Treatment of cutaneous neurofibromas with carbon dioxide laser: Technique and patient experience

Cutaneous neurofibromas (cNF) are one of the hallmarks of neurofibromatosis 1 (NF1). The number of cNFs varies between individuals from a few to hundreds or even thousands and increases throughout adult life. cNFs cause a significant disease burden to adult patients and constitute an unmet need for therapy, since they may cause itch and pain and, being conspicuous and unsightly, stigmatize the patient. There is a lack of reports on how the outcome of various treatment options are perceived by the patients. Here we describe a technique for cNF removal using CO2 laser, and report how patients experience the procedure. Questionnaires were sent to patients who had had CO2 laser surgery in the French Referral Center for Neurofibromatoses, and in the Turku University Hospital, Finland, to retrospectively evaluate the patients’ global satisfaction of the procedure, treatment indications, and reasons for withdrawal from treatment, if this was the case. The number of returned questionnaires was 233/473 in France and 23/27 in Finland. The results showed that the most important indications for cNF removal were esthetic, and pain and itch caused by the tumors. In general, the procedure was well tolerated, and the degree of satisfaction was 8–10 on a scale from 0 to 10. For those 30% who discontinued the tumor removal program, the main reasons were organizational constraints, a non-satisfactory esthetic result, too many cNFs to treat, or problems with healing. Thus, the CO2 laser method is well tolerated but does not fully answer to the needs of the patients. Since medical treatment is not yet available, we encourage the use of laser removal of cNFs as a feasible method to decrease the tumor burden of the patients.</p

Développement d’une technique de dosage cutané non invasive des lactones macrocycliques dans le modèle porcin de la gale

Human scabies remains a major health problem worldwide but suitable therapeutics are still lacking. The development of an experimental pig model of scabies allowed the evaluation of new treatments, notably molecules from the macrocyclic lactone family. The aim of the study was to develop a non-invasive procedure for the detection and the dosage of moxidectin (MOX) and ivermectin (IVM) in the skin to extend the drugs cutaneous pharmacokinetics data. Four pigs received simultaneously MOX (0.3 mg/kg at day 0) and IVM (0.2 mg/kg at days 0 and 8) both orally. Blood samples, skin biopsies and stratum corneum samples collected with adhesive discs were realized for 11 days post-treatment. Stratum corneum quantification was performed by three different methods. MOX and IVM were dosed in each sample. The MOX pharmacokinetic profile was similar in the skin and in the stratum corneum with a peak at day 1 and then a progressive decline. Values obtained with both methods were positively correlated. The IVM pharmacokinetic profile was similar to MOX profile in the skin with lower concentrations although its distribution in the stratum corneum was different with a plateau reached at day 2. Adhesive discs samples standardisation and quantification should be improved. Differences between the two drugs distribution in the skin and in the stratum corneum have now to be studied with humans.La gale demeure un enjeu majeur de santé publique et les possibilités thérapeutiques sont insuffisantes. La mise en place d’un modèle porcin de la gale a permis l’évaluation de nouveaux traitements, notamment des molécules de la famille des lactones macrocycliques. L’objectif de cette étude était d’optimiser le modèle porcin par le développement d’une technique non invasive de dosage cutané de la moxidectine (MOX) et de l’ivermectine (IVM) afin de faciliter et d’approfondir les données de pharmacologie cutanée. Quatre porcs ont reçu simultanément de la MOX orale (0,3 mg/kg à J0) et de l’IVM orale (0,2 mg/kg à J0 et J8). Des prélèvements plasmatiques, cutanés par biopsies et de stratum corneum recueillis par des disques adhésifs ont été effectués pendant 11 jours après traitement. La quantification des prélèvements de stratum corneum a été réalisée par trois méthodes différentes. La MOX et l’IVM ont été dosées dans chaque prélèvement par HPLC. Les profils cinétiques de la MOX dans le stratum corneum et dans la peau étaient comparables avec un pic à J1 puis une décroissance progressive et les valeurs dosées par les deux techniques étaient positivement corrélées. L’IVM présentait une cinétique similaire à la MOX avec des concentrations inférieures dans la peau mais sa distribution dans le stratum corneum était différente avec un plateau obtenu à partir de J2. La standardisation et la quantification des prélèvements par disque adhésif restent à améliorer. Les différences de distribution des deux molécules dans le stratum corneum devront maintenant être étudiées chez l’homme

Skin cancer and COVID ‐19: was the diagnosis safeguarded by teledermatology? a study on 1229 cases

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Orogenital Transmission of Neisseria meningitidis Causing Acute Urethritis in Men Who Have Sex with Men

Neisseria meningitidis sequence type 11 is an emerging cause of urethritis. We demonstrate by using whole-genome sequencing orogenital transmission of a N. meningitidis sequence type 11 isolate causing urethritis in a monogamous couple of men who have sex with men. These results suggest dissemination of this clonal complex among low-risk patients

Association Between Severe Acute Contact Dermatitis Due to Nigella sativa Oil and Epidermal Apoptosis

International audienceImportance Nigella sativa oil (NSO) is widely used for cosmetic and culinary purposes. Cases of severe acute contact dermatitis due to NSO are poorly described, with no histologic description.Objectives To describe the clinical and histologic features of severe acute contact dermatitis due to NSO and investigate the components responsible for such eruptions.Design, Setting, and Participants A case series study of 3 patients with contact dermatitis admitted to the dermatology department between August 21, 2009, and February 19, 2017, was conducted. All patients had been referred to the dermatology department for acute contact dermatitis due to NSO and had patch tests performed.Main Outcomes and Measures Clinical and histologic features of the cutaneous eruptions, length of hospital stay, chemical analysis of NSO, and results of patch tests.Results Three patients (3 women; median age, 27 years [range, 20-47 years]) were included in the case series. All patients had polymorphic skin lesions spreading beyond the area of NSO application: typical and atypical targets, patches with central blisters, erythematous or purpuric plaques with a positive Nikolsky sign mimicking Stevens-Johnson syndrome, or toxic epidermal necrolysis. Two patients had pustules. They had severe impairment, with more than 15% skin detachment and fever. The results of skin biopsies showed epidermal apoptosis characterized by vacuolar alteration of the basal layer, keratinocyte apoptosis, and a moderate perivascular infiltrate of lymphocytes in the dermis. The results of patch tests using the patients’ NSO were all positive. The results of gas chromatography combined with mass spectrometry performed on the NSO of 1 patient identified several constituent substances, mainly terpenes, thymoquinone, linoleic acid, and fatty acids.Conclusions and Relevance These cases suggest that acute contact dermatitis due to NSO may induce topically triggered epidermal apoptosis, previously described as the concept of acute syndrome of apoptotic pan epidermolysis. Thymoquinone and p-cymene may be the main agents involved in the pathophysiologic characteristics of this acute contact dermatitis. Clinicians should be aware of such severe reactions to NSO and report these cases to pharmacovigilance authorities

Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients

International audienceData regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3–93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question

Severe phenotype in patients with large deletions of NF1

International audienceComplete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients

Cemiplimab for locally advanced and metastatic cutaneous squamous-cell carcinomas: Real-life experience from the French CAREPI study group

International audienceAlthough cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients