Cyclosporine in the Treatment of Dermatologic Disease: An Update

Abstract

Treatment with cyclosporine is beneficial for many dermatologic diseases such as psoriasis, lichen planus, Behçet disease, atopic dermatitis, pyoderma gangrenosum, and epidermolysis bullosa acquisita. The selective action of cyclosporine on helper T cells and its rapid therapeutic action and weak myelotoxicity are the key advantages in the treatment of many dermatologic diseases. Nevertheless, drug toxicity, especially nephrotoxicity, high rates of relapse after treatment cessation, and high cost have limited its use to those diseases refractory to other therapies. Herein we discuss the use of cyclosporine for dermatologic diseases relative to efficacy, dosage, safety profile, and monitoring. In addition, we review the formulations and metabolism of cyclosporine; discuss its mechanism of action, clinical indications in dermatology, and side effects; and provide usage guidelines for this drug. Cyclosporine can be safely administered when potential toxicities, dosing, and monitoring guidelines are known.

Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype.

“…Recent evidence implicates aberrant activation of the immune system and T lymphocyte localization in skin as critical components in the pathogenesis of psoriasis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), but the etiologic defect(s) in this disease remain elusive. A role for upregulated expression of autocrine regulatory networks in the pathogenesis of psoriasis has emerged from previous investigations that have suggested that epidermal hyperplasia and aberrant differentiation may result from dysregulation of the epidermal keratinocyte EGF receptor-ligand system (26, 31-35, 38, 39).…”

“…Although the etiology of psoriasis has not been elucidated, the development of psoriatic skin lesions has been shown to be associated with infiltration of cells from the immune system, including T lymphocytes, macrophages, and neutrophils. The aberrant activity of activated T lymphocytes is thought to be paramount in the pathogenesis of psoriasis, as immunosuppressive agents such as methotrexate, cyclosporine, tacrolimus, IL-2 receptor-targeted toxins, and corticosteroids are efficacious for this disease (1)(2)(3)(4)(5)(6). Furthermore, activated CD4-positive T lymphocytes from patients with psoriasis have been shown to initiate psoriatic lesion formation in uninvolved human psoriatic skin grafted onto SCID/SCID (severe combined immunodeficient) 1 (7,8), and SCID/SCID mice reconstituted with naive CD4-positive T lymphocytes possessing a minor histocompatibility mismatch have been reported recently to initiate a psoriatic-like cutaneous reaction (9).…”

Topical Cyclosporin in the Treatment of Dermatologic Diseases

“…Pre-and post-therapy biopsies have revealed decreased T cell infiltrate and reduced expression of ICAM -1 and HLA -DRafter topical cyclosporin (36). Topical cyclosporin therapy may be more effective in oral lichen planus than in cutaneous lichen planus because of the relatively higher absorption through mucous membranes (29).…”

“…Behcet Disease -Cyclosporin is effective in controlling the ocular complications and mucocutaneous and musculoskeletal manifestations of Behcet disease (29). Ergun et al (30), reported beneficial results with topical cyclosporin in treating oral ulcers of Behcet's disease.…”

Mechanisms of Calcineurin Inhibitor Nephrotoxicity in Chronic Allograft Injury

“…It is extensively biotransformed to approximately 15 metabolites, which are almost completely eliminated via the biliary system. Less than 3% of the parent compound is excreted in urine and thus higher blood levels of CsA do not occur in patients with renal dysfunction (Lim et al, 1996). CsA plasma levels peak in 2 to 4 hours and the serum half life ranges from 6.3 hours to 20.4 hours.…”