e636 Letters to the Editor Describing the burden of the self-reporting COVID-19, the association between mental health and worsening psoriasis was assessed using a fully adjusted logis- COVID-19 pandemic in people tic regression model including covariates selected a priori as with psoriasis: findings from a potentially influential on psoriasis severity and anxiety/depres- sion. Participants scoring ≥3 in GAD-2 or PHQ-2 defined a pos- global cross-sectional study itive mental health screen.5 4043 people with psoriasis from 86 countries were included Editor, (Table 1). 1728 (42.7%) reported worsening psoriasis in the Indirect excess morbidity in the COVID-19 pandemic may arise pandemic. A total of 3575 (88.4%) returned information on from public health risk-mitigation efforts such as stay-at-home their mental health, with a greater proportion of those reporting orders and re-purposing of healthcare services.1 Increased men- worsening psoriasis having a positive mental health screen (814/ tal health disorders and shortfalls in the care of long-term condi- 1621, 50.2%) compared to those without worsening psoriasis tions are described.2,3 We used global self-reported cross- (562/1954, 28.8%). A greater proportion of females reported sectional data to characterise the factors associated with worsen- worsening psoriasis (1322/2684, 49.3%) compared with males ing psoriasis in the pandemic, focussing on the impact of anxiety (406/1354, 30.0%). and depression. A fully adjusted regression model for worsening psoriasis esti- Data from a cross-sectional survey (PsoProtectMe4) were mated an odds ratio (OR) 2.01 (95% CI, 1.72–2.34) for those extracted on 15th January 2021. After excluding participants with a positive screen for anxiety or depression compared to Table 1 Patient demographics and clinical characteristics stratified by disease state Total Missing data Non-worsening disease Worsening disease P-value N = 4,043 N = 2,315 N = 1,728 Shielded 2,224 (55.1%) 9 (0.2%) 1,240 (53.8%) 984 (56.9%) 0.045 Advised to shield 742 (33.6%) 1,833 (45.3%) 465 (37.5%) 277 (28.6%) <0.001 Female gender 2,684 (66.5%) 5 (0.1%) 1,362 (59.0%) 1,322 (76.5%) <0.001 Age, mean (SD) 47.2 (15.1) 31 (0.8%) 49.5 (15.3) 44.2 (14.3) <0.001 White European ethnicity 3,016 (74.6%) 0 1,707 (73.7%) 1,309 (75.8%) 0.15 BMI, mean (SD) 27.6 (6.0) 369 (9.1%) 27.4 (5.8) 28.0 (6.3) 0.003 Alcohol >14 units a week 495 (13.8%) 455 (11.3%) 295 (15.0%) 200 (12.3%) 0.018 Current smoker 559 (15.8%) 498 (12.3%) 291 (15.0%) 268 (16.7%) 0.18 Full time employed 1,929 (47.7%) 0 1,072 (46.3%) 857 (49.6%) 0.038 Household number, mean (SD) 2.8 (1.8) 26 (0.6%) 2.8 (1.7) 2.9 (1.9) 0.003 Key worker 1,131 (28.1%) 22 (0.5%) 595 (25.9%) 536 (31.1%) <0.001 Psoriasis severity prior to COVID-19 pandemic 284 (7%) <0.001 Clear 451 (12.0%) 299 (14.6%) 152 (8.9%) Nearly clear 767 (20.4%) 463 (22.7%) 304 (17.7%) Mild 989 (26.3%) 477 (23.3%) 512 (29.9%) Moderate 892 (23.7%) 442 (21.6%) 450 (26.2%) Moderate-severe 480 (12.8%) 273 (13.4%) 207 (12.1%) Severe 180 (4.8%) 90 (4.4%) 90 (5.2%) Systemic therapy 522 (12.9%) <0.001 No systemic therapy 1,980 (56.2%) 938 (49.4%) 1,042 (64.2%) Standard systemic therapy 560 (15.9%) 309 (16.3%) 251 (15.5%) Targeted therapy 981 (27.9%) 652 (34.3%) 329 (20.3%) Non adherent to systemic therapy 284 (18.4%) 2507 (62%) 114 (11.9%) 170 (29.6%) <0.001 1 or more comorbidity 1,606 (39.7%) 0 908 (39.2%) 698 (40.4%) 0.45 Anxiety 1,069 (30.1%) 489 (12.1%) 408 (21.0%) 661 (41.0%) <0.001 Depression 977 (27.5%) 494 (12.2%) 392 (20.1%) 585 (36.5%) <0.001 Anxiety or depression 1,376 (38.5%) 468 (11.6%) 562 (28.8%) 814 (50.2%) <0.001 Targeted therapy was defined as anyone taking TNF inhibitors (adalimumab, certolizumab, etanercept, infliximab), IL-17 inhibitors (ixekizumab, secukinumab, brodalumab), IL-23 inhibitors (guselkumab, risankizumab, ustekinumab; apremilast). Standard systemic therapy was defined as anyone taking acitretin, ciclosporin, or methotrexate and not taking a targeted therapy. BMI, body mass index; SD, standard deviation. JEADV 2021, 35, e619–e698 © 2021 European Academy of Dermatology and Venereology Letters to the Editor e637 Figure 1 Fully adjusted model for associations with worsening psoriasis. Odds ratios for associations with worsening psoriasis. Anxiety/ depression is defined as those who screened positive for either anxiety or depression. Obesity is defined as a BMI >30. those without a positive screen (Fig. 1). Associations were also Our findings parallel data from the general population indi- observed for female gender (OR, 1.82, 95% CI, 1.56–2.13); obe- cating an increased mental health burden during the pandemic, sity (OR, 1.22, 95% CI, 1.09–1.36) and shielding (OR, 1.18, 95% particularly in women.8 People with psoriasis – especially those CI, 1.03–1.35). with severe psoriasis, and women – have a high prevalence of There were inverse associations with systemic therapy use [s- anxiety and depression and may thus be particularly vulnerable tandard systemic OR 0.69 [95% CI, 0.56–0.86] and targeted to the adverse impact of the pandemic on mental health.9 Whilst therapy OR 0.49 (95% CI, 0.38-0.64)]. Of 1541 (38.1%) partici- men are known to be at greater risk of severe outcomes from pants receiving standard systemic or targeted therapies for psori- COVID-19, our data suggest that women may be more suscepti- asis, 284 (18.4%) reported non-adherence during the pandemic ble to indirect excess morbidity – poor mental health and wors- (Table 1). The commonest reason was concern regarding com- ening skin disease – than men. plications related to COVID-19 (n = 217). Non-adherence was The generalisability of results is limited given the self-selecting associated with worsening psoriasis (OR, 2.90, 95% CI, 2.31– bias of our study population towards UK white women. Individ- 3.63). A positive mental health screen was more common in uals non-adherent to treatment, with low computer literacy or those reporting non-adherence compared to those who were less anxiety, may be disinclined to participate, which may intro- adherent (42.8% vs. 32.4%). duce ascertainment bias. These data indicate a burden due to the COVID-19 pandemic Our data underscore the importance of holistic models of care in people with psoriasis; worsening psoriasis is common and is and indicate a need to provide access to psychological support. associated with poor mental health. We find that in the subset on In those with worsening psoriasis, possible non-adherence systemic therapy, non-adherence is associated with worsening dis- should be explored. Evidence-based communication around ease and is driven by concerns about immunosuppressant-related medication-related COVID-19 risks and behavioural approaches risks of COVID-19. This is an important observation since current for supporting adherence may help address fears, anxieties and guidelines (informed by reassuring data on drug-related risks of confusion.10 Attention given now to address this may mitigate a severe COVID-196) recommend continuing immunosuppression long-lasting detrimental impact of the pandemic on health out- in people without COVID-19 to maintain disease control.7 comes in people with psoriasis. JEADV 2021, 35, e619–e698 © 2021 European Academy of Dermatology and Venereology e638 Letters to the Editor Acknowledgements Ingelheim, Roche and Merck. Dr. Mason reports personal fees We are grateful to all the patients who have contributed to from LEO Pharma and Novartis, outside the submitted work. PsoProtectMe, the professional and patient organisations who Ms. Moorhead reports personal fees from Abbvie, personal fees supported or promoted PsoProtectMe and for the input of Prof from Celgene, personal fees from Janssen, personal fees from Lars Iversen, Prof Nick Reynolds, Prof Joel Gelfand, Ms Chris- LEO Pharma, personal fees from Novartis, personal fees from tine Janus and Ms Melissa Sweeney through their vital contribu- UCB, outside the submitted work. Dr. Puig reports grants and tions. We would also like to acknowledge the following personal fees from AbbVie, grants and personal fees from Almi- individuals for help with translating the PsoProtectMe survey; rall, grants and personal fees from Amgen, grants and personal Dr Haleema Alfailakawi, Dr Wisam Alwan, Dr Rosa Andres Ejar- fees from Boehringer Ingelheim, personal fees from Bristol que, Dr Ines Barbosa, Ms Carmen Bugarin Diz, Ms Katarzyna Myers Squibb, personal fees from Fresenius-Kabi, grants and Grys, Dr Mahira Hamdy El Sayed, Mr Tran Hong Truong, Mr personal fees from Janssen, grants and personal fees from Lilly, Masanori Okuse, Ms Dagmara Samselska, Ms Isabella Tosi, Ms personal fees from Mylan, grants and personal fees from Novar- Ya-Hsin Wang, and the Engine Group UK for their generous tis, personal fees from Pfizer, personal fees from Sandoz, per- creative input and website expertise. sonal fees from Sanofi, personal fees from Samsung-Bioepis, grants and personal fees from UCB, outside the submitted work. Conflict of interest Dr. Mahil reports departmental income from Abbvie, Celgene, Nothing to disclose: Dr Yates, Dr Dand, Prof. Langan, Dr. Nor- Eli Lilly, Janssen-Cilag, Novartis, Sanofi, UCB, outside the sub- ton, Dr. Tsakok, Dr. Yiu, Dr De La Cruz, Dr. Contreras, Ms. mitted work. Dr. Di Meglio reports grants and personal fees Vesty, Ms. Vincent, Mr. Bola Coker, Ms. Meynell, Dr. Lambert, from UCB, personal fees from Novartis, personal fees from Prof. Brown, Prof. Naldi. Prof. Barker reports grants and per- Janssen, outside the submitted work. Prof. Warren reports sonal fees from Abbvie, grants and personal fees from Novartis, grants and personal fees from Abbvie, grants and personal fees grants and personal fees from Lilly, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants from J&J, from null, during the conduct of the study. Prof. and personal fees from Novartis, personal fees from Sanofi, Griffiths reports grants and personal fees from AbbVie, grants grants and personal fees from UCB|, grants and personal fees from Amgen, grants from BMS, grants and personal fees from from Almirall, grants and personal fees from Amgen, grants and Janssen, grants from LEO, grants and personal fees from Novar- personal fees from Janssen, grants and personal fees from Leo, tis, grants from Pfizer, grants from Almirall, grants and personal grants and personal fees from Pfizer, personal fees from Arena, fees from Lilly, grants and personal fees from UCB Pharma, personal fees from Avillion, personal fees from Bristol Myers outside the submitted work. Prof. Jullien reports personal fees Squibb, personal fees from Boehringer Ingelheim, outside the and non-financial support from Abbvie, personal fees and non- submitted work. Prof. Smith reports grants from Abbvie, Sanofi, financial support from Novartis, personal fees and non-financial Novartis, and Pfizer and through consortia with multiple aca- support from Janssen-Cilag, personal fees and non-financial demic partners (psort.org.uk, BIOMAP-IMI.eu), outside the support from Lilly, personal fees and non-financial support submitted work. Dr. Torres reports grants and personal fees from Leo-Pharma, personal fees and non-financial support from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biogen, from MEDAC, personal fees and non-financial support from Biocad, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celgene, personal fees from Amgen, outside the submitted Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sam- work. Dr. Capon reports consultancy fees from AnaptysBio, sung-Bioepis, Sandoz, during the conduct of the study. Dr. grants from Boheringer-Ingelheim, outside the submitted work. Waweru is on the Board of the International Federation of Pso- Prof. Bachelez reports personal fees from Abbvie, personal fees riasis Associations who have received grants from Abbvie, Almi- from Janssen, personal fees from LEO Pharma, personal fees rall, Amgen, Bristol Meyers Squibb, Boehringer Ingelheim, from Novartis, personal fees from UCB, personal fees from Celgene, Janssen, Leo Pharma, Eli Lilly, Novartis, Sun Pharma, Almirall, personal fees from Biocad, personal fees from Boehrin- Pfizer, and UCB, outside the submitted work. Mr. Urmston ger-Ingelheim, personal fees from Kyowa Kirin, personal fees reports grants from Almirall, grants from Abbvie, grants from from Pfizer, outside the submitted work. Prof. Gisondi reports Amgen, grants from Celgene, grants from Dermal Laboratories, personal fees from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, grants from Eli Lilly, grants from Janssen, grants from LEO Pierre Fabre, Sandoz, UCB, outside the submitted work. Dr. Pharma, grants from T and R Derma, grants from UCB, outside Galloway reports personal fees from Abbvie, personal fees from the submitted work. Ms. McAteer reports grants from Abbvie, Sanofi, personal fees from Novartis, personal fees from Pfizer, grants from Almirall, grants from Amgen, grants from Celgene, grants from Eli Lilly, personal fees from Janssen, personal fees grants from Dermal Laboratories, grants from Eli Lilly, grants from UCB, outside the submitted work. Prof. Weinmann has from Janssen, grants from LEO Pharma, grants from UCB, presented talks for Abbvie, Abbott, Bayer, Chiesi, Boehringer grants from T and R Derma, outside the submitted work. JEADV 2021, 35, e619–e698 © 2021 European Academy of Dermatology and Venereology Letters to the Editor e639 Funding sources S. Norton,21 L. Puig,22 P. Spuls,23 T. Torres,24 We acknowledge financial support from the Department of R.B. Warren,4 H. Waweru,10 J. Weinman,25 M.A. Brown,2,3 Health via the National Institute for Health Research (NIHR) J.B. Galloway,3,4 C.M. Griffiths,4 J.N. Barker,2,15 Biomedical Research Centre based at Guy’s and St Thomas’ C.H. Smith,1,2,* the PsoProtect study group 1 St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS NHS Foundation Trust and King’s College London, the Foundation Trust and King’s College London, London, UK, 2NIHR NIHR Manchester Biomedical Research Centre and the Psori- Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation asis Association. The views expressed are those of the author Trust and King’s College London, London, UK, 3Centre for Rheumatic (s) and not necessarily those of the NHS, the NIHR, or the Diseases, King’s College London, London, UK, 4Dermatology Centre, Department of Health and Social Care. SKM is funded by a Salford Royal NHS Foundation Trust, The University of Manchester, Medical Research Council (MRC) Clinical Academic Research Manchester Academic Health Science Centre, NIHR Manchester Partnership award (MR/T02383X/1). ND is funded by Health Biomedical Research Centre, Manchester, UK, 5Faculty of Epidemiology, Data Research UK (MR/S003126/1), which is funded by the and Population Health, London School of Hygiene and Tropical Medicine, UK MRC, Engineering and Physical Sciences Research Coun- London, UK, 6Department of Medical and Molecular Genetics, School of cil; Economic and Social Research Council; Department of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, Health & Social Care (England); Chief Scientist Office of the King’s College London, London, UK, 7Health Data Research UK, London, UK, 8School of Medicine, Keele University, Keele, UK, 9The Psoriasis Scottish Government Health and Social Care Directorates; Association, Northampton, UK, 10International Federation of Psoriasis Health and Social Care Research and Development Division Associations (IFPA), Bromma, Sweden, 11Department of Dermatology, (Welsh Government); Public Health Agency (Northern Ire- ^pital Saint-Louis, Paris, France, 12INSERM U1163, Imagine AP-HP Ho land); British Heart Foundation; and Wellcome Trust. ZZNY Institute for Human Genetic Diseases, Universite  de Paris, Paris, France, is funded by an NIHR Academic Clinical Lectureship through 13 Catedra de Dermatologia, Hospital de Clinicas, Facultad de Ciencias the University of Manchester. CEMG is an NIHR Emeritus Medicas, Universidad Nacional de Asuncion, San Lorenzo, Paraguay, Senior Investigator and is funded in part by the MRC (MR/ 14 Clinica Dermacross, Santiago, Chile, 15St John’s Institute of 101 1808/1). CEMG and RBW are in part supported by the Dermatology, School of Basic & Medical Biosciences, Faculty of Life NIHR Manchester Biomedical Research Centre. SML is sup- Sciences & Medicine, King’s College London, London, UK, 16Section of ported by a Wellcome senior research fellowship in clinical Dermatology and Venereology, University of Verona, Verona, Italy, 17 science (205039/Z/16/Z); this research was funded in whole Department of Dermatology, Edouard Herriot Hospital, Hospices Civils de Lyon, University of Lyon, Lyon, France, 18Groupe de Recherche sur le or in part by the Wellcome Trust [205039/Z/16/Z]. For the Psoriasis (GrPso) de la Soci et e Francßaise de Dermatologie, Paris, France, purpose of Open Access, the author has applied a CC BY 19 Department of Dermatology, Ghent University, Ghent, Belgium, public copyright licence to any Author Accepted Manuscript 20 Centro Studi GISED, Bergamo, Italy, 21Psychology Department, Institute (AAM) version arising from this submission. SML is also of Psychiatry, Psychology and Neuroscience, King’s College London, supported by Health Data Research UK (grant no. LOND1), London, UK, 22Department of Dermatology, Hospital de la Santa Creu i which is funded by the UK MRC, Engineering and Physical Sant Pau, Universitat Auto noma de Barcelona, Barcelona, Spain, Sciences Research Council, Economic and Social Research 23 Department of Dermatology, Amsterdam Public Health/Infection and Council, Department of Health and Social Care (England), Immunology, Amsterdam University Medical Centers, Location AMC, Chief Scientist Office of the Scottish Government Health and Amsterdam, The Netherlands, 24Department of Dermatology, Centro Social Care Directorates, Health and Social Care Research Hospitalar do Porto, Porto, Portugal, 25School of Cancer and and Development Division (Welsh Government), Public Pharmaceutical Sciences, King’s College London, London, UK *Correspondence: C.H. Smith. E-mail: catherine.smith@kcl.ac.uk Health Agency (Northern Ireland), British Heart Foundation † Joint first authors and Wellcome Trust. 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Lancelot,10 matol 2021; 185: 80–90. https://doi.org/10.1111/bjd.19755 L. Moorhead,1 H. Bachelez,11,12 F. Capon,2,6 5 Kroenke K, Spitzer RL, Williams JBW, L€ owe B. An ultra-brief screening C.R. Contreras,13 C. De La Cruz,14 P. Di Meglio,2,15 scale for anxiety and depression: the PHQ-4. Psychosomatics 2009; 50: P. Gisondi,16 D. Jullien,17,18 J. Lambert,19 L. Naldi,20 613–621. JEADV 2021, 35, e619–e698 © 2021 European Academy of Dermatology and Venereology e640 Letters to the Editor 6 Mahil SK, Dand N, Mason KJ et al. Factors associated with adverse lactam antibiotics (n = 17/21; 81.0%). Within the remaining COVID-19 outcomes in patients with psoriasis-insights from a global reg- 11 patients (n = 11/32; 28.2%), five patients were favoured istry-based study. J Allergy Clin Immunol 2021; 147: 60–71. 7 Gelfand JM, Armstrong AW, Bell S et al. National Psoriasis Foundation to have a drug reaction within 28 days of culprit drug COVID-19 task force guidance for management of psoriatic disease dur- exposure based on clear documentation from chart review. ing the pandemic: version 1. J Am Acad Dermatol 2020; 83: 1704–1716. The remaining six patients had insufficient data to ade- 8 Pierce M, Hope H, Ford T et al. Mental health before and during the quately confirm the aetiology of their late-onset rash, though COVID-19 pandemic: a longitudinal probability sample survey of the UK population. Lancet Psychiat 2020; 7: 883–892. drug exposure was suspected based on the timeline. 9 Lamb RC, Matcham F, Turner MA et al. Screening for anxiety and Exanthems can present a diagnostic conundrum in distin- depression in people with psoriasis: a cross-sectional study in a tertiary guishing medication hypersensitivity versus viral infection as referral setting. Br J Dermatol 2017; 176: 1028–1034. likely aetiologies. Exanthems due to viral infections typically 10 Read S, Morgan J, Gillespie D et al. Chronic conditions and behavioural change approaches to medication adherence: rethinking clinical guidance present within 14 days of viral symptom onset.4 Skin rashes and recommendations. Patient Prefer Adherence 2020; 14: 581–586. in COVID-19 are believed to present around the same time as other symptoms, typically during the first few days of DOI: 10.1111/jdv.17450 fever and respiratory symptoms.1 In this cohort, only a minority of exanthems (n = 7/39; 17.9%) developed within 14 days of COVID-19 symptom onset to be considered for a viral rash. One of these seven patients was evaluated by The significance of exanthems in dermatology and confirmed to have a drug hypersensitivity reaction by skin biopsy. The remaining six patients, 0.49% COVID-19 patients hospitalized of all patients overall, could be potentially compatible with at a tertiary care centre a viral aetiology for their exanthem based on timing of symptom onset. Dear Editor, Drug eruptions can result within 14 days of initial adminis- Cutaneous manifestations have been associated with COVID-19 tration of the culprit drug but may also be delayed further by up infection, and their significance in hospitalized patients remains to several weeks.5 The majority (n = 21/39; 53.8%) of exanthems unclear.1–3 This study catalogues the exanthems observed in in this cohort developed within 14 days of clear exposure to a hospitalized COVID-19 patients to determine prevalence common culprit drug and also after the 14-day window of and inform clinicians in devising diagnostic and management COVID-19 symptom onset and resolved with cessation of drug strategies. use, supporting a medication-induced aetiology. In general, A retrospective review of 1216 adults hospitalized with labora- cutaneous drug reactions are estimated to develop in approxi- tory-confirmed SARS-CoV-2 infection from 12 March 2020 to mately 2% of patients,6 increasing to 8% with exposure to cer- 31 May 2020 at a single institution was conducted. Keyword tain antibiotic groups.5 This is similar to the incidence of 3.2% search of patient records combined with manual chart review by (n = 39/1216) found within this study. at least two dermatologists, with a third dermatologist for adju- In this study population of 1216 patients admitted with dication, identified patients with cutaneous manifestations based COVID-19, rashes from SARS-CoV-2 were exceedingly uncom- on chart documentation (Fig. 1). mon. These findings suggest that rashes previously ascribed to Exanthems occurred in 39 patients (3.2%) and were cate- SARS-CoV-2 may have alternate explanations and highlight the gorized clinically as morbilliform eruptions (n = 37/39; importance of routinely considering medication exposures in 94.9%) and urticarial eruptions (n = 2/39; 5.1%) based on the evaluation of generalized rashes occurring in hospitalized chart documentation and visual morphology (Table 1). patients. Clinicians encountering exanthems in hospitalized Reviewers were aided by photographs for 26 patients patients with COVID-19 should maintain their usual standard (66.7%) and inpatient dermatology consultations for 16 of care for drug rashes7 in providing symptomatic treatment if patients (41.0%). A minority of patients (n = 7/39; 17.9%) necessary and considering withdrawal of the offending agent if a had exanthems occurring within 14 days of COVID-19 prolonged course of exposure is anticipated. symptom onset and thereby could be considered a possible viral reaction. The remaining 32 patients developed a rash Conflict of interest more than 14 days after initial COVID-19 symptom onset. The authors have no conflicts of interest to declare. 21 patients (n = 21/32; 65.6%) developed a rash within 14 days of a clear causative medication exposure, suggesting Funding source a drug reaction aetiology. Dermatology reviewers identified None. likely culprit drugs in these patients, most commonly beta- JEADV 2021, 35, e619–e698 © 2021 European Academy of Dermatology and Venereology