Effect of percutaneous absorption of hydrocortisone on adrenocortical responsiveness in infants with severe skin disease

Abstract

Percutaneous absorption of hydrocortisone was studied in 18 children (aged from 6 weeks to 14 1/2 years) with atopic or seborrhoeic dermatitis, by measuring their serum cortisol before and after application of 1% hydrocortisone cream. Endogenous secretion of cortisol was suppressed with dexamethasone. A 24 h absorption test was performed on nine children. In six, percutaneous absorption was detected. The highest serum cortisol level was reached within the first 6 h. A 4 h absorption test was developed on the basis of the 24 h test. This short absorption test was performed on nine children, and in eight of them absorption of hydrocortisone was detected. The rise of serum cortisol ranged from 98 to 2669 nmol/l. The 2 h ACTH test was performed to evaluate the effect of previous treatment with topical glucocorticoids. Suppressed adrenocortical function was found in five of 13 children, and was associated significantly with high post-application serum cortisol levels. This occurred more often in infants with a severe skin disorder than in older children or in those with mild or moderate skin disease.

Safety and Tolerability of 1% Pimecrolimus Cream Among Infants: Experience With 1133 Patients Treated for Up to 2 Years

“…In this context, it should be noted that no long-term study has been performed on the risk of malignancies among patients with AD treated with TCSs, despite the fact that systemic corticosteroid treatment induces immunosuppression and has been associated with increased risks of skin cancer and lymphomas 55,56 and despite the evidence that TCSs can penetrate through the skin sufficiently to cause clinically evident systemic effects. 8,15 We think this review of data from a large number of patients provides useful information on the type of side effects infants can experience during treatment with 1% pimecrolimus cream for AD and on the risk of developing those side effects. Because of the low level of systemic absorption and the good tolerability during intermittent use in the long term, 1% pimecrolimus cream may represent an alternative to TCSs for young pediatric patients, because they represent, at the same time, the segment of the population affected most frequently by AD 1,3-5 and the segment of the affected population most susceptible to the systemic effects of prolonged TCS treatment.…”

“…The major risk factors for increased percutaneous absorption of TCSs are disease extent and patient age, with young pediatric patients being at the highest risk 13 because of their large skin surface area/body mass ratio. 14,15 The perceived risks of side effects from TCS use have generated concern, resulting in "corticosteroid phobia" and poor compliance with treatment, particularly in the pediatric population. [16][17][18] One percent pimecrolimus cream (Elidel, SDZ ASM 981; Novartis Pharma AG, Basel, Switzerland) is a topical calcineurin inhibitor that blocks the transcription and release of inflammatory cytokines and mediators that are produced by T lymphocytes and mast cells and are involved in the pathogenesis of AD and other inflammatory skin disorders.…”

“…This issue should be addressed particularly among infants, because the risk of systemic absorption of topical drugs for these individuals is higher than that for older children and adults. [13][14][15] The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants with AD, on the basis of the combined data from 4 pharmacokinetic studies and 6 clinical trials conducted with 1133 patients. the lymphoid tissue.…”

“…Although TCSs are undoubtedly effective in treating acute manifestations of the disease, their prolonged unrestricted use is limited by local and systemic side effects. [8][9][10][11][12][13][14][15] Systemic side effects occur as a result of the penetration of topically applied corticosteroids through the skin into the circulation (percutaneous absorption). The major risk factors for increased percutaneous absorption of TCSs are disease extent and patient age, with young pediatric patients being at the highest risk 13 because of their large skin surface area/body mass ratio.…”

Effective use of transdermal drug delivery in children

“…While exposure to tacrolimus, when given as an ointment to treat atopic dermatitis, is usually low [90], systemic absorption of the drug has been reported for 3 patients (3, 5, and 14 y old) with Netherton syndrome and erythroderma [91]. The systemic absorption of topical steroids used to treat skin diseases has been frequently reported [92][93][94], and some extreme cases have resulted in depressed adrenal function [93,95] and development of Cushing syndrome [93,96]. It is well known that hydrocortisone accumulates in the skin upon topical administration and, interestingly, application of a moisturizer containing propylene glycol to the same skin site caused an increase in plasma cortisol levels, presumably due to mobilisation of drug in the skin 'reservoir' [97].…”