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Diagnosing Tuberous Sclerosis Complex for Dermatologists

Diagnosing Tuberous Sclerosis Complex for Dermatologists

Fri, 09/11/2020 - 19:49

Dr Thiele

Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disease that is estimated to affect 1 in 6,000 to 1 in 10,000 live births and has a population prevalence of 1 in 20,000.1 The diagnosis is made clinically and based on the major and minor criteria outlined in the Table.1,2 Cutaneous manifestations can be present in early life but are also known to appear as patients age, and skin findings can be subtle in young patients.3 Many of the cutaneous symptoms can be painful and disfiguring, and they can significantly impact quality of life.3 Thus, a dermatologist plays an important role in TSC treatment.

In an interview with The Dermatologist, Elizabeth Thiele, MD, PhD, discussed common skin findings associated with this disease and recommendations for dermatologists treating patients with confirmed or suspected TSC. Dr Thiele is a professor of neurology at Harvard Medical School and the director of the Carol and James Herscot Center for Tuberous Sclerosis Complex in Boston, MA.

The Dermatologist: What are some of the common cutaneous presentations of TSC?

Dr Thiele: The most common skin features of TSC include facial angiofibroma (AF), hypopigmented macules, periungal fibroma, and shagreen patch. All of these are major diagnostic criteria for TSC. The diagnosis of TSC is made via clinical criteria, and to be diagnosed with definite TSC, an individual has to have two major criteria or one major and two minor criteria.


Therefore, if a dermatologist sees an adolescent patient for acne but realizes this patient has AF rather than acne and performs a complete skin exam where they identify several hypopigmented skin macules, the dermatologist could make the diagnosis of TSC.

Large forehead plaques (fibromas), skin tags, and erythematous collagenoma are also commonly seen in TSC; many physicians do not realize that the latter two are TSC-related skin findings.

The Dermatologist: What are your recommendations for dermatologists for managing patients with TSC?

Dr Thiele: I would recommend referral to a TSC center if possible. There are now over 65 TSC clinics in the United States, with the majority directed by neurologists. Seizures occur in about 85% of individuals with TSC, so neurologists are usually involved in the care of individuals with TSC.3

At a TSC clinic, the patient would have a comprehensive clinical evaluation for possible TSC, which would include brain, abdominal, and cardiac imaging and an ophthalmologic and skin examination.

If a dermatologist is seeing a patient with known TSC who is not being followed by a neurologist, it is important for the dermatologist to ask about possible seizure activity, as well as maintain good communication with neurologists and other specialists involved in this patient’s care.

The Dermatologist: What treatment options are available for patients with TSC?

Dr Thiele: Treatment options depend on symptoms being treated, such as seizures, TSC-associated neuropsychiatric disorders (TAND), renal involvement, pulmonary involvement, and skin involvement.  

Current treatments for skin manifestations include laser therapy and topical mammalian target of rapamycin (mTOR) inhibitor therapy for AF and erythematous collagenoma, and removal of periungal fibroma, skin tags, and large forehead plaques.  

The only FDA-approved treatments specifically for TSC include mTOR inhibitors, which are indicated for renal angiomyolipoma, pulmonary lymphangioleiomyomatosis, brain subependymal giant cell tumors and epilepsy.  Cannabidiol (CBD), which was also recently approved by the FDA for seizures associated with TSC in patients 1 year of age and older.4

The Dermatologist: What key takeaways would you like to leave with dermatologists about this condition?

Dr Thiele: Many individuals with TSC have significant anxiety and often become obsessed and/or fixated with worrying about particular aspects of this disease For example, AF can have a very significant negative impact on individuals’ self-concept/self-esteem, as some patients see it as a constant reminder of TSC when they look in the mirror.

The most important takeaway is that TSC is not that rare and should be considered in any patient with any of the above skin findings. Also, it is important to diagnosis TSC and refer for appropriate care, as we are getting better and better at keeping people with TSC healthy.


1. Northrup H, Krueger DA; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):243-254. doi:10.1016/j.pediatrneurol.2013.08.001

2. Northrup H, Koenig MK, Pearson DA, Au KS. Tuberous sclerosis complex. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington; 1993-2020. Updated April 16, 2020. Accessed September 3, 2020.

3. Cardis MA, DeKlotz CMC. Cutaneous manifestations of tuberous sclerosis complex and the paediatrician's role. Arch Dis Child. 2017;102(9):858-863. doi:10.1136/archdischild-2016-312001

4. FDA approves new indication for drug containing an active ingredient derived from cannabis to treat seizures in rare genetic disease. News release. US Food and Drug Administration; July 31, 2020. Accessed September 3, 2020.


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