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.

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

Acne microbiome: From phyla to phylotypes.

Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be: (1) altered sebum production, (2) inflammation, (3) excess keratinization and (4) colonization with the commensal Cutibacterium acnes. However, the role of C. acnes has been unclear, since virtually all adults have C. acnes on their skin yet not all develop acne. In recent years, understanding of the role of C. acnes has expanded. It is still acknowledged to have an important place in acne pathogenesis, but evidence suggests that an imbalance of individual C. acnes phylotypes and an alteration of the skin microbiome trigger acne. In addition, it is now believed that Staphylococcus epidermidis is also an actor in acne development. Together, C. acnes and S. epidermidis maintain and regulate homeostasis of the skin microbiota. Antibiotics, which have long been a staple of acne therapy, induce cutaneous dysbiosis. This finding, together with the long-standing public health edict to spare antibiotic use when possible, highlights the need for a change in acne management strategies. One fertile direction of study for new approaches involves dermocosmetic products that can support epidermal barrier function and have a positive effect on the skin microbiome.

Multidisciplinary patient-centered approach to the management of skin cancer.

In recent years, new approaches for optimal patient management of cancer have focused on patient-centered care, with integration of tumour-directed treatment and patient-directed supportive and palliative care throughout the disease journey from prevention through screening, diagnosis, treatment, and follow-up. In 2022, at the International Forum of Dermatology (IFD), a scientific session was entirely dedicated to highlight recent developments on patient-centered approaches in skin cancer. An international panel of different groups of participants involved in a patient's journey on the management of skin cancer presented and discussed challenges and barriers that persist in the field of skin cancer prevention and care pathways. Although primary prevention remains a crucial step in the prevention of melanoma, the different surveys performed during the last 20 years demonstrate that the use of sunscreen increases very slowly. Secondary prevention that includes skin screening and diagnostic measures may benefit from the development of digital tools. To improve adherence, patients need accurate, reliable information about their disease and the treatment options, and this type of content that can also be made available on digital tools. Shared decision-making is a hallmark of a patient-centered approach and requires health care providers who can communicate well to patients and their families, underscoring the pivotal role of health care professionals all through the patient journey. Health care providers have a crucial role in supporting patients through their journey in skin cancer. They will benefit from mobile apps and technologies that have been developed recently to address challenges in skin cancer prevention, detection and care, including those that are primarily directed to the patient. However, more peer-reviewed studies are needed as well as regulations to ensure that apps are accurate, reliable, and up to date.

International expert consensus recommendations for the use of dermocosmetics in acne.

BACKGROUND: A wide variety of dermocosmetics (products with both active skincare and cosmetic activity) are available for the management of acne vulgaris. These products are important because they may be the first line of approach for patients desiring to self-treat and they can also have beneficial effects-reducing lesion counts and improving global acne severity. When used in conjunction with medical therapy, dermocosmetics can improve tolerability and enhance results. We reviewed available evidence and combined it with our clinical experience to help guide clinicians in selecting skincare products with acne-targeting ingredients. METHODS: An international panel of dermatologists with an interest and expertise in managing acne performed a literature review, formulated clinical questions related to the role of dermocosmetics in the acne setting, used a modified GRADE approach to evaluate available evidence and then utilized an online iterative Delphi process to create consensus recommendations. It should be noted that due to the limited number of available studies, the category of dermocosmetics was evaluated rather than specific ingredients. RESULTS: The quality of evidence was found to be low to moderate. Key recommendations were made based on available evidence for the use of dermocosmetics in acne to improve acne global assessment, reduce acne lesion counts, reduce superficial skin oiliness and serve as maintenance therapy after medical treatment, while providing a good tolerability. Recommendations were also made for using dermocosmetics as adjuncts to medical treatment. CONCLUSIONS: While there is a need for better quality evidence, dermocosmetics have demonstrated some benefit for acne both when used alone in its milder clinical presentations or in maintenance post acne medication and as adjunct to acne treatments.

European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

Early diagnosis of melanoma: a randomized trial assessing the impact of the transmission of photographs taken with a smartphone from the general practitioner to the dermatologist on the time to dermatological consultation.

BACKGROUND: Difficulty obtaining a dermatological consultation is an obstacle to the early diagnosis of melanoma. On the one hand, patients survival depends on the lesion thickness at the time of diagnosis. On the other hand, dermatologists treat many patients with benign lesions. Optimizing patient care pathways is a major concern. The aim of the present study was to assess whether the e-mail transmission of photographs of suspected melanoma lesions between general practitioners (GPs) and dermatologists reduces the time to dermatological consultation for patients whose suspicious skin lesions ultimately require resection. METHODS: We conducted a cluster-randomized controlled study in primary care involving 51 French GPs between April 2017 and August 2019. A total of 250 patients referred to a dermatologist for a suspected melanoma lesion were included GPs were randomized to either the smartphone arm or the usual care arm. In the smartphone arm, the GPs referred patients to the dermatologist by sending 2 photographs of the suspicious lesion using their smartphone. The dermatologist then had to set up an appointment at an appropriate time. In the usual care arm, GPs referred patients to a dermatologist according to their usual practice. The primary outcome was the time to dermatological consultation for patients whose lesion ultimately required resection. RESULTS: 57 GPs volunteered were randomized (27 to the smartphone arm, and 30 to the usual care arm). A total of 125 patients were included in each arm (mean age: 49.8 years; 53% women) and followed 8 months. Twenty-three dermatologists participated in the study. The time to dermatological consultation for patients whose suspicious skin lesion required resection was 56.5 days in the smartphone arm and 63.7 days in the usual care arm (mean adjusted time reduction: -18.5 days, 95% CI [-74.1;23.5], p = .53). CONCLUSIONS: The e-mail transmission of photographs from GPs to dermatologists did not improve the dermatological management of patients whose suspicious skin lesions ultimately required resection. Further research is needed to validate quality criteria that might be useful for tele-expertise in dermatology. TRIAL REGISTRATION: Registered on ClinicalTrials.gov under reference number NCT03137511 (May 2, 2017).

A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients.

Kidney transplant survival is shortened by chronic rejection and side effects of standard immunosuppressive drugs. Cell-based immunotherapy with tolerogenic dendritic cells has long been recognized as a promising approach to reduce general immunosuppression. Published trials report the safety and the absence of therapy-related adverse reactions in patients treated with tolerogenic dendritic cells suffering from several inflammatory diseases. Here, we present the first phase I clinical trial results using human autologous tolerogenic dendritic cells (ATDC) in kidney transplantation. Eight patients received ATDC the day before transplantation in conjunction with standard steroids, mycophenolate mofetil and tacrolimus immunosuppression with an option to taper mycophenolate mofetil. ATDC preparations were manufactured in a Good Manufacturing Practice-compliant facility and fulfilled cell count, viability, purity and identity criteria for release. A control group of nine patients received the same standard immunosuppression, except basiliximab induction replaced ATDC therapy and mycophenolate tapering was not allowed. During the three-year follow-up, no deaths occurred and there was 100% graft survival. No significant increase of adverse events was associated with ATDC infusion. Episodes of rejection were observed in two patients from the ATDC group and one patient from the control group. However, all rejections were successfully treated by glucocorticoids. Mycophenolate was successfully reduced/stopped in five patients from the ATDC group, allowing tacrolimus monotherapy for two of them. Regarding immune monitoring, reduced CD8 T cell activation markers and increased Foxp3 expression were observed in the ATDC group. Thus, our results demonstrate ATDC administration safety in kidney-transplant recipients.

The role of dermocosmetics in the management of cancer-related skin toxicities: international expert consensus.

Skin toxicities are very common in patients undergoing cancer treatment and have been found to occur with all types of cancer therapeutic interventions (cytotoxic chemotherapy, targeted therapies, immunotherapy, and radiotherapy). Further, skin toxicities can lead to interruption or even discontinuation of anticancer treatment in some patients, translating to suboptimal outcomes. Dermocosmetics (or cosmeceuticals)-defined as skincare solutions incorporating dermatologically active ingredients (beyond vehicle effects) that directly improve symptoms of various skin conditions-are increasingly being used in cancer care to prevent and manage skin toxicities. The active ingredients in these products have a measurable biological action in skin; they typically improve skin integrity (barrier function/hydration and other factors) while relieving skin symptoms. The Association Francophone des Soins Oncologiques de Support (AFSOS) and Multinational Association of Supportive Care in Cancer (MASCC) partnered to select a multidisciplinary group of healthcare professionals involved in the management of patients with cancer and skin toxicities. The group reviewed existing literature and created a summary of recommendations for managing these toxicities through online meetings and communication. In this publication, the group (1) reviews new skin toxicities seen with oncology drugs and (2) evaluates the role of dermocosmetics in improving patient outcomes and minimizing cancer treatment interruptions. We provide general recommendations for initiation and selection of skin care in all oncology patients as well as recommendations for what factors should be considered when using dermocosmetics in specific types of skin toxicities.

Truncal Acne in Adolescents and Young Adults: Self-reported Perception.

No epidemiological information about truncal acne is available. This study assessed the self-reported impact of truncal acne in adolescents and young adults, using an internet survey in France in 1,001 adolescents and young adults with truncal acne. Participants' mean age was 18.6 ± 4.3 years, 75.7% were females, 52.9% reported severe and 16.0% very severe truncal acne; 90.0% of participants with truncal acne also reported past or ongoing facial acne. Stress (46.3%), a diet high in lipids (33.2%), and sleeplessness (27.0%) were considered to be triggers of truncal acne; 44.7% consulted at least 1 healthcare professional and 28.1% searched the internet or social network for information about truncal acne. Of subjects with truncal acne, 68.4% thought constantly about their condition. Overall, 79.9% of the participants with severe acne vs 41.8% with mild or moderate acne: 41.8% thought about their acne all the time (p < 0.0001). Truncal acne heavily or very heavily impacted quality of life of 38.7% of participants. It impacted females significantly more than males (p < 0.0001). Significantly (p < 0.001) more females than males reported facial acne. A significant (p = 0.0067) association was observed between the severities of facial and truncal acne. The self-perceived impact of truncal acne in adolescents and young adults highlights the need for information as well as reinforced medical and psychological care.

Sun exposure behaviours as a compromise to paradoxical injunctions: Insight from a worldwide survey.

BACKGROUND: Behavioural interventions can improve attitudes towards sun protection but the impact remains inconsistent worldwide. OBJECTIVE: To assess awareness of and attitudes towards the multiple facets of sun exposure and suggest ways to improve prevention from overexposure to the sun in all geographical zones and multiple skin types. METHODS: Online survey was conducted from 28 September to 18 October 2021. Study population was selected from the Ipsos online Panel (3,540,000 panellists), aged ≥18 years, from 17 countries around the five continents. Demographics, sun-exposure habits and practices, understanding of risks and information on phototypes were documented and analysed using descriptive statistics. RESULTS: Eighty-eight per cent of participants knew that sunlight can cause skin health problems (90% phototypes I-II, 82% phototypes V-VI, >90% in American and European countries, 72% in Asia and 85% in Africa). Eighty-five per cent used some form of protection against sunlight, predominantly: Seeking shade (77%), avoiding the midday sun (66%), facial application of sunscreen (60%) and wearing protective clothing (44%). The perception of sunlight itself is positive ('it gives energy' for 82%; 'tanned skin looks attractive' for 72%), although less in Asian countries and among individuals with dark skin phototypes. Eighty-three per cent reported having experienced sunburn, mainly in Australia, Canada, USA, Germany, France and Russia, and among individuals with dark skin phototypes. Only 12% systematically/often used all types of protection during exposure to the sun and 23% believed it is safe to go out in the sun with no protection when their skin is already tanned. From 13% (skin phototype I) to 26% (phototype VI) reported not using any form of protection against the sun. Knowledge and habits were significantly superior among people who are accustomed to seeing a dermatologist for a complete skin exam. CONCLUSIONS: Dermatologists could play a crucial role in relaying novel prevention messages, more finely tailored to specific risks, populations and areas of the world.

Efficacy of imiquimod in the management of lentigo maligna.

BACKGROUND: Lentigo maligna (LM) is a melanocytic proliferation occurring on photo-exposed skin that may progress to LM melanoma. Surgery is recommended as first-line treatment. Excision margins of 5-10 mm remain, without international consensus. Several studies have shown that imiquimod, an immunomodulator, induces LM regression. This study investigated the effect of imiquimod versus placebo in neoadjuvant settings. PATIENTS AND METHODS: We performed a prospective, randomized, multicentre, phase III clinical study. Patients were randomly assigned in 1:1 ratio to receive imiquimod or placebo for 4 weeks, followed by LM excision 4 weeks after the last application of imiquimod or placebo. The primary endpoint was extra-lesional excision, with a 5 mm margin from the residual pigmentation after imiquimod or vehicle. Secondary endpoints included the gain on the surface removed between the two groups; number of revision surgeries to obtain extra-lesional excisions; relapse-free time; and number of complete remissions after treatment. RESULTS: A total of 283 patients participated in this study; 247 patients, 121 patients in the placebo group and 126 in the imiquimod group, accounted for the modified ITT population. The first extralesional extirpation was performed in 116 (92%) imiquimod patients and in 102 (84%) placebo patients; the difference was not significant (p = 0.0743). Regarding the surface of LM, imiquimod reduced the LM surface (4.6-3.1 cm2 ) significantly (p < 0.001) more compared to the placebo (3.9-4.1 cm2 ). CONCLUSION: Imiquimod reduces the lentigo maligna surface after 1 month of treatment, without a higher risk of intralesional excision and with a positive aesthetic outcome.

Ceramide-Containing Adjunctive Skin Care for Skin Barrier Restoration During Acne Vulgaris Treatment.

Barrier damage caused by facial acne vulgaris can be magnified by topical medication, such as adapalene (0.3%) and benzoyl peroxide (2.5%)(A/BPO), which utilizes a retinoid to normalize follicular keratinization and BPO to decrease the C. acnes population. Disease-induced irritation combined with topical medication-induced irritation results in dryness and enhanced inflammation leading to lower compliance and increased skin healing time. Ceramide-based moisturizers have documented barrier repair benefits for eczema but have not been studied for acne. The objective of this double-blind study was to measure the impact of acne treatment on skin barrier function and tolerance when paired with a ceramide routine. Participants were prescribed an A/BPO gel once daily. The treatment group received a ceramide-containing foaming facial cleanser and facial lotion, and the control group received basic foaming face wash for twice-daily use. Participant and investigator tolerability and efficacy were evaluated by both ordinal and clinical measures. Acne lesion counts and Investigator’s Global Assessments (IGA) of acne were obtained along with transepidermal water loss (TEWL) measurements for barrier function. TEWL for the treatment group remained significantly lower than the control at all timepoints and significantly improved from baseline by week 12. The treatment group had statistically lower mean investigator scores for dryness at all timepoints. Inflammatory lesion counts were significantly lower for the treatment group. A/BPO damaged the skin barrier, demonstrated by elevated TEWL, contributing to dryness, redness, and scaling. Use of a ceramide-containing cleanser and moisturizer significantly reduced severity and incidence of dryness, erythema, and scaling while more quickly resolving barrier damage and restoring function. Draelos ZD, Baalbaki N, Colon G, et al. Ceramide-containing adjunctive skin care for skin barrier restoration during acne vulgaris treatment. J Drugs Dermatol. 2023;22(6):554-558. doi:10.36849/JDD.7142 .

A Salicylic Acid-Based Dermocosmetic is Effective as an Adjunct to Benzoyl Peroxide for Mild to Moderate Acne and as Monotherapy in Maintenance Post Benzoyl Peroxide.

BACKGROUND: A dermocosmetic (DC) containing salicylic acid, niacinamide, and thermal spring water has been developed for the management of mild to moderate acne. AIM: To assess the efficacy of DC as an adjunct to benzoyl peroxide (BPO) every other day compared with BPO over 3 months, and its efficacy as maintenance post-BPO care compared with vehicle for another 3 months. METHODS: Single-center, randomized, double-blind study in 100 patients with mild to moderate facial acne according to the Global Acne Severity (GEA) Scale. During phase 1, subjects received either BPO + vehicle (vehicle group) or BPO + DC (DC group) for 12 weeks. During phase 2, patients were re-randomized to receive either the vehicle or the DC for 12 weeks. Assessments included inflammatory and non-inflammatory lesion count, acne severity using the GEA Scale, local tolerance, quality of life, and quantity of product used. RESULTS: During phase 1, both groups, DC and vehicle, reached the same level of efficacy at month 3, although the quantity of BPO used was significantly reduced in the DC group (P=0.0001). During phase 2, acne continued to significantly improve (all P<0.05) in the DC group, as did clinical signs and symptoms; while patients randomized to vehicle reported relapses of their acne and related symptoms. CONCLUSION: The use of DC significantly reduces the need for BPO with no impact on the efficacy of mild to moderate acne. The use of DC as a maintenance post-BPO allowed a significant reduction of acne relapse compared with vehicle after 3 months of follow-up, with a good tolerance. J Drugs Dermatol. 2023;22(12):1172-1177. doi:10.36849/JDD.7449R1.

Management of Acne Vulgaris With Trifarotene.

Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid approved for treatment of acne. RAR-γ is the most common isoform of RARs in skin, and the strong selectivity of trifarotene for RAR-γ translates to efficacy in low concentration. Trifarotene, like other topical retinoids, acts by increasing keratinocyte differentiation and decreasing proliferation, which reduces hyperkeratinization. Retinoids have also been shown to inhibit inflammatory pathways via effects on leukocyte migration, toll-like receptors, and Activator Protein (AP)-1. Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne. However, unlike all other retinoids, trifarotene is the first topical retinoid with rigorous clinical data on safety and efficacy in truncal acne. Data supporting use of trifarotene to manage acne are reviewed in this publication.

Cutibacterium acnes and Staphylococcus epidermidis: the unmissable modulators of skin inflammatory response.

Acne is a multifactorial inflammatory dermatose that affects all age categories from teenagers to adults, resulting in important psychological impacts. Multiple hypotheses currently attempt to decrypt the physiopathology of this disease, and four main actors were identified as highly implicated in it: hyperkeratinization of the pilosebaceous follicle, hyperseborrheae, host factors (innate immunity) and skin microbiota. In this letter, we present results illustrating the impact of skin microbiota on inflammatory skin response, and how far the proper balance between each bacterial community, especially C. acnes and S. epidermidis, is crucial to maintain an appropriate inflammatory response on the skin. The data presented in this study demonstrate that within the skin microbiota, an imbalance between Cutibacterium acnes and Staphylococcus epidermidis, is able to induce the activation of inflammation-related markers such as IL-1ra, IL-6, IL-8, G-CSF and the molecules C5/C5a, soluble CD14 MIP-3beta, Serpin E1, VCAM-1 and beta-defensin-2. Moreover, S. epidermidis appears to have a more important role than C. acnes on the induction of inflammation-related markers, particularly on IL-6. This work is the basis of future in vitro studies to further understand acne physiopathology, inspiring the development of future innovative therapies based on skin microbiota modulation.

Change in lentigo maligna score assessed by in vivo reflectance confocal microscopy after 1 month of imiquimod treatment for lentigo maligna management.

BACKGROUND: Treatment of lentigo maligna (LM) is challenging because of the potential functional and esthetic surgical sequelae. Imiquimod has been proposed as a treatment for LM. Reflectance confocal microscopy (RCM) is a noninvasive method for the diagnosis of LM and margin assessment. OBJECTIVES: To compare the overall LM score (LMS) assessed by RCM before and 1 month after the start of imiquimod treatment compared to placebo and to define the immunohistochemical (IHC) profile of responders to imiquimod. METHODS: A controlled randomized study was conducted. Forty patients underwent RCM examination with calculation of the LMS at baseline and after 1 month of treatment. An IHC analysis of excised tissues was performed. RESULTS: The 1-month LMS was significantly lower in patients treated with imiquimod compared to those treated with placebo (P < .001). The criteria in the imiquimod-treated patients that demonstrated significant decrease were nonedged papillae; large, round pagetoid cells; atypical cells at the dermoepidermal junction; and follicular location of atypical cells. IHC analysis showed a higher level of interferon gamma in the resected specimens of patients responding to imiquimod (P = .04). LIMITATIONS: Sample size was small. CONCLUSION: Assessing the LMS by RCM was useful to monitor LM response to imiquimod accurately.

Late-onset adverse events of anti-PD1 therapy in melanoma patients: An observational study from MELBASE, a nationwide prospective cohort.

BACKGROUND: Late-onset adverse events (AEs) of anti-programmed cell death 1 (anti-PD1) antibodies have not been systematically described. OBJECTIVES: The purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 administered for at least 2 years in a real-life setting. METHODS: Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow up of unresectable stage III or IV melanoma. The study included 119 patients who received anti-PD1 during at least 2 years from January 2013 to November 2019. Median follow up was 41.7 months (range, 25.2-57.5 months). Fifty-three patients received nivolumab and 66 patients received pembrolizumab. RESULTS: AEs occurred in 99 patients (83%) with a median time of 13.3 months (range, 0-53.9 months), including severe AEs (grade 3 or 4) in 30 patients (30%). Late-onset AEs, mostly grades 1 or 2, occurred in 51 (43%) patients and led to 5 (4%) hospitalizations, of which 4 were severe. Factors associated with late-onset AEs in multivariate analysis were early-onset AEs (within the first 2 years of treatment) and treatment duration (P = .02 and P = .03, respectively). CONCLUSIONS: Our data demonstrate the possibility of late-onset AEs occurring after 2 years of anti-PD1 therapy. Late-onset AEs appear frequently and were mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may increase the risk of late-onset AEs.

Should Targeted Therapy Be Continued in BRAF-Mutant Melanoma Patients after Complete Remission?

BACKGROUND: Targeted therapy is used to treat patients with a BRAF-mutated metastatic melanoma and is continued until disease progression or severe toxicity. No robust data on the management of patients achieving a complete remission (CR) are available. MAIN OBJECTIVE: To determine the relapse rate in the first year after targeted therapy discontinuation in patients in CR. SECONDARY OBJECTIVES: To determine the relapse rates throughout the follow-up and to identify prognostic factors for relapse at 1 year. METHODS: A retrospective, monocentric observational study was conducted in patients with advanced melanoma included in the RIC-Mel database who discontinued targeted therapy after achieving a CR confirmed by CT scan and PET/CT scan. RESULTS: Twenty-nine patients were included. Seventeen (58.6%) patients were treated with BRAF inhibitor (BRAFi) alone and 12 (41.4%) with a BRAFi combined with a MEK inhibitor (BRAFi + MEKi). The median treatment duration was 9.7 months. The relapse rates after discontinuation were 69% at 12 months (BRAFi: 70.6%; BRAFi + MEKi: 66.7%) and 76% at 36 months (BRAFi: 76.5%; BRAFi + MEKi: 75%). A non-significant trend towards a higher risk of relapse was found in women (p = 0.1; RR 3.36; 95% CI 0.77-17.07), in patients with an LDH level greater than the upper limits of normal (p = 0.58; RR 2.43; 95% CI 0.10-56.71), and when more than two metastatic sites were involved (p = 0.19; RR 4.6; 95% CI 0.46-46.51). After relapse, targeted therapy was resumed in 17 patients (7 with BRAFi; 10 with BRAFi + MEKi) with a response rate of 53%. CONCLUSIONS: This real-life study provided long-term data in patients who discontinued targeted therapy after CR. Most patients experienced a relapse in the first year after targeted therapy discontinuation, of whom 50% were in the first 3 months. After targeted therapy resumption, 53% of relapsing patients achieved an objective response. Patients should be followed during the first year after treatment discontinuation. In addition, patients with less than 3 metastatic sites, a baseline LDH level with normal ranges, men, and patients responding rapidly to treatment would be more likely to maintain a CR after treatment discontinuation.

Update: Mechanisms of Topical Retinoids in Acne.

Topical retinoids are the cornerstone of current acne management due to their actions on multiple facets of acne pathophysiology. Retinoids are a family of compounds that structurally and functionally resemble vitamin A, an essential nutrient with a key role in cellular growth and differentiation. In the skin, retinoids exert their effects by binding retinoic acid receptors (RARs) in the cell nucleus with subsequent regulation of gene transcription. There are three subtypes of RARs, and the topical retinoids currently approved for acne have differing receptor binding profiles which may translate to clinical differences, since the specific RAR subtypes activated dictate the biological response of target cells. The activity of a retinoid depends on cellular transport, receptor-binding pattern and affinity, and the genes activated. This review discusses physiologic pathways in skin that are affected by topical retinoids during acne therapy, with a focus on new data from trifarotene, a retinoid which is highly selective for the RAR-γ receptor. Recently, bioinformatic data comparing gene expression in acne lesions treated with trifarotene versus spontaneously resolving acne lesions showed that trifarotene significantly modulates 67 genes that do not appear in the spontaneously resolving lesion. These genes are involved in cellular migration, activation of adaptive immunity, inflammation, and matrix reorganization. Expression of these trifarotene-regulated genes after treatment and in an active lesion occurred in opposite directions, providing clues to the molecular and genetic response to trifarotene in resolving acne. J Drugs Dermatol. 2022;21(7):734-740. doi:10.36849/JDD.6890.