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Background: Little is known about phototype and the response to systemic treatment in psoriasis., Objectives: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype., Methods: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index (DLQI) 0/1., Results: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, and more frequently initiated ustekinumab. Patients in the V-VI group maintained the initial biologic prescribed as did the other phototype groups, even though the proportion of patients reaching PASI 90 and DLQI 0/1 at 12 months was lower in this group than the other groups., Conclusions: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. The phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient., Competing Interests: Conflicts of interest F.T. is Head of the Clinical Research Unit at Pitié-Salpêtrière Hospital and the Centre de Pharmacoepidemiologie (Cephepi) (Pharmacoepidemiology Centre) of the Assistance Publique–Hôpitaux de Paris (Paris Hospitals); she has received research funding, grants and fees for consultancy activities from a large number of pharmaceutical companies that have contributed to employee salaries (but no personal remuneration for F.T.). M.V. has undertaken activities as a paid consultant, advisor or speaker for AbbVie, Arrow, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Janssen, LEO Pharma, Lilly, medac, MSD, Novartis and Pfizer. M.B.-B. offers a consultancy service and is an investigator for AbbVie, Amgen, Celgene, Janssen, LEO Pharma, Lilly, MSD, Novartis and Pfizer. N.B. has been an investigator for Novartis and Pfizer; she is a consultant for Janssen and has received speaker remuneration from Janssen. P.J. is a consultant for GSK, Lilly, Principia Biopharma, Roche and Sanofi Aventis. D.J. is a consultant for AbbVie, Biogen, Celgene, Fresenius Kabi, Janssen, Lilly, medac, Merck Sharp & Dohme, Novartis, Pfizer and UCB. E.M. is a consultant for AbbVie, Janssen, Novartis and Pfizer; she has also been an investigator for AbbVie, Amgen, AstraZeneca, LEO Pharma, Novartis and Pfizer; and has received speaker remuneration from AbbVie, Janssen, Novartis and Pfizer. C.P. has been an investigator and consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, GSK, Janssen, LEO Pharma, Lilly, Novartis and Pfizer. M.-A.R. is a consultant for AbbVie, BMS, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer and Pierre Fabre. H.B. has undertaken activities as a paid consultant, advisor or speaker for AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharmaceuticals and UCB; he has also received grant funding from Pfizer. The other authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest The full list is provided in Appendix S1 (see Supporting Information).

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic., Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence., Methods: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence., Results: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49)., Conclusions: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes., Competing Interests: Conflict of interests J.W. has presented talks for Abbott, AbbVie, Bayer, Boehringer Ingelheim, Chiesi, Merck and Roche. K.J.M. reports personal fees from LEO Pharma and Novartis, outside the submitted work. H.M. reports grants from AbbVie, Almirall, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. D.U. reports grants from AbbVie, Almirall, Amgen, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. L.M. reports personal fees from AbbVie, Celgene, Janssen, LEO Pharma, Novartis and UCB, outside the submitted work. Additional disclosures from L.M. include Almirall, BMS and Lilly. H.B. reports personal fees from AbbVie, Almirall, Biocad, Boehringer-Ingelheim, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer and UCB, outside the submitted work. F.C. reports consultancy fees from AnaptysBio, grants from Boehringer Ingelheim, outside the submitted work. C.D.l.C. reports personal fees from Boehringer Ingelheim and UCB Pharma; grants from Janssen, Pfizer, Sandoz, Sanofi; grants and personal fees from AbbVie, Novartis, outside the submitted work. P.D.M. reports grants and personal fees from UCB; personal fees from Janssen and Novartis, outside the submitted work. P.G. reports personal fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pierre Fabre, Sandoz and UCB, outside the submitted work. D.J. reports personal fees and nonfinancial support from AbbVie, Celgene, Janssen-Cilag, Lilly, LEO Pharma, MEDAC and Novartis; and personal fees from Amgen, outside the submitted work. L.P. reports grants and personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Lilly, Novartis and UCB; and personal fees from Bristol Myers Squibb, Fresenius-Kabi, Mylan, Pfizer, Samsung-Bioepis, Sandoz, Sanofi, outside the submitted work. P.S. has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid); has received departmental independent research grants for TREAT NL registry from pharma companies since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of diseases such as psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; and is chief investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children, as well as one of the main investigators of the SECURE-AD registry. T.T. reports grants and personal fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis and Sandoz, during the conduct of the study. R.B.W. reports grants from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO, Lilly, Medac, Novartis, Pfizer and UCB. R.B.W. also reports consultancy fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, LEO, Lilly, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION. H.W. is on the Board of the International Federation of Psoriasis Associations who have received grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma and UCB, outside the submitted work. J.B.G. reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. C.E.M.G. reports grants and personal fees from AbbVie, Janssen, Lilly and Novartis and UCB Pharma; and grants from Almirall, Amgen, BMS, LEO and Pfizer, outside the submitted work. J.N.B. reports grants and personal fees from AbbVie, J&J, Lilly and Novartis during the conduct of the study. J.N.B. has attended advisory boards, and/or received consultancy fees, and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sun Pharma and UCB. C.H.S. reports grants from AbbVie, Novartis, Pfizer and Sanofi; and through consortia with multiple academic partners (psort.org.uk, BIOMAP-IMI.eu), outside the submitted work. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, Novartis, Sanofi and UCB, outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest: M.B.-B. is a consultant for AbbVie, Celgene, Janssen-Cilag, Lilly, Novartis, Medac and UCB. N.B. is a consultant for Novartis, Celgene, MSD, Janssen, Lilly, Pfizer and AbbVie. P.J. is a consultant for AbbVie, Celgene, Janssen-Cilag, Lilly and Novartis. D.J. is a consultant for AbbVie, Amgen, Celgene, Fresenius-Kabi, Janssen-Cilag, LEO, Lilly, Pfizer, MEDAC, Novartis and UCB. E.M. is a consultant for AbbVie, LEO Pharma, Celgene, Pfizer, Janssen-Cilag and Novartis. C.P. is a consultant for AbbVie, Almirall, Amgen, Boerhinger, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Pfizer, Novartis, Pierre Fabre, Sanofi and UCB. M.-A.R. is a consultant for AbbVie, Amgen, Boehringer, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Nordic, Novartis, Pfizer and Medac. H.B. is a consultant for AbbVie, Almirall, Amgen, Biocad, Boerhinger, Celgene, Dermavant, Janssen, LEO Pharma, Eli Lilly, Mylan, Novartis, Pfizer, Pierre Fabre, Sun Pharmaceuticals and UCB. H.A. is a consultant for AbbVie, Novartis, Janssen-Cilag, Almirall, Leo and Lilly.

Background: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials., Objectives: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials., Methods: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials., Results: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients., Conclusions: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear., Objectives: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus., Methods: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included., Results: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL., Conclusions: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations., (© 2021 British Association of Dermatologists.)

Background: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments., Objectives: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation., Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model., Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations., Conclusions: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis., Objectives: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis., Methods: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure., Results: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID., Conclusions: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments., (© 2018 British Association of Dermatologists.)

Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug-induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets., (© 2018 British Association of Dermatologists.)

Background: ABP 501, a U.S.A. Food and Drug Administration- and European Medicines Agency-approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics., Objectives: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate-to-severe plaque psoriasis (clinical trial: NCT01970488)., Methods: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed., Results: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8-88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments., Conclusions: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population., (© 2017 British Association of Dermatologists.)

Background: Infections are associated with biological therapies in psoriasis., Objectives: To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody., Methods: Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported., Results: Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation., Conclusions: Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Around two-thirds of patients with psoriasis do not adhere to topical treatment. The Topical Treatment Optimization Programme (TTOP), a five-element tool, includes guidance for the conversation between dermatologists/nurses and patients, patient information material, telephone/e-mail helpdesks and treatment reminders. It has been developed by patients and dermatologists to help increase adherence to treatment in psoriasis., Objectives: To compare TTOP with standard of care ('non-TTOP') within a large European investigator-initiated study, PSO-TOP (clinicaltrials.gov NCT01587755)., Methods: Patients with mild-to-moderate psoriasis received calcipotriol/betamethasone dipropionate gel as standardized study medication and were randomized 1 : 1 to either TTOP or non-TTOP management. Study medication was applied once daily for 8 weeks followed by 'as needed' application for an additional 56 weeks. Response was defined as a Physician's Global Assessment (PGA) of 'clear' or 'almost clear'., Results: In 1790 patients (full analysis set), response rates after 8 weeks (primary objective) were significantly higher for TTOP (36·3%) than for non-TTOP (31·3%, P = 0·0267). Better clinical outcome was accompanied by higher rates of patients feeling well informed about their skin condition, treatment and other factors related to adherence, but the Dermatology Life Quality Index was not statistically different. TTOP patients regarded the structured one-to-one conversations with their dermatologist/nurse as the most important element of TTOP., Conclusions: Patients randomized to the TTOP intervention had a better clinical response than patients receiving standard of care. Improved communication between the healthcare provider and patient might be an important element in increasing adherence to topical therapy in psoriasis., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Psoriasis, Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders with overlapping genetic architecture. However, data on the frequency and risk of CD and UC in psoriasis are scarce and poorly understood., Objectives: To investigate the association between CD and UC in patients with psoriasis., Methods: All Danish individuals aged ≥ 18 years between 1 January 1997 and 31 December 2012 were linked in nationwide registers. Psoriasis severity was defined in two models: hospital visits and medication. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios (IRRs) were estimated by Poisson regression., Results: In the total cohort (n = 5 554 100) there were 75 209 incident cases of psoriasis, 11 309 incident cases of CD and 30 310 incident cases of UC, during follow-up. The adjusted IRRs (95% confidence intervals) of CD were 1·28 (1·03-1·59), 2·56 (1·87-3·50), 2·85 (1·72-4·73) and 3·42 (2·36-4·95) in patients with mild psoriasis, severe psoriasis (hospital), severe psoriasis (medication) and psoriatic arthritis, respectively. Similarly, the adjusted IRRs of UC were 1·49 (1·32-1·68), 1·56 (1·22-2·00), 1·96 (1·36-2·83) and 2·43 (1·86-3·17), respectively. The 10-year incidence of CD was 2-5 per 1000 patients and of UC 7-11 per 1000 patients, depending on psoriasis severity and the presence of psoriatic arthritis. Additionally, an increased risk of incident psoriasis was found following CD or UC., Conclusions: We observed a psoriasis-associated increased risk of CD and UC, which was higher in severe psoriasis, and an increased risk of psoriasis in patients with inflammatory bowel disease. Increased focus on gastrointestinal symptoms in patients with psoriasis may be warranted., (© 2016 British Association of Dermatologists.)

Background: Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results., Objectives: To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies., Methods: Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI)., Results: Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects., Conclusion: Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL-1-inhibiting strategies in pustular psoriasis., (© 2014 British Association of Dermatologists.)

Idiopathic CD4(+) lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established; however, skin dysimmune diseases, including psoriasis, have been scarcely reported up to now. We report herein the severe course of psoriasis in four patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4(+) FoxP3(+) T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T-cell defect, a model that might also apply to other immune deficiencies associated with psoriasis., (© 2014 British Association of Dermatologists.)

Background: Alemtuzumab has been proposed as salvage therapy for refractory cutaneous T-cell lymphomas (CTCLs). Long-term follow-up data are scarce., Objectives: To assess the efficacy and safety of alemtuzumab in the treatment of advanced CTCL., Methods: A multicentre retrospective analysis was carried out of 39 patients with advanced CTCL treated with alemtuzumab between 2003 and 2013., Results: Thirty-nine patients (median age 62 years, range 20-83) with Sézary syndrome (SS, n = 23) or advanced mycosis fungoides (MF, n = 16) received alemtuzumab 30 mg two to three times per week for a median duration of 12 weeks (range 1-35). Fifteen patients received maintenance therapy for a median duration of 24 weeks (range 6-277). Eleven patients (28%) had transformed disease (MF, n = 10; SS, n = 1). After a median follow-up of 24 months (range 0.3-124), eight patients (21%) were still alive. The overall response rate was 51% in the whole study group (partial response, n = 13; complete response, n = 7); 70% in patients with SS and 25% in patients with MF (P = 0.009). The median time to progression was 3.4 months (range 0.4-42). Six patients (15%; SS, n = 5; MF, n = 1) remained progression free for > 2 years (median 56 months, range 28-117). Five patients experienced cutaneous large T-cell transformation during alemtuzumab treatment and one patient developed primary cutaneous large B-cell lymphoma. Twenty-four patients (62%) had a grade three or higher infectious adverse event and 10 (26%) a haematological toxicity, which led to treatment discontinuation in 17 cases (44%) and death in two (5%)., Conclusions: Alemtuzumab may induce long-term remission in SS but seems ineffective in MF and transformed CTCL., (© 2014 British Association of Dermatologists.)

Background: In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment., Methods: Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied., Results: All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response., Conclusions: HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.

The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the pathogenic mechanisms that constitute psoriasis. In September 2012, a workshop was held at the 42nd Annual European Society for Dermatological Research in Venice, Italy. By assembling a panel of global dermatology and immunology experts, the objective was to evaluate the current status of the science explaining the mechanism of disease in psoriasis, e.g. dysregulation of the skin immune system and perturbations of epidermal homeostasis. The workshop consisted of four oral presentations, which addressed key topics in psoriasis, delivered by Hervé Bachelez (Paris, France), Antonio Costanzo (Rome, Italy), Michelle Lowes (New York, NY, U.S.A.) and Frank Nestle (London, U.K.). A global expert panel was assembled to stimulate dialogue and debate: Kevin Cooper (Cleveland, OH, U.S.A.), Michel Gilliet (Lausanne, Switzerland), Joerg Prinz (Munich, Germany), Martin Röcken (Tubingen, Germany), Jens Schroeder (Kiel, Germany), Manuelle Viguier (Paris, France), Mayte Suárez-Fariñas (New York, NY, U.S.A.) and Cristina Zielinski (Berlin, Germany). Collectively, the presentations demonstrated the significant advances in understanding immune regulation that have occurred over the past decade by virtue of the study of psoriasis subtypes, phenotypic manifestations and genetic associations. Elucidating the pathogenic and genetic basis of psoriasis holds the promise of a complete understanding of disease mechanisms, predictors of treatment response, novel drug development strategies and customized therapeutic regimens for the individual patient., (© 2013 The Authors BJD © 2013 British Association of Dermatologists.)

Background: There is a low rate of systemic treatment usage in moderate to severe psoriasis., Objectives: The primary objective of the present study was to assess the time period between lack of control of moderate to severe psoriasis with topical treatment or phototherapy as perceived by patients and the medical decision to introduce a systemic treatment., Methods: This was a prospective multicentre study, which included patients with moderate to severe psoriasis. A standardized questionnaire was completed by physicians and patients at the time the decision was taken to introduce a systemic treatment. The primary outcome was the duration of uncontrolled psoriasis, as estimated by the patient, prior to the introduction of systemic treatment. Factors associated with a delay in systemic treatment defined as > 2 years of uncontrolled psoriasis were assessed. The agreement between patients and physicians on the duration of uncontrolled psoriasis was estimated., Results: The study included 142 patients. The mean age was 48 years, the mean Psoriasis Area and Severity index (PASI) was 18·5 and the mean Dermatology Life Quality Index (DLQI) was 12. The median duration of uncontrolled psoriasis estimated by patients and physicians was 3 years and 2 years, respectively. Factors associated with a delay in the introduction of systemic treatment as assessed by patients were fewer than three physician visits since psoriasis was uncontrolled [odds ratio (OR) 3·05; 95% confidence interval (CI) 1·29-7·21], Hospital Anxiety and Depression (HAD) scale < 10 (OR 2·83; 95% CI 1·19-6·71), continuous psoriasis evolution (OR 2·67; 95% CI 1·12-6·42), low consumption of topical treatment (OR 2·35; 95% CI 1·03-5·34)., Conclusions: There is a significant delay in the introduction of systemic treatment in moderate to severe psoriasis. Patients with low level anxiety and limited use of healthcare resources appear to be at higher risk of experiencing long delays., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have been scarcely reported., Objectives: To address the efficacy and safety of biologics in patients with erythrodermic psoriasis., Methods: A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention-to-treat analysis., Results: We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n=24), adalimumab (n=7), etanercept (n=6), ustekinumab (n=3) or efalizumab (n=2). A 75% improvement of BSA or Psoriais Area and Severity Index 12-14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events, consisting of bacterial infection in seven of them, were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was administered for up to 48 weeks in 34% of flares., Conclusions: Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side-effects is frequently observed on a longer term, with only one-third of patients still receiving the same drug after 1 year. The most significant safety concern consists of severe infections., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: A CD8 cutaneous lymphoinfiltrative disease has been described in human immunodeficiency virus (HIV)-infected patients presenting with a severe erythroderma. The true nature of this severe skin infiltrative disorder is still elusive. Although some clinical features of this syndrome have raised the hypothesis of its malignant nature in initial observations, several studies have provided stronger support to the hypothesis that it is a reactive pseudotumoral process., Methods: From 1995 through 2008, 8 HIV type 1 (HIV-1)-infected patients presenting with a chronic skin eruption, diagnosed as CD8 T cell infiltration of the skin, were studied., Results: All patients showed diffuse infiltrated skin with superficial lymphadenopathy. A profound CD4(+) lymphocytopenia and eosinophilia were other major features. Histological and immunostaining analysis revealed a predominant dermal and epidermal infiltration by CD8(+) T cells belonging to the cytotoxic lineage, without evidence for a monoclonal status by polymerase chain reaction-based molecular analysis of lesional skin. A remission of skin symptoms occurred in all cases following highly active antiretroviral therapy, which paralleled the decrease of HIV-1 RNA load and the increase of CD4(+) peripheral blood absolute count., Conclusions: Altogether, these results emphasize the reactive, nonmalignant nature of this syndrome and strongly support the coupling between HIV-induced immune deficiency and uncontrolled CD8 activation.

Background: Primary cutaneous T-cell lymphomas (CTCLs) are malignancies characterized by a clonal T-cell infiltrate involving the skin. CTCLs often show resistance to conventional antineoplastic chemotherapy. Gemcitabine is a pyrimidine analogue which has shown efficacy and a favourable safety profile in solid tumours and haematological malignancies., Objectives: We report a multicentre retrospective study of 23 patients who received gemcitabine for advanced-stage CTCL and emphasize the high incidence of serious unusual adverse events., Methods: We collected data from 23 patients with refractory CTCL (14 mycosis fungoides, six Sézary syndrome and three other CTCL). Gemcitabine was given weekly within a 21- or 28-day schedule. Response was evaluated after three and six cycles of chemotherapy. For each patient, all adverse events were recorded., Results: Of the 16 patients who received at least three cycles of gemcitabine, 10 achieved a response (62.5%). Only five patients reached the sixth cycle of treatment and four still had a favourable response. Haematological toxicity was recorded in 15 cases with severe grade 3 or 4 neutropenia in seven patients (30%) and six serious infections (26%). Other serious adverse events were observed in six cases (26%): one haemolytic-uraemic syndrome, one severe capillary leak syndrome, one acute heart failure related to cardiac arrhythmia, two bullous and erosive dermatitis, and one recurrent influenza-like syndrome with altered general condition., Conclusions: Our study confirms the early efficacy of gemcitabine in advanced-stage CTCL. However, our results contradict the safety profile of gemcitabine previously reported and underline the high incidence of severe complications including visceral and cutaneous involvement.

Infliximab, a tumour necrosis factor (TNF)-alpha antagonist, has shown striking efficacy in the treatment of chronic inflammatory rheumatological diseases such as rheumatoid arthritis and ankylosing spondylitis. However, long-term follow-up studies support that treatment with infliximab is associated with an increased risk of non-Hodgkin lymphoma. So far, few cases of cutaneous lymphoma have been reported in patients receiving TNF-alpha-blocking agents. We report a patient who developed Sézary syndrome 17 months after the onset of infliximab therapy for ankylosing spondylitis. Cutaneous lesions partially remitted following infliximab withdrawal and methotrexate treatment. Although the causal link between infliximab and the emergence of Sézary syndrome is uncertain, the present case raises the need for exhaustive long-term registries of malignancies, including primary cutaneous lymphomas, in patients receiving TNF-alpha-blocking agents.

Background: Case reports have suggested that extracorporeal photochemotherapy (ECP) might be beneficial for the treatment of erosive oral lichen planus (OLP) recalcitrant to conventional immunosuppressive therapies., Objectives: To evaluate over a long-term period the clinical efficacy and toxicity of ECP in a series of patients with refractory OLP, and to monitor peripheral blood lymphocyte subset counts under treatment., Methods: Twelve patients with refractory OLP underwent a standardized protocol of ECP. Sessions were performed twice weekly for 3 weeks, and then the treatment schedule was adapted according to clinical benefit. The disease severity was evaluated monthly on a clinical basis. Complete remission was defined as the absence of any erosion and partial remission as a decrease of at least 50% of erosion surface. Blood cell counts with CD4+ and CD8+ lymphocyte subsets were evaluated every 3 months., Results: All patients showed a decrease of the erosive surface; nine (75%) achieved a complete remission and three (25%) a partial remission. Seven of the eight patients followed for more than 3 years had recurrences of erosions when ECP sessions became less frequent or were stopped. After resumption of an initially accelerated regimen of ECP, all again showed partial or complete remission. Blood lymphocyte counts decreased during treatment, without statistically significant changes in CD4+/CD8+ ratio, and increased during relapse., Conclusions: ECP is an effective alternative therapy in erosive OLP showing resistance to classical treatments. The decrease in blood lymphocyte counts appears to parallel the clinical improvement under treatment.

Background: Infliximab, an antitumour necrosis factor-alpha chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti-dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis., Objectives: To investigate biological and clinical signs of autoimmunity in 28 patients receiving infliximab for severe, recalcitrant forms of psoriasis, and the clinical response to treatment., Methods: Twenty-eight patients, 15 men and 13 women (median age 39.4 years) with psoriasis refractory to three or more systemic treatments were included. Twenty presented with plaque-type psoriasis [median Psoriasis Area and Severity Index (PASI) score 25.9; range 7.2-48], five with psoriatic erythroderma (median PASI score 54; range 48-72) and three with generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13 patients (46.4%). Infliximab 5 mg kg(-1) was given at week (W) 0, W2, W6 and every 8 weeks thereafter. Clinical data were assessed at baseline and before each infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay, respectively., Results: The mean number of infliximab infusions was 5.5 (range 2-15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%) and three of five reached a PASI improvement of 75% or more, respectively, while rapid improvement of clinical and biological signs was observed in all three patients with GPP. The prevalence of positive detection of ANA raised from 12% at baseline to 72% at W22 (P = 0.0001), an increase which was also observed for IgM anti-dsDNA-ab (68% vs. 0%, P < 0.0001), while no significant change was observed for the IgG isotype (16% vs. 0%, P = 0.125). Three patients developed nonerosive polyarthritis, without any other criteria for systemic lupus., Conclusions: The incidence of biological autoimmunity is high in patients with refractory psoriasis receiving infliximab. The concomitant onset of polyarthritis in three cases raises the need to investigate the incidence of autoimmune manifestations in psoriatic patients receiving infliximab in further large-scale studies.

Background: There is a need for alternative therapy in severe adult atopic dermatitis (AD). Intravenous immunoglobulin (IVIG) treatment has been shown to be beneficial in a few open observations, but evidence of effectiveness is still lacking., Objective: To investigate whether treatment with IVIG is effective in adults with severe AD., Methods: In a randomized evaluator-blinded trial, 10 patients with severe AD were randomized to immediate or delayed (by 1 month) treatment with IVIG 2 g kg-1. Patients received an 8-h infusion of 1 g kg-1 daily for two consecutive days. They were assessed clinically at days 15, 30, 60 and 90. The primary efficacy criterion was measurement of the severity scoring of AD (SCORAD) index at day 30., Results: The SCORAD values were not significantly different between the two groups at day 30. Similarly, global evaluation of disease severity by patients did not show any clinically significant change at day 30. In the cohort of 10 patients, the mean percentage decrease in SCORAD as compared with baseline was, respectively, 15%[95% confidence interval (CI) 6-24%] and 22% (95% CI 5-39%) at 30 and 60 days after IVIG infusion., Conclusions: IVIG treatment was not associated with clinically significant improvement of AD signs and symptoms in this randomized study. Although this study may have been too small to detect a beneficial effect in a small subset of patients, the results do not support the common use of IVIG in refractory AD.

Three human immunodeficiency virus (HIV)-infected patients presented with disseminated pityriasis versicolor-like skin lesions. Histological examination showed features characteristic of epidermodysplasia verruciformis (EV). Hybridization studies demonstrated the presence of human papillomavirus (HPV) type 5 (HPV5) DNA in two patients and HPV20 in one. A relative increase in CD8+, CD57+ cells, which are known to inhibit cell-mediated cytolysis, was observed in all patients. HLA-DQB 0301 haplotype, which has been associated with EV, was detected in two patients. The findings suggest that infection with EV-associated HPV types can complicate HIV infection. Both cellular immune defects and a hitherto unknown genetic background might explain the occurrence of EV in HIV-infected patients.

Severe disseminated infection due to Mycobacterium avium intracellulare, with unusual cutaneous features, is reported in a patient with acquired immunodeficiency syndrome (AIDS). The eruption appeared as disseminated pustular lesions which showed necrotic features and which led to varioliform scarring. Bacterial culture from the skin, blood, and bone marrow, and ultimately from the bronchoalveolar fluid and sputum, was positive for M. avium intracellulare. The patient was successfully treated using a multiple agent anti-mycobacterial regimen including clarithromycin, which appeared to be the most effective drug. This resulted in resolution of the cutaneous and general symptoms. Our patient illustrates the wide spectrum of skin presentations that may be seen with mycobacterial infections in subjects infected with the human immunodeficiency virus (HIV). Clarithromycin is an important agent for the treatment of these severe infections.

Three cases of cutaneous bacillary angiomatosis in HIV-infected patients are reported. They differed profoundly with respect to the extent of the lesions and the clinical course. In two cases, Rochalimaea quintana was identified by direct sequencing of the DNA amplified with the polymerase chain reaction (PCR), whereas an easy, rapid method based on the restriction length of polymorphism analysis of PCR products (PCR-RFLP) was used in the third case. This report illustrates the variations in clinical presentations and evolutive profiles in patients with bacillary angiomatosis, and confirms the causal role of R. quintana in this disease.

A cross-sectional study was done to determine the seroprevalence of Mycoplasma penetrans in human immunodeficiency virus (HIV) type 1-seropositive and -seronegative persons recruited in France. The data were analyzed with respect to the sociodemographic, clinical, and biologic status of the patients. M. penetrans seropositivity was associated with HIV infection (18.2% of HIV-seropositive vs. 1.3% of HIV-seronegative persons were M. penetrans-seropositive; P < .001). M. penetrans infection was predominantly but not exclusively associated with homosexual practices in HIV-seropositive subjects and thus presumably sexually transmitted. M. penetrans seroprevalence increased with progression of HIV-associated disease. No association was found between M. penetrans and Kaposi's sarcoma. Thus, there is an unambiguous association between M. penetrans and HIV, particularly among homosexual persons, but its clinical significance remains to be investigated.