Search Results (25)

Tyrosine kinase 2 (TYK2) mediates the signaling pathways of proinflammatory cytokines such as interleukin (IL)-12, IL-23, and type I interferons (IFNs) and plays a pivotal role in the pathogenesis of psoriasis and various other immune-mediated diseases. Deucravacitinib, a selective oral TYK2 inhibitor, has been approved for the treatment of psoriasis and demonstrated high efficacy and a favorable safety profile. This review summarizes the potential for expanding deucravacitinib indications based on case reports, clinical trials, and preclinical studies. Diseases in which TYK2 pathway has been demonstrated to be involved and for which clinical benefit of deucravacitinib has been reported include discoid lupus erythematosus, systemic lupus erythematosus, alopecia areata, lichen planus, palmoplantar pustulosis, psoriatic arthritis, systemic sclerosis, interstitial pneumonia, inflammatory bowel disease, and chronic recurrent multifocal osteomyelitis. Furthermore, emerging research suggests potential therapeutic applications in neurodegenerative diseases such as Alzheimer’s disease, and malignancies such as type 1 diabetes, vascular calcification in chronic kidney disease, T-cell acute lymphoblastic leukemia, and multiple sclerosis. Deucravacitinib may exert therapeutic effects by broadly suppressing cytokine signaling in a diverse range of inflammatory disorders. Ongoing clinical trials and mechanistic studies are required to clarify the efficacy and support its future indications. Full article

Background and Objectives: Psoriasis and atopic dermatitis (AD) are immune-mediated inflammatory diseases traditionally viewed as distinct. However, a subset of patients may present with overlapping features, leading to diagnostic and therapeutic challenges. This study aims to characterize the clinical, histopathological, and therapeutic features of patients with psoriasis–AD overlap. Materials and Methods: A retrospective review was conducted on patients diagnosed with both psoriasis vulgaris and AD between January 2021 and October 2024 at a single tertiary dermatology center. Inclusion required histopathological confirmation of psoriasis and a clinical diagnosis of AD based on Hanifin and Rajka criteria. Clinical features, histopathology, treatment history, and 6-month outcomes were analyzed. Results: Out of 469 patients screened, 24 (5.1%) had both conditions. Psoriasis preceded AD in 91.6% of cases. Most patients had intrinsic AD subtypes and moderate-to-severe diseases. Palmoplantar involvement was present in 66.6%, often refractory to biologics alone. Histological overlap complicated diagnosis, with repeated biopsies required in 58.3% of cases. Patients with dual diseases often required combination therapy, and JAK inhibitors showed favorable outcomes in refractory cases. Conclusions: Psoriasis–AD overlap represents a distinct clinical entity requiring individualized diagnosis and management. Recognition of this phenotype is critical for optimizing therapeutic outcomes. Full article

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterized by recurrent pustules, erythema, and scaling on the palms and soles, leading to a significantly reduced quality of life. Although PPP shares some immunopathological features with psoriasis vulgaris, it is distinguished by unique genetic predispositions, including a higher prevalence in East Asian populations, and a complex immune profile, particularly dysregulation of the IL-23/Th17 axis and IL-36 cytokines. Recent advances in psoriasis treatment have highlighted IL-23 inhibitors, which target the p19 subunit to suppress Th17 activation and inflammatory cytokines. Clinical trials show that IL-23 inhibitors significantly improve disease severity and patient-reported outcomes in PPP while maintaining favorable safety profiles. Notably, guselkumab and risankizumab have recently been approved for PPP treatment in Japan and Korea. In contrast, IL-17 inhibitors and IL-36 blockers have yielded mixed results. A recent phase 3 trial in Japan demonstrated the significant efficacy of apremilast in treating PPP, with a favorable safety profile, suggesting that apremilast may be a promising treatment option for PPP. Due to PPP’s lower prevalence compared with psoriasis vulgaris, clinical trials remain limited. Further large-scale, controlled studies are needed to clarify the efficacy and long-term safety of these therapies in diverse populations. This review summarizes emerging evidence on IL-23 inhibitors and other treatments for PPP, detailing their mechanisms of action, clinical efficacy, safety profiles, current challenges, and future perspectives in optimizing therapy. Full article

Deucravacitinib is an allosteric, selective tyrosine kinase 2 (TYK2) inhibitor that has demonstrated significant efficacy in the treatment of psoriasis. TYK2, a member of the Janus kinase (JAK) family, plays a critical role in intracellular signaling pathways for pro-inflammatory cytokines. Unlike traditional JAK inhibitors, which target active domains, deucravacitinib selectively binds to the pseudokinase domain of TYK2. This binding induces a conformational change that locks the enzyme in an inactive state, ensuring superior selectivity for TYK2 over JAK 1/2/3. This unique mechanism specifically inhibits key pro-inflammatory cytokines, including IL-12, IL-23, and type I interferons, critical in the pathogenesis of psoriasis and other immune-mediated diseases. As a result, deucravacitinib represents a promising option for targeted therapy in immune-mediated diseases and may reduce adverse events commonly associated with broader immunosuppressive treatments. Furthermore, its oral administration offers a convenient alternative to injectable biologics, potentially improving patient adherence and treatment satisfaction. This review highlights recent studies suggesting that deucravacitinib may also have therapeutic benefits in psoriatic arthritis, palmoplantar pustulosis, systemic lupus erythematosus, Sjogren’s disease, and inflammatory bowel disease. Given its expanding therapeutic potential, deucravacitinib may provide a safer and more effective alternative to current therapies, offering a tailored approach to treatment. Full article

Synovitis–acne–pustulosis–hyperostosis–osteitis (SAPHO) syndrome is a rare disease characterized by a sterile inflammatory osteitis and/or arthritis associated with a wide range of dermatological manifestations, such as acne, palmoplantar pustulosis, and psoriasis. This review, providing up-to-date knowledge on this disease, aims at informing researchers and clinicians to help them program future studies in order to improve patients’ care. Due to the vast clinical heterogeneity that characterizes this disease, SAPHO syndrome has received various names; among these, chronic recurrent multifocal osteomyelitis represents the most used one. The various nomenclatures in use also reflect different approaches to its management. Indeed, considering the world-wide distribution and the vast onset age (from children to late adulthood), in addition to the multiform clinical presentation, its diagnosis and treatment are often challenging for clinicians. In this review, we provide valuable insights on SAPHO syndrome, delving into its many aspects: epidemiology, pathogenesis, clinical presentation, diagnosis, and classification. Most importantly, this paper addresses the continuously changing treatment panorama of this disease, from established drugs to newly introduced ones. Furthermore, a peculiar focus regards nonpharmacologic approaches, including traditional Chinese medicine, the apheresis technique, and surgery. Similarly, this review also discusses patients’ lifestyle, including quality of life. To improve SAPHO syndrome’s management, different knowledge gaps should be filled, such as its current epidemiology and pathogenesis. In turn, perfected knowledge in these fields could also advance research in therapy. Full article

Special areas of involvement in psoriasis include the scalp region, the palms and soles, genital areas, as well as intertriginous sites. The involvement of these topographical regions is associated with important physical and emotional implications, resulting in reduced quality of life, social isolation, and work disability. Palms and soles can be affected as part of the generalized form of psoriasis or can be exclusively affected as palmo-plantar psoriasis. Nail involvement may be encountered in 10–55% of patients with psoriasis, while scalp involvement occurs in 45–56% of individuals with psoriasis. Genital involvement may be the only manifestation of cutaneous psoriasis in 2–5% of patients. Inverse or intertriginous psoriasis represents a special variant of psoriasis as it may mimic and be difficult to differentiate from other dermatological entities that involve the intertriginous skin, such as bacterial or fungal infections, eczema, or lichen planus. Treatment of psoriasis in special areas is challenging due to the facts that special areas are more resistant to standard therapies and are more sensitive to potent local treatments. Biological therapies, proven to be more efficient than standard therapies, are not widely available in the absence of extensive skin involvement. This manuscript aims to provide an up-to-date literature review on psoriasis in special areas, benefiting the everyday clinical practice of physicians in optimizing the evaluation and treatment of their patients. Full article

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected. Full article

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment. Full article

In recent years, genetic studies have brought new insights into psoriasis, a chronic inflammatory disease with multiple determining and favoring factors. Recent advances in the technology of genetic analysis have enabled the discovery of many loci with causal or susceptibility roles and the finding of correlations related to different types of treatment responses. In this study, genomic deoxyribonucleic acid (DNA) was extracted from 2 mL peripheral blood for the evaluation of rs10204525 for Programmed Cell Death 1 (PDCD1) gene and rs550675 for Collagen Type IX Alpha 1 Chain (COL9A1) gene in 45 psoriasis patients and 43 healthy subjects without a personal pathological history of dermatological diseases. All patients were diagnosed by clinical and histopathological examination, and the severity of disease and its impact on quality of life were evaluated by Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores. Comparisons were made between controls and patients, but also between different clinical types of psoriasis according to disease severity. The rank of C/T alleles for rs550675 (COL9A1 gene) was higher in the patients versus the control group (p = 0.026), while the G/A alleles for rs10204525 (PDCD1 gene) had no differences between the two groups (p = 0.450). Case and control comparisons also showed statistical significance between homozygous CC/TT genotypes (p = 0.039). After subdividing the three types of psoriasis (plaque psoriasis, arthropathic psoriasis and palmoplantar psoriasis) according to disease severity, there were differences between CC/CT genotype (p = 0.0246) and CC/TT (p = 0.007) genotype in patients with plaque psoriasis in favor of severe disease. At the same time, the GA/GG versus AA pattern was significantly higher in patients with plaque psoriasis. Full article

The epidermis serves many vital roles, including protecting the body from external influences and healing eventual injuries. It is maintained by an incredibly complex and perfectly coordinated keratinization process. In this process, desquamation is essential for the differentiation of epidermal basal progenitor cells into enucleated corneocytes, which subsequently desquamate through programmed death. Numerous factors control keratinocyte differentiation: epidermal growth factor, transforming growth factor-α, keratinocyte growth factor, interleukins IL-1-β and IL-6, elevated vitamin A levels, and changes in Ca²⁺ concentration. The backbone of the keratinocyte transformation process from mitotically active basal cells into fully differentiated, enucleated corneocytes is the expression of specific proteins and the creation of a Ca²⁺ and pH gradient at precise locations within the epidermis. Skin keratinization disorders (histologically characterized predominantly by dyskeratosis, parakeratosis, and hyperkeratosis) may be categorized into three groups: defects in the α-helical rod pattern, defects outside the α-helical rod domain, and disorders of keratin-associated proteins. Understanding the process of keratinization is essential for the pathogenesis of many dermatological diseases because improper desquamation and epidermopoiesis/keratinization (due to genetic mutations of factors or due to immune pathological processes) can lead to various conditions (ichthyoses, palmoplantar keratodermas, psoriasis, pityriasis rubra pilaris, epidermolytic hyperkeratosis, and others). Full article

We examined the effect of a dietary seaweed extract—sulfated xylorhamnoglucuronan (SXRG84)—on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ (p = 0.041), IL-1β (p = 0.030), TNF-α (p = 0.008) and the anti-inflammatory cytokine IL-10 (p = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, p = 0.0005) and the DQLI score (mean difference -2.0, p = 0.049), compared to the ‘non-responders’. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements. Full article

Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52. Full article

Pustular and erythrodermic psoriasis are rare and difficult-to-treat conditions. It has recently been shown that interleukin (IL)-17 inhibitors can be very effective among patients with these forms of psoriasis; however, the potential of IL-23 inhibitors is largely unknown. The aim of this multicentre, retrospective study was to compare the safety, effectiveness, and drug survival of IL-17 and IL-23 inhibitors among patients affected by these rare forms of psoriasis. The study involved 27 patients with erythrodermic psoriasis and 59 with pustular psoriasis (36 with generalised pustular psoriasis and 23 with palmoplantar pustular psoriasis) treated with an IL-17 or IL-23 inhibitor. The effectiveness of the two drug classes was assessed using the disease-specific Psoriasis Area Severity Index (PASI) and the Investigator Global Assessment, which were evaluated at different time points. There was a consistent trend towards a higher rate of PASI 100 responses in the patients treated with IL-17 inhibitors compared with those treated with IL-23 inhibitors, and the other efficacy outcomes showed a similar trend. There was no significant between-drug class difference in efficacy at any of the time points in the erythrodermic psoriasis cohort, whereas PASI 90 and PASI 100 response rates were significantly higher among the pustular psoriasis patients receiving IL-17 inhibitors at week 12 (IL-23 19% vs. IL-17 54% and IL-23 6% vs. IL-17 40%, respectively) and the percentage of responders to IL-17 inhibition was significantly higher at week 24 (IL-23 25% vs. IL-17 74%). In conclusion, it is therefore reasonable to assume that IL-17 and IL-23 inhibitors are both effective when treating pustular and erythrodermic psoriasis. Full article

Background: Nail involvement has a tremendous impact on psoriasis patients. Early detection and prompt intervention of psoriatic nail damage are necessary. Methods: A total of 4290 patients confirmed to have psoriasis between June 2020 and September 2021 were recruited from the Follow-up Study of Psoriasis database. Among them, 3920 patients were selected and divided into the nail involvement group (n = 929) and the non-nail involvement group (n = 2991) by inclusion and exclusion criteria. Univariate and multivariable logistic regression analyses were performed to identify the predictors of nail involvement for the nomogram. Calibration plots, the receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the discriminative and calibrating ability and clinical utility of the nomogram. Results: Sex, age at onset, duration, smoking, drug allergy history, comorbidity, sub-type of psoriasis, scalp involvement, palmoplantar involvement, genital involvement, and PASI score were selected to establish the nomogram for nail involvement. AUROC (0.745; 95% CI: 0.725–0.765) indicated the satisfactory discriminative ability of the nomogram. The calibration curve showed favorable consistency, and the DCA showed the good clinical utility of the nomogram. Conclusion: A predictive nomogram with good clinical utility was developed to assist clinicians in evaluating the risk of nail involvement in psoriasis patients. Full article

Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features with chronic eczema, hyperkeratotic hand dermatitis and allergic contact dermatitis. The present study aims to characterize the histologic features of PP on a series of 21 cases. The following morphological features and their distribution were included: parakeratosis, dilated vessels in papillary dermis, psoriasiform acanthosis with elongation of rete ridges, perivascular lymphocytic infiltrate, decrease/loss of granular layer, Munro’s microabscesses, spongiform pustules of Kogoj, spongiosis and lymphocytic exocytosis. The main diagnostic clues and histologic differential diagnoses are also discussed. Full article