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Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant keratosis. This led to introducing the term autoinflammatory keratinization diseases encompassing entities in which monogenic mutations cause spontaneous activation of the innate immunity and subsequent disruption of the keratinization process. Originally, autoinflammatory keratinization diseases were attributed to pathogenic variants of CARD14 (generalized pustular psoriasis with concomitant psoriasis vulgaris, palmoplantar pustulosis, type V pityriasis rubra pilaris), IL36RN (generalized pustular psoriasis without concomitant psoriasis vulgaris, impetigo herpetiformis, acrodermatitis continua of Hallopeau), NLRP1 (familial forms of keratosis lichenoides chronica), and genes of the mevalonate pathway, i.e., MVK, PMVK, MVD, and FDPS (porokeratosis). Since then, endotypes underlying novel entities matching the concept of autoinflammatory keratinization diseases have been discovered (mutations of JAK1, POMP, and EGFR). This review describes the concept and pathophysiology of autoinflammatory keratinization diseases and outlines the characteristic clinical features of the associated entities. Furthermore, a novel term for NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) describing the spectrum of autoinflammatory keratinization diseases secondary to NLRP1 mutations is proposed., (© 2023. The Author(s).)

Introduction: Scalp psoriasis frequently goes with other disease location and may lead to a significant burden and impairment of quality of life (QoL). Adherence to local treatments is a frequent problem. A keratolytic and hydrating shampoo containing 2% salicylic acid, 5% urea, and 1% glycerin (active shampoo) has been developed for psoriasis-prone scalp., Objective: To assess the efficacy and tolerability of an active shampoo in subjects with mild to moderate scalp psoriasis., Materials and Methods: A single-center, randomized, double-blind, vehicle-controlled study was conducted on 67 adults with mild to moderate psoriasis. The active shampoo or its vehicle were applied daily for 14 days and 3 times/week for another 14 days. Assessments included the Psoriasis Scalp Severity Index (PSSI), Investigator Global Assessment (IGA), calculated total surface affected hair, scalp greasiness, irritation, and assessed scalp dermatitis-specific quality-of-life issues using SCALPDEX and product acceptability., Results: The active shampoo significantly (p < 0.05) reduced the PSSI by 39.0%, 37.2%, 63.0%, and 69.0% immediately after washing compared to a 22.8%, 5.5%, 19.6%, and 13.0% with the vehicle at Days 1, 8, 15, and 30, respectively. SCALPDEX items, IGA, and irritation significantly (p < 0.05) reduced with the active shampoo. Hair and scalp greasiness improved continuously with both products until Day 21. Subject-reported symptom scores paralleled the positive evolution of clinical signs. The active shampoo was well tolerated, subjects were highly satisfied and had an improved QoL., Conclusion: The active shampoo significantly improved clinical signs, symptoms, and QoL of mild-to-moderate scalp psoriasis compared to the vehicle. It was very well tolerated and highly appreciated by the subjects., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Background: The common inflammatory scalp diseases, such as psoriasis, seborrheic dermatitis, lichen planopilaris, discoid lupus erythematosus, contact dermatitis, or pemphigus may share similar clinical features., Objective: To identify and systematically review the available evidence on the accuracy of trichoscopy in inflammatory scalp disorders., Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 articles were included in the analysis., Results: The following trichoscopy features were found to show the highest specificity for the respective diseases: in psoriasis: diffuse scaling, simple and twisted red loops, red dots and globules, and glomerular vessels; in seborrheic dermatitis: atypical vessels, thin arborizing vessels, and structureless red areas; in discoid lupus erythematosus: follicular plugs and erythema encircling follicles; in lichen planopilaris: milky red areas or fibrotic patches; in contact dermatitis: twisted red loops; in pemphigus foliaceus: white polygonal structures and serpentine vessels; in pemphigus vulgaris: red dots with whitish halo and lace-like vessels; and in dermatomyositis: lake-like vascular structures., Limitations: Different nomenclature and variability in parameters, which were analyzed in different studies., Conclusion: This systemic analysis indicates that trichoscopy may be used with high accuracy in the differential diagnosis of inflammatory scalp diseases., (© 2021 S. Karger AG, Basel.)

Introduction: Literature data on dermoscopic features of psoriasis vulgaris are inconsistent. The aim of the study was to evaluate whether dermoscopic features of psoriatic plaques differ with anatomic location or any clinical characteristics., Materials and Methods: Clinical evaluation and videodermoscopy of psoriatic plaques located on the face, chest, abdomen, forearms, lower legs, back, and scalp were performed in 50 patients with psoriasis vulgaris., Results: A total of 306 plaques were evaluated. Videodermoscopy with a 20-fold magnification revealed red dots and globules in 306/306 (100%) plaques, arranged in diffuse (170/306, 56%), patchy (117/306, 38%), or polygonal (19/306, 6%) pattern. A 70 fold magnification of these vessels revealed the presence of bushy vessels (213/306, 70%) and twisted loops (107/306, 35%), with the latter occurring more commonly on the scalp and face (P < .001). In lesions lasting less or equal 5 weeks on forearms and scalp, patchy distribution of the scale predominated, whereas in older lesions-diffuse type (forearm P = .005, scalp P = .017). Diffuse distribution of the scale in lesions located on the face was more common in women, than men (P = .003)., Conclusions: Videodermoscopic picture of psoriatic plaques may differ with the anatomic location and duration of the psoriatic plaque and with patient's sex., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Palmoplantar pustulosis (PPP) is a chronic, recurrent skin disease belonging to the spectrum of psoriasis. It is characterized by an eruption of sterile pustules on the palms and soles. Recent studies in PPP have focused on genetic differences between pustular phenotypes and the role of the innate immunological system and the microbiome in the etiopathogenesis of the disease. Mutations in IL36RN (a major predisposing factor for generalized pustular psoriasis) were found in selected patients with PPP and were associated with earlier disease onset. Studies have shown that the interleukin (IL)-17 and IL-36 pathways might be involved in the pathogenesis of PPP. A microbiome has been demonstrated in the vesicopustules of PPP, and an abundance of Staphylococcus appears to be increased by smoking. Improved understanding of the underlying etiopathogenesis of PPP has led to advances in treatment options, and targeted therapies for PPP have been evaluated or are under evaluation against more than 12 molecules in ongoing clinical trials. These targets include CXCR2 (IL-8 receptor type B), granulocyte colony-stimulating factor receptor, IL-1 receptor, IL-8, IL-12, IL-23, IL-17A, IL-17 receptor, IL-36 receptor, phosphodiesterase-4, and tumor necrosis factor-α.

Background: Gut dysbiosis and increased intestinal permeability play a significant role in the pathogenesis of psoriasis and its comorbidities. Claudin-3 is a key component of tight junctions, which may serve as marker of gut barrier integrity., Objectives: The aim of the study was to investigate circulating plasma claudin-3 in patients with psoriasis and to evaluate clinical and metabolic factors, which determine its concentration., Methods: This cross-sectional study included 60 patients with psoriasis (39 men and 21 women, mean age: 45.6 ± 12.1 years) and 30 healthy controls (18 men and 12 women, mean age: 46.3 ± 15.5 years) age, sex and body mass index-matched. Plasma claudin-3 concentration was measured using an enzyme-linked immunosorbent assay., Results: Plasma claudin-3 concentration was significantly higher in patients with psoriasis in comparison with healthy control [median (interquartile range), 50.7 ng/mL (47.3-54.2) vs. 43.3 ng/mL (42.3-44.2), P < 0.001]. Patients who achieved ΔPASI90 response after 16 weeks of treatment showed tendency to decrease in circulating claudin-3 plasma concentration. Positive correlations between claudin-3 concentration and the PASI score (r = 0.828; P < 0.001) as well as claudin-3 and neutrophil-to-lymphocyte ratio (r = 0.847; P < 0.001) were found. A multivariable linear regression analysis confirmed association of claudin-3 with the PASI score (P < 0.001), neutrophil-to-lymphocyte ratio (P < 0.01) and active smoking (P < 0.05)., Conclusion: Claudin-3, a biomarker for gut permeability, is increased in psoriasis and correlates with disease severity and smoking. Further investigations are needed to determine whether reinforcing intestinal barrier may be a new therapeutic target in psoriasis., (© 2019 European Academy of Dermatology and Venereology.)

Psoriasis has been linked to several comorbidities, including metabolic syndrome, atopy, and celiac disease. However, the association between immune thrombocytopenia and psoriasis has rarely been described. We report the case of an adolescent with severe psoriasis and concomitant immune thrombocytopenia who obtained remission during treatment with adalimumab. Increased concentration of tumor necrosis factor-α seems to be a pathogenic linkage and therapeutic target for both diseases.

Dermoscopy is a non-invasive in-office method, which enables the diagnosis of many dermatoses and reduces the need for performing biopsies. To date, no systematic review about the diagnostic usability of dermoscopy in psoriasis has been available. The objective of this article was to summarize and critically analyse literature data on the dermoscopy of skin, scalp and nail changes in psoriasis. A systematic search of three medical databases was performed. A total of 45 articles were included into the analysis. Cutaneous psoriatic lesions assessed in all studies at a low magnification showed regularly distributed red dots. At a 50-fold or higher magnification capillary bushes (glomerular vessels) with a diameter range of 50-146 μm were observed. The background colour was described as reddish or pinkish with white or yellowish scales. The most frequent dermoscopic (trichoscopic) feature of scalp psoriasis was the presence of red dots/globules and twisted red loops. Typical dermoscopic (onychoscopic) signs of nail psoriasis were onycholysis, salmon patches and splinter haemorrhages. There is an accumulating body of evidence that dermoscopy (both handheld and videodermoscopy) is a useful tool in differential diagnosis in doubtful cases of psoriasis of the skin, scalp, nails, palms, soles and genital regions., (© 2018 European Academy of Dermatology and Venereology.)

Psoriasis is a chronic inflammatory systemic disease. Growing evidence suggests that human homeostasis depends on a mutualistic relationship with gut bacteria that produce a number of biologically active compounds. Therefore, enteric microbiota dysbiosis with gut barrier disruption may be an important factor in the development of chronic inflammatory diseases. The aim of our study was to assess non-invasive markers of intestinal barrier integrity in patients with moderate to severe psoriasis. Concentrations of claudin-3 (intestinal epithelial tight junction structure) and intestinal fatty acid binding protein (I-FABP; marker of enterocyte damage) were determined in the blood of patients with chronic plaque psoriasis (n = 20) and healthy individuals (n = 20) using commercially available enzyme-linked immunoassay test kits. Claudin-3 concentration was higher in patients with psoriasis compared with healthy control (median, 54.07 vs 42.36 ng/mL; P < 0.001). Patients with psoriasis also had elevated concentration of plasma I-FABP (median, 708.8 vs 147.1 pg/mL; P < 0.05). Our results support the hypothesis that dysfunction of the intestinal barrier in psoriasis disturbs the homeostatic equilibrium between the microbiota and immune system. Further studies are needed in order to develop new therapeutic interventions based on modulation of intestinal permeability., (© 2018 Japanese Dermatological Association.)

The aim of this prospective study was to analyze comorbidities in patients with palmoplantar pustulosis (PPP). The current study comprised 63 consecutive patients with palmoplantar pustulosis. The control group consisted of 37 patients with psoriasis vulgaris (PSV). The study included a standardized anamnesis, a clinical examination, blood tests for thyroid hormones, as well as calcium, magnesium, antiendomysial antibody, and patch tests. Hypertension was observed in 28/63 (44.44%) patients with PPP. Eight (12.7%) had ischaemic heart disease, and 7/63 (11.11%) had type 2 diabetes mellitus. There was no statistically significant difference between the patients with PPP and those in the control group. Metabolic syndrome was diagnosed in 19/63 (30.16%) patients with PPP and in 12/37 (32.43%) patients with PSV. Thyroid disease was more prevalent among patients with PPP in comparison to patients with PSV (31.75% vs. 13.51%; p=0.0421). Body mass index was statistically significantly higher in patients with PSV (28.25 vs. 25.86 kg/m², p=0.0144). BMI was higher than 25 kg/m2 in 18.03% patients with PPP and 26.47% patients with PSV (p=0.333). Positive patch tests were observed in 12/39 (30.77%) patients with PPP. The most common allergens were nickel chloride (5/12, 41.67%) and fragrances (5/12, 41.67%). In the control group, patch tests were positive in 2/11 (18.18%) cases (p<0.05). Patients with PPP, like patients with PSV, often presented with hypertension and metabolic syndrome. Given that many studies have focused on cardiovascular risk in PSV, there is a need for further research on the association between PPP and cardiovascular risk. In addition, patients resistant to PPP treatment should be screened for contact allergies.

Although fungal colonization is implicated in the pathogenesis of psoriasis, its prevalence remains unclear. The aim of this systematic review and meta-analysis was to provide an overview on the prevalence of Candida species in patients with psoriasis. We searched databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and http://clinicaltrials.gov) to identify studies involving subjects of any age with an established diagnosis of psoriasis and healthy controls, who were tested for carriage of Candida spp. on the skin or mucosal membranes (or saliva and stool), or presented with clinical candidiasis with microbiologically confirmed etiology. We identified nine cross-sectional studies including a total of 1038 subjects with psoriasis (psoriatics) and 669 controls. We found Candida species detection rates for psoriatics were significantly higher than those in the controls, especially in the oral mucosa milieux. These results suggest psoriasis may be one of the systemic diseases that predispose to oral Candida spp. carriage and infection.

Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of individuals worldwide. An improved understanding of the pathogenesis of psoriasis has led to the development of targeted biologic therapies. Briakinumab (ABT-874) is a recombinant human antibody that blocks the biological activity of the cytokines interleukin (IL)-12 and IL-23 through their shared subunit p40. IL-12 and IL-23 are key mediators in T-cell differentiation and have been shown to play a significant role in maintaining inflammation and abnormal keratinocyte function in psoriasis patients through development and stimulation of Th1 and Th17 subsets, respectively. In one phase II and four phase III studies (including two 52-week trials), the Psoriasis Area and Severity Index (PASI)-75 score at weeks 12 and 52 was achieved by at least 80.6% and 66.2% (p < 0.001) of patients receiving more than one dose of briakinumab every 4 weeks, respectively, with high proportions of patients achieving PASI-90 and PASI-100 scores (at least 55.4% and 28.8%, respectively; p < 0.001). These studies indicate safety and tolerance of briakinumab therapy for patients with moderate-to-severe chronic plaque psoriasis. In one clinical trial, therapy was associated with increased incidence of major cardiac events. Available results from two briakinumab trials show its positive impact on health-related quality of life. However, the manufacturer has now withdrawn the application in the EU and US.

Interleukin (IL)-23 is an important regulator of T helper-17 lymphocytes, which influence the cutaneous immune system by production of IL-17 and several other proinflammatory cytokines. This pathway has been recently linked to the pathogenesis of psoriasis and numerous other skin diseases. A newly developed biologic drug, ustekinumab (CNTO-1275), which targets the p40 subunit of IL-12 and IL-23, was approved by the US FDA and the European Medicines Agency in 2009 for the treatment of moderate to severe psoriasis. Administered as subcutaneous injections of 45 mg at weeks 0 and 4, and then every 12 weeks, ustekinumab produces a 75% improvement in the Psoriasis Area and Severity Index (PASI) in 66.4-75.7% of patients and a Dermatology Life Quality Index (DLQI) score of 0 or 1 in 55-56% of patients after 12 weeks of therapy. A recent clinical trial also indicates the possible efficacy of ustekinumab in psoriatic arthritis. The proportion of patients who had at least one adverse event through 12 weeks in clinical studies was 51.6-57.6% in the ustekinumab group and 50.4% in the placebo group. Serious adverse events were observed in 1.4-1.6% of patients treated with ustekinumab and in 1.4% of patients receiving placebo. Injection-site reactions occurred in 1-2% of patients and 5% of patients developed anti-ustekinumab antibodies. Further studies are needed to evaluate the long-term efficacy and safety of ustekinumab. Another biologic drug that targets the same molecules, briakinumab (ABT-874), has recently had its approval application withdrawn in the US and Europe to conduct further analysis and clinical trials. The company plans resubmission at a later date. Other IL-23 pathway inhibitors in the pipeline include anti-p19 monoclonal antibody and apilimod (STA-5326), which interfere with IL-23 activity, as well as secukinumab (AIN-457), LY-2439821, and AMG-827, which exhibit their activity at other targets of the IL-23 pathway.

Aim: There are some reports about the relatively frequent occurrence of depression in the case of psoriasis and some hypothesis about interactions between those two diseases. However there are no studies verifying those hypothesis based on reliable structured psychiatric interviews according to the current diagnostic criteria of mental disorders. The aim of the study was to compare the frequency of depression in patients suffering from psoriasis and from other chronic skin diseases with the use of a structured questionnaire for the diagnosis of the main mental disorders Mini International Neuropsychiatric Interview., Method: 32 consecutive outpatients (9 males and 23 females), age M = 43.9 with psoriasis were examined by a team of dermatologists, psychiatrists and a psychologist using a standard set of methods. In addition, 32 patients with other chronically occurring skin diseases, including 11 males and 21 females, age M = 31.6, were also examined and formed the control group. RESULTS; The point prevalence of mental disorders was significantly higher in the psoriatic group--20 (62.5%) versus 5 (15.62%) in the control group (p < 0.001). In all of the cases, affective disorders were diagnosed. Mild anxiety disorders were additionally found in 10 psoriatic patients (31.25%) and in 2 controls (6.25%) (p < 0.001). The level of depression was much higher in the study group than in the control group, both in the Beck Depression Inventory (M = 15.28, SD = 8.72 versus M = 8.13, SD = 6.31, p < 0.001 respectively) and in the Hamilton Rating Scale for Depression (M = 9.63, SD = 5.71 versus M = 5.09, SD = 4.26, p < 0.001 respectively). The neurotic symptoms measured by the Symptoms Check List-II by Aleksandrowicz were also significantly more intense in the psoriatic group (M = 54.37; SD = 40.99) than in the control group (M = 35.28; SD 23.96) (F = 8.55, p < 0.005)., Conclusion: The results imply the need for the careful examination of the mental state of patients with psoriasis in order to offer and provide treatment of any concomitant psychiatric conditions.

Adalimumab is a biological agent, one of the tumour necrosis factor-alpha inhibitors. Pivotal studies evaluating its efficacy in plaque psoriasis (CHAMPION, REVEAL) and psoriatic arthritis (PsA) (ADEPT) were carried out in recent years. Adalimumab proved highly effective in psoriasis patients and in PsA patients previously unresponsive to nonsteroidal anti-inflammatory drugs. Results of smaller studies suggest therapy with the drug may be successful in psoriasis resistant to other biologics and PsA unresponsive to disease-modifying antirheumatic drugs. Adalimumab has also been shown to improve patients' quality of life significantly. Although they should be further extended as far as dermatological conditions are concerned, available data indicate adalimumab is safe and well tolerated. Numerous case reports featuring its off-label use suggest the drug could be helpful in treating hidradenitis suppurativa, pyoderma gangrenosum, Sweet's syndrome, cutaneous sarcoidosis, pemphigus, systemic vasculitides, multicentric reticulohistiocytosis and stomatitis.

The recent approval of several monoclonal antibodies in dermatological treatment in recent years appears to be only only the phase in development of monoclonal antibody therapy for skin diseases. Several analyses point to the growth of the market for these drugs, and forecast an even higher expansion of the use of monoclonal antibodies in dermatologic therapy. The possible application of several monoclonal antibodies, including, adalimumab, efalizumab, infliximab, rituximab, in skin diseases is discussed.