Steroid-free pimecrolimus for monotherapy of lichen planus

Journal of Drugs in Dermatology, Sept-Oct, 2004 by Scott J.M. Lim, W. Elliot Love

Abstract

Lichen planus (LP) is a disease distinguished by pruitic violaceous planar papules containing reticulated white striae. It can occur just about anywhere, but most commonly occurs in the mouth, genital, and distal extremity areas. The general treatment for LP consists of topical or systemic steroids, although a standard accepted treatment is still to be determined. Pimecrolimus has generated recognition as a topical non-steroidal drug labeled for treatment of atopic dermatitis. The proposed mechanism of action of pimecrolimus is inhibition of cytokine production and proliferation. Cytokine obstruction results in the limitation of T-cell propagation, which is the inciting factor in the pathological process of LP. This element may prove be advantageous in the treatment of LP.

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Case Report

Our patient is a 56-year-old male with a medical history significant for hypercholesterolemeia, non-insulin dependent diabetes and alopecia totalis. He presented to the office with a chief complaint of a pruritic rash on his hands and feet, persisting for about six weeks. His medications at that time consisted of metformin and atorvastatin. His only know drug allergy is to penicillin.

The review of systems was negative except for a transient rash on his hands and feet. On physical exam the primary lesion appeared papular and polygonal with fine reticulated lines on the top. The papules were well demarcated and had a purple hue about them. A biopsy was performed on one of the primary lesions. Upon biopsy confirmation, the patient was diagnosed with lichen planus and placed on clobetasol gel 0.05%. Atorvastatin was stopped from the patient's regimen as well.

Three months later he returned to the office complaining of new eruptions extending to his arms. His rash was increasingly pruritic, despite the Clobetasol gel. The patient was prescribed pimecrolimus (Elidel) cream 1% for b.i.d. application to use in concordance with the clobetasol gel.

He returned for his follow up appointment one month later. His rash had greatly improved and he stated that he had stopped using the clobetasol gel for the last month. He had solely been using the pimecrolimus cream as monotherapy.

Discussion

Lichen planus (LP) is a member of the papulosquamous dermatoses that most commonly occurs on the hands, wrist, ankles, mouth, and genital regions. It can also affect the nails, esophagus, scalp, extremities, and perianal areas. This disease is idiopathic and usually affects adults between the fourth and seventh decade, although 2 to 3% of reported cases involve children (1). It is important to screen LP patients for HCV due to its strong association with the virus, having a prevalence of up to 60% in some populations (2). Skin that has undergone trauma may also encourage the development of fresh LP lesions, known as Koebner's phenomenon (3).

Purple, papular, polygonal, pruritic, planar, punctate, lesions (don't forget pterygium on the nails) are the pathomnemonic "P's" of lichen planus. Evaluation of the primary lesion of LP reveals a violaceous flat-topped angular papule that contains fine white reticulated or punctate lines called Wickham's striae. These lesions generate varying degree of pruritis. As described above, our patient presented with the archetypal manifestation of LP in one of the clinically standard areas. Pathologically a cell-mediated immune reaction may be the basis for the disease. Histologically, LP develops as lymphocytic infiltrate at the dermal-epidermal junction coupled with destruction of basal keratinocytes. The dead keratinocytes are referred to as Civatte bodies. Sawtooth ridges and Max-Joseph spaces, which are converging dermal-epidermal vacuoles, may also be observed (4). There have been multiple attempts to discover a stable treatment for LP. Standard therapies include antibiotics, PUVA, interferon alpha, cyclosporin, tacrolimus (Protopic), and other immunomodulators. Oral corticosteroids are the most widely used therapy for generalized cutaneous LP. To date there has not been a treatment that proves to be consistently effective (3,5,6).

Pimecrolimus' development stemmed from attempts to create an anti-inflammatory which did not diminish systemic immunity. Pimecrolimus cream stands alone from other anti-inflammatory drugs because it was fashioned to specifically treat inflammatory skin disorders (7,8). The drug is FDA approved to treat atopic dermatitis in patients age 2 years and older (7). Pimerolimus binds to macrophilin-12 and inhibits the phosphatase calcineurin. This in turn inhibits T-cell activation and proliferation as well as release of inflammatory-promoting substances such as cytokines and anaphylatoxins (8,9). Pimecrolimus has been shown not only to cause low probability of systemic immune response, in contrast to tacrolimus and cyclosporin, but does not possess the atrophogenic properties of steroids (10,11). These differences in pharmacodynamic properties give pimecrolimus a therapeutic advantage for treating LP, as well as other cutaneous inflammatory diseases.