Guidelines 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 10 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) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (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.

Prurigo-like atopic dermatitis in a child with CARD11-associated severe combined immunodeficiency successfully treated with dupilumab.

A 12-year-old boy affected by severe combined immunodeficiency due to a heterozygous variant in the CARD domain of CARD11, c.169G>A; p.Glu57Lys, developed severe atopic dermatitis and alopecia areata. After failure of conventional systemic therapy, dupilumab was administered at a dose of 400 mg subcutaneously, followed by 200 mg every 14 days. The patient had an excellent clinical response after 1 month and complete remission after a year, with the absence of side effects, demonstrating good efficacy and safety profile.

"Your Skin Tells You" Campaign for Keratinocyte Cancers: When Individuals' Selection Makes the Difference.

BACKGROUND: Prevention campaigns for skin cancers have focused primarily on melanoma, and over time there has been increasing awareness of the need to select the population to be screened to maximize program effectiveness. OBJECTIVES: The objective of the study was to report the results of a free dermatological initiative, as part of an awareness campaign dedicated to keratinocyte cancers, targeting individuals pre-selected through a short questionnaire. METHODS: One day of dermatological consultations was held at 15 dermato-oncology referral centers during May 22-June 30, 2021. For selection, individuals answered a telephone interview consisting of 7 yes/no questions on risk factors. Demographics, clinical characteristics of suspicious tumors, and histopathologic diagnosis of excised lesions were collected. Suspicion rate, detection rate, and positive predictive values (PPVs) for any skin cancer, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were calculated. RESULTS: A total of 320 individuals (56.9% males; 43.1% females) with a median age of 69.6 (range 21-91) years qualified for the screening initiative. Overall, skin cancers and precancerous lesions were diagnosed in 65.9% of the patients. Suspicion rate was 28.7% for any skin cancer (92/320), 22.8% for BCC (73/320), 4.7% for cSCC (15/320), and 1.2% for melanoma (4/320). Detection rate was 23.4% for any skin cancer (PPV 93.7%), 18.1% for BCC (PPV 95.1%), 4.4% for cSCC (PPV 93.3%), and 0.9% for melanoma (PPV 75%). CONCLUSIONS: Selection of individuals at high risk is a cost-effective approach for early detection campaigns for keratinocyte cancers.

Concern about the Effectiveness of mRNA Vaccination Technology and Its Long-Term Safety: Potential Interference on miRNA Machinery.

After the outbreak of the pandemic due to COVID-19 infection, several vaccines were developed on short timelines to counteract the public health crisis. To allow the administration of mRNA vaccines through a faster-paced approval process, the Emergency Use Authorization (EUA) was applied. The Ba.5 (omicron) variant of SARS-CoV-2 is the predominant one at this moment. Its highly mutable single-stranded RNA genome, along with its high transmissivity, generated concern about the effectiveness of vaccination. The interaction between the vaccine and the host cell is finely regulated by miRNA machinery, a complex network that oversees a wide range of biological processes. The dysregulation of miRNA machinery has been associated with the development of clinical complications during COVID-19 infection and, moreover, to several human pathologies, among which is cancer disease. Now that in some areas, four doses of mRNA vaccine have been administered, it is natural to wonder about its effectiveness and long-term safety.

Sequential treatments of Hailey-Hailey disease with photodynamic therapy, botulinum toxin type A and dapsone: A case report.

Hailey-Hailey disease is a rare autosomal dominant chronic recalcitrant blistering genodermatosis involving the intertriginous areas. Therapeutic options are various, depending on the type and size of the lesion, and include topical and systemic corticosteroids, topical and systemic retinoids, and DMARDs, but the only true curative approach is represented by the destruction of the affected areas through different techniques like carbon dioxide laser, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A. We report a case of Hailey-Hailey disease successfully treated with a consequential regimen of PDT, botulinum toxin type A and dapsone.

Hidradenitis Suppurativa in a Large Cohort of Italian Patients: Evaluation of the Burden of Disease.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). OBJECTIVE: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. METHODS: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). RESULTS: A total of 308 patients (56.2% women; mean age 35.2 ± 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 ± 23.3, Skindex-16: 60.3 ± 26.9, and DLQI: 10.8 ± 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. CONCLUSION: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Characterization of Basosquamous Cell Carcinoma: A Distinct Type of Keratinizing Tumour.

Basosquamous carcinoma is a rare clinical entity, which comprises 1.7-2.7% of all skin carcinomas. It is described as a basal cell carcinoma with features of squamous differentiation. To date, studies of the epidemiology of basosquamous carcinoma have been few and small in size. We report here the most extensive series of basosquamous carcinomas published to date, highlighting the differences between basosquamous carcinoma and other keratinizing tumours. Patients undergoing surgical excision for keratinizing tumours were enrolled in this study. Age, sex and tumour characteristics were recorded. A total of 1,519 squamous cell carcinomas, 288 basosquamous carcinomas and 4,235 basal cell carcinomas were collected. Basosquamous features were compared with those of basal cell and squamous cell carcinomas. For basosquamous carcinomas, 70.5% were located on the head and neck, particularly on the nose, forehead and cheeks, and represented almost 10% of the keratinizing tumours on the ears. Significant differences were found between basosquamous carcinoma and basal cell or squamous cell carcinomas. Basosquamous carcinoma should be considered a distinct type of keratinizing tumour with different anatomical, sex and age distributions.

Secukinumab Improves Patient Perception of Anxiety and Depression in Patients with Moderate to Severe Psoriasis: A Post hoc Analysis of the SUPREME Study.

This study evaluated whether secukinumab treatment for patients with moderate to severe plaque psoriasis correlates with improvements in symptoms of anxiety and depression. SUPREME was a 24-week, phase IIIb, multicentre, prospective study conducted across 50 centres in Italy with an extension period of up to 72 weeks. Assessments used were: Psoriasis Area Sever-ity Index (PASI), Hospital Anxiety and Depression Scale (HADS) - Anxiety (HADS-A), and HADS - Depression (HADS-D) scores and Dermatology Quality Life Index (DLQI). Compared with baseline, a significantly greater proportion of patients who reported moderate to severe clinical symptoms of anxiety or depression (HADS-A or HADS-D ≥ 11) were free of moderate to severe symptoms at weeks 16 and 48. The PASI and DLQI scores reduced over time with secukinumab treatment. Psoriasis treatment with secukinumab for 48 weeks resulted in significantly improved skin clearance and a parallel improvement in symptoms of anxiety and depression, assessed by HADS.

Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Wound Repair and Extremely Low Frequency-Electromagnetic Field: Insight from In Vitro Study and Potential Clinical Application.

Wound healing is a complex, staged process. It involves extensive communication between the different cellular constituents of various compartments of the skin and its extracellular matrix (ECM). Different signaling pathways are determined by a mutual influence on each other, resulting in a dynamic and complex crosstalk. It consists of various dynamic processes including a series of overlapping phases: hemostasis, inflammation response, new tissue formation, and tissue remodeling. Interruption or deregulation of one or more of these phases may lead to non-healing (chronic) wounds. The most important factor among local and systemic exogenous factors leading to a chronic wound is infection with a biofilm presence. In the last few years, an increasing number of reports have evaluated the effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on tissue repair. Each experimental result comes from a single element of this complex process. An interaction between ELF-EMFs and healing has shown to effectively modulate inflammation, protease matrix rearrangement, neo-angiogenesis, senescence, stem-cell proliferation, and epithelialization. These effects are strictly related to the time of exposure, waveform, frequency, and amplitude. In this review, we focus on the effect of ELF-EMFs on different wound healing phases.

Effect of immunosuppressive drugs in immune-mediated inflammatory disease during the coronavirus pandemic.

The safety of immunosuppressive treatment in patients with Immune-Mediated Inflammatory Diseases (IMIDs) during the Coronavirus pandemic is questioned and it is utmost important for public health. We searched studies trough MEDLINE/EMBASE database, including patient with IMID, undergoing immunosuppressive treatment with a positive diagnosis for SARS-CoV 2. We included 11 studies for the descriptive analysis and 10 studies for the pooled analysis, with a total population of 57 and 53 IMID-affected SARS-CoV-positive patients respectively. Overall no death was reported; 16 patients were hospitalized (30.2%) and only two cases were admitted to Intensive Care Unit (ICU) (3.8%). We found a significant association between the risk of hospitalization and older age (P .03), obesity (P .02), and presence of multi-comorbidity (P .03). No significant association was found between the risk of hospitalization and the use of biological or conventional DMARDs (respectively P .32 and .26), neither when they are used combined (P .85). We found consistent results in the sub-analysis of Psoriasis: 10 patients were hospitalized (31.3%) and only one case was admitted to Intensive Care Unit (ICU) (3.1%) Particular attention should be placed for patients with older age, obesity and multi-comorbidity that are at higher risk of hospitalization.

COVID-19 and psoriasis: Should we fear for patients treated with biologics?

The new coronavirus pandemic poses question and challenges for dermatologists. One of question is if psoriasis patients treated with immunomodulating and immunosuppressive drugs have to discontinue their treatment in the midst of fears for the infection and its consequences. One of the challenges is how can we support our patients in this critical time. Previous coronaviruses outbreaks reports, current published evidences on pathogenesis and on clinical reports of COVID infection in immunosuppressed patients are used to make a scientifically based decision.

Validation and Field Performance of the Italian Version of the Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire.

Psoriatic arthritis (PsA) is a potentially severe inflammatory condition (entheso-arthro-osteopathy), and early diagnosis is important to guide treatment choices in patients with psoriasis. The objective of this study is to further validate the PsA Screening and Evaluation (PASE) questionnaire, and to assess its field performance. Data were collected in 10 Italian centres, and the PASE was administered at baseline, after 3 days and after 3 months. The Skindex-29 was also administered. To determine the best cut-off value to identify patients with PsA we produced receiver operating characteristic (ROC) curves using the rheumatologist's diagnosis as outcome. Of the 298 patients that were enrolled, 28% were classified as having PsA according to the CASPAR criteria, while 19% had received a diagnosis of PsA from a rheumatologist. PASE score were always significantly different in patients with or without PsA, while Skindex-29 scores never were. The internal consistency of the PASE was very good (Cronbach's α of 0.90-0.95), the test-retest reliability was also very high (intraclass correlation coefficients 0.91-0.93), and the PASE scores showed good responsiveness to clinical change over time. The optimal cut-off identified through the ROC curves was ≥ 48 on the total PASE score, which was able to distinguish PsA from non-PsA patients with a 73.2% sensitivity and a 76.1% specificity. Our results confirm the good psychometric properties of the PASE, and indicate that it may be a useful tool for the dermatologists, both to screen for PsA and to obtain a standardized patient-reported measure to monitor and evaluate the health status of the patients with PsA.