Molluscum contagiosum

Abstract

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) has been shown to be safe and effective for a variety of skin concerns. The case report described is the first successfully documented use of ALA/PDT in the therapy of recalcitrant molluscum contagiosum in HIV-positive individuals.

**********

Introduction

Photodynamic therapy (PDT) with the topical application of 5-aminolevulinic acid (ALA) has been shown to be safe and effective for the treatment of a variety of skin concerns. The use of ALA-PDT in the United States has received Food and Drug Administration (FDA) approval for the treatment of nonhyperkeratotic actinic keratoses, specifically actinic keratoses present on the face and scalp (1-3). A number of researchers have shown that the use of ALA-PDT is effective for a variety of other skin lesions commonly encountered in everyday dermatology practices. These include seborrheic keratoses. Bowen's disease, basal cell carcinomas, squamous cell carcinomas, and cutaneous T-cell lymphomas (4 12). Several investigators have also shown the effectiveness of ALA-PDT in the treatment of viral skin lesions, including recalcitrant verrucous lesions of the skin (13-21). This case report demonstrates the use of this modality in the treatment of recalcitrant molluscum contagiosum lesions which appeared on the head and neck area of an HIV-afflicted individual.

Case Report

The patient is a 34-year-old gentleman with a history of HIV disease who presented to Gold Skin Care Center in Nashville. Tennessee with a several month history of multiple, enlarging raised lesions on the face and neck area. Mucous membrane involvement (lips) was also evident on physical examination of this individual. Initial therapy consisted of cryotherapy with liquid nitrogen to the affected areas on a two-week treatment schedule. The patient also was instructed to use tretinoin 0.1% cream on a daily basis every evening. Despite this aggressive treatment approach, the molluscum contagiosum lesions remained resistant.

As an alternative therapeutic option to surgical excision and its potential for widespread scarring, the use of ALA-PDT as a treatment approach was entertained. The patient was explained all of the potential risks and benefits of the ALA-PDT therapy and that this was an FDA off-label use for this product. The patient signed an informed consent. The ALA applied to the molluscum contagiosum lesions was a 20% aminolevulinic acid solution known as the Levulan[TM] Kerastick[TM] (aminolevulinic acid HCI) manufactured by Dusa Pharmaceuticals (Wilmington, MA). Sixteen hours after application of the ALA, the patient had the lesions treated with the BLU-U[TM] Blue Light Photodynamic Therapy Illuminator. Dusa Pharmaceuticals, Inc. The patient had the lesions treated for 16 minutes, 40 seconds with the Blue Light Illuminator as per the standard protocol used to treat actinic keratoses. During the therapy, cool water was applied to the skin to help reduce the associated discomfort from the therapy. A fan was also used to help the patient tolerate the therapy. The patient received systemic and topical corticosteroids post-treatment to minimize pain and the associated inflammatory response.

The patient underwent 4 separate treatment sessions with the ALA-PDT system. The treatments were performed at two week intervals and after the fourth treatment session, the number of molluscum lesions had dramatically decreased. Figures 1-3 demonstrate the response to ALA-PDT therapy in this individual.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

Discussion

This case report demonstrates the effectiveness of ALA-PDT in the use of recalcitrant molluscum contagiosum lesions. To our knowledge, this is the first published report of the use of this modality in the treatment of molluscum contagiosum lesions in our literature. Orenstein has used ALA-PDT in the treatment of many types of cutaneous lesions with many years of experience and did relay to the authors the use of this therapy in one patient successfully in his practice (22).

Molluscum contagiosa are common viral infections caused by large DNA poxviruses predominantly affecting children, rarely adults, and numerous HIV-infected individuals (23-28). They are described as discrete skin-colored smooth papules with an umbilicated center. The lesions occur anywhere on the body but are more common on the face and neck area in HIV-affected individuals (29). Molluscum contagiosum lesions in HIV patients are also described to be larger than typical lesions and are more resistant to traditional modes of therapy. There are many therapies reported to be successful in treating molluscum contagiosum lesions. These include cryotherapy with liquid nitrogen, cantharidin, tretinoin cream, podophyllin 20-25%, salicylic acid, tincture of iodine, silver nitrate, trichloroacetic acid, and surgery with curettage followed by electrodesiccation. In HIV-infected individuals with disseminated molluscum contagiosum lesions, antiretroviral therapy, intralesional interferon-alfa, and topical injection of streptococcal antigen OK-432 have been reported as useful therapeutic options (26).

Photodynamic therapy is a term which describes the application of a photosensitizing chemical to a specific cutaneous lesion which, when followed by exposure to visible light, results in an excitation of the photosensitizer. Once this photosensitizer is irradiated and activated by an appropriate light source, reactive oxygen species are produced affecting subcellular structures, which leads to cytotoxicity. Due to this phototoxic effect, malignant and non-malignant hyperproliferative tissue can be destroyed or decreased in size, and eventually be eradicated (11).

Aminolevulinic acid itself is not a photosensitizer. ALA is part of the endogenous heme synthesis cycle and a metabolic precursor of protoporphyrin IX (PpIX). This precursor is a natural photosensitizer. Hyperproliferative cells are metabolically more active than normal cells and convert more of the ALA pro-drug to PpIX (11).

The extent of the phototoxic effect with any kind of PDT is determined by several factors, such as the dose of the photosensitizer, the total light dose, and the oxygen concentration in the tissue being treated. In the case of ALA-PDT, PpIX formation depends largely on the interval between ALA application and light treatment (11).

The wavelength of light determines the depth of tissue penetration for the light. The predominant absorption peaks for PpIX are at 405 nanometers (nm) and 630 nm. For the ALA-PDT system described in this report. PpIX absorption with the BLU-U[TM] light source matches the PpIX peak at 405 nm.

Treatment with ALA-PDT does have several associated adverse effects, such as burning, stinging, and pruritus during the treatment's light exposure. The burning and stinging seems to be directly correlated to the area being treated, with more stinging and burning when larger body surfaces are treated and exposed to the light source. Personal observations have shown that oilier-skinned individuals also have more stinging and burning with the treatment. Erythema and edema of the treatment sites are also common effects seen as a result of ALA-PDT treatment but these usually resolve during the first 24-48 hours post-therapy. Crusting, scaling, pruritus, and some minor pain have also been reported following the therapy, and complete healing usually occurs within 2-8 weeks post-therapy (11). More commonly, however, patients treated with ALA-PDT report an overall improvement in the cosmetic appearance of the treated areas of their skin.

ALA-PDT therapy has been successfully used to treat a variety of benign and malignant skin lesions. The US FDA has approved the Levulan[TM] Kerastick[TM] system for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp region. Other lesions reported treated with ALA-PDT include seborrheic keratoses. Bowen's disease, basal cell carcinomas, squamous cell carcinoma, cutaneous T-cell lymphoma, and verrucae vulgaris. The use of ALA-PDT in the treatment of molluscum contagiosum has not yet been reported in the medical literature. This case illustrates the successful use of ALA-PDT in the treatment of recalcitrant molluscum contagiosum. A further, larger investigation to further confirm this data is currently underway.

References

1. Jeffes EW, et al. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid: A pilot dose-ranging study. Arch Dermatol 1997 Jun: 133(6):727-32.

2. Omrod D, Jarvis B. Topical aminolevulinic acid HCI photodynamic therapy. Am J Clin Dermatol 2000 Mar-Apr: 1(2):133-139.

3. Jeffes EW, et al. Photodynamic therapy of actinic keratoses with topical aminolevulinic acid, hydrochloride, and fluorescent blue light. J Am Acad Dermatol 2001; 45:96-104.

4. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B 1990; 14:275-292.

5. Wolf P. Rieger E. Kerl H. Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid: an alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas. J Am Acad Dermatol 1993; 28:17-21.

6. Wolf P, Fink-Puches R, Cerroni L. Kerl H. Photodynamic therapy for mycosis fungoides after topical photosensitization with 5-aminolevulinic acid. J Am Acad Dermatol 1994; 31:678-680.

7. Cairnduff F, Stringer MR, Hudson EJ, Ash DV, Brown SB. Superficial photodynamic therapy with topical 5-aminolevulinic acid for superficial primary and secondary skin cancer. Br J Cancer 1994; 69:605-608.

8. Fijan S, Hoenigsmann H, Ortel B. Photodynamic therapy of epithelial skin tumors using delta-aminolevulinic acid and disferrioxamine. Br J Dermatol 1995; 133:282-288.

9. Calzavara-Pinton PG. Repetitive photodynamic therapy with topical delta-aminolevulinic acid as an appropriate approach to the routine treatment of superficial nonmelanoma skin tumors. J Photochem Photobiol B 1995; 29:53-57.

10. Svanberg K, et al. Photodynamic therapy of nonmelanoma malignant tumors of the skin using topical d-aminolevulinic acid sensitization and laser irradiation. Br J Dermatol 1994; 130:743-751.

11. Kalha K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol 2000; 42:389-412.

12. Morton CA. Whitehurst C, McColl JH, Moore JV, Mackie RM. Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma. Arch Dermatol 2001; 137:319-324.

13. Ammann R, Hunziker T, Braathen LR. Topical photodynamic therapy in verrucae. Dermatol 1995; 191:346-347.

14. Stender IM, Wulf HC. Treatment of recalcitrant verrucae by photodynamic therapy with topical application of d-aminolevulinic acid. Clin Exp Derm 1996; 21:390.

15. Stender IM, Wulf HC. Photodynamic therapy of recalcitrant warts with 5-aminolevulinic acid: a retrospective analysis. Acta Derm Venereol 1999; 79(5):400-401.

16. Stender IM, Lock-Anderson J, Wulf HS. Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study. Clin Exp Derm 1999; 24(3):154-159.

17. Karrer S, Szeimies RM, Abels C, et al. Epidermodysplasia verruciformis treated using topical 5-aminolevulinic acid photodynamic therapy. Br J Dermatol 1999; 24(3):935-938.

18. Smetana Z, Malik Z, Orenstein A, et al. Treatment of viral infections with 5-aminolevulinic acid and light. Lasers Surg Med 1997; 21:351-358.

19. Stender IM, Na R, Fogh H, et al. Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts: randomized double-blind trial. The Lancet 2000; 335:963-966.

20. Sterling JC. Handfield-Jones S, Hudson PM. Guidelines for the management of cutaneous warts. Br J Dermatol 2001; 144:4-11.

21. Fabbrocini G, et al. Photodynamic therapy with topical delta-aminolevulinic acid for the treatment of plantar warts. J Photochem Photobiol B 2001; 61(1-2):3-34.

22. Orensten A. Personal communication 2002.

23. Siegfried EC. Warts and molluscum contagiosum on children: an approach to therapy. Dermatol Ther 1997; 2:51-67.

24. Verbov J. How to manage warts. Arch Der Child 1999; 80:97-99.

25. Lewis EJ, Lam M., Crutchfield CE. An update on molluscum contagiosum. Cutis 1997; 60:29-34.

26. Husar K, Skerlev M. Molluscum contagiosum from infancy to maturity. Clinics in Dermatol 2002; 20:170-172.

27. Coldiron BM, Bergstresser PR. Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus. Arch Dermatol 1989; 125:357-361.

28. Czelasta A, Yen-Moore A, Vander Straten M, Carrasco D, Tyring SK. An overview of sexually transmitted diseases. Part III: Sexually transmitted diseases in HIV-infected patients. J Am Acad Dermatol 2000; 43:409-432.

29. Schwartz JJ, Myskowsk PL. Molluscum contagiosum in patients with human immunodeficiency virus infection: a review of twenty-seven patients. J Am Acad Dermatol 1992; 27:583-588.

MICHAEL H GOLD MD, MOLLY M BORING RN MSN FNP-C, TANCY M BRIDGES RN MSN FNP-C, VIRGINIA L BRADSHAW RN MSN GNP-C

GOLD SKIN CARE CENTER, NASHVILLE, TENNESSEE

ADDRESS FOR CORRESPONDENCE:

Michael H Gold MD

Gold Skin Care Center

2000 Richard Jones Road. Suite 220

Nashville, TN 37215

Phone: (615) 383-2400

COPYRIGHT 2004 Journal of Drugs in Dermatology
COPYRIGHT 2004 Gale Group