AReassuring Rejoinder Against Malignant Influences of Topical Calcineurin Use in Children

The topical calcineurin inhibitors tacrolimus and pimecroli-mus are useful and effective anti-inflammatory immuno-modulator adjuncts in managing atopic dermatitis (AD). Unfortunately, because of the increased risk of lymphoma in transplant recipients receiv-ing systemic tacrolimus and because of malignant neo-plasms in animal studies with pimecrolimus, their use as topical agents has raised concerns.1 Yet the topical use of these drugs in humans since the mid-1990s has not appeared to cause any clear immuno-suppressive propensity toward malignancy. Topical tacrolimus ointment, 0.03 % and 0.1%, became available in late 2000 as short-term therapy for moderate to severe AD in adults and children whose condition had not responded adequately to topical corticosteroid therapy. Pimecrolimus cream, 1%, was approved by the Food and Drug Administration (FDA) in December 2001 for treatment of mild to moderate AD in adults and in children older than 2 years. Both were categorized as second-line agents for inter-mittent, noncontinuous therapy, and these limitations were cited in an American Academy of Dermatology Consensus Conference in 2003.2 However, the effectiveness and appar-ent safety after use of these drugs in several thousand chil-dren sparked great optimism and even direct-to-consumer advertising in the United States. In response, the Pediatric Advisory Committee of the FDA in early 2005 issued a rec-ommendation for a “black box ” warning in the package inserts of the topical calcineurin inhibitors, noting off-label use in younger children and postmarketing reports of malig-nant neoplasms in adults and children and in a study that showed occurrence of lymphoma in monkeys receiving 30-fold oral dosing of pimecrolimus.3,4 The black box warn-ing stated the following3(p1233)