Ann Dermatol.  2019 Oct;31(5):555-558. 10.5021/ad.2019.31.5.555.

Use of Topical Rapamycin as Maintenance Treatment after a Single Session of Fractionated COâ‚‚ Laser Ablation: A Method to Enhance Percutaneous Drug Delivery

• Oh J
• Kim J
• Lee WJ
• Lee JH

• KMID: 2456233
• DOI: http://doi.org/10.5021/ad.2019.31.5.555

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 5,000 to 10,000 live births. TSC has various clinical manifestations such as multiple hamartomas in systemic organs, including the skin. Angiofibromas are the most common skin lesions in patients with TSC. Although benign, angiofibromas develop in childhood and puberty, and can be psychosocially disfiguring for patients. Skin lesions in TSC, specifically angiofibromas, have no significant risk of malignant transformation after puberty; thus, they require no treatment if not prominent. However, the presentation of TSC is important owing to its impact on patient cosmesis. Surgical treatment and laser therapy are the mainstream treatments for angiofibromas. Although the evidence is limited, topical mammalian target of rapamycin inhibitors such as sirolimus (rapamycin) are effective in facial angiofibroma treatment. We describe an adult patient with an angiofibroma who had an excellent response to treatment with topical rapamycin after a single session of carbon dioxide (COâ‚‚) laser ablation. The patient showed no sign of relapse or recurring lesions for a year. COâ‚‚ laser ablation may serve as a new paradigm of treatment for angiofibromas in TSC. Since the selection of laser devices can be limited for some institutions, we suggest a rather basic but highly effective approach for angiofibroma treatment that can be generally applied with the classic COâ‚‚ device.

Keyword

Angiofibroma; COâ‚‚ laser; Sirolimus; Tuberous sclerosis complex

MeSH Terms

Adolescent
Adult
Angiofibroma
Carbon Dioxide
Hamartoma
Humans
Incidence
Laser Therapy*
Live Birth
Methods*
Neurocutaneous Syndromes
Puberty
Recurrence
Sirolimus*
Skin
Tuberous Sclerosis
Carbon Dioxide
Sirolimus

Figure

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  Fig. 1 Improvement of facial angiofibroma lesions in a 20-year-old patient with tuberous sclerosis complex during rapamycin therapy after a single session of CO2 laser ablation. Left panels, labeled 0: before the administration of laser ablation. Pronounced improvement was observed at 1, 3, 6, and 8 months after the start of systemic rapamycin therapy after a single session of CO2 laser ablation.

Reference

1. Schwartz RA, Fernández G, Kotulska K, Jóźwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007; 57:189–202.

2. Jóźwiak S, Schwartz RA, Janniger CK, Michałowicz R, Chmielik J. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998; 37:911–917.

3. Staley BA, Vail EA, Thiele EA. Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and commonly missed signs. Pediatrics. 2011; 127:e117–e125.

4. Bittencourt RC, Huilgol SC, Seed PT, Calonje E, Markey AC, Barlow RJ. Treatment of angiofibromas with a scanning carbon dioxide laser: a clinicopathologic study with long-term follow-up. J Am Acad Dermatol. 2001; 45:731–735.

5. Fioramonti P, De Santo L, Ruggieri M, Carella S, Federico LT, Onesti MG, et al. Co2/Erbium:YAG/Dye laser combination: an effective and successful treatment for angiofibromas in tuberous sclerosis. Aesthetic Plast Surg. 2014; 38:192–198.

6. Papadavid E, Markey A, Bellaney G, Walker NP. Carbon dioxide and pulsed dye laser treatment of angiofibromas in 29 patients with tuberous sclerosis. Br J Dermatol. 2002; 147:337–342.

7. Weiss ET, Geronemus RG. New technique using combined pulsed dye laser and fractional resurfacing for treating facial angiofibromas in tuberous sclerosis. Lasers Surg Med. 2010; 42:357–360.

8. Balestri R, Neri I, Patrizi A, Angileri L, Ricci L, Magnano M. Analysis of current data on the use of topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis complex. J Eur Acad Dermatol Venereol. 2015; 29:14–20.

9. Kavanagh KT, Cosby WN. Shave excision and dermabrasion of midline angiofibroma in tuberous sclerosis. Arch Otolaryngol Head Neck Surg. 1986; 112:886–888.

10. Del Bufalo D, Ciuffreda L, Trisciuoglio D, Desideri M, Cognetti F, Zupi G, et al. Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus. Cancer Res. 2006; 66:5549–5554.

11. Paghdal KV, Schwartz RA. Sirolimus (rapamycin): from the soil of Easter Island to a bright future. J Am Acad Dermatol. 2007; 57:1046–1050.

12. Jóźwiak S, Sadowski K, Kotulska K, Schwartz RA. Topical use of mammalian target of rapamycin (mTOR) inhibitors in tuberous sclerosis complex-a comprehensive review of the literature. Pediatr Neurol. 2016; 61:21–27.

13. Tu J, Foster RS, Bint LJ, Halbert AR. Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: follow up of a pilot study and promising future directions. Australas J Dermatol. 2014; 55:63–69.

14. Ma G, Wu P, Lin X, Chen H, Li W, Hu X, et al. Nd:YAG laser for “fractional” treatment of angiofibromas. Int J Dermatol. 2014; 53:638–642.

15. Pasyk KA, Argenta LC. Argon laser surgery of skin lesions in tuberous sclerosis. Ann Plast Surg. 1988; 20:426–433.

16. Tope WD, Kageyama N. “Hot” KTP-laser treatment of facial angiofibromata. Lasers Surg Med. 2001; 29:78–81.

17. Omi T, Numano K. The role of the CO2 laser and fractional CO2 laser in dermatology. Laser Ther. 2014; 23:49–60.

18. Tierney EP, Hanke CW, Petersen J. Ablative fractionated CO2 laser treatment of photoaging: a clinical and histologic study. Dermatol Surg. 2012; 38:1777–1189.

19. Ong CT, Khoo YT, Mukhopadhyay A, Do DV, Lim IJ, Aalami O, et al. mTOR as a potential therapeutic target for treatment of keloids and excessive scars. Exp Dermatol. 2007; 16:394–404.

20. Yoshizaki A, Yanaba K, Yoshizaki A, Iwata Y, Komura K, Ogawa F, et al. Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosis. Arthritis Rheum. 2010; 62:2476–2487.