Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

Treatment of locally advanced and metastatic basosquamous carcinoma, navigating among sonic hedgehog pathway inhibitors, immune checkpoint inhibitors, chemotherapy, and radiotherapy: A case series and literature review.

Locally advanced (laBSCs) and metastatic basosquamous carcinomas (mBSCs) represent a therapeutic challenge. By definition, these forms are not amenable to surgery or radiotherapy, but according to literature reports, sonic hedgehog pathway inhibitors (HHIs), anti-programmed death 1 receptor antibodies (anti-PD-1), and other treatment approaches involving chemotherapy, surgery, and radiotherapy have been used. This work features 5 real-life cases of advanced BSCs, treated at the Dermato-Oncology Unit of Trieste (Maggiore Hospital, University of Trieste). In addition, a review of the current treatment options reported in the literature for laBSC and mBSC is provided, collecting a total of 17 patients. According to these preliminary data, HHIs such as sonidegib and vismodegib could represent a safe and effective first line of treatment, while the anti-PD-1 cemiplimab may be useful as a second-line option. Chemotherapy and combined approaches involving surgery and radiotherapy have been also reported to be suitable in some patients.

Synchronous occurrence of primary cutaneous B-cell lymphoma and cutaneous Rosai-Dorfman disease in distinct lesions: A unique association.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma.

Phenotypic and Dermoscopic Patterns of Familial Melanocytic Lesions: A Pilot Study in a Third-Level Center.

Cutaneous melanoma is a highly aggressive skin cancer. It is estimated that 5% to 10% of the underlying mutations are hereditary and responsible for familial (or hereditary) melanoma. These patients are prone to the early development and higher risk of multiple melanomas. In recent years, an increasing number of genes have been identified thanks to genetic testing, allowing the subsequent surveillance of individuals at risk, yet it is still difficult to predict the presence of these mutations on a clinical basis. In this scenario, specific phenotypic and dermoscopic features could help clinicians in their identification. The aim of this work has been to correlate mutations to prevalent dermoscopic patterns, paving the way for reference models useful in clinical practice. In our cohort, out of 115 patients referred to genetic counseling for melanoma, 25 tested positive (21.7%) for critical mutations: CDKN2A (n = 12), MITF (n = 3), BAP1 (n = 1), MC1R (n = 3), PTEN (n = 1), TYR (n = 2), OCA2 (n = 1), and SLC45A2 (n = 2). The phenotype profiles obtained through the digital acquisition, analysis, and description of both benign and malignant pigmented lesions showed a predominance of the type II skin phenotype, with an elevated mean total nevus number (182 moles, range 75-390). As for dermoscopic features, specific mutation-related patterns were described in terms of pigmentation, areas of regression, and vascular structures. Although further studies with larger cohorts are needed, our work represents the beginning of a new approach to the study and diagnosis of familial melanoma, underlining the importance of clinical and dermoscopic patterns, which may constitute a reference model for each gene, enabling comparison.

Retinoid-associated myopia in dermatologic patients: a systematic review.

PURPOSE: Systemic retinoids are among the most prescribed drugs in dermatology, thanks to their activity as proliferation modulators and keratinisation normalisers. Common side effects such as blood lipid disorders, xerosis and photosensitivity are well established and usually dose dependent. Conversely, retinoid-associated ocular disturbances have been reported, yet with differences in terms of frequency and manifestations As data regarding a potential correlation with refractive errors are heterogenous and have not been previously thoroughly addressed, we performed a systematic review of the literature with the aim of comprehensively evaluating the current evidence regarding retinoid-associated myopia in dermatologic patients. MATERIALS AND METHODS: A systematic review of the literature was carried out according to the PRISMA guidelines. A search on MEDLINE, Pubmed, Scopus, Cochrane Library was conducted using the MeSH terms: retinoid, isotretinoin, acitretin, bexarotene, etretinate, alitretinoin, myopia, refractive errors, via the Boolean term AND. Only manuscripts in English were considered, there was no restriction on type of article. Animal research and in vitro studies were excluded. RESULTS: Six articles were finally included in this systematic review. One well designed prospective study was able to show a slight myopic shift in the first six months, but id did not evaluate further development of the refractive error nor the effects of drug discontinuation. Another prospective study, with a smaller sample size showed no myopic progression at 12 months. Two case reports showed a myopic shift after two weeks from therapy start. Another case report showed a myopic shift associated with narrowing of the anterior chamber after one week from therapy start. Finally a large retrospective study based on spontaneous reporting systems and world's literature classified myopia as a certain side effect. CONCLUSION: Considering the current literature, it is not possible to define a clear correlation between the use of retinoids and the development or worsening of myopia. Some studies suggest that retinoids may cause a myopic shift and the pathophysiologyical mechanism is supported by some animal and in vitro studies, but there is a lack of large prospective and well-controlled studies. In case of ocular disturbances after retinoid use a prompt ophthalmological referral is advisable and in case of the detection of a myopic refractive error a relationship to retinoids should be ruled out, considering also other possible causes such as age and previous refractive status.

SARS-CoV-2 vaccine-related cutaneous manifestations: a systematic review.

To date, over 250 million people have been reportedly infected by COVID-19 disease, which has spread across the globe and led to approximately 5.1 million fatalities. To prevent both COVID-19 and viral transmission, DNA-based/RNA-based vaccines, non-replicating viral vector vaccines, and inactivated vaccines have been recently developed. However, a precise clinical and histological characterization of SARS-CoV-2 vaccine-related dermatological manifestations is still lacking. A systematic review of 229 articles was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to provide an extensive overview of SARS-CoV-2 vaccine-related skin manifestations. Data on demographics, number of reported cases with cutaneous involvement, vaccine, and rash type (morphology) were extracted from articles and summarized. A total of 5941 SARS-CoV-2 vaccine-related dermatological manifestations were gathered. Local injection-site reactions were the most frequently observed, followed by rash/unspecified cutaneous eruption, urticarial rashes, angioedema, herpes zoster, morbilliform/maculopapular/erythematous macular eruption, pityriasis rosea and pityriasis rosea-like eruptions, and other less common dermatological manifestations. Flares of pre-existing dermatological conditions were also reported. Cutaneous adverse reactions following SARS-CoV-2 vaccine administration seem to be heterogeneous, rather infrequent, and not life-threatening. Vaccinated patients should be monitored for skin manifestations, and dermatological evaluation should be offered, when needed.

Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma.

About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biological traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less dependent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma.