Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen’s disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.