Correlation between Dermatology Life Quality Index and Psoriasis Area and Severity Index in Patients with Psoriasis: A Cross-sectional Global Healthcare Study on Psoriasis.

Quality of life impairment in dermatology patients and severity of psoriasis are quantified by the Dermatology Life Quality Index (DLQI) and the Psoriasis Area and Severity Index (PASI), respectively. The aim of this study is to compare the correlation between PASI and DLQI in patients from different geographical areas and to identify predictors of high DLQI across geographical regions. Correlations between PASI and DLQI were evaluated using Spearman's rank correlation tests and quantile regression. The study included 1,158 patients with psoriasis, with a median (interquartile range) PASI and DLQI of 6.0 (3.0-12.0) and 8.0 (4.0-15.0), respectively. Correlations were demonstrated between PASI and DLQI, both overall and stratified by geographical region. Quantile (median) regression yielded coefficients of 0.75 (95% confidence interval (95% CI) 0.62, 0.88) for Switzerland, 0.50 (95% CI 0.42, 0.58) for Latin America, 0.34 (95% CI 0.16, 0.51) for Asia, and 0.31 (95% CI 0.08, 0.53) for the USA. Current age, age at diagnosis, sex, body mass index, and psoriasis arthritis affected DLQI in Latin America, while education had an impact among patients treated in Switzerland. Few countries were included within each continent; hence, more data from different countries are necessary for generalizability. The study showed correlations between PASI and DLQI among patients in all included geographical regions. The patients' characteristics affecting DLQI vary worldwide.

Infections in the era of immunobiologicals.

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study.

BACKGROUND: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

Cumulative life course impairment in patients with dermatological diseases, with a focus on psoriasis.

The concept of "Cumulative Life Course Impairment" (CLCI) characterizes the set of factors harmful to the lives of patients resulting from the stigma and physical and psychological impairment associated with different chronic diseases, which can accumulate irreversibly over the course of patients lives. The sum of these factors often makes it impossible for these individuals to enjoy their lives fully, intensely and adequately. On the other hand, CLCI also incorporates coping strategies, including external factors and personality characteristics, which may act as modulating or protective factors of vulnerability to the CLCI. Although psoriasis is the most studied dermatological disease in relation to its impact on quality of life and CLCI, several other chronic inflammatory diseases such as atopic dermatitis, hidradenitis suppurativa, and alopecia areata have also been evaluated in relation to the magnitude of the damage to patients lives.

Sensitive Scalp and Trichodynia: Epidemiology, Etiopathogenesis, Diagnosis, and Management.

Sensitive scalp (SSc) is considered a sensitive skin on the scalp, with its particularities. Although it is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature. The etiopathogenesis is still uncertain, and the sensitivity may be associated with hair loss. Clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia, often with scalp erythema. SSc can be triggered by several factors (endogenous or exogenous). The diagnosis is guided by the anamnesis, and there are still no specific trichoscopic features. Trigeminal trophic syndrome and postherpetic neuralgia are the main differential diagnosis to be considered. We organized the therapeutical approach in three steps: scalp care, topical and systemic treatment.

The Overview of the Immunobiology of Interleukin-23 Associated With Immune-Mediated Inflammatory Disorders: A Narrative Review.

BACKGROUND: Interleukin (IL)-23, a member of the IL-12 family, has emerged as an important cytokine that bridges the innate and adaptive immune systems and plays a critical role in the development of a wide spectrum of immune-mediated inflammatory disorders (IMIDs). It can be considered a gatekeeper of T helper 17 (Th17) cells development and expansion that subsequently produces several mediators that promote inflammation. The inhibition of IL-23 is a potential therapeutic approach for several inflammatory diseases, such as psoriasis, psoriatic arthritis, and inflammatory bowel disease. OBJECTIVE: This work aims to address the overview of the immunobiology of IL-23 associated with some of the most frequent IMIDs and the current pipeline of its inhibition. METHODS: We conducted a narrative review elucidating data about 1) the overview of the immunobiology of IL-23 associated with immune-mediated inflammatory disorders in specific diseases, such as psoriasis, psoriatic arthritis, and inflammatory bowel disease; 2) therapeutic approaches targeting the IL-23 pathway (IL-23 inhibitor drugs approved by international agencies); and 3) novel therapeutic perspectives. The search strategy was conducted in the relevant database with terms related to the proximity to IL-23 or immuno-mediated. RESULTS AND CONCLUSIONS: Existing and emerging therapeutic biologics targeting the IL-23/IL-17 pathway are promising options to treat IMIDs while the knowledge of the pathophysiology of those conditions and the contribution of the IL23/IL-17 continues to grow. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7017 Citation: Galli Sanchez AP, Castanheiro da Costa A, Del Rey C, et al. The overview of the immunobiology of interleukin-23 associated with immune-mediated inflammatory disorders. A narrative review. J Drugs Dermatol. 2023;22(4):375-385. doi:10.36849/JDD.7017.

Diversity in the clinical presentation of generalized pustular psoriasis (GPP): A series of case vignettes from around the world.

A key principle of clinical studies and case reports is that they should reflect the demographics and epidemiology of the patient population concerned. Here, we have compiled a diverse group of clinical cases of generalized pustular psoriasis (GPP) to showcase the differences in GPP presentation in patients worldwide. We attempt to capture the broad spectrum of clinical presentations of GPP and showcase the diversity of the patient population. The patients included in this series are diverse in age, genetic background, skin phototype and medical history. Moreover, they present with a variety of clinical courses of GPP and different degrees of systemic involvement, and experience flares triggered by different inciting factors. The key learnings from this case series may support physicians in identifying and managing patients with this rare and multifaceted disease that can affect patients both physically and psychologically.

Small fiber neuropathy and intractable scalp pruritus in dermatomyositis patients.

Background: Scalp pruritus is a common symptom in Dermatomyositis (DM) patients. There are indications that small nerve fibers neuropathy could be involved in this symptom, however the etiology of scalp pruritus is not fully understood. Objectives: To assess epidermal nerve fiber (ENF) density of dermatomyositis patients with scalp pruritus by biopsy by confocal microscopy and immunohistochemistry with subsequent imaging analysis. Methods: DM patients with severe scalp pruritus from the dermatology outpatient clinic were compared to healthy volunteers. Two 4-mm scalp skin biopsies were obtained above the right ear in the parietal region and below the occipital protuberance in the occipital region. Biopsy specimens were incubated with primary antibodies to protein gene product (PGP 9.5), calcitonin gene-related peptide (CGRP), substance P (SP) were used to visualize nerve fibers (ENF) and collagen IV was used to label the epidermal basement membrane. The number of ENFs per millimeter was counted and recorded as the mean of ± SD of counts in 16 images at two micrometer increments/sections, two from each of the samples. ENF densities were compared between groups and a multiple linear regression model was applied to associated factors with ENF density. Results: Fifteen DM patients with severe scalp pruritus and 12 healthy volunteers were included in the study. The mean number of ENF/mm in occipital region of DM group was 16.0 ± 13.9 while the control group in the same region was 99.8 ± 33.1. In parietal region the number of ENF/mm of DM group was 18.0 ± 20.7 while in control group was 50.4 ± 17.4 (p < 0.001). Conclusion: DM patients with pruritus could have some impairment of small nerve fiber density that could explain their recalcitrant scalp pruritus.

Generalized pustular psoriasis: A global Delphi consensus on clinical course, diagnosis, treatment goals and disease management.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and highly heterogeneous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP. OBJECTIVES: Conduct a Delphi panel study to identify current evidence and gain advanced insights into GPP. METHODS: A systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare definition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by ≥80%. RESULTS: Twenty-one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the 'clinical course and flare definition', 'diagnosis', 'treatment goals' and 'holistic management of GPP' domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered helpful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long-term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed. CONCLUSIONS: Global consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice.

Access to psoriasis treatment in Brazil and Chile: A cross-sectional multicentre Global Healthcare Study on Psoriasis.

BACKGROUND: Sufficient data on access to systemic treatment for patients with psoriasis living in Latin America (LA) including Brazil and Chile are lacking. Understanding the availability and limiting factors of access to treatments can help to improve patient care and decrease long-term healthcare costs. OBJECTIVES: In association with the Global Psoriasis Atlas, this cross-sectional survey study analysed the availability and insurance reimbursement of systemic treatments for adult patients with psoriasis in Brazil and Chile. METHODS: A multicentre, cross-sectional Global Healthcare Study on Psoriasis was performed in Brazil and Chile in 2020. For each eligible adult patient with psoriasis, doctors and nurses completed a 48-item questionnaire about clinical aspects of psoriasis including the Psoriasis Area Severity Index (PASI), body surface area (BSA) score and the Dermatology Life Quality Index (DLQI), as well as the availability of systemic treatments and insurance reimbursement status. Between-country differences were compared with Wilcoxon rank sum tests for continuous variables, and a χ2-test or Fisher's exact test, where appropriate, for categorical variables. The median and interquartile range (IQR) was calculated for non-normal distributed data. RESULTS: A total of 1424 patients with psoriasis from 43 centres [27 centres in Brazil (n = 826) and 16 in Chile (n = 598)], were included with a mean (SD) age of 49.1 (16.3) and 49.2 (15.1) years, respectively. Unstratified analyses revealed that patients with psoriasis in Chile had more severe disease than those in Brazil [PASI 11.6 vs. 8.4 (P < 0.001) and BSA 14.7 vs. 12.0 (P = 0.003), respectively]. For patients with moderate-to-severe psoriasis, defined as PASI and/or BSA ≥ 10, systemic nonbiologic drugs were available (81.2% in Brazil and 65.3% in Chile, P ≤ 0.001), but only 37.0% of patients in Brazil and 27.3% in Chile received biologics (P = 0.01). Lack of availability and/or lack of insurance reimbursement for biologic drugs for patients with moderate-to-severe psoriasis was reported for 22.2% (50 of 225) in Brazil and 67.9% (148 of 218) in Chile (P < 0.001). Patients with no access to biologic therapies due to lack of availability/insurance reimbursement had a median PASI of 9.15 (IQR 3.00-14.25) in Brazil and 12.0 (IQR 5.00-19.00) in Chile (P = 0.007), as well as a median BSA of 7.0 (IQR 3.00-15.00) and 12.0 (IQR 5.00-22.50) (P = 0.002), and median DLQI of 11.0 (6.00-15.00) and 21.0 (6.50-25.00) (P = 0.007), respectively. CONCLUSIONS: Chilean patients had significantly more severe psoriasis compared with Brazilian patients in our study. While nonbiologic treatments for moderate-to-severe psoriasis were available in both LA countries, there is a high need for improvement in access to more effective psoriasis treatments including biologics. Our results highlight a significant gap between treatment recommendations in international psoriasis guidelines and real-world situations in Brazil and Chile.

Comorbidities in Chilean patients with psoriasis: a Global Healthcare Study on Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. AIM: To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. METHODS: This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. RESULTS: In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. CONCLUSIONS: We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting.

Areata-Like Lupus as a Clinical Manifestation of Cutaneous Lupus Erythematosus.

Introduction: Lupus erythematosus (LE) is a chronic autoimmune disease that frequently causes hair loss and scalp lesions. Hair loss can be scarring and nonscarring, diffuse, or patchy. The nonscarring patchy alopecia is usually related to systemic LE (SLE) and may simulate alopecia areata (AA), reason why it is named areata-like lupus. Our case was diagnosed with areata-like lupus but did not meet criteria for SLE. Case Report: A 63-year-old woman presented with irregular nonscarring patchy alopecia in the temporal and frontoparietal scalp. Trichoscopy showed exclamation mark hairs, vellus hairs, and sparse yellow dots. Histology revealed epidermal vacuolar interface dermatitis, lymphohistiocytic infiltrate around the bulbs of anagen follicles, and eccrine glands. Direct immunofluorescence showed deposits of C3, IgA, and IgG in the basement membrane zone. Discussion: Patients with cutaneous LE can also manifest as nonscarring patchy alopecia that is clinically similar to AA, despite the absence of systemic manifestations. Areata-like lupus is secondary to the lupus autoimmune infiltrate that affects the skin including the hair follicles. Trichoscopy, histology, and direct immunofluorescence are important to differentiate this form of alopecia from AA, which is believed to have a higher incidence in lupus patients.

Lichen planopilaris and frontal fibrosing alopecia: review and update of diagnostic and therapeutic features.

Lichen planopilaris and frontal fibrosing alopecia are primary scarring alopecias where diagnosis can be suggested by clinical and trichoscopy features, especially in the early stages, but scalp biopsy is the standard exam for definitive diagnosis. Frontal fibrosing alopecia is considered a variant of lichen planopilaris, as the histopathological findings are similar, with a perifollicular lymphohistiocytic infiltrate, sometimes with a lichenoid pattern. A thorough clinical examination, trichoscopy and photographic documentation are essential to assess the evolution and therapeutic response. To date, there are no validated treatments or guidelines for these diseases, but there are recommendations that vary with the individual characteristics of each patient. This article presents a comprehensive review of the literature, including an update on topics related to the diagnosis, follow-up, histopathological aspects and available treatments for lichen planopilaris and frontal fibrosing alopecia, highlighting their similarities, differences and peculiarities.

Atualização do custo-efetividade por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe no tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / An update of a cost-effectiveness per response of adalimumab, etanercept, guselcumab, infliximab, ixekizumab, secukinumab and ustekinumab for treatment of moderate to severe plaque psoriasis from the perspective of the Brazilian Supplementary Health System

Objetivo: Os agentes biológicos representam um grande avanço no tratamento da psoríase em placas moderada a grave. No entanto, variações de eficácia, segurança e custos dos tratamentos podem dificultar a escolha do agente terapêutico. Este estudo teve como objetivo atualizar o custo por resposta dos agentes biológicos disponíveis para psoríase no ROL de Procedimentos e Eventos em Saúde (ROL) da Agência Nacional de Saúde Suplementar (ANS). Métodos: Uma análise de custo por resposta foi utilizada para avaliar a razão de custo pelo desfecho Índice de Gravidade e Área da Psoríase (PASI) 90. Os resultados foram apresentados para o primeiro ano (ano I), que compreende a fase de indução e a fase manutenção até completar 52 semanas e foi realizada uma análise da efetividade do tratamento num cenário de orçamento fixo. Os custos dos tratamentos foram calculados com base nos preços de fábrica (PF18%) da Tabela da Câmara de Regulação do Mercado de Medicamentos de junho de 2021. Resultados: Para o ano I, o guselcumabe apresentou melhor resultado para custo por resposta (R$ 130.467) PASI 90, seguido por ixequizumabe, ustequinumabe, secuquinumabe, adalimumabe, infliximabe e etanercepte. No cenário com orçamento fixo, o guselcumabe demonstrou ser o agente capaz de tratar com sucesso (PASI 90) o maior número de pacientes. Atualização do custo-efetividade por resposta para psoríase em placas moderada a grave. Conclusão: Sob a perspectiva do Sistema de Saúde Suplementar do Brasil, o guselcumabe apresentou o melhor custo por resposta PASI 90, sendo, assim, a terapia com melhor custo-efetividade no tratamento da psoríase em placas moderada a grave disponível no ROL.

Objective: Biological agents represent a major advance in the treatment of moderate-to-severe plaque psoriasis. However, variations of efficiency, safety and costs of treatments make it difficult to select the drug. This study aims to update the cost per response of biological agents available in the Health Procedures and Events Roll (ROL) of the National Supplementary Health Agency (ANS). Methods: A cost-per-response analysis was used to assess the cost per outcome of Psoriasis Area and Severity Index (PASI) 90. Results were presented for the first year (I), which comprises induction and maintenance for 52 weeks and a fixed budget scenario analysis. Treatment costs were calculated based on the prices of the 2021 Medicines Market Regulation Chamber Table. Results: Analysis of year I, guselkumab showed the best result for cost per cost (R$ 130,467) PASI 90, followed by ixekizumab, ustekinumab, secukinumab, adalimumab, infliximab, and etanercept. In the fixedbudget analysis, guselkumab is the therapy capable of successfully treating (PASI 90) the largest number of patients. Conclusion: From the perspective of the Supplementary Health System in Brazil, guselkumab showed the best cost per response PASI 90, thus being the most cost-effective therapy in the treatment of moderate to severe plaque psoriasis available in the Brazilian ROL.