Anti-Herpes zoster vaccination in patients with dermatologic diseases: a position statement from the Italian SIDeMaST group of sexually transmitted, infectious and tropical diseases.

Herpes zoster (HZ) is a condition caused by the reactivation of varicella-zoster virus (VZV), the virus responsible for chickepox, which is the clinical manifestation of the primary infection. Congenital or acquired immune system deficiencies, as well as the physiological decline in immune response occurring in the elderly, known as immune senescence, can allow VZV reactivation and, consequently, HZ. One out of 3 people develops HZ during their lifetime. Moreover, thirty percent of the affected subjects develop post-herpetic neuralgia, the most frequent complication after HZ skin rash. Patients with dermatological conditions characterized by alteration of the immune system, such as systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous diseases, and cutaneous lymphomas, are at higher risk of developing HZ and post-herpetic neuralgia, even when their disease is in remission. In the present work, we described the currently available vaccinations against HZ and provided recommendations for the vaccination against HZ in patients with dermatological diseases.

Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022.

Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022.

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022.

A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("tumor board"). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600  E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600  E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

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 moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Treatment adherence with diclofenac 3% gel among patients with multiple actinic keratoses: an integrated low-intensity intervention program versus standard-of-care.

BACKGROUND: Diclofenac 3% gel is a widely used topical treatment with proven efficacy in reducing the burden of actinic keratosis (AK); however, clinical benefit might not fully translate in clinical practice as nonadherence is substantial for prolonged treatment regimens. We evaluated the efficacy of an integrated low-intensity intervention program versus standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3%. METHODS: We designed an open label, randomized, parallel group, interventional, multicenter, longitudinal cohort study including patients with multiple, grade I/II AKs. Visits were scheduled for end of treatment (T4), follow-up 1 (T5) and follow-up 2 (T6) at 90, 180 and 365 days from baseline, respectively. Patients in the intervention group received additional visits at 30 and 60 days from baseline, a brief health education intervention, an enhanced patient-physician communication, a weekly SMS reminder to medication prescriptions. RESULTS: Patients were equally allocated between intervention (intervention group [IG], N.=86) and control group ([CG] N.=86); at baseline, both groups had similar socio-demographic and clinical characteristics. Change scores from baseline showed a slight increment in quality of life related to AK in both groups (CG: ΔT4-T1=-0.079; IG: ΔT4-T1=-0.006; P=0.39) and in quality of physician-patient interaction reported by IG (ΔT3-T2=0.18; P<0.0001). Adherence rate was not statistically different between IG and CG (28.4% vs. 40.7%; P=0.11). Patients reported similar satisfaction for effectiveness, convenience and side effects of treatment. Clinical conditions improved over time and results did not differ between groups; complete clearance rate at 1 year was 18% and 29% for CG and IG, respectively. CONCLUSIONS: Our findings showed no difference in adherence rate between the two groups, suggesting that enhanced follow-up interventions and health care education may not be sufficient drivers to promote adherence among this clinical population. Further studies are needed to explore barriers to adherence with treatments for AKs.

Impact of psoriatic disease on women aged 18 to 45: Results from a multinational survey across 11 European countries.

BACKGROUND: Plaque psoriasis (PSO) is a long-term inflammatory condition that can cause concomitant joint symptoms (psoriatic arthritis [PsA]) in up to 30% of patients. The impact of psoriatic disease on disease outcomes and quality of life is greater in women than men. OBJECTIVE: We evaluated the impact of psoriatic disease on women aged 18 to 45 years across Europe. METHODS: Women aged 18 to 45 years with moderate to severe PSO, PsA, or PSO + PsA (PSO with progression to PsA) and prior biologic experience were recruited from market research panels and patient association groups of the International Federation of Psoriasis Associations, European Federation of Psoriasis Patient Associations, and Arthritis Ireland and asked to complete a survey. Questions covered social and psychological wellbeing, employment, and family planning. Question types included 5- or 7-point agreement scales, where the highest/lowest two ratings were considered agreement/disagreement, respectively. The results are reported as proportions of those who selected the answer, divided by overall respondents for each question. Women were not required to answer all questions. RESULTS: Survey respondents (N = 573) had a diagnosis of PSO (n = 236), PsA (n = 173), or PSO + PsA (n = 164). Women self-reported similar mean scores for physical (57.0 of 100) and mental (59.0 of 100) health. A fifth (21%) had not achieved their desired career due to PSO/PsA; career dissatisfaction and increased sick leave were linked to poor mental health. Some women reported having a limited social life (33%), smaller families (34%), and being more likely to adopt children (27%) due to PSO/PsA. A quarter of women (27%) reported not understanding enough about PSO/PsA (nonmembers vs. members of patient association groups: 37% vs. 8%). CONCLUSION: Our findings highlight the considerable burden of psoriatic disease on women of childbearing age. Increased provision of information tailored to women, training for health care professionals, and shared decision-making between patients and health care professionals may help better support women with psoriatic disease.

5-Aminolaevulinic acid patch photodynamic therapy for the treatment of actinic keratoses: preliminary results from an Italian study in the real-life setting.

BACKGROUND: Photodynamic therapy (PDT) is recommended for both lesion and field therapy of actinic keratoses (AKs). The 5-aminolaevulinic acid (5-ALA) patch PDT is indicated for the treatment of isolated mild AKs (≤1.8 cm) on the face and bald scalp. It was demonstrated to be effective and safe in clinical trials with a good tolerability profile. METHODS: In this retrospective multicenter real-life study, 33 patients with a total of 99 AKs of the scalp, face, ears, and/or hands and 2 actinic cheilitis were treated with one treatment session of 5-ALA patch PDT with a red light source (total dose of 37 J/cm2). RESULTS: Overall, 12 weeks after treatment, 68/99 (69%) lesions were completely cleared. Complete response was obtained in 82% of AKs on the ears, 78% on the face, 57% on the hands, and 56% on the scalp and in the two actinic cheilitis. The treatment was very effective on grade I AKs, cleared in 87% of the cases and less efficient on grade II-III lesions, cleared in 47% of the cases. 5-ALA patch PDT was well tolerated with a good to excellent cosmetic outcome in 97% of the patients and with 94% of the patients being satisfied or very satisfied with the treatment. CONCLUSIONS: Our results confirm that 5-ALA patch PDT is a good option for AK treatment in clinical practice, it is easy to use, effective and well tolerated even in difficult-to-treat-areas. Moreover, it has an excellent cosmetic outcome.

Intralesional Methotrexate for the Treatment of Advanced Keratinocytic Tumors: A Multi-Center Retrospective Study.

INTRODUCTION: Keratinocyte tumors (KT) are frequently observed. Surgery is the treatment gold standard. In some cases, a surgical approach might not be the best option. Radiotherapy (RT) and systemic treatments can frequently cause side effects or be contraindicated. Intralesional methotrexate (MTX) can be a conservative yet effective alternative. We decided to evaluate the effectiveness and safety of intralesional chemotherapy with MTX for the treatment of squamous cell carcinoma (SCC), keratoacanthoma (KA), and basal cell carcinoma (BCC). METHODS: All patients had a histologically confirmed diagnosis of BCC, SCC, or KA and no indication to surgery or RT. MTX was injected subcutaneously proceeding from the periphery of the lesion toward the center. Different protocols in terms of dose, frequency, and length of treatment were used to compare them. Treatment efficacy was evaluated in terms of tumor size reduction. Patients were divided into three groups: responders (improvement of more than 50%), partial responders (< 50%), and non-responders (no improvement or worsening). All data were analyzed using the chi-squared test (χ2). RESULTS: Thirty-five patients were included. Twenty-one patients suffered from SCC, 12 from KA, and 2 from BCC. KA showed a higher response rate than SCC and BCC. For AK, 92% of patients had a complete resolution; 8% were partial responders. For SCC, 47.6% of cases were responders and 14.3% partial responders, while 38% non-responders. All BCCs showed no improvement. A treatment protocol of weekly injections, performed for 4 to 6 weeks, was the most efficient. Doses of 25 mg/ml per session seemed to be most effective. About one third of our patients developed side effects with mild anemia being the most frequent. CONCLUSIONS: For selected cases, intralesional MTX can be a safe and effective option for the treatment of KT, especially in case of KA and, to a lesser extent, SCC.

Efficacy and safety of Vismodegib treatment in patients with advanced basal cell carcinoma and multiple comorbidities.

Basal cell carcinoma (BCC) is the most common malignancy in Caucasians, and its incidence is increasing. Most BCCs are treated surgically, nevertheless surgery is not an effective treatment for locally advanced or metastatic BCC. Alterations in hedgehog signaling pathway, a key regulator of cell growth and differentiation during development, are implicated in the pathogenesis of basal-cell carcinoma. Vismodegib is a small-molecule inhibitor of smoothened (SMO), a key component of the hedgehog (Hh) signaling pathway, administered in BCC patients, especially when surgery and radiotherapy treatments have failed. We report a series of eight elderly patients treated with vismodegib for advanced BCC and affected by concomitant multiple comorbidities. The efficacy and tolerability of vismodegib in patients with single and/or multiple comorbidities has been poorly studied. In our observation an overall high safety and tolerability has been observed over the course of treatment, with side effects of grade I and II and no changes in vital parameters, electrocardiography and echocardiogram. Vismodegib has been shown to be a safe and well tolerated treatment option for elderly patients affected by multiple comorbidities and advanced BCC.

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study.

Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra-tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies.

Cutaneous squamous cell carcinoma. Italian Guidelines by SIDeMaST adapted to and updating EADO/EDF/EORTC guidelines.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, accounting for 20% of all cutaneous malignancies, and has an increasing incidence in the elderly as well as in the younger population. Although most cSCC is treated with simple therapeutic procedures, advanced cSCC can lead a significant risk for morbidity, negative impact on quality of life, and death. Proper management includes distinguishing between high-risk and low-risk lesions and determining treatment accordingly. A collaboration of multidisciplinary Italian experts has given birth to these recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing European (EADO-EDF-EORTC) guidelines and the expert's experience. Topics covered include diagnostic path and histopathologic assessment, tumor staging, surgical and nonsurgical procedures, follow-up and management of localized and advanced disease.

Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study.

AIM: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. MATERIALS & METHODS: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. RESULTS: In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p = 0.0024), disease control rate (p = 0.0161), median time to treatment failure (p = 0.0203) and median overall survival (p = 0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p = 0.0268 and p = 0.0272, respectively). CONCLUSION: This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy.

Clinical experience of imiquimod 3.75% for actinic keratosis: results from a case series.

BACKGROUND: In clinical studies, imiquimod 3.75% was shown to detect and treat actinic keratosis (AK) lesions across an entire sun-exposed field such as the full face or balding scalp. The aim of this study was to evaluate imiquimod 3.75% in a real-life clinical setting. METHODS: Ten AK patients applied imiquimod 3.75% to the full face or scalp once-daily in two 2-week treatment cycles separated by a two-week treatment-free interval and were followed-up eight weeks later. Seven patients rated imiquimod 3.75% versus prior treatments (cryotherapy, photodynamic therapy, diclofenac sodium 3%, imiquimod 5%, ingenol mebutate). RESULTS: The median clinical lesion count at baseline was 12.5. This increased to a median Lmax (maximum lesion count during treatment) of 22.5 as imiquimod 3.75% unmasked previously invisible subclinical lesions. At final follow-up, the median lesion count was 0. Local skin reactions such as erythema, scabbing and erosion occurred during each treatment cycle and were easy to manage. All patients considered imiquimod 3.75% easier to apply than prior treatments and 5 reported fewer or similar side effects. CONCLUSIONS: In this cohort, imiquimod 3.75% effectively cleared clinical and subclinical lesions across the entire affected field and was well tolerated.

Staging and follow-up of cutaneous melanoma patients.

Melanoma is responsible for the greatest number of deaths caused by skin malignancies. The purpose of monitoring patients diagnosed with melanoma is to allow early detection of recurrence and any subsequent primary tumors. Several dermatological and oncological societies developed their own set of guidelines for the surveillance and management of melanoma patients depending on the stage of the disease. The object of this article is to provide a comprehensive, systematic overview that summarizes and interprets previous studies, to characterize current practices regarding progression of melanoma, division into stages of development, and subsequent surveillance. We have performed a systematic review search to December 2016 using the MEDLINE database and performed a manual search of selected references. We examined the staging system and the different surveillance programs for melanoma patients. Consistent recommendations with proven evidence are available for staging melanoma patients. Conversely, recommendations are more controversial for follow-up procedures. Given the inadequate number of randomized controlled trials, consensus on the best, universally-applicable follow-up procedure has not been reached and interpretation of the roles of imaging and laboratory tests, as well as of the appropriate frequency and duration of physical examinations, vary widely. Based on a universally-accepted staging system different surveillance procedures have been developed, which may be mainly classified in two groups: low- and high-intensity strategies.

Treatments of advanced basal cell carcinoma: a review of the literature.

Advanced basal cell carcinoma (aBCC) encompasses locally advanced BCC (laBCC) and metastatic BCC (mBCC), two variants of BCC with a limited prevalence worldwide. Treatment of aBCC is still very challenging for the lack of randomized controlled trials/guidelines and the scarcity of available therapeutic options. Based on current data, surgical procedures and radiotherapy are considered the treatments of choice for aBCC although often associated with substantial morbidity and/or deformity. Alternatively, systemic chemotherapy and electrochemotherapy can be used but standardized treatment schedules and randomized clinical trials are not available for both treatments. In recent years, novel tumor-specific and pathogenesis-based molecules have been developed for the treatment of aBCC. A number of clinical trials have recently demonstrated the efficacy and tolerability of vismodegib, the first novel systemic, anti-Smo target cancer therapy for aBCC. Additional molecules currently investigated in phase I-III clinical trials include other Smo antagonists and itraconazole. The contribution of a multidisciplinary team composed of dermatologists, surgeons, oncologists, pathologists, radiologists and radiotherapists is required to deal with the spectrum of issues that emerge from managing patients affected by aBCC.