Format

Send to

Choose Destination
J Am Acad Dermatol. 2015 Nov;73(5):802-8. doi: 10.1016/j.jaad.2015.07.018. Epub 2015 Sep 11.

Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus.

Author information

1
Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland; Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
2
Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland.
3
Dermatology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland.
4
Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
5
Department of Dermatology, Uniformed Services University of Health Sciences, Bethesda, Maryland. Electronic address: thomas.darling@usuhs.edu.

Abstract

BACKGROUND:

Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC).

OBJECTIVE:

We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects.

METHODS:

A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment.

RESULTS:

Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment).

LIMITATIONS:

This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis.

CONCLUSION:

Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated.

KEYWORDS:

angiofibromas; lymphangioleiomyomatosis; mechanistic target of rapamycin inhibitor; shagreen patch; sirolimus; tuberous sclerosis complex; ungual fibroma

PMID:
26365597
PMCID:
PMC4609596
DOI:
10.1016/j.jaad.2015.07.018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center