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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