Adult-onset Still's Disease Research Articles

Immune cartography of macrophage activation syndrome in the COVID-19 era.

A hyperinflammatory ‘cytokine storm’ state termed macrophage activation syndrome (MAS), culminating from a complex interplay of genetics, immunodeficiency, infectious triggers and dominant innate immune effector responses, can develop across disparate entities including systemic juvenile idiopathic arthritis (sJIA) and its counterpart adult-onset Still disease (AOSD), connective tissue diseases, sepsis, infection, cancers and cancer immunotherapy. Classifying MAS using the immunological disease continuum model, with strict boundaries that define the limits of innate and adaptive immunity, at one boundary is MAS with loss of immune function, as occurs in the ‘perforinopathies’ and some cases of sJIA–AOSD. Conversely, at the other boundary, immune hypersensitivity with gain of immune function in MHC class II-associated sJIA–AOSD and with chimeric antigen receptor (CAR) T cell therapy also triggers MAS. This provides a benchmark for evaluating severe inflammation in some patients with COVID-19 pneumonia, which cripples primary type I interferon immunity and usually culminates in a lung-centric ‘second wave’ cytokine-driven alveolitis with associated immunothrombosis; this phenomenon is generally distinct from MAS but can share features with the proposed ‘loss of immune function’ MAS variant. This loss and gain of function MAS model offers immune cartography for a novel mechanistic classification of MAS with therapeutic implications.

Diagnosis and Treatment of Adult-Onset Still’s Disease

Adult-onset Still’s disease (AOSD) is an obscure disease that is usually diagnosed after the exclusion of other febrile diseases, including other autoimmune, infectious, and malignant diseases. Although definitive diagnostic criteria and treatment guidelines for AOSD are thus far lacking, the typical manifestations of AOSD have been identified and effective medications for remission and maintenance have been proposed. The pathophysiology of the AOSD is unclear, but diagnostic criteria and treatment guidelines for AOSD can be established by determining its core etiology and conducting clinical trials of previously tested immunosuppressants and biologics.

IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives.

Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

Characteristics and risk factors of relapses in patients with adult-onset Still's disease: a long-term cohort study.

To describe the detailed characteristics and explore the potential risk factors of relapses in patients with adult-onset Still's disease (AOSD). We enrolled patients with AOSD admitted to the Department of Rheumatology and Immunology, Ruijin Hospital from August 2016 to September 2019. Kaplan-Meier curves and the log rank test were used to estimate the cumulative relapse probability and persistent remission rate before the first occurrence of relapse. The multivariate Cox proportional hazard method was utilized to identify risk factors associated with relapses of AOSD. A total of 122 patients with AOSD were enrolled with a median follow-up of 12.6 months. Among them, 26 (21.3%) patients had at least one relapse. The cumulative relapse rates of AOSD patients were 14.42%, 21.79%, 24.81% and 28.57% at 6, 12, 18 and 36 months, respectively. According to the multivariate analysis, intensive treatment (odds ratio: 6.848; 95% CI: 2.441, 19.211) and macrophage activation syndrome (odds ratio: 4.020, 95% CI: 1.564, 10.322) were associated with increased risk of relapse. Our study indicated that relapses occurred in at least one-fifth of patients with AOSD, and patients with high disease severity at initial attack may have an increased risk of relapse, which needs more intensive therapy and close follow-up.

Cytokine Storm in Coronavirus Disease 2019 and Adult-Onset Still’s Disease: Similarities and Differences

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still’s disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1β and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.

Dissecting the clinical heterogeneity of adult-onset Still's disease: results from a multi-dimensional characterization and stratification.

To stratify adult-onset Still's disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14724 (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10 (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88 (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457 (1298) ng/ml and 54.98 (48.67) mg/l, respectively]. Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients.

Clinical Characteristics of Japanese Patients with Elderly-Onset Adult-Onset Still's Disease.

The aim of this study was to compare the characteristics of Japanese patients with elderly-onset Adult-onset Still's disease (AOSD) and those with younger-onset AOSD. Patients were classified into elderly-onset (≥ 65 years, n = 20) and younger-onset (< 65 years, n = 62) groups according to age at AOSD diagnosis. Analyses included the comparison of clinical features, treatments, and Pouchot and modified Pouchot (mPouchot) scores between the two groups. The frequencies of sore throat, lymphadenopathy, and splenomegaly were significantly lower in the elderly-onset group than in the younger-onset group (30.5% vs. 80.6%, p = 0.0004; 15.0% vs. 54.8%, p = 0.0019; 30.0% vs. 61.3%, p = 0.0203; respectively). There were no significant differences in the frequencies of complications, such as macrophage activation syndrome and disseminated intravenous coagulation, between the patients with elderly-onset or younger-onset AOSD. Serum ferritin levels were higher in the elderly-onset group than in the younger-onset group, albeit without statistical significance (median, 9,423 vs. 4,164 ng/mL, p = 0.1727). Pouchot score was lower in the elderly-onset group than in the younger-onset group (median score, 5.5 vs. 4.0, p = 0.0008); however, there was no significant difference in the mPouchot score between the two groups. Our analyses revealed that elderly-onset AOSD was associated with certain characteristics that were distinct from those of younger-onset AOSD and that the disease severity in patients with elderly-onset AOSD, determined by Pouchot score at the time of AOSD diagnosis, was similar to or less than that in patients with younger-onset AOSD.

ALLERGIC DISEASES IN ADULT-ONSET STILL'S DISEASE AND RHEUMATOID ARTHRITIS

A high prevalence of allergic diseases was found in patients with adult-onset Still's disease (AOSD). However, the relative prevalence is unknown compared with other diseases. We sought to compare the prevalence of allergic diseases in the control group of patients with rheumatoid arthritis (RA). We retrospectively examined consecutive patients diagnosed with AOSD or RA in our hospital from 2010 to 2020. The patients with AOSD met the preliminary criteria for classification of AOSD. The patients with RA met the EULAR/ACR 2010 criteria. We included patients with RA without other rheumatic diseases. The analysis was performed on six types of allergic reactions: food allergy, drug allergy, allergic contact dermatitis, allergic rhinitis and/or allergic conjunctivitis, and asthma. Twenty-four patients with AOSD and 409 patients with RA were enrolled. The median ages (AOSD, RA) were 46.6, 68.2 years old. Females were 83.3%, 78.0%. Fifty% of AOSD patients and 34.5% of RA patients presented at least one type of allergic diseases (p = 0.12). These included food allergy (4.2%, 6.4%: p = 1.0), drug allergy (37.5%, 16.6%: p = 0.02), allergic rhinitis/allergic conjunctivitis (25.0%, 8.6%: p = 0.02), contact dermatitis (4.2%, 4.4%: p = 1.0), and asthma (4.2%, 5.9%: p = 1.0). Patients with AOSD had a higher prevalence of drug allergy, and allergic rhinitis/allergic conjunctivitis than patients with RA.

A New Predictive Scoring Model for Differential Diagnosis of Adult-Onset Still's Disease and Lymphoma in Patients with FUO: A Cross-Sectional Pilot Study

Background: Adult-onset still's disease (AOSD) and lymphoma are the most common benign and malignant causes of fever of unknown origin (FUO), respectively. This study aimed to establish a reliable and easy-to-used scoring model based on clinical information, laboratory characteristics and 18 F-FDG PET/CT images for the differential diagnosis of these two diseases. Methods: A development cohort including AOSD (n=70) and lymphoma (n=37) patients was used to establish a scoring model based on the features of 18 F-FDG PET/CT images. The scoring model was then validated in a validation cohort of 15 AOSD and 12 lymphoma patients. The features of involved bone marrow, spleen, lymph nodes, and other organs or tissues displayed on PET/CT images were compared. Multiple logistics regression and decision tree analysis were used to establish the scoring model. Findings: Six features that could significantly differentiate these two diseases were selected to establish a scoring model discriminating AOSD from lymphoma, including (1) WBC count ≤ 10×10 9 /L (one point); (2) Ferritin ≤ ULN (one point); (3) No abnormal bone marrow metabolism (one point); (4) TLG total > 9·0 (one point). After decision tree analysis, it showed that a score ≤ 1 indicates AOSD, and a score ≥ 3 strongly suggested lymphoma, with a sensitivity of 81·1% and specificity of 90·0% in the development cohort, and a sensitivity of 58·3% and specificity of 100% in the validation cohort. Interpretation: Our scoring model showed good diagnosis performance in distinguishing AOSD from lymphoma. Funding: (YG2017QN58, YG2017MS61), Shanghai Municipal Key Clinical Specialty (shslczdzk03403), and Shanghai Garden Rising Star Youth Medical Talent Training Funding Program. Declaration of Interest: We declare no competing interest. Ethical Approval: This study was approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Adult-Onset Still Disease, their Relationship with Baseline Disease Activity and Subsequent Disease Course: A Single-Center Retrospective Cohort Study

Introduction: Adult-onset Still Disease (AoSD) is a rare systemic polygenic nonfamilial autoinflammatory disease of unknown aetiology. The long-term course of the disease can be categorised in three different definitions including self-limited course, intermittent course or chronic course. Recently, Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) were investigated in various rheumatic diseases as an informative markers in evaluating severity of inflammation and disease activity. Aim: To explore association between baseline NLR, PLR, disease activity score and subsequent disease course in patients with AoSD. Materials and Methods: This retrospective cohort study enrolled 61 patients with AoSD and 61 age-matched patients with Fibromyalgia Syndrome (FMS). Pouchot score was specifically used in AoSD patients to assess disease activity based on symptoms, physical examination findings and laboratory results from April 2020 to July 2020. Patients with AoSD were subgrouped into three groups: self-limited; intermittent; and chronic course. The association of NLR and PLR with disease activity score was analysed between groups by using independent samples t-test, Mann-Whitney U test and Kruskal Wallis Variance Analysis. Differences between categorical variables were analysed using chi-square test. A p≤0.05 was considered statistically significant. Results: The mean follow-up of the 61 patients with AoSD was 74 months (range, 14-169). Eighteen patients (29.5%) had a self-limited disease course, nine (14.8%) an intermittent disease course and thirty four (55.7%) a chronic disease course. AoSD patients had significantly higher serum NLR, PLR and lower Mean Platelet Volume (MPV) values than FMS patients {6.68 (1.67-19.7), 1.83 (1.1-4) p=0.0001; 187 (82.9-549), 114 (72-246) p=0.0001; 8.3 (6.4-11.3), 9.3 (7.7-11.7) p=0.0001, respectively}. NLR, PLR and Pouchot score were similar among AoSD subgroups, which were grouped according to disease pattern. The majority of patients in the self-limited and chronic course groups had higher baseline Pouchot score without statistical significance. The NLR and C-Reactive Protein (CRP) were significantly higher in AoSD patients with active disease than inactive disease {7.02 (1.8-19.7), 4.17 (1.67-14.8) p=0.06; 13 (1.9-29.5), 9 (1.6-20.9) p=0.046, respectively)}. Conclusion: High NLR and elevated CRP levels are related to active disease in AoSD patients. Although NLR, PLR and Pouchot score were similar among subgroups, patients with a chronic course or self-limited course had higher NLR values and more active disease at diagnosis compared with patients with an intermittent course.

Update on the therapy of adult-onset Still's disease with a focus on IL-1-inhibition: a systematic review.

Introduction:The past decade has seen increasingly rapid advances in understanding the pathogenic nature of adult-onset Still’s disease (AOSD) and its shared symptoms with the systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) blocking agents are key elements in the treatment. In this updated systematic review, we focus on studies on efficacy and safety of IL-1 blockers published in the past 5 years and review on latest available therapies.Methods:We conducted searches using Medline, Biosis, Embase, and Cochrane databases between 2016 and 2021 using the terms AOSD, IL1, IL-18, canakinumab, anakinra, tadekinig, and rilonacept and if applicable their trade names. Duplicates, case reports, and manuscripts with incomplete data were excluded.Results:Of the 1013 screened publications, 17 were eligible after careful selection. We only found two published randomized controlled studies in the past 5 years. Review manuscripts of rare diseases, like our work, usually rely on retrospective studies and case series. Anakinra and canakinumab can be successfully used as first- or further-line treatment in patients with AOSD refractory to steroids. A homogeneous outcome is not established yet. Thus, a combination of clinical and laboratory tests can support the experienced clinician in the decision-making process.Conclusion:The approval of IL-1 inhibitors for AOSD brought us into a new era in the treatment of AOSD. The overall efficacy-safety profile of the IL-1 inhibitors is favorable reflecting a targeted approach as standard of care. We can expect that the successful treatment of AOSD with IL-1 inhibition will facilitate further clinical and basic research with impact on other auto-inflammatory and hyper-inflammatory conditions.

The role of platelet to mean platelet volume ratio in the identification of adult-onset still's disease from sepsis

OBJECTIVES:Inflammatory factors exert a significant role in the development of adult-onset Still’s disease (AOSD) and sepsis. Although platelet counts and platelet parameters have long served as indicators for inflammatory diseases, their role in the differential diagnosis between adult-onset stilĺs disease and sepsis remains unclear. We designed this retrospective study to explore whether the platelet to mean platelet volume (MPV) ratio (PMR) can help to distinguish AOSD from sepsis.METHODS:A total of 110 AOSD patients and 84 sepsis patients were enrolled in the study. Seventy-three AOSD patients and 56 sepsis patients between January 2010 and June 2017 were enrolled in the test cohort to analyze PMR values, which was then validated in the validation cohort (37 AOSD patients and 28 sepsis patients between June 2017 and December 2019).RESULTS:The values of PMR were significantly higher in AOSD patients than in sepsis patients (test cohort, validation cohort, and entire cohort), In the test cohort, logistic regression analysis showed that PMR was an independent risk factor of AOSD (odds ratios [OR]: 9.22, 95% confidence interval [CI] 2.15-39.46, p=0.003). Further receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve was 0.735 (95% CI 0.631-0.839, p<0.001) for PMR alone and 0.925 (95% CI 0.869-0.980, p<0.001) for the combination of PMR and serum ferritin. Consistently, the validation cohort exhibited analogous results.CONCLUSIONS:PMR could be used as a single indicator or a complementary indicator to distinguish AOSD from sepsis.

Adult-onset Still's disease in pregnancy: case report and literature review

Background: Adult-onset Still’s disease (AOSD) is a clinical syndrome whose etiology and pathogenesis remain unclear. The clinical symptoms of AOSD mainly include fever, erythema, arthralgia and muscle pain, which cannot be diagnosed by specific auxiliary examination and can initially attack during pregnancy. The identification of the disease is revealed by a diagnosis of exclusion. Currently, the relationship between pregnancy and AOSD remains unclear. Here, we report on one case of AOSD during pregnancy that was admitted to the Beijing Anzhen Hospital affiliated to Capital Medical University. A 24-year-old woman was admitted to hospital due to intermittent fever, a history of pain and swelling of the large joints at 33 weeks gestation. After the diagnosis of AOSD, the symptoms relieved with medication. The patient delivered a premature, 3450 g baby successfully. Conclusions: The diagnostic criteria of pregnancy complicated by AOSD mainly depends on a diagnosis of exclusion. The literature both at home and abroad shows that the onset of AOSD is closely related to pregnancy, and that pregnancy is one of its predisposing factors. Its clinical manifestations are arthritis, arthromyalgia, fever, pharyngitis and so on, which involve multiple systems. There is no highly specific approach available in the laboratory examination and imaging for this disease.

Derivation and Validation of Adult Still Activity Score (SAS)

Background/Aim: Adult-onset Still’s disease (AOSD) is a multi-systemic, autoinflammatory disorder. Several activity scores have been proposed but none of them have been adopted universally. Our aim was to create a clinician-friendly activity scoring system by using simple clinical and laboratory parameters. Methods: AODS patients according to Yamaguchi criteria were included in this cross-sectional, multi-center study. Derivation and validation cohorts were constituted. Demographic, clinical and laboratory evaluation at study visit; patients’, and physicians’ global assessments of disease activity (both VAS/ Likert scale) were recorded. To develop the score; ordinal logistic regression model was used to determine independent predictors of patient’ global assessments of disease activity. Clinically and statistically significant variables were weighted according to regression coefficients. Then, performance of the score was tested on the validation cohort. Results: Total of 197 consecutive AOSD patient (125 in derivation, 72 in validation cohorts) were included. Final Still Activity Score was fever (2 points), arthralgia (2 points, plus 1 point if arthritis was present in ≥2 joints), neutrophilia≥65% (1 point) and ferritin≥350 ng/mL (1 point) (maximum of 7 points). The SAS yielded an AUC value of 0.98(0.96-1.00) in the derivation cohort and 0.91(95%CI:0.85-0.98) in the validation cohort to discriminate high AOSD activity from moderate-inactive AOSD. Correlation of SAS with PtGA was 83% for the derivation cohort and 76% for the validation cohort. Conclusions: SAS has shown a good test performance to distinguish active AOSD patients from the others. SAS may be a useful method for evaluating disease activity of AOSD patients in daily practice. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The present study was conducted in compliance with the Helsinki Declaration and was approved by the Local Ethics Committee of Hacettepe University (GO- 20/824). A written informed consent form was completed by all participants.

A case report of Adult Onset Still’s Disease and Kikuchi Fujimoto lymphadenitis-challenges and learning points

Background: Adult Onset Stills Disease (AOSD) and Kikuchi Fujimoto Lymphadenitis (KFL) are both rare Rheumatological diseases. Co-occurrence is very rare. Case Presentation: This is a case of AOSD and KFL co-occurrence presenting with polyarthritis, rash, and B Symptoms. Elevated serum lactate dehydrogenase and ferritin with anemia and lymphadenopathy raised suspicions of lymphoma. Histology confirmed KFL and clinical features, and raised ferritin confirmed AOSD. After starting sulfasalazine, the patient was admitted to the hospital with ‘Drug Reaction with Eosinophilia and Systemic Symptoms’ (DRESS) Syndrome. Prior to sepsis exclusion, Gentamicin was given and subsequent hearing loss was noted. Sustained remission was achieved with Tocilizumab and azathioprine. Tocilizumab was stopped during pregnancy. Conclusion: The diagnostic challenges of two rare overlapping Rheumatological diseases are highlighted. An early distinction of disease flares or drug reactions from sepsis is difficult. Risk-benefit ratio consideration of continuing successful treatments in pregnancy is acknowledged.

Water-exacerbated Pruritus and a Flagellate Eruption: Adultonset Still’s Disease Occurring in Association with Influenza A Virus Infection

Adult-onset Still’s disease (AOSD) presents with fever, systemic symptoms and rash. Atypical presentations are increasingly described. Uncommonly, viral-associated AOSD occurs. We report AOSD presenting in a 30-year-old male with waterexacerbated pruritus, a subsequent flagellate eruption, and associated influenza A virus infection.

Adult-onset still's disease masquerading as hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematological condition caused by the overactivation of macrophages leading to widespread tissue destruction and organ dysfunction. The disease has a clinical overlap with adult-onset still's disease (AOSD) and hence poses a diagnostic challenge. We report the case of a 20-year-old female who presented with prolonged febrile illness, anemia, hepatosplenomegaly, and generalized lymphadenopathy. She was diagnosed with HLH and was readmitted 6 weeks later with recurrent fever, polyarthralgia, and pharyngitis. A diagnosis of AOSD with secondary HLH was made.

Adult-onset Still’s disease possibly consequent to asymptomatic COVID-19

Background: In some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), an uncontrolled release of inflammatory cytokines is characteristic. COVID-19 and adult-onset Still’s disease (AOSD) have been included by some authors in the “hyperferritinemic syndromes.” Another hyperinflammatory syndrome (with variable features of Kawasaki disease) called multisystem inflammatory syndrome (MIS) has been described in patients who have had SARS-CoV-2 infection. Case Presentation: We present a previously healthy patient who developed hyperinflammatory reaction compatible with MIS; the clinical presentation is additionally compatible with AOSD, complicated with a mild myocarditis. The patient had a positive SARS-CoV-2 serology (immunoglobulins G and immunoglobulins M ), but multiple reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on nasopharyngeal swab were negative or indeterminate, so we considered that it is possible that an asymptomatic SARS-CoV-2 infection could have been the trigger for Still’s disease. 24 hours after starting methylprednisolone treatment, the fever was resolved and symptoms improved over the next few days, with persistent arthralgias. Conclusion: Asymptomatic SARS-CoV-2 infection could trigger MIS with AOSD-like features.

Adult Onset Still’s Disease Presenting with Tuberculous Bronchopneumonia: A Case Study

Introduction: The occurrence of Post primary Tuberculosis [TB] can be due to reactivation of previous infection or reinfection. Reactivation of TB could occur due to many conditions including immunosuppressive drug therapy and immunosuppressive diseases. In countries where latent TB is common a good vigilance is needed for early detection of TB when such conditions are managed. Adult onset Still’s disease (AOSD) is a rare systemic disorder of unknown etiology where fever, rash, lymphadenopathy and multi organ involvement occur. ASOD is a challenging condition to diagnose as there are no pathognomonic physical signs or markers. Early diagnosis and initiation of treatment is important as diagnostic delays could lead to serious consequences. Occurrence of tuberculosis in a patient with AOSD has not been documented in literature to-date. Here we describe a 46-year-old male who presented with low grade fever and arthralgia for more than one month with organomegaly and pericardial effusion managed as AOSD, later developed Tuberculous bronchopneumonia.

A Cohort Study of Liver Involvement in Patients With Adult-Onset Still's Disease: Prevalence, Characteristics and Impact on Prognosis.

Objective: Adult-onset Still's disease (AOSD) is a systemic disorder commonly accompanied by liver involvement. This study aims to illustrate the detailed information of liver abnormalities in patients with AOSD and evaluate the impact on the prognosis.Methods: A total number of 128 hospitalized patients, who met the Yamaguchi criteria of AOSD in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2016 to August 2019 were consecutively enrolled and followed up. The demographic characteristics, clinical features, laboratory tests, treatments and prognosis were recorded. Correlations of liver function tests (LFTs) with disease activity and laboratory parameters were analyzed by the Spearman test. Risk factors of the refractory AOSD were evaluated by multivariate logistic regression analysis.Results: Liver involvement was presented in 104 (81.3%) patients with AOSD. We observed that 34 (32.7%) patients were with mild elevation, 32 (30.8%) patients were with moderate elevation, and 38 (36.5%) patients were with severe elevation. The majority of elevated ALT, AST and ALP decreased to normal within the range of 2 months, except for GGT. Furthermore, the LFTs were found significantly correlated with disease activity. Besides, we found patients with higher levels of LFTs tended to require more intensive treatments and suffered from poorer prognosis. Multivariate logistic regression analysis showed ALP ≥ 141 IU/L and GGT ≥ 132 IU/L are independent risk factors of refractory AOSD.Conclusion: Liver involvement is common in patients with AOSD, the levels of LFTs are associated with disease activity and related to the treatment strategies and prognosis.