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Background Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with an increasing incidence and unknown aetiology. Aim To identify possible environmental and hormonal factors related to FFA. Methods We conducted a multicentre case-control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease. Results For women, there was a statistical association between alopecia and history of pregnancy (OR = 1.6; 95% CI 1.06-2.41), use of facial sunscreen (OR = 1.6; 95% CI 1.06-2.41) and hormone replacement therapy (HRT) (OR = 1.76; 95% CI 1.11-2.8) or raloxifene (no controls exposed therefore OR was not calculated), exposure to alkylphenolic compounds (OR = 1.48; 95% CI 1.05-2.08), and presence of rosacea (OR = 1.91; 95% CI 1.07-3.39), lichen planus pigmentosus (LPP) (OR = 5.14; 95% CI 1.11-23.6) or hypothyroidism (OR = 1.73; 95% CI 1.11-2.69). For men, there was a statistical association between alopecia and use of facial sunscreens (OR = 11.6; 95% CI 1.7-80.9) or antiageing creams (OR = 1.84; 95% CI 1.04-3.23). Conclusions FFA seems to be associated with hormonal exposure (pregnancy, HRT and raloxifene), comorbidities (hypothyroidism, LPP and rosacea) and environmental factors (facial sunscreens, antiageing creams and occupational exposure). Further research is required to analyse the exact mechanism in which these environmental factors participate in the development of this alopecia.

This review assesses molecular aspects of the rescue of disease-causing mutations in genodermatoses by means of naturally occurring secondary genetic phenomena. Such data have important implications for the design of gene therapy approaches for inherited skin diseases. Reversal of the phenotype depends on three elements: the number of cells involved; the degree of gene reversal; and the specific timing of the reversion. If reversion occurs in somatic cells, revertant mosaicism may occur. This is the situation in which a patient's skin is generally affected by the genodermatosis, but islands of normal skin stand out. These reflect the presence of revertant cells that are sufficient to restore a normal local skin phenotype. Reversion of the original mutation may also be partial, in which case the phenotype may display no, or only limited, improvement. Nevertheless, the phenotype may ameliorate with age if the reverted cells preferentially expand in time or if the time of onset of reversion is after birth. In essence, the complexities of naturally occurring rescue processes are important to understand because the inherent mechanisms may provide clues and insight into optimal therapeutic gene manipulation, and the possibility of mimicking nature in the management of patients with diverse genodermatoses.