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Advances in dermatology and venereology Acta Dermato-Venereologica
Successful Treatment with Dupilumab in a Patient with Severe, Difficult to Treat Atopic Dermatitis: Beware of Symptomatic Adrenal Insufficiency due to Abrupt Discontinuation of Potent Topical Corticosteroids
Lieneke F. M. ARIENS 1, Jorien VAN DER SCHAFT 1, ALINE M. E. STADES 2, Anthonie A. VAN DE WOESTIJNE 2 and Marjolein S. DE BRUIN-WELLER 1
1
Department of Dermatology and Allergology, Room G02.124, and 2 Department of Internal Medicine, University Medical Center Utrecht, NL-3508 GA Utrecht, The Netherlands. E-mail: l. f. m. ariens @ umcutrecht. nl Accept Mar 27, 2018; Epub ahead of print Mar 27, 2018
Topical corticosteroids are widely used in the treatment of chronic inflammatory skin diseases, including atopic dermatitis( AD)( 1). Long-term treatment with potent topical corticosteroids can have systemic effects due to percutaneous corticosteroid absorption( 2). Potentially serious systemic effects include Cushing’ s syndrome and suppression of the hypothalamic-pituitary-adrenal( HPA) axis( 3). Prolonged suppression of the HPA-axis may result in tertiary adrenal insufficiency caused by adrenal atrophy, which is a potential life-threatening disorder( 3). The risk of tertiary adrenal insufficiency depends on several factors, e. g. age, the quantity and potency of the topical corticosteroids, the extent of the treated body surface, the condition of the skin( barrier) at the time of application, and the use of concomitant( corticosteroid-containing) drugs. Topical corticosteroidinduced HPA-axis suppression has been described; however, the development of symptomatic adrenal insufficiency is rare( 4 – 6).
We report here a case of clinically relevant adrenal insufficiency as a result of abrupt discontinuation of topical corticosteroid treatment in a patient treated successfully with dupilumab for severe AD.
CASE REPORT
A 50-year-old man with a history of inflammatory bowel disease, anxiety disorder and hypertension was treated at our clinic for severe AD. Relevant medication use included fluoxetine( 40 mg / day) for panic attacks. He had uncontrolled AD, despite treatment with potent topical corticosteroids in both outpatient and inpatient settings and treatment with various oral immunosuppressive drugs. Treatment with cyclosporine A( CsA) was effective, but had to be discontinued after several months due to kidney failure. Enteric-coated mycophenolate sodium and, subsequently, azathioprine were discontinued after > 12 weeks of treatment due to ineffectiveness. After discontinuation of extended-release tacrolimus because of side-effects, the patient was treated with high-potency topical corticosteroids and systemic corticosteroids. Severe, difficult-to-control AD was the motivation to participate in a phase 3 double-blind, placebo-controlled trial investigating the efficacy, safety and tolerability of dupilumab in patients with severe AD that was inadequately
controlled or ineligible for treatment with CsA( CAFÉ study)( 7). Treatment with systemic corticosteroids was gradually tapered over several weeks and stopped 24 weeks before the start of dupilumab. At baseline, the patient had a severe, generalized AD with an Eczema Area Severity Index( EASI) score of 44.60. During the 16-week treatment period, the patient was treated with placebo without clinical response( Fig. 1). In this period, the patient used medium-to-high-potency topical corticosteroids( mainly betamethasone dipropionate 0.05 % ointment) 1 – 2 times daily with a mean amount of 150 g / week. After completing the 16-week treatment period, the patient participated in the Open-Label Extension( OLE) study in which he was treated with 300 mg dupilumab weekly. Four weeks after enrollment, disease severity improved significantly( EASI 3.70)( Fig. 1). The rapid clinical improvement was followed by abrupt cessation of self-supplied topical corticosteroids. Two weeks after discontinuation of topical corticosteroids the patient presented at our clinic with flu-like symptoms, including dizziness, pains in the joints and muscles, lack of appetite and fatigue, suspected for adrenal insufficiency. The patient’ s morning serum cortisol level was 69.1 nmol / l( normal 09.00 h plasma cortisol 150 – 802 nmol / l), which was consistent with suspected HPA axis suppression( 8).
The patient was diagnosed with symptomatic tertiary adrenal insufficiency as a result of abrupt discontinua-
Fig. 1. Eczema Area and Severity Index( EASI) score during the CAFÉ and Open-Label Extension( OLE) studies.
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2936 Acta Derm Venereol 2018; 98: 601 – 602