Doi:10.1067/s0022-3476(03)00251-8

Unexpected high serum levels of tacrolimus after a single topical application in an infant Research Institute for Environmental Health at the Heinrich- Topical tacrolimus has been found to be effective and safe for the treatment of atopic dermatitis in adults and Supported by the Elterninitiative Kinderkrebsklinik e. V., Du¨sseldorf, and children.We report an infant with severe combined Deutsche Krebshilfe Projekt Nr.702428.
immunodeficiency (SCID) in whom we performed bone Reprint requests: PD Dr med T. Niehues, Zentrum fu¨r Kinderheilkunde der marrow transplantation at the age of five months. Two months Heinrich Heine Universita¨t Du¨sseldorf, 40001 Du¨sseldorf, Germany. E-mail: later the boy developed a generalized erythema with pruritus, lichenification, and an ichthyosiform appearance at the scalp.
The skin biopsy showed chronic dermatitis. A single application of tacrolimus ointment (Protopic [FujisawaHealthcare, Deerfield, Ill], 0.1%; total dose, 15 g) wasfollowed by disappearance of the erythema within one day.
Surprisingly, there were extremely high serum levels oftacrolimus (24 ng/mL) measured 20 hours after application.
Over seven days, tacrolimus levels gradually decreased to Ruzicka T, Bieber T, Schopf E, Rubins A, Dobozy A, Bos JD, et al. A undetectable when the dermatitis reappeared. A much lower short-term trial of tacrolimus ointment for atopic dermatitis. European dose of topical tacrolimus (Protopic, 0.03%; total dose, 0.3 g) Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med again resulted in elevated serum tacrolimus levels (7 ng/mL; Boguniewicz M, Fiedler VC, Raimer S, Lawrence ID, Leung DY, 20 hours after application). This time a transient tremor of the Hanifin JM. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group.
Bouguniewicz reported that 7 of 258 children (7-16 years J Allergy Clin Immunol 1998;102:637-44.
of age) treated with topical tacrolimus (10 g/day) showed Allen DM, Esterly NB. Significant systemic absorption of tacrolimus systemic levels >1.0 ng/mL.The more than ten times higher after topical application in a patient with lamellar ichthyosis. Arch Dermatol2002;138:1259-60.
serum tacrolimus level in our patient is puzzling. Young age Allen A, Siegfried E, Silverman R, Williams ML, Elias PM, Szabo SK, may have facilitated systemic tacrolimus absorption because et al. Significant absorption of topical tacrolimus in 3 patients with Netherton infants have an increased surface/body ratio compared with syndrome. Arch Dermatol 2001;137:747-50.
older children. Certain skin diseases are associated witha decreased skin barrier function. Increased serum tacrolimus levels have been reported in a 28-month-old child with lamellarichthyosis and in three patients with ichthyosis and Netherton syndrome (3-14 years) after treatment with topical tacrolimus We read with interest the article by Tse et al, entitled (3-15 g dailThese cases and our case demonstrate that, in ‘‘Early treatment with intravenous immunoglobulin in pa- children of young age and diseases with decreased skin barrier tients with Kawasaki disease’’.Our discussions raised two function, caution with the use of topical tacrolimus is warranted. A single application can already lead to markedly First, the report’s authors attributed the statistically elevated serum levels and may put children at risk for toxic side significant outcome improvements to early treatment with IVIG. It appears, however, that aspirin therapy was instituted at the same time as IVIG in both groups of patients. The authors do not discriminate between the effects of immuno- globulin and aspirin. The outcome observed therefore could Department of Pediatric Haematology, Oncology, and potentially be the result of aspirin therapy alone, or the combination of aspirin and IVIG. Because IVIG is an ex- pensive therapy with potentially serious side effects, we feel that hard evidence of its particular benefit is required before moving towards an early treatment protocol. We would Department of Clinical and Laboratory Diagnostics suggest that further investigation with a prospective random- The University Medical Center Heinrich-Heine-University of ized clinical trial is necessary to distinguish the benefits of early aspirin and or early immunoglobulin therapy.

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