. The criteria for study inclusion were (i) patient(s) with a diagnosis of actinic prurigo, (ii) patient(s) treated for actinic prurigo with reported outcomes, and (iii) studies that were observational or experimental in nature, including case reports, case series, and retrospective cohort studies.
A total of 371 therapies had documented outcomes. The most common were thalidomide (31.5%, 117/371), topical corticosteroids (16.7%, 62/371), and cyclosporine (8.6%, 32/371). Treatment duration was specified in 54.2% (201/371) of instances, with a mean duration of 11.4 weeks (range: 1.4–36.9 days). Complete resolution (CR) was observed most frequently among the JAKis baricitinib, upadacitinib, and tofacitinib (100%, 3/3), in addition to hydroxychloroquine (100%, 3/3) and topical tacrolimus (100%, 2/2). Recurrence following initial resolution was noted with 30% (56/244) of treatments, most commonly involving thalidomide (34%, 39/115; Table 1). AEs were reported with 7.3% (27/371) of treatments, including diarrhea (5.4%, 2/371; tetracycline), epigastric pain (5.4%, 2/371; tetracycline), and erythema (5.4%, 2/371; psoralen + UVA). Follow-up data were available in 51.8% (192/371) of instances, reflecting a mean duration of 24.5 months (range: 1–48 months).
Treatment outcomes of actinic prurigo.
AEs: adverse events; CAR: case report; CAS: case series; CR: complete resolution; NOR: no resolution; NR: none reported; PCS: prospective cohort study; PR: partial resolution; PUVA: psoralen and ultraviolet A radiation; RCS: retrospective cohort studies; UVA: ultraviolet A; UVB: ultraviolet B.
While the pathogenesis of AP is not fully elucidated, evidence supports a type IVb (Th2-mediated) hypersensitivity reaction to UV radiation in genetically susceptible individuals. 9 Th2 cytokines (IL-4, IL-5, IL-13) drive IgE and IgG4 production, thereby activating the eosinophils and mast cells prominent in AP lesions. 9 JAKis likely act by disrupting JAK-STAT signaling, thereby reducing eosinophilic inflammation and IgE-mediated responses.10–12 This mechanism likely underpins the efficacy of JAKi in the case presented and the systematic review (CR: 100%, 4/4).
Limitations include potential reporting bias (reflecting the predominance of case reports and series) and a small total sample size (n = 334). Larger-scale studies and those involving JAKis are warranted.
Conclusion
AP remains a challenging photodermatosis with limited evidence-based treatment options, particularly for Indigenous patients who bear a disproportionate burden of disease. In this case and systematic review, JAKis, especially upadacitinib, demonstrated consistent and complete clinical resolution in refractory AP, with favorable safety profiles. These findings highlight the therapeutic potential of targeting JAK-STAT-mediated inflammation in AP and underscore the need for broader access to advanced treatments in underserved communities. While larger, controlled studies are required, JAKi represents a promising, mechanistically rational option for patients with treatment-resistant AP.
Supplemental Material
sj-docx-1-sco-10.1177_2050313X251411129 – Supplemental material for Treatments for actinic prurigo: A case report with upadacitinib and systematic review
Supplemental material, sj-docx-1-sco-10.1177_2050313X251411129 for Treatments for actinic prurigo: A case report with upadacitinib and systematic review by Jonah W. Perlmutter, Romy Levy and Cathryn Sibbald in SAGE Open Medical Case Reports
Supplemental Material
sj-docx-2-sco-10.1177_2050313X251411129 – Supplemental material for Treatments for actinic prurigo: A case report with upadacitinib and systematic review
Supplemental material, sj-docx-2-sco-10.1177_2050313X251411129 for Treatments for actinic prurigo: A case report with upadacitinib and systematic review by Jonah W. Perlmutter, Romy Levy and Cathryn Sibbald in SAGE Open Medical Case Reports
Supplemental Material
sj-docx-3-sco-10.1177_2050313X251411129 – Supplemental material for Treatments for actinic prurigo: A case report with upadacitinib and systematic review
Supplemental material, sj-docx-3-sco-10.1177_2050313X251411129 for Treatments for actinic prurigo: A case report with upadacitinib and systematic review by Jonah W. Perlmutter, Romy Levy and Cathryn Sibbald in SAGE Open Medical Case Reports
Footnotes
Ethical considerations
This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was not required for this single case report and systematic review.
Consent to participate
Written informed consent was obtained from the patient prior to their participation in this case report.
Consent for publication
Written consent was obtained from the patient to anonymously publish their medical information, including clinical details and accompanying photographs, prior to data collection.
Author contributions
J.W.P. contributed to study conceptualization, study identification, data collection, data analysis, and manuscript writing. R.L. was responsible for study identification and data extraction. C.S. supervised the project, provided critical revisions, and oversaw clinical content and interpretation. All authors reviewed and approved the final manuscript.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.S. has received honoraria from Abbvie, Leo, Pfizer, Miravo, Novartis, UCB, Sanofi/Regeneron unrelated to this work. J.W.P. and R.L. have no conflicts of interest to disclose.
Data availability statement
All relevant data supporting the findings of this study are included within the article and supplementary materials.
Supplemental material
Supplemental material for this article is available online.
References
Supplementary Material
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