Recent reports on BHD and skin symptoms – misdiagnosis and new manifestations

Patients with Birt-Hogg-Dubé (BHD) syndrome usually develop benign hair follicle tumours (BHFTs) which appear as multiple whitish papules developing primarily on the face, neck and torso (Menko et al., 2009). BHFTs such as fibrofolliculomas and trichodiscomas (skin-coloured tumours occurring on the upper body) can be associated with various genetic conditions and their histology is often key to differential diagnosis. The morphology and histology of various BHFTs is discussed in a recent review from Tallechea et al. (2015).

Del Rosso et al. (2016) reported a case of BHD that was initially misdiagnosed as acne. The patient declared having face acne for 20 years. Past medical history revealed a collapsed lung and a family history of pneumothorax and kidney neoplasms. Clinical examination revealed multiple off-white indurated papules on the face. Biopsies of the papules demonstrated fibrofolliculoma. Inquiry into further family history revealed that a relative with kidney malignancy had a FLCN mutation which led to the diagnosis of BHD. Several dermatologic conditions may simulate facial acne, including other papulopustular disorders and inherited syndromes that produce multiple facial papules that mimic acne. The authors summarize genetic syndromes associated with facial papules that may simulate acne and alert to the importance of considering other conditions in the presence of facial papular lesions. The presence of multiple skin lesions on a patient could be caused by conditions other than BHD – some of which are discussed in Del Rosso et al. (2016) report and here. Suspicion of BHD should be higher in patients with a family history of similar skin growths, pneumothoraces or renal cancer. Although presence of adult onset fibrofolliculomas or trichodiscomas can be suggestive of BHD, it is recommended that patients undergo genetic testing to confirm diagnosis.

Amim et al. (2016) recently reviewed the cutaneous lesions manifested in BHD and Von Hippel-Lindau (VHL) syndromes associated with an increased risk of renal cell carcinoma (RCC). Authors discuss the importance of early recognition of these lesions given that they may be the first presenting sign for RCC since they usually appear at a young age. In addition, therapeutic options for the treatment of advanced RCC and their dermatologic toxicities are briefly reviewed.

DiCicco et al. (2016) reported the case of a male with multiple papules on the face and trunk and a periungual papule on a digit of the right hand. Histology analysis found an angiofibroma on a facial papule, fibrofolliculomas on the papules of the trunk and, unique to this case, the presence of a Koenen’s tumour on the digit lesion. The patient also reported a family history of facial papules and pneumothoraces. BHD diagnosis was confirmed by genetic analysis. Koenen’s tumours are typically associated with tuberous sclerosis complex (TS), however, genetic analysis of the patient found no mutations indicative of TS. Significant cutaneous and internal manifestations are similar between BHD and TS. In addition, both FLCN and TS proteins appear to play important roles in the mTOR pathway. Whereas the hallmarks of BHD were fibrofolliculomas and trichodiscomas, facial angiofibromas indistinguishable from those in TS have also been reported (Shaffer et al., 2005; Spring et al., 2013) suggesting that there may not be distinct histological entities, and that a morphological spectrum may exist. Likewise, there is a report of fibrofolliculomas in a patient with TS (Misago et al., 2009). In summary, this case adds to the list of cutaneous manifestations of BHD and illustrates the overlap between BHD and TS and how genetic testing is important to establish a firm diagnosis.

DeMartino et al. (2016) reported the case of a non-smoking male with obesity, hypertension and hyperlipidemia and a history of recurrent pneumothoraces over the past 9 years. The patient had no pneumothorax on his family history. Skin exams showed thorascostomy scars and numerous follicular based white papules on the face and neck. CT scans detected multiple cysts on both lungs but no renal lesions. Histology analysis found dermal follicular structures consistent with the fibrofolliculomas of BHD.

It is crucial that dermatologists and doctors in general are aware of BHD as a potential cause of cutaneous lesions to avoid erroneous diagnosis and management. Even though BHD skin manifestations are benign and of little health risk they are a visible sign of the disease and their development can therefore cause discomfort and stress. Doctors should be prepared to discuss treatment options with patients. Continuing research into the underlying pathology of BHFTs and their association with genetic conditions will enable more efficient diagnosis and treatments.

  • Del Rosso JQ, Silverberg N, & Zeichner JA (2016). When Acne is Not Acne. Dermatologic clinics, 34 (2), 225-8 PMID: 27015783

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