Birt-Hogg-Dubé (BHD) syndrome was initially described as a heritable dermatological condition based on the presence of multiple fibrofolliculomas, trichodiscomas and acrochordons in a Canadian kindred (Birt et al., 1977). Now it is known that BHD patients can also develop pulmonary cysts, with an associated risk of pneumothorax, and bilateral, multifocal renal tumours. Due to the risk of tumour development it is important that patients are diagnosed early, enabling them to access regular screening and earlier treatment if required.
The pale and skin-coloured growths characteristic of BHD predominantly develop on patients’ faces and necks, and whilst some patients develop only a small number, others develop hundreds. They usually begin to appear in early adulthood, worsening with age, and are therefore often the first sign that a patient has a condition associated with cancer-predisposition. As such it is important that dermatologists are aware of BHD as a potential cause of dermal lesions when patients are referred for assessment and treatment.
Benign hair follicle tumours (BHFTs) can be associated with various conditions and their histology is often key to differential diagnosis. Tallechea et al., (2015) recently reviewed the histology of several BHFTs including fibrofolliculomas and trichodiscomas. These BHD-associated BHFTs have distinct characteristics and can both occur on the same patient, even sometimes in very close proximity suggestive of a shared pathogenesis. If BHD is suspected it is important to take punch biopsies, due to the deep nature of these lesions, rather than shave biopsies to increase the accuracy of diagnosis.
The presence of multiple pale or skin coloured lesions on a patient could be caused by conditions other than BHD – some of which are discussed here. Suspicion should however be higher in patients with a family history of similar dermatological growths, pneumothoraces or renal cancer. The presence of at least five adult onset fibrofolliculomas or trichodiscomas, one of which has been histologically confirmed, can be used as the basis of a diagnosis of BHD (Menko et al., 2009). However, it is recommended that patients undergo genetic testing to identify mutations in the FLCN gene for a firm diagnosis.
Two recent case reports highlight the potential of dermatologists to identify BHD patients carrying previously undetected renal cysts or tumours. Menzies et al. (2016) describe a 42-year-old woman with multiple skin papules that developed in her late 30s and a family history of similar lesions. Punch bioposies and genetic testing confirmed BHD and she was found to have a benign renal cyst in a follow-up ultrasound. Ge and Lowe (2016) describe a 52-year-old man with multiple facial lesions, a personal history of bilateral pneumothorax and whose sons also experienced dermatological growths and recurrent pneumothorax. BHD was confirmed by genetic testing, and subsequently a renal tumour was identified on his left kidney – after removal this was determined to be a hybrid oncocytoma/chromophobe tumour (HOCT), a subtype characteristic of BHD. These patients and their families will now be regularly monitored for tumour growth, ensuring timely treatment.
Fibrofolliculomas, although benign and of little or no health risk, are a visible sign of the disease and their development can therefore be distressing. Dermatologists should therefore be willing to discuss treatment options with patients; although patients should be aware that none of the current treatments can permanently remove the growths. Continuing research into the underlying pathology of fibrofolliculomas could identify new therapeutic targets enabling more efficient treatments to be developed.
- Birt AR, Hogg GR, Dubé WJ (1977). Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 113(12):1674-7. PMID: 596896.
- Ge L, Lowe P (2016). Not just a cosmetic problem: facial papules in Birt-Hogg-Dubé syndrome. Med J Aust. 204(1):28-9. PMID: 26763815.
- Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, Nordenskjöld M, Hansen TV, Solly J, Maher ER; European BHD Consortium (2009). Birt-Hogg-Dubé syndrome: diagnosis and management. Lancet Oncol. 10(12):1199-206. PMID: 19959076.
- Menzies S, Fabre A, Lally A (2016). Birt-Hogg-Dubé syndrome: identifying patients at risk of renal cell carcinoma, pulmonary cysts and pneumothoraces. BMJ Case Rep. Jan 13;2016 pii: bcr2015213865 PMID: 26762352.
- Tellechea O, Cardoso JC, Reis JP, Ramos L, Gameiro AR, Coutinho I, & Baptista AP (2015). Benign follicular tumors. Anais brasileiros de dermatologia, 90 (6), 780-98 PMID: 26734858.