Serosal involvement in adult-onset Still's disease: A multicentre and retrospective study.

OBJECTIVES: This study evaluated the characteristics of serosal involvement in adult-onset Still's disease (AOSD). METHODS: Patients meeting the Yamaguchi classification criteria were classified into AOSD with and without serosal involvement according to their manifestations and sonography/radiography. Clinical data was retrospectively reviewed from 102 patients with AOSD in two centres. RESULTS: Forty-two patients (41.2%) had serosal involvement. The frequencies of pulmonary infiltrate and impaired liver function were significantly higher in patients with serosal involvement (p = .002 and p = .007, respectively), who also had a higher modified systemic score (p = .009). In addition, the percentages of CD3+ T cells (p < .001) and, especially, the CD8+ T cells (p = .004) were significantly increased in the peripheral blood of AOSD patients with serosal involvement. Notably, patients with serosal involvement were more likely to develop macrophage activation syndrome (p = .047) and a chronic pattern (p = .016) during the follow-up. CONCLUSIONS: Patients with serosal involvement demonstrated the more severe disease activity and different immune phenotypes; these patients were more likely to develop macrophage activation syndrome, and they may require more aggressive treatment at an early time to control their systemic inflammation.

Effectiveness of Profiling Serum IL-18 and Neopterin in Diagnosis of Adult-Onset Still's Disease Complicated by Pulmonary Tuberculosis: A Case Report.

Adult-onset Still's Disease (AOSD) is a systemic inflammatory disorder characterized by high fever, skin rashes, and joint pains, and is extremely rare in patients over 80 years of age. An 88-year-old woman was admitted with high fever lasting for > 2 weeks and arthritis of the right knee and bilateral wrists. Further examination revealed that the patient fulfilled the Yamaguchi criteria, the most sensitive and extensively used classification criteria for AOSD. After ruling out other causes and considering a greatly raised serum interleukin-18 (IL-18) level, the patient was diagnosed with AOSD. Before prednisolone therapy, active tuberculosis was excluded using chest computed tomography (CT) and an interferon-gamma release assay (IGRA). After starting the treatment, serum levels of IL-18 and acute-phase reactants were decreased gradually. However, during prednisolone tapering, fever relapsed along with increasing serum acute phase reactant levels. Her serum IL-18 level was decreased but remained at a high level, and the neopterin level was further increased. These findings suggested the onset of another disease, but not AOSD recurrence. A chest CT scan revealed new lung infiltrates. Despite the initial negative IGRA result, cultures and polymerase chain reaction tests of bronchoalveolar lavage and sputum were positive for Mycobacterium tuberculosis. She was placed on a 9-month course of anti-tuberculosis therapy and continued prednisolone tapering. She showed steady improvement and her cytokine profile showed a decrease in the IL-18 and neopterin levels. In conclusion, cytokine profiling is useful in making the diagnosis of AOSD and subsequent pulmonary tuberculosis developed during steroid therapy.

The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET). METHODS: Prospective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT. RESULTS: 240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still's disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001). CONCLUSION: 18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.

Musculoskeletal Manifestations of Non-RA Connective Tissue Diseases: Scleroderma, Systemic Lupus Erythematosus, Still's Disease, Dermatomyositis/Polymyositis, Sjögren's Syndrome, and Mixed Connective Tissue Disease.

The most common systemic rheumatologic conditions are connective tissue diseases (including rheumatoid arthritis [RA]) followed by spondyloarthropathy. With the advent of biotherapies and imaging biomarkers, development in the imaging of RA and spondyloarthropathies has received substantial attention in the literature. This article details the various musculoskeletal imaging features of the other connective tissue diseases such as scleroderma and progressive systemic sclerosis, systemic lupus erythematosus, Still's disease, dermatomyositis and polymyositis, Sjögren's syndrome, and mixed connective tissue disease.

Adult-onset Still's disease initially thought to be an odontogenic infection: A case report.

OBJECTIVE: To present a case of Adult-onset Still's disease (AOSD) initially suspected to be odontogenic inflammation. BACKGROUND: Adult-onset Still's disease is a rare, complex autoinflammatory disease and a known cause of fever of unknown origin. MATERIALS AND METHODS: The patient had both a fever and dental pain. Following meticulous examination, the patient was diagnosed with AOSD. CONCLUSION: Clinicians should keep in mind that a patient such as AOSD may visit their clinics.

[Remission of steroid-resistant Stills disease treated with anakinra, evidenced by FDG-PET/CT examination: case report]. / Remise steroid-rezistentní Stillovy nemoci pri lécbe anakinrou dokumentovaná FDG-PET/CT vysetrením: kazuistika.

After elimination of infectious causes, neoplastic causes and the systemic autoimmune disease of connective tissue, a patient with high fevers over 39 °C was diagnosed with Stills disease. High doses of prednisone led to resolution of symptoms, however after reducing the doses of prednisone to 15 mg, high fevers over 39 °C returned, as well as joint pains. The high doses of prednisone led to decompensation of diabetes mellitus even with 4 daily insulin dosages. Therefore it was proceeded to regular subcutaneous administration of anakinra once a day. Anakinra enabled the reduction of prednisone to as much as the currently administered 2.5 mg a day, but it has not so far allowed for removing glucocorticoids from the treatment completely. Activity of the disease is shown by the findings within the FDG-PET/CT examination. At the time of maximum activity of the disease there was distinct lymphadenopathy with pathological accumulation of FDG visible as well as increased accumulation of FDG in the hematopoietic bone marrow. As the disease activity decreased, the size of nodules regressed and FDG accumulation in both the lymphatic nodes and bone marrow declined. FDG-PET/CT is a suitable method for monitoring the activity of Stills disease.Key words: anakinra - Adult-onset Stills disease.

Clinical value of ¹8F-fluoro-dexoxyglucose positron emission tomography/computed tomography in patients with adult-onset Still's disease: a seven-case series and review of the literature.

OBJECTIVES: While there are a few reports describing 18F-fluoro-dexoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) findings in patients with adult-onset Still's disease (AOSD), no summary report has yet been published. In this study, we evaluated the usefulness of FDG-PET/CT for diagnosis and activity evaluation in patients with AOSD by summarizing the findings of our patients and those reported in the literature. METHODS: Seven consecutive AOSD patients who had undergone PET/CT at our department between 2007 and 2012 were included. We evaluated FDG uptake for characteristic findings in patients with AOSD. In addition, we reviewed the literature on seven previously reported AOSD patients who had undergone PET/CT. RESULTS: FDG accumulation was positive mainly in the bone marrow (100%), spleen (90.9%), lymph nodes (80.0%) and joints (75.0%). In addition, FDG uptake was positive in the pericardium, pleura, salivary glands, eyelids, muscle and major blood vessels. Six patients underwent follow-up FDG PET/CT for evaluation of treatment efficacy. Follow-up PET/CT showed diminished FDG accumulation in the bone marrow, spleen and lymph nodes, with maximum standardized uptake value (SUVmax) being substantially reduced from 4.03 ± 0.95 to 2.20 ± 0.75 (p = 0.04), 4.04 ± 1.10 to 2.55 ± 1.13 (p = 0.04) and 5.63 ± 4.99 to 2.10 ± 1.91 (p = 0.11), respectively. No significant correlation was found between SUVmax in each lesion and the laboratory data, except for a significant correlation between lactate dehydrogenase (LDH) and spleen SUV. CONCLUSIONS: FDG-PET/CT is useful for long-term assessments of AOSD activity in individual patients. However, PET/CT findings alone are not sufficient to make a differential diagnosis of AOSD versus malignant lymphoma.

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.

Whole-body fluorodeoxyglucose positron emission tomography/computed tomography in patients with active polymyalgia rheumatica: evidence for distinctive bursitis and large-vessel vasculitis.

OBJECTIVES: To investigate fluorodeoxyglucose (FDG) accumulation in large joints, bursas, and large vessels in patients with polymyalgia rheumatica (PMR) using 18-FDG positron emission tomography/computed tomography (PET/CT) and to differentiate PMR from similar diseases. METHODS: Fourteen untreated patients with active PMR and 17 control patients with rheumatoid arthritis (n = 11) or other active rheumatic diseases (n = 6) underwent 18-FDG PET/CT. FDG uptake in large joints, bursas and vertebral spinous processes was evaluated by calculating maximum standardised uptake values and by visual scoring (scale 0-4). PET scan images were scored in seven vascular regions, and total vascular scores (range 0-21) were calculated. RESULTS: Polymyalgia rheumatica patients showed increased FDG uptake in ischial tuberosities, greater trochanters, and lumbar spinous processes. Positive results at two or more of these sites showed high sensitivity (85.7%) and specificity (88.2%) for the diagnosis of PMR, and shoulder or hip-joint involvement showed low disease specificity. High FDG accumulations were found in the aortas and subclavian arteries of two PMR patients who were asymptomatic for temporal arteritis and scanty synovium and perisynovium, based on FDG uptake. PET/CT images of the 12 PMR patients without apparent vascular involvement showed synovitis and/or perisynovitis. CONCLUSIONS: Fluorodeoxyglucose-PET/CT may be useful for the detection of PMR lesions, which are difficult to identify using other methods.

[Adult refractory Still disease with atypical articular manifestations: efficacity of interleukin-6 antagonists (tocilizumab)]. / Atteintes articulaires atypiques au cours d'une maladie de Still de l'adulte réfractaire : efficacité des antagonistes de l'interleukine-6 (tocilizumab).

INTRODUCTION: Tocilizumab is a humanized monoclonal antibody directed against interleukin-6 receptor and is beginning to be reported as effective in some cases of Still's disease refractory in adults (ASD). ASD is rare, heterogeneous, with unpredictable evolution. The distal destructive arthritis represents a possible complication. PATIENT: We report an unusual case of adult-onset Still's disease with severe distal interphalangeal destructive arthritis with refractory early and prolonged remission after the first tocilizumab infusion. CONCLUSION: Tocilizumab can be used in patients with refractory ASD after failure or intolerance of conventional treatments.

Adult onset Still's disease: review of 41 cases.

OBJECTIVES: To describe the clinical, laboratory and radiological features, treatment and prognosis of patients with adult onset Still's disease (AOSD). METHODS: Specific clinical features were retrospectively recorded in 41 patients fulfilling the Yamaguchi criteria. Patients were reviewed in two academic hospitals with a referral area of 700,000-1,000,000 inhabitants. Laboratory tests including haemogram, ferritin, biochemistry and autoimmunity were reviewed. Radiological studies, treatment and ACR functional class were determined. RESULTS: Forty-one patients with AOSD were identified, 25 of whom were female. Mean age at diagnosis: 38.19 years (range 17-68). Feverish polyarthritis was the most common clinical presentation. Acute phase reactants were invariably high in all patients. Serum ferritin levels were elevated in 86% of patients. Anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) were negative in all patients except one. The course of the disease was monocyclic in 44% of the patients, polycyclic in 26%, and chronic articular in 30%. ACR class was as follows: 29 (72.5%) class I, 7 (17.5%) class II, 2 (5%) class III and 2 (5%) class IV. As for the treatment received, aspirin or NSAIDs controlled the disease in eight patients (19.5%) and high-dose corticosteroids (0.5-1 mg/kg/day) in 32 (78%). Almost half of the patients (49%) required an additional diseasemodifying agent, usually methotrexate. Finally, in seven of them (17%) a biological treatment with TNF-α or specially anti-IL-1 had to be added to control the disease. CONCLUSIONS: The clinical and laboratory findings were similar to previous studies. Anti-CCP antibodies were almost always negative. A monocyclic course was associated with a good prognosis. Most of the patients were in ACR functional class I and II. Biological agents were required in 7 patients (17%).

A case of adult-onset Still's disease complicated with atypical pulmonary defect.

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition of unknown origin and pathogenesis. Pulmonary involvement is rare and includes pleural effusion and transient pulmonary infiltrates. We describe and discuss difficulties in the diagnosis of severe respiratory symptoms with uncommon radiological and histological findings and serious prognostic implication in a 24-year-old woman with a severe form of AOSD with destructive arthritis and hematological complications.

Total metabolic lesion volume of lymph nodes measured by 18F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still's disease.

BACKGROUND: To investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still's disease (AOSD). METHODS: Fifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated. RESULTS: High 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%. CONCLUSIONS: The glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.

Evaluating the multivisceral involvement on adult-onset Still's disease to retrieve imaging-based differences in patients with and without macrophage activation syndrome: results from a single-centre observational study.

In this study, we aimed at describing the multivisceral involvement on adult-onset Still's disease (AOSD) to retrieve imaging-based differences in patients with and without macrophage activation syndrome (MAS). From our historical cohort, patients were assessed among those who underwent a total body CT scan. Clinical and CT scan characteristics of AOSD patients with and without MAS were compared. Out of 39 AOSD patients evaluated, 14 were complicated by MAS. These patients showed higher values of ferritin and systemic score. AOSD patients with MAS presented a higher prevalence of lung disease, hepatomegaly, splenomegaly, abdominal effusions, and lymph node enlargement than others without this complication. In addition, the presence of these manifestations significantly correlated with the systemic score, furtherly reinforcing its prognostic value. Due to the specific design of our study, our findings could be burdened by a selection bias since assessing those patients underwent a total body CT scan. Thus, these data should be prudently generalised suggesting the need of further studies to fully elucidate this issue. Our findings showed a higher prevalence of multiorgan involvement in AOSD patients with MAS, suggesting imaging-based differences, although other studies are needed to fully assess this issue. Pulmonary disease, hepatomegaly, splenomegaly, lymph node enlargement, and abdominal effusions were associated with a more aggressive subset of AOSD. Key Points •The importance of an accurate assessment AOSD multivisceral involvement is suggested since it is associated with life-threatening complications. •A higher prevalence of multiorgan involvement in AOSD patients with MAS could be recognised, than others without this complication, suggesting imaging-based differences. •AOSD multivisceral involvement may correlate with the systemic score, furtherly reinforcing its prognostic value.

Efficacy of abatacept in a refractory case of adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder, characterized by spiking fever, skin rash, and arthritis. First-line treatment consists of corticosteroids. Methotrexate is commonly used in resistant cases or as a steroid-sparing drug. The availability of biologic drugs in the rheumatic diseases, such as anti-TNFs and IL-1ra, has allowed to treat very refractory cases of AOSD and provided new clues for the pathophysiology. However, anakinra and anti-TNFs may also fail or may be contraindicated in AOSD, and other treatment strategies are then necessary. Given that T cell activation may be a relevant part of the AOSD pathophysiology, abatacept, CTLA4IgFc, was administered in a 57-year-old man with AOSD failing traditional DMARDs and to anti-IL-1 and anti-TNF therapies, with a good outcome.

Use of methotrexate in adult-onset Still's disease.

Adult-onset Still's disease, a febrile, multisystem rheumatic disease, has variable outcomes. Some patients experience remission after a single or multiple inflammatory episodes, while others progress to a chronic course with substantial joint destruction. Although no controlled clinical trials with immunosuppressive agents in this disease have been reported, a number of small uncontrolled studies and case reports describe the use of methotrexate therapy. Methotrexate has shown efficacy for the control of systemic and articular symptoms and its favourable safety profile appears similar to that seen in other rheumatic diseases, when for this indication. The combination of methotrexate and corticosteroids has, over the years, become the first step in the standard of care in adult-onset Still's disease. If the response to this treatment is incomplete, additional therapies, such as biologic agents may be appropriate.

Clinical significance of ¹8F-fluoro-dexoxyglucose positron emission tomography in patients with adult-onset Still's disease: report of two cases and review of literatures.

Adult-onset Still's disease (AOSD) is a multi-systemic inflammatory disease that usually presents with high fever and variable systemic features. The pathogenesis and etiology of AOSD have not yet been clearly determined. In addition, there is no diagnostic test for AOSD. Even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, useful imaging studies for the diagnosis or follow-up of AOSD have not been developed. We performed (18)F-fluoro-dexoxyglucose positron emission tomography ((18)F-FDG PET) on two AOSD patients who presented with a fever of unknown origin. In these patients, we initially identified abnormally increased FDG uptake in multiple lymph nodes, the spleen, or bone marrow. We then identified significantly decreased uptake during a follow-up study. On the basis of these cases, we suggest that (18)F-FDG PET may have the potential in the diagnosis of AOSD, as well as monitor clinical changes in the disease. More further investigation of (18)F-FDG PET in AOSD is needed in larger population.

Delayed ascending aortic pseudoaneurysm in an adult onset Still's disease patient with previous mitral valve and aortic root replacement.

A 59-year-old female patient with adult onset Still's disease (AOSD) presented with hemoptysis and pseudoaneurysm from an aortic root vent cannulation site that was created 4 years earlier for combined mitral and aortic valve surgery. The pseudoaneurysm was successfully repaired and the patient remained well during a follow-up period of 20 months.

FDG PET/CT used in identifying adult-onset Still's disease in connective tissue diseases.

PURPOSE: To explore the 18F-fluoro-dexoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging characteristics of adult-onset Still's disease (AOSD) and its significance in differential diagnosis from other connective tissue diseases (CTDs). METHODS: FDG PET/CT images of 54 patients with AOSD and 66 with other CTD from patients suffering from fever of unknown origin (FUO) were retrospectively studied and compared with 40 healthy controls. Clinical and PET/CT characteristics of AOSD and other CTDs were compared, and SUVmax (maximum standardized uptake value) was used to analyze the differences of FDG uptake in the blood pool, liver, spleen, bone marrow, and hyperplastic lymph nodes between the AOSD and other CTDs. The SUVmax ratios of the spleen, bone marrow, and lymph nodes to the liver were used to establish the diagnostic criteria for differential diagnosis of AOSD, and its diagnostic efficiency was evaluated. RESULTS: Positive findings are presented in 53/54 (98.1%) AOSD patients and 61/66 (92.4%) other CTD patients in PET/CT imaging. AOSD manifested as diffusely increased FDG uptake in the spleen and bone marrow, and multiple reactive hyperplasia lymph nodes are symmetrically distributed mainly in the neck and axilla, while other organs were seldom involved. Although these abnormalities could be seen in other CTDs, its incidence and uptake value were both higher in AOSD. If two or more of the following three standard were met, the sensitivity, specificity, and accuracy of diagnosing AOSD could reach 90.7%, 92.4%, and 91.7%, respectively: ① spleen SUVmax/liver SUVmax ≥ 1.2 and/or bone marrow SUVmax/liver SUVmax ≥ 1.4; ②symmetrically distributed reactive hyperplastic lymph nodes mainly in the neck and axilla with a lymph node SUVmax/liver SUVmax ≥ 1.8; and ③ no other abnormal uptake found in other organs. CONCLUSION: Characteristic manifestations in AOSD were found on FDG PET/CT. These findings could help to identify AOSD from the other CTDs, especially in cases of fever of unknown origin, where it can assist in identifying the cause. Key Points • Image characteristics of FDG PET/CT in adult-onset Still's disease were described. • FDG PET/CT helps in identifying adult-onset Still's disease from the other connective tissue diseases. • FDG PET/CT imaging standard for diagnosing adult-onset Still's disease were established.

A case of adult-onset Still's disease complicated with diffuse alveolar hemorrhage.

Adult-onset Still's disease (AOSD) is an inflammatory disease that presents with a variety of clinical symptoms. Pulmonary involvement is well-known in AOSD and is seen in up to 53% of AOSD cases, with the most common pulmonary diseases being pleural effusion and transient pulmonary infiltrates. We present the first case of chronic AOSD complicated with diffuse alveolar hemorrhage during the acute flare of the disease.