In August 2011, a blog post highlighted a study by Starink et al. (2011), which described a condition known as familial multiple discoid fibromas (FMDF). This rare skin disorder is characterised by the early onset of multiple firm papules on the face and ears. Although FMDF shares some characteristics with BHD syndrome, no systemic symptoms or FLCN mutations are observed. A recent study now describes siblings with FMDF which appears to respond to treatment with topical rapamycin (Wee et al., 2013).
In this study, a 27-year old man and his 22-year old sister presented with multiple skin lesions, but no family history of skin, lung or renal abnormalities. In both cases the lesions developed during childhood/adolescence and involved the face/ears, which helps distinguish FMDF from BHD syndrome. In addition, no systemic manifestations or pathogenic mutations in FLCN were detected. Furthermore, no mutations were identified in TSC1 and TSC2, which also discounts tuberous sclerosis complex (TSC). Much like the lesions described by Starink et al. (2011), hair follicles were seen at the periphery of the papules. However, biopsies also noted an unusual histological feature in some lesions involving a keloidal-like pattern.
Surgical treatment with shave excision, hyfrecation and curettage and cautery was attempted on some lesions with unsatisfactory results. Since rapamycin was shown to improve the appearance of skin lesions in TSC (Haemel et al., 2010; Mutizwa et al., 2011), Wee et al. trialled the application of topical rapamycin at 1 mg/ml on the facial skin of the affected brother. Only a once daily application was tolerated due to local skin irritation, but there was a noticeable improvement in the redness and size of the lesions after 8 weeks of treatment. Further (but less significant) improvement was noted at 16 weeks of treatment, with no detectable absorption of rapamycin into the bloodstream.
The genetic defect which causes FMDF is still under investigation, but the lack of a family history suggests an autosomal recessive pattern of inheritance or a parent with germline mosaicism. Nevertheless, the potential efficacy of rapamycin indicates that dysregulated mTOR signalling may play a role in this disorder (much like TSC and BHD syndrome).
- Haemel AK, O’Brian AL, Teng JM. Topical rapamycin: a novel approach to facial angiofibromas in tuberous sclerosis. Arch Dermatol. 2010 Jul;146(7):715-8. doi: 10.1001/archdermatol.2010.125.
- Mutizwa MM, Berk DR, Anadkat MJ. Treatment of facial angiofibromas with topical application of oral rapamycin solution (1mgmL(-1) ) in two patients with tuberous sclerosis. Br J Dermatol. 2011 Oct;165(4):922-3. doi: 10.1111/j.1365-2133.2011.10476.x.
- Starink TM, Houweling AC, van Doorn MB, Leter EM, Jaspars EH, van Moorselaar RJ, Postmus PE, Johannesma PC, van Waesberghe JH, Ploeger MH, Kramer MT, Gille JJ, Waisfisz Q, & Menko FH (2011). Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus. Journal of the American Academy of Dermatology PMID: 21794948
- Wee, J., Chong, H., Natkunarajah, J., Mortimer, P., & Moosa, Y. (2013). Familial multiple discoid fibromas: unique histological features and therapeutic response to topical rapamycin British Journal of Dermatology DOI: 10.1111/bjd.12315