ORIGINAL ARTICLE A series of 22 patients with adult-onset Still's disease presenting with fever of unknown origin. A difficult diagnosis? Gerasimos Baxevanos & Thomas Tzimas & Georgios Pappas & Nikolaos Akritidis Received: 20 January 2010 / Revised: 1 April 2011 / Accepted: 19 April 2011 / Published online: 21 May 2011 # Clinical Rheumatology 2011 Abstract Adult-onset Still's disease (AOSD) remains a perplexing, difficult to diagnose clinical entity, with clinical characteristics that are often broad and encountered in numerous other clinical entities. This vague clinical presentation is depicted in the commonly used diagnostic criteria, as the ones by Yamaguchi and Fautrel. The authors sought to investigate how diagnostic criteria apply in a series of 22 new cases of AOSD patients presenting with fever of unknown origin (FUO) and diagnosed at the Internal Medicine Department of Hatzikosta General Hospital of Ioannina, Greece. The aims of the study were: (1) to study the incidence of AOSD and (2) to retrospec- tively apply different classifications to the data of these patients in search of a more efficient way of diagnosing these patients in the future. The annual incidence of AOSD was estimated at two new cases per 10 5 . The clinical manifestations of the patients are discussed, with an emphasis on specific manifestations being considered as criteria by Yamaguchi and Fautrel classifications. Four patients exhibited markedly increased serum D-dimers, a finding of which the potential pathophysiologic implica- tions are discussed. Serum ferritin levels have additive values, both for diagnostic and cost-reduction purposes in cases presenting as FUO; serum ferritin values are not included in any diagnostic set of criteria at present. The finding of high levels of D-dimers in AOSD needs further studies. Keywords Adult-onset Still's disease . Ferritin . Fever of unknown origin Introduction Adult-onset Still's disease (AOSD) is a systemic inflamma- tory disorder of unknown etiology that has been puzzling clinicians and researchers ever since its first description by Bywaters in 1971 [1]. Its pediatric counterpart, idiopathic systemic juvenile onset arthritis, was first observed by George Still in 1897 [2]. AOSD remains a significant differential diagnostic possibility in patients presenting with fever of unknown origin (FUO) in certain settings [3]. We have previously described a series of 16 patients diagnosed in our department up to 1995, along with their long-term follow-up and evolution [4, 5]. We here present a series of 22 patients presenting with FUO and diagnosed subse- quently with AOSD in the same department (1996 onwards), focusing on individual characteristics of the patients' clinical presentation that may be of diagnostic (according to existing disease criteria), differential diagnos- tic, or even disorientating origin (when not typical of the disease). The rationale behind our approach was that the diagnosis of AOSD is still one of exclusion and based on the fulfillment of certain criteria, the most widely accepted of which are Yamaguchi's [6]; novel, more complex in their demands, criteria, have also been recently suggested by Fautrel and colleagues [7] (Table 1). Yet, these criteria most often include broad clinical syndromes that may be G. Baxevanos : T. Tzimas : N. Akritidis Department of Internal Medicine, General Hospital of Ioannina, Ioannina, Greece G. Pappas Institute of Continuing Medical Education of Ioannina, Ioannina, Greece N. Akritidis (*) Internal Medicine Department, General Hospital “G. Hatzikosta”, Makrygianni Avenue, Ioannina 45110, Greece e-mail: nakritid@cc.uoi.gr Clin Rheumatol (2012) 31:49–53 DOI 10.1007/s10067-011-1761-y