Off-Label Use of Topical Calcineurin Inhibitors in Dermatologic Disorders

Abstract

Off-label prescribing is a common practice in dermatology, particularly when uncommon dermatologic diseases have limited or no approved treatment options. Topical calcineurin inhibitors are approved for the treatment of eczema, and their anti-inflammatory, immunomodulatory, and steroid-sparing effects make them an attractive therapeutic option for a wide variety of other dermatologic diseases. This review summarizes and qualifies the available evidence supporting the clinical effectiveness of tacrolimus ointment and pimecrolimus cream in non-eczema indications. There is high-quality evidence supporting the effectiveness of topical calcineurin inhibitors in multiple dermatological disorders including vitiligo; psoriasis of the face, folds, and genitals; seborrheic dermatitis; chronic hand dermatitis; contact dermatitis; oral lichen planus; lichen sclerosus; morphea; and cutaneous lupus erythematosus. Lower-quality evidence suggests they may be considered as an option in many other cutaneous disorders.

A comparative study of topical tacrolimus and topical triamcinolone acetonide in nodular scabies

“…[1][2][3][4][5][6][7]14 Although the term PSP has been suggested to be more apt than NS to represent a true prurigo with nodular lesions appearing or persisting despite successfully treated scabies (confirmed by the microscopic, dermoscopic and histopathologic confirmation of absence of mites and its components in the lesions), the release histamine and other mediators from mast cells and basophils, and reducing eosinophil activation. 6,[8][9][10] Although they are free from the adverse effects of TCS such as skin atrophy, transient burning sensation especially over sensitive skin is a well-known issue with tacrolimus ointment. 20,21 And while topical CNIs are becoming preferred alternative first line therapy for NS/PSP lesions, excepting one observational therapeutic study from Baghdad, 11 the current evidence favoring their use in NS/PSP is limited to anecdotal reports/small case series.…”

“…Tacrolimus and pimecrolimus are now being increasingly used as steroid-alternatives both for approved indications such as atopic dermatitis, and diverse off-label indications such as psoriasis, eczemas, morphea, lichen planus (LP), lichen sclerosus (LS), and vitiligo among others. 10 Topical CNIs reduce pruritus, induce regression of cutaneous lesions resulting from unchecked T-cell activation by blockade of T-cell activation and further elicitation of inflammatory cytokines, and inhibition of release of histamine and other mediators from mast cells and basophils. In addition to proven albeit variable efficacy of tacrolimus and pimecrolimus in treatment of NS, both as primary treatment option as well as in TCS-resistant cases, their use is free of the adverse effects associated with prolonged or injudicious use of TCS.…”

Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

“…These drugs are potent inhibitors of T cell proliferation, and thus indirectly impair B cell functions due to a reduced crosstalk with T-helper cells and T-follicular cells, which is necessary for autoantibody production. The availability of topical drug formulations is of specific interest in CAD, yet, the therapeutic effects of topical tacrolimus and pimecrolimus do not reach the efficacy of topical glucocorticoids [159].…”

Contemporary Role of Topical Calcineurin Inhibitors: A Pediatric Dermatology Perspective

“…63 They classified off-label prescribing as well supported by evidence, suppositional (ie, low level of certainty of net benefit), or investigational (ie, use should be limited to the context of research protocols because of the very low certainty of net benefit). 63 For a comprehensive review of the off-label uses of TCIs, including the level of evidence supporting their use in a wide range of skin diseases, see the accompanying article by Guenther et al 64…”