Early diagnosis, treatment of renal tumours and prevention of pneumothoraces are major aspects to consider in management of BHD. However, treatment of a rare disease like BHD should go beyond care of only the physical symptoms. Clinicians should be aware of and consider the psychosocial aspects of having a rare disease and be able to offer patients additional resources to manage this aspect of their condition.
Currently, there are no standardised guidelines for the management of BHD. This document collates advice on how BHD is managed to aid clinical practice.
Management of Skin Manifestations
Fibrofolliculomas are benign skin lesions that do not require treatment. However, they have the potential to severely affect a person’s mental health and self-confidence, and this should always be considered when discussing potential management options. Currently, there are no available treatments that can remove fibrofolliculomas permanently, and as such recurrence can be a problem; this should be discussed with the patient. Information on available treatment options can be found here.
Management of Lung Manifestations
Lung cysts associated with BHD do not normally affect lung function and there is currently no specific treatment or preventative measures for cystic lung disease. Management of the lung manifestations of BHD is therefore largely concerning prevention and treatment of pneumothoraces. This high recurrence rate of pneumothorax should also be taken into consideration when treating BHD-related pneumothoraces. In a study of 198 patients from 89 families with BHD, 75% were found to have recurrent pneumothorax (1). Information on treatments for pneumothorax can be found here.
Any patients that do show a reduction in lung function should be monitored periodically to assess lung function. Although there is currently no causal association between smoking and BHD-related lung cysts or pneumothorax, smoking should be discouraged and advice on stopping smoking should be offered (2).
Other considerations for the management of pneumothoraces in BHD patients include activities that result in a change of air pressure, such as diving or air travel. While diving is discouraged, air travel is generally not discouraged unless there is impairment of lung function, or a pneumothorax is ongoing or recently treated. In these instances, patients should consult with their pulmonologist before travelling by air (3).
Patients should be fully informed of the symptoms and risks of pneumothorax and should be advised to carry medical information regarding previous pneumothorax episodes and treatments. They should also consider the risks of travelling to remote locations where access to medical treatment may be difficult.
Management of Kidney Manifestations
People affected by BHD are at risk of developing one or more renal tumours in their lifetime and they are often multifocal. As such, it is proposed that all BHD patients are offered renal screening from 20 years of age (4). The type of screening, and frequency of screens may depend on geographic location and access to healthcare/health insurance. Screening methods include MRI, high resolution ultrasound or CT scan. However, there are disadvantages to all these methods, including high cost (MRI), frequent exposure to radiation (CT) and sensitivity for detecting small tumours (ultrasound) (3). Frequency of scans can vary from yearly to every 2-4 years depending on the individual case. For example, in a patient with no renal tumours, screening may be more infrequent than a patient who has a renal tumour (3,5).
Most BHD-associated renal tumours are oncocytoma, chromophobe, or a mixture of the two, and are normally slow-growing and do not metastasise. It is recommended that tumours are surgically removed when they reach >3cm in size (4). However, as more tumours may develop over time, nephron-sparing surgery should be considered to preserve kidney function where possible. When surgery is not feasible, radiofrequency ablation or cryoablation are alternative treatment strategies (3). More information on treatment strategies for renal tumours can be found here.
As BHD is an autosomal dominant disorder, first degree relatives have a 50% risk of having inherited the pathogenic variant of FLCN. As such, genetic molecular testing for the pathogenic FLCN variant should be offered to at-risk individuals to diagnose BHD as early as possible and implement monitoring for the development of renal tumours. There is currently no consensus on the recommended age for asymptomatic individuals and this will be dependent on the genetic testing centre guidelines. However, symptomatic individuals should be tested regardless of age. Patients should be offered and referred to genetic counselling to enable this process and help families get a diagnosis, find out who else in the family has the disease, learn about the disease, and give advice about family planning, genetic discrimination and health insurance.
1. Toro JR, Pautler SE, Stewart L, Glenn GM, Weinreich M, Toure O, et al. Lung Cysts, Spontaneous Pneumothorax, and Genetic Associations in 89 Families with Birt-Hogg-Dubé Syndrome and 4 Molecular Imaging Program, 5 Biostatistics and Data Management Section, and AT A GLANCE COMMENTARY Scientific Knowledge on the Subject. Am J Respir Crit Care Med [Internet]. 2007 [cited 2021 Jul 21];175:1044–53. Available from: www.atsjournals.org
2. N G, K S, FX M. Pulmonary manifestations of Birt-Hogg-Dubé syndrome. Fam Cancer [Internet]. 2013 Sep [cited 2021 Jul 20];12(3):387–96. Available from: https://pubmed.ncbi.nlm.nih.gov/23715758/
3. Daccord C, Good JM, Morren MA, Bonny O, Hohl D, Lazor R. Birt–hogg–dubé syndrome. Eur Respir Rev [Internet]. 2020 Sep 30 [cited 2021 May 20];29(157):1–14. Available from: https://doi.org/10.1183/16000617.0042-2020].
4. Stamatakis L, Metwalli AR, Middelton LA, Linehan WM. Diagnosis and Management of BHD-Associated Kidney Cancer. Fam Cancer [Internet]. 2013 Sep [cited 2021 Jul 21];12(3):397. Available from: /pmc/articles/PMC4175415/
5. Sattler EC, Steinlein OK. Birt-Hogg-Dubé Syndrome. GeneReviews® [Internet]. 2020 Jan 30 [cited 2021 Jul 20]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK1522/
Last Updated: July 2021
Review date: July 2024