Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Treatment strategies and safety of rechallenge in the setting of immune checkpoint inhibitors-related myositis: a national multicentre study.

OBJECTIVES: The occurrence of immune-related myositis (irM) is increasing, yet there are no therapeutic guidelines. We sought to analyse the current therapeutic strategies of irM and evaluate the outcomes of immune checkpoint inhibitors (ICIs) rechallenge. METHODS: We conducted a nationwide retrospective study between April 2018 and March 2020 including irM without myocardial involvement. Depending on the presence of cutaneous signs or unusual histopathological features, patients were classified into two groups: typical or atypical irM. Therapeutic strategies were analysed in both groups. The modalities and outcomes of ICI rechallenge were reviewed. RESULTS: Among the 20 patients, 16 presented typical irM. Regardless of severity, most typical irM were treated with steroid monotherapy (n = 14/16) and all had a complete response within ≤3 weeks. The efficacy of oral steroids for non-severe typical irM (n = 10) was the same with low-dose (≤0.5 mg/kg/day) or high-dose (1 mg/kg/day). Severe typical irM were successfully treated with intravenous methylprednisolone. Atypical irM (n = 4) had a less favourable evolution, including one irM-related death, and required heavy immunosuppression. ICIs were safely reintroduced in nine patients presenting a moderate (n = 6) or a severe (n = 3) irM. CONCLUSION: Our data highlight that steroid monotherapy is an effective treatment for typical irM, either with prednisone or with intravenous methylprednisone pulses depending on the severity. The identification of unusual features is important in determining the initial therapeutic strategy. The outcomes of rechallenged patients are in favour of a safe reintroduction of ICI following symptom resolution and creatin kinase (CK) normalization in moderate and severe forms of irM.

Predictive Factors of Non-Response to Vismodegib in Locally Advanced Basal-Cell Carcinoma.

BACKGROUND: Vismodegib has shown clinical efficacy in the management of locally advanced basal cell carcinomas (laBCC). However, non-response to vismodegib is observed in 2-13.5% of patients in clinical studies. The purpose of this study was to identify factors associated with non-response to vismodegib in patients with laBCC. METHODS: We carried out a retrospective multicenter study, including patients with laBCC treated with vismodegib, from July 2011 to May 2019. Response to treatment was assessed according to the RECIST 1.1 criteria. Patients were categorized as responders with a complete response or a partial response or non-responders with a stable disease or a progressive disease according to what has been observed during follow-up. Patient demographics, tumor profile, and treatment modalities were compared in responders and non-responders. RESULTS: Eighty-three patients with laBCC were included in the study. Twenty-five (30.1%) were non-responders to vismodegib. History of treatment with radiotherapy, presence of muscle involvement and intermittent treatment with vismodegib were significantly associated with a non-response (p < 0.001, p = 0.025, p < 0.001). Bone involvement (p = 0.2) and morpheaform IaBCC subtype (p = 0.056) were more frequent in non-responders without reaching statistical significance. CONCLUSION: In this study, non-response of laBCC to vismodegib therapy was associated with muscle involvement. Previous radiotherapy and intermittent use of vismodegib have been identified as causes favoring non-response to vismodegib. Due to the low numbers of patients included in the study, it is difficult to draw firm conclusions. Further studies are needed to confirm these data.

Impregnated acetate gauze compared with lipido-colloid contact layer at dressing removal pain: a single-blind cross-over randomised control trial.

OBJECTIVE: To evaluate the performance of Jelonet Plus (JP) and UrgoTul (UT), assessing pain at dressing removal when managing acute or chronic wounds at granulation and epithelialisation stages. METHODS: This was a randomised, multicentre, controlled single-blinded study using a cross-over design. Hospitalised and ambulatory patients presenting with non-infected acute or chronic wounds (at least 40% of wound area of ≤100cm2 covered with granulation tissue) were randomly allocated to be treated with either JP or UT dressings applied according to a standardised local care procedure for two days. At the following visit, patients received the other dressing for a second 2-day period. Pain was evaluated after two days of dressing application and immediately after its removal using a 100mm Visual Analog Scale (VAS). A pain level >30mm was considered as clinically relevant. A lower limit of -12% was determined as the threshold necessary to demonstrate the non-inferiority of JP compared to UT. RESULTS: For the 99 patients completing the study, a difference of 7.9% was observed in favour of JP (83.8% JP versus 75.9% UT) for pain immediately after dressing removal (VAS score < 30mm) with a confidence interval (CI) lower limit of -2.6%, demonstrating non-inferiority (pre-defined limit of -12%). Concerning pain at dressing removal, a difference of 19.6% was observed in favour of JP (81.6% versus 62.0%; p=0.029 for superiority analysis), with a CI lower limit ranging from 2.4% to 38.9%. Therefore, superiority could be concluded. A statistically significant period effect was detected (p=0.003) with fewer patients experiencing pain after the second period day 2 (D2) to day 4 (D4) than the first day 0 (D0) to D2. A statistically significant cross-over effect was also detected (p=0.047), with fewer patients experiencing pain when JP was applied first followed by UT. This suggests a carry-over effect thus preventing a full cross-over design analysis. Adherence of the dressing was less frequent with the JP than the UT dressing (2.0% JP versus 6.9% with UT). CONCLUSION: Non-inferiority of pain at dressing removal was demonstrated with JP. Superiority on this criteria was non-significant but we found adherence of the dressing to the wound bed to be more rare.

The analgesic effect of electrostimulation (WoundEL®) in the treatment of leg ulcers.

This study aims to demonstrate the analgesic efficacy of electrostimulation (ES), a recognised treatment for leg ulcers. Patients treated by ES for leg ulcers between 2011 and 2013 were included in the study. The pain score obtained with the numerical rating scale (NRS) was reported before the start of the ES (D0), after 3 days (D3) and 1 week following treatment initialisation. The analgesic treatments (AT) were reported at each assessment. Seventy-three patients were included (mean age 75·19 years): 31 venous leg ulcers, 21 mixed venous leg ulcers, 2 arterial ulcers, 17 hypertensive ischaemic ulcers, 1 Hydrea(®)-induced ulcer and an amputation stump ulcer. The NRS at D0 was on average 5·3 (median = 6) while it was 2·2 at D7 (median = 2), that is P < 0·001. The results were also significant between D0 and D3 (P < 0·001). A decrease in the number of AT used was observed between D0 (2·0 AT per patient on average) and D7 (1·7 AT on average) (P < 0·001). We also observed a decrease in the consumption of grade 3 analgesics on D0 and D7 (P = 0·03). This study demonstrates the rapid analgesic efficacy of ES in leg ulcers, with a clear impact on the NRS score and especially on the decrease in analgesic consumption.

Duration of efficacy increases with the repetition of botulinum toxin A injections in primary palmar hyperhidrosis: a study of 28 patients.

BACKGROUND: Intradermal injections of botulinum toxin are effective but transitory in primary palmar hyperhidrosis. These injections are repeated when the symptoms recur. We do not know how the duration of efficacy changes when injections are repeated. OBJECTIVE: In this retrospective study, we aimed to investigate the change in the duration of efficacy of botulinum toxin A (Dysport, Ipsen, Boulogne-Billancourt, France) with the repetition of injections in patients with primary palmar hyperhidrosis. METHODS: From May 2001 to April 2012, 28 patients were treated with a dose of 250 U of botulinum toxin A per palm. We compared the duration of efficacy of the first and last toxin injections. RESULTS: The median duration of efficacy was 7 months for the first injection and 9.5 months for the last, the difference being statistically significant (P = .0002). LIMITATIONS: Study limitations include a relatively small number of patients treated at a single center and evaluated retrospectively. CONCLUSION: To our knowledge, this study is the first to report a significant increase in the duration of efficacy of botulinum toxin A injections with the repetition of injections in patients with primary palmar hyperhidrosis. The reasons for this effect may be linked to the mechanism of action of botulinum toxin, and may improve our understanding of its pharmacologic effects.

Duration of efficacy increases with the repetition of botulinum toxin A injections in primary axillary hyperhidrosis: a study in 83 patients.

BACKGROUND: Intradermal injections of botulinum toxin are effective but transitory in primary axillary hyperhidrosis. These injections are repeated when the symptoms recur. The reported duration of efficacy is variable, from 2 to 24 months, but it is unknown how the duration of efficacy changes when injections are repeated. OBJECTIVE: In this retrospective study, we aimed to evaluate changes in the duration of efficacy of botulinum toxin injections (Dysport, Ipsen, Boulogne-Billancourt, France) with the repetition of injections in patients with axillary hyperhidrosis. METHODS: From May 2001 to April 2012 inclusive, 83 patients were treated with a dose of 125 U per underarm. We compared the duration of effect of the first and last toxin injections. RESULTS: The median duration of efficacy for the first injection was 5.5 months, whereas that for the last injection was 8.5 months. The difference between these 2 durations is statistically significant (P = .0002). LIMITATIONS: Although retrospective and based on the declarative, this work is the first to our knowledge to highlight this benefit of treatment and to evaluate botulinum toxin over such a long period (11 years). CONCLUSION: There appears to be an increase in the duration of efficacy of botulinum toxin A injections with the repetition of injections in patients with primary axillary hyperhidrosis. The reasons for this effect may be linked to the mechanism of action of botulinum toxin, and may improve our understanding of its pharmacologic effects.

Impact of Distribution of a Tip Sheet to Increase Early Detection and Prevention Behavior among First-Degree Relatives of Melanoma Patients: A Randomized Cluster Trial.

BACKGROUND: First-degree relatives (FDRs, defined as parents, children, and siblings) of melanoma patients are at a two-to-fivefold increased risk of developing melanoma themselves. FDRs are advised to perform self-skin examination (SSE) and annual medical total cutaneous examination (TCE) performed either by a dermatologist or a general practitioner, and to change their sun-related behavior. This advice is given orally to melanoma patients who are asked to relay the information to their FDRs. OBJECTIVE: Our aim was to determine the impact of providing a tip sheet to melanoma patients intended to their first-degree relatives (FDRs) on early detection and sun-related behaviors in this group at increased risk of melanoma. METHODS: A superiority, cluster-randomized trial was conducted at nine hospital centers. In the intervention group, dermatologists were asked to deliver to melanoma patients (index cases) the tip sheet and oral advice intended to their FDRs. The control group were asked to deliver the usual oral advice alone. The primary outcome was early detection of melanoma in FDRs with a medical TCE performed within one year after the first visit of the index case. Secondary outcomes were SSE and sun-related behaviors in FDRs. RESULTS: A total of 48 index cases and 114 FDRS in the control group, 60 index cases and 166 FDRS in the intervention group were recruited. In the intervention group, 36.1% of FDRs performed a medical TCE as compared to 39.5% of FDRs in the control group (OR 0.9 [95% CI 0.5 to 1.5], p = 0.63). We did not find a between-group difference in SSE and sun-related behaviors. CONCLUSION: A tip sheet added to the usual oral advice did not increase medical TCE among FDRs of melanoma patients. Overall, the rate of TCE among FDRs was low. Research on other strategies is needed to increase melanoma detection in this population.

Epidemiology and characteristics of acral lentiginous melanoma compared to lentigo melanoma in France: a multicentric retrospective study from the French cohort RIC-Mel database

Background: Skin phototype, latitude and sun exposure are classic risk factors for melanomas but are not relevant to acrolentiginous melanomas (ALM). ALM is not related to chronic sun exposure because the thick stratum corneum acts as a barrier to penetration of UV rays, whereas LMM occurs in skin with high photoaging due to chronic sun exposure. Objectives: This study aimed to determine if any difference exists between "solar" melanomas and "non-solar" melanomas based on a comparison between LMM and ALM. Materials & Methods: We extracted all data for ALM and LMM patients, from March 2012 to September 2020, from the RIC-Mel national database to perform a descriptive cohort analysis of 1,056 Caucasian cases. Conclusion: The profiles of solar-related and non-solar melanoma seem to be different, and prognostic factors of ALM at diagnosis are less favourable compared to LMM, suggesting that non-solar melanoma is more aggressive than solar-related melanoma and that sentinel lymph node biopsy should be performed.

Esophageal Achalasia Induced by Ipilimumab and Nivolumab Combination: A Rare Neurological Manifestation of Immune-related Autonomic Neuropathy.

Immunotherapy with immune checkpoint inhibitors (ICIs) has improved the prognosis of many cancers; a combination of nivolumab (anti-programmed cell death protein 1) and ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) is approved as first-line therapy for advanced melanoma, with objective responses obtained in more than half of patients. However, this combination is associated with a high rate of immune-related adverse events, which are often severe and multiple. Neurological immune-related adverse events are rare but feared because they can be life-threatening, their diagnosis and management are challenging, and patients can have irreversible sequelae. We reported a case of a young patient treated by nivolumab and ipilimumab combination for metastatic melanoma. Severe dysphagia with regurgitations, major weight loss, uveitis, and vitiligo occurred after 3 infusions of nivolumab and ipilimumab. Magnetic resonance imaging and positron emission tomography scan showed complete remission of melanoma. The endoscopic examination did not find any digestive toxicity. Esophageal manometry revealed achalasia. This was associated with mydriasis, pathologic deep breath test, and alteration of the cutaneous sympathetic response on electromyogram, which was consistent with autonomic neuropathy. This rare etiology of atypical vomiting under ICI should be known by prescribers, as ICI prescription is widening in many new cancers.

Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group.

Although 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.

Management of adjuvant settings for Stage III melanoma patients in France prior to checkpoint inhibitors: epidemiological data from the RIC-Mel database.

BACKGROUND: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma. OBJECTIVES: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies. MATERIALS AND METHODS: A subgroup data analysis. RESULTS: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients. CONCLUSION: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost.

Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sézary syndrome.

OBJECTIVE: To assess the rate of objective response to pegylated liposomal doxorubicin hydrochloride (Caelyx) in patients with advanced or refractory cutaneous T-cell lymphoma (CTCL). DESIGN: Prospective, open, multicenter study. SETTING: Thirteen dermatology departments in France. PATIENTS: Twenty-five patients with either (1) stage II to stage IV CTCL previously unsuccessfully treated with at least 2 lines of treatments or (2) histologically transformed epidermotropic CTCL requiring chemotherapy. INTERVENTION: Administration of Caelyx intravenously once every 4 weeks at a dose of 40 mg/m(2). MAIN OUTCOME MEASURES: The response to treatment was evaluated by clinical evaluation. RESULTS: At the end of treatment, we observed an objective response (primary end point) in 56% of the patients (14 of 25): 5 complete responses and 9 partial responses. The median overall survival time was 43.7 months. For the 14 patients who experienced an objective response, the median progression-free survival time after the end of treatment was 5 months. CONCLUSIONS: This prospective study demonstrates the effectiveness of Caelyx in treating CTCL, with an overall response rate of 56% in spite of the high proportion of patients with advanced-stage disease. Responses were observed in 2 subpopulations of patients in which the prognosis is known to be poorer: Sézary syndrome (overall response rate, 60%) and transformed CTCL (overall response rate, 50%). Moreover, this study shows that dose escalation to 40 mg/m(2) does not seem to improve the effectiveness but increases toxic effects (especially hematologic toxic effects) compared with the dose previously tested of 20 mg/m(2).

PGL-1 antigen and antibody detection in leprosy patients: evolution under chemotherapy

Multibacillary (MB) and paucibacillary (PB) leprosy patients were tested for circulating phenolic glycolipid-I (PGL-I) antigen and antibodies before treatment. In the 27 MB patients tested, 27 (100%) were antigen positive with levels ranging from 50 to 5000 ng/ml, and 26 (96%) were antibody positive with titers ranging from 1000 to 64,000. Although the antigen and antibody levels were much higher in MB than in PB patients, we could not demonstrate a correlation between the number of acid-fast bacilli/mg of skin biopsy and these two parameters in 14 MB patients. After starting daily multidrug therapy, 10 MB patients were monitored monthly. As much as 88.75% +/- 10.8% of the PGL-I antigen was cleared from the bloodstream after 1 month while the anti-PGL-I antibody remained stable. This rapid decrease in the PGL-I antigen level strongly suggests the usefulness of this test for monitoring MB patients under chemotherapy

Implementation of chemoprophylaxis of leprosy in the southern marquesas with a single dose of 25 mg kg rifampin

Between 1967 and 1987 in the Southern Marquesas, a remote archipelago in French Polynesia, the detection rate of leprosy was 48.9 per 100,000 when it was 8.6 per 100,000 for French Polynesia as a whole. In 1988, a program of chemoprophylaxis of leprosy with a single dose of 25 mg/kg rifampin was implemented, and 2751 persons (98.7% of the population) were treated in the Southern Marquesas. In addition, 678 South Marquesans and 2466 members of their families living in the Northern Marquesas and in the Society Archipelago, received the same chemoprophylaxis. Among 2676 persons studied in the Southern Marquesas (97.4% of the treated population), 130 had elevated IgM anti-phenolic glycolipid-I antibodies by ELISA without any evidence of leprosy. The onset of a skin lesion of borderline leprosy in a boy 3 months after chemoprophylaxis raises the question of the nature of such a skin lesion and, indirectly, of the effectiveness of the chemoprophylaxis