Spitz nevus and melanoma: evaluation with dermoscopy and reflectance confocal microscopy.

Introduction: Spitz nevi (SN) include a wide range of benign melanocytic nevi, which are controversial due to their morphologic resemblance to melanoma (MM). Aim: To describe dermoscopic and reflectance confocal microscopic (RCM) features of SN compared to MM and assess the RCM utility in the differential diagnosis. Material and methods: We performed a multicentre retrospective analysis of MM and SN evaluated with dermoscopy and reflectance confocal microscopy. Three RCM mosaics were obtained for each lesion. Nine dermoscopic and twenty-one microscopic features were assessed for each lesion. Results: A total of 26 lesions (15 SN and 11 MM) were included. Dermoscopically, most SN showed a "starburst" pattern. Asymmetry was marked in 8 MM. There were 6 dermoscopic features significantly more prevalent in MM than in SN. RCM showed that an atypical honeycomb pattern, atypical infiltration, and disarray of the epidermis were significant for MM. SN mostly revealed a typical honeycomb pattern. At the DEJ, most of SN had a meshwork pattern; MM revealed an atypical meshwork pattern. Atypical cells and sheet-like structures were observed in most MM. Conclusions: A combined approach using dermoscopy and RCM supports the differential diagnosis of SN and MM. Although our study showed some significant differences between SN and MM in RCM, further research on a larger group should be considered.

Dupilumab as promising treatment for prurigo nodularis: current evidences.

Prurigo nodularis (PN) is a debilitating chronic disease characterized by intense itching and excoriated hyperkeratotic nodules distributed on the trunk and extremities, especially the extensor surfaces. The pathophysiology includes complex and not yet well-understood mechanisms involving inflammation and dysregulation of the nervous system. Currently, there are no approved therapies by the Food and Drug Administration (FDA) and the few treatment approaches for this condition are often ineffective and related to severe side effects. An emerging therapeutic option is dupilumab, a monoclonal antibody for adults and adolescents with moderate-to-severe atopic dermatitis, that inhibits interleukin-4 receptor alpha subunit (IL4-Rα) and the signaling pathways activated by interleukin (IL)-4 and IL-13. These cytokines seem to be involved in the development and perpetuation of PN and other type-2 inflammation diseases. Data on this topic are limited, but the emergent positive effects of this drug, reported in the literature and summarized in this review, suggest that it can be a safe and efficient therapy in PN.

Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma.

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.

Synthesis of the Data on COVID-19 Skin Manifestations: Underlying Mechanisms and Potential Outcomes.

The incidence of coronavirus disease 2019 (COVID-19)-related skin manifestations has progressively grown, in parallel with the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. The available evidence indicates that cutaneous signs are heterogeneous and can be divided as follows: a) erythematous rashes, b) lesions of vascular origin, c) vesicular rashes, d) urticarial rashes, and e) acute generalized exanthematous pustulosis (AGEP), erythema multiforme (EM) and other polymorphic/atypical reactions. Most cutaneous manifestations appear simultaneously or after respiratory and/or systemic symptoms such as fever, even if rarely urticaria has been reported as the first sign of the disease. It has been proposed that erythematous and vesicular rashes, as well as urticaria, are the result of immunological activation against Sars-CoV-2, similarly to other viral exanthems; alternatively, reactivation or co-infection of herpesviruses and drug hypersensitivity represent possible etiologic diagnosis that has to be considered. Regarding lesions of vascular origin, ischemic ones are the result of systemic hypercoagulability established in severe infections, whereas chilblains seem to be linked to the type I-interferon massively produced to halt virus replication. AGEP is triggered by drugs, whereas EM could represent a delayed immune response to the virus or a hypersensitivity reaction to drugs elicited by the inflammatory process built to fight the infection. A further pathogenic hypothesis is that the virus, or its particles detected in the skin (particularly in endothelium and eccrine glands), could be responsible for certain skin reactions, including chilblains and EM. From the available data, it appears that chilblains are correlated with younger age and less severe disease, while ischemic manifestations occur in the elderly with severe infection. In conclusion, larger studies are needed to confirm the suggested pathogenetic mechanisms of COVID-19-related skin reactions and to determine the potential prognostic significance of each one.

What makes an inflammatory disease inflammatory? An overview of inflammatory mechanisms of allergic contact dermatitis, atopic dermatitis and psoriasis.

Inflammatory response in the skin is important for host defense against a broad spectrum of insults including microorganisms, chemicals, radiation and physical trauma. When the inflammatory process becomes prolonged and self-perpetuating, illness occurs. In this review, we discuss recent findings regarding the complex inflammatory mechanisms in allergic contact dermatitis, atopic dermatitis and psoriasis.

Current therapies for actinic keratosis.

Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp, neck, hands, and forearms. AKs must be considered an early squamous cell carcinoma (SCC) for their probable progression into invasive SCC. For this reason, all AK should be treated, and clinical follow-up is recommended. The aims of treatment are: (i) to clinically eradicate evident and subclinical lesions, (ii) to prevent their evolution into SCC, and (iii) to reduce the number of relapses. Among available treatments, it is possible to distinguish lesion-directed therapies and field-directed therapies. Lesion-directed treatments include: (i) cryotherapy; (ii) laser therapy; (iii) surgery; and (iv) curettage. Whereas, field-directed treatments are: (i) 5-fluorouracil (5-FU); (ii) diclofenac 3% gel; (iii) chemical peeling; (iv) imiquimod; and (v) photodynamic therapy (PDT). Prevention plays an important role in the treatment of AKs, and it is based on the continuous use of sunscreen and protective clothing. This review shows different types of available treatments and describes the characteristics and benefits of each medication, underlining the best choice.

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death-1 inhibitors: A review of the literature.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent nonmelanoma skin cancer (NMSC). The majority of in situ cSCC [cSCC (Tis)] can be cured surgically, while local advanced and metastatic ones require other treatments, but there are no therapies approved by U.S. Food and Drug Administration (FDA). Available treatments for these stages included radiotherapy, chemotherapy as cisplatin, but responses to these treatments are usually of short duration. Programmed death-1 (PD-1) inhibitors (pembrolizumab, nivolumab, and cemiplimab) are an innovative immunologic treatment that now has been shown to be useful for the treatment of advanced cSCC. Nowadays, data about the response rate with the use of PD-1 inhibitors in cSCC are still few and, especially, the duration of the response after the start of treatment is short. Moreover, the number of cases is too small to express the beneficial effects of these treatments, although most data reported in the literature show quite good response rates. This review focused on some of the studies and associated results through an interesting research on search engines of all the cases about these systemic drugs, analyzing effects and side effects, and the research has been conducted considering published cases since March 2016 to October 2019.