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.

The Impact of Atopic Dermatitis on Sexual Function and Reproductive Desires in Women.

Atopic dermatitis is a prevalent skin condition that affects up to 17% of adult population. It can lead to itching, pain, and other symptoms such as sleep disturbance, anxiety, and depression. Due to its high prevalence and limiting symptoms, atopic dermatitis often has a great impact on patients' quality of life but there is scarce information regarding how atopic dermatitis affects women's sexual health and reproductive desires. The purpose of this article was to assess the impact of atopic dermatitis on sexual function and reproductive wishes in women. A cross-sectional study was conducted from February to March 2022. A total of 102 women with atopic dermatitis were recruited through online questionnaires sent through the Spanish Atopic Dermatitis Association; 68.6% of the patients acknowledged impairment in sexual function, especially those with more severe disease and those with genital and gluteal involvement. In addition, 51% of the women considered that atopic dermatitis may have an influence on their gestational desire, particularly those with gluteal involvement. In conclusion, atopic dermatitis has a great impact on sexual function and reproductive desires in women.

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.

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.

A multicenter case-control study comparing sun exposure habits and use of photoprotection measures in patients diagnosed with different types of skin cancer.

BACKGROUND: While skin cancer awareness programs have significantly furthered public understanding about the harmful effects of the sun, there is a disparity between photoprotection knowledge and protection practices. OBJECTIVE: To compare sun exposure habits and photoprotection measures in patients diagnosed with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma versus controls. METHODS: Multicentre case-control observational study carried out by 13 Spanish dermatologists between April 2020 and August 2022. Patients diagnosed with BCC, SCC, or melanoma were considered cases. The control group consisted of individuals with no history of skin cancer. RESULTS: Of the 254 cases (56.2% female; mean age, 62.67 ± 15.65), 119 (31.2%) had BCC, 62 (16.27%) SCC, and 73 (19.1%) melanoma. The control group consisted of 127 (33.33%) individuals. Avoiding sun exposure between 12:00 and 16:00 was the most commonly used photoprotection measure (habitually/always: 63.1%), followed by the use of sunscreen (habitually/always: 58.9%). Patients with melanoma were less likely to use clothing and shade to avoid sun exposure (p < .05), whereas those with BCC and SCC reported greater use of head coverings (p = .01). BCC and SCC groups reported greater sun exposure 15 years prior, whereas controls reported greater use of sunscreen. However, at the time of this study all groups reported using SPF ≥ 21, and the majority SPF > 50. No differences were observed in photoprotection measures between people with and without a previous history of skin cancer. CONCLUSIONS: We describe differences in photoprotection measures and sun exposure patterns among patients diagnosed with different skin tumor types. Whether these differences may influence the type of tumor each developed will require further investigation.

The impact of photodynamic therapy on skin homeostasis in patients with actinic keratosis: A prospective observational study.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AKs), but there is little information on how PDT affects skin barrier function. The objectives of this study are: To compare skin barrier function between skin with AKs and healthy skin and to evaluate the impact of PDT on skin homeostasis in patients with AKs. METHODS: A prospective observational study was conducted in patients with AKs to evaluate epidermal barrier function and skin homeostasis before and 1 ek after receiving PDT. RESULTS: A total of 21 subjects were included in the study, male/female ratio was 17:4, mean age was 75.86 years. The number of AKS observed before starting treatment was reduced with respect to those diagnosed 1 month after starting PDT (14.83 vs. 1.91, p < 0.0001). Application of PDT for treating AKs modifies epidermal barrier function. Immediately after the first session temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH) and total antioxidant capacity (TAC) increased while pH decreased on lesional skin. After 1-month follow-up, the only remained change was the increased in SCH. Higher increases in temperature were observed when using occlusive PDT compared to mixed modality. 5-ALA and M-ALA seem to have a similar impact on skin barrier. CONCLUSIONS: PDT can improve skin barrier function in patients with AKs. Skin homeostasis parameters can be used to assess efficacy and optimize dosing.

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.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

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.

Frontal Fibrosing Alopecia and Sunscreen Use: A Cross-sectional Study of Actinic Damage.

Patients with frontal fibrosing alopecia report higher rates of sunscreen use than control subjects. However, it is not known whether the higher use of sunscreens is a cause or a consequence of the alopecia. A greater use of sunscreens should be associated with a lower incidence of signs of actinic damage. The aim of this study is to assess the presence of actinic damage in patients with frontal fibrosing alopecia. A cross-sectional study was carried out on 101 patients with frontal fibrosing alopecia and 40 control subjects. The presence of actinic damage, in the form of solar lentigines, actinic keratoses, and basal and squamous cell carcinomas, was recorded in both groups, together with sunscreen use. Trichoscopy and skin biopsy were performed on patients. Actinic damage was present more frequently in patients with frontal fibrosing alopecia (69.3%) than in control subjects (50%) (p = 0.031). Patients used sunscreens more frequently than did control subjects (83.2% vs 62.5%, p = 0.008). However, the prevalence of trichoscopic inflammatory signs, peripheral alopecia, and inflammatory infiltrate and sebaceous gland involvement in skin biopsy, were similar in patients who used sunscreens and those who did not use them. In conclusion, patients with frontal fibrosing alopecia had greater actinic damage than did control subjects, and this is hypothesized as a reason for the higher use of sunscreens among patients. Thus, use of sunscreens may not be the trigger for frontal fibrosing alopecia that dermatologists have proposed.

Assessment of hand hygiene strategies on skin barrier function during COVID-19 pandemic: A randomized clinical trial.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has increased the frequency of handwashing. There is scarce evidence regarding the impact of different hand hygiene procedures on skin barrier function in clinical practice. OBJECTIVE: To compare the impact on skin barrier function of different hand hygiene measures in healthcare workers in daily practice. METHODS: A randomized controlled clinical trial was conducted. Participants were randomized to sanitize their hands with water and soap, alcohol-based hand sanitizers (ABHSs), or disinfectant wipes during their 8-hour working shift. Epidermal barrier functional parameters, such as transepidermal water loss (TEWL), and the microbial load were assessed before and immediately after the working day. Tolerance and acceptability of each product were recorded after work. RESULTS: Sixty-two participants were included and 20, 21, and 21 were randomized to use water and soap, ABHS, and disinfectant wipes, respectively. After the 8-hour shift, TEWL increase was higher with disinfectant wipes than with soaps or ABHS (+5.45 vs +3.87 vs -1.46 g h-1  m-2 , respectively; P = .023). Bacteria and fungi colony-forming unit (CFU) count reductions were lower for the water and soap group than for ABHS and disinfectant wipes. Disinfectant wipes were considered more difficult to use (P = .013) compared with water and soap and ABHS. CONCLUSION: Daily hand hygiene with ABHS showed the lowest rates of skin barrier disruption and the highest reduction of CFU.

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.

Epidermal barrier changes in patients with psoriasis: The role of phototherapy.

BACKGROUND: Some skin diseases may modify epidermal barrier function. Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Phototherapy is an option for treating psoriasis, but little is known about how epidermal barrier function is modified by phototherapy in psoriatic patients. OBJECTIVES: (a) To compare skin homeostasis between involved and uninvolved skin in psoriatic patients with healthy controls (b) To evaluate changes in the epidermal barrier function in psoriatic patients treated with phototherapy. METHODS: Sixty patients with plaque-type psoriasis and sixty gender and age-matched healthy controls were enrolled. Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH, elasticity, erythema and melanin index were measured using non-invasive tools in the healthy control and involved and uninvolved psoriatic skin before and after phototherapy. RESULTS: Healthy controls had lower TEWL and erythema index and higher SCH than psoriatic patients, both at uninvolved psoriatic skin and psoriasis plaques. TEWL was higher at psoriasis plaques than at uninvolved skin (19.20 vs 11.57 g/h/m2 ; P < .001). Following phototherapy, a decreasing trend was observed for TEWL, of 1.03 (SD 0.75) and 0.97 (SD 0.81) g/h/m2 for uninvolved and involved skin respectively. SCH was significantly lower at psoriatic plaques than at uninvolved skin (7.32 vs 36.62Arbitrary Units [AU]; P < .001). SCH increased by 1.15AU (SD 0.26) on psoriatic plaques after the phototherapy session (P < .001). CONCLUSION: Psoriatic plaques showed epidermal barrier dysfunction compared to uninvolved skin and healthy controls. Phototherapy may improve epidermal barrier function in psoriatic patients. SCH increased after a phototherapy session on the psoriatic plaques.

Review of adverse cutaneous reactions of pharmacologic interventions for COVID-19: A guide for the dermatologist.

The new coronavirus, severe acute respiratory syndrome coronavirus 2, is associated with a wide variety of cutaneous manifestations. Although new skin manifestations caused by COVID-19 are continuously being described, other cutaneous entities should also be considered in the differential diagnosis, including adverse cutaneous reactions to drugs used in the treatment of COVID-19 infections. The aim of this review is to provide dermatologists with an overview of the cutaneous adverse effects associated with the most frequently prescribed drugs in patients with COVID-19. The skin reactions of antimalarials (chloroquine and hydroxychloroquine), antivirals (lopinavir/ritonavir, ribavirin with or without interferon, oseltamivir, remdesivir, favipiravir, and darunavir), and treatments for complications (imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine and low molecular weight heparins) are analyzed. Information regarding possible skin reactions, their frequency, management, and key points for differential diagnosis are presented.

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.

Paradoxical Hidradenitis Suppurativa in Patients Receiving TNF-α Inhibitors: Case Series, Systematic Review, and Case Meta-Analysis.

BACKGROUND/AIMS: TNF-α inhibitors represent the most advanced approved therapeutic option for moderate and severe forms of hidradenitis suppurativa (HS). However, in recent years, cases of paradoxical HS secondary to the use of these biological drugs have been described, with very few cases reported in the literature. The aims of this study are (1) to present 2 new cases of paradoxical HS and (2) to perform a systematic review of scientific evidence regarding paradoxical HS with TNF-α inhibitors. MATERIAL AND METHODS: This is a retrospective study in which we searched all the cases of paradoxical HS secondary to the use of TNF-α inhibitors published in the literature and included two additional cases observed in our clinical practice. RESULTS: A total of 34 patients under TNF-α inhibitor treatment were included (adalimumab = 21; infliximab = 9; etanercept = 4). The median delay from exposure to TNF-α inhibitor and the development of paradoxical HS was 12 months (range 1-72). The majority of patients were Hurley stage II (58.8%). Clinical improvement and complete remission were more frequent when the TNF-α inhibitor was stopped or switched to another biological agent with a different therapeutic target rather than maintenance or change to another TNF-α inhibitor. CONCLUSIONS: Paradoxical HS is an unusual adverse effect of TNF-α inhibitors. When this adverse effect appears, interruption or substitution of treatment is associated with a better clinical outcome.