PEDIATRICS Vol. 105 No. 4 April 2000, pp. 794-799

Hypothalamic-Pituitary-Adrenal Function and Glucocorticoid Sensitivity in Atopic Dermatitis

Received Jul 2, 1999; accepted Oct 28, 1999.

Julie A. Ellison^*, Leena Patel^*, David W. Ray, PhD; Timothy J. David^*, and Peter E. Clayton

From the ^* Department of Child Health, and the  Endocrine Sciences Research Group, University of Manchester, Manchester, United Kingdom.

Objectives.  Topical glucocorticoids (GCs) fail to produce a clinical response in some children with atopic dermatitis (AD), suggesting that GC resistance may be present. To determine whether such resistance is generalized or specific to diseased skin, hypothalamic-pituitary-adrenal (HPA) axis function has been assessed in children with moderate to severe AD, who showed a variable response to treatment with topical GC.

Study Design.  Thirty-five patients (.7-18.7 years old; median: 9.3 years) with AD requiring topical GCs from infancy underwent a low-dose adrenocorticotrophin hormone (ACTH; Synacthen) test (LDST) (500 ng/1.73 m² ACTH). Groups 1 (7 patients), 2 (17 patients), and 3 (4 patients) used mild, moderate, or potent/very potent topical preparations, respectively. Group 4 (7 boys with severe, treatment-resistant disease) had received GC in at least 1 form (inhaled ± intranasal ± oral) in addition to varying potencies of topical GC. Fourteen healthy subjects (3.8-17.3 years old) served as control subjects. Group 4 patients had a daytime plasma cortisol profile and 08.00 hours measurement of plasma ACTH and its precursors.

Results.  The response to ACTH for groups 1 and 2 did not differ from that of control subjects. Group 3 had lower peak, increment, and area under curve cortisol responses than those in controls, whereas group 4 had lower baseline, peak, and area under curve cortisol responses. Eight patients failed the LDST (peak cortisol <500 nmol/L and increment <200 nmol/L): controls = 0/14, group 1 = 0/7, group 2 = 1/17, group 3 = 4/4, and group 4 = 3/7. Treatment score (based on GC potency, area treated, and duration) was the only factor to influence peak cortisol response on LDST (r² = 24%). In group 4, only 1 of 7 patients had a cortisol profile within the normal range but he failed the LDST. In the 5 subjects with an 08.00 hours cortisol <300 nmol/L, the matched ACTH level was inappropriately low.

Conclusions.  HPA suppression was rarely found in children or adolescents with moderate to severe AD who used mild or moderately potent topical GCs over many years. However, HPA suppression was common in those receiving potent topical GC preparations or a combination of GC routes of administration. In those with severe AD, evidence of HPA suppression but lack of clinical response to GC treatment excluded significant generalized GC resistance. This would suggest that localized resistance to GCs within the diseased skin may be part of the aetiopathogenesis of severe AD.  Key words:  atopic dermatitis, adrenal suppression, glucocorticoid sensitivity, glucocorticoid resistance.

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