Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis.

BACKGROUND: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients. METHODS: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot. RESULTS: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. CONCLUSION: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response.

Sex differences in adverse events from systemic treatments for psoriasis: A decade of insights from the Swiss Psoriasis Registry (SDNTT).

BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.

MicroRNA-125a-5p regulates the effect of Tregs on Th1 and Th17 through targeting ETS-1/STAT3 in psoriasis.

BACKGROUND: Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear. METHODS: The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo. RESULTS: miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells. CONCLUSIONS: miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.

Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts.

OBJECTIVE: A lack of representation in pivotal trials currently limits guidance for the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in psoriatic arthritis (PsA) patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with low vs high number of affected joints. METHODS: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or < 3 swollen joints or high joint count patients (HJC) with > =3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. RESULTS: 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC were less often on conventional synthetic (cs) DMARDs. Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC in both crude and adjusted analyses (Hazard Ratio (HR) 1.09 [0.76-1.58], p= 0.52). Furthermore, bDMARD retention was significantly better (HR 0.63 [0.47-0.85], p< 0.002) when administered with csDMARD co-therapy. CONCLUSIONS: Biological DMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count.

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition.

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.

Long-Term Effectiveness and Drug Survival of Apremilast in Treating Psoriasis: A Real-World Experience.

BACKGROUND: Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor used for the treatment of moderate to severe psoriasis. Long-term data on the effectiveness and drug survival of patients treated with apremilast are limited. OBJECTIVE: The aim of this study was to analyze the characteristics, effectiveness, and drug survival of patients treated with apremilast in a real-world setting. METHODS: We conducted a retrospective cohort study of patients with psoriasis who received at least 1 dose of apremilast between 2015 and 2018. We documented sex; age; type, duration, and severity (using Psoriasis Area Severity Index [PASI] and Dermatology Life Quality Index [DLQI]) of psoriasis; comorbidities; previous treatment modalities; adverse events; and reasons for therapy discontinuation. For drug survival, estimates and efficacy analysis with Kaplan-Meier statistics were used. RESULTS: The drug survival rate of the 93 reviewed patients was 69.5% at 6 months, 34.7% at 12 months, and 25.8% at 24 months after initiating therapy. The median survival duration was 8.0 months. Therapy was discontinued in 66.6 and 27.8% due to loss of efficacy and adverse events, respectively. At 24 months, 35.9% had achieved PASI75 response and 23.7% had achieved PASI90 response. Most observed adverse events were gastrointestinal issues, weight loss, and headache. CONCLUSIONS: Apremilast is an effective and well-tolerated therapy for patients with moderate to severe psoriasis, especially for patients with difficult-to-treat locations and/or contraindications to other biologics. Furthermore, apremilast was used for patients with a history of nonresponse to biologics and was favored for patients with relatively low PASI (<10) and a high DLQI.

Identification of proteins associated with development of psoriatic arthritis in peripheral blood mononuclear cells: a quantitative iTRAQ-based proteomics study.

BACKGROUND: Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. METHODS: We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. RESULTS: We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p < 0.05) in the comparison of all psoriatic patients versus healthy controls, PsO group versus healthy controls, PsA group versus healthy controls, and PsA group versus PsO group, respectively. Among these proteins, 14 proteins may represent promising biomarkers for PsA: SIRT2, NAA50, ARF6, ADPRHL2, SF3B6, SH3KBP1, UBA3, SCP2, RPS5, NUDT5, NCBP1, SYNE1, NDUFB7, HTATSF1. Furthermore, western blotting confirmed that SIRT2 expression was significantly higher in PBMCs from PsA patients than PsO and healthy controls, and was negatively correlated with the phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK; p = 0.006, r = - 0.582). CONCLUSIONS: This pilot study provided a broad characterization of the proteome of PBMCs in PsA as compared to PsO and healthy controls, which may help to provide prospective strategies for PsA diagnosis.

The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients.

BACKGROUND: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients' genetic background seems promising in its explanation. OBJECTIVES: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. METHODS: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. RESULTS: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245-0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280-0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). CONCLUSIONS: The CC ge-notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.

Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway.

Topical treatment is crucial for the successful management of plaque psoriasis. Topicals are used either as a stand-alone therapy for mild psoriasis or else in combination with UV or systemic treatment for moderate-to-severe disease. For the choice of a suitable topical treatment, the formulation matters and not just the active substances. This expert opinion paper was developed via a non-structured consensus process by Swiss dermatologists in hospitals and private practices to illustrate the current treatment options to general practitioners and dermatologists in Switzerland. Defining treatment goals together with the patient is crucial and increases treatment adherence. Patients' personal preferences and pre-existing experiences should be considered and their satisfaction with treatment and outcome regularly assessed. During the induction phase of "classical" mild-to-moderate psoriasis, the fixed combination of topical calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g once daily is frequently used for 4-8 weeks. During the maintenance phase, a twice weekly (proactive) management has proved to reduce the risk of relapse. Of the fixed combinations, Cal/BD aerosol foam is the most effective formulation. However, the individual choice of formulation should be based on a patient's preference and the location of the psoriatic plaques. Tailored recommendations are given for the topical management of specific areas (scalp, facial, intertriginous/genital, or palmoplantar lesions), certain symptoms (hyperkeratotic or hyperinflammatory forms) as well as during pregnancy or a period of breastfeeding. As concomitant basic therapy, several emollients are recommended. If topical treatment alone does not appear to be sufficient, the regimen should be escalated according to the Swiss S1-guideline for the systemic treatment of psoriasis.

Successful Treatment of Iatrogenic Cutaneous Siderosis with Pigment Lasers: A Retrospective Study in 15 Consecutive Patients.

Intravenous ferric carboxymaltose is increasingly used to treat iron deficiency. However, a common side-effect is paravenous extravasation of iron preparations, resulting in cutaneous siderosis. Quality-switched (QS) lasers and, recently, picosecond (PS) lasers have been used to treat these hyperpigmentations with variable success. The optimal treatment protocol remains unclear. The aims of this study were to assess the response of cutaneous siderosis to treatment with pigment lasers and to determine the optimal wavelength, number of treatment sessions and pulse duration. Fifteen patients with cutaneous siderosis on the arms were included. The effectiveness of laser treatment was evaluated using a 5-point standard Physician Global Assessment (PGA) grading system. Differences in continuous variables between distinct groups of patients were assessed with a Mann-Whitney U test. In all 15 patients clearance of at least 50% was obtained. In 12 patients, at least 75% of pigment was removed. In conclusion, pigment lasers are an effective and safe method to treat cutaneous siderosis.

Smoking does not Alter the Therapy Response to Systemic Anti-psoriatic Therapies: A Two-country, Multi-centre, Prospective, Non-interventional Study.

Psoriasis can involve the skin, joints, nails and cardiovascular system and result in a significant impairment in quality of life. Studies have shown a lower response rate to systemic anti-psoriatic therapies in smokers, and smoking is a trigger factor for psoriasis. The aim of this study was therefore to analyse the response to systemic therapies for psoriasis, with a focus on smoking. Prospectively collected data from patients with moderate to severe psoriasis included in the national psoriasis registries for Germany and Switzerland (PsoBest and SDNTT) were analysed. Therapy response was defined as reaching a Psoriasis Area and Severity Index (PASI) reduction of 75%, PASI ≤ 3 or Dermatology Life Quality Index (DLQI) ≤ 1. Out of 5,346 patients included in these registries, 1,264 met the inclusion criteria for this study. In the smoking group, 715 (60.6%) reached therapy response at month 3, compared with 358 (63.7%) in the non-smoking group (p ≤ 0.269), 659 (74.1%) vs. 330 (77%) reached therapy response at month 6 (p ≤ 0.097), and 504 (76.6%) vs. 272 (79.0%) at month 12 (p ≤ 0.611). Therefore, these data do not show that smoking affects the response rate of anti-psoriatic therapy after 3, 6 and 12 months.

Elevated levels of the antimicrobial peptide LL-37 in hidradenitis suppurativa are associated with a Th1/Th17 immune response.

Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL-37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL-37 in HS lesions, and therefore, the aim of this study was to compare levels of LL-37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL-37 in HS. We confirm an upregulation of the LL-37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL-37 in HS with the presence of T cells, macrophages, neutrophils, IFN-γ, IL-17, IL-23, TNF-α, IL-32 and IL-1ß. Mechanistically, LL-37 boosts the proliferation of unspecifically activated CD4+ T cells via an increased calcium signalling independent of antigen-presenting cells. Targeting LL-37 may therefore represent a new therapeutic option for the treatment of this recalcitrant disease, but it has to be kept in mind that LL-37 also has an antimicrobial function.

TNFα and IL-17A are differentially expressed in psoriasis-like vs eczema-like drug reactions to TNFα antagonists.

BACKGROUND: Tumor necrosis factor α (TNFα) blocking drugs are in use for a wide range of autoimmune disorders. In up to 5% of patients, this class of drugs produces puzzling cutaneous side effects that are the subject of this investigation, namely psoriasiform and eczema-like skin inflammation. These side effects can occur after any time of treatment and regardless of the underlying disorders. The exact pathophysiology is as yet unknown. METHODS: A total of 33 patients (19 female, average age 52 years) who had a cutaneous reaction to infliximab, adalimumab or etanercept were included. The type of inflammatory reaction was determined, and the corresponding cytokine expression was evaluated by immunohistochemistry for TNFα, IL-1ß, IL-22, IL-6, IL-17A, IL33, IL-8 and IL-36α (semi-quantitative grading system from - to ++++). In addition, RNA expression levels of IL-17A and TNFα were confirmed by quantitative real-time PCR. RESULTS: IL-17A (P < .039) and TNFα (P < .008) were expressed at significantly higher levels in psoriasis or pustular-like reactions (PPR) compared to eczematous-like reactions (ELR). There was no significant difference in the expression of IL-1ß, IL-22, IL-6, IL-33, IL-8 and IL-36α between PPR and ELR. CONCLUSION: TNFα and IL-17A are both cytokines known to be involved in psoriasis but less so in non-psoriasiform dermatitis or eczema. Therefore, their overexpression in PPR is plausible and suggests that the pathogenesis of PPR mirrors at least in part those of psoriasis. Further investigations will define the exact role of these cytokines in rare cutaneous side effects of anti-TNFα therapy. Our results suggest that IL-17A inhibition could be a therapeutic option in patients with anti-TNF induced psoriasis.

Development of psoriasis in IBD patients under TNF-antagonist therapy is associated neither with anti-TNF-antagonist antibodies nor trough levels.

BACKGROUND: The cause of anti-TNF-induced psoriasis is still unknown. OBJECTIVE: We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels. METHODS: In this case-control study we identified 23 patients (21 with Crohn's disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n = 20), adalimumab (ADA, n = 2), and certolizumab pegol (CZP, n= 1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis. RESULTS: Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p = 0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p = 0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6 µg/mL [IQR 0.9-5.5] vs. 3.4 µg/mL [IQR 1.4-8.1], p = 0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies. CONCLUSION: Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.

Prognostic markers in lentigo maligna patients treated with imiquimod cream: A long-term follow-up study.

BACKGROUND: More data are needed to define factors that predict long-term success after imiquimod therapy for lentigo maligna (LM). OBJECTIVE: We sought to determine the demographic, clinical, and histologic prognostic markers of relapse-free survival in patients with LM who were treated with imiquimod. METHODS: This was a single-arm, open-label, nonrandomized, prospective study. RESULTS: Eighty-nine patients with histologically confirmed LM and a median follow-up time of 4.8 years after imiquimod treatment were included in our study. Sixteen patients (18%) relapsed. Statistically significant indicators of an increased risk of local recurrence included: the total number of melanocytes, the number of basal and suprabasal melanocytes and the number of pagetoid spreading melanocytes. LIMITATIONS: Our study was a single-center, nonrandomized study. CONCLUSION: An assessment of different melanocyte fractions in the diagnostic baseline biopsy specimen may help to predict the response of LM to imiquimod therapy.

Ingenol Mebutate for Lentigo Maligna: A Case Report.

BACKGROUND: Lentigo maligna (LM) is a melanoma in situ on sun-damaged skin, with a strong predilection to the head and neck area of the elderly. Many therapeutic modalities have been proposed in the treatment of this pathology, including surgery, cryotherapy, radiotherapy and topical imiquimod. Up to date surgical excision remains the treatment of choice with the lowest recurrence rate. Recently, a new topical treatment with ingenol mebutate has been described to be efficacious and well tolerated in the treatment of melanoma in situ. OBJECTIVE: We sought to demonstrate that ingenol mebutate might be an efficacious and well-tolerated treatment in a patient suffering from LM on an aesthetically challenging location. METHODS: Case report. RESULTS: After therapeutic failure with imiquimod 5% cream, a new topical treatment with ingenol mebutate gel 0.015% once daily on 3 consecutive days was initiated. Despite visible inflammation, no macroscopic lesion clearance was observed. While the first follow-up using reflectance confocal microscopy (RCM) performed at 6 weeks after the completion of the therapy showed no signs of LM, the second follow-up examination at 12 weeks using RCM and biopsy confirmed recurrence of the lesion. CONCLUSION: Ingenol mebutate cannot be considered a standard treatment modality for all types of LM. Further studies are needed to evaluate the prerequisites that can ensure therapeutic success.

Swiss S1 Guidelines on the Systemic Treatment of Psoriasis Vulgaris.

Psoriasis vulgaris is a common, chronic inflammatory skin disease with a prevalence of 1.5-2% in Western industrialized countries. A relevant percentage of patients suffer from moderate-to-severe psoriasis and experience a significant reduction in quality of life. The choice of an adequate therapy could help to prevent disease and exacerbation of comorbidity, which could increase quality of life, avoid hospitalization and avoid reduction of working days. The present guidelines are focused on the initiation and management of systemic therapies in cases of moderate-to-severe plaque-type psoriasis in adults to optimize treatment response, adherence and quality of life. This first version of the Swiss S1 guidelines presents therapeutic recommendations which are based on a systematic literature search as well as an informal expert consensus of dermatologists in Switzerland.