Systemic juvenile idiopathic arthritis versus adult-onset Still´s disease: the pertinence of changing the current classification criteria.

BACKGROUND: Systemic Juvenile Idiopathic Arthritis (sJIA) is a rare systemic inflammatory disease wich represents a subtype of a Juvenile Idiopathic Arthritis (JIA) according to the Classification of Edmonton. It is distinguished from other subtypes by its pathophysiology, systemic extra-articular involvement and treatment. This disease has strong similarities with Adult-onset Still`s Disease (AOSD). These diseases differing mainly in the diagnostic criteria. OBJECTIVE: To identify the similarities between sJIA and AOSD given the benefits that a change to the classification criteria would make. METHODS: Research Portuguese and English scientific papers in Pubmed database and published between 1992 and 2019 using the keywords "juvenile idiopathic arthritis"; "systemic juvenile idiopathic arthritis"; "Still´s disease" and "Adult-onset Still`s disease", having been selected the most clinically and historically relevant ones. RESULTS: The pathophysiology of SJIA has marked differences when compared to other subtypes of JIA, with a more prominent role of innate immunity and an increased production of interleukins (IL-1, IL-6 and IL-18). The sJIA presents several pathophysiological, clinical and analytical similarities with AOSD. Regarding the current diagnostic criteria (Edmonton´s for sJIA and Yamaguchi´s for AOSD), they differ mainly in the presence of arthritis, which is an essential criterion in the classification of Edmonton, while according to the classification of Yamaguchi, it is only required the presence of arthralgia. The requirement of arthritis in the initial presentation leads to delayed diagnosis in patients who present with other features of sJIA. Concerning treatment, new drugs are currently used in sJIA, allowing for a more oriented therapy in those systemic symptoms are the main problem in the long term. CONCLUSIONS: In a pathology associated to great mortality and morbidity as is sJIA, a timely diagnosis is essential, so a highly suggestive clinical history of sJIA, even in the absence of arthritis, can not be disregarded. Thus, a review of the criteria will allow a faster detection of the pathology in question and an earlier onset of the therapy aiming at a better prognosis.

Adult-onset Still's disease as a cutaneous marker of systemic disease.

Adult-onset Still's disease (AOSD) is a rare, systemic, inflammatory disorder characterized by spiking fevers, an evanescent eruption, arthritis, and multiorgan involvement. The disease has been recently classified as a polygenic autoinflammatory disorder at the "crossroads" of autoinflammatory and autoimmune diseases. The highly characteristic salmon-colored eruption is a cutaneous manifestation of a generalized inflammatory reaction and an important diagnostic criterion. In addition to the evanescent eruption, there are atypical persistent papules and plaques in many patients with AOSD. Emerging data suggest that AOSD with this typical evanescent eruption has a different clinicopathologic presentation and clinical course than AODS with atypical cutaneous manifestations. It appears that there are two subtypes of AOSD with different immunologic profiles, including (1) a systemic disease with high fever, organ involvement, and elevated levels of ferritin, and (2) a chronic disease course with arthritis as the predominant finding. These observations provide novel insight into the disease pathogenesis, suggesting that the underlying mechanisms might differ between these two forms, partially explaining the reported differences in drug response. Recent advances in the understanding of AOSD are summarized with a focus on the spectrum of cutaneous manifestations and its relationship to systemic inflammation.

[Pathophysiology, subtypes, and treatments of adult-onset Still's disease: An update]. / Données actualisées sur la physiopathologie, les phénotypes et les traitements de la maladie de Still de l'adulte.

Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.

Diagnosis and classification of adult Still's disease.

The cornerstone of adult onset Still's disease is the triad of daily fever, arthritis and rash. This syndrome remains enigmatic and most often a disease of exclusion. There are both musculoskeletal as well as systemic features. More importantly, reactive hemophagocytic syndrome may occur in patients. In this review we attempt to place this syndrome in perspective, including data on geoepidemiology, clinical and laboratory features.

Clinical manifestations of Adult-onset Still's disease presenting with erosive arthritis: Association with low levels of ferritin and Interleukin-18.

Objective: Adult-onset Still's disease (AOSD) is a clinical entity with heterogeneous etiology. We have encountered patients with AOSD who had severe polyarthritis and who fulfilled the classification criteria for rheumatoid arthritis (RA); however, most patients with AOSD typically exhibit mild arthritis. In this study, we proposed two clinical subsets of AOSD and investigated the clinically significant characteristics of the two subtypes. Methods: We retrospectively analyzed 71 consecutive patients with AOSD. We reviewed the medical records of all patients who were followed up for more than 2 years. We classified all the patients with AOSD into the following 2 subsets: an RA subtype for patients who met the criteria for RA according to the American College of Rheumatology and a non-RA subtype for patients who did not meet the criteria for RA. Results: Our results indicated that the non-RA subtype was accompanied by severe inflammatory complications, including pleuritis and hemophagocytic syndrome. In addition, the serum ferritin and serum IL-18 levels were significantly higher in patients with the non-RA subtype than in those with the RA subtype. Interestingly, only 1 patient with the RA subtype had anti-CCP antibodies, and 1 non-RA subtype patient had rheumatoid factor. These findings distinguish these patients from patients with true RA. Conclusions: There were two subsets of patients with AOSD in the examined population. Patients with high levels of IL-18 or ferritin presented with severe systemic inflammatory disorders (the non-RA subtype), and patients with low levels of IL-18 or ferritin developed severe arthritis (RA subtype).

Is Still's disease still one disease? A case of Adult-onset Still's disease showing accumulation in the carotids and the large vessels of the legs on positron emission tomography: CT images.

Adult-onset Still's disease (AOSD) is known as a systemic inflammatory disease of unknown etiology and pathogenesis, characterized by fever, skin eruptions, systemic organ involvement, and arthralgias. AOSD is difficult to diagnose because of its heterogeneous clinical manifestations and prevalence (although more prevalent in the young, onset of AOSD after the age of 60 has also been described), and absence of pathognomonic clinical features. The disease also lacks a specific diagnostic test. To date, association studies between AOSD and HLA loci have failed to indentify a genetic predisposition. The recent publication of entirely different PET-CT manifestations found in three patients who were supposed to have the same disease (AOSD), as well as the surprisingly different PET-CT images of our AOSD patient (accumulation in the carotids and large vessels of the legs), raises our suspicion that AOSD is actually not one entity but a constellation of disorders whose varying underlying pathologies are now being revealed by new imaging techniques.

[Adult onset Still's disease]. / Der adulte Morbus Still.

Adult onset Still's disease is a rare, febrile, multisystem rheumatic disease with unknown etiology, which runs an intermittent course and can either go into remission after months to years or progress to a chronic course with substantial joint destruction. The prevalence of this disease has been increasing in the last decade presumably caused by better diagnostic tools but also by a higher awareness among physicians taking care of patients with "fever of unknown origin". This review is intended to augment this trend, since research on the role of proinflammatory cytokines in this disease has led to an improved diagnostic and therapeutic repertoire over the last few years. Ferritin and interleukin-18 serum levels are valuable diagnostic parameters and blockade of interleukin-1, interleukin-6, and tumor-necrosis-factor alpha can effectively control the inflammatory activity of this disease in most cases and also in life-threatening conditions.

[Adult-onset Still's disease and hepatic angiosarcoma, a fortuitous association or a paraneoplastic syndrome: a case-report]. / Maladie de Still de l'adulte et angiosarcome hépatique, une association fortuite ou un syndrome paranéoplasique: à propos d'un cas.

Adult-onset Still's disease is a systemic disorder without specific histological feature. Diagnosis requires to rule out any other disorder including neoplasia. Nevertheless, patients with paraneoplastic adult-onset Still's disease have been reported. We report a patient with an adult-onset Still's disease who presented with a liver involvement at onset. Two years later, a liver angiosarcoma was diagnosed. This report underlines the difficulty of the diagnosis of the adult-onset Still's disease even in the presence of Yamaguchi et al.'s [J Rheumatol 19 (1992) 424-30] and Fautrel et al.'s [Medicine 81 (2002) 194-200] classification criteria and may suggest a link between the initial clinical picture and the discovery nearly two years later, of a liver angiosarcoma.

"Adolescent-onset Still's disease": characteristics and outcome in comparison with adult-onset Still's disease.

OBJECTIVES: To determine if adolescent onset systemic juvenile idiopathic arthritis (JIA) and adult onset Still's disease (AOSD) represent the same clinical continuum of disease. METHODS: Retrospective review of available clinical data on all pediatric and adult patients diagnosed with Still's disease within the last 10 years at a university hospital. Assessment of functional outcomes at last visit by clinical evaluation and HAQ or c-HAQ. RESULTS: Nine patients were identified as adolescent onset systemic JIA and were compared with 10 patients with AOSD (onset > 18 years old). No statistically significant differences were found between the two groups in terms of clinical presentation at onset and outcome at follow up. CONCLUSION: Adolescent patients presenting with systemic JIA have a disease onset and course undistinguishable from that of AOSD patients, suggesting that they represent a continuum of a single disease entity.

[Still's disease in adults: treatment with intravenous immunoglobulins]. / Maladie de Still de l'adulte: traitement par immunoglobulines intraveineuses.

INTRODUCTION: Adult onset Still's disease is a rare systemic disorder of unknown etiology occurring in young adults. The diagnosis is based upon Yamaguchi criteria. Treatment is difficult and not well codified. CURRENT KNOWLEDGE AND KEY POINTS: Non steroidal anti-inflammatory drugs (salicylates, indomethacin) are used as first-line therapy but are not efficient. Steroids are needed in 80% of cases to control systemic manifestations of adult onset Still's disease. Immunosuppressive agents, such as methotrexate, are necessary when a high dose of steroids are required. The use of intravenous immunoglobulin was rarely reported, in particular in patients refractory to non steroidal anti-inflammatory drugs. Intravenous immunoglobulin was administered at 2 g/kg of body weight during two or five days. Infusion was given monthly for four-six cycles. Long-term remission was obtained in half of the patients. Precise mechanisms of action of intravenous immunoglobulin in adult onset Still's disease remain unclear. FUTURE PROSPECTS AND PROJECTS: Intravenous immunoglobulin may represent a new treatment, particularly in patients refractory to non steroidal anti-inflammatory drugs before the use of steroids. Further prospective works are needed to confirm these preliminary optimistic data.

[Clinical study of Still's disease as a distinct disease entity].

There seems to be yet unresolved questions as to whether child-onset and adult-onset Still's disease are truly the same disease and whether adult-onset Still's disease is a disease entity independent of other rheumatic diseases in the adult. In order to clarify these issues, we have analyzed statistically the clinical features of Still's disease of various age-onset and also compared the features of adult-onset Still's disease with those of other rheumatic diseases having similar manifestations. Clinical data used for the study were those collected from 32 institutions in Japan through questionnaire method by Adult Still's Disease Research Committee, and the patients with adult Still's disease and with other rheumatic diseases were definitely diagnosed by the Committee. When the sensitivity of each of total 90 clinical items was compared between child-onset adult Still's disease (11 cases) and adult-onset Still's disease (77 cases), and between young adult-onset (16-35 years) Still's disease (48 cases) and aged adult-onset (45 years or older) Still's disease (15 cases), only 7-9% of the items showed significant difference by chi 2-test. This was the same range as when the sensitivity of the clinical items obtained from the literature of child-onset Still's disease (26 cases) was compared with that of adult-onset Still's disease (77 cases). On contrary to this range, over half of the items showed the significant difference in sensitivity when adult-onset Still's disease was compared with other rheumatic diseases such as seronegative rheumatoid arthritis (31 cases), malignant rheumatoid arthritis (25 cases), and polyarteritis nodosa (31 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult-onset Still's disease with a significant rheumatoid factor: examining proper use of diagnostic and classification criteria.

A case is presented of a 32-year-old man with classic clinical adult-onset Still's disease, who had an initially elevated (1:320) but not persistently high rheumatoid factor. Since lack of a high rheumatoid factor is one feature in the proposed classification criteria for adult-onset Still's disease, the patient was given a diagnosis of rheumatoid arthritis. The faulty reasoning behind this diagnosis of rheumatoid arthritis is discussed, focusing on the inappropriate use of classification criteria for individual clinical diagnosis, as well as the occasional need for longitudinal diagnosis.

Preliminary criteria for classification of adult Still's disease.

We have attempted to design classification criteria for adult Still's disease by analyzing the data obtained through a multicenter survey of 90 Japanese patients with this disease and of 267 control patients. The proposed criteria consisted of fever, arthralgia, typical rash, and leukocytosis as major, and sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction, and the absence of rheumatoid factor and antinuclear antibody as minor criteria. Requiring 5 or more criteria including 2 or more major criteria yielded 96.2% sensitivity and 92.1% specificity. However, an exclusion process will be needed for an accurate classification, since this disease is relatively rare.