Adult-Onset Still Disease

We conducted a retrospective observational study to describe a cohort and identify the prognostic factors in adult-onset Still disease (AOSD). Patients enrolled in this retrospective chart review fulfilled either Yamaguchi or Fautrel criteria. Candidate variables were analyzed with logistic unadjusted and adjusted regression models. Fifty-seven patients were seen in the internal medicine (75%) and rheumatology (25%) departments over a mean period of 8.4 years. The median time to diagnosis was 4 months. The course of AOSD was monocyclic in 17 patients, polycyclic in 25, and chronic in 15. The assessment of glycosylated ferritin (GF) in 37 patients was correlated with early diagnosis. Nine F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans identified the lymph nodes and glands as the main sites of hypermetabolism. Complications were frequent (n = 19), including reactive hemophagocytic syndrome (n = 8). None of the 3 deaths could be attributed to AOSD. Corticosteroid dependence, as predicted by a low GF level, occurred in 23 patients (45%). A quarter of the patients received tumor necrosis factorα blockers or anakinrawith good tolerance. Fever >39.5°C was predictive of monocyclic AOSD, while arthritis and thrombocytopenia were associated with chronic and complicated AOSD, respectively. The youngest patients had the highest risks of resistance to first-line treatments. AOSD remains difficult to diagnose. Mortality is low despite frequent complications. GF and FDG-PET scans were of value in the diagnostic approach. The condition in highly symptomatic patients evolved to systemic AOSD, whereas more progressive patterns with arthritis predicted chronic AOSD. (Medicine 2014;93: 91–99) Abbreviations: AE = adverse event, AOSD = adult-onset Still disease, BM = bone marrow, CI = confidence interval, CRP = C-reactive protein, CSs = corticosteroids, CT = computed tomography, DMARDs = disease-modifying antirheumatic drugs, ESR = erythrocyte sedimentation rate, FDG-PET = F-fluorodeoxyglucose positron emission tomography, GF = glycosylated ferritin, IL = interleukin, IVIg = polyvalent intravenous immunoglobulins, MTX = From the Hospices Civils de Lyon, Department of Internal Medicine (MGV, CB, PS), Croix-Rousse University Hospital, Lyon and Université Lyon I, Villeurbanne; Hospices Civils de Lyon, Service de Biostatistiques (DMB, JI), Lyon, CNRS UMR 5558, Equipe Biostatistique Santé, Pierre-Bénite, and Université Lyon I, Villeurbanne; Hospices Civils de Lyon, Department of Internal Medicine (AH, JN), Edouard Herriot University Hospital, Lyon; and Hospices Civils de Lyon, Department of Internal Medicine (ID), Centre Hospitalier Lyon Sud, Pierre-Bénite; France. Financial support and conflicts of interest: The author listed here has received financial support (personal or institutional) from the listed companies, unrelated to the present work: PS: Pfizer, LFB, and GlaxoSmithKline. No funding source or sponsor has been involved in the current study. The authors have no conflicts of interest to disclose. Correspondence: Pascal Sève, MD, PhD, Department of Internal Medicine, Hôpital de la Croix-Rousse, 103 Grande Rue de la Croix-Rousse, F-69317 Lyon Cedex 04, France (e‐mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000021 Medicine • Volume 93, Number 2, March 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unau methotrexate, NSAIDs = nonsteroidal antiinflammatory drugs, OR = odds ratio, PMN = polymorphonuclear neutrophils, RA = receptor antagonist, RHS = reactive hemophagocytic syndrome, SD = standard deviation, SF = serum ferritin, TNF-α = tumor necrosis factor α. INTRODUCTION First described in 1971 by Bywaters, adult-onset Still disease (AOSD) is an uncommon systemic inflammatory disorder of unknown etiology. Its prevalence is estimated to be less than 1 case per 100,000 people, and it affects predominantly young adults.30 The precise pathogenesis of this disease remains unknown, but it seems that genetically predisposed hosts develop autoinflammatory disorders triggered by macrophage cell activation and TH1 cytokines such as interleukin (IL)-1, IL-2, IL-6, IL-18, tumor necrosis factor (TNF)-α, and interferon γ. The main features of AOSD are a high spiking fever, evanescent rash, sore throat, polyarthralgia, lymphadenopathy, hepatosplenomegaly, serositis, and leukocytosis, as well as elevated liver enzymes, polymorphonuclear neutrophils (PMN), erythrocyte sedimentation rate (ESR), and serum ferritin (SF). Despite the diagnostic value attributed to high SF associated with low glycosylated fraction of ferritin (<20%), the diagnosis of AOSD remains one of exclusion. The clinical course of the disease may have 1 of 3 patterns: a self-limiting or monocyclic systemic course, an intermittent or polycyclic systemic course, and a chronic articular course. The treatment of AOSD remains empirical. Nonsteroidal antiinflammatory drugs (NSAIDs); corticosteroids (CSs); diseasemodifying antirheumatic drugs (DMARDs), such as methotrexate (MTX); and polyvalent intravenous immunoglobulins (IVIg) are usually used.11 The recent use of biologic agents in AOSD has been shown capable of improving considerably the condition of different subgroups of patients. Data have shown a most impressive response with anakinra in patients with systemic disease, whereas TNF-α blockers and tocilizumab had better results in chronic AOSD. Within this context, determining whether the clinical and laboratory features found at diagnosis can predict the outcome of AOSD would be of great value in patient management. Thus, we conducted the present study to describe a cohort of AOSD patients, identify the baseline prognostic factors that influence the clinical course of the disease, and monitor the response to treatment and the appearance of complications. PATIENTS AND METHODS