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.
4.3.1 Estimating the Width of a Room RevisedThe unconditional analysis of the room width estimated by two groups ofstudents in Chapter˜3 led to the conclusion that the estimates in metres areslightly larger than the estimates in feet. Here, we reanalyse these data in aconditional framework. First, we convert metres into feet and store the vectorof observations in a variable y:R> data("ro
ZUSAMMENFASSUNG DER MERKMALE DES ARZNEIMITTELS<30 ml/min) oder dialysepflichtiger termina-dosis gesteigert werden, soweit verträglich. ler Niereninsuffizienz nicht angewendet wer-lung für 1 bis 2 Wochen zu unterbrechen,Es gibt bei der Behandlung von IPF keinendamit die Symptome abklingen können. relevanten Nutzen von Esbriet bei KindernJede Kapsel enthält 267 mg Pirfenidon. Photo