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.

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.

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.

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.

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.

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.

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.

[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.

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.

Atypical form of Adult-onset Still's Disease with Distal Interphalangeal Joints Involvement.

BACKGROUND: A distal interphalangeal (DIP) joint involvement in the adult-onset Still's disease (AOSD) has been described in some publications but is rarely reported to be severe. We report severe DIP joints damages in a young patient with AOSD. CASE REPORT: A 22 years old patient presented to our department complaining of inflammatory joints pain associated with prolonged fever and cutaneous rash. Physical examination identified polyarthritis and hepatosplenomegaly but no lymphadenopathies. After an extensive screening for neoplastic, infectious or hematologic diseases, the patient was finally diagnosed with AOSD. Treatment based on corticosteroids was then initiated with a good response on systemic signs. However, the patient continued to have recurrent arthritis affecting wrists and proximal interphalangeal joints. A Few years later, he developed a severe and disabling DIP arthritis with signs of joint destruction on conventional radiographs and MRI. Despite the initiation of methotrexate with optimal dosage, the patient continued to have polyarticular flares. The combination of methotrexate and sulfasalazine was responsible for drug-induced hepatotoxicity and this treatment was stopped. Anti-TNFα treatment was then indicated as general signs improved but severe joints damage persisted. Unfortunately, and due to healthcare system considerations, the patient was not able to benefit from TNFα inhibitors, and remained on methotrexate treatment only. Conculsion: The distal destructive arthritis during AOSD is rare and controversial. Our patient had a severe form with resistance to conventional therapies.

Imaging Characteristics of Chemotherapy Related Adult-Onset Still Disease.

A 60-year-old man with lymphoma completed chemotherapy on October 21, 2016, with complete remission. He then received rituximab maintenance therapy. Since March 2017, he has had progressive fatigue, myalgias, rash, weight loss, diarrhea, and recurrent low-grade fever. Subsequent bone marrow biopsy and FDG PET/CT demonstrated no active lymphoma. An In-white blood cell scan showed abnormal tracer uptake on 20-hour postinjection, but not on 3-hour postinjection images, including innumerable skeleton muscle foci, multiple cutaneous foci, and persistent diffuse increased uptake in the lungs. Diagnosis of adult-onset Still disease was made accordingly. The patient's cytopenia was deemed a chemotherapy-related adverse effect.

Imaging characteristics of adult onset Still's disease demonstrated with 18F-FDG PET/CT.

The diagnosis of adult onset Still's disease (AOSD) is non­specific, and requires the exclusion of other diseases including infectious, inflammatory and malignant diseases. The current study aimed to summarize the imaging characteristics of fluorodeoxyglucose (18F­FDG) positron emission tomography (PET)/computerized tomography (CT) in patients with AOSD. The 18F­FDG PET/CT characteristic observations of 32 patients with definite AOSD were retrospectively reviewed based on visual interpretation and the semi­quantitative index of standard uptake value of maximum (SUVmax). Among 32 patients, no normal case was observed. Abnormal FDG accumulation by the spleen, bone marrow and lymph nodes was the main observation of the PET/CT images. Totals of 27 (84.4%) and 26 cases (81.3%) were identified with diffusely elevated FDG uptake by the spleen and bone marrow, respectively, and the average SUVmax was 4.2±1.1 and 4.6±0.6, respectively. A total of 20 cases (62.5%) showed lymphadenopathy with FDG uptake, with the range of SUVmax from 2.2­13.9. In addition, 7 patients (21.9%) were observed to exhibit effusion without FDG uptake, 1 case presented with abnormal FDG uptake by the skin, and another by the right shoulder joint. In addition, no abnormally elevated FDG uptake by the liver or large vessels was observed. Due to non­specific imaging features, 18F­FDG PET/CT could not be directly helpful in diagnosing AOSD. However, 18F­FDG PET/CT serves important roles in evaluating the involved extent of AOSD, and guiding the biopsy of lymph nodes, bone marrow or other tissues, which may aid in the development of novel clinical management strategies.

Tocilizumab for uncontrollable systemic inflammatory response syndrome complicating adult-onset Still disease: Case report and review of literature.

RATIONALE: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, fever spikes, arthralgia, and lymphadenopathy. AOSD usually has a good prognosis, but it can sometimes be fatal, especially when it is complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure. PATIENT CONCERNS: A previously healthy 26-year-old woman was referred to our hospital for persistent high fever and mild systemic edema. Five days later, the patient presented with dyspnea, hypotension, and anuria. Anasarca developed with massive pleural effusion, ascites, and systemic edema, resulting in an increase of 47 kg in body weight. DIAGNOSES: The patient was diagnosed as AOSD after infection, malignancy, hematologic disorders, and other autoimmune diseases were excluded. INTERVENTIONS: We administered tocilizumab, an IL-6 receptor inhibitor, intravenously in addition to cyclosporine, prednisolone, plasma exchange, and continuous hemodiafiltration. OUTCOMES: The patient's systemic condition improved. After stabilization by all medications, the patient was managed and responded to tocilizumab alone. To the best of our knowledge, this was the first case of severe SIRS complicating AOSD that was successfully treated with an anti- IL-6 receptor antibody. LESSONS: SIRS should not be overlooked in a patient with steroid-resistant AOSD and edema. Inhibitors of the IL-6 receptor can be used safely and effectively to control AOSD complicated with severe SIRS.

The role of 18F-fluorodeoxyglucose positron emission tomography in the assessment of disease activity of adult-onset Still's disease.

BACKGROUND/AIMS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been suggested as a reliable imaging technique for monitoring of disease activity in patients with adult-onset Still's disease (AOSD). Therefore, we investigated the clinical significance of 18F-FDG PET/CT in Korean AOSD patients. METHODS: Thirteen AOSD patients were included in the study. The PET/CT images were evaluated with visual and semiquantitative method using standardized uptake values (SUVs). RESULTS: The presence of increased 18F-FDG uptake was noted in 90% of clinically active AOSD patients. 18F-FDG uptake was located in the lymph node, spleen, and bone marrow. Visual grade and SUV intensity of lymph node was significantly correlated with the systemic score of AOSD. Visual grade of spleen was significantly correlated with the systemic score, erythrocyte sedimentation rate (ESR), and ferritin. Additionally, visual grade and SUV intensity of bone marrow was significantly correlated with the systemic score, ESR, leukocyte, and neutrophil. CONCLUSIONS: Visual grade and SUV intensity of lymph node, spleen, and bone marrow on 18F-FDG PET/CT scan showed significant correlations with known disease activity markers. The data suggest that 18F-FDG PET/CT scan may be a useful imaging technique for evaluation of disease activity in AOSD patients.

Parenchymal lung involvement in adult-onset Still disease: A STROBE-compliant case series and literature review.

Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971-2014) on AOSD-related PLI cases.Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non-PLI-complicated AOSD cases from the same cohort).AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD.PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication.

[Pseudo-adult Still's disease, anasarca, thrombotic thrombocytopenic purpura and dysautonomia: An atypical presentation of multicentric Castleman's disease. Discussion of TAFRO syndrome]. / Pseudo-maladie de Still, anasarque, microangiopathie thrombotique et dysautonomie : présentation atypique d'une maladie de Castleman multicentrique. Discussion du syndrome TAFRO.

INTRODUCTION: Multicentric Castleman's disease can mimic adult-onset Still disease. It is exceptionally associated with anasarca, thrombotic microangiopathy and dysautonomia. CASE REPORT: We report a 32-year-old woman with an association of oligoanuria, anasarca, thrombotic microangiopathy with features compatible with adult-onset Still disease. The outcome was initially favorable with corticosteroids, immunoglobulins and plasmapheresis but with the persistence of relapses marked by severe autonomic syndrome and necessity of high dose corticosteroids. The diagnosis of mixed type Castleman's disease, HHV8 and HIV negative, was obtained four years after the onset of symptoms by a lymph node biopsy. The outcome was favorable after tocilizumab and corticosteroids but tocilizumab had to be switched to anakinra to ensure a proper and long-lasting control of the disease. CONCLUSION: Our patient partially fits the description of TAFRO syndrome (Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly), a MCM rare variant, recently described in Japanese patients.