Clinical determinants of clinical response to Sonidegib in advanced basal cell carcinoma: a monocenter experience.

OBJECTIVE: The purpose of this study is to evaluate the clinical determinants of complete response in locally advanced basal cell carcinoma (laBCC) patients receiving Sonidegib in a real-life, retrospective, observational study.  Hedgehog pathway inhibitors (Vismodegib and Sonidegib) are approved for the systemic treatment of locally advanced basal cell carcinoma (laBCC). The objective response rate was the primary endpoint of the trials for both drugs. PATIENTS AND METHODS: Adult patients with laBCC treated with Sonidegib at the Dermato-Oncology Unit of IFO San Gallicano between June 2020 and September 2022 were included in the study. Patient, tumor, and treatment characteristics were recorded. The complete response rate was the primary outcome. The median time to the best response and complete response were the secondary outcomes. Treatment-related adverse events (TRAEs) and dose adjustments were recorded. RESULTS: Of the 19 patients included in the study, eight (42.1%) achieved a complete response, seven (36.8%) had a partial response, and four experienced progressive disease (21%). The median time to the best response was 3 months in the group of patients with partial response (range 2.0-4.0, with three patients not evaluable) and 3.5 months in the group of patients with complete response (range 2-5). TRAEs occurred in 14 (73.6%) patients, with 8 (57.1%) reporting ≤2 TRAE categories and 6 (42.8%) >2. A total of 78.9% of patients received a modified treatment schedule; 12.5% of patients who achieved a complete response received full dosage from the beginning to the end of treatment, compared with 27.3% of those with a partial response. CONCLUSIONS: The associations between the clinical outcome of interest (objective response rate) and the clinicopathological and treatment characteristics were evaluated. No statistically significant association was observed. Our analysis confirms the observation that no statistically significant correlation exists between clinical response and Sonidegib alternate dose regimen.

Pola-R-CHP for frontline therapy in DLBCL: Are we saving money by spending more?

The study by Kambhampati et al. offers the first European perspective on cost-effectiveness of pola-R-CHP in the frontline line treatment of DLBCL patients. Nevertheless, the applicability of these results in other European settings remain questionable: Germany is indeed a wealthy country with wide access to cellular therapies in earlier lines, while this might not be the case for other European countries. The presented data must be re-assessed when long term data on PFS and OS from the POLARIX trial are available, ideally considering also real-life data. Similar CEAs in other European health care systems as well as in specific subgroups of patients are welcome to offer a broader perspective on the potential role of pola-R-CHP in Europe. Commentary on: Kambhampati et al. Cost effectiveness of polatuzumab vedotin in combination with chemoimmunotherapy (pola-R-CHP) in previously untreated diffuse large B-cell lymphoma in Germany. Br J Haematol 2023;202:771-775.

Alopecia neoplastica as a sign of visceral malignancies: a systematic review.

Alopecia neoplastica (AN) from visceral tumours is a rare form of cutaneous metastasis in which internal malignancies spread to the scalp. The diagnosis of AN may be very challenging, especially when its onset precedes the diagnosis of the primary tumour. We aimed to improve the knowledge on AN, highlighting that in case of scarring localized alopecia, a differential diagnosis with metastasis should always be considered. We performed a systematic review to describe the main demographic and clinical features associated with AN from visceral malignancies; a survival analysis was also performed. In 118 reports, accounting for 123 patients, we found that women were more affected by AN than men (53.7% vs. 46.3%). The most frequent site of the primary tumour was the gastrointestinal tract (24.4%), followed by breast (17.9%), kidney (8.1%), lung (7.3%), thyroid (7.3%), uterus (6.5%), central nervous system (6.5%), liver (3.3%) and other anatomic areas for 18.7% of cases. Furthermore, in more than half of the cases (66.1%), AN lesions were single and were mainly diagnosed after the primary visceral tumour (71.5%). Finally, survival analysis highlighted a lower progression-free survival in men; while, no significant differences in overall survival were reported among genders. In conclusion, metastatic skin disease should always be taken into consideration when dealing with patients with localized scarring alopecia.

Sclerosing nevus with pseudomelanomatous features: dermoscopic and confocal aspects.

BACKGROUND: Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. OBJECTIVE: The aim of our study was to describe the dermoscopic and confocal features of SNPF. METHODS: Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. RESULTS: The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. CONCLUSIONS: The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.

Physician-patient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (AK-TRAIN): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in Italy.

BACKGROUND: Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients' adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician-patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. OBJECTIVES: We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies. METHODS: In this observational, multicentre, longitudinal, cohort study, we included 1136 adult patients with discrete, clinically detectable, visible, multiple (three or more lesions in a 25 cm2 area), Grade I/II AKs, for whom the attending dermatologist has prescribed treatment with a topical field-directed therapy. We matched self-reported data and medical information recorded by dermatologists in standard clinical forms. Patients were followed up at two time points (T1: 8 days; T2: 25-30 days) RESULTS: Most patients were elderly, married, men with poor socio-economic status and multiple lesions of the scalp or face. The majority (n = 961) had a prescription of ingenol mebutate (IMB) and 175 received either diclofenac 3% in hyaluronic acid (DHA) or imiquimod 5% (IMQ). Clearance rate at 1 month was 84%. Most patients felt very supported (n = 819, 73%) and rated dermatologist's explanations very clear (n = 608, 54%). Treatment satisfaction (effectiveness and convenience scales) increased along the follow-up, especially for those on IMB (Δpre-post  = -4.00; other: Δpre-post  = -0.25; interaction P < 0.001). Communication clarity was associated with higher treatment satisfaction scores (ß = 0.4-0.6, P < 0.01) and lower risk of non-adherence among IMB patients (risk difference: 16%, P < 0.01). CONCLUSION: Communication clarity was associated with patient-reported outcomes and adherence beyond AK-related clinical parameters. Our study questions the current episodic approach to AK management and provides the rationale to develop chronic care models fostering patients' engagement and treatment alliance.

Successfully treated superficial basal cell carcinomas with ingenol mebutate 0.05% gel: Report of twenty cases.

Surgery is the therapy of choice in the guidelines to treat basal cell carcinomas (BCCs) but a variety of non-surgical options are available. The objective of this study is to evaluate the efficacy and safety of ingenol mebutate 0.05% gel for the treatment of superficial BCCs. We accepted twenty patients with superficial BCCs on the body and we treated them once daily for two consecutive days with ingenol mebutate 0.05% gel. We examined the lesions at the screening visit and after four days from the gel application to describe the local skin reaction due to the therapy. Then we followed the patients after two and six months from the first visit. All the lesions were clinically and dermoscopically documented with a digital camera and we used the LSR (local skin reaction) grading scale based on a 0-4 numerical index of severity with specific clinical parameters and a characteristic photographic image for each rating, to assess the local side effects related to the therapy.

Combination therapy with hydrogen peroxide (4%), salicylic acid (0.5%) and D-panthenol (4%): efficacy and skyn tolerability in common acne vulgaris during sun exposure period.

OBJECTIVE: Acne vulgaris is a disease of the sebaceous follicle which affects up to 90% of adolescent patients. Topical retinoids, benzoyl peroxide and antibiotics are the main treatments for mild to moderate acne vulgaris. The use of such topical treatments is often associated with local irritation and dryness making the skin more sensitive to the sun. The aim of our study was to assess the efficacy and skin tolerability of a fixed-dose combination therapy with hydrogen peroxide (4%), Salicylic acid (0.5%) and D-panthenol (4%) (HSD) gel, in mild-moderate acne vulgaris, during the period of sun exposure. PATIENTS AND METHODS: We retrospectively observed 30 patients of Central Italy with mild to moderate acne between April and September 2012. All the patients selected underwent only therapy with HSD gel once a day in the evening for 60 days, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. RESULTS: The mean GES value showed a statistically significant reduction: 2.03 (SD 0.81) at baseline, 1.63 (SD 0.81) and 0.90 (SD 0.71) respectively at 30 and 60 days (p < 0.01). 21 (70%) and 27 patients (90%) did show good or very good tolerability at 30 and 60 days respectively. CONCLUSIONS: Topical treatments with retinoids, antibiotics and antiseptics may increase skin irritation reducing patient adherence to the treatment. HSD gel has shown a good skin tolerability and efficacy in reducing acne lesions, even during the sun exposure period in which traditional treatments should be cautiously used.

Combination therapy with retinaldehyde (0.1%) glycolic acid (6%) and efectiose (0.1%) in mild to moderate acne vulgaris during the period of sun exposure--efficacy and skin tolerability.

OBJECTIVES: Acne vulgaris is the most common disease of the adolescence age (70-94%). Main topical treatments for acne vulgaris are retinoids, benzoyl peroxide and antibiotics in mono or combination therapy. Topical retinoids, some antibiotics and antiseptics although effective on acne lesions, can due photosensitivity or make the skin more sensitive to the sun. Our study is aimed to evaluate the efficacy and tolerability of a combination therapy with Retinaldheyde (0.1%), Glycolic acid (6%) and Efectiose (0.1%) (RGE) cream in patients affected by acne vulgaris, during the lasting period of sun exposure. PATIENTS AND METHODS: We retrospectively observed 30 patients of Central Italy with mild or moderate acne between April and September. All the patients selected underwent only therapy with RGE cream once a day in the evening for 8 weeks, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. RESULTS: The mean GES value showed a statistically significant reduction: 1.83 (SD 0.83) at baseline 1.57 (SD 0.77) and 0.90 (SD 0.76) respectively at 30 and 60 days (p < 0.01). Side effects were very uncommon. CONCLUSIONS: Topical treatments with retinoids, antibiotics and antiseptics can be associated with an increased occurrence of facial dryness and erythema restricting their use in sun exposure period. RGE cream has shown a good skin tolerability and efficacy, so it can be considerate an effective maintaining therapy to treat mild to moderate acne during the sun exposure period in which retinoids, antibiotics or antiseptic treatments are not recommended.

Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Topical anesthetics for cosmetic dermatologic procedures.

AIM: The aim of our study is to value the vasoconstrictor effect of two most utilized topical anesthetics, the first one containing a mixture 2.5% lidocaine and 2.5% prilocaine and the second one containing 4% liposomal lidocaine, in the treatment of vascular lesion during cosmetic dermatologic procedures. METHODS: Ten healthy volunteers were enrolled in our department. They showed telangiectasias, measuring between 0.5 and 1 millimeter in diameter on their face and limbs. Five volunteers were randomized to receive topical 4% liposomal lidocaine and five to receive 2.5% lidocaine and 2.5% prilocaine. In all treated areas, the 4% liposomal lidocaine was left for at least 30 minutes and the 2.5% lidocaine and 2.5% prilocaine was left for at least 60 minutes. RESULTS: Clinically, the volunteers who received the 4% liposomal lidocaine showed minimal vasoconstrictor difference between before and after treatment; while the others who received the 2.5% lidocaine and 2.5% prilocaine showed a major vasoconstrictor effect. Furthermore the 4% liposomal lidocaine cream has the advantage of an anesthetic effect after 30 minutes, rather than 60 minutes for the 2.5% lidocaine and 2.5% prilocaine cream. CONCLUSION: This study demonstrated that the 4% liposomal lidocaine has relatively minor vasoconstrictor effect when compared to the other anesthetic, and it shows how this type of anesthetic allows a clear vision of the lesion during the dermatologic procedures. Furthermore, this cream achieves an anesthetic effect in 30 minutes rather than the 60 minutes required for the other cream, making the first one more suitable for cosmetic dermatologic procedures and for the emergency.

Cost-effectiveness analysis of topical treatments for actinic keratosis in the perspective of the Italian health care system.

Actinic keratosis (AK) is the most common cutaneous malignant neoplasm and its prevalence continues to increase. According to the most recent findings, AK is currently considered the initial stage, in situ, of squamous cell carcinoma. Field-directed therapies for AKs are the preferred treatment since they have the advantage to clear the clinically visible lesions and also subclinical lesions within the cancerous field. We assessed the cost-effectiveness of topical treatments for AKs including 3% diclofenac in 2.5% hyaluronic acid (HA) gel, imiquimod 5% cream and photodynamic therapy with methyl aminolevulinate (MAL-PDT) in the perspective of the Italian Health Care System (SSN). We used a decision tree analytical approach and efficacy data were drawn from published clinical trials. Cost was evaluated from the SSN perspective during a time horizon of 3 months. A responder was defined as a patient with all lesions clinically cleared and showing an excellent cosmetic result. Based on the applied model, the cost per complete responder was calculated. Diclofenac 3% in HA was less expensive (Euro 256) than MAL-PDT (Euro 320) and imiquimod (Euro 342). Effectiveness was similar and better for diclofenac 3% in HA and MAL-PDT (0.813%) in comparison to 0.734% of imiquimod, respectively. The one-way and probabilistic sensitivity analyses confirmed the results of base case scenario. Based on this cost-effectiveness model, diclofenac 3% in HA can be considered the treatment of choice for AK lesions and surrounding field under a pharmacoeconomic point of view.

Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario).

BACKGROUND: Scabies is a very common skin infection in convicts. The SIMSPE Society (Società Italiana di Medicina e Sanità Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion. METHODS: A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured. RESULTS: At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group. CONCLUSION: Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.

[Usefulness of the immunologic profile in "creeping disease." Apropos of a case appearing autochthonously]. / Utilità dell'indagine immunologica nella "creeping disease." A proposito di un caso ad insorgenza autoctona.

A case of "autochthonous" cutaneous larva migrans observed in a patient from the Lazio region (Italy) is described and rarity of the case is stressed. The epidemiological aspects, the pathogenetic problems and the contribution of the sero-immunological methods to the diagnosis are discussed.

Cyclosporin A and psoriasis: a thermographic study.

The thermographic method permits the making of a rigorous evaluation of the cutaneous blood flow by means of thermal recovery times after thermostimulation at 5 degrees C for 20 sec. The aim of the present study was to examine the blood flow of the psoriatic skin of 7 patients before and after a course of cyclosporin therapy, by means of this method. The results show a constant, initial hyperthermia with precocious thermal recovery times, in comparison with the healthy perilesional skin. Following therapy, a prolongation of the thermal recovery time was observed in all of the patients, together with a significant improvement of the dermatosis.

[Thermographic study of the percutaneous absorption of corticosteroids]. / Studio termografico sull'assorbimento percutaneo dei corticosteroidi.

The results of a study on the percutaneous absorption of two corticosteroids, Halcinonide at 0.1% and Triamcinolone acetonide at 0.1%, employing an original thermographic method, are reported. In a first group of subjects treated with one application of the two corticosteroids a stronger activity of the Halcinonide was found than in a second group of subjects, after repeated applications, resulting progressively more evident and of longer duration in comparison with Triamcinolone.