Adalimumab-Induced Paradoxical Psoriasis Treated with Biologics Targeting the IL-17/IL-23 Axis in Patients with Hidradenitis Suppurativa.

BACKGROUND: Paradoxical psoriasis (PP) has been mainly described in patients receiving tumor necrosis factor-α (TNFα) inhibitors for inflammatory bowel disease or psoriasis vulgaris, while such data in the context of hidradenitis suppurativa (HS) are scarce. The purpose of this study was to demonstrate the course of PP and the underlying HS upon switching from adalimumab to a biologic agent targeting the interleukin (IL)-17/IL-23 axis. METHODS: The electronic medical database of the outpatient department for HS of a tertiary hospital for skin diseases was searched to identify patients with moderate-to-severe HS under treatment with adalimumab, who developed PP and were switched to biological therapy with an IL-17 or IL-23 inhibitor between February 2016 and January 2022. Disease assessment scores were evaluated at baseline, at time of PP development, as well as six and 12 months thereafter. RESULTS: Among the 83 patients who received adalimumab for the treatment of HS between February 2016 and January 2022, 10 patients (12%) developed paradoxical psoriasiform skin reactions after a median time of seven (range, 2-48) months. There were four females (40%) and six males (60%) with a median age of 42.5 (range, 33-56) years. Five patients presented with plaque psoriasis and five with palmoplantar pustulosis, while four had intertriginous and three nail involvement. In most of the patients, HS responded well to adalimumab at onset of PP. Eight patients were changed to secukinumab, one to ustekinumab, and one to risankizumab. HS further improved in all but 2 patients, one receiving secukinumab and one receiving risankizumab. In addition, all patients achieved improvement of PP. CONCLUSION: Despite the small number of patients, this study provides support that patients with adalimumab-induced PP may benefit from biologics targeting the IL-17/IL-23 axis. Further studies are needed to establish the optimal therapeutic strategy of the anti-TNFα-induced PP in the context of HS.

Self-Esteem, Depression, Anxiety and Quality of Life in Patients with Melasma Living in a Sunny Mediterranean Area: Results from a Prospective Cross-Sectional Study.

INTRODUCTION: Melasma is a common acquired disorder of hyperpigmentation and has a significant effect on quality of life. The aim of this prospective cross-sectional study was to assess the effect of melasma on depression, social anxiety and self-esteem in the Greek population. METHODS: The study included a total of 254 participants: 127 patients with melasma and an equal sample of healthy controls. Both participant groups completed the following psychometric measures: the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression and Rosenberg's Self-esteem Scale (RSES) for self-esteem. Furthermore, in patients with melasma, quality of life was assessed using Melasma Quality of Life (MELASQoL). RESULTS: Melasma patients (7.47 ± 4.53) presented statistically significantly higher anxiety compared to healthy controls (6.06 ± 3.59, p = 0.006), while no differences emerged with regard to depression or self-esteem. It is important to note that the difference regarding anxiety remained significant (b = 1.25, p = 0.003) even after adjusting for age, depression and self-esteem. A higher disease severity (MASI) correlated statistically significantly with longer disease duration (r = 0.24, p < 0.001), higher depression (r = 0.28, p = 0.002), and a more impaired health-related quality of life (MelasQol; r = 0.29, p < 0.001). Notably, a more impaired health-related quality of life was also correlated with higher depression (r = 0.19, p = 0.027) and lower self-esteem (r = - 0.31, p < 0.001). CONCLUSION: The results of this study highlight the importance of evaluating quality of life, anxiety and depression in patients with melasma. The therapeutic approach should not be based solely on clinical findings; it should also include an evaluation of the patient's psychological aspects. Dermatologists can further improve their patient care by being supportive or requesting psychological intervention when needed, resulting in better compliance with treatment and an improved social and psychological status.

Efficacy of Subantimicrobial, Modified-Release Doxycycline Compared to Regular-Release Doxycycline for the Treatment of Hidradenitis Suppurativa.

Introduction: Antibiotics are frequently used to treat hidradenitis suppurativa (HS), but the evidence-based literature available on their use is limited. Considering that HS is not primarily an infectious disease, we sought to evaluate the efficacy of subantimicrobial, modified-release doxycycline (MR-DC) compared to regular-release doxycycline (RR-DC) for the treatment of HS. Materials and Methods: Patients were randomly assigned to receive treatment with either MR-DC 40 mg once daily or RR-DC 100 mg twice daily for a period of 12 weeks. The treatment efficacy was assessed after 12 weeks of treatment using the International Hidradenitis Suppurativa Severity Score System (IHS4), the Dermatology Life Quality Index (DLQI), and the Hidradenitis Suppurativa Clinical Response (HiSCR). Results: A total of 49 patients (25 in the MR-DC group and 24 in the RR-DC group) were included in the study. A statistically significant (p < 0.05) reduction of IHS4 and DLQI was observed in both groups at week 12. HiSCR was achieved by 64% of patients receiving MR-DC and 60% of those receiving RR-DC. Conclusion: MR-DC demonstrated comparable efficacy to RR-DC in the treatment of HS. MR-DC may serve as a valuable alternative to other antibiotic regimes, considering its anti-inflammatory properties and its lower potential to induce antibiotic resistance.

Perception and Knowledge of Hidradenitis Suppurativa in Greece: A Cross-Sectional Study of 1301 Individuals.

Background: Hidradenitis suppurutiva (HS) is a chronic auto-inflammatory disease with recurrent painful deep-seated nodules. Aims: The aim of this study was to qualitatively assess patients' perception for HS. Methods: A descriptive two-step questionnaire survey was conducted from January 2017 to December 2018. The survey was performed through self-assessed, online, standardized questionnaires. Clinico-epidemiological characteristics, medical history, comorbidities, personal perceptions and the impact of the disease on participants' professional and everyday life were recorded. Results: A total number of 1301 Greek people completed the questionnaire. Of them, 676 (52%) reported symptoms resembling HS, whereas 206 (16%) reported that have been officially diagnosed with HS. The mean age of the study group was 39.2 ± 11.3 years. More than half of the diagnosed patients (n = 110, 53.3%) reported that they developed their first symptoms between 12 and 25 years of age. Of the diagnosed patients (n = 206), the majority (n = 140, 68.0%) were females and active smokers (n = 124, 60.1%). Seventy-nine (n = 79, 38.3%) patients reported a positive family history for HS. Ninety-nine (n = 99, 48.1%) patients reported that HS has a negative effect on their social life, 95 (46.1%) on personal life, 115 (55.8%) on sexual life, 163 (79.1%) on their mental health and 128 (62.1%) on their overall quality of life. Conclusion: Our study showed that HS seems to be an underteated, time-consuming and cost-intensive disease.

Colchicine Improves Clinical Outcomes and Quality of Life in Hidradenitis Suppurativa Patients: A Retrospective Study.

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the follicular epithelium. The aim of the study was to investigate the effectiveness of colchicine on the clinical outcomes of HS patients, and to evaluate wither colchicine as monotherapy or in combination with doxycycline would provide better outcomes. Methods: A retrospective study was conducted including 44 patients with established HS, divided into three groups. The first group (n = 15 patients) received colchicine as monotherapy, the second group (n = 14 patients) received colchicine and doxycycline 100 mg/d, while the third group (n = 15 patients) received colchicine and doxycycline 40 mg/d. Disease severity during treatment was assessed at baseline and follow-up, using the Hurley Scoring System and the International Hidradenitis Suppurativa Severity Score System (IHS4). All patients were also asked to complete a Dermatology Life Quality Index (DLQI) questionnaire. These scores were compared among the study groups. Results: The DLQI and IHS4 scores significantly improved after treatment with colchicine (p < 0.001) in all groups. All colchicine regimes, including the single colchicine regime, colchicine plus doxycycline 100 mg regime, and colchicine plus doxycycline 40 mg regime, resulted in significant improvements in the DLQI and IHS4 scores (p < 0.001). Clinical improvement based on DLQI and IHS4 scores was similar in all groups. None of the patients had to discontinue the treatment due to adverse events. Discussion: In conclusion, our findings suggest that colchicine may improve clinical severity and quality of life in HS patients, either as monotherapy or in combination with doxycycline, both at antimicrobial (100 mg) and sub-antimicrobial (40 mg) doses.

Thyroid Disease and Active Smoking May Be Associated with More Severe Hidradenitis Suppurativa: Data from a Prospective Cross Sectional Single-Center Study.

INTRODUCTION: Hidradenitis suppurativa (HS) is an obscure disease presenting with painful, deep-seated nodules and abscess formation in body areas rich in apocrine glands. Several factors, including thyroid disease and active smoking, have been reported to be associated with HS, but it remains unclear if such associations are related to clinical HS severity. The aim of this prospective cross-sectional study is to investigate the association between active smoking and thyroid disease and HS, as well as to determine if these associations are related to HS severity. METHODS: Eligible were all patients seen in our HS outpatient clinic between September 2018 and February 2020. Data regarding demographic characteristics, clinical disease severity, comorbidities, and treatment modalities were registered. Descriptive statistics of demographic and disease characteristics was conducted. In order to evaluate the association between the disease stage and certain variables of interest, ordered logistic regression was performed. RESULTS: A total of 290 patients were included in the study. Of these, 48.9% were males, and 51.1% females. The patients had a mean age of 37.3 years. A total of 42.4% of the patients were at Hurley stage I, 43.1% at stage II, and 14.5% at stage III. According to the IHS4 score system, 30.7% of the patients had mild, 50.3% moderate, and 19.0% severe disease. The median duration of disease was 10 years. Among the patients, 56.5% were active smokers, and 55.5% patients reported that stress triggers the disease's flares. Univariable analyses demonstrated that among the various covariates, active smoking and thyroid disease were associated with a higher stage of disease. CONCLUSION: We conclude that thyroid disease and active smoking may be associated with more severe HS.

The use of ingenol mebutate to treat actinic keratosis in standard clinical practice: a prospective phase IV multicenter observational cohort study.

BACKGROUND: Actinic keratosis (AK) is a chronic, precancerous skin disease. Various treatments options exist, including ingenol mebutate gel. The aim of this study was to compare its effectiveness and tolerability as well as the impact of therapy on patients' quality of life in standard clinical practice. METHODS: A multicenter study was carried out involving a 12-month follow-up period. A sample of 440 patients was included. Medical history details were recorded. Effectiveness, compliance to treatment, quality of life (EQ-5D-5L), and treatment satisfaction questionnaire for medication (TSQM-9) at week 8 were assessed. RESULTS: Of the total 440 patients, 428 (97.3%) attended at 8 weeks assessment. The number of patients with complete clearance was 337 (78.7%). EQ VAS score was significantly increased (P < 0.001). As far as TSQM-9 is concerned, patients with complete clearance reported statistically significantly higher satisfaction in effectiveness, convenience, and global satisfaction. At the 12-month follow-up visit, 323 patients (95.8%) retained their clearance status. Nineteen patients did not apply the ingenol mebutate gel on consecutive days. For these patients, the complete clearance rate was 42.1%, while for those who were treated on consecutive days, the complete clearance rate was 80.6%. None of our patients developed skin cancer. CONCLUSIONS: This study supports that ingenol mebutate is effective for the treatment of AK with a good safety profile. It significantly improves quality of life. Limited adherence to treatment might be associated with reduced effectiveness.

Chemical Peels in Skin Cancer: A Review.

Background: Chemexfoliation is widely used to reverse signs of photodamage. Although photodamage can eventually lead to skin cancer, it remains unclear whether chemical peels also affect photocarcinogenesis. Moreover, concerns about the systemic and/or cutaneous toxicity of peeling agents have already arisen. Objective: This review sought primarily to summarize the data available on the effects of chemical peels on ultraviolet-induced skin carcinogenesis, focusing particular attention on actinic keratoses and cutaneous field cancerization. In addition, considerations about the systemic and/or cutaneous toxicity of peeling agents, particularly trichloracetic acid, are briefly discussed. Methods: The PubMed, MEDLINE, and SCOPUS databases were searched using the keywords "chemical peeling," "actinic keratosis," "cutaneous field cancerization," "skin cancer," "skin cancer prevention," and "cutaneous and systemic carcinogenicity," both alone and in combination with one another. Additional relevant references were also isolated from citations in the reviewed literature. Results: A total of 42 articles involving both in-vitro and in-vivo human and animal models were included for analysis. The data were mainly confined to laboratory animals. Conclusion: Apart from efficacy in clearing visible actinic keratoses, the findings point towards the possible clinical use of chemical peeling for the prevention of skin cancer. To date, no evidence on systemic toxicity following dermal exposure of humans to chemical peels has been identified.

Management Strategies Of Palmar Hyperhidrosis: Challenges And Solutions.

Palmar hyperhidrosis is a potentially disabling condition for which management remains a therapeutic challenge. Given the significant impact on quality of life, various treatment options are available, ranging from topical agents and medical devices to systemic therapies and surgical interventions. Nonsurgical approaches, i.e. topical antiperspirants, botulinum toxin injections, iontophoresis, and systemic agents, are all supported by the current literature. Patients with mild-to-moderate disease can often benefit from topical therapies only. As disease severity progresses, systemic oral medication, such as anticholinergic drugs, usually becomes necessary. Last-line surgical approaches (sympathetic denervation) should be reserved for severe refractory cases. Recently, therapeutic strategies have been evolving with several new agents emerging as promising alternatives in clinical trials. In practice, however, each modality comes with its own benefits and risks. An individual therapeutic ladder is generally recommended, taking into account disease severity, benefit-to-risk profile, treatment cost, patient preference, and clinician expertise. This review will provide an update on current and emerging concepts of management for excessive hand sweating to help clinicians optimize therapeutic decision-making.

Combination of 30% Salicylic Acid Peels and Mechanical Comedo Extraction for the Treatment of Favre-Racouchot Syndrome.

Dear Editor, Favre-Racouchot syndrome is a cutaneous disease characterized by cysts, comedones, and elastotic nodules in actinically damaged skin, typically on the face (1). It has been specifically connected to sun exposure and heavy smoking, which may act synergistically (2). Available medical and surgical therapies are of variable efficacy. We present a combined therapeutic approach: 30% salicylic acid peels followed by manual extraction of cystic and comedonal material in the same visit. Five male patients, aged between 60-75 years with the clinical diagnosis of Favre-Racouchot syndrome, were treated with salicylic acid peel 30% followed by cyst and mechanical comedo extraction. Local anesthesia was considered unnecessary. Patients were subjected to the above therapies every two weeks for a series of four treatments. Photographs were taken before the beginning of treatment, as well as before and after each session (Figures 1a, b and 2a, b). At the end of the study, physician and patient global assessment scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25-50% fair, 50-75% good, and 75-100% excellent response). We have previously used this assessment scale in published research. Safety was assessed by evaluating early and delayed adverse events. Physician assessment found a fair to good improvement in 80% of the patients based on the reduction of comedones and solar elastosis, as well as the improvement in overall skin appearance and texture. The numbers for each specific categories of improvement were as follows: 1 patient poor; 3 patients fair, and 1 patient good improvement. Based on the patients' self-assessment, all patients (100%) acknowledged an improvement. Three patients rated the improvement fair (60%) and two rated it good (40%). The treatment was well-tolerated and no side-effects were noted. No clinical progression was observed on 6-month follow-up visit. Favre-Racouchot syndrome was originally described in 1932 by Favre and later reviewed in detail by Favre and Racouchot in 1951. Lesions are usually distributed on the temporal and periorbital areas. However, there have been reports of similar findings in atypical locations such as the forearms and chest. The underlying skin is sun-damaged, diffusely thickened, and furrowed (1). The eruption is usually bilaterally symmetrical. The precise pathogenesis of Favre-Racouchot syndrome is not known. Nevertheless, it most commonly presents in patients with a history of long-term sun exposure, heavy smoking, and, although rare, a history of radiation exposure. Unilateral manifestation of the disease has been previously described and was attributed to prolonged occupational unilateral sun exposure or observed following radiation therapy (3). It is mostly reported in Caucasian men (with a prevalence of 6% in adults older than 50 years). Its incidence increases with age, although it has been reported in younger patients. Differential diagnosis includes dermatoses that present with lesions of similar morphologies, such as acne vulgaris, epidermoid cysts, sebaceous hyperplasia, and colloid milium (4). Diagnosis is primarily clinical. Although the histologic features of the disease are very characteristic, skin biopsy is rarely required. The comedones found are histologically indistinguishable from the primary comedones of acne vulgaris, with the exceptions of a lack of inflammation and the presence of a marked actinic elastosis in the surrounding dermis (epidermal atrophy and massive basophilic degeneration of the upper dermis). Measures to stop the progression of the disease include smoking cessation and sun protection. Treatment options include topical retinoids, excision, curettage, dermabrasion, comedo extraction, and carbon dioxide laser ablation. Daily oral isotretinoin (0.05-0.10 mg/kg/day) used in conjunction with topical tretinoin has also been found effective. Treatment results are usually unsatisfactory when these techniques are used independently, but when used in conjunction with one another they may provide a very favorable outcome (1). For the best therapeutic outcome, solar elastosis, the nodulocystic lesions, and the comedones that require mechanical removal should be targeted. Salicylic acid is a lipophilic beta-hydroxy acid possessing keratolytic, comedolytic, and anti-inflammatory properties. At concentrations between 20% and 30% it is used in the treatment of acne vulgaris and mild photodamage. It decreases sebum secretion and disrupts intercorneocyte cohesion, leading to desquamation (5). Its lipid solubility permits better penetration into the pilosebaceous unit. Salicylic acid extends up to the mid-portion of the follicular canal (upper dermis) where excessive keratinization, the initial event in comedo formation, takes place. Furthermore, it activates epidermal basal cells and underlying fibroblasts, resulting in reorganization of the epidermis and a rebuilding of the superficial dermal connective tissue. The above actions of salicylic acid may be responsible for the reduction in comedonal lesions and the improvement in solar elastosis and overall skin texture. Additionally, its keratolytic effect facilitates comedo extraction. On the basis of our results, we suggest an alternative therapeutic approach with salicylic acid peels followed by mechanical comedo extraction in patients suffering from Favre-Racouchot syndrome.

The Association of Various Metabolic Parameters with Multiple Skin Tags.

Background: Skin tags (STs) are benign skin lesions. Their definite etiology remains unknown. We aim to examine the association of obesity, diabetes mellitus, hyperlipidemia, thyroid abnormalities, acanthosis nigricans, and multiple STs in a Greek primary population. Methods: Phototype and body weight were recorded. Fasting serum blood samples were analyzed for cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, and thyroid-stimulating hormone. Univariate ordinal logistic regression multivariate analysis was performed. Results: The univariate analysis showed that patients who were overweight with Fitzpatrick Skin Type III, acanthosis nigricans, and hypothyroidism were more likely to present with multiple skin tags as compared with patients at a normal weight with Skin Type I. Statistically significant associations were also found with the presence of cholesterol and triglycerides. In the multivariate analysis, a significant association between hypercholesterolemia and STs was demonstrated. Those with skin tags were more likely to have hypothyroidism. Conclusion: STs are often associated with obesity. An association between lipid profile and STs has been reported. Multiple STs have been independently associated with acanthosis nigricans. Although a possible relationship between STs and thyroid disease has not yet been proved, our review reveals a possible trend. Future investigations with larger sample sizes might clarify the association between skin tags and hypothyroidism.