How to integrate surgery and targeted therapy with biologics for the treatment of hidradenitis suppurativa: Delphi consensus statements from an Italian expert panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified ten areas of interest based on published evidence and personal experience: 1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); 2) tailoring surgery to HS characteristics; 3) wide local excision; 4) pre-surgery biologic treatment; 5) concomitant biologic and surgical treatments; 6) pre- and post-surgery management; 7) antibiotic systemic therapy; 8) biologic therapy after radical surgery; 9) management of adverse events to biologics; 10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Comparison of Perceptions of Skin Condition, Product Use and Allergen Reactivity Between People with Psoriasis and Controls in the European Dermato-Epidemiology Network (EDEN) Fragrance Study.

Psoriasis, a chronic inflammatory skin disease, goes beyond visible symptoms and affects the general well-being of patients. The aim of this study is to understand how patients with psoriasis perceive their skin characteristics and reactivity to allergens. The study population includes 11,283 participants within the European Dermato-Epidemiology Network (EDEN) Fragrance study, covering several European regions. The study compared perceptions of skin dryness, sensitivity, product avoidance and reactivity to allergens between patients with psoriasis and controls, evaluating the potential influence of psoriasis severity. The results showed that subjects with psoriasis reported dry skin (71.1%) and sensitive skin (49.4%) more often than did controls (51.6% and 38.5%, respectively). Psoriasis patients were more likely to avoid specific products. Interestingly, there were no significant differences in patch-test results between the 2 groups and the severity of psoriasis did not have a consistent impact on these perceptions. In conclusion, people with psoriasis tend to perceive their skin as drier and more sensitive. Notably, the severity of psoriasis did not consistently influence these perceptions and objective reactivity to allergens did not align with subjective perception. Understanding these aspects is crucial for tailoring treatments to improve the well-being of patients with psoriasis, which warrants further research to explore subjective perceptions of skin well-being in patients with psoriasis.

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Ablative CO2-Assisted Laser for Topical Drug Delivery in Nail Psoriasis: A Systematic Review.

Background: Nail psoriasis poses challenges for effective treatment, and topical drug delivery through the nail plate is limited. A novel approach to address this challenge involves the use of ablative fractional laser as a pretreatment strategy to enhance topical drug delivery for nail psoriasis. Summary: This systematic review, conducted in accordance with PRISMA guidelines, involved an extensive literature search across PubMed/MEDLINE, EMBASE, and the Cochrane Library up to July 2023. The primary focus was on exploring studies that investigated the application of ablative laser technology to augment drug delivery for nail psoriasis. Key Messages: (1) The review included seven randomized controlled trials, all examining the combination of fractional CO2 laser with topical treatments. These trials demonstrated varying degrees of improvement in nail psoriasis. (2) Patients undergoing laser treatment reported experiencing moderate levels of pain, effectively managed through the application of topical anesthesia. (3) Commonly observed side effects included erythema, swelling, and crusting, with the Koebner phenomenon being a rare occurrence. (4) Notably, patient satisfaction levels with the combined approach of laser and topical treatments were consistently high. In conclusion, the utilization of ablative CO2-assisted laser pretreatment, when used in conjunction with topical therapy, appears to be both effective and well-tolerated for the treatment of nail psoriasis. However, the establishment of optimal parameters and treatment intervals for fractional laser therapy remains an area for further research. Standardized studies are imperative to identify the most effective strategy for enhancing topical drug delivery in the context of nail psoriasis treatment.

CO2 Laser-Assisted Nail Sampling for Mycological Testing in Onychomycosis.

Introduction: Onychomycosis is the most common nail infection, predominantly caused by Trichophyton spp., and is divided into four main types. Confirmatory testing is crucial, but obtaining an adequate sample may be challenging. We suggest the use of carbon dioxide (CO2) laser for painlessly detaching the nail plate during mycological examination and ensuring a sufficient specimen. Methods: We retrospectively enrolled 25 patients with distolateral onychomycosis, treated according to the following protocol: (1) multiple passes of CO2 laser at 10 W in continuous mode along the proximal border of the affected nail plate; (2) the nail plate was gently cut; (3) the nail bed was curetted; (4) subungual debris and plate fragments were collected for KOH test and culture. Results: The mean visual analog score (VAS) for pain experienced during the procedure was 0.7 (SD: 2.1), indicating that the sampling was relatively painless for the majority of patients. There were no permanent changes observed in the nail unit of any patients during the follow-up visits as a result of using the CO2 laser. Conclusion: We firmly believe that the use of lasers offers numerous advantages, including ease of use, reduced pain perception, and the ability to target the proximal margin of fungal infections where viable hyphae are significantly represented.

Efficacy of Fractional Versus Fully Ablative CO2 Laser for Distolateral Onychomycosis: Experience With 20 Patients.

INTRODUCTION: Oral antifungals are the treatment choice for onychomycosis, and topical therapies are favored in cases of limited nail involvement. Recently, carbon dioxide (CO2) laser treatment has emerged as an option to enhance the effectiveness of topical therapies. OBJECTIVES: Our objective was to compare the efficacy of fractional ablative and fully ablative CO2 laser treatments for distolateral subungual onychomycosis affecting a single toenail and caused by dermatophytes. METHODS: The records of 10 patients treated with a single fully ablative CO2 session were matched with those of 10 patients who underwent a single CO2 fractional treatment. All had previously failed topical antifungal lacquers and were discharged with the prescription of topical ciclopirox nail lacquer (8%) for 3 months. RESULTS: The clinical response rates were 80% for the fully ablative group and 60% for the fractional group. Additionally, the mean reduction in Onychomycosis Severity Index from baseline to 8.6±1.6 weeks after treatment completion was 6.9±5.4 in the fully ablative group and 3.6±6.6 in the fractional group. The relapse rate among responders was 12.5% in the fully ablative and 33.3% in the fractional group after a mean follow-up time of 29.4±2.3 weeks. CONCLUSIONS: Fractional and fully ablative CO2 laser in combination with ciclopirox lacquer could increase the response rate in onychomycosis resistant to topical antifungals when systemic therapy is contraindicated or not yet pursued. Fully ablative mode therapy is significantly more effective than fractional (P < 0.05). Further studies are needed to identify prognostic response factors and assess the long-term effectiveness of CO2 laser treatment.

Biologics and small molecules treatment for moderate-to-severe atopic dermatitis patients with comorbid conditions and special populations: an Italian perspective.

This comprehensive review offers a detailed look at atopic dermatitis (AD) treatment in Italy, focusing primarily on the use of biologics and small molecules. In response to advancing knowledge of AD's causes and treatments, there's a global need for updated guidelines to provide physicians with a more comprehensive clinical perspective, facilitating personalized treatment strategies. Dupilumab, a groundbreaking biologic, gained approval as a significant milestone. Clinical trials demonstrated its ability to significantly reduce AD severity scores, with an impressive 37% of patients achieving clear or nearly clear skin within just 16 weeks of treatment. Real-world studies further support its efficacy across various age groups, including the elderly, with a safety profile akin to that of younger adults. Tralokinumab, a more recent approval, shows promise in clinical trials, particularly among younger populations. However, its real-world application, especially in older individuals, lacks comprehensive data. Janus Kinases inhibitors like Upadacitinib, Baricitinib, and Abrocitinib hold substantial potential for AD treatment. Nevertheless, data remains limited for patients over 75, with older adults perceived to carry a higher risk profile. Integrated safety analyses revealed individuals aged 60 and above experiencing major adverse cardiovascular events and malignancies, underscoring the need for cautious consideration. While these therapies offer promise, especially among younger patients, further research is essential to determine their safety and efficacy in various populations, including pediatric, geriatric, and those with comorbidities. Biologics and small molecules are improving AD treatment, as shown in this review.

Italian healthcare resource consumptions and direct costs of adults with atopic dermatitis before and after dupilumab treatment.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous disease, associated with comorbidities, and high healthcare consumptions and costs. This study assessed the burden before and after treatment with dupilumab in adults with severe AD from 2018 to 2020, from the perspective of the Italian National Health Service (SSN). METHODS: From Fondazione Ricerca e Salute's administrative healthcare database (~5 million inhabitants/year), adults treated with dupilumab from 09/01/2018 to 31/12/2020 (index date) and a five-year lookback were identified. Age, sex and comorbidities at baseline, concomitant drugs, overnight hospitalizations, outpatient specialist services and direct costs charged to the SSN one year before/after index date were assessed. RESULTS: Of 337 adults treated with dupilumab (5.8x100,000 adult inhabitants/2019; 8.0x100,000/2020; 55% males; mean age 43±19), 68% (228/337) had ≥12-month follow-up available. Asthma was a common comorbidity (23% patients). Rates of patients treated with nearly all concomitant AD-related therapies reduced from 12 months before to 12 months after dupilumab treatment: antibacterials (from 59% to 50%), systemic corticosteroids (55% to 29%), antihistamines (54% to 38%) and cyclosporine (52% to 7%). A similar trend was observed among patients with asthma as comorbidity. Within 12 months before/after dupilumab, patients hospitalized halved from 14% to 7%, and patients receiving outpatient specialist care reduced from 72% to 65%. Annual mean direct total costs per patient treated with dupilumab charged to the SSN, net of dupilumab cost, were €1384 and €773, before and after dupilumab dispensation, respectively. CONCLUSIONS: Before dupilumab, observed patients had higher healthcare resource consumptions and direct SSN costs than after dupilumab.

Drug Survival of Upadacitinib and Predicting Factors of Discontinuation in Adult Patients Affected by Moderate-to-Severe Atopic Dermatitis: An Italian Multicenter Analysis.

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18-75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020-August 2023. Upadacitinib survival was investigated through Kaplan-Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

Italian S3-Guideline on the treatment of Atopic Eczema - First Update, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Vitiligo: Epidemiology and Economic Impact.

INTRODUCTION: Vitiligo is an acquired disorder of pigmentation, characterized by the development of white patches on the skin, often with a typical symmetrical distribution and progressive extension . Although vitiligo does not cause direct physical impairment, it can produce a relevant psychosocial burden. Despite this burden, effective treatments are lacking, emphasizing the need for new therapeutic options. OBJECTIVES: The aim of this study was to systematically scan the scientific literature for studies dealing with vitiligo epidemiology. Additionally, the study aimed to assess the social costs of vitiligo, ultimately raising awareness about the societal impact of the condition. The focus was on Italian data. METHODS: Our research employed a comprehensive methodology. For the epidemiology, we systematically searched PubMed database up to October 2023 and complemented the analysis with Real World Evidence. For social costs, we conducted an in-depth literature review, administered a web-survey to 20 Italian dermatologists and conducted an equivalent number of interviews during the same period in March 2022. RESULTS: The data suggest that in Italy the prevalence of vitiligo increases with age, and it varies from 0.19% (age 18-21) to 0.6% (age >45) . We estimated 152,000 patients diagnosed with Non-Segmental Vitiligo (NSV) in Italy; based on Body Surface Area (BSA), 33% are Not Severe, 31% Mild, 27% Moderate/Severe, 9% Very Severe. The yearly social costs of vitiligo amount to €0.5Bln. CONCLUSIONS: There is a remarkable association of vitiligo with anxiety and depression , and Mental Health is associated with 30% of social costs. Moreover, vitiligo social costs distribution highlights inequity, with patients bearing 55% of them.

Relapsing subcutaneous nodules of the penis in a pediatric patient.

A 14-year-old boy presented with a history of non-tender, subcutaneous coalescing nodules located on the ventral-lateral aspects of the penis shaft for one year. Laboratory investigations for blood count and autoimmunity were within normal limits. Complete excision was performed, and on histology, the dermis showed necrobiotic material composed of altered collagen bundles, surrounded by a palisade of histiocytes and scattered lymphocytes, thus allowing a diagnosis of subcutaneous granuloma annulare. Only 18 published cases reported penile granuloma annulare. Medical management was advocated in 7/18 cases, either as a first-line or adjuvant therapy where surgery was not radical. Three patients received high-potency local steroids: two cases underwent adjuvant sessions of intralesional triamcinolone, and one patient received pentoxifylline orally. Surgery should be considered a second-line option since 5/8 of treated cases eventually recurred. The pentoxifylline-treated case witnessed a relapse after drug discontinuation, while topical steroids lead to complete recovery without relapses.