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The surface receptor for advanced glycosylation end-products (RAGE) and its soluble (sRAGE) and endogenous secretory (EN-RAGE) forms belong to the superfamily of toll-like receptors and play important roles in inflammation and autoimmunity, directly or through binding with advanced glycosylation end-products (AGE) and advanced oxidation protein products (AOPP). We reviewed the literature on the role of RAGE in skin diseases. Research in this field is still rather limited (28 articles) but suggests the involvement of RAGE and RAGE-related pathways in chronic inflammatory diseases (lupus, psoriasis, atopic dermatitis, and lichen planus), infectious diseases (leprosy, Staphylococcus aureus-induced skin lesions), alterations of the repairing processes in diabetic skin, systemic sclerosis, and ulcers. These data prompt further research in this field, which not only will be useful to better understand the pathogenetic mechanisms of diseases, but is also likely to have intriguing clinical implications. Indeed, when their role in the complex and multifactorial inflammatory balance will be adequately defined, RAGE and related molecules could be used as markers of disease severity and/or response to treatment. Moreover, future promising therapeutic perspectives could be topical administration of some of these molecules (e.g., sRAGE) to modulate local inflammatory response and/or the development of anti-RAGE antibodies for systemic treatment.

Atopic dermatitis is a common chronic/chronically relapsing inflammatory skin disease, with increasing worldwide prevalence. Etiopathogenesis is complex and multifactorial, with a mix of genetic, immunological and environmental aspects. Like in other chronic inflammatory diseases, oxidative stress plays an important pathogenetic role. We reviewed in vivo research studies on humans about oxidative stress and atopic dermatitis. Although sometimes contrasting, overall, they suggest that oxidative stress may have a significant role in atopic dermatitis, but our understanding is still incomplete, at least concerning in vivo data, because of limitations of available literature. Research consists of 33 papers published in 28 years, was not always performed on large study populations, represents a limited number of countries and ethnicities—not always in proportion to their size—and is scattered over multiple papers that, in the majority of cases, cannot be pooled and/or compared because many biomarkers were studied, in different tissues and with different methods. Further, larger studies appear warranted and necessary to shed more light on this aspect of atopic dermatitis, which is important not only to improve our understanding of this disease, but also for potential clinical and therapeutic implications.

Relapsing polychondritis is an immune-mediated systemic disease characterized by recurrent episodes of inflammation of cartilaginous and proteoglycan-rich tissues, resulting in progressive anatomical deformation and functional impairment of the involved structures. Auricular and nasal chondritis and/or polyarthritis represent the most common clinical features, but potentially all types of cartilage may be involved. Because of the pleomorphic nature of the disease, with non-specific symptoms at the onset, the diagnosis of relapsing polychondritis is often delayed. In this review article we provide a comprehensive look into clinical presentation, laboratory and instrumental investigations, diagnostic criteria, and therapeutic options.

Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.

Oxidative stress plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest. In particular, regarding psoriasis, vitiligo, and lichen planus, excess reactive oxygen species and a decline in endogenous antioxidant systems are observed. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. To date, clinical trials in dermatology on these treatments are limited. We reviewed the available studies on the efficacy of antioxidant therapies in psoriasis, vitiligo, and lichen planus. The role of herbal derivatives, vitamins, and trace elements was analyzed. The antioxidant properties of conventional therapies were also evaluated. Data from the literature suggest that antioxidants might be useful, but available studies on this topic are limited, heterogeneous, not completely standardized, and on small populations. Furthermore, in most cases, antioxidants alone are unable to induce significant clinical changes, except perhaps in mild forms, and must be used in conjunction with standard drug treatments to achieve measurable results. Further studies need to be conducted, considering larger populations and using internationally validated scales, in order to compare the results and clinical efficacy.

Background and Objectives: Chronic ionizing radiation has biological effects on exposed healthcare workers, particularly on the skin. Capillaroscopy of the nail bed represents an easy, low cost, and non-invasive test to obtain information on the effects of chronic radiation exposure in healthcare workers. The aim of this study was to evaluate which capillaroscopic parameters are most associated with biological damage by chronic radiation exposure. Materials and Methods: We conducted a case-control study, in which cases were represented by healthcare workers exposed to ionizing radiations and controls by healthy subjects. We recorded anamnestic and personal data, including age and gender, before capillaroscopic examination of proximal nail folds of the fingers of both hands. Ten morphological qualitative/quantitative parameters were taken into consideration, assigning each of them a score on a scale from 0 to 3 (0 = no changes, 1 = <33% abnormal capillaries, 2 = 33–66% of abnormal capillaries, 3 = >66% of abnormal capillaries, for single magnification field at 200×). The parameters evaluated were: changes in the length, distribution and density of capillary loops, reduced visibility, decreased flow, visibility of the sub-papillary plexus, and presence of morphological atypia, such as ectasia, tortuosity, hemorrhage, and signs of neoangiogenesis. Results: We enrolled 20 cases and 20 controls. The two groups did not differ significantly for gender and age. Cases differed from controls in a statistically significant way for the following parameters: decreased capillary length (number of shortened capillaries) (p < 0.05), increased visibility of the subpapillary venous plexus (p < 0.05), tortuosity (p < 0.01), neoangiogenesis (p < 0.01), and ectasias (p < 0.001). Conclusions: We found that some capillaroscopic parameters, such as variability in length of capillaries, visibility of subpapillary venous plexus, presence of ectasias, tortuosity, and neoangiogenesis signs, are particularly associated with exposure to ionizing radiation in healthcare professionals. Alterations of these parameters may represent capillaroscopic clues of biological damage by chronic radiation exposure in healthcare professionals. Based on these observations, capillaroscopy may provide clinical data useful to the prevention and follow-up of radiation-exposed healthcare professionals.

Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.

The current knowledge about the mechanisms of action of light-based treatments (chiefly photodynamic therapy and phototherapy) in skin diseases leans to the possible involvement of epigenetic and oxidative stress mechanisms. To better understand and exploit, to the fullest, these relatively safe and reproducible treatments, several studies have focused on miRNAs, small non-encoding RNAs (22–24 nucleotides), after light-based treatments. The current narrative review focused on 25 articles. A meta-analysis was not deemed appropriate. The results gather the most recurrent skin-related miRNAs up- or downregulated after light treatment. Five of these, miR-21, -29, -125, -145 and -155, are either the most consistently related to efficacy/resistance to treatment or identified as helpful diagnostic tools. A specific class of miRNAs (angioMIRs) requires further studies. Future treatments and imaging techniques could benefit greatly from the use of antagomirs as a possible co-adjuvant therapy along with light-based treatments.

Introduction Chronic hand eczema (CHE) is an inflammatory skin condition characterized by different pathomechanisms, clinical presentations, and prognoses. Treatment is often challenging because of limited approved drugs, and severe CHE is associated with reduced quality of life (QoL) and poor overall health measures in terms of psychological, functional, and occupational challenges. This study aims to describe the real-life management practices of Italian dermatologists who frequently treat patients with CHE, compare these practices with existing guidelines, and propose practical clinical recommendations for the management of these patients. Methods An 11-question survey was administered to 14 participating dermatologists to gather their insights on the diagnosis, treatment, and management of CHE. Moreover, a comprehensive literature search was conducted over the previous 10 years as a starting point for discussion among experts. Results CHE was the reason for 6.9% of dermatological consultations by the 14 experts. Median time to CHE diagnosis was 12 (range: 2–24) months. Fissuring and itching (85.7% for both) were the most frequently reported signs and symptoms of CHE. The survey highlighted the need for long-term treatment that is effective and well tolerated, with experts emphasizing the importance of improving disease awareness among physicians and patients. Practical clinical approaches were proposed, emphasizing the significance of a thorough medical history and identification of symptoms in the management of CHE. Experts advocated for specifically developed CHE treatment approaches, concentrating on alleviating symptoms and signs, minimizing adverse events/safety issues, enhancing the QoL of patients, and long-term disease control. Findings from this survey were further discussed and compared to recommendations of the available guidelines for the management of CHE. Conclusions Managing CHE requires a comprehensive approach that considers both objective clinical factors and subjective patient expectations. Experts emphasized the need for effective and well-tolerated long-term therapies, improved disease awareness, and communication among physicians and patients.

Background and objectives: Dermoscopy is a useful tool for the early and non-invasive diagnosis of skin malignancies. Besides many progresses, heavily pigmented and amelanotic skin tumors remain still a challenge. We aimed to investigate by dermoscopy if distinctive morphologic characteristics of vessels may help the diagnosis of equivocal nodular lesions. Materials and Methods: A collage of 16 challenging clinical and dermoscopic images of 8 amelanotic and 8 heavily pigmented nodular melanomas and basal cell carcinomas was sent via e-mail to 8 expert dermoscopists. Results: Dermoscopy improved diagnostic accuracy in 40 cases. Vessels were considered the best clue in 71 cases. Focusing on the diameter of vessels improved diagnosis in 5 cases. Conclusions: vascular diameter in addition to morphology and arrangement may be a useful dermoscopic clue for the differential diagnosis of clinically equivocal nodular malignant tumors.