- Norval M, Halliday GM. The consequences of UV-induced immunosuppression for human health. Photochem Photobiol 2011;10: 586–602. - Patra V, Byrne SN, Wolf P. The skin microbiome: is it affected by UV-induced immune suppression? Front Microbiol 2016;10:3225. Patra V, Trajanoski S, Joshi A, Lenief V, Goyet C, Cornu A, et al. Urocanasepositive skin-resident bacteria metabolize *cis*-urocanic acid and in turn reduce the immunosuppressive properties of UVR. J Investig Dermatol 2025;145:2839–53.e6. See related article on pg 2891 - Schwarz T. Mechanisms of UV-induced immunosuppression. Keio J Med 2005;54:165–71. - Wang Z, Choi JE, Wu CC, Di Nardo A. Skin commensal bacteria Staphylococcus epidermidis promote survival of melanocytes bearing UVB-induced DNA damage, while bacteria Propionibacterium acnes inhibit survival of melanocytes by increasing apoptosis. Photodermatol Photoimmunol Photomed 2018;34:405–14. - Zhang Z, Yan J, Geng Y. Bacterial degradation of histidine and urocanic acid. J Bacteriol 2003;185:2161–70. # The Visceral Relationship of Psoriasis and Obesity ![](https://assets.reachrx.ai/images/10.1016%E2%98%8Dj.jid.2025.04.013/_page_0_Picture_9.jpeg) Joel M. Gelfand^1,2 Journal of Investigative Dermatology (2025) 145, 2657–2658; doi:10.1016/j.jid.2025.04.013 ![](https://assets.reachrx.ai/images/10.1016%E2%98%8Dj.jid.2025.04.013/_page_0_Picture_11.jpeg) soriasis, which is characterized by chronic T helper (Th)1/Th17 inflammation in the skin, is intricately related to cardiometabolic disease. Previously thought to be "just a skin disease," advances in genetics, immunology, and epidemiology have redefined psoriasis as a systemic disease in which patients are especially susceptible to obesity, metabolic syn- drome, diabetes, nonalcoholic steatohepatitis, chronic kidney disease, and major cardiovascular (CV) events, resulting in 5 years of life lost (Gelfand et al, 2025). Although these associations persist when controlling for body mass index (BMI), obesity has emerged as a major driver of psoriasis morbidity. Obesity is a risk factor for developing psoriasis on the basis of epidemiological and Mendelian randomization (genetic) studies. In the iHOPE (incident health outcomes and psoriasis events) study, we demonstrated that increasing body surface area affected by psoriasis (eg, severity of skin disease) is directly related to increasing BMI and that obesity is a risk factor for developing psoriatic arthritis independent of its effects on psoriasis severity (Langan et al, 2012; Ogdie et al, 2022). Obesity is also associated with reduced response to psoriasis treatments, including biologics, as well as loss of response to biologics (Vata et al, 2023). The scale of the prevalence of psoriasis and obesity is massive, with the average BMI of patients with psoriasis seen by dermatologists in the United States for a pragmatic (eg, real-world) study being 30 kg/m² (Gelfand et al, 2024). In this context, Ramessur et al (2025) demonstrated in a cross-sectional analysis of UK Biobank data that (i) central (visceral) adiposity measured by traditional measures (eg, waist-to-hip ratio) or more advanced imaging measures (eg, magnetic resonance imaging) is associated with psoriasis and that this effect may be stronger in women than in men and (ii) that waist-to-hip ratio had a stronger association with HLA-C\*06:02—negative psoriasis; however, this difference in association by HLA-C\*06:02 status was not observed when waist-to-hip ratio was proxied by its genetic predictors. These findings add to the existing literature that the source of adiposity associated with psoriasis is visceral in nature, which has important implications for patients. For example, visceral adiposity (eg, fat surrounding internal organs) is associated with increasing severity of psoriasis and is metabolically active, promoting insulin resistance, dyslipidemia, systemic inflammation, and atherosclerosis (Sajja et al, 2020). Moreover, at the population level, obesity is a major driver of poor cardiometabolic health among people with psoriasis (Wang et al, 2023). Despite the strong relationship between psoriasis with obesity, most of our treatments, with the exception of perhaps apremilast, have no benefit on adiposity, and TNF and Jak inhibitors may promote weight gain (Xiong et al, 2025). With the emergence of obesity as a major driver of psoriasis morbidity, attention has recently turned to incretin therapy for psoriatic disease. Incretins are gut-derived hormones, principally glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, that regulate glucose, digestion, and appetite. Incretin-based treatments augment glucose-dependent insulin release and reduce glucagon secretion and gastric emptying, resulting in improvement in insulin resistance and a reduction in food intake. They are approved for treatment of diabetes, obesity, and obesityassociated obstructive sleep apnea and are demonstrated to reduce CV events and kidney disease while improving nonalcoholic steatohepatitis, all of which are psoriasis-associated conditions. Indeed, GLP1RA has been shown to modulate key inflammatory pathways (IL-17 and TNF $\alpha$ ) that drive psoriasis activity, GLP-1 receptors are over expressed in psoriasis plaques, and psoriasis is reported to improve in patients undergoing GLP1RA therapy (Bendotti et al, 2022). ^<sup>1Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; and ²Center for Clinical Sciences in Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Correspondence: Joel M. Gelfand, Department of Dermatology, University of Pennsylvania, 3400 Civic Center Boulevard, 730 South Tower, Philadelphia, Pennsylvania 19104, USA. E-mail: joel.gelfand@pennmedicine.upenn.edu © 2025 The Author. Published by Elsevier, Inc. on behalf of the Society for ^{© 2023} The Author. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. ### COMMENTARY ### **Clinical Implications** Obesity is a major driver of psoriasis morbidity - It is a risk factor for developing psoriasis and psoriatic arthritis. - It is associated with more severe skin involvement with psoriasis. - It is associated with a reduced response to psoriasis treatment and reduced persistence on biologics. - Psoriasis patients have increased visceral adiposity (fat surrounding internal organs) which is metabolically active, promoting insulin resistance, dyslipidemia, systemic inflammation, and atherosclerosis. - Obesity needs to be addressed in the context of treating patients with psoriatic disease. The strong relationship between psoriasis and obesity and the emerging promise of GLP1RA for reducing psoriasis morbidity is a call to action for large scale clinical trials of GLP1RA monotherapy for treatment of psoriasis. There is a need to determine the impact of GLP1RA on the immunology of psoriasis and skin and joint manifestations of psoriatic disease and their cardiometabolic effects in a psoriasis population. Our current paradigm of just focusing on the skin and joint manifestations when treating psoriasis is outdated in the context of our evolving understanding of the tight relationship of psoriasis, obesity, and cardiometabolic disease. The next generation of psoriasis trials should focus on the role treating cardiometabolic disease and obesity has on disease modification of psoriasis. #### **CONFLICT OF INTEREST** JMG served as a consultant for Abbvie, Artax (DSMB), BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies), GSK, Inmagene (DSMB), Lilly, Leo, Moonlake (DSMB), Janssen Biologics, Novartis, UCB (DSMB), Neuroderm (DSMB), and Oruka, See related article on pg 2896 receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Amgen, BMS, and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by pharmaceutical sponsors. JMG is a Deputy Editor for the *Journal of Investigative Dermatology*, receiving honoraria from the Society for Investigative Dermatology; is Chief Medical Editor for Healio Dermatology (receiving honoraria); and is a member of the Board of Directors for the International Psoriasis Council and the Medical Dermatology Society, receiving no honoraria. #### REFERENCES - Bendotti G, Montefusco L, Lunati ME, Usuelli V, Pastore I, Lazzaroni E, et al. The anti-inflammatory and immunological properties of GLP-1 Receptor agonists. Pharmacol Res 2022;182:106320. - Gelfand JM, Armstrong AW, Lim HW, Feldman SR, Johnson SM, Claiborne WCC, et al. Home- vs office-based narrowband UV-B phototherapy for patients with psoriasis: the LITE randomized clinical trial [published correction appears in JAMA Dermatol 2025;161:342]. JAMA Dermatol 2024;160:1320–8. - Gelfand JM, Song WB, Langan SM, Garshick MS. Cardiodermatology: the heart of the connection between the skin and cardiovascular disease. Nat Rev Cardiol 2025;22:354–71. - Langan SM, Seminara NM, Shin DB, Troxel AB, Kimmel SE, Mehta NN, et al. Prevalence of metabolic syndrome in patients with psoriasis: a populationbased study in the United Kingdom. J Invest Dermatol 2012;132:556–62. - Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxford) 2022;61:1877–84. - Ramessur R, Saklatvala J, Løset M, Thomas LF, Budu-Aggrey A, Mahil SK, et al. Investigating the genetic basis of the influence of adiposity on psoriasis: a cross-sectional study in a large UK population-based biobank. J Invest Dermatol 2025;145:2891–5.e12. - Sajja A, Abdelrahman KM, Reddy AS, Dey AK, Uceda DE, Lateef SS, et al. Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time. JCI Insight 2020;5:e142534. - Vata D, Tarcau BM, Popescu IA, Halip IA, Patrascu AI, Gheuca Solovastru DF, et al. Update on obesity in psoriasis patients. Life (Basel) 2023;13:1947. - Wang S, Shin DB, Bhutani T, Garshick MS, Gelfand JM. Cardiovascular health in people with psoriasis: a population-based study in the United States. J Invest Dermatol 2023;143:2075–8. - Xiong G, Yu E, Heung M, Yang J, Lowe M, Abu-Hilal M. Weight gain secondary to the use of oral Janus kinase inhibitors: a systematic review and meta-analysis. JAAD Int 2025;19:1–9. ## Toward Pharmacogenomic Approaches to Hidradenitis Suppurativa ![](https://assets.reachrx.ai/images/10.1016%E2%98%8Dj.jid.2025.04.013/_page_1_Picture_25.jpeg) Richie Jeremian¹ and Vincent Piguet^2,3 Journal of Investigative Dermatology (2025) 145, 2658-2661; doi:10.1016/j.jid.2025.05.001 $^\circledast$ 2025 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. ![](https://assets.reachrx.ai/images/10.1016%E2%98%8Dj.jid.2025.04.013/_page_1_Picture_31.jpeg) ![](https://assets.reachrx.ai/images/10.1016%E2%98%8Dj.jid.2025.04.013/_page_1_Picture_32.jpeg) ^<sup>1Division of Dermatology, Department of Medicine, McGill University, Montréal, Canada; ²Division of Dermatology, Department of Medicine, Women's College Hospital, Toronto, Canada; and ³Division of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada Correspondence: Vincent Piguet, Division of Dermatology, Department of Medicine, Women's College Hospital, 76 Grenville Street, Office 6425, Toronto M5S 1B2, Canada. E-mail: vincent.piguet@utoronto.ca