A role for dermatologists in diagnosing BHD earlier

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.

 

 

3 thoughts on “A role for dermatologists in diagnosing BHD earlier

  1. Is there an explanation, or even clues, for why distribution is limited to predominantly face, neck. & and upper trunk? [“The areas on the face most often involved are the nose, then cheeks, forehead, and ears. Oral examination is important, as these patients may have multiple, discrete, soft, papules of the lips, gingival, and buccal mucosa.” “Multiple trichilemmomas are seen in Cowden syndrome. These lesions look similar to fibrofolliculomas and are located around the mouth, nose, and ears.” (1)] Is it just exposure to UV light? (seems unlikely.) Expression of signaling pathways? Morphological origin? Specific mesenchymal interactions?

    Skin involvement apparently isn’t seen in the rat model. “In addition, there are distinct differences in the types of skin tumors that occur in the two hereditary syndromes [human BHD vs canine RCND, the latter being due to mutations in the canine BHD gene]. In BHD, the skin tumors are hamartomas of the hair follicle termed fibrofolliculomas, composed of elongated, delicate epithelial strands in a dense stroma. RCND-affected dogs do not present with hamaratomas, do not show the strands of epithelial cells, and the hair follicles are generally not involved.” (2) What explains the differences?

    1) https://www.ncbi.nlm.nih.gov/books/NBK45326/
    2) http://hmg.oxfordjournals.org/content/12/23/3043.long

  2. Thank you for your comments Richard. Unfortunately it is unclear why fibrofolliculomas predominantly develop on the face, neck and upper trunk, and why similar growth are not seen in rat models. Hopefully further research can help answer some of these questions.

  3. Very little research appears to have been happening to identify the cause or a treatment for the fibrofolliculomas. In the research that has taken place the participant numbers have been extremely small. One gets the impression that despite regular encouraging comments on the site that suggest research is underway, in reality there is very little funding being allocated to this research so very little occurring. Can the myrolytis trust step the amount of funding up on researching a treatment for these lesions please. At least this way we can all live a normal life for the majority of our lives. Everyone dies in the end, but half living virtually our entire life due to being covered in ugly lesions is worse.

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