Fibrous Forehead Plaque

Hypomelanotic macules were the overwhelmingly most common early findings in TSC. Infants with seizures or other possible stigmata of TSC should be carefully evaluated for these hypomelanotic macules as well as for other associated findings. Hypomelanotic macules can appear anywhere on the body, except the hands, feet, and genitalia; they are most commonly found on the lower extremities. Wood lamp examination reveals an accentuation of the hypopigmentation, which is a decrease in but not an absence of pigmentation. Lance ovate hypomelanotic macules are pathognomonic for TSC, thus the presence of 3 or more macules in an infant seriously suggests the diagnosis of TSC and echocardiography should be performed. The combination of white macules and seizures also increases the likelihood of TSC.¹⁸

Angiofibromas typically are found in the butterfly region of the face. Nico et al¹⁹ reported 2 patients with the complete syndrome of TSC who had multiple papules on the genital area in addition to classic facial lesions. Thus, it is important to examine the genital region of TSC patients and not misdiagnose these lesions as genital warts.

Jóźwiak et al¹⁸ screened 106 children with TSC and listed the prevalence of the most common cutaneous lesions. The results are presented in Table 2.

In a study by Webb et al,² 131 patients with TSC were examined and 126 (96%) exhibited skin signs. Although there was considerable variation in the age of expression of all the skin lesions, there was a trend toward the earlier expression of hypomelanotic macules and forehead fibrous plaques compared with facial angiofibromas and ungual fibromas. Shagreen patches usually were present by puberty. Ungual fibromas appeared for the first time as late as the fifth decade of life and were the only clinical feature in 3 patients. Ungual fibromas were present in 36% (47/131). Ten patients (8%) presented because of the skin manifestations and 21% (28/131) received treatment of symptomatic skin lesions. Two patients had large hamartomas at unusual sites, the occiput and forearm.²

Our 30-year-old patient presented to our clinic accompanied by her grandmother who served as legal guardian and historian for the patient. The patient experienced her first seizure at 15 months of age. She was evaluated by the neurology department at that time and was diagnosed with epilepsy. In the months following, she developed strabismus of the eyes and was examined by the ophthalmology department. Retinal hamartomas were discovered and she was diagnosed with TSC. Her seizure disorder was managed by a neurologist with the use of topiramate. In her 20s, she had renal and cardiac workups, which were negative, and she continued to be free of any genitourinary or cardiac concerns. One year prior to presentation she underwent a brain computed tomography scan after a bicycle accident and was informed that she had “scarlike” lesions within the cerebral cortex. There was no known history of TSC in other family members. On physical examination, she was noted to be delayed in mental development and intelligence. She stated her first notable skin lesions appeared at 10 years of age and were skin tags of the upper back and neck and over the face. Soon after, the cheeks and nose developed numerous shiny brownish pink papules (Figure 1). Over the course of the next 20 years she developed other skin findings noted on our present skin examination. The superior aspect of the mid forehead revealed a 4×2-cm, raised, flesh-colored, firm tumorous plaque. The neck and upper back had multiple 2- to 5-mm, soft, pedunculated, polypoid, brownish pink papules. Her mid back revealed ill-defined, slightly elevated, rosy plaques and macules with a roughened speckled appearance (Figure 2). Several of the toenails and fingernails showed firm, fleshy, spiculelike papules around and under the nail bed (Figure 3). The lower anterior tibia revealed several oval-shaped, flat, well-demarcated, hypopigmented macules (Figure 4). Lesions on the face and mid back were biopsied and histopathology confirmed angiofibroma and shagreen patch, or connective tissue nevus, respectively. Our patient did not undergo treatment of any of these skin lesions, particularly the facial angiofibromas. Cosmetic treatment options such as laser or surgical removal were presented to her, but she declined.

Figure 1. Angiofibromas of the nose and cheeks.

Figure 2. Shagreen patches on the lower back

A brief review of the literature for treatment options of facial angiofibromas and the fibrous forehead plaque indicated that current treatments include but are not limited to cryotherapy, electrocautery, electrosurgery, shave excision, chemical peels, argon laser, CO₂ laser, and radiofrequency equipment.²⁰ For the best outcome, these treatments have to be repeated throughout childhood and teenage years. Rapamycin, also known as sirolimus, and its analogs are new therapeutic options for TSC. Rapamycin is an inhibitor of the mechanistic target of rapamycin and can normalize this unregulated pathway in a TSC patient. Various preclinical models have shown that rapamycin treatment reduces TSC-related tumors, including brain, skin, and kidney tumors.²¹ A pilot study by Foster et al²² revealed improvement in the facial angiofibromas of 4 children treated with 2 topical preparations of rapamycin. The study revealed that younger patients with smaller angiofibromas had the best response with near-complete clearance. Rapamycin topical preparations were more cost effective than pulsed dye laser under general anesthesia.²²