Search

Introduction: A number of new, highly effective biologic drugs for psoriasis have been approved over the past few decades, which raises the question whether psoriasis is still a disease that requires inpatient treatment., Methods: We conducted a retrospective analysis of inpatient data between 2010 and 2019 (the last 10 years prior to the coronavirus disease 2019 [COVID-19] pandemic) from three German dermatology departments at university hospitals (Aachen, Bonn, and Essen). The data collected included age, gender, the primary admission diagnosis, length of stay (LOS), and number of all comorbidities recorded during hospitalization., Results: A total of 59,500 patients were admitted to the three dermatological departments in the defined 10-year period. Of these patients, psoriasis (L40.-) was the main diagnosis for 4322 (7.3%). An almost continuous increase was observed in all inpatient dermatological cases, which was as high as 27% in 2016 compared to 2010. For psoriasis patients, the most substantial increase in the number of admissions was reached in 2016 compared to 2010 and was as high as 45%. While there was a statistically significant reduction of the mean LOS for all dermatological inpatient cases from 6.4 ± 6.6 days in 2010 to 5.1 ± 4.6 days in 2019 (p < 0.001), the decrease in 2019 compared to 2010 (from 12.2 ± 5.5 to 8.9 ± 3.3 days) was significantly greater for the inpatient psoriasis patients compared to the inpatient population overall (p < 0.001)., Conclusions: Our data show a stable need for inpatient psoriasis facilities in Germany. Further analysis of hospital admissions after the end of the COVID-19 pandemic is needed to understand the ongoing influence of modern systemic treatment options on inpatient psoriasis care in Germany., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Atopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease ("Flip-Flop" [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy., Methods: The objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK-CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning., Results: Three hundred adult Caucasian patients were included in the validation study (n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data (p < .001). The predictive mean generalized Youden-Index of the initial model was 78.9% [95% confidence interval 72.0%-85.6%] and the accuracy was 89.7%. Disease group-specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively., Conclusion: The FF algorithm represents the first validated tool to identify FF patients., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives: This study evaluated musculoskeletal ultrasound (MSUS) use by dermatologists previously trained on a novel handheld, chip-based ultrasound device (HHUD) to screen for early PsA., Methods: Twelve dermatologists were recruited to screen psoriasis patients for PsA using the novel HHUD in one major hospital in Bonn (Germany) and six private practices in surrounding regions. Patient screening was based on medical history, clinical examination, and the GEPARD questionnaire paired with an MSUS examination of up to three painful joints. All screened patients were then referred to rheumatologists, who determined the final diagnosis. The screening effect of MSUS was assessed according to its sensitivity and specificity before and after its application., Results: Between 1 October 2020 and 26 May 2021, a total of 140 psoriasis patients with arthralgia participated in this study. PsA was diagnosed in 19 (13.6%) cases. Before applying MSUS, dermatologists' screening sensitivity and specificity were recorded as 88.2% and 54.4%, respectively, while after applying MSUS the sensitivity and specificity changed to 70.6% and 90.4%, respectively. MSUS led to a change of PsA suspicion in 46 cases, with PsA no longer being suspected in 45 of them., Conclusion: This study was able to demonstrate that PsA screening using MSUS by previously trained dermatologists can lead to more precise PsA detection and potentially decreased rheumatologist referral rates., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The study of psoriasis has yielded fundamental new insights into immunologic regulation and innovative therapies in a way that few other diseases have. In this review, we summarize the main features of current psoriasis research with emphasis on pathophysiological processes and the milestones in the approval of various biologics and small molecule drugs. Thus, through psoriasis research, we are gaining a better understanding of the interplay between the components of the innate and adaptive immune systems. New therapeutics interfere with crucial regulatory networks. Based on current knowledge, we outline what we believe to be some of the most important future research directions and therapeutic and clinical developments in psoriasis. These span multiple areas, ranging from the study of genetic, epigenetic, cellular, and immunological mechanisms to studies of particular clinical forms of psoriasis, individual systemic effects of the disease and its treatment, and the incorporation of large connected data sets and artificial intelligence. The goal is to understand psoriasis holistically, from the molecular to the organismic and societal levels, in order to develop individualized prevention and treatment strategies. Despite impressive progress, psoriasis research must continue to evolve at both the smallest and largest scales to comprehensively address the needs of both physicians and patients., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterised by neutrophilic granulocyte (neutrophil)-filled pustules on the palms and soles. The pathogenesis of PPP is poorly understood. This study conducted an identification of the immune mediators associated with PPP and an exploration of apremilast treatment effects on them. We screened for immune mediators elevated in blood taken from 68 patients with PPP versus control participants and included the most promising parameters in the protocol of phase the 2, multicentre study of apremilast (PDE4 inhibitor) in 21 patients with moderate-to-severe PPP (APLANTUS; EudraCT 2016-005122-11) for respective analysis of blood and skin samples of study patients. We investigated stimulated neutrophils and three-dimensional reconstituted epidermis cultures. Interleukin (IL)-19 was found to be the most upregulated immune mediator in the blood of PPP patients. IL-19 serum levels were independent of patients' age, gender, and BMI but were associated with strongly upregulated cutaneous IL-19 expression and correlated with the number of palmoplantar pustules. In patients participating in the APLANTUS study, apremilast reduced pustules more effectively than erythema and scaling. Moreover, this treatment significantly reduced IL-19 blood and skin levels. The reduction in IL-19 blood levels at week 4 correlated with the reduction in pustule counts at week 20 (end of treatment). IL-19 was expressed by neutrophils activated in vitro and induced CXCL6, a neutrophil-attracting chemokine, in epidermis models. This work demonstrates elevated IL-19 levels in the blood and skin of PPP patients and suggests a relevant role of this cytokine in the appearance of pustules in this disorder. It also suggests the suitability of IL-19 blood levels as a predictive biomarker for the treatment response of PPP patients, which should be validated in further studies.

Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4 + cytotoxic T lymphocytes and other CD4 + effector cells were increased in generalized pustular psoriasis, whereas the frequencies of naïve CD4 + T cells were significantly lower. The expression of FGFBP2 marking CD4 + cytotoxic T lymphocytes and CD8 + effector memory T cells was elevated in patients with generalized pustular psoriasis with disease-contributing variants compared with that in noncarriers (P = 0.0015). In neutrophils, differentially expressed genes were significantly enriched in genes of the classical complement activation pathway. Future studies assessing affected cell types and pathways will show their contribution to generalized pustular psoriasis's pathogenesis and indicate whether findings can be transferred to the acute epidermal situation and whether depletion or inactivation of CD4 + cytotoxic T lymphocytes may be a reasonable therapeutic approach., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Generalized pustular psoriasis (GPP) is a rare, severe, potentially life-threatening, autoinflammatory, neutrophilic skin disease that may be accompanied by fever and leukocytosis. This paper describes the current state of knowledge on GPP in terms of classification, (differential) diagnosis and prevalence. We present a comparison of the genetics and pathoimmunology of GPP and psoriasis vulgaris with the central mechanisms of autoimmunology and autoinflammation. The currently available therapeutic options, expert recommendations for therapy, and data from early clinical trials investigating targeted therapies will be summarized. We present the results of our discussion with 13 experts for psoriasis vulgaris and GPP and give an integrated overview of indication and therapy based on our personal experience and present an outlook on further research questions. Collectively, this article highlights the high unmet need in GPP, as there exists no satisfactory method of diagnosis or treatment to date and new treatment options will be of great therapeutic benefit to those affected., (© 2022 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

There have been multiple systemic drugs approved for the therapy of psoriasis vulgaris and psoriasis arthritis (PsA) in the last decade. However, treatment decisions are difficult to make in women planning a pregnancy and in pregnant and lactating women due to the paucity of data for such cases. The strongest evidence for psoriasis therapy during pregnancy exists for topical corticosteroids. Medically controlled use of UVB-therapy is also considered safe. The best evidence regarding systemic therapy during pregnancy and lactation is available for the group of TNF-alpha inhibitors, which is also reflected in the respective medical product information. This is especially important in cases of psoriatic arthritis. Among traditional systemic therapeutics, the largest clinical experience exists for ciclosporin, which, if medically necessary, may be continued during gestation. However, TNF-alpha inhibitors, especially the pegylated form, should be preferred in case of pregnancy. Furthermore, an elective pregnancy termination is not necessary due to systemic therapy of psoriasis with many further substances during the first pregnancy weeks. The current work provides a comprehensive review of the scientific literature on treatment of psoriasis during pregnancy and lactation. Based on the available scientific information, severity of psoriasis and patient's comorbidities, the best possible therapeutic approach can be found in consensus with the patient., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Guselkumab is an anti-interleukin-23p19 monoclonal antibody approved as a first-line medication in patients with moderate-to-severe plaque-type psoriasis and second-line in active psoriatic arthritis. In the clinic, patients who have shown a lack of previous treatment efficacy and/or tolerability are often prescribed guselkumab. These patients generally have less severe psoriasis compared to clinical trial cohorts, reflected in lower Psoriasis Area and Severity Index (PASI). To evaluate treatment response in a real-world setting, we conducted a multicenter-retrospective chart review in three specialized dermatological centers. Seventy-four patients who received guselkumab treatment were included in the study and baseline characteristics were described. The mean PASI at baseline was 13.0 (± 6.7). After 12 weeks of treatment 40 patients could be followed up at the participating centers and efficacy was assessed: 72.5% of these patients achieved an absolute PASI ≤5 (55.0% ≤3; 42.5% ≤2) whereas only 57.5% of patients were able to gain a delta PASI reduction of at least 75%. Using the absolute PASI as a treatment goal rather than response rate revealed that guselkumab was highly effective in this real-world setting. In conclusion, the absolute PASI proved to be a more valuable tool to measure treatment outcome., (© 2021 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Introduction: Biologic switching is common in psoriasis patients with non-response to or adverse events under therapy with a biologic. However, evidence on efficacy of switching between newly approved biologics of similar mode of action is scarce. The objective was to assess the efficacy of treating psoriasis patients with an IL-17-receptor A antagonist after failure of any IL-17A antagonist and to identify predictors of treatment response., Methods: A retrospective multicenter chart review on psoriasis patients who received brodalumab after failure of ixekizumab or secukinumab therapy was conducted in five German University Medical centers., Results: Overall, 23 patients were identified. PASI75 response to brodalumab was reached by 47.8% (11/23) of all patients at week 12 and at week 24. 3 patients experienced mild adverse events which did not lead to drug discontinuation., Conclusions: Brodalumab appears to be an efficacious and safe treatment option in psoriasis patients with prior exposure to IL-17A antagonists.

Background: Moderate to severe plaque psoriasis can be treated effectively with immunomodulating biologicals such as the interleukin-17A inhibitor secukinumab. In practice, however, questions often arise as to how to proceed in special situations, such as infections, comorbidity, pregnancy, or surgery., Objectives: To address frequent questions about the treatment of plaque psoriasis with secukinumab in a consensus document of German psoriasis experts that supplements current guidelines., Methods: In a virtual expert meeting in May 2020, practical aspects of the treatment of psoriasis were discussed based on the experience of the participants and on current literature. The results of this discussion were summarized in the present consensus document., Results: This article provides practical guidance on case history, documentation of previous therapies, severity of psoriasis, and comorbidities before starting therapy with secukinumab. For patients treated with secukinumab, the course of action in case of vaccinations, chronic or acute infections, surgical interventions, special manifestations of psoriasis, and comorbidities including history of cancer and autoimmune disorders is discussed. Questions regarding family planning and health policy regulations are also addressed., Discussion: The recommendations for the treatment of psoriasis with secukinumab summarized in this consensus document may contribute to achieve optimal therapy for patients and to improve their quality of life., (© 2021. The Author(s).)

Background and Objectives: Depression is a highly prevalent comorbidity in psoriatic patients. The aim of this prospective study was to follow up psoriasis patients at risk for depression and to evaluate individual pathways to mental health care and the efficacy of depression screening in a real-life setting., Patients and Methods: In this prospective multicenter study, 355 patients with psoriasis were screened for depressive symptoms with the revised Beck Depression Inventory (BDI-II). General practitioners of patients at risk for depression were asked for further evaluation. One year later, information on mental health care provision was gathered., Results: 130 patients were screened positive for depressive symptoms, and 71 patients were followed-up (follow-up rate: 54.6 %). Psychiatric treatment was recommended for 28.2 % and accepted by 23.9 % of patients. Parameters of disease activity of psoriasis (PASI: 3.1, ∆: -1.7, P = 0.018), quality of life (Dermatology Life Quality Index [DLQI]: 6.5, ∆: -2.8, P = 0.005), and depressive symptoms (BDI-II: 13.2, ∆: -8.3, P < 0.001) improved significantly. Decrease of the BDI-II score was more pronounced in patients with higher PASI decrease., Conclusions: Screening for depressive symptoms led to increased utilization of mental health care and improvement of psoriasis, depressive symptoms, and quality of life. Thus, such screening should be implemented in routine care to optimize patient management., (© 2021 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background and Objectives: Documenting patient data in psoriasis clinical practice can improve care, but standardized and transparent documentation is rare. The current project aimed to develop a data set for the documentation of psoriasis in daily practice., Material and Methods: In four online Delphi rounds and one in-person meeting, 27 psoriasis experts allocated variables to a standard, an optimal and an optional data set. Most of the questions were standardized. Open questions were included to allow for the provision of reasons and to enlarge the data sets. Furthermore, in the in-person meeting we considered a) patients' attitudes and b) dermatologists' information on the current usage and acceptability in Germany., Results: The consensus approach resulted in a data set with 69 variables. The standard data set includes 20, the optimal data set 31 and the optional data set 18 variables. In summary, the data set can mainly be grouped into master data, general status and medical history data, medical history of psoriasis, status of psoriasis, diagnostics and comorbidity, therapies and patient-reported outcomes., Conclusions: The consensus recommendation of a standard, an optimal and an optional data set for routine care of psoriasis intends to be a decision-making aid and an orientation for both daily practice and further development of documentation systems., (© 2021 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Background: Palmoplantar pustulosis (PPP) is a chronic skin disease with painful erythematous scaly or crusty lesions and pustules on the palms and soles. Apremilast is a phosphodiesterase 4 inhibitor that has proven effective in the therapy of psoriasis, psoriatic arthritis and in oral ulcers associated with Behcet's disease., Objective: To explore the efficacy of apremilast in PPP., Methods: APLANTUS was a phase 2 single-arm multicentre study of apremilast in 21 subjects with moderate-to-severe PPP. Primary endpoint was the per cent change of the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at week 20 compared to baseline., Results: 20 weeks of oral treatment with apremilast in patients with moderate-to-severe PPP resulted in a significant decrease of the PPPASI with a median reduction of 57.1% (p < 0.001), and 61.9% of patients achieved at least a 50% improvement of the PPPASI relative to baseline. The total number of pustules per patient decreased significantly relative to baseline with 76.2% of patients achieving at least a 50% reduction in total pustules count at week 20. Improvement of PPP was also apparent in a significant decrease of the dermatologic life quality index (DLQI). The median DLQI score dropped from 8.5 at baseline to 2.0 at week 20 (p = 0.030). Apremilast was generally well tolerated, and no serious adverse events occurred., Conclusions: Patients with PPP treated with apremilast showed benefit both in objective and subjective disease parameters. Apremilast should be investigated further in this difficult-to-treat skin condition. EudraCT number: 2016-005122-11., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Apart from biologics, no systemic drugs are approved in Europe for children with moderate-to-severe psoriasis. Retrospective observational studies have shown promising results for fumaric acid esters (FAE) in this setting., Objectives: To show superiority of FAE over placebo in terms of treatment response after 20 weeks in children and adolescents aged 10-17 years., Methods: In a multicentre, randomized, double-blind, placebo-controlled phase IIIb study, patients aged 10-17 years with moderate-to-severe plaque psoriasis requiring systemic therapy were randomized 2 : 1 to receive FAE (n = 91) or placebo (n = 43) over 20 weeks, followed by an open-label FAE treatment phase. The coprimary endpoints were ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and Physician's Global Assessment (PGA) score of 0 or 1 (clear or almost clear) at week 20. The study was registered with EudraCT number 2012-000035-82., Results: At week 20, 55% [95% confidence interval (CI) 0·44-0·65] of FAE-treated patients achieved a PASI 75 response vs. 19% (95% CI 0·08-0·33) in the placebo group (absolute difference 36%, 95% CI 0·20-0·53; P < 0·001). In total, 42% (95% CI 0·32-0·53) in the FAE group vs. 7% (95% CI 0·01-0·19) in the placebo group achieved a PGA score of 0 or 1 at week 20 (absolute difference 35%, 95% CI 0·21-0·49; P < 0·001). During the double-blind period, drug-related adverse events occurred more frequently in patients receiving FAE compared with placebo (76% vs. 47%). Gastrointestinal disorders were the most common adverse events., Conclusions: FAE administered over a period of 20 weeks demonstrated a better response than placebo; the difference was statistically significant and clinically meaningful. Application up to 40 weeks was generally well tolerated. However, further studies are required., (© 2020 Biogen GmbH. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening inflammatory skin disease. Our aim was to assess patient and disease characteristics and analyze drug survival rates in the treatment of GPP in a real-life setting. In this retrospective study, 201 treatment series of 86 patients with GPP treated at five University Medical Centers were analyzed. Overall, excellent response was reached in 41.3% of all treatment courses, partial response in 31.4%, and nonresponse in 27.3%. Biological treatment was significantly more effective than non-biological therapies (excellent response: 47.4% vs 35.9%; P = .02). Overall, the median drug survival was 14.0 months (biologicals: 36.0 months vs nonbiologicals: 6.0 months; P < .001). The crude probability of survival was highest for secukinumab (hazard ratio [HR] of drug discontinuation compared with acitretin: 0.22), followed by ixekizumab and ustekinumab (HR: 0.38 each), adalimumab (HR: 0.59), etanercept (HR: 0.62), infliximab (HR: 0.69), cyclosporine (HR: 1.00), acitretin (reference for HR), fumaric acid esters (HR: 1.06), methotrexate (HR: 1.26), and apremilast (HR: 3.44); no drug discontinuation with guselkumab. Our results reveal high efficacy and drug survival, particularly for IL-17 and IL-(12)/23 antagonists. Thus, these biologics may be considered early in the therapeutic algorithm of GPP., (© 2021 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Background: Depression is frequently underdiagnosed and insufficiently treated in psoriatic patients in their daily routine. The aim of this study was to screen and analyze the impact of patient and disease characteristics on depression scores., Patients and Methods: In this cross-sectional multicenter cohort study, adult psoriasis patients were screened for depression with two validated tools: the Whooley questions and the revised Beck Depression Inventory (BDI-II)., Results: Overall, 538 patients (median PASI 3.0, mean DLQI 5.3) were screened for depressive symptoms (mean BDI-II score 8.3). 24.2 % of all participants reached a BDI-II score ≥ 13, suggesting a depression that was at least mild. The results of the Whooley questions were positive for 28.2 % of the patients. There was a strong correlation between the two tools (p < 0.001). In the subgroup with a BDI-II score ≥ 13, disease activity (median PASI 3.8 vs. 2.8, p = 0.06) and DLQI scores (mean 10.1 vs. 3.7, p < 0.0001) were higher, and psoriatic arthritis and diabetes were more prevalent (52.6 % vs. 37.8 %, p = 0.002, and 16.2 % vs. 10.0 %, p = 0.04, respectively) than in the subgroup with a BDI-II score < 13., Conclusions: In specialized psoriatic outpatient clinics, a BDI-II score ≥ 13 was present in almost every fourth patient despite a low median PASI. The Whooley questions might be easy to use as a screening tool for depression in psoriasis patients., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Generalized pustular psoriasis (GPP) is a severe multi-systemic inflammatory disease characterized by neutrophilic pustulosis and triggered by pro-inflammatory IL-36 cytokines in skin. While 19%-41% of affected individuals harbor bi-allelic mutations in IL36RN, the genetic cause is not known in most cases. To identify and characterize new pathways involved in the pathogenesis of GPP, we performed whole-exome sequencing in 31 individuals with GPP and demonstrated effects of mutations in MPO encoding the neutrophilic enzyme myeloperoxidase (MPO). We discovered eight MPO mutations resulting in MPO -deficiency in neutrophils and monocytes. MPO mutations, primarily those resulting in complete MPO deficiency, cumulatively associated with GPP (p = 1.85E-08; OR = 6.47). The number of mutant MPO alleles significantly differed between 82 affected individuals and >4,900 control subjects (p = 1.04E-09); this effect was stronger when including IL36RN mutations (1.48E-13) and correlated with a younger age of onset (p = 0.0018). The activity of four proteases, previously implicated as activating enzymes of IL-36 precursors, correlated with MPO deficiency. Phorbol-myristate-acetate-induced formation of neutrophil extracellular traps (NETs) was reduced in affected cells (p = 0.015), and phagocytosis assays in MPO-deficient mice and human cells revealed altered neutrophil function and impaired clearance of neutrophils by monocytes (efferocytosis) allowing prolonged neutrophil persistence in inflammatory skin. MPO mutations contribute significantly to GPP's pathogenesis. We implicate MPO as an inflammatory modulator in humans that regulates protease activity and NET formation and modifies efferocytosis. Our findings indicate possible implications for the application of MPO inhibitors in cardiovascular diseases. MPO and affected pathways represent attractive targets for inducing resolution of inflammation in neutrophil-mediated skin diseases., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Acrodermatitis continua of Hallopeau (ACH) is a rare chronic inflammatory skin disease. Treatment is extremely challenging and mostly based on empirics as there is only scarce evidence from case reports and few small case series. In this retrospective study, patients with ACH treated at five university medical centers were analyzed according to patient and disease characteristics and treatment experience. We identified 39 patients with ACH with a mean age of 54.4 years at onset, of whom 22 (56.4%) were female. A total of 115 systemic treatment courses were analyzed with methotrexate as the most common therapy (27.0%). Overall, effectiveness of systemic treatments was low (excellent response rate: 14.8%). Among non-biologics, excellent response was noted in 21.1% (4/19) of treatment courses with methotrexate, followed by acitretin (13.3%; 2/15). Among biologics, guselkumab (excellent response: 100%; 2/2), secukinumab (excellent response: 42.9%; 3/7) and adalimumab (excellent response: 20.0%; 2/10) were most efficacious. The median drug survival was 7.0 months and did not differ significantly between the subgroup of non-biologic and biologic therapies. To our knowledge, this is the largest case series in ACH investigating patient characteristics and treatment outcomes. Based on our treatment experience, we suggest a treatment algorithm starting with acitretin or methotrexate as first-line therapy, followed by biologics. Cyclosporin may be used for short-term control. However, none of the applied systemic therapies yielded satisfying efficacy in our cohort. In patients with primary non-response, switch of treatment should be evaluated timely on an individual basis, considering possible irreversible disease complications such as nail loss. More research with prospective design is needed to further evaluate traditional and also particularly newer antipsoriatic drugs in ACH., (© 2020 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

In Germany, approximately 2% of the population suffers from psoriasis, which is no longer considered only a cutaneous, but rather a systemic disease. Accordingly, common comorbidities and potential joint involvement in psoriasis must be recorded. If necessary, interdisciplinary patient care has to be organized. The use of validated scores is recommended to complete the patient's medical history. The individual treatment should include intensified topical therapies as well as short-term phototherapy in case of an acute phase. In addition to conventional systemic therapies (e.g., fumarates, methotrexate), a number of new therapeutics for psoriasis are in development. Apart from the PDE‑4 inhibitor apremilast, targeted therapies are currently available to block TNF-alpha, IL-17A, the IL-17 receptor and IL-23. Decisions on individualized, patient-centered psoriasis management should be based on assessment of disease severity and the existence of comorbidities. Furthermore, economic aspects should be taken into account.

Switching of biologic agents in treatment of plaque psoriasis is a common strategy. Only a few studies are available on switching between IL17A-blockers. In a retrospective study, we identified 22 psoriasis patients who, after failing secukinumab as a first IL17A-blocker received ixekizumab with an observation period of at least 24 weeks. At last observation 10/22 patients had a good response (PASI75 or PASI&lt;3) using ixekizumab therapy. None of five patients with primary non-response to secukinumab reached a good, durable response to ixekizumab. In conclusion, ixekizumab appears to be a therapeutic option as a second IL17A-blocker in psoriasis patients who did not show a primary non-response to secukinumab.

Psoriasis is a chronic inflammatory skin disease with a genetic and autoimmune background. The involvement of sex hormones as a trigger factor for psoriasis has been suspected. Recently, low serum testosterone has been associated with autoimmune diseases in males, and the role of testosterone in psoriasis is unknown. To investigate serum testosterone levels in male psoriasis patients compared to control individuals with regards to the severity of psoriasis. A total of 121 male psoriasis patients and 217 control individuals were enrolled. The severity of psoriasis was documented using the Psoriasis Area Severity Index (PASI). Serum testosterone, sex hormone binding globulin (SHBG), and albumin were analysed. Moreover, psoriasis medication and the incidence of metabolic syndrome were recorded. In 52.1% psoriasis patients, low total testosterone values were detected. Compared to the control cohort, total testosterone (tT) and free testosterone (fT) in psoriasis patients were significantly lower. Despite psoriasis-specific medication, there was a significant inverse correlation between tT or fT and PASI, irrespective of age above or below 40 years. Low tT levels also correlated with the prevalence of metabolic syndrome. Nevertheless, in psoriasis patients without metabolic syndrome, higher PASI (≥10) was associated with significantly lower tT values. In addition, low tT was associated with clinical symptoms of testosterone deficiency. Severe psoriasis is associated with low serum testosterone. However, further studies are required to investigate whether this observation is an epiphenomenon and whether testosterone substitution might decrease the severity of psoriasis.

Palmoplantar pustular psoriasis, also termed palmoplantar pustulosis (PPP), is a rare disease affecting the palmoplantar regions characterized by sterile, yellow to brown pustules mostly on erythematous skin. PPP is related to a high burden due to painful, impaired and stigmatizing character. Several isoforms of interleukin (IL) have been implicated in its pathophysiology. Here, we report on four patients with PPP treated with the novel IL-17 receptor A blocker brodalumab, in whom this therapy was not successful or showed moderate improvement combined with adverse events., (© 2019 Japanese Dermatological Association.)

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease-related to psoriasis. Its treatment is challenging, and little is known about the sustainability of different medications. The aim of this study was to analyze drug survival rates and drug discontinuation in the treatment of PPP under real-world conditions., Patients and Methods: Patients with PPP treated in the dermatology departments of five German university medical centers between 01/2005 and 08/2017 were included in our retrospective study. Drug survival of systemic therapies was assessed with Kaplan-Meier analysis and multivariate regression., Results: Overall, 347 patients with 935 treatment courses were identified. Within the group of non-biologic systemic agents, apremilast showed the highest median drug survival (15 months), followed by cyclosporine (12 months), the combination of acitretin and topical PUVA (9 months), MTX (8 months), acitretin monotherapy (6 months), alitretinoin (5 months), and fumaric acid esters (3 months). Among biologicals, the highest maintenance rate was detected for certolizumab pegol (restricted mean: 47.4 months), followed by infliximab (median: 26 months), golimumab (22 months), ustekinumab (21 months), adalimumab (18 months), secukinumab (9 months), and etanercept (8 months)., Conclusions: Biologicals and apremilast may serve as second-line options for treatment of PPP and should be further evaluated., (© 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Generalized pustular psoriasis (GPP) is a potentially life-threatening disease that can be attributed to mutations in IL36RN in a subgroup of patients. In small trials, interleukin (IL)-17A and IL-17RA antagonists have been shown to be effective in patients with generalized pustular psoriasis in Japan. We identified seven patients who received the IL-17A antagonists secukinumab (six cases) or ixekizumab (one case) in two dermatological centers. All patients showed a good or excellent clinical response. Anti-IL-17A therapy was well tolerated and ongoing in all patients after an average therapy duration of 12.9 months. Analysis of IL36RN mutation status was performed in six patients, one patient carried a heterozygous mutation, while the other five patients did not show a mutation in IL36RN. This is the first report of a successful treatment of GPP patients without IL36RN mutations responding to anti-IL-17A therapy., (© 2018 Japanese Dermatological Association.)

Background: Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles., Objective: To identify and characterize pathogenetic players in PPP., Methods: Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry., Results: Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1β and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1β and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin., Conclusions: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1β in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP)., Objectives: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN., Methods: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort., Results: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers., Conclusions: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Palmoplantar pustulosis (PPP) is a recalcitrant chronic inflammatory skin disease. Data relevant for the medical care of patients with PPP are scarce. Thus, the aim of this work was to investigate the disease burden, clinical characteristics, and comorbidity of PPP patients in Germany., Patients and Methods: PPP patients were examined in a crosssectional study at seven specialized psoriasis centers in Germany., Results: Of the 172 included patients with PPP, 79.1% were female and 69.8% were smokers.In addition, 25.0% suffered from psoriasis vulgaris, 28.2% had documented psoriatic arthritis, and 30.2% had a family history of psoriasis. In 77 patients the mean Dermatology Life Quality Index (DLQI) was 12.2 ± 7.7 (mean ± SD). The mean Psoriasis Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 12.6 ± 8.6. Mean body mass index was above average at 27.1 ± 5.5. The PPP patients had previously received an average of 2.6 ± 2.1 different anti-psoriatic systemic drugs or UV-therapies. The systemic drugs that had been used most frequently were corticosteroids in 40.1% of patients, followed by acitretin (37.8%), and methotrexate (27.9%). The PPPASI was 13.4 ± 8.9 in patients without current systemic therapy and 10.4 ± 7.9 in patients with systemic therapy., Conclusion: Many PPP patients had a concomitant diagnosis of psoriasis vulgaris and/or psoriatic arthritis or had a family history of psoriasis. Despite the fact that many of the patients were using anti-psoriatic therapies, there was still a high burden of disease within this PPP cohort. This insufficient control of symptoms demonstrates the urgent need for new PPP treatments.

Background: Methotrexate is one of the most commonly used systemic drugs for the treatment of moderate to severe psoriasis; however, high-quality evidence for its use is sparse and limited to use of oral dosing. We aimed to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis., Methods: We did this prospective, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (METOP) at 16 sites in Germany, France, the Netherlands, and the UK. Eligible patients were aged 18 years or older, had a diagnosis of chronic plaque psoriasis for at least 6 months before baseline, had currently moderate to severe disease, and were methotrexate treatment-naive. Participants were randomly assigned (3:1), via a computer-generated random number sequence integrated into an electronic data capture system, to receive either methotrexate at a starting dose of 17·5 mg/week or placebo for the first 16 weeks, followed by methotrexate treatment of all patients up to 52 weeks (methotrexate-methotrexate vs placebo-methotrexate groups). Dose escalation to 22·5 mg/week was allowed after 8 weeks of methotrexate treatment if patients had not achieved at least a 50% reduction in baseline Psoriasis Area and Severity Index score (PASI), with corresponding volume increases in placebo injections. Treatment was combined with folic acid 5 mg/week. Group allocation was concealed from participants and investigators from the time of randomisation until an interim database lock at week 16, and was open label from week 16 onwards, with no masking of participants or investigators. The primary efficacy endpoint was a 75% reduction in PASI score (PASI 75) from baseline to week 16. We did analysis by modified intention to treat, with non-responder imputation. This study is registered with EudraCT, number 2012-002716-10., Findings: Between Feb 22, 2013, and May 13, 2015, we randomly assigned 120 patients to receive methotrexate (n=91) or placebo (n=29). At week 16, a PASI 75 response was achieved in 37 (41%) patients in the methotrexate group compared with three (10%) patients in the placebo group (relative risk 3·93, 95% CI 1·31-11·81; p=0·0026). Subcutaneous methotrexate was generally well tolerated; no patients died or had serious infections, malignancies, or major adverse cardiovascular events. Serious adverse events were recorded in three (3%) patients who received methotrexate for the full 52 week treatment period., Interpretation: Our findings show a favourable 52 week risk-benefit profile of subcutaneous methotrexate in patients with psoriasis. The route of administration and the intensified dosing schedule should be considered when methotrexate is used in this patient group., Funding: Medac., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Psoriasis is a chronic skin disease with deregulation of proteins in the immune system. These proteins include members of the heterogeneous S100 family, which have been discussed as potential biomarkers for disease severity., Objective: The aim of this study was to evaluate the impact of S100A7, S100A8, S100A9 and S100A12 as possible markers for disease activity in patients with psoriasis skin disease., Patients and Methods: S100A7, S100A8, S100A9 and S100A12 mRNA expression was determined in the skin of patients with psoriasis and controls (N = 341) by gene expression analyses. In addition, S100 serum levels were investigated by ELISA in an independent cohort of psoriasis patients (i) untreated, with different manifestations (skin/joints), (ii) under treatment (etanercept) and (iii) healthy controls, (N = 55)., Results: All S100-subtypes included are significantly upregulated in psoriasis skin lesions when compared with atopic dermatitis, lichen ruber and healthy donors. In untreated psoriasis patients, S100A12-serum levels showed the closest association with disease activity (PASI) (r = 0.542; P < 0.01). Serum levels decreased under treatment with etanercept (P < 0.05)., Conclusion: Among the investigated S100-proteins, S100A12 showed the closest association with disease activity and therapeutic response and might therefore provide a valuable biomarker for psoriasis., (© 2015 European Academy of Dermatology and Venereology.)

A number of pustular skin diseases share clinical, pathogenetic, and epidemiological aspects with plaque-type psoriasis, and their classification as a separate clinical entity or as a subtype of psoriasis remains controversial, which is also reflected in the multitude of their names. They include generalized pustular psoriasis with its subtypes, acrodermatitis continua suppurativa (Hallopeau), acute pustulosis palmopantaris, palmoplantar pustular psoriasis, and pustular variants of a mostly TNF-blocker triggered paradoxical psoriasiform dermatitis. In this article, the epidemiology, clinical picture, pathogenesis, genetics, and therapy of these pustular skin diseases are described.

In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

Cyclosporine is an established therapy for psoriasis that provides rapid relief of symptoms but has long-term toxic side effects. The objective of this study was to demonstrate the efficacy of etanercept as replacement therapy for cyclosporine in patients with moderate-to-severe plaque psoriasis. Patients with plaque psoriasis were given cyclosporine 5 mg/kg/day until achievement of PASI50 at which point cyclosporine was tapered to 0 over 6 weeks. At week 6, patients were randomised (1:1) to receive etanercept (50 mg/week) or placebo for an additional 24 weeks. Patients in the etanercept group (n = 58) experienced a reduction of -1.1 in mean PASI score (p = 0.233 vs. cyclosporine) at week 30; patients in the placebo group (n = 62) had mean PASI increase of 3.7 (p < 0.001 vs. cyclosporine). The incidence of patients reporting any adverse events was not significant between groups (77% etanercept, 74% placebo; p = 0.675). Etanercept demonstrated higher efficacy and good tolerability as replacement therapy for cyclosporine in plaque psoriasis.

Background: In the literature as well as in existing psoriasis guidelines, only little evidence is available on combination regimens with systemic antipsoriatic agents. However, if systemic monotherapy is not efficacious enough to control the disease, a combination therapy might be necessary., Objective: To evaluate the use of fumaric acid esters (FAEs) in combination with other antipsoriatic agents in 6 specialized dermatological departments in Germany., Methods: A systematic retrospective chart review of patients receiving FAEs was performed., Results: A total of 17 cases of patients receiving FAEs combined with at least one other systemic therapy (methotrexate, acitretin, etanercept, cyclosporine, leflunomide and infliximab) to treat psoriasis or psoriatic arthritis were identified., Conclusion: FAEs can be combined in an off-label setting with conventional as well as biological agents to treat recalcitrant psoriasis or psoriatic arthritis. Safety monitoring should be taken seriously as no controlled data for these combination regimens exist., (© 2015 S. Karger AG, Basel.)

Background: Diseases of the scalp are a severe burden for affected patients because they are often visible, frequently pruritic and hard to treat. Therefore, a proper diagnosis is extremely important., Diagnosis: If the patient presents with erythematous, scaly skin lesions of the scalp, psoriasis has to be differentiated from atopic eczema, seborrheic eczema and contact eczema (allergic or toxic). The inspection of the entire body as well as a detailed history are essential for establishing the diagnosis., Therapy: Topical corticosteroids are the therapeutic agents of choice for all of these scalp diseases. In individual cases immunosuppressive systemic treatments may be required. Azole antimycotics are not only used for seborrheic dermatitis but may also be indicated for treatment of atopic dermatitis or psoriasis of the scalp., Objectives: This review provides an overview of the clinical differences between scalp psoriasis and the various forms of eczema and of their therapeutic options. It also highlights the differential diagnosis between toxic and allergic contact eczema of the scalp.

In contrast to the treatment of rheumatoid arthritis, there are few data in psoriasis vulgaris regarding the efficacy of combining tumor necrosis factor (TNF)-alpha inhibitors and methotrexate (MTX). Indeed, combination of MTX with different TNF-alpha inhibitors may enhance the therapeutic effects and reduce side effects because of less dosage of the single agent. The present authors present five cases in which low-dose MTX combined with TNF-alpha inhibitors led to impressive improvement in Psoriasis Area and Severity Index scores. Here, the present authors initiated very low-dose MTX treatment in addition to existing TNF-alpha inhibitor therapy to exhaust current therapy and prevent premature change of the biologic. These observations support the concept of combined treatment in recalcitrant cases of psoriasis, which need a systemically lifelong treatment when both first-line and second-line monotherapies fail to provide sufficient clinical response., (© 2013 Wiley Periodicals, Inc.)

Background: Monotherapy with TNF-α inhibitors does not always produce a sufficient response in psoriasis patients. Combinations of TNF-α antagonists such as adalimumab with systemic antipsoriatic therapies such as methotrexate are not approved for use in psoriasis, and the published data are scarce., Patients and Methods: The charts of 39 psoriasis patients from 6 dermatology departments were reviewed retrospectively. All patients were given adalimumbab with another systemic antipsoriatic drug., Results: Combination therapy with methotrexate was most common (n = 32), followed by acitretin (n = 4) and cyclosporine (n = 3). Combination therapy with methotrexate lasted 10.8 ± 11.2 months (mean), with cyclosporine for 6.8 ± 3.3 months, and with acitretin 12.9 ± 12.4 months. Combinations were effective in the majority of patients: 30/39 (76.9 %) had a good (n = 9) or excellent (n = 21) response. Two patients had a moderate response and 7 patients had a poor response and were switched to another treatment. Overall, safety was very good. Eighteen patients experienced 24 adverse events; none was severe and/or required hospitalization. Of these, 10/24 adverse events were infections, most often infections of the upper respiratory tract (n = 5), bronchitis (n = 2), and influenza (n = 1)., Conclusions: Combinations of adalimumab with traditional systemic antipsoriatic treatments offer a promising method for managing severe or recalcitrant psoriasis. More data are needed to determine the long-term safety and efficacy of these combinations., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Atopic dermatitis (AD) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases. It has been assumed for a long time that these diseases have a completely different background. Recent findings about the genetic, epidemiologic and pathophysiologic factors of both diseases have remarkably improved our knowledge about the complex mechanisms underlying AD and Pso. Beyond that, in view of these findings, the question arises, which similarities and differences between AD and Pso exist. In order to address this point, we provide an overview about the current knowledge in the field of AD and Pso.