Background Topical treatments are the foundation for patients with psoriasis; however, adherence can be limited by patient preferences and treatment burden.Methods The Harris Poll conducted an online survey of US patients with psoriasis who use prescription topical therapy to examine their preferences and perspectives on topical treatments.Results Among patients with psoriasis who use topical treatment (n = 507), most participants described their psoriasis symptoms as mild (31%) or moderate (59%). The body areas most often reported to be affected by psoriasis were the scalp, elbows, legs, intertriginous areas, arms, and knees. Participants reported psoriasis affecting the scalp (39%), elbows (20%), and legs (excluding knees; 19%) caused the greatest impact on quality of life. Most participants (76%) preferred topical therapies to treat their psoriasis, while 20% preferred pills, and 4% preferred injections. The most common product attributes that participants wanted in a topical psoriasis treatment and that would help them to continue to use the treatment were: improvement in plaques (68%), itch relief (68%), and easy to apply (63%).Conclusion The respondents to this survey reported that they prefer topical treatments to pills or injections (76%) and most (89%) reported they are interested in trying a new topical treatment.

Dermatitis®Ahead of Print LettersDupilumab for the Treatment of Severe Atopic Dermatitis in an Immunosuppressed Transplant PatientAfsoon Ghafari-Saravi and Teri M. GreilingAfsoon Ghafari-Saravihttps://orcid.org/0000-0002-3660-2308Department of Dermatology, Oregon Health and Science University, Portland, OR, USA. Search for more papers by this authorEmail the corresponding author at [email protected] and Teri M. GreilingDepartment of Dermatology, Oregon Health and Science University, Portland, OR, USA.Search for more papers by this authorPublished Online:10 Aug 2023https://doi.org/10.1089/derm.2023.0181AboutSectionsView articleView Full TextSupplemental MaterialPDF/EPUBView Supplemental Data Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Dupilumab for the Treatment of Severe Atopic Dermatitis in an Immunosuppressed Transplant Patient." Dermatitis®, , pp. FiguresReferencesRelatedDetails Volume 0Issue 0 Information© 2023 American Contact Dermatitis Society. All Rights Reserved.To cite this article:Afsoon Ghafari-Saravi and Teri M. Greiling.Dupilumab for the Treatment of Severe Atopic Dermatitis in an Immunosuppressed Transplant Patient.Dermatitis®.ahead of printhttp://doi.org/10.1089/derm.2023.0181Online Ahead of Print:August 10, 2023PDF download

To the Editor: Pityriasis rubra pilaris (PRP) is a rare, often severe, papulosquamous disease. The largest case series of PRP have characterized morphology, histopathology, and comorbidities, but lack corresponding patient signs and symptoms.1-3 Our recent qualitative study identified patient-reported cutaneous descriptors of PRP,4 all of which are captured by the Psoriasis Signs and Symptoms Diary (PSSD).5 We assessed PSSD in 14 consecutive patients with a clinical and histopathologic diagnosis of moderate to severe PRP seen at Oregon Health & Science University from October 2019 to August 2022 (Table I), and compared this to clinician-assessed Psoriasis Area and Severity Index (PASI) and patient-reported Dermatology Life Quality Index (DLQI) at baseline (on no systemic therapy) and over 36 weeks of systemic therapy.

Introduction: Teledermatology, defined as the use of remote imaging technologies to provide dermatologic healthcare services to individuals in a distant setting, has grown considerably in popularity since its widespread implementation during the COVID-19 pandemic. Teledermoscopy employs a smartphone dermatoscope attachment paired with a smartphone camera to visualize colors and microstructures within the epidermis and superficial dermis that cannot be seen with the naked eye ABCD criteria alone. Methods: Our retrospective observational cohort and case–control study evaluated the utility of loaning a smartphone dermatoscope attachment to patients for remote triage of self-selected lesions of concern for skin cancer. The primary outcome was the number (percentage) of in-person follow-up visits required for patients who submitted lesion images, either with or without accompanying dermoscopic images. A medical record review was conducted on all Oregon Health & Science University Department of Dermatology spot check image submissions utilizing the smartphone dermatoscopes between August 2020 and August 2022. De-identified dermoscopic images of lesions that included corresponding non-dermoscopic clinical images in their submission (n = 70) were independently reviewed by a blinded expert dermoscopist. The expert used standard clinical algorithms (ABCD criteria for clinical images; dermoscopy three-point checklist for dermoscopic images) to determine whether the imaged lesion should be converted to an in-person visit for further evaluation and consideration for biopsy. Results: Of the 70 lesions submitted with corresponding clinical and dermoscopy images, 60 met the criteria for in-person evaluation from clinical (non-dermoscopic) image review compared to 28 meeting the criteria for in-person evaluation from dermoscopic images of the same lesion. Thus, a 53% reduction in conversion to an in-person consultation with the addition of smartphone dermatoscope images in virtual lesion triage was observed (p < 0.001, McNemar’s Test). Conclusion: Implementing patient-led teledermoscopy may reduce the frequency of in-person visits for benign lesions and consequently improve access to in-person dermatology consultations for patients with concerning and possibly malignant lesions.

Background: Patients with skin lesions suspicious for skin cancer or atypical melanocytic nevi of uncertain malignant potential often present to dermatologists, who may have variable dermoscopy triage clinical experience. Objective: To evaluate the clinical utility of a digital dermoscopy image-based artificial intelligence algorithm (DDI-AI device) on the diagnosis and management of skin cancers by dermatologists. Methods: Thirty-six United States board-certified dermatologists evaluated 50 clinical images and 50 digital dermoscopy images of the same skin lesions (25 malignant and 25 benign), first without and then with knowledge of the DDI-AI device output. Participants indicated whether they thought the lesion was likely benign (unremarkable) or malignant (suspicious). Results: The management sensitivity of dermatologists using the DDI-AI device was 91.1%, compared to 84.3% with DDI, and 70.0% with clinical images. The management specificity was 71.0%, compared to 68.4% and 64.9%, respectively. The diagnostic sensitivity of dermatologists using the DDI-AI device was 86.1%, compared to 78.8% with DDI, and 63.4% with clinical images. Diagnostic specificity using the DDI-AI device increased to 80.7%, compared to 75.9% and 73.6%, respectively. Conclusion: The use of the DDI-AI device may quickly, safely, and effectively improve dermoscopy performance, skin cancer diagnosis, and management when used by dermatologists, independent of training and experience.

ImportanceThere is no US Food and Drug Administration-approved treatment for pityriasis rubra pilaris (PRP), and it is common for patients to fail to experience improvement with several systemic options. Involvement of interleukin (IL) 23 suggests a potential therapeutic target. ObjectiveTo determine whether guselkumab, an IL-23p19 inhibitor, provides clinical improvement for participants with PRP and better understand gene and protein dysregulation in PRP. Design, Setting, and ParticipantsThis single-arm, investigator-initiated nonrandomized trial was conducted from October 2019 to August 2022 at a single-center academic university with participants from 8 states in the US. In total, 14 adults with moderate to severe PRP were enrolled; 12 completed the trial. Age-matched and sex-matched healthy controls provided skin and blood for proteomic and transcriptomic studies. The primary outcome was observed at 24 weeks, and additional follow-up occurred at 36 weeks. InterventionGuselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that selectively binds and inhibits the p19 subunit of IL-23. Subcutaneous injections were given at the US Food and Drug Administration-approved dosing schedule for psoriasis over a 24-week period. Main Outcomes and MeasuresThe primary outcome was the mean change in the Psoriasis Area Severity Index (PASI) score at week 24. Secondary outcomes included pruritus, Dermatology Life Quality Index score, clinical response at week 36, and association with transcriptomics and proteomics expression. ResultsA per-protocol analysis was performed for the cohort of 4 female and 8 male patients who had a mean (SD) age of 56.5 (18.7) years. The mean improvement in PASI score, pruritus, and Dermatology Life Quality Index score was 61.8% (P < .001), 62.3% (P = .001), and 60.2% (P < .001), respectively. Nine participants (75%) achieved a 50% improvement in PASI. Among these clinical responders, at week 36, 8 of 9 achieved PASI75, and 6 of 9 achieved PASI90. No participants had pathogenic CARD14 gene variations. There was 1 serious adverse event that was not associated with the study drug. Proteomics and gene expression profiles identified dysregulation of a predominance of inflammatory pathways (such as T helper 17 and nuclear factor kappa B) in participants with PRP who later responded well to treatment with guselkumab and stronger dysregulation of keratinocyte development pathways in individuals who did not respond to guselkumab. Conclusion and RelevanceThe results of this nonrandomized trial suggest that guselkumab has efficacy in treating refractory moderate to severe adult PRP.

Human visual function depends on the biological lens, a biconvex optical element formed by coordinated, synchronous generation of growth shells produced from ordered cells at the lens equator, the distal edge of the epithelium. Growth shells are comprised of straight (St) and S-shaped (SSh) lens fibers organized in highly symmetric, sinusoidal pattern which optimizes both the refractile, transparent structure and the unique microcirculation that regulates hydration and nutrition over the lifetime of an individual. The fiber cells are characterized by diversity in composition and age. All fiber cells remain interconnected in their growth shells throughout the life of the adult lens. As an optical element, cellular differentiation is constrained by the physical properties of light and its special development accounts for its characteristic symmetry, gradient of refractive index (GRIN), short range transparent order (SRO), and functional longevity. The complex sinusoidal structure is the basis for the lens microcirculation required for the establishment and maintenance of image formation.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder associated with significant patient morbidity (Eastham et al., 2019; Ji-Xu et al., 2022). Recent discoveries in the pathophysiology of PRP, including alterations in IL-17 signaling (Boudreaux et al., 2022; Feldmeyer et al., 2017; Haynes et al., 2020; Strunck et al., 2022), phospholipase A2 processing (Shao et al., 2021), and novel germline CARD14 genetic variations (Fuchs-Telem et al., 2012), have yielded new diagnostic and therapeutic insights.

AbstractBackgroundPityriasis rubra pilaris (PRP) is a rare and often severe inflammatory skin disorder with major detriment to patients' quality of life. While past studies have described in detail the morphologic and histopathologic presentations of PRP, little attention has been given to the patient experience.ObjectivesTo identify the physical, mental, and daily living impacts of patients living with PRPMethodsFour focus groups involving 47 participants with PRP from six countries were conducted in English. Sessions were recorded and codified by themes, which were used to compose a 23‐question follow‐up survey.ResultsCommon physical symptoms that impacted a majority of PRP patients included severe pruritus, pain (generalised in involved skin, localised to palmoplantar fissures, and arthralgias), poor sleep, fatigue, anhidrosis, body temperature dysregulation, joint pain, buildup of material in the ears, and rhinorrhea. Participants felt that PRP was associated with a strong negative mental impact that caused depression, anxiety, embarrassment, loneliness, loss of self‐esteem, and memory loss or brain fog. 38% endorsed passive suicidal ideation and 4% active suicidal ideation. Common daily activity impacts included loss of fine motor ability and difficulty walking from palmoplantar keratoderma, difficulty wearing normal clothing, difficulty working, and difficulty leaving the home. Participants reported a mean of six applications of topical creams or ointments daily.ConclusionsThis study illustrates the debilitating daily life impacts of PRP in a variety of domains. In addition to care by a dermatologist, patients should be evaluated for the need for referral to ophthalmology, otolaryngology, and podiatry. Patients with PRP felt strongly that the mental health impact of PRP was not given enough attention by providers. Given the high rate of depression, anxiety, and passive and active suicidal ideation, providers should evaluate patients' mental health and offer a referral to psychiatry and other mental health providers.

Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that is occasionally associated with primary immunodeficiency. Though contributions from dysregulation of the innate immune system, neutrophil dysfunction and genetic predisposition have been postulated, the precise pathogenesis of PG has not yet been elucidated. This article reviews reported cases of coexisting PG and primary immunodeficiency in order to gain insight into the complex pathophysiology of PG. Our findings suggest that variations in genes such as RAG1 , ITGB2 , IRF2BP2 and NFκB1 might play a role in genetically predisposing patients to develop PG. These studies support the feasibility of the role of somatic gene variation in the pathogenesis of PG which warrants further exploration to guide targeted therapeutics.

What is known about this subject in regard to women and their families? Rosacea commonly affects women in their childbearing years, but it is not known how the physiologic changes of pregnancy affect rosacea severity. What is new from this article as messages for women and their families? A survey of women with a diagnosis of rosacea prior to pregnancy found that about half of women reported their rosacea worsened during pregnancy. Approximately one-third of women reported no change in rosacea severity during pregnancy, and the remaining respondents reported improvement. Thus we conclude that rosacea, like acne, lacks a predictable group effect and instead each individual may have a different response to the physiologic changes of pregnancy. Dear Editors, Rosacea is an inflammatory skin disorder with clinical manifestations that include centrofacial erythema, inflammatory papules and pustules, and recurrent flushing.1 The onset of rosacea is common in women during childbearing years and may be influenced by hormones,2,3 but little data beyond case reports are available about the course of rosacea during pregnancy. Rosacea pathogenesis includes innate and adaptive immune dysfunction and neurovascular dysfunction.1 Each of these systems also undergoes physiologic changes during pregnancy. For example, decreased Th1/Th17 immunity, with increased Th2 immunity during the third trimester of pregnancy,4 could suggest an environment that favors an improvement in rosacea. Conversely, decreased peripheral vascular resistance and hormone elevations during pregnancy may lead to exacerbation of rosacea.3 We conducted a descriptive retrospective survey study examining rosacea severity during and after pregnancy. Eligible participants were women ≥18 years with a diagnosis of rosacea (ICD10 L71) recorded in the electronic medical record prior to the onset of pregnancy, admitted to Oregon Health & Science University for labor and delivery from June 27, 2015 to June 27, 2020, who were able to be reached by telephone (n = 48). The study was approved by the Oregon Health & Science University institutional review board (#16647). Thirty nine of forty eight eligible women assented to participate (81.3% survey response rate). Patient global assessment (clear [0], mild [1], moderate [2], or severe [3]) was rated across 5 time-points: 1–3 months preconception, first, second, and third trimesters, and 6 weeks postpartum. The mean (SD) age of the participants at delivery was 35.5 (4.3) years, and the mean (SD) gestational age at the date of delivery was 39.4 (2.1) weeks. Thirty eight of thirty nine (97.4%) were singleton pregnancies and 7/39 (17.9%) had undergone fertility treatments to achieve pregnancy, which likely reflects the average age of rosacea onset.2 Thirty eight of thirty nine (97.4%) reported symptoms of erythematotelangiectatic rosacea and 26/39 (67%) reported symptoms of papulopustular rosacea. Nearly half (19/39, 48.7%) of the participants said their rosacea worsened during pregnancy; 13/39 (33.3%) reported no change in rosacea severity during pregnancy; and 7/39 (17.9%) reported their rosacea improved during pregnancy (Fig. 1A). The mean rosacea severity score was mild prior to conception, 1.10 (95% CI [0.92–1.29]), with no significant difference over time calculated by a generalized estimating equation method when averaging all participants together (all P > 0.05), reflecting the individual variation (Fig. 1B). Most participants did not use prescription rosacea treatments prior to (40/48, 83.3%) or during pregnancy (43/48, 89.6%). Limitations of the study include the small sample size, single institution study, overall prevalence of mild disease limiting the ability to detect change, and recall bias.Fig. 1.: Changes in rosacea during pregnancy. (A) Patient overall assessment of rosacea severity from prior to conception to pregnancy. (B) Patient global assessment of rosacea over time. Each dot represents 1 participant. Black line shows change between trimesters calculated by a generalized estimating equation method (all P > 0.05).Despite these limitations, this study expands the current knowledge base by providing observational data on changes in rosacea during pregnancy and suggests that, like acne,5 rosacea lacks a predictable group effect. While the mean change in severity during pregnancy was not significant across a population, most women reported changes in rosacea severity during pregnancy. More individuals reported worsening (one-half of the study group), but some reported improvement (one-sixth of the study group) and only about one-third of individuals reported no change in rosacea severity during pregnancy. Conflicts of interest None. Funding None. Study approval The study was approved by the Oregon Health & Science University institutional review board (#16647). Author contributions GB: Participated in research design, performance of the research, data analysis, and writing of the manuscript. CS: Participated in data analysis, writing of the manuscript, and approval of the final manuscript. RV: Participated in performance of the research and approval of the final manuscript. EL: Participated in data analysis and approval of the final manuscript. SC: Participated in data analysis and approval of the final manuscript. KS: Participated in research design and approval of the final manuscript. TMG: Participated in research design, data analysis, writing of the manuscript, and approval of the final manuscript.

Clinical problem Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that frequently affects the axillae. Axillae are also targeted for societal hygiene practices: namely, the use of deodorants and antiperspirants and techniques for hair removal. HS is associated with an increased risk of hyperhidrosis and female hirsutism due to polycystic ovarian disease, further increasing the impact of these practices on quality of life.1,2 Patients with HS are often unsure how to appropriately target physiological body odor and hair removal without worsening their HS. A 1982 case-control study concluded simply that deodorant, shaving, and chemical depilatories are not causative of HS,3 but little guidance beyond this is available for patients or their providers. Therapeutic solution We conducted a single-center survey of 87 individuals, in which participants living with axillary HS consistently identified spray deodorant and laser hair removal as the most beneficial underarm hygiene practices to avoid exacerbation of HS. Conversely, solid stick deodorant and shaving with a razor were associated with increased HS severity. Over half of those surveyed reported that all deodorants/antiperspirants worsened their HS; however, topical antimicrobials (chlorhexidine or benzoyl peroxide) were beneficial for the control of body odor related to perspiration. These group experiences can be used to guide providers who advise patients about HS. The study conclusions were drawn from a 22-question survey about HS hygiene practices. The authors attempted to call all adult patients with a diagnosis of HS seen at the Oregon Health & Science University (OHSU) dermatology clinic between October 2020 and March 2021 (n = 170). Eighty-seven patients answered their phone, of which 68 (78.2%) assented to complete the survey (Table 1). Fifty (74.6%) patients were women, reflecting the female predominance of HS.4 Table 1 - Characteristics of survey respondents Characteristic No. (%) Age, y 6 (9.0) 18–24 22 (32.8) 25–34 23 (34.3) 35–44 12 (17.9) 45–54 0 (0) 55–64 4 (6.0) 65+ Sex 17 (25.4) Male 50 (74.6) Female Race 48 (64.0) White 10 (13.3) Black/African American 5 (6.7) Hispanic/Latino 3 (4.0) Native American 2 (2.7) South Asian 3 (4.0) East Asian 1 (1.3) Middle Eastern 2 (2.7) Pacific Islander 1 (1.3) Other Mean Hurley Score 1.8 Mean BMI 37.2 Smoker Yes, current 15 (22.4) Yes, past 23 (34.3) No 29 (43.3) BMI, body mass index. Of the 59 participants who used deodorant/antiperspirant on their axillary HS, 31 (52.5%) reported that all products worsened their HS. Solid stick deodorant, used by 84.7% of participants, received the most ratings of “very harmful” to users’ HS (24.0%) (Fig. 1A). Spray, used by 49.1%, received the most “helpful” ratings (31.0%). Notably, the majority of participants (84.7%) had tried solid stick deodorant, whereas only 49.2% had tried spray—this likely represents a North American bias, since spray deodorants tend to be favored in the European market.5 Topical antimicrobials recommended for HS were perceived to have a positive impact on physiological body odor, with 29 of 45 (64.4%) and 18 of 27 (66.7%) of participants who used chlorhexidine solution and benzoyl peroxide wash respectively reporting these products were helpful for controlling body odor.Figure 1.: Survey respondents’ report of how types of deodorant/antiperspirant (A) or hair removal methods (B) affected their hidradenitis suppurativa severity.When questioned about hair removal, 45 of 50 (90%) female and 11 of 17 (64.7%) male participants had attempted some form of depilation. Eighteen of 22 (85.7%) participants who tried laser hair removal indicated it was helpful for their HS (Fig. 1B). A higher proportion of women (38.0%) than men (11.8%) had tried this method of hair removal, and it appeared to be helpful for both genders. In contrast, shaving was rated as harmful for HS in 36/48 (75%) participants. Conflicts of interest None. Funding None. Study approval N/A. Author contributions All authors participated in the study design, data acquisition, analysis and interpretation of the data, drafting and revising the manuscript, and final approval.

Background Fiber-poor diets are linked to a reduction in gut microbiota diversity and gut barrier integrity, which is thought to promote the susceptibility to chronic inflammatory disorders 1,2 . We have previously shown that dietary resistant starch (RS) improves lupus-like disease in a murine model of SLE 3 through the modulation of microbiota composition. If similar dysbiotic microbial community structures exist in subsets of SLE patients and if a RS intervention may be efficacious in those patients remains unclear. Objectives To test if the dietary RS content in SLE and SLE-related antiphospholipid syndrome (APS) affect gut microbial taxa associated with SLE in published cohorts to date. Methods We obtained stool and blood samples as well as diet history for up to 3 visits (0, 4 and 8 weeks) from 12 SLE (n=28) and 15 APS (n=44) patients as well as 20 controls (n=48) as previously published 4-6 . Microbiota composition was defined by 16S rRNA V4 region sequencing on the Illumina platform and correlated with dietary fiber content extracted from a diet questionnaire. We used the FDA reference list to determine dietary RS contents in patients` regular diets and defined RS quantities as being low if less than 2.5 g/day and as medium if 2.5 to 15 g/day. None of the patients achieved high RS greater than 15 g/day. Mann-Whitney or Kruskal-Wallis tests were performed to compare bacteria relative abundances among the different groups. Simple linear regression was performed to relate the bacterial abundance to RS content and other metadata. Results Medium intake of RS was associated with beneficial Bifidobacterium spp. in SLE patients (p=0.016) but not APS (p=0.509). Instead, APS patients who consumed medium quantities of RS in their diets had less gut bacterial taxa that are capable of producing cardiolipins (among them Collinsella ; p=0.009) and Ruminococcus gnavus (p=0.0142), a species previously associated with lupus nephritis 7 . A recent Japanese metagenome-wide study 8 associated Streptococcus spp. and related redox reaction genes with SLE, which may also affect oxidative processes in APS 9 . We therefore also explored Streptococcus levels in SLE and APS patients and found unexpectedly a significant reduction of streptococci in a subset of APS (p=0.004) but not SLE patients (p=0.451) in medium compared to low RS dietary content. Streptococcus abundance was correlated with both Collinsella (R 2 =0.3141; p=<0,0001) and Ruminococcus gnavus (R 2 =0.1687; p=<0,0056) in APS patients. Conclusion Medium compared to low RS quantities in the regular diets of SLE and APS patients were associated with unique alterations in gut microbial community structures. Bifidobacterium increased in SLE patients with diets containing medium RS whereas APS patients with medium RS carried less cardiolipin-synthesizing taxa and lupus-related pathobionts. In particular, Streptococcus species recently strongly associated with SLE and redox reactions in Japanese patients in a metagenome-wide study 8 , were significantly suppressed in APS patients on medium RS diets. This modulatory effect was not seen in SLE patients or control subjects consuming medium RS. Together, these findings support distinct dietary effects on autoimmune gut microbiomes depending on the disease state. They also suggest potential beneficial effects of increased RS content on gut microbiota in SLE and APS patients. Fully resolving gut microbial signatures and clinical characteristics in these patients may identify the ideal subset to benefit from an interventional pilot trial with RS. References [1] Thorburn et al., 2014, Immunity 19, 833-842 [2] Ruff et al, 2020, Nat Rev Microbiol 18, 521-538 [3] Zegarra-Ruiz et al., 2019, Cell Host Microbe 25, 113-127 [4] Greiling et al., 2018, Science Transl Med 10, 1–15 [5] Manfredo Vieira et al, 2018, Science 359, 1156-1161 [6] Ruff et al., 2019, Cell Host Microbe 26, 1–14 [7] Azzouz et al., 2019, Ann Rheum Dis 78, 947–956 [8] Tomofuji et al., 2021, Ann Rheum Dis 80, 1575–1583 [9] Giannakopoulos and Krilis, 2013, New Engl J Med 368, 1033-1044 Acknowledgements The work was supported by grants from the National Institutes of Health (NIH) (R01AI118855, T32AI07019), Arthritis National Research Foundation, Arthritis Foundation, Lupus Research Alliance, and Maren Foundation. Disclosure of Interests Márcia Pereira: None declared, Iryna Kulyk: None declared, Sylvio Redanz: None declared, William E Ruff: None declared, Teri M. Greiling: None declared, Carina Dehner: None declared, Odelya Pagovich: None declared, Daniel Zegarra Ruiz: None declared, Cassyanne Aguiar: None declared, Doruk Erkan: None declared, Martin Kriegel Speakers bureau: Novartis, BMS, GSK, MSD, Grant/research support from: AbbVie, Employee of: Roche.

Pityriasis rubra pilaris (PRP) is a rare, severe inflammatory skin disease associated with high morbidity and debilitating effects on QOL (Eastham et al., 2019; Ross et al., 2016). Classical features include follicular hyperkeratosis; erythematous plaques often progressing to erythroderma with islands of sparing; and waxy, palmoplantar keratoderma. The pathogenesis and etiology of PRP remain poorly understood. Small case series have shown dysregulation of the IL-23/IL-17 axis (Adnot-Desanlis et al., 2013; Feldmeyer et al., 2017; Nagai et al., 2020).

Journal Article Features that define clinical severity of ulcerative pyoderma gangrenosum: a Delphi consensus study of experts and patients on behalf of the US Medical Dermatology Society Get access Matthew A Pimentel, Matthew A Pimentel Conceptualization, Project administration, Writing - original draft, Writing - review & editing Department of Dermatology, Oregon Health and Science University, Portland, OR, USA Search for other works by this author on: Oxford Academic Google Scholar May M Li, May M Li Conceptualization, Writing - original draft, Writing - review & editing https://orcid.org/0000-0002-0508-9978 Search for other works by this author on: Oxford Academic Google Scholar Megan H Noe, Megan H Noe Conceptualization, Writing - review & editing https://orcid.org/0000-0001-8481-4711 Search for other works by this author on: Oxford Academic Google Scholar Emile Latour, Emile Latour Data curation, Formal analysis, Methodology, Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Lucia Seminario-Vidal, Lucia Seminario-Vidal Methodology, Writing - review & editing https://orcid.org/0000-0002-6004-2451 Search for other works by this author on: Oxford Academic Google Scholar Teri Greiling, Teri Greiling Writing - review & editing Department of Dermatology, Oregon Health and Science University, Portland, OR, USA https://orcid.org/0000-0002-0028-8986 Search for other works by this author on: Oxford Academic Google Scholar Kanade Shinkai, Kanade Shinkai Writing - original draft, Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Andrew Hamilton, Andrew Hamilton Methodology Search for other works by this author on: Oxford Academic Google Scholar Afsaneh Alavi, Afsaneh Alavi Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Jean L Bolognia, Jean L Bolognia Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar ... Show more Edward W Cowen, Edward W Cowen Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Arturo Dominguez, Arturo Dominguez Writing - review & editing https://orcid.org/0000-0001-8488-3194 Search for other works by this author on: Oxford Academic Google Scholar Anthony P Fernandez, Anthony P Fernandez Writing - review & editing https://orcid.org/0000-0003-4490-8427 Search for other works by this author on: Oxford Academic Google Scholar David Fivenson, David Fivenson Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar William W Huang, William W Huang Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Lauren M Madigan, Lauren M Madigan Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Melissa Mauskar, Melissa Mauskar Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Alexander D Means, Alexander D Means Writing - review & editing https://orcid.org/0000-0001-8921-9786 Search for other works by this author on: Oxford Academic Google Scholar Caroline A Nelson, Caroline A Nelson Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Aikaterini Patsatsi, Aikaterini Patsatsi Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Douglas Pugliese, Douglas Pugliese Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Nathan W Rojek, Nathan W Rojek Writing - review & editing https://orcid.org/0000-0001-8829-4178 Search for other works by this author on: Oxford Academic Google Scholar Misha Rosenbach, Misha Rosenbach Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Gideon P Smith, Gideon P Smith Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Robert A Swerlick, Robert A Swerlick Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Michael P Heffernan, Michael P Heffernan Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Arash Mostaghimi, Arash Mostaghimi Conceptualization, Methodology, Writing - original draft, Writing - review & editing Search for other works by this author on: Oxford Academic Google Scholar Alex G Ortega-Loayza Alex G Ortega-Loayza Conceptualization, Project administration, Writing - review & editing Department of Dermatology, Oregon Health and Science University, Portland, OR, USA Correspondence: A.G. Ortega-Loayza. Email: ortegalo@ohsu.edu https://orcid.org/0000-0001-5028-9269 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 188, Issue 4, April 2023, Pages 566–568, https://doi.org/10.1093/bjd/ljac137 Published: 19 December 2022 Article history Accepted: 17 December 2022 Published: 19 December 2022 Corrected and typeset: 07 February 2023

Pityriasis rubra pilaris (PRP) is a severe inflammatory skin disorder with major impacts on patients' quality of life. Current treatment plans focus on dermatologic symptoms, however PRP may also cause severe deficits in other areas, including mobility, thermoregulation, and mental well-being. This qualitative study aimed to identify the diversity of symptoms experienced by PRP patients in order to capture a broader disease experience. To this end, we conducted four, two-hour focus group sessions (n=45 English-speaking participants with PRP from six different countries) mediated by a representative from the PRP Alliance, followed by a post-session 23-question survey (completed by n=45 (100%) participants). In regards to most impactful physical symptoms, participants reported severe skin itch and pain, as well as palmoplantar involvement that caused difficulty with performing daily activities and mobility. Non-skin impacts included body temperature dysregulation, anhydrosis, skin buildup in the ears that affecting hearing, rhinorrhea, and joint pain. Difficulty sleeping and excessive daytime fatigue was one of the most often cited systemic impacts. Furthermore, most participants agreed that the mental aspect of PRP was equal to or worse than the physical impact, citing depression, loss of self-worth, feelings of isolation, and passive suicidal ideation. Participants felt that their providers did not adequately address the mental health impacts of PRP. In conclusion, this study found that PRP has debilitating health effects from a broad variety of symptoms and quality of life impacts. These included skin and non-skin symptoms, as well as systemic symptoms and mental health. PRP patients are best treated by a multidisciplinary team that includes mental health management.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder associated with significant patient morbidity. The pathophysiology of PRP has been under ongoing investigation with studies implicating alterations in Th17 signaling, phospholipase processing, and novel germline CARD14 gene variations. In this study, 11 patients with moderate-to-severe PRP (as defined by a Psoriasis Area and Severity Index [PASI] ≥ 10) had lesional skin biopsies taken prior to and following 24 weeks of Il-17A inhibitor therapy for RNA sequencing analysis. Differential expression analysis was conducted using the R package "DESeq2" comparing age- and sex-matched controls to pre- and post-treatment patients, with delimitations by depth (epidermis vs dermis) and response to treatment (≥50% improvement in PASI [responder] vs <50% [non-responder]). Results were filtered to an adjusted false discovery rate of < 0.05 and absolute log2 fold change (log2FC) > 2. Prior to treatment, 2012 dermal and 4532 epidermal genes were found to be differentially expressed in PRP patients, with mean ± SD absolute log2FC of 3.00 ± 1.26 and 3.23 ± 1.41, respectively. Following treatment, mean absolute log2FC improved to 1.73 ± 1.24 and 1.69 ± 1.43 in dermis and epidermis, respectively (p<0.001 by paired t-test). When stratifying pre-treatment IL-17A expression by therapeutic response, both pre-treatment dermis (log2FC 6.02) and epidermis (log2FC 7.60) had elevated expression of IL-17A, whereas neither epidermis nor dermis of non-responders were significantly different. Pretreatment epidermal IL-17C and CCL20, two cytokines in the IL-17 pathway previously implicated during proteomic analysis of PRP, were more expressed in responders (log2FC 10.80 and 7.68, respectively) than non-responders (log2FC 9.03 and 6.07, respectively). Together, these findings demonstrate that IL-17A inhibition improved the cutaneous transcriptomic profile of patients with PRP and identified potential screening targets for treatment success.