The onset of FD before 25 years of age and the presence of pustules within the alopecic patch were associated with severe FD. Tetracyclines and the combination of clindamycin and rifampicin were the most useful treatments.
Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the
HLA-B*07:
02 allele. At 2p22.1, we implicate a putative causal missense variant in
CYP1B1
, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by
HLA-B*07:
02.
Summary
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.
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