Multicenter Retrospective Andalusian Study of the Use of Sonidegib for the Treatment of Local Advanced Basal Cell Carcinoma in Real Clinical Practice.

INTRODUCTION: Locally advanced basal cell carcinoma (LA-BCC) is defined as that BCC in which there is radiological confirmation of invasion of certain neighboring structures in depth and also, usually, a BCC that is of a sufficient size and invasion (although there is no radiological demonstration of deep invasion) in which surgery and radiotherapy are not adequate, are insufficient or are contraindicated to achieve the cure of the tumor, either due to characteristics of the tumor itself or of the patient. Sonidegib is indicated for the treatment of adult patients with locally advanced basal cell carcinoma that is not amenable to curative surgery or radiotherapy. MATERIAL AND METHODS: This is a retrospective, multicenter and descriptive study in nine centers in Andalusia, Spain. Patients treated with sonidegib for >3 months for locally advanced BCC were included from 1 January 2021 to 1 January 2023. Epidemiological, efficacy and safety data were collected. RESULTS: In the present study, a total of 38 patients were included, with a median age of 76.23 years (range 40-101). Prior treatment was surgery (31.57%; n = 25), radiotherapy (15.78%; n = 6), vismodegib (31.57%; n = 12). Eleven patients had not received prior treatment. LA-BCC were located in the cephalic pole, face or scalp. There was a total response in 9/38 patients (23.7%), partial response in 25/38 patients (65.8%) and no response in 4 patients (10.52%). In 6/34 patients, the dose was reduced to 200 mg every other day until it was discontinued due to adverse effects. The main adverse effects reported were dysgeusia (n = 8), asthenia (n = 8), = 6), muscle spasms (n = 6), alopecia (n = 4) and gastrointestinal intolerance (n = 4). DISCUSSION: Sonidegib is the second iHh authorized for the treatment of adult patients with locally advanced BCC who are not amenable to curative surgery or radiotherapy, based on the results of the phase II clinical trial, BOLT. Sonidegib shows good effectiveness and an acceptable safety profile in routine clinical practice in the sample presented.

Guselkumab as a switching strategy after anti-TNFα, anti-IL17, or anti-IL12/23 therapies in moderate-to-severe psoriasis.

The IL23/Th17 axis plays a strategic role in psoriasis (PSO). Guselkumab (GUS) is a selective inhibitor of the IL23p19 subunit. Its introduction has managed to increase the levels of efficacy, safety and survival in PSO. In real clinical practice, patients can loss effectiveness or suffered adverse events that forces a change in their treatments. There is scarce evidence of the effectiveness, safety, and survival of GUS in real clinical practice after anti-TNFα, anti-IL17, and/or anti-IL12/23. This is multicenter, observational and retrospective study of real clinical practice includes patients with moderate-to-severe plaque PSO in treatment with GUS. The objective of the study was to evaluate the effectiveness of GUS after anti-TNFα, anti-IL17, and anti-IL12/23. The study includes clinical information from February 2019 to February 2022. PASI, BSA, Pruritus, DLQI, survival, and safety were evaluated up to 76 weeks. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. A total of 103 patients were included in the analysis. At baseline there were significant differences between the anti-TNF, anti-IL17, and anti-IL12/23 groups for (1) dyslipidemia; (2) number of previous biological treatments and (3) PASI, BSA, VAS Pruritus, and DLQI scores. The effectiveness of GUS in terms of PASI, BSA, Pruritus, and DLQI was not impacted by previous biological alternatives. Treatment survival including discontinuations due to lack of effectiveness or safety reasons was 100%, 92.7%, and 92.1% for anti-TNFα, anti-IL17, and anti-IL12/23, respectively, at 130 weeks. No differences were found between groups. One adverse event was reported in the anti-LI12/23 group. The mid-term effectiveness, safety and survival of GUS if not impacted by previous biological therapy as anti-TNFα, anti-IL17, and/or anti-IL12/23. Our results indicate that GUS could be a switching strategy in patients who fail or present AE to other biological alternatives in moderate-to-severe PSO.

Drug survival, discontinuation rates, and safety profile of secukinumab in real-world patients: a 152-week, multicenter, retrospective study.

BACKGROUND: Psoriasis is a chronic systemic disease that requires long-term management. Despite data on follow-up studies going back 5 years, little is known about the condition's sustainability based on patient profiles. The aim of this study was to analyze drug survival and discontinuation rates for secukinumab treatment under real-world conditions. PATIENTS AND METHODS: Patients with moderate-to-severe plaque psoriasis treated in the dermatology department of five Spanish medical centers between 2015 and 2019 were included in our retrospective study. Drug survival was assessed with Kaplan-Meier analysis plots and multivariate regression. RESULTS: In total, 171 treated patients were retrospectively recorded and analyzed for 152 weeks (37.40% had been diagnosed with psoriatic arthritis [PsA]). The discontinuation rate in the PsA group was 14.10% vs. 12.10% among those who had no PsA. The mean survival time of discontinuation was 63 weeks for PsA vs. 65 weeks for no PsA (P = 0.913). Secukinumab's estimated mean survival in PsA patients was 86% (estimated mean survival time 130 weeks) vs. 88% (estimated mean survival time of 133 weeks) in non-PsA patients (P = 0.676). CONCLUSION: The mean survival time of patients in secukinumab treatment was comparable in all patient profiles and better than the data found in clinical trials and real-life studies.

Histological Features, p53, c-Kit, and Poliomavirus Status and Impact on Survival in Merkel Cell Carcinoma Patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy from neuroendocrine cells in the skin. Despite being one of the most life-threatening of skin cancers, little is known about the potential signaling mechanism that drives carcinogenesis in MCC. The purpose of this study is to assess the impact of Merkel cell polyomavirus (MCPyV), p53, and c-kit on the histological features and clinical prognosis of MCC treated in our regional hospitals. METHOD: The design was a retrospective study. The specimens were taken between 1993 and 2013 in 2 referral hospitals of Southern Spain. Data were collected retrospectively and analyzed using SPSS software. RESULTS: Thirteen lesions from 13 subjects were included in the study. Positivity for c-kit was associated with the absence of MCPyV viral DNA (P = 0.048) and positivity for p53 (P = 0.002). More rate of mitoses per high-power field was presented significantly in those specimens with: positivity for c-kit (P = 0.046), positivity for p53 (P = 0.05), lesions with infiltrative growth pattern (P = 0.008), and lymphovascular invasion (P = 0.034). We observed an inverse relationship between p53 expression and MCPyV infection (Pearson's coefficient: -0.524; P = 0.046) and between c-kit expression and MCPyV infection (Pearson's coefficient: -0.548; P = 0.05), whereas the relationship was positive between p53 expression and c-kit expression (Pearson's coefficient: 0.884; P < 0.001). CONCLUSION: We conclude that presence of MCPyV DNA has no effect on overall survival. MCCs with p53 and c-kit expressions are associated with the absence of or low MCPyV DNA showing an inverse relationship. A multifactorial molecular pathogenesis where positivity for p53 and c-kit are associated with other mechanisms different than MCPyV (such as pro-mitotic factors) may lead to aggressive clinical behavior.

Verrucous tumor mimicking squamous cell carcinoma in immunocompetent patient.

Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals. An increase in non-tuberculous mycobacterial (NTM) infections targeting skin has been described. Many hypotheses have been developed in order to explain it: the increasing burden of immunocompromised individuals, immigration from endemic countries, improved laboratory identification techniques, and changes inhuman behavior that expose individuals to this NTM. Mycobacterium mucogenicum group comprises M. mucogenicum, Mycobacterium aubagnense, and Mycobacterium phocaicum. This group of organisms was first named Mycobacterium chelonae-like organism in 1982. Most clinically significant cases of those organisms involved catheter-related infections. Nevertheless, we report an interesting patient with a cutaneous infection produced by M. mucogenicum mimicking a squamous cell carcinoma; an excellent response to combined therapy with rifampicin and clarythromicin was observed.

Resultados del uso de etanercept en pacientes con psoriasis / Results from the use of etanercept in psoriatic patients

La psoriasis es una enfermedad crónica, inflamatoria, mediada inmunológicamente, con una considerable repercusión en la calidad de vida de los pacientes. Su importancia, además, está dada, entre otros factores, por su elevada prevalencia en la población. Los avances en el conocimiento de la inmunopatología de esta enfermedad y de la biología molecular han permitido el desarrollo de nuevos fármacos que representan una nueva forma de abordar la situación de estos pacientes, y que se encuadran en la denominada terapia biológica. El etanercept se empleó por primera vez en estudios clínicos con seres humanos en 1992 y ya son varios cientos de miles los enfermos tratados en todo el mundo por diferentes afecciones. Actualmente, la Agencia Europea de Evaluación de Medicamentos tiene aprobada la indicación de etanercept en las siguientes enfermedades: 1. Psoriasis en placa en adultos (“adultos con psoriasis en placa, de moderada a grave, que no han respondido o que tienen contraindicada, o no toleran, otra terapia sistémica incluyendo ciclosporina, metotrexato o PUVA”); 2. Psoriasis pediátrica grave en placa. 3. Artritis psoriásica; 4. Artritis reumatoidea; 5. Artritis idiopática juvenil poliarticular; 6. Espondilitis anquilosante. Su utilización en la psoriasis, ya bien conocida, ha hecho que poco a poco empiecen a surgir cuestiones sobre su manejo en situaciones especiales que requieren tener en cuenta las particularidades de su aplicación (lactancia, vacunaciones, infecciones) que abordaremos en este trabajo...

Skin nodules with a linear distribution - a case study.

A man, 35 years of age, with an unremarkable past medical history, attended after developing purplish nodules on the left arm. The nodules were in a linear distribution and had developed during recent months after a minor initial injury. The nodules were moderately painful, but it was mainly the appearance of new nodules that motivated him to consult his general practitioner. On dermatological examination, six purple nodules were observed following a linear distribution along the back of the left hand and arm (Figure 1). They were of variable size. Some of the lesions had a discrete superficial ulceration and a serous crust. The patient had no fever. Small lymph nodes were detected in the left axilla. Systemic examination showed no abnormalities. Laboratory data, including full blood count, general biochemistry and urine analysis were normal. Culture was unremarkable. Histopathologic examination revealed a mixed granulomatous and pyogenic inflammatory process. Cigar shaped organisms were identified by periodic acid-Schiff (PAS) staining.

LEOPARD syndrome: what are café noir spots?

Lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome (multiple lentigines syndrome) is most often characterized by multiple lentigines and cardiac conduction defects. Café noir spot is a term proposed, by analogy to café au lait spots, for the larger and darkly pigmented patches that are frequently observed in patients with this syndrome. Although presumed by some authors to represent lentigines, the histologic features of café noir spots have not been well documented in the literature. Only two previous cases have been reported in which a biopsy of the café noir spots than melanocytic nevi. We describe the histologic characteristics of seven café noir spots in six patients with lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome. Three lesions represented melanocytic nevi (one with dysplastic features), and four were compatible with lentigo simplex. These findings help our understanding of the histologic spectrum of pigmented lesions in lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome.