Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

Risk Factors of Quality-Of-Life and Sexual Function Impairment in Chronic Spontaneous Urticaria Patients: Cross-Sectional Study.

BACKGROUND: Chronic spontaneous urticaria (CSU) has been associated with poor quality of life and mood disturbances. However, factors associated with these dimensions have not been properly assessed. Moreover, there is a lack of studies regarding sexual dysfunction (SxD) and CSU. Therefore, the aims of this study were to assess quality of life associated factors and to evaluate the prevalence and potential impact of SxD in patients with CSU. METHOD: Cross-sectional study of patients suffering from CSU. Sociodemographic and disease activity variables, quality of life, sleep, SxD, anxiety, and depression were collected using validated questionnaires. RESULTS: Seventy-five patients were included, with a female-to-male ratio of 2.40. Female sex, worse disease control, and sexual dysfunction were associated with poor quality-of-life indexes (p < 0.001). SxD was detected in 52% of female and 63% of male patients. SxD was associated with poor disease control (p < 0.001). Female SxD, but not male, was associated with poorer quality of life (p = 0.02) and an increased risk for anxiety 85% and depression 90% (p < 0.05). CONCLUSIONS: Female patients and those with an inadequate control of CSU are in higher risk of having poorer quality of life. SxD seems to be frequent in patients with CSU. Moreover, female SxD seems to have a more profound impact on quality of life and mood disturbances when compared to males. Assessment of SxD in Urticaria Clinic might be of benefit to identify patients at a higher risk of poor quality of life.

Effectiveness and Safety of Acitretin for the Treatment of Hidradenitis Suppurativa, Predictors of Clinical Response: A Cohort Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle which presents with painful nodules, abscesses, and fistulae in apocrine gland-bearing areas of the skin. Approved treatments include antibiotics and biologic drugs such as adalimumab. Despite these treatments, HS management is challenging. Acitretin is an oral retinoid used for its management as 3rd or 4th line therapy. There is little evidence regarding the effectiveness and safety of acitretin treatment for HS, and no reports have previously explored the potential clinical predictors associated with the response to the treatment. METHODS: Retrospective cohort study to assess the effectiveness and safety of acitretin treatment in HS patients who failed to respond to topical therapies. RESULTS: Sixty-two patients with moderate to severe HS were included. A significant decrease in the International HS Severity Scoring System (IHS4) score was found over time. Higher basal IHS4 score, family history of HS, follicular phenotype, and history of follicular plugging conditions were potential predictors of response. Most patients did not suffer any adverse events, and no severe side effects were observed. The main cause of discontinuation was lack of efficacy. CONCLUSION: Acitretin can be considered as a therapeutic option for patients with HS. The presence of follicular phenotype or a history of components of follicular occlusion syndrome is associated with better outcomes.

Patterns of Surgical Recurrence in Patients with Hidradenitis Suppurativa.

BACKGROUND: Surgery is an essential part of hidradenitis suppurativa (HS) treatment. Understanding and reducing surgical recurrence are crucial to obtaining the best results in patients' treatment. OBJECTIVE: The aim of the study was to characterize surgical recurrences in a cohort of patients with HS treated with wide excision and second-intention healing. METHODS: A prospective nested case-control study was conducted. A cohort of patients with HS treated with wide excision and second-intention healing was monitored for 68 weeks. The surgical procedure was classified as case (recurrence) or control (no recurrence). The type of recurrence was classified according to the elementary lesion in tunnel or abscess and inflammatory nodule (AN) recurrence. Sociodemographic and clinical data likely related to recurrence and the type of recurrence were evaluated. RESULTS: Sixty-three patients were included, receiving a total of 82 surgical procedures. The mean age of the patients was 36.18 years, and the surgical site presented a Hurley stage II severity in 79.26% (65/82) of the interventions. Tunnel recurrence was observed in 8.5% (7/82) and AN recurrence in 15.85% (13/82) of the interventions. Obesity was associated with a higher risk of recurrence, for both tunnel and AN recurrence. Hurley III at the surgical site, a history of pilonidal sinus, and higher International Hidradenitis Suppurativa Severity Score System (IHS4) after surgery and at week 68 increased the risk of tunnel recurrence. CONCLUSION: We propose classifying surgical recurrence based on the elemental type of lesion. Tunnel recurrence could originate in the depth of the surgical scar and could be associated with both surgical site factors and inflammatory load. AN recurrence could originate in the borders of the surgical scar and may particularly benefit from preoperative ultrasound.

Factors Influencing Major Life-Changing Decisions in Patients with Psoriasis: A Cross-sectional Study.

Psoriasis is a chronic inflammatory disease associated with significant impairment in quality of life. Although quality of life in patients with psoriasis has been widely studied, there is little evidence regarding the impact of psoriasis on major life-changing decisions (MLCD). The aims of this study are to describe the impact of psoriasis on MLCD and to explore the potential clinical factors associated with MLCD. This cross-sectional study included 113 patients with psoriasis, regardless of disease severity, duration, or current treatment. The impact of the disease on different MLCD, including those related to professional career, decision of having children, choice of clothing, and leisure activities, was explored using Likert scales. Mean age was 51 years old and female to male ratio was 1.08 (54/50). The mean Psoriasis Area Severity Index was 3.75, and 30% (35/113) of the patients had psoriatic arthropathy. The most affected MLCD were career choice (median (interquartile range) score 3 (2-4)), social relationships (2 (1-3)), choice of clothing (2 (1-3)), job performance, absenteeism, and choice of holiday destination (1 (0-2)). Female sex, early age of onset and psoriatic arthropathy were associated with a greater impact of the disease on MLCD (p < 0.05). The results showed that a range of MLCD are affected in patients with psoriasis, such as career choice, job performance, absenteeism, or choice of clothing. Female sex,  psoriatic arthritis and early age of onset are factors associated with a greater impact on MLCD. In order to limit the long-term negative effects of psoriasis on patients, special attention should be paid to detection of psoriatic arthritis, and to patients with early disease onset.

Type D Personality as a Marker of Poorer Quality of Life and Mood Status Disturbances in Patients with Skin Diseases: A Systematic Review.

Type D personality is characterized by social inhibition and negative affectivity. Poorer outcomes and worse quality of life have been linked to type D personality in patients with a variety of non-dermatological diseases. Despite increasing evidence of the importance of type D personality in skin diseases, there are no reviews on this subject. The aim of this review is to summarize the current evidence regarding type D personality and skin diseases. A systematic search was performed using Medline and Web of Science databases from inception to 11 October 2022. Studies addressing the presence of type D personality, its associated factors, its impact on the outcomes of the disease or the quality of life of the patients were included in the systematic review. A total of 20 studies, including 3,124 participants, met the eligibility criteria and were included in the review. Acne, hidradenitis suppurativa, psoriasis, melanoma, atopic dermatitis, chronic spontaneous urticaria and pruritic disorders were the main diseases assessed. Type D personality was more frequent among patients with skin diseases than among controls. Type D personality was found to be associated with poorer quality of life and higher rates of psychological comorbidities in patients with skin diseases. In conclusion, type D personality appears to be a marker of patients with increased risk of poorer quality of life and higher rates of psychological comorbidities. Screening for type D personality in specialized dermatology units might be beneficial to identify patients who are more psychologically vulnerable to the consequences of chronic skin diseases.

Prevalence and implications of type D personality in patients with alopecia areata: A marker of quality-of-life impairment and mood status disturbances, a comparative study.

INTRODUCTION: Distressed personality (or Type D personality, TDp) is a personality trait that has been associated with poor quality of life in patients suffering from a variety of skin diseases such as psoriasis or urticaria. To date the potential association between Alopecia areata (AA) and TDp has not been studied. The aim of this study was to compare the prevalence of TDp between patients with AA and controls, and to analyse the impact of TDp on patients with AA regarding mood status disturbances, quality of life and sexuality. METHODS: Cross-sectional study includes patients suffering from mild-to-severe AA and sex- and age-matched healthy controls. Socio-demographic and clinical variables, quality of life, sexual disfunction, anxiety, depression and TDp were collected using validated questionnaires. RESULTS: A total of 120 participants (60 patients and 60 controls) were included. Patients with AA showed higher prevalence of TDp than controls (35% vs. 15% p = 0.01), as well as higher rates of anxiety, depression and sexual dysfunction (p < 0.05). TDp was found to be linked to disease severity (p = 0.04), anxiety and depression scores (p < 0.001) and worse quality of life (p = 0.001). No relationship was found between TDp and sexual dysfunction. DISCUSSION: Type D personality prevalence is higher in patients with AA than in controls. It is associated with higher rates of anxiety, depression and worse quality of life. Screening for this type of personality could be useful to detect patients who could benefit from additional psychological support as a complement to their medical treatment.

The impact of dupilumab on skin barrier function: A systematic review.

Skin barrier dysfunction plays an important role in atopic dermatitis (AD) aetiopathogenesis. Dupilumab, a drug that inhibits IL-4 and IL-13, is an effective treatment for AD but there is scarce evidence about its impact on epidermal barrier. The objective of this systematic review is to evaluate the influence of dupilumab on skin barrier in patients with AD using non-invasive tools. A systematic review was designed following PRISMA guidelines. The literature search identified 73 references and, finally, only 6 were selected, including a total of 233 participants. All the studies were prospective observational studies. Dupilumab improved clinical scores in all the research. Skin barrier function parameters were mainly measured on the volar forearm. Transepidermal water loss (TEWL) was the parameter most frequently measured, evaluated in all the studies. Dupilumab decreased TEWL on eczematous lesions and non-involved skin. About 33.6% (2/6) studies reported that dupilumab also increased stratum corneum hydration (SCH) on eczematous lesions while one study did not report any changes in this parameter. This drug also decreased temperature and improved ceramide composition. In conclusion, dupilumab improved skin barrier function in AD patients, mainly reflected in a decreased in TEWL values.

Blueberry muffin baby secondary to ganglioneuroblastoma.

We report the case of a neonate presenting with the clinical features of blueberry muffin syndrome caused by ganglioneuroblastoma, a rare variant of neuroblastoma. This syndrome may be the only visible manifestation of a neonatal tumor and highlights the importance of early recognition and initiation of therapy to reduce mortality.

Intralesional Treatments in Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is an inflammatory chronic disease with difficult management. In some scenarios, intralesional (IL) treatments could be useful. However, the scientific evidence available is limited and heterogeneous. We aimed to synthesize the available scientific evidence on IL treatments in HS. We conducted a systematic review in July 2021. The clinical databases reviewed included MEDLINE and Embase. All types of epidemiological studies and case series with at least 10 patients were included; reviews, guidelines, protocols, conference abstracts, case series with less than 10 patients, and case reports were excluded. Fifteen articles representing 599 patients and 1,032 lesions were included for review. Corticosteroid injections were the most reported treatment. They showed effectiveness for the treatment of acute inflammatory lesions and fistulas in terms of reduction of lesion counts, symptoms, and signs of inflammation and were safe in general terms. Light-based therapies were the other main treatment group, including photodynamic therapy and 1,064-nm diode laser. They were also effective, but more local and systemic adverse events were reported. Other treatments included botulinum toxin type B and punch-trocar-assisted cryoinsufflation (cryopunch). They were effective and safe, although were reported anecdotally. The main limitation of the systematic review was the general quality of the articles included. In conclusion, IL treatments such as corticosteroid injections and light-based therapies seem to be effective and safe for both acute inflammatory lesions and fistulas, although more prospective studies, with higher sample sizes and with standardized outcomes are needed to provide more scientific evidence on the subject.

Type D Personality Is Associated with Poorer Quality of Life in Patients with Chronic Spontaneous Urticaria: A Cross-sectional Study.

Type D personality (TDp) is a stable personality type that has been associated with poor quality of life in the general population and in patients with a variety of diseases, such as cancer, cardiac diseases, and dermatological diseases (e.g. psoriasis). To date, the potential association between chronic spontaneous urticaria and TDp has not been studied. The aim of this study is to analyse the impact of TDp on patients with chronic spontaneous urticaria, regarding mood disturbances, quality of life, sexuality, and sleep disturbances. A cross-sectional study including 75 patients with chronic spontaneous urticaria was performed. Data on socio- demographic variables and disease activity, quality of life, sleep, sexual dysfunction, anxiety, depression and TDp were collected using validated questionnaires. TDp was present in 28% (21/75) of the patients. Although TDp was not related to worse disease control, the presence of anxiety and depression was higher in patients with TDp. Regarding quality of life, TDp was associated with poorer quality of life and higher frequency of sleep disturbances. Prevalence of TDp in patients with chronic spontaneous urticaria is similar to that in the general population. It is associated with mood status disturbances and worse quality of life regardless of disease severity, especially in the emotional and psychological domains. This group of patients could benefit from additional psychological support as a complement to their medical treatment.

Treatment challenges in clinically amyopathic dermatomyositis: A case series and review of new therapeutic options for skin involvement.

The term clinically amyopathic dermatomyositis (CADM) is used to represent a subgroup of patients with the typical cutaneous features of dermatomyositis (DM) in the absence of muscle involvement. Similar to classic DM, CADM can be associated with other connective tissue disorders and systemic manifestations such as interstitial lung disease and malignancy. Owing to the frequent discordance between muscle response and skin disease, the therapeutic approach to CADM represents a challenge. The current literature suggests that CADM treatment should follow a specific protocol, influenced by visceral involvement and the expression of certain myositis-specific antibodies, and different from the recommendation in the presence of myositis. Here, we present five new cases of CADM. We describe the available therapeutic options for skin manifestations in this type of DM, and we propose a step-by-step therapeutic scheme, using the cutaneous dermatomyositis disease area and severity index to assess response. Our literature review establishes mycophenolate mofetil and intravenous immunoglobulin as the most frequently successful therapies in refractory skin disease.

The role of biologic treatment in special scenarios in hidradenitis suppurativa: Facial and nape phenotype, dissecting cellulitis of the scalp, and lymphedema.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder affecting the hair follicle which typically affects the axilla, inguinal, submammary, and perianal areas. Atypical HS, such as facial HS, dissecting cellulitis of the scalp (DCS), nape HS, and HS lymphedema has also been described. There is scarce evidence about the treatment of atypical HS. To describe the efficacy of biologic drugs and adjuvant therapeutic interventions used in patients with atypical HS who had an inadequate response to systemic antibiotics. Prospective case series study of patients with atypical HS (facial HS, DCS, nape HS, and HS lymphedema) treated with biologic drugs in a HS Clinic setting. Disease activity indexes, sociodemographic, clinical, and safety variables were collected. Two patients met criteria for Facial HS, three met criteria for DCS/nape HS and three patients met criteria for HS lymphedema. Patients with facial HS achieved rapid improvement without requiring other therapies. Patients with DCS, nape HS, and HS lymphedema showed variable response, with decrease of activity indexes, and requiring adjuvant treatments. Biologic drugs are useful in the management of special HS locations. In the case of facial HS, biologic therapy seems to be quite effective as monotherapy. In the cases of DCS, HS lymphedema and nape HS, treatment combination or intensification may be needed.

Implications of Hidradenitis Suppurativa Phenotypes in Cardiovascular Risk and Treatment Decisions: A Retrospective Cohort Study.

BACKGROUND: New integrative hidradenitis suppurativa (HS) lesion pattern phenotypes have been proposed, an inflammatory phenotype (IP) and a follicular phenotype (FP). They are characterized by different lesion patterns, symptoms, and risks of disease progression. OBJECTIVES: To evaluate whether lesion pattern phenotypes (1) have a different cardiovascular risk factor profile, and (2) are associated with a different therapeutic approach in the setting of an HS clinic. METHODS: A retrospective cohort study was conducted on 233 patients with HS. They were classified according to lesion pattern phenotype criteria. Data regarding cardiovascular risk factors and treatment decisions were gathered. RESULTS: One hundred and seventeen HS patients (50.21%) were classified as FP and 112 (48.07%) as IP. IP was associated with more severe disease and greater impairment of quality of life. Regardless of disease severity, patients with IP may have a higher cardiovascular risk, assessed according to higher C-reactive protein (CRP) levels (12.75 vs. 5.89, p = 0.059). The lesion pattern phenotype also influenced treatment decisions regardless of disease severity. Patients with IP were more likely to be treated with systemic corticosteroids and adalimumab, showing that lesion pattern phenotypes are associated with different therapeutic approaches. CONCLUSIONS: IP is associated with higher CRP values, suggesting a greater cardiovascular risk in these patients and also a different therapeutic approach. This information could help guide dermatologists in the management of HS patients and help to determine future treatment recommendations.

Clinical selection criteria in new clinical trials of hidradenitis suppurativa: External validity and implications on the daily clinical practice.

INTRODUCTION: There are an increasing number of biologic drugs in the pipeline for treating hidradenitis suppurativa (HS). Clinical trials for these drugs usually share the same clinical selection criteria. OBJECTIVES: (a) To describe the clinical profile of HS patients receiving first-line biologic treatment in an HS clinic setting, (b) to assess how this population would meet clinical criteria to participate in a clinical trial, and (c) to assess treatment effectiveness at week 16 in eligible vs non-eligible patients. METHODS: Prospective observational study. Patients were grouped according to their eligibility for clinical trials. The effectiveness of adalimumab was assessed by HiSCR, IHS4-category-change and a-50%-reduction on IHS4 at week 16. RESULTS: Thirty-eight patients were included in the study: eight (21.05%) were eligible for clinical trials and 30 (78.95%) were not. The main reason for non-eligibility was not having an AN count ≥5. Both groups presented similar number of draining tunnels. Effectiveness at week 16 was lower in non-eligible than eligible patients when evaluated by HiSCR-response but similar if evaluated by the IHS4-category-change or the 50%-reduction in IHS4. CONCLUSION: In our population, the external validity of current eligibility criteria for clinical trials is low. Most patients receiving adalimumab in real-life setting would not be eligible for clinical trials.

Is vegetative area, photosynthesis, or grape C uploading involved in the climate change-related grape sugar/anthocyanin decoupling in Tempranillo?

Foreseen climate change is expected to impact on grape composition, both sugar and pigment content. We tested the hypothesis that interactions between main factors associated with climate change (elevated CO2, elevated temperature, and water deficit) decouple sugars and anthocyanins, and explored the possible involvement of vegetative area, photosynthesis, and grape C uploading on the decoupling. Tempranillo grapevine fruit-bearing cuttings were exposed to CO2 (700 vs. 400 ppm), temperature (ambient vs. + 4 °C), and irrigation levels (partial vs. full) in temperature-gradient greenhouses. In a search for mechanistic insights into the underlying processes, experiments 1 and 2 were designed to maximize photosynthesis and enlarge leaf area range among treatments, whereas plant growth was manipulated in order to deliberately down-regulate photosynthesis and control vegetative area in experiments 3 and 4. Towards this aim, treatments were applied either from fruit set to maturity with free vegetation and fully irrigated or at 5-8% of pot capacity (experiments 1 and 2), or from veraison to maturity with controlled vegetation and fully irrigated or at 40% of pot capacity (experiments 3 and 4). Modification of air 13C isotopic composition under elevated CO2 enabled the further characterization of whole C fixation period and C partitioning to grapes. Increases of the grape sugars-to-anthocyanins ratio were highly and positively correlated with photosynthesis and grape 13C labeling, but not with vegetative area. Evidence is presented for photosynthesis, from fruit set to veraison, and grape C uploading, from veraison to maturity, as key processes involved in the establishment and development, respectively, of the grape sugars to anthocyanins decoupling.