title: Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease.
abstract: Erdheim-Chester disease (ECD) pathophysiology remains largely unknown. Its treatment is not codified and usually disappointing. Interferon (IFN)-α therapy lacks efficacy for some life-threatening manifestations and has a poor tolerance profile. Because interleukin (IL)-1Ra synthesis is naturally induced after stimulation by IFN-α, we hypothesized that recombinant IL-1Ra (anakinra) might have some efficacy in ECD. We treated 2 patients who had poor tolerance or contraindication to IFN-α with anakinra as a rescue therapy and measured their serum C-reactive protein, IL-1β, IL-6, and monocytic membranous IL-1α (mIL-1α) levels before, under, and after therapy. Another untreated ECD patient and 5 healthy subjects were enrolled as controls. After treatment, fever and bone pains rapidly disappeared in both patients, as well as eyelid involvement in one patient. In addition, retroperitoneal fibrosis completely or partially regressed, and C-reactive protein, IL-6, and mIL-1α levels decreased to within the normal and control range. Beside injection-site reactions, no adverse event was reported. Therefore, our results support a central role of the IL-1 network, which seemed to be overstimulated in ECD. Its specific blockade using anakinra thereby opens new pathophysiology and therapeutic perspectives in ECD.
authors: Department of Internal Medicine, French National Referral Center for Langerhans Cell Histiocytosis, Hôpital Cochin, Université de Paris Descartes, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. achille.aouba@nck.aphp.fr
authors: Achille
authors: A
authors: Aouba
authors: Sophie
authors: S
authors: Georgin-Lavialle
authors: Christian
authors: C
authors: Pagnoux
authors: Nicolas
authors: N
authors: Martin Silva
authors: Amédée
authors: A
authors: Renand
authors: Françoise
authors: F
authors: Galateau-Salle
authors: Sophie
authors: S
authors: Le Toquin
authors: Henri
authors: H
authors: Bensadoun
authors: Frederique
authors: F
authors: Larousserie
authors: Stéphane
authors: S
authors: Silvera
authors: Nicole
authors: N
authors: Provost
authors: Sophie
authors: S
authors: Candon
authors: Raphaèle
authors: R
authors: Seror
authors: Mathilde
authors: M
authors: de Menthon
authors: Olivier
authors: O
authors: Hermine
authors: Loïc
authors: L
authors: Guillevin
authors: Boris
authors: B
authors: Bienvenu
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D004361:Drug Tolerance; D031249:Erdheim-Chester Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology / Q000627:therapeutic use; D053582:Interleukin-1alpha / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D002097:C-Reactive Protein