Screening for Adrenal Insufficiency During Dermocorticoid Reduction in Bullous Pemphigoid (BP)

The braking of the corticotropic axis is well established during the induction phase of superpotent topical corticosteroid therapy (clobetasol propionate) in bullous pemphigoid (BP). But the evolution of the corticotropic axis in the following months, especially during the tapering of topical steroids has never been studied. The objective of this study is to evaluate the prevalence of adrenal insufficiency during the topical corticosteroid therapy tapering in patients treated according to current recommendations.

The secondary objectives of the study are :

* to evaluate the presence of other clinico-biological signs of adrenal insufficiency (hypotension, hypoglycemia and/or hyponatremia)
* to compare the characteristics of patients with adrenal insufficiency to those without in order to identify potential risk factors for adrenal insufficiency in BP.

BP is the most common autoimmune bullous dermatosis, with 400 incident cases per year in France and an estimated annual mortality rate of 30%. It affects very old and frail patients, with an average age of 80 years.

High potency topical corticosteroids is the first line therapy, with a high dose applied to the entire tegument for at least 4 months according to current guidelines. In this high potency topical therapy, a braking of the corticotropic axis has been reported during the initial phase of treatment, at the highest doses, explained by the transdermal and systemic passage of dermocorticoids. Monitoring if natural cortisol secretion will start again has never been studied during the tapering of topical corticosteroid therapy, and its under-diagnosis could be deleterious for patients. The French guidelines currently recommends hydrocortisone supplementation at the time of waning from less than 20 g of clobetasol propionate per week, but without any data supporting it.

Prospective multicenter study coordinated by the Bordeaux Dermatology Department and conducted within the French study Group on autoimmune bullous diseases, will aim to include 50 patients with a diagnosis of bullous pemphigoid and treated according to recommendations.

Serum dosage of Cortisol concentration will be measured on two occasions, at the last two steps of the corticosteroid tapering (20-40g, twice a week and 20-40g once a week). If necessary, a Synacthen® test will be performed in addition.

Eligibility Criteria:
Inclusion Criteria:

* Male or female at least 18 years of age
* BP diagnosis with at least 3 of the following 4 criteria:

  * Age greater than 70 years
  * Absence of mucosal involvement
  * Absence of atrophic scarring
  * No predominance of head and neck
* Skin biopsy with subepidermal cleavage and :

  * FD with Ig and/or C3 deposits along the basement membrane
  * And/or positive serum anti-BP180 and/or anti-BP230 antibodies
* Treated with clobetasol propionate, with or without background treatment (methotrexate, mycophenolate mofetil, IV Ig, omalizumab, rituximab)
* Treatment with clobetasol propionate 0.05%, 20 to 40 g per application, twice a week for at least one month
* Affiliated to a social security regimen ( without AME)
* Free, informed and expressed consent (confirmed in writing)

Exclusion Criteria:

* Old or ongoing adrenal insufficiency
* Systemic corticosteroid therapy of more than 1 month in the previous 3 months and/or more than 3 months in the previous 12 months, or in the 7 days prior to the cortisol test
* Immuno-induced bullous pemphigoid (anti-PD1, PDL1 and/or anti-CTLA4)
* Impossible to perform a blood test between 7:30 and 8:30 am