You are asked to see a 9-year-old girl with a history of asymptomatic erythematous papules on her chin and cheeks (fig. 1). She has been compulsive about applying tretinoin 0.05% cream nightly and washing with benzoyl peroxide for 4 months, and she and her mother see no improvement. She is health, and growing and developing normally. What's the diagnosis
Diagnosis and Clinical Presentation
The diagnosis of angiofibroma was confirmed with a biopsy of a papule on her chin( fig. 2) Angiofibromas, are common benign neoplasms that typically present as solitary firm dome shaped smooth shiny red papules on the face particularly on and around the nose. The presence of multiple angiofibromas, particularly in children, should prompt consideration of the associated genodermatoses tuberous sclerosis (TS) and multiple endocrine neoplasia 1 (MEN1). Tuberous sclerosis is an autosomal dominant disorder that often presents with a triad of seizures, mental retardation and facial angiofibromas. Diagnosis includes 2 major features or one major and two minor features. Major features include: facial angiofibromas, shagreen patch, >3 hypomelanotic macules, ungual or periungual fibromas, lymphangioleiomyomatosis, renal angiomyolipoma, cardiac rhabdomyoma, multiple retinal nodular harmartomas, cortical tuber, subependymal nodules, and subependymal giant cell astrocytomas. Minor features include: gingival fibromas, dental pits, harmartomatous rectal polyps, multiple renal cysts, nonrenal harmartomas, bone cysts, and a retinal achromic patch. Of note, the presence of seizures is no longer considered a diagnostic criterion for TS, because they do not increase sensitivity or specificity of diagnosis. Only a third of patients will have a family history of clinical findings with up to 2/3 being spontaneous mutations, and the wide variability in clinical phenotype can result in a delay in diagnosis. Genetic testing for the two major mutations TSC1 and TSC2 should detect 85% of affected individuals, but does not predict severity of disease. A negative test is Less helpful particularly since patients with genetic mosaiciasm and significant phenotype may have negative genetic markers. MEN1 is an autosomal dominant disorder associated with an increased risk of endocrine tumors including Parathyroid- most common presentation is hypercalcemia Pituitary- most common is prolactinoma, presenting with oligomenorrhea/amenorrhea and galactorrhea Pancreatic/GI- commonly presents with Zollinger-Ellison syndrome, secondary to gastrinoma. Less common: insulinoma, glucagonoma, VIPoma Dermatologic findings in MEN1 include Facial angiofibromas, collagenomas, and lipomas (subcutaneous, or rarely visceral). 90% of individuals with MEN1 have a positive family history of the disease, while only 10% arise de novo. Specific guidelines for surveillance for patients with known MEN1 mutation include the following: Yearly: Prolactin (age 5), Calcium (age 8), Gastrin (age 20) Every 3-5 Years: Cranial MRI (age 5), Abdominal CT/MRI (age 20)
Skin biopsy of facial lesions typically shows fibrosis of the papillary and periadnexal dermis (fig. 2).
Treatment of the angiofibromas has included pulsed dye laser therapy, carbon dioxide laser therapy, other destructive measures, and topical sirolimus in patients with tuberous sclerosis.
Our patient had a negative renal ultrasound, chest x-ray, and brain imaging. No other family members have skin or systemic findings, and we are considering genetic screening. Her angiofibromas improved with topical sirolimus 0.1% solution applied twice daily for 4 months.
Multiple facial angiofibromas should trigger an evaluation for tuberous sclerosis and multiple endocrine neoplasia type 1.
- 1. http://dermatology.cdlib.org/134/case_presentations/fibrous/elifritz.html 2. http://emedicine.medscape.com/article/1093723-diagnosis