Dermatomyositis unleashed by immune checkpoint inhibitors. Three additional cases and a review of the literature.

OBJECTIVES: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of several locally advanced and metastatic tumors. They enhance the effector function of the immune system, consequently leading to different immune-related adverse events. The aim of the present study was to describe three cases of dermatomyositis (DM) triggered by ICI diagnosed at our institution and to perform a review of the literature. METHODS: We performed a retrospective clinical, laboratory, and pathological evaluation of three cases of DM triggered by ICI belonging to a cohort of 187 DM patients from the Clinic Hospital Muscle Research Group of Barcelona from January 2009 to July 2022. Moreover, we undertook a narrative review of the literature from January 1990 to June 2022. RESULTS: Cases from our institution were triggered by avelumab, an anti-PD-1 ligand (PD-L1), nivolumab, and pembrolizumab, both anti-programmed death-1 (PD-1). One of these patients had locally advanced melanoma, and two had urothelial carcinoma. The severity and response to treatment were heterogeneous among the different cases. All were positive at high titers for anti-TIF1γ autoantibodies; in one of them, serum before the onset of ICI was available, and anti-TIF1γ autoantibodies were already present. RNA expression of IFNB1, IFNG and genes stimulated by these cytokines were markedly elevated in these patients. CONCLUSIONS: In conclusion, data from our patients and the narrative review suggest that early positivity to anti-TIF1γ unleashed by ICI may play a role in the development of full-blown DM, at least in some cases.

High-risk mucosal human papillomavirus-associated squamous cell carcinoma of the fingers presents distinctive clinicopathological characteristics and outcomes: a bicentric retrospective study.

BACKGROUND: High-risk mucosal human papillomavirus (HR-HPV) seems to play a role in cutaneous squamous cell carcinoma (cSCC), particularly in nail tumours, where genitodigital transmission has been suggested. The role of HR-HPV in nonungual cSCC of the finger needs to be clarified. AIM: To evaluate the prevalence, clinicopathological characteristics, surrogates and outcomes of HR-HPV in cSCC of the finger. METHODS: This was an observational bicentric study including patients with an excised in situ or invasive cSCC located on the finger. Differences in HR-HPV and non-HR-HPV tumours were evaluated. RESULTS: Forty-five patients (45 tumours) were included. HR-HPV was detected in 33% of cases (22% HPV type 16). The mean age was lower in patients with HR-HPV than in those with non-HR-HPV (62·4 vs. 81·1 years, P = 0·001). HR-HPV tumours were smaller (10 mm vs. 15 mm, P = 0·07) and more frequently intraepidermal (60% vs. 20%, P = 0·004). The absence of elastosis (P = 0·030) and inflammation (P = 0·026) and the presence of basaloid morphology (P = 0·003) were surrogates of HR-HPV detection. Mean p16 positivity was 61% in HR-HPV and 36% in non-HR-HPV tumours (P = 0·061). Recurrence after surgery was more common in HR-HPV tumours (58% vs. 34%), although this was not statistically significant. HR-HPV was detected in 27% of the nonungual tumours. CONCLUSION: HR-HPV-associated cSCC of the finger appears in younger patients, is smaller and is less infiltrative than non-HR-HPV tumours. The presence of a basaloid morphology and the absence of elastosis and inflammation could be used as markers for HR-HPV detection. The high prevalence of HR-HPV in nonungual cSCC suggests its aetiopathogenic role in these tumours.

Photoprotection for people with skin of colour: needs and strategies.

Skin of colour or pigmented skin has unique characteristics: it has a higher eumelanin-to-pheomelanin ratio, more mature melanosomes, an increased amount of melanin distributed in the upper layers of the epidermis, and more efficient DNA repair compared with lighter skin. However, individuals with skin of colour are at a significant risk of skin damage caused by ultraviolet radiation, including the development of photodermatoses and photoageing changes such as uneven skin tone, and are predisposed to pigmentary disorders. In fact, one of the most common conditions leading to dermatology consultations by patients with skin of colour is photoexacerbated pigmentary disorders. Unfortunately, individuals with skin of colour may be less prone to engage in photoprotective measures, including the use of sunscreens. Physicians are also less likely to prescribe sunscreens for them. There is thus a clear need for better education on photodamage and for more efficient and suitable photoprotection in populations with skin of colour. However, this need has thus far only partially been met, and the development of sunscreen products designed to provide optimal photoprotection for people with skin of colour remains a challenge. Targeted sunscreens for individuals with skin of colour require optimal cosmetic appeal (leaving no white residue and not disrupting skin tone). They should include broad-spectrum [ultraviolet (UV)B/UVA] protection with high sun protection factor, as well as protection against long-wave UVA (UVA1) and visible light, as these wavelengths are capable of inducing or augmenting pigmentary disorders. They may also contain depigmenting agents for patients with pigmentary disorders.

Melasma: The need for tailored photoprotection to improve clinical outcomes.

BACKGROUND/PURPOSE: Melasma is a frequent photoexacerbated hyperpigmentary disorder, which can significantly impact on the quality of life. We sought to review the pathogenesis of melasma, and the role of photoprotection in the prevention and treatment of this disorder. METHODS: We conducted a narrative review of the literature. We performed literature searches with PubMed from January 1990 to December 2021 using the keywords "melasma," "pathogenesis," "ultraviolet radiation," "visible light," "photoprotection," and "sunscreens." RESULTS: The physiopathology of melasma includes a complex interaction between genetics, sex hormones, and sun exposure. Visible light, in particular high-energy visible light (HEVL), and long-wave UVA (UVA1) play a key role in melasma pathophysiology, and recent research suggests that melasma shares many features with photoaging disorders. Melasma disproportionately affects dark-skinned individuals. Some 30% to 50% of South Americans and Asians, among other ethnicities, can present with melasma. Dark-skinned patients take fewer photoprotective measures. Also, the majority of melasma patients do not adequately follow photoprotection recommendations, including the application of sunscreen. Intensive use of a broad-spectrum sunscreen can prevent melasma in high-risk individuals, can lessen melasma severity (associated or not with depigmenting agents), and can reduce relapses. CONCLUSIONS: Due to the physiopathology of melasma, sunscreens should be broad-spectrum with high sun protection factor, and provide high protection against UVA1 and VL. Sunscreens should be cosmetically acceptable and leave no white residue. Tinted sunscreens are an excellent choice, as pigments can protect from HEVL and UVA1, and may provide camouflage, but they must offer colors that match the skin tone of each patient.

Tratamiento de la escabiosis / Treatment of scabies

La escabiosis afecta a más de 200 millones de personas en el mundo, y ocasiona un importante impacto socioeconómico. El mecanismo de contagio es por contacto directo prolongado. El contagio por fómites es infrecuente, aunque puede ser importante en la sarna noruega. La terapia con permetrina tópica al 5% es recomendada como tratamiento de primera línea. Puede indicarse durante el embarazo y la lactancia, y parece ser segura en niños <2 meses. Sin embargo, últimamente se ha reportado una disminución de la efectividad de este fármaco. Otra alternativa en primera línea terapéutica es la ivermectina oral. Se puede administrar durante la lactancia, y estudios recientes sugieren que es segura en niños y lactantes pequeños. Diversas revisiones sistemáticas y metaanálisis han concluido que la ivermectina oral es tan efectiva y segura como la permetrina tópica. La administración terapéutica «en masa» de ivermectina oral es una excelente opción para el manejo de escabiosis en comunidades con alta prevalencia o de brotes en instituciones.

Scabies affects more than 200 million people around the world, and causes a significant socioeconomic impact. Prolonged skin-to-skin contact is the primary mode of transmission. Fomite-mediated transmission is uncommon, although it can be significant in crusted scabies. Topical therapy with permethrin 5% is recommended as first-line treatment. It can be indicated during pregnancy and lactation, and appears to be safe in children <2 months. However, a decrease in the effectiveness of this drug has recently been reported. Another first-line therapeutic alternative is oral ivermectin. It can be administered during lactation, and new evidence suggests that it is safe in children >15kg. Diverse systematic reviews and meta-analysis have concluded that oral ivermectin is as effective and safe as topical permethrin. Mass drug administration of oral ivermectin is an excellent option for the management of scabies in communities with high prevalence, or for scabies outbreaks in institutions.