as PR-like eruptions may have peripheral eosinophilia, interface dermatitis and eosinophils on histopathology, with no evidence of HHV-6 and HHV-7 systemic reactivation. 3 Our cases had overlapping features of both PR and PR-like eruptions.COVID-19 has been associated with cases of PR and PRlike eruptions following the acute infection. 6,7 Skin biopsies may demonstrate positivity for the SARS-CoV-2 virus spike protein on endothelial cells and lymphocytes suggesting a direct relationship between SARS-CoV-2 infection and PR. 7 SARS-CoV-2 may also trigger PR by reactivation of HHV-6 or HHV-7. 5 PR eruptions have developed following vaccination for influenza and H1N1 8-10 and may be secondary to reactivation of HHV-6 and HHV-7, which may be detected in skin biopsies via in situ hybridization and immunohistochemistry. 9 Another possible cause for PR in the setting of vaccination is a T-cell-mediated response triggered by molecular mimicry from a viral epitope. 8 Given worldwide vaccination efforts against COVID-19 with mRNA vaccines, it is important for doctors and patients to recognize possible adverse events including PR. Further study is required to confirm the causative link, including direct examination of tissue and serological studies for evidence of HHV-6 and HHV-7 reactivation.
Opinion statementRecently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.
Introduction: Few data on possible local factors that can influence the achievement of response in nonsegmental vitiligo (NSV) treated with narrowband ultraviolet B (Nb-UVB) phototherapy are available. Our objective is to evaluate possible correlations between therapeutic outcomes and dermoscopic and local (lesional) clinical findings of vitiligous lesions undergoing Nb-UVB phototherapy to find positive and/or negative response predictor factors to such treatment. Methods: For each target patch, we calculated the extension area using a computer-aided method and assessed dermoscopic and local (lesional) clinical findings at baseline. After 30 phototherapy sessions (twice weekly), surface area of the lesions was reevaluated to assess clinical improvement, correlating the therapeutic outcome with initial clinical and dermoscopic features. Results: A total of 70 lesions were finally included in the study. At the end of therapy, 18 patches (25.7%) achieved improvement, and the presence of perifollicular pigmentation on baseline dermoscopic examination was found to be associated with a 12-fold higher probability of having a positive therapeutic outcome. Similarly, face localization was also correlated with clinical amelioration, with a sevenfold higher probability for improvement. No association (p [ 0.05) between therapeutic outcomes (either good or poor) and other dermoscopic or local clinical variables (including leukotrichia) was observed. Conclusions: Therapeutic response of vitiligo to Nb-UVB phototherapy may be positively affected by local features of the lesions, i.e., face localization and presence of perifollicular pigmentation on baseline dermoscopic examination, which might be considered as positive response predictor factors to optimize treatment of vitiligo.
Melanoma diagnosed during childbearing period or up to 1 year after delivery is defined as pregnancy-associated melanoma (PAM). There is some evidence that PAM has worse prognosis if compared with melanoma in nonpregnant women, although literature is still inconclusive. Many biological mechanisms could explain this behavior, such as hormonal and immune status, increased lymphangiogenesis but also delay in diagnostic and therapeutic management. If PAM is suspected, a prompt excisional biopsy under local anesthesia can be performed regardless of the gestational period. Conversely, additional staging procedures (such as sentinel lymph node biopsy or imaging) and systemic therapy are still debatable during pregnancy. A multidisciplinary tailored approach should be preferred, together with exhaustive counseling of the mother.
We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already after the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nevi and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice.
Background: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs). Summary: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions. Key messages: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts.
Cutaneous vasculitides encompass a heterogeneous group of clinicopathological entities, which may occur as single-organ vasculitis of the skin or present as skin-limited variant of systemic vasculitis (i.e., skin-limited ANCA-associated vasculitis), and are triggered by various factors, including infections, drugs and vaccines. The COVID-19 pandemic has challenged us with a variety of both disease- and vaccine-associated skin manifestations, including vasculitis. Among the latter, cutaneous small-vessel vasculitis, previously known as leukocytoclastic vasculitis, seems to be the most reported in either scenario, i.e., natural infection and vaccination. Vasculopathy without true vasculitic changes on histology develops in but a minority of cases, mostly severe/critical COVID-19 patients, and appears to be the result of endothelial injury due to pauci-immune thromboembolic mechanisms. Herein, we provide an overview of the available literature on COVID-19-associated and anti-SARS-CoV-2-vaccine-associated cutaneous vasculitis. Although evidence is mostly limited to isolated reports, with a proportion of cases lacking histopathological confirmation, ample overlap with pre-pandemic forms is shown.
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