Patients with BHD syndrome usually develop benign hair follicle tumours, clinically known as fibrofolliculomas, which appear as multiple whitish papules after the age of 20 (Menko et al., 2009). Fibrofolliculomas develop primarily on the face, but can also appear on the neck, ears and the upper torso (Menko et al., 2009).
Previously, fibrofolliculomas and trichodiscomas (skin-coloured tumours occurring on the upper body) were considered separate hallmarks of BHD syndrome, but studies suggest that they may not be distinct histological entities, and that a morphological spectrum of these benign skin tumours may exist (Fujita et al., 1981; Misago et al., 2009). Several case studies suggest that this spectrum could also be expanded to include perifollicular fibromas (Kamada et al. 2015). In addition Aivaz et al., (2015) reported BHD patients with comedonal and cystic fibrofolliculomas; which can be associated with a range of other dermatological conditions.
The number of fibrofolliculomas per BHD patient can range from under 10 to over 100 (Toro et al., 1999). It has been postulated that fibrofolliculomas arise from sebaceous glands, rather than hair follicles, because epithelial strands within fibrofolliculomas are continuous with the sebaceous gland, and are usually localised to areas with a high concentration of sebaceous glands, such as the peri-nasal area (Claessens et al., 2012; Vernooij et al., 2013). The morphology and histology of various benign hair tumours is discussed in a review from Tallechea et al., 2015.
Retrospective analysis of 62 Asian cases of BHD reported in the literature showed that Asian patients are less likely to develop skin lesions, and that there are only four reported cases of Asian BHD patients developing all three symptoms of BHD (Murakami et al., 2014).
Aivaz et al., (2015) reported on four BHD case studies (only two genetically confirmed) where comedonal and cystic fibrofolliculomas were present. Such fibrofolliculomas have not been well characterised in BHD patients and whislt open comedones are associated with a range of other dermatological conditions, BHD should be included in differential diagnoses.
Gijezen et al., (2014) performed a small clinical trial testing Rapamycin as a treatment for fibrofolliculomas. 19 BHD patients completed the 6 month double-blind, randomised, facial left-right controlled trial. The number of patients who reported cosmetic improvement with Rapamycin was not significantly more than those patients who reported no improvement at all or improvement with the placebo drug. Additionally, 13 out of 19 patients reported one or more side effects, burning, redness, dryness and itching. Overall, these results suggest that Rapamycin is not an effective treatment for fibrofolliculomas.
Starink et al. (2011) described the syndrome Familial Multiple Discoid Fibromas (FMDF), characterised by the presence of multiple discoid fibromas which resemble fibrofolliculomas and develop on the face and pinnae during childhood or early adulthood. Although clearly a genetic syndrome, FMDF is not linked to the FLCN locus therefore represents a distinct syndrome. Wee et al. (2013) report that an 8 week course of topical rapamycin reduced the size and redness of skin lesions in two siblings with FMDF, suggesting that dysregulated mTOR signalling may contribute to the development of skin lesions