A systematic meta-analysis of observational studies of melanoma and one of the most important risk factors, the number of naevi, was conducted in order to clarify aspects of the aetiology of this disease. Following a systematic literature search, relative risks (RRs) were extracted from 46 studies published before September 2002. Dose-response random effects models were used to obtain pooled estimates. Sub-group analysis and meta-regression were carried out to explore sources of between-study variation and bias. Sensitivity analyses investigated the reliability of the results and any publication bias. Number of common naevi was confirmed an important risk factor with a substantially increased risk associated with the presence of 101-120 naevi compared with <15 (pooled Relative Risk (RR) = 6.89; 95% Confidential Interval (CI): 4.63, 10.25) as was the number of atypical naevi (RR = 6.36 95%; CI: 3.80, 10.33; for 5 versus 0). The type of study and source of cases and controls were two study characteristics that significantly influenced the estimates. Case-control studies, in particular when the hospital was the source for cases or controls, appeared to present much lower and more precise estimates than cohort studies.

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.

The possibility of a causal influence of emotional stress, especially of stressful life events, on the course of various skin diseases has long been postulated. Clinical wisdom and experience, as well as many anecdotal observations and uncontrolled case series, support this opinion. We reviewed the available evidence on the role of stressful life events in triggering or exacerbating skin diseases. The role of stressful events in vitiligo, lichen planus, acne, pemphigus and seborrhoeic dermatitis was either controversial or insufficiently explored. The role of stressful events in psoriasis, alopecia areata, atopic dermatitis and urticaria was apparently clearer. However, only a few studies met acceptable methodological standards for stress measurement. Also, few studies considered common potential confounding factors (e.g. age, duration of illness, familial factors), and no study controlled adequately for the influence of other crucial factors (e.g. discontinuation of treatment, seasonal effects). Adding that the large majority of studies were retrospective, it seems wise to conclude that only preliminary evidence has been published so far on the role of stressful life events in bringing on or worsening any dermatological disease. Further research is mandatory, either in the form of prospective studies or, more feasibly, of well-designed case-control studies with adequate statistical power. Future studies should also pay more attention to protective as well as vulnerability factors in stressful events. Further, it would be important to investigate other sources of psychological stress, such as chronic stress and everyday stress. Measuring stress appraisal, although difficult, would also be important.