Cases

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Lichen sclerosus et atrophicus (LSA): LSA remains a disease of unknown pathogenesis that often severely affects the patient's quality of life. LSA affects 14 people per 100,000 population per year and has a predilection for females, with up to 15% of cases involving patients in the first or second decades of life (Powell, 1999; Hengge, 2000). Alopecia areata, vitiligo, and serologic and clinical disorders of the thyroid appear to be associated with LSA. Experimental studies have revealed the presence of autoantibodies to the extracellular matrix (ECM) protein, which suggests an autoimmune pathogenesis (Oyama, 2003).

The clinical presentation includes symptoms affecting the anogenital area (vulva, penis, anus). Although any skin site, including the oral mucosa, may be affected (Jensen, 2002), LSA most frequently occurs on the vulva, where it may be asymptomatic or cause intractable itching and soreness (Powell, 1999; Hengge, 2000). Typical clinical findings are telangiectasia, purpura, erosions, variable degrees of sclerosis, and polygonal papules and plaques with atrophic fragile skin. With time, progression to destructive sclerosis commonly leads to narrowing of the anogenital orifices. Extragenital sites affected include the thighs; the submammary region; the neck; the shoulders; and, sometimes, the oral mucosa. Differential diagnoses include erosive lichen planus, scaring pemphigoid of mucous membranes, lichen simplex, morphea, and balanitis obliterans xerotica.

The inflammatory infiltrate of LSA has recently been shown to contain CD8/CD57-positive epidermotropic lymphocytes, which commonly serve as markers for a chronic excessive antigen deposition (Carlson, 2000). In addition, intraepidermal major histocompatibility complex (MHC) class II–positive cells are also increased (Farrell, 1999). Furthermore, levels of interleukin (IL)–4 and transforming growth factor–b are elevated in LSA (Scrimin, 2000).

Asymptomatic extragenital LSA generally requires no treatment other than that to control pruritus. Various attempts to treat genital LSA have been undertaken. The only treatment proven to be effective seems to be long-term therapy with topical steroids of decreasing potency, as evidenced in nonrandomized controlled studies (Dahlmann-Ghozlan, 1999; Sinha, 1999). Randomized studies have not shown a significant effect of topical testosterone or estrogen, vitamins, cyclosporin, retinoids, or antibiotics.

Photodynamic therapy has been used (Hillemanns, 1999), but this treatment can be painful. Destructive surgical therapy should be used only if squamous cell cancer is detected. In general, the lifetime risk of squamous cell cancer as a complication of long-standing LSA is estimated to be 4-6% (Powell, 1999). LSA tends to recur, especially after circumcision in males, and may lead to radical surgery.

Given the prominent symptoms and limited therapeutic options of LSA, novel treatments are highly desirable. The novel topical immunomodulator (TIM) tacrolimus was evaluated as a therapeutic alternative for this difficult-to-treat patient. In this case, tacrolimus 0.1% ointment was applied two times per day. All of the patient's symptoms and signs, except for sclerosis, subsided after 6 weeks of treatment (Image B). She did not experience any worsening of burning or itching while receiving treatment.

Topical tacrolimus belongs to the new class of topical TIMs, which also includes cyclosporin and pimecrolimus. It has been approved for the treatment of atopic dermatitis (Reitamo, 2001). Tacrolimus is a lipophilic compound that inhibits the phosphatase calcineurin, blocking the transcription of proinflammatory cytokines such as IL-2 and interferon-g (Assmann, 2001). Calcineurin inhibitors reduce antigen processing and T-cell activation. They also affect other cell types involved in itching and inflammation, such as mast cells and eosinophilic and basophilic granulocytes (via inhibition of IL-3, IL-8, IL-13, granulocyte/macrophage colony-stimulating factor [GM-CSF], histamine, and tryptase) (Scrimin, 2000). FceR1 receptor expression is also reduced on epidermal antigen-presenting cells (Wollenberg, 2001).

Although many effects of topical tacrolimus parallel those of corticosteroids, adverse effects such as skin atrophy and telangiectasias do not occur with TIMs. This drug has been used for off-label indications such as the treatment of eczema of the eyelids (Mayer, 2001), perioral dermatitis and rosacea (Goldman, 2001), lichen planus (Kaliakatsou, 2002), pyoderma gangrenosum (Reich, 1998), and vitiligo (Grimes, 2002; Lepe, 2003).

Patient-applied tacrolimus, the first TIM for chronic inflammatory diseases, bears potential in the treatment of LSA. A trial has been initiated to confirm its effect on this condition.

For more information on LSA, see the eMedicine articles Lichen Sclerosus et Atrophicus and Balanitis Xerotica Obliterans (within the Dermatology specialty).