Are Sunscreen Particles Involved in Frontal Fibrosing Alopecia?—A TEM-EDXS Analysis on Formalin-Fixed Paraffin-Embedded Alopecia Biopsies (Pilot Study)

To the Editor: Frontal fibrosing alopecia (FFA) is an idiopathic form of scarring alopecia, which presents with selective alopecia of the frontal hairline and eyebrows. Since the initial description, the incidence of FFA has increased. It has been suggested that environmental factors may play a role. One hypothesis is that the increased popularity of mineral-based sunscreens may be a significant etiologic factor. Mineral-based sunscreens contain zinc oxide (ZnO) or titanium dioxide (TiO2) as the active ingredients because of their UV-reflective properties, which are “micronized” to make them translucent to visible light and therefore more cosmetically acceptable. There is belief that these particles may be able to migrate into the follicular ostia. Perhaps the presence of these particles within the hair follicle units elicits an immune response. This would explain the characteristic pattern of hair loss that presents in the eyebrows and the entire frontal hairline, but spares other areas of the scalp. Moreover, a relatively recent X-ray spectroscopy study by Brunet–Possenti and colleagues1 has reported the presence TiO2 particles along the hair shafts. However, Thompson and colleagues2 have also demonstrated the presence of TiO2 on the hair of patients without FFA. Therefore, the causal relationship between sunscreen particles and FFA is controversial so far. Prompted by these observations, we conducted a pilot study to determine the presence of TiO2 and ZnO particles in skin biopsy specimens from 2 patients with a confirmed diagnosis of FFA and routine sunscreen usage, and to correlate the location of these particles within the follicular unit and perifollicular stroma. Two formalin-fixed, paraffin-embedded, horizontally sectioned whole tissue sections were retrieved from our dermatopathology archive. By light microscopy, the sections demonstrated classic features of FFA, characterized by lichenoid interface dermatitis and concentric perifollicular fibrosis, predominantly involving the infundibulum and isthmus (Fig. 1). The ultrastructural examination was performed and viewed on a Tecnai 12 transmission electron microscope. There were no particles within the follicular epithelium and perifollicular stroma. After detailed observations, 6 regions with active inflammation and lamellar fibroplasia were selected for additional energy-dispersive X-ray spectrometry analysis. We confirmed that no sunscreen particles (ZnO or TiO2) were present (Fig. 2).FIGURE 1.: FFA showing a perifollicular chronic inflammation and lamellar fibroplasia with dyskeratosis and lymphocytic exocytosis (H&E horizontal section ×100).FIGURE 2.: Representative transmission electron microscope image (A) and energy dispersive spectroscopy spectrum (B) from FFA specimen reveal no significant peaks; of note, the Be peak is present because of the Be-tipped EDXS holder. Copper grids were used to lay the sections, hence the Cu peak is high.To the best of our knowledge, this study is the first ultrastructural analysis to determine the existence of sunscreen particles in various regions of the FFA hair follicle units. We demonstrated no significant penetration of sunscreen particles within the regions of active inflammation and fibrosis. This lack of association may suggest that there is no direct link between sunscreen usage and FFA. However, our results cannot exclude the possibility that the initial application of sunscreen on the surface epidermis could trigger the immune response of FFA, although several previous studies have already shown no significant association of FFA with positive reaction to several cosmetic-related substances (containing Ti).3,4 The current sample size is clearly insufficient to draw firm conclusions and the possibility of false negative cannot be entirely excluded in this small pilot. Future larger studies examining the samples after using the sunscreen for several days in a row may also be helpful in exploring any relationship between sunscreen usage and FFA. As previously suggested,5 however, we also suspect that FFA most likely represents a multifactorial and complex disease, and simply avoiding sunscreen without conclusive evidence could have other potential health implications.