For Rare Disease Day on February 29, Topical Conversations will be exploring some of the rare diseases seen in dermatology. In this installment, Naiem Issa, MD, PhD, gives his perspective on tuberous sclerosis complex (TSC) along with a helpful treatment tip. 

Watch Part 1 to hear Dr Todd Schlesinger discuss subacute cutaneous lupus erythematosus and dermatomyositis.

Understanding tuberous sclerosis complex 

Tuberous sclerosis complex (TSC) is a rare genetic disorder resulting from mutations in the TSC1 and TSC2 genes. It follows an autosomal dominant pattern and affects approximately 50,000 individuals in the United States. TSC is difficult to treat and requires a multidisciplinary, multimodal treatment paradigm. 

TSC presents with multiple comorbidities, including central nervous system abnormalities, brain tumors causing seizures or developmental delays, angiomyolipoma and kidney cysts, cardiac rhabdomyelomas, pulmonary cysts, and lymphangioleiomyomatosis. 

Cutaneous manifestations include periungual fibromas, typically developing around the feet, and facial angiofibromas. Dermatologists play a crucial role in addressing patients' concerns related to facial angiofibromas, one of the most visible manifestations of TSC. 

Challenges with traditional treatments 

Facial angiofibromas are often a primary concern for patients with TSC, as they can present with hundreds of lesions. Traditionally, treatment options have been limited to destructive modalities such as curettage, laser therapy, and excisions, all of which come with side effects. 

Role of mTOR signaling in TSC 

The pathogenesis of TSC involves the dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway. Inhibition of mTOR has shown promise in addressing both cutaneous and systemic effects of TSC. Oral sirolimus has been a standard therapeutic approach, but recent advancements have introduced a topical sirolimus 0.2% gel approved for ages 6 and above. 

Topical sirolimus gel for facial angiofibromas 

The approval of topical sirolimus gel is a significant advancement in TSC treatment. As a nondestructive alternative that inhibits mTOR locally, it provides a targeted treatment that minimizes side effects associated with systemic administration. 

Dr Issa encourages dermatologists to consider incorporating topical sirolimus gel into their treatment armamentarium for patients with TSC who present with multiple facial angiofibromas. This novel approach not only enhances the management of the cutaneous manifestations of TSC but also aligns with a patient-centered approach by minimizing the impact of side effects associated with traditional therapies.