Hypothalamic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis

Objectives. Topical glucocorticoids (GCs) fail to produce a clinical respon se in some children with atopic dermatitis (AD), suggesting that GC resista nce may be present. To determine whether such resistance is generalized or specific to diseased skin, hypothalamic-pituitary-adrenal (HPA) axis functi on has been assessed in children with moderate to severe AD, who showed a v ariable response to treatment with topical GC. Study Design. Thirty-five patients (.7-18.7 years old; median: 9.3 years) w ith AD requiring topical GCs from infancy underwent a low-dose adrenocortic otrophin hormone (ACTH; Synacthen) test (LDST) (500 ng/1.73 m(2) ACTH). Gro ups 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 fo rm (inhaled +/- intranasal +/- oral) in addition to varying potencies of to pical 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 o f control subjects. Group 3 had lower peak, increment, and area under curve cortisol responses than those in controls, whereas group 4 had lower basel ine, peak, and area under curve cortisol responses. Eight patients failed t he 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. Treat ment score (based on GC potency, area treated, and duration) was the only f actor to influence peak cortisol response on LDST (r(2) = 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 wi th moderate to severe AD who used mild or moderately potent topical GCs ove r many years. However, HPA suppression was common in those receiving potent topical GC preparations or a combination of GC routes of administration. I n those with severe AD, evidence of HPA suppression but lack of clinical re sponse to GC treatment excluded significant generalized GC resistance. This would suggest that localized resistance to GCs within the diseased skin ma y be part of the aetiopathogenesis of severe AD.