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

Ellison, Julie A.; Patel, Leena; Ray, David; David, T J; Clayton, Peter

doi:10.1542/peds.105.4.794

Cited by 108 publications

(70 citation statements)

References 19 publications

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“…Specifically, long‐term, uninterrupted use of glucocorticoids can cause striae, increase the risk of adrenal suppression, and slow linear growth 12, 13. Calcineurin inhibitors are associated with the potential risk of malignancy (skin cancer, lymphoma), although a direct causal relationship has not been established 2.…”

Section: Discussionmentioning

confidence: 99%

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Zane¹,

Kircik

Call³

et al. 2016

Pediatric Dermatology

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BackgroundPhosphodiesterase‐4 (PDE4) is a promising target in atopic dermatitis (AD) treatment. The pharmacokinetics (PK), safety, and efficacy of crisaborole topical ointment, 2% (formerly AN2728) (Anacor Pharmaceuticals, Palo Alto, CA), a boron‐based benzoxaborole PDE4 inhibitor, were evaluated in children with mild to moderate AD.MethodsThis phase 1b, open‐label, maximal‐use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg/cm2) for 28 days enrolled patients ages 2 to 17 years with extensive AD involving 25% or more or 35% or more treatable body surface area, depending on age. Primary PK and safety assessments included systemic exposure to crisaborole and its metabolites after 7 days of treatment and the incidence of treatment‐emergent adverse events (TEAEs). Secondary efficacy assessments included change from baseline in Investigator Static Global Assessment (ISGA), treatment success (ISGA score ≤1 with a two‐grade or greater improvement from baseline), and improvement in five AD signs and symptoms.ResultsOf 34 patients enrolled, 31 completed the study. Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8. Twenty‐three of 34 patients reported one or more TEAEs; 95% were mild or moderate and one patient discontinued because of a TEAE. Mean ISGA scores declined from 2.65 at baseline to 1.15 at day 29, 47.1% of patients achieved treatment success, and 64.7% of patients achieved ISGA scores of clear (0) or almost clear 1. Mean severity scores for AD signs and symptoms declined throughout the study.ConclusionsThis open‐label study provides evidence that crisaborole topical ointment, 2% was well tolerated, with limited systemic exposure under maximal‐use conditions in patients ages 2 years and older.

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Section: Discussionmentioning

confidence: 99%

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Zane¹,

Kircik

Call³

et al. 2016

Pediatric Dermatology

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“…This may be due to the occlusive effects which increase percutaneous absorption. Topical use of corticosteroids in those who have a generalized glucocorticoid resistance of skin causes a lowering in systemic adverse effects, despite enhanced percutaneous absorption and potent topical corticosteroids to suppress the HPA axis [37]. Risk factors for the development of adrenal insufficiency from using topical corticosteroids may include the amount of application, the frequency of application, patient age, quality of previous skin problems, long-term application, the use of highly potent topical corticosteroids, application in widespread areas of the skin and use with occlusive dressings.…”

Section: Discussionmentioning

confidence: 99%

Exogenous Cushing’s syndrome due to topical corticosteroid application: case report and review literature

Tempark

Phatarakijnirund

Chatproedprai

et al. 2010

Endocr

105

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Prolonged use of topical corticosteroids causes systemic adverse effects including Cushing's syndrome and hypothalamic-pituitary-adrenal (HPA) axis suppression, which is less common than that of the oral or parenteral route. At least 43 cases with iatrogenic Cushing syndrome from very potent topical steroid usage (Clobetasol) in children and adult have been published over the last 35 years particularly in developing countries. In children group (n = 22), most are infants with diaper dermatitis and two cases who had started topical application at a very early age and died from severe disseminated CMV infection. For the adult group (n = 21), the most common purpose of steroid use was for treatment of Psoriasis. The recovery period of HPA axis suppression was 3.49 ± 2.92 and 3.84 ± 2.51 months in children and adult, respectively. We report on an 8-month-old female infant who developed Cushing's syndrome and adrenal insufficiency after diaper dermatitis treatment through the misuse of Clobetasol without doctor's prescription. Physiologic dose of hydrocortisone was prescribed to prevent an adrenal crisis for 3 months and discontinued when HPA axis recovery was confirmed by normal morning cortisol and ACTH levels.

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“…89 While all effective topical corticosteroids possess the potential to suppress the HPA axis, 87,90-92 an increase in steroid penetration has been shown to augment the potential for HPA suppression, especially in children with atopic dermatitis. [93][94][95] Application of corticosteroids to large surface areas, occlusion, higher concentrations, or more potent derivatives directly increase the risk of HPA suppression. 96 The advent of superpotent derivatives such as clobetasol propionate, betamethasone dipropionate, and diflorasone diacetate have an increased ability to suppress adrenal function.…”

Section: Suppression Of the Hypothalamic-pituitaryadrenal (Hpa) Axismentioning

confidence: 99%

Adverse effects of topical glucocorticosteroids

Hengge

Ruzicka

Schwartz

et al. 2006

Journal of the American Academy of Dermatology

926

682

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

Cited by 108 publications

References 19 publications

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Exogenous Cushing’s syndrome due to topical corticosteroid application: case report and review literature

Adverse effects of topical glucocorticosteroids

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