Skin and dental findings important for diagnosing tuberous sclerosis complex

By Will Boggs MD

Skin and dental findings make an important contribution to the diagnosis of tuberous sclerosis complex, according to a recently published review of the 2012 International Tuberous Sclerosis Complex Consensus Statements.

"It is more important now than ever to correctly diagnose tuberous sclerosis complex, since there are new treatments that can significantly improve the lives of these individuals," Dr. Thomas N. Darling from the Uniformed Services University of the Health Sciences, Bethesda, Maryland told Reuters Health by email.

Tuberous sclerosis complex (TSC) is a genetic order that manifests as cognitive impairment, seizures, and hamartomas of the brain, eye, kidneys, heart, lungs, and skin. Skin and dental findings comprise four of 11 major features and three of six minor features in the diagnostic criteria.

Dr. Darling and colleagues review the dermatological and dental aspects of the updated diagnostic criteria and management recommendations in their July 16th JAMA Dermatology online report.

"The major change in the diagnostic criteria is the addition of a genetic criterion; the presence of a pathogenic mutation in TSC1 or TSC2 in normal tissue is sufficient for the diagnosis of TSC," Dr. Darling said.

In the 1998 criteria, there was a numerical requirement only for hypomelanotic macules (at least three), but in the updated criteria, several lesions now have numerical requirements: at least three angiofibromas, at least two ungual fibromas, at least three dental pits, and at least two intraoral fibromas.

Skin biopsies are required only when there is uncertainty regarding the clinical diagnosis.

Detailed clinical dermatologic evaluation is recommended at the time of diagnosis for both children and adults, and close surveillance is recommended for TSC-related skin lesions that are rapidly changing, causing functional interference, pain, or bleeding, or inhibiting social interactions. The statement recommends an annual skin examination for children with TSC.

Oral exam should be done every six months, or even more often for patients with special needs and difficulty maintaining oral hygiene.

Surgery is commonly used to treat skin lesions when there is bleeding, pain, impaired function, and disfigurement.

"Consideration should be given for the use of oral mTOR inhibitors to treat certain individuals with TSC and renal angiomyolipomas, subependymal giant cell astrocytomas, or lymphangioleiomyomatosis," Dr. Darling said. "The topical application of mTOR inhibitors is a promising approach for treating TSC-related skin lesions, particularly angiofibromas. This is an off-label use and a topical formulation is not yet commercially available."

"Large-scale, placebo-controlled trials are needed to evaluate the long-term safety and efficacy of these topical therapies," the researchers conclude.

The paper includes photos of representative lesions and descriptions to improve the recognition of these dermatological and dental manifestations of TSC.

Dr. Allen Wong from the University of the Pacific Arthur A. Dugoni School of Dentistry, San Francisco, California has studied the dental manifestations of TSC. He told Reuters Health by email, "Early evaluation of skin and intraoral lesions with appropriate radiography of the body would be ideal. Not only would it benefit dermatologic and oral health, early detection of tuberous growths in other internal organs areas would be significant."

"Consider looking at hallmark signs of gingival growths and dental pits on the enamel surfaces, refer patients for preventive dental therapy at an early age to avoid dental caries risk, and remember that most prescription medications can have a xerostomic (drying) effect which can increase the risk of caries," Dr. Wong said.

He added, "Emphasize a team approach and more communication with all parties involved to have maximum therapeutic outcome on those patients that are not able to tolerate tests in a routine setting or even referring for dental preventive services if (patients are taking) medications that induce xerostomia (lack of saliva)."

SOURCE: http://bit.ly/1naAYer

JAMA Dermatol 2014.

(c) Copyright Thomson Reuters 2014. Click For Restrictions - http://about.reuters.com/fulllegal.asp