Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome with variable expression and is manifested by hamartomatous tumors in multiple organs. Skin lesions occur in almost all affected individuals and are critical for diagnosis. Herein, we report a compelling case of TSC with an unusual eyelid lesion showing mild improvement after treatment with systemic everolimus.

A 5-year-old girl presented with a localized erythematous indurated plaque of the left lower eyelid. She was born by cesarean section at 41 weeks. The patient was diagnosed with TSC at 28 months of age; when she presented with seizure, developmental delay, multiple subcortical tubers in the bilateral cerebral hemisphere, subependymal nodule with internal calcification suspicious of subependymal giant cell astrocytoma at the left lateral ventricle, and angiomyolipomas in both kidneys. On genetic testing, she was found to have the TSC2 mutation.

Physical examination revealed an erythematous indurated plaque of the left lower eyelid and skin-colored to brownish plaques on the forehead (Fig. 1A, B). Histological examination of an eyelid specimen showed irregular proliferation of fibrous tissue and blood vessels and hyperplasia of hair follicles, consistent with fibrous facial plaque (Fig. 2). She was treated with oral everolimus for subependymal giant cell astrocytoma for 14 months. Reduced thickness and erythema of the lesion was noted on follow-up (Fig. 1C). There was no adverse event related to treatment with everolimus.

Fibrous facial plaques and angiofibromas are characterized by dermal fibrosis and together are considered major features of the diagnostic criteria for TSC1. Hyperplasia of hair follicles in frontal plaques has also been documented2. Fibrous facial plaque is an irregular, soft-to-firm connective tissue nevus that is either the color of the normal surrounding skin, red, or hyperpigmented. The consensus conference recommended that the terminology “fibrous cephalic plaque” be used in place of “forehead plaque,” as lesions may occur on any part of the face or scalp1.

A previous study reported positive results with oral sirolimus used for angiofibromas and shagreen patches3. Everolimus, a derivative of sirolimus, works as an inhibitor of mammalian target of rapamycin, inhibiting tumorigenesis and angiogenesis4. In the present case, the patient was treated with oral everolimus for 14 months, resulting in an improvement in the thickness and erythema of the eyelid lesion.

To the best of our knowledge, reports of unusual eyelid lesions in TSC have been rare5. In addition, this case suggests that everolimus may be an effective treatment for fibrous facial plaques as well as facial angiofibromas and shagreen patches.