Tazarotene

Abstract

Nevus comedonicus is a rare developmental defect of the pilosebaceous unit. It is also thought to be a variant of epidermal nevus. Previously reported treatments include surgical excision, C[O.sup.2] laser, dermabrasion, extraction, topical retinoic acid, and numerous topical keratolytics.

We present a case of a 7-year-old boy with bilateral nevus comedonicus who experienced cosmetic improvement with topical tazarotene and calcipotriene cream. This combination represents a novel therapeutic approach to the treatment of this cutaneous abnormality.

**********

Case Report

A 7-year-old boy presented for an evaluation of an asymptomatic congenital eruption involving his face. Previous therapies with topical retinoic acid and keratolytics failed to provide a clinical improvement. The patient's past medical history was notable for allergic rhinitis and chronic sinusitis. He performed well in school and has no history of visual defects, seizures, or skeletal abnormalities.

Examination revealed linear hyperpigmented papules and plaques containing numerous open and closed comedones and scattered pustules and milia distributed across the right medial forehead, nasal sidewalls and zygomatic cheeks (Figure 1).

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

[FIGURE 3 OMITTED]

Tazarotene 0.05% and calcipotriene 0.005% creams were initially applied twice daily to the affected area. However, because of significant peeling and irritation, these medications were decreased to once daily.

After 8 weeks of therapy, the number of comedones and pustules had decreased (Figure 2). Both the patient and mother were pleased with the decreased number of lesions and improved cosmetic appearance. Topical therapy was continued once daily, but occasionally was decreased to every-other-day application due to irritation. The patient returned one year later and noted continued improvement (Figure 3).

Discussion

Kofmann first described nevus comedonicus in 1895 (1). Some believe nevus comedonicus is a hamartoma of the mesodermal component of the pilosebaceous complex with abnormal differentiation of the epithelial portion (2). Others believe nevus comedonicus is an uncommon variant of epidermal nevus involving the hair follicle (3).

Nevus comedonicus typically presents as a confluent patch of dilated follicular orifices plugged with keratin giving the appearance of open comedones. Some lesions may develop milia, inflammatory cysts, and fistulae. Nevus comedonicus has a predilection for the face, neck, trunk, and upper arms. Distribution is frequently unilateral, following the lines of Blaschko, although bilateral lesions have been reported. Nevus comedonicus is often present at birth, but may appear at any age.

Nevus comedonicus may be a sign of cutaneous and systemic disorders including ichthyosis, linear basal cell nevus, trichilemmal cysts, follicular tumors, cataracts and Sturge-Weber syndrome (4-9). Multiple associated skeletal and central nervous system abnormalities have also been reported. These include scoliosis, fused hemivertebrae, spina bifida occulta, seizures, and transverse myelitis (10). Our patient was believed to have an isolated nevus comedonicus.

Several different treatments for nevus comedonicus have been previously reported. Surgical excision and C[O.sup.2] laser can be curative, but in some cases these may not be practical. Surgical methods to temporarily remove the keratin plug include comedone extraction and dermabrasion. Comedone extraction may be performed manually or with commercially available pore strip tape (11,12). Topical treatments include keratolytic agents such as [alpha]-hydroxy acids, salicylic acid and 12% ammonium lactate (13). Oral isotretinoin has not been found to be beneficial, but topical retinoic acid has been effective in some patients (13,14). Topical therapies, however, provide only temporary benefits and must be used indefinitely to maintain their therapeutic effects.

Prior to presentation, our patient failed therapeutic trials of several different topical medications. With our understanding of the proposed pathogenesis of nevus comedonicus, we believed a therapeutic trial of topical tazarotene and calcipotriene was warranted.

Tazarotene is hydrolyzed in target tissues to its active metabolite, tazarotenic acid. Tazarotenic acid acts by binding to nuclear retinoic acid receptors (RAR-[alpha], RAR-[beta], RAR-[gamma]) thereby modulating the expression of various retinoid-responsive gene products which in turn regulate cell proliferation, cell differentiation and inflammation (15). Tazarotene is approved for the treatment of psoriasis and acne but carries a category X label and should not be used during pregnancy.

Calcipotriene is a synthetic analog of calcitriol (1,25-dihydroxyvitamine D3), the active form of vitamin D and acts by binding to the vitamin D receptor. The resulting drug/receptor complex interacts with specific deoxyribonucleic acid sequences thereby influencing expression of specific vitamin D-responsive gene products. The vitamin D receptor is present in numerous cell types including keratinocytes. In vitro and in vivo data suggest that vitamin D inhibits cell proliferation, modulates differentiation, and has an anti-inflammatory effect (16).

Calcipotriene is approved for the treatment of plaque-type psoriasis but has also been reported to be effective in inflammatory dermatoses and numerous disorders of keratinization (17). Calcipotriene is thought to be safe and effective for the treatment of children with psoriasis. Long-term use in children has not been shown to alter serum calcium or phosphate levels. However, prolonged calcipotriene use may lower endogenous vitamin D levels. The long-term effects of this are not known (18,19).

Conclusion

Nevus comedonicus is a rare cutaneous disorder. It is usually benign in nature, but associated cutaneous and systemic defects have been reported. Nevus comedonicus can be cosmetically disfiguring. We present a case of bilateral nevus comedonicus of the face in a 7-year-old boy in the absence of any associated disorders.

Daily application of tazarotene and calcipotriene creams resulted in an objective decrease in the number of comedones and pustules and an improved cosmetic appearance. Our understanding of the pathogenesis of nevus comedonicus and the mechanism of action of tazarotene and calcipotriene support the hypothesis that these medications represent a novel therapeutic approach to the treatment of this cutaneous abnormality.

References

1. Kofmann S. Ein fall von seltener lokalisation und verbreitung von Comedonen. Arch Dermatol Syphilis 1895; 32:177-8.

2. Lefkowitx A, et al. Nevus comedonicus. Dermatology 1999; 199:204-7.

3. Kim SC, Kang WH. Nevus comedonicus associated with epidermal nevus. J Am Acad Dermatol 1989; 21:1085-8.

4. Piers F. Linear comedo naevus and ichthyosis. Br J Dermatol 1945; 57:138-47.

5. Carney RG. Linear unilateral basal-cell nevus with comedones: report of a case. Arch Dermatol 1952; 65:471-6.

6. Leppard BJ. Trichilemmal cysts arising in an extensive comedo naevus. Br J Dermatol 1977; 96:545-8.

7. Dudley K, et al. Nevus comedonicus in association with widespread, well differentiated follicular tumors. J Am Acad Dermatol 1986; 15:1123-7.

8. Whythe HJ. Unilateral comedo nevus and cataract. Arch Dermatol 1968; 97:533-5.

9. Rook AJ. Naevus comedonicus unilateralis with partial Sturge-Weber syndrome and extensive vascular naevi with haemangiectatic hypertrophy of leg. Proceedings of the 10th International Dermatology Congress. British Medical Association, London 1953; 421-2.

10. Engber PB. The nevus comedonicus syndrome: a case report with emphasis on associated internal manifestations. Int J Dermatol 1978; 17:745-9.

11. Beck MH, Dave VK. Extensive nevus comedonicus. Arch Dermatol 1980; 116:1048-50.

12. Inoue Y, et al. Two cases of nevus comedonicus: successful treatment of keratin plugs with a pore strip. J Am Acad Dermatol 2000; 43:927-9.

13. Milton GP et al. Treatment of nevus comedonicus with ammonium lactate lotion. J Am Acad Dermatol 1989; 20:324-8.

14. Decherd JW et al. Naevus comedonicus--treatment with retinoic Acid. Br J Dermatol 1972; 86:528-9.

15. Duvic M, et al. Molecular mechanisms of tazarotene action in psoriasis. J Am Acad Dermatol 1997; 37:S18-S24.

16. Sachs D, et al. Topical Vitamin D3. In: Wolverton SE (ed.), Comprehensive Dermatologic Drug Therapy. Edited by SE Wolverton. W.B. Saunders Company Philadelphia, 2001; 685-94.

17. Holm EA, Jemec GE. The therapeutic potential of calcipotriol in diseases other than psoriasis. Int J Dermatol 2002; 41:38-43.

18. Darley CR, et al. Safety and efficacy of calcipotriol ointment (dovonex) in treating children with psoriasis vulgaris. Br J of Dermatol. 1996; 135:390-393.

19. Park SB, et al. A pilot study to assess the safety and efficacy of topical calcipotriol treatment in childhood psoriasis. Ped Dermatol. 1999; 16:321-325.

STEVEN B DELIDUKA MD (1), PEARL C KWONG MD PHD (2)

1. DEPARTMENT OF DERMATOLOGY, MAYO CLINIC

2. CHIEF, DIVISION OF DERMATOLOGY, NEMOURS CHILDREN'S CLINIC JACKSONVILLE, FL

ADDRESS FOR CORRESPONDENCE:

Pearl C. Kwong MD PhD

Chief, Division of Dermatology

Nemours Children's Clinic

807 Childrens Way

Jacksonville, FL 32207

Phone: (904) 390-3490

Fax: (904) 858-3889

E-mail: pkwong@nemours.org

THE JOURNAL OF DRUGS IN DERMATOLOGY IS PLEASED TO ANNOUNCE AN ONGOING DERMATOLOGY CASE REPORT CONTEST, OPEN TO RESIDENTS, FELLOWS, AND PRACTICING PHYSICIANS.

IN EACH ISSUE OF THE JOURNAL, SIX WINNING CASE REPORTS--AS JUDGED BY A LEADING PANEL OF DERMATOLOGISTS--WILL BE PUBLISHED IN THIS SECTION, WITH THE WINNERS RECEIVING A COMPLIMENTARY ONE-YEAR SUBSCRIPTION TO THE JOURNAL OF DRUGS IN DERMATOLOGY.

WINNERS WILL BE SELECTED BASED ON NOVELTY, RELEVANCE, AND OVERALL QUALITY OF THEIR SUBMISSIONS, AND MULTIPLE ENTRIES ARE ENCOURAGED. FULL RULES AND AN ENTRY FORM CAN BE FOUND ON THE LAST PAGE OF THE JOURNAL, OR ONLINE AT WWW.DRUGSINDERMATOLOGY.COM.

COPYRIGHT 2004 Journal of Drugs in Dermatology, Inc.
COPYRIGHT 2005 Gale Group