Lichen Sclerosus et Atrophicus Medication

Topical testosterone was mainstay of treatment for female genital lichen sclerosus for decades, although it was never shown useful in male genital or extragenital cases. More recent studies suggest it may not be any more efficacious than placebo. Systemic therapies, including anti-Borrelia antibiotics, potassium benzoate, penicillamine, and systemic steroids, have not proven reliably effective.

Systemic retinoids have been useful in limited studies with isotretinoin, etretinate, and acitretin. Topical corticosteroids, especially in the superpotent class, have been found to be useful in genital lichen sclerosus in both sexes and in all age groups.^[20] These have been used long term (weeks to months) or daily, without significant adverse cutaneous effects, although patients should always be monitored regularly for adverse effects (especially atrophy of nearby uninvolved areas).

Therapy with tazarotene (Tazorac) off label for this medication in this location and for this indication. Especially in genital and other occluded areas, short-contact therapy is used, in which the gel (or cream) is initially applied for 15 min and washed off. Every 2-3 wk, the time applied may be increased by about 15 min until either therapeutic effect or limiting adverse effects are noted. If a patient is applying the medication for 3 h or more, they may consider leaving the medication in place. For extragenital lichen sclerosus, this may be applied and left in place. This may be done in conjunction with topical steroid use. Tazarotene has not been well studied for lichen sclerosus in children, but application should be similar to adult usage. A pregnancy test is recommended before starting therapy, and the drug is category X (contraindicated). Tazarotene may be irritating and is not likely to be tolerated on open and denuded areas.

Systemic administration of the vitamin D analogs calcitriol and calcipotriene (Dovonex, Vectical, Taclonex [with topical corticosteroid]) has been shown anecdotally to be effective for generalized morphea. While not universally effective, topical forms of this category have helped some patients with localized sclerotic diseases. They can be irritating in genital and occluded areas and may require alternate-day therapy. They are usually not used as monotherapy for sclerotic disorders but, rather, are usually combined with topical corticosteroids. Daily to twice-daily application is suggested. Use with caution in patients with compromised renal function, and prolonged use of large amounts warrants laboratory monitoring (with particular attention to serum calcium values). Pediatric dosing is the same as adult dosing. These agents are pregnancy category C.

One report describes successful treatment of refractory generalized extragenital lichen sclerosus with pulsed high-dose corticosteroids combined with methotrexate.^[21] Methotrexate and other immune suppressing medications have been used, alone and in combination with topical and systemic corticosteroids. Standard dosages are used with the usual contraindications, and monitoring is recommended. Because of the risk of squamous cell carcinoma, some medications known to increase squamous cell carcinoma risk (eg, cyclosporine) should be used with caution with very careful monitoring of the patient for suspicious lesions, which should undergo biopsy immediately. The use of potent immunosuppressant medications in patients with active intraepithelial dysplasia or even significant condyloma acuminata should only be performed after careful informed consent and consideration of other options. Most of the immunosuppressant agents are pregnancy category C and D, but some are X.

Class Summary

Reducing inflammation helps reduce symptoms and, in some cases, helps resolve the lesion.^{[22, 23]}

Clobetasol (Temovate)

Class I superpotent topical steroid, Suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Other superpotent steroids would be expected to have the same results; however, most published studies showing benefit of such medications have used clobetasol.

Pulse dosing (2 consecutive d/wk) may be used long-term, even in genital cases. On off-days, a milder steroid or emollient alone may be used. No additional benefit in using potent and super-potent steroids >qd. Especially in genital applications, bid application of such a medication will more quickly lead to steroid adverse effects.

Hydrocortisone topical (Westcort, Dermacort, Cortaid, DermaGel)

An adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. It has mineralocorticoid and glucocorticoid effects resulting in anti-inflammatory activity.

Class Summary

Mechanism of action for successful effects systemic retinoids have had in lichen sclerosus (usually studied in female genital cases) is not clear but may have to do with down-regulation of fibroblast function.

Acitretin (Soriatane)

Retinoic acid analog, like etretinate and isotretinoin. Etretinate is main metabolite and has demonstrated clinical effects close to those seen with etretinate. Mechanism of action is unknown. Has been reported to benefit both symptoms and induce resolution of lesion. Although not well studied, combining a medication in this class with a topical corticosteroid as described above may be useful in refractory cases.

Isotretinoin (Accutane)

Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A.

Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization. Has been reported to benefit both symptoms and may help resolution of lesion itself. Although not well studied, combining a medication in this class with a topical corticosteroid as described above may be useful in refractory cases.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Class Summary

Many have concerns about the use of potent topical corticosteroids in occluded areas such as the genitals. They often do not work as well or as fast as the corticosteroids when used as monotherapy, but this class of medications may have a role either as maintenance medications after steroid-driven improvement or in conjunction with them in a pulse-steroid regimen (ie, superpotent corticosteroid on weekend days and a TIM during the week). Some believe this may delay or obviate the onset of tachyphylaxis and reduce the risk of steroid atrophy. This is an off-label use for both medications. Recently, some have raised concerns about the use of these medications long term, especially in young children and infants. The exact risks of long-term use, if any, remain to be defined, but the prescriber should be aware of the issues.

Tacrolimus ointment (Protopic)

Mechanism of action in atopic dermatitis is not known. Reduces itching and inflammation by suppressing release of cytokines from T cells. Also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in the early stages of T-cell activation. Additionally, may inhibit release of preformed mediators from skin mast cells and basophils and may down-regulate expression of FCeRI on Langerhans cells. Indicated in dermatitis patients as young as 2 y. Drugs of this class are more expensive than topical corticosteroids. Available as an ointment in concentrations of 0.03% and 0.1%.

Pimecrolimus (Elidel)

First nonsteroid cream approved in the United States for mild-to-moderate atopic dermatitis. Derived from ascomycin, a natural substance produced by Streptomyces hygroscopicus var. ascomyceticus. Selectively inhibits production and release of inflammatory cytokines from activated T cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy not observed in clinical trials, a potential advantage over topical corticosteroids. Indicated only after other treatment options have failed