Alopecia Areata Past Paper PDF - J Am Acad Dermatol 2023

138 Research Letters J AM ACAD DERMATOL JULY 2023...

138 Research Letters J AM ACAD DERMATOL JULY 2023 Key words: alopecia areata; janus kinase; upada- citinib; safety; efficacy. Reprints not available from the authors. Correspondence to: John W. Frew, MBBS, MMed, MS, PhD, Laboratory of Translational Cutaneous Medicine, Department of Dermatology, Liverpool Hospital, Suite 7, Level 1, 45-47 Goulburn St, Liverpool, NSW 2170, Australia E-mail: [email protected] Conflicts of interest J.W.F. has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, ChemoCentryx, AbbVie, Azora, Novartis, and UCB; participated in trials for Pfizer, UCB, Boehringer- Ingelheim, Eli Lilly, CSL, and Azora; and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB, and La Roche Posay. REFERENCES 1. Strazzulla LC, Wang EHC, Avila L, et al. Alopecia Areata: an Appraisal of new treatment approaches and overview of current therapies. J Am Acad Dermatol. 2018;78:15-24. 2. Rajabi F, Drake LA, Senna MM, Rezaei N. Alopecia Areata: a review of disease pathogenesis. Br J Dermatol. 2018;179(5): Fig 2. The improvement in quality of life scores in 1033-1048. alopecia areata as measured by the DLQI at baseline, 3. Phan K, Sebaratnam DF. JAK Inhibitors for alopecia areata: a 12 weeks, and 24 weeks of therapy. Significant differences systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019;33(5):850-856. between groups were observed when evaluated via one 4. King B, Ohyama M, Kwon O, et al. Two phase 3 trials of way analysis of variance (P \.0001). DLQI, Dermatology baricitinib for alopecia areata. N Engl J Med. 2022;386(18): Life Quality Index. 1687-1699. 5. Gilhar A, Keren A, Paus R. JAK inhibitors and alopecia areata. The Lancet. 2019;393(10169):318-319. regrowth of hair and significant improvement in quality of life. The study’s limitations include https://doi.org/10.1016/j.jaad.2022.12.056 the small size of the cohort, lack of a placebo- controlled arm, short duration of the study, and Systematic review of the clinical the relatively young age of the cohort. Further characteristics and natural history evaluation in larger cohorts is necessary to compare of solar urticaria the safety and efficacy of upadacitinib to other JAK inhibitors. To the Editor: Solar urticaria (SU) is a rare, idiopathic photodermatosis characterized by cutaneous mast Akshay Flora, MD, MMed,a,b,c Emily Kozera, BSc, cell degranulation following exposure to specific MD, MPH, MBeth,a,b and John W. Frew, MBBS, wavelengths of solar electromagnetic radiation. Its MMed, MS, PhDa,b,c clinical manifestations comprise recurrent wheals and/or angioedema and are typically treated From the Department of Dermatology, Liverpool with photoprotection and antihistamines.1 To date, Hospital, Sydney, Australiaa; Laboratory of the presentation of SU has been described Translational Cutaneous Medicine, Ingham predominantly in single-center observational Institute, Sydney, Australiab; and School of studies, which limits global understanding of its Clinical Medicine, University of New South clinical features and natural history.2 Therefore, this Wales, Sydney, Australia.c systematic review was undertaken to summarize the Funding: None. clinical and photobiologic features of SU, as well as its natural history. IRB approval status: This study was approved by the A systematic search of literature databases human research ethics committee of South West (MEDLINE, Embase, CENTRAL, and Web of Science) Sydney Area Health Service. was performed on November 7, 2021, with support J AM ACAD DERMATOL Research Letters 139 VOLUME 89, NUMBER 1 IU/mL) in 39.3%. Consistently reported treatments included H1-antihistamines (74.0%), phototherapy (35.7%), and omalizumab (2.1%). There were limited data on SU natural history and available study estimates could not be directly compared. However, analysis of 371 cases demonstrated that 35.3% experienced complete disease resolution 5 years following disease onset. Photoprovocation was performed in 97.2% and most centers used combinations of monochromator/ broadband electromagnetic sources (50.1%) or broad- band sources alone (43.6%). There was little standard- ization of photoprovocation protocols. Symptoms were not elicited in 14.0%. Amongst those with positive photoprovocation, the most common trig- gering wavebands were visible light only (29.3%) or combinations of UVA and visible light (24.9%) (Fig 1). Within the limits of the data available, this system- Fig 1. Triggering wavebands in 583 solar urticaria cases; atic review indicates that SU is sporadic, occurs UVA (315-400 nm wavelengths), UVB (280-315 nm worldwide, and can affect all skin phototypes. wavelengths), and visible light (400-700 nm wavelengths). Symptoms predominantly comprise pruritus and er- UVA, Ultraviolet A; UVB, ultraviolet B; VL, visible light. ythema or wheals, but these cannot be provoked in many using available phototesting protocols. This from a medical librarian (CRD42020181948). Article may be attributable to observed variations in photo- screening and data extraction were performed in testing practices, but also implies that more compli- duplicate, in accordance with recognized guidelines.3 cated interactions can occur between skin and Full-text observational studies published in English radiant sunlight in SU. This and other features of SU that described SU clinical features (including could be better understood via prospective data photoprovocation results) in $3 patients were collection in an international registry and standard- included. Qualitative and quantitative data syntheses ization of international phototesting practices. were performed. Twenty-three observational case series were Sheila M. McSweeney, MB, BSc, MSc, MRCP,a Ewa included (Supplementary Table I, available via Kloczko, MBBS, iBSc,b Mehak Chadha, MBBS, Mendeley at https://data.mendeley.com/datasets/ BSc(Hons),c Robert Sarkany, MD,a Hiva Fassihi, 6wyjs7d6pz/1), comprising 854 SU cases MD, PhD,a Christos Tziotzios, MA, MPhil, MB (Supplementary Table II, available via Mendeley at BChir (Cantab), PhD,a and John A. McGrath, https://data.mendeley.com/datasets/6wyjs7d6pz/1). MDa Cases were derived from 12 countries, of which 6 From the St. John’s Institute of Dermatology, Guy’s were European, although reported cases incorpo- Hospital, London, UKa; Department of Derma- rated all skin phototypes. There were no reports of tology, University College Hospital, London, UKb; familial disease. The mean age of onset was 30.6 years and St. Peter’s Hospital, Chertsey, UK.c (standard deviation 19.8) and there was a female preponderance (63.7%). Symptom onset was rapid Funding sources: Dr McSweeny is currently sup- and 94.8% developed symptoms \15 minutes after ported by a Medical Research Council Clinical sun exposure. Most patients experienced pruritus or Research Training Fellowship (MR/V006746/1). burning (87.4%), as well as erythema or wheals IRB approval status: Not applicable. (81.4%), and presentations such as erythema alone (10.8%) or angioedema (2.4%) were infrequent. Previous presentation: British Association of Der- Symptom resolution varied more substantially, matologists’ Annual Meeting 2021 (interim resolving in #1 hour in 64.1% and persisting up to results). 24 hours in 33.5%. Systemic symptoms were Key words: angioedema; itch; mast cell; photobi- uncommon (4.4%), as was anaphylaxis (0.9%), and ology; urticaria; wheals. there were no deaths. SU was associated with atopic disorders in 31.6% and amongst those with available Correspondence and reprint requests to: Sheila M. data (n ¼ 183), serum IgE levels were raised ([100 McSweeney, MB, BSc, MSc, MRCP, St. John’s 140 Research Letters J AM ACAD DERMATOL JULY 2023 Institute of Dermatology, Guy’s Hospital, 9th Floor, the study team from pathology reports and catego- Tower Wing, London, SE1 9RT, UK rized into brisk, non-brisk, or absent. Multivariable logistic regression was used to examine associations E-mail: [email protected] between TIL presence or absence and cirAE/irAE Conflicts of interest characteristics. Additional methodological details are McSweeny is a sub-investigator and Tziotzios is a discussed in the Supplemental File 1, available via principal and (national) chief investigator on the Pfizer- Mendeley at https://data.mendeley.com/datasets/ funded ALLEGRO clinical trial in alopecia areata. Dr bp7f6gn8ks/1. Tziotzios provides consulting services to Pfizer and has received speaker fees from Leo Pharma. Drs Kloczko, Among patients with melanoma with cirAEs Chadha, Sarkany, Fassihi, and McGrath have no conflicts of (n ¼ 123, median age: 66, 33.3% female), 4 (3.3%) interest to declare. had brisk TIL, 98 (79.7%) had non-brisk TIL, and 21 (17.1%) had absent TIL. In the non-cirAE group (n ¼ 87, median age: 63, 26.4% female), 2 (2.3%) REFERENCES had brisk TIL, 65 (74.7%) had non-brisk TIL, and 20 1. Botto NC, Warshaw EM. Solar urticaria. J Am Acad Dermatol. 2008;59(6):909-920. https://doi.org/10.1016/j.jaad.2008.08.020 (23.0%) had absent TIL (Table I). Multivariable anal- 2. Du-Thanh A, Debu A, Lalheve P, Guillot B, Dereure O, Peyron JL. ysis demonstrated no significant associations between Solar urticaria: a time-extended retrospective series of 61 TIL status and cirAE/irAE development or cirAE patients and review of literature. Eur J Dermatol. 2013;23(2): severity. When examining cirAE subtypes, TIL pres- 202-207. https://doi.org/10.1684/ejd.2013.1933 ence at time of primary biopsy showed a trend toward 3. Higgins J, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions Version 6.2. Cochrane; decreased later incidence of vitiligo (odds ratio: 0.21, 2021. 95% CI: 0.04-1.22, P ¼.081), though the association did not reach statistical significance (Table II). https://doi.org/10.1016/j.jaad.2023.01.039 In this study, we found no significant associations between TIL status at time of primary biopsy and cirAE development. The presence of TIL is thought Tumor-infiltrating lymphocytes as a to be a positive prognostic factor in patients with predictive biomarker of cutaneous melanoma, though results may depend on the pop- immune-related adverse events after ulation of individual lymphocyte subsets comprising immune checkpoint blockade in tumor infiltrates.2,5 Our negative results may thus be patients with advanced melanoma a consequence of having more T cells with limited To the Editor: Predictive clinical biomarkers that can be prognostic impact in the setting of immune- used to monitor immunotherapeutic responses after checkpoint blockade, such as FOXP31 T-regs.5 immune checkpoint inhibitor (ICI) therapy are These regulatory lymphocyte subsets may have becoming increasingly necessary for effectively plan- also contributed to less immune activation and ning cancer treatment.1 Tumor-infiltrating lympho- autoreactivity after ICI therapy, potentially explain- cytes (TIL) have been identified as a favorable ing the trend towards a lower incidence of vitiligo. prognostic indicator in melanoma,2-5 though little is Although difficult to quantify, the fact that our cohort known about TIL as a potential biomarker for cuta- of patients had advanced melanoma necessitating neous or non-cutaneous immune-related adverse ICI therapy may reflect the low incidence of brisk TIL event (cirAE/irAE) development. We thus sought to in the overall cohort, and by extension, decreased examine the association between TIL status on primary anti-tumor T-cell activity at baseline. melanoma biopsy and cirAE or irAE development Study limitations include the small sample size, among a cohort of melanoma patients receiving ICIs. notably of patients with brisk TIL; single-center Using billing codes, we screened patients with retrospective design; and inability to examine spe- melanoma initiating ICI therapy at our institution cific lymphocyte subtypes, limiting our ability to between January 1, 2016 and June 29, 2021 who examine more granular associations related to tumor developed possible cirAEs and confirmed cirAE microenvironment. Nonetheless, our findings repre- status through manual chart review. Demographics, sent an important exploratory analysis examining clinical history, TIL status on primary biopsy, and potential associations between TIL and cirAE risk. cirAE/irAE history was abstracted. The same vari- Larger studies are needed to better elucidate the ables were collected for melanoma patients predictive role of TIL and other prognostic tumor- receiving ICIs between January 1, 2016 and June related biomarkers and the development of ICI- 29, 2021 without cirAEs. TIL status was abstracted by mediated immunotoxicities.