Adult-onset Still's Disease Research Articles

Serum Interleukin-18 Provides a Clue to the Diagnosis of Adult-Onset Still's Disease: Findings from 6 Japanese Patients with Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder accompanied by skin eruption. However, typical skin eruptions, such as evanescent, salmon-pink erythema, are not specific to AOSD and dermatologists often face difficulty in diagnosing AOSD. In this study, we examined serum IL-18 levels as well as IL-6, ferritin and C-reactive protein in 6 Japanese patients with AOSD. Serum levels of IL-6 and IL-18 were evaluated in the acute phase and at the time of remission. Serum levels of IL-6 were analyzed using a commercial chemiluminescent enzyme immunoassay (CLEIA; SRL, Tokyo, Japan). Serum IL-18 levels were measured using a commercial ELISA kit (Medical & Biological Laboratories Co., LTD. Nagoya, Japan). In active AOSD, serum ferritin levels and CRP levels were above normal range in 6 patients. In remission, serum ferritin levels of 3 patients were slightly above the normal range, while CRP serum levels of 6 patients were all normalized. Serum IL-18 levels were markedly elevated in 5 cases during the acute phase. In remission, serum IL-18 levels remained at higher values than the normal range in 5 cases. Serum IL-6 levels were also highly elevated in 5 patients in active AOSD and became normalized in remission except in case 2. High levels of serum IL-18 will be a clue to the diagnosis of AOSD. CRP is also useful biomarker for monitoring disease activity compared with IL-6 and IL-18.

The hyper-expression of NLRP4 characterizes the occurrence of macrophage activation syndrome assessing STING pathway in adult-onset Still's disease.

To assess stimulator of interferon genes (STING) pathway in patients with adult-onset Still's disease (AOSD) who were complicated or not by macrophage activation syndrome (MAS), evaluating peripheral blood mononuclear cells (PBMCs), and synovial tissues. The relative mRNA expression of key molecules of the STING pathway (i.e. CGAS, NLRP4, PKDC, STING1, XRCC5, and XRCC6) and interferon (IFN)-γ was assessed in PBMCs obtained from patients with AOSD, who were complicated or not by MAS, and healthy controls (HCs). A bulky RNA sequencing was performed in synovial tissues from two patients with AOSD. Finally, the ability of heavy ferritin subunit (FeH) to induce the expression of NLRP4 was evaluated in cultured macrophages. Twenty patients with AOSD were analysed. Out of them, seven patients were complicated by MAS. Assessing mRNA relative expression in PBMCs, STING1, NLRP4, XRCC6, and IFN-γ were significantly expressed in AOSD than HCs. The mRNA relative expression of CGAS, PKDC, and XRCC5 did not differ between patients and HCs. Furthermore, NLRP4 and IFN-γ resulted to be significantly increased in patients with AOSD complicated by MAS than others. By RNA-sequencing analysis, we observed that Nlrp4 gene was significantly up-regulated in patients with AOSD. Following the stimulation with FeH, an increased expression of NLRP4 was observed in cultured macrophages. In conclusion, an increased expression of some key molecules of STING pathway characterized patients with AOSD. In addition, our results suggested that a hyper-activity of NLRP4 may be observed in patients with MAS. Furthermore, FeH increased the expression of NLRP4 in cultured macrophages.

Enhanced type I interferon signature induces neutrophil extracellular traps enriched in mitochondrial DNA in adult-onset Still's disease

Adult-onset Still's disease (AOSD) is a rare but clinically well-known auto-inflammatory disorder. Cytokine storm, the hallmark of AOSD, is mediated by neutrophil hyperactivation and enhanced neutrophil extracellular trap (NET) formation. Type I interferons (IFNs), having a primary role in the initiation of proinflammation responses, can induce subsequent inflammatory cytokine production. However, the role of type I IFNs in AOSD is unclear. Indeed, high levels of IFN-α and IFN-β expression are presented by AOSD patients. In this investigation, hierarchical unsupervised clustering was performed on IFN-α and IFN-β data to identify a cluster of AOSD patients who had a serious condition. Neutrophils from treatment-naïve active AOSD patients showed very strong enrichment in their IFN-α response, as shown by RNA-seq and confirmed by the IFN score. Whether IFN-α stimulates NET formation was also tested. IFN-α had the ability to form NETs that contained oxidized mitochondrial DNA (ox-mtDNA). Moreover, the JAK inhibitor could be used to dampen type I IFN-induced NET formation and eventually control ox-mtDNA release. Our results demonstrated the important roles of type I IFNs in the pathogenesis of AOSD through their promotion of NET formation, as characterized by the enhanced level of ox-mtDNA. The findings open up new avenues of research into therapeutic approaches for AOSD.

Parvovirus Infection Triggering Still's Disease.

We present the case of a 59-year-old man with acute B19 parvovirus infection who developed a systemic inflammatory reaction similar to adult-onset Still’s disease (AOSD). We discuss the clinical challenge due to overlapping symptoms to distinguish between a primary B19 viral infection and the autoimmune disease it can trigger.LEARNING POINTSDistinguishing between primary B19 parvovirus infection and autoimmune diseases can be difficult in view of the significant symptom overlap.In our patient, recurrence of symptoms during follow-up and response to treatment were in favour of adult-onset Still’s disease triggered by B19 parvovirus.

Disparities in the prevalence of clinical features between systemic juvenile idiopathic arthritis and adult-onset Still's disease.

ObjectiveTo compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD).MethodsThe clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered.ResultsA total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA.ConclusionWe found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

Similar Clinical Outcomes in Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease Treated with Canakinumab: Bayesian and Population Model-Based Analyses.

IntroductionSystemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) represent pediatric and adult variants of the Still’s disease continuum. To determine whether clinical outcomes between patients with sJIA and AOSD were similar, Bayesian and population model-based analyses were conducted on endpoints from studies of canakinumab in both patient populations. The objective was to further support the efficacy of canakinumab in patients with AOSD.MethodsA Bayesian analysis of endpoints from a study of canakinumab in AOSD was conducted borrowing information from five pooled sJIA studies using a robust meta-analytic predictive (MAP) approach. Similarity of clinical outcomes across populations was fulfilled if the AOSD study posterior median fell within the 95% predicted credible interval for the outcome of interest, based on the pooled sJIA data. Population model-based analyses (pharmacokinetic [PK] and PK/pharmacodynamic [PKPD]) were conducted to compare the pharmacokinetics and exposure–response relationships between populations.ResultsThe AOSD study posterior medians for adapted American College of Rheumatology (ACR)30 response, continuous adapted ACR response, number of active joints, C-reactive protein, and absence of fever were within the 95% credible interval for the prediction of the MAP analysis from the pooled sJIA data, supporting the similarity in outcomes between patient populations. PK analysis demonstrated comparable exposure across sJIA age groups and patients with AOSD. PKPD relationships were consistent across patient populations. Analyses indicated that no therapeutic benefit can be expected from a dose increase in patients with AOSD.ConclusionThe analyses presented support the similarity of clinical outcomes following treatment with canakinumab in patients with sJIA and AOSD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00422-9.

New-onset Adult-onset Still's disease-like syndrome after ChAdOx1 nCoV-19 vaccination-a case series with review of literature.

We report a series of 3 Adult-onset Still’s disease (AOSD)-like presentations in previously healthy females following vaccination with the ChAdOx1 nCoV-19 vaccine, and also compare them with similar cases reported in literature through a PubMed database search. Our first patient had a high spiking bi-quotidian type of fever with myalgia, sore throat, and arthritis with onset 10-day post-vaccination, with laboratory features of hyper inflammation responding to only naproxen. She was off treatment after 2 months. The second patient, with onset 3-week post-vaccination, had a more severe illness, requiring high dose immunosuppression. In our third case, the onset of illness was slightly delayed i.e., 3-month post-vaccination, but she had the most severe disease with macrophage activation syndrome at presentation requiring immunosuppression and biologicals. The underlying mechanism may be linked to the activation of Toll-like receptors (TLR)—TLR-7 and TLR-9—leading to a robust immune response. These 3 cases highlight the immunogenicity of COVID-19 vaccines, with the possibility of occurrence of new-onset systemic hyper-inflammation illness which can happen a few days following the vaccination, sometimes even delayed to months, and can range in severity from mild to even life-threatening. More cases need to be studied to understand the profile and prognosis of these syndromes in the long run.

The Role of Interleukin 18/Interleukin 18-Binding Protein in Adult-Onset Still's Disease and Systemic Juvenile Idiopathic Arthritis.

Interleukin 18 (IL-18) is a pro-inflammatory cytokine of the IL-1 family, whose activity is tightly controlled at the level of production, as well as signalization. Notably, it is buffered by its natural inhibitor, IL-18 binding protein (IL-18BP), which is massively present in circulation in normal and in most pathological conditions, thus preventing harmful pro-inflammatory systemic effects of IL-18. IL-18 has long been considered to be involved in the pathophysiology of various inflammatory diseases. However, a first clinical trial using recombinant IL-18BP for the treatment of rheumatoid arthritis and psoriasis gave disappointing results. Direct measurements of unbound, bioactive, free form of circulating IL-18 demonstrated that IL-18 was more specifically involved in adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) but also in their most severe complication, macrophage activation syndrome (MAS). More importantly, administration of recombinant IL-18BP to patients with AOSD, and sJIA with MAS, showed promising results. This review summarizes available data regarding IL-18 and IL-18BP in AOSD and sJIA in mouse models and humans and shows the importance of IL-18/IL-18BP imbalance in these conditions, leading to the conclusion that IL-18, particularly free IL-18, may be a useful biomarker in these diseases and an interesting therapeutic target.

Extreme Hyperferritinemia in a Filipino Male Patient with Adult Onset Still’s Disease: A Case Report

Background: Elevated serum ferritin is more commonly due to reactive causes such as infection, hepatic disorders, rheumatologic conditions, and malignancy than true iron overload. Extreme hyperferritinemia (>10,000 ng/mL), on the other hand, should prompt consideration of rare conditions such as adult-onset Still’s disease (AOSD) or hemophagocytic lymphohistiocytosis. This paper aims to present the case of the highest reported extreme hyperferritinemia (actual level 256,000 ng/mL) in a patient eventually diagnosed with adult onset Still’s Disease (AOSD). Case Presentation: A 55-year-old male, Filipino, was admitted due to acute onset fever and shortness of breath. He was initially assessed to have community-acquired pneumonia and a suspect for coronavirus disease 2019 (COVID-19), hence inflammatory markers were requested. Ferritin was notably elevated at 44,255 ng/mL. He eventually tested negative for COVID-19 RT-PCR. He was investigated for other causes of markedly elevated ferritin levels. His complete blood count (CBC) only showed leukocytosis with no peripheral blasts, iron level and liver function tests were normal, HIV immunoassay was negative, ANA was 1:80 speckled with normal complement level, rheumatoid factor negative, and positron emission tomography (PET) scan revealed presence of lymphadenopathies and did not show solid tumors. He was treated for urinary tract infection and pneumonia but still had intermittent fever and increasing ferritin trend, with the highest documented level at 256,000 ng/mL. Fulfilling the Yamaguchi criteria, he was managed as a case of severe AOSD and received tocilizumab. He had lysis of fever and decreasing trend of ferritin levels thereafter, with ferritin level of 34,184 ng/mL three weeks after tocilizumab infusion. He was discharged and improved with prednisone and methotrexate as home medications. Conclusion: To our knowledge, the highest level of extreme hyperferritinemia recorded in literature as of 2016 is 143,931 ng/mL, which was associated with hematologic malignancy. This case documents the highest noted ferritin level of 256,000 ng/mL associated with AOSD. AOSD remains a diagnosis of exclusion due to its nonspecific symptoms and absence of definitive tests. The treatment comprises NSAIDs, steroids, and immunosuppressives; however biological treatments such as tocilizumab can be considered in severe cases.

Prognostic factors for adult-onset Still disease: a retrospective analysis of 90 patients in China.

Adult-onset Still disease (AOSD) is a systemic auto-inflammatory disorder that can be divided into monocyclic, polycyclic and chronic arthritis subtypes based on the clinical course. Since the prognoses of the three patterns of AOSD are substantially different, it is important to identify clinical indices that can be used to differentiate them. To investigate the clinical features of the three patterns of AOSD in order to determine possible prognostic factors. Clinical records of inpatients admitted with a probable diagnosis of AOSD to the Second Xiangya Hospital of Central South University between 2009 and 2019 were retrospectively studied. Ninety patients were divided into a monocyclic group, a polycyclic group and a chronic arthritis group. The average age at onset was 39.01 ± 13.04 years, and female to male ratio was 3.3. Elevated white blood cell (WBC) count, even beyond 15 × 109/L, and increased serum level of interleukin-6 (IL-6) >5.3pg/mL (upper limit of normal value) were associated with the recurrence of AOSD, while the presence of rash and increased level of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) were more commonly seen in the monocyclic group. Our results indicate that gender, presence of rash, WBC count, serum level of IL-6, and ALT and/or AST are promising prognostic factors for AOSD. However, larger cohorts are needed to validate these factors due to the limitations of the retrospective study design and relatively small sample size.

Know Case of Hyperthyroidism with Newly Diagnosed Adult Onset Stills Disease

To our knowledge, the possible unveiled interaction between adult-onset Still’s disease (AOSD) withautoimmune thyroid disease (AITD) has never been reported although it is well established that systemicautoimmune disease may usually occur in relation to AITD. As increasingly clear links of AITD withother autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), andprimary Sjögren’s syndrome (pSS) have been reported, and the incidence of AOSD concurrent AITDdraws our attention rapidly. In this study, we searched relevant literatures published in the past 30 yearsto explore that condition.

Adult-onset Still's disease with elderly onset: results from a multicentre study.

In this study, we aimed at describing the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p<0.0001), and mortality (p=0.023). Age predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012). Clinical features of AOSD patients in the elderly were described in our cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a negative prognostic factor in AOSD.

Adult-Onset Still’s Disease: Novel Biomarkers of Specific Subsets, Disease Activity, and Relapsing Forms

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recent studies have demonstrated that the hallmark of AOSD is a cytokine storm, which is characterized by the excessive production of interleukin (IL)-1, IL-6, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), suggesting how pro-inflammatory cytokines play an important role in the pathogenesis of this disease. Actually, a certain proportion of patients (around 17–32%) with severe clinical symptoms achieves only partial remission or is resistant to both first-line corticosteroids and second-line DMARDs. These patients are defined as refractory AOSD patients, requiring higher dosage glucocorticoids, longer treatment duration, or the simultaneous introduction of immunosuppressive drugs, further leading to AOSD relapses. In this narrative review, we will analyze the latest literature data to unravel potential pathogenetic factors associated with specific patterns of AOSD disease or relapses in order to identify biomarkers that may guide clinical decisions, eventually leading to new therapeutic options.

Reasons for Initiating Canakinumab among Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease in the U.S. Real-World Settings.

IntroductionThe aim of this study was to understand the reasons for canakinumab initiation among patients with Still’s disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD), in US clinical practice.MethodsPhysicians retrospectively reviewed the medical charts of patients with Still’s disease (regardless of age at symptom onset) who were prescribed canakinumab from 2016 to 2018. Patients aged < 16 years at symptom onset were classified as having SJIA and those aged ≥ 16 years at symptom onset (calculated from case-record forms) were classified as having AOSD. Patient treatment history and physician reasons for canakinumab initiation were analyzed. Overall results were presented as SJIA/AOSD. Sensitivity analyses were performed for the robustness of the results.ResultsForty-three physicians in the USA (rheumatologists/dermatologists/immunologists/allergists: 51.2/27.9/11.6/9.3%; subspecialty in adults/pediatrics: 67.4/32.6%) abstracted information for 72 patients with SJIA/AOSD (SJIA/AOSD/age unknown at symptom onset: 75.0/18.1/6.9%; mean age 19.4 years; children 61.1%; females 56.9%). Most patients (90.3%) received treatment directly preceding canakinumab initiation (etanercept 27.7%; anakinra 18.5%; adalimumab 16.9%); the respective treatment was discontinued due to lack of efficacy/effectiveness (43.1%) and availability of a new treatment (27.8%). Most common reasons for canakinumab initiation were physician perceived/experienced efficacy/effectiveness of canakinumab (77.8%; children/adults: 81.8/71.4%), lack-of-response to previous treatment (45.8%; children/adults: 36.4/60.7%), convenient administration/dosing (26.4%; children/adults: 29.5/21.4%) and ability to discontinue/spare steroids (25.0%; children/adults: 20.5/32.1%). The sensitivity analysis provided similar results.ConclusionsIn US clinical practice, physician perceived/experienced efficacy/effectiveness of canakinumab and lack-of-response to previous treatment were the primary reasons for canakinumab initiation among patients with SJIA/AOSD. Physician perceived/experienced efficacy/effectiveness and convenient administration/dosing of canakinumab were the most common reasons for canakinumab initiation among children, whereas lack-of-response to previous treatment and ability to discontinue/spare steroids being the most frequent reasons among adults.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00402-z.

Case Report: Adult Onset Still’s Disease after vaccination against Covid-19

Vaccination against the virus responsible for COVID-19 has become a key in preventing mortality and morbidity related to the infection. Studies have shown that the benefits of vaccination outweigh the risks. However, there are concerns regarding serious adverse events of some vaccines, although they are fortunately rare. Here, we report a case of a 47-year-old female from Kathmandu who presented with high grade fever, dry cough and erythematous rash a week after exposure to the Oxford-AstraZeneca vaccine. She had hepatosplenomegaly, persistent leucocytosis, anaemia and thrombocytosis along with markedly raised inflammatory markers. Her tests for infectious causes and haematological malignancies was negative and she showed no response to multiple antibiotics. Finally, she had a dramatic response to steroids with disappearance of fever and normalization of other laboratory parameters. Hence, she was diagnosed with Adult-onset Still’s Disease (AOSD). She was under methotrexate and prednisolone tapering dose and doing well as at time of writing. The trigger for the disease was hypothesized to be the vaccine because of the strong temporal association.

Antidepressant in the Treatment of Chronic Pain: A Case Report of Adult-Onset Still's Disease

Adult-onset Still’s disease (AOSD) is a rare multisystemic autoinflammatory disease with symptoms, including spiking fever, evanescent rash, arthralgia or arthritis, sore throat, lymphadenopathy, hepatosplenomegaly, and myalgia. The prevalence of anxiety and depressive symptoms in rheumatological diseases is quite high, which impacts social as well as occupational functioning. Depression and anxiety are known to be the most common psychiatric comorbidities in patients with arthritis and other rheumatological disorders. Here, we report the case of an adult white female with AOSD who showed improvement in symptoms of AOSD with monoclonal antibodies and steroids; however, significant worsening of pain along with depression & anxiety were noted. With the use of antidepressant serotonin-norepinephrine reuptake inhibitor (SNRI), specifically duloxetine, our patient was able to experience improvement in depression, anxiety, and pain.

An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease.

Neutrophils are innate immune phagocytes that play a key role in immune defense against invading pathogens. The main offensive mechanisms of neutrophils are the phagocytosis of pathogens, release of granules, and production of cytokines. The formation of neutrophil extracellular traps (NETs) has been described as a novel defense mechanism in the literature. NETs are a network of fibers assembled from chromatin deoxyribonucleic acid, histones, and neutrophil granule proteins that have the ability to kill pathogens, while they can also cause toxic effects in hosts. Activated neutrophils with NET formation stimulate autoimmune responses related to a wide range of inflammatory autoimmune diseases by exposing autoantigens in susceptible individuals. The association between increased NET formation and autoimmunity was first reported in antineutrophil cytoplasmic antibody-related vasculitis, and the role of NETs in various diseases, including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, has since been elucidated in research. Herein, we discuss the mechanistic role of neutrophils, including NETs, in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD), and provide their clinical values as biomarkers for monitoring and prognosis.

What is confirmed in the treatment of autoinflammatory fever diseases?

In den letzten 20 Jahren hat die Aufklärung von monogenetisch verursachten periodischen Fiebererkrankungen zum eigenständigen Konzept der Autoinflammation geführt. In diese heterogene Gruppe werden inzwischen auch polygenetisch verursachte, komplexe Erkrankungen eingruppiert. Das Spektrum der Krankheitsbilder wächst kontinuierlich. Hauptunterschied zur Autoimmunität ist eine übermäßige Aktivierung des angeborenen Immunsystems ohne Autoantikörperbildung oder antigenspezifische T‑Zellen. Als Kardinalsymptom treten rezidivierende Fieberschübe, begleitet von Entzündungszeichen, auf; diese wechseln sich bei den periodischen Krankheitsbildern mit Intervallen allgemeinen Wohlbefindens ab. Die klassischen monogenetischen Erkrankungen werden auch als hereditäres rezidivierendes Fieber (HRF) bezeichnet. Beispiele sind das familiäre Mittelmeerfieber (FMF), das Cryopyrin-assoziierte periodische Syndrom (CAPS), das Tumor-Nekrose-Faktor-Rezeptor-1-assoziierte periodische Syndrom (TRAPS), die Adenosindesaminase(ADA2)-Defizienz und die Mevalonatkinasedefizienz (MKD; Hyper-IgD-Syndrom). Die polygenetischen Erkrankungen werden auch als nichthereditäre Fiebersyndrome bezeichnet. Hierzu zählen die adulte Form der Still-Erkrankung („adult-onset Still’s disease“, AoSD), die Adamantiades-Behçet-Erkrankung, das PFAPA-Syndrom (periodisches Fieber, aphthöse Stomatitis, Pharyngitis und zervikale Adenitis) und die Gichtarthritis. Alle autoinflammatorischen Fiebersyndrome gehen mit einem von individuellem Schweregrad und Therapieerfolg abhängigen Langzeitrisiko für die Entwicklung einer Amyloid-A-Amyloidose einher. Bei einigen Erkrankungen können z. T. schwere Komplikationen auftreten.

USAID Associated with Myeloid Neoplasm and VEXAS Syndrome: Two Differential Diagnoses of Suspected Adult Onset Still's Disease in Elderly Patients.

Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusions: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.

Adult onset stills disease: Newly diagnosed in pregnancy with rare clinical presentation as pleural effusion

Adult onset Still’ disease (AOSD) is a rare inflammatory disease which involves multiple systems and is of unknown etiology first described in 1971.It has more prevalence among young females and few studies show the exacerbation of symptoms during pregnancy. Patients usually presents with high grade fever, arthritis, arthralgia, salmon pink rash, organomegaly, lymphadenopathy but rarely can present with pleural symptoms, cardiac symptoms. Several criteria’s are used for diagnosis but Yamaguchi’s has the highest sensitivity of 93.5%. Yamaguchi’s classification criteria includes major and minor criteria’s and exclusion criteria’s. Although diagnostic criteria are there but AOSD till date is a diagnosis of exclusion. All the causes of clinical symptoms should be excluded which involves malignancies, infections, inflammatory conditions, autoimmune diseases before the diagnosis of AOSD is made. A 26-year-old female with G2P0010 and POG 6 weeks presented to medicine OPD with high grade fever associated with chills and rigors from 1 week. She was also complaining of stiffness and pain in multiple joints with chest pain, easy fatigability. She was having rashes on upper back below nape of neck. All the necessary investigations were carried out. It was found that she was also having right sided pleural effusion and severe microcytic hypochromic anemia. After batteries of investigations and consultation by obstetrician, rheumatologist, dermatologist diagnosis of Adult Onset Still’s disease was made. It was a diagnosis of exclusion. Patient was started on steroids and she responded well. All the symptoms including pleural effusion was subsided. Adult onset still’s disease is a form of still’s disease. It is a rare systemic auto-inflammatory disease. Yamaguchi is the most sensitive criteria but till date it is diagnosed after excluding possible causes of malignancies, infections and autoimmune conditions. Sometimes patients do present with rare symptoms like pleural effusion, pericarditis some may present as acute respiratory distress syndrome or mild symptoms like cough, pleuritic chest pain. In our case also all the possible causes were excluded as patient presented with pleural effusion for the first time during pregnancy, so the impact of the disease on the fetal outcome was also considered. AOSD has always been a diagnosis of exclusion but as in our case and cases with similar presentation AOSD should be consider as a differential diagnosis. Although there are only few studies which shows that there is fatal outcome of pregnancy in AOSD however there are studies showing exacerbation of symptoms of AOSD during pregnancy. Its early diagnosis and prompt treatment can be helpful in the better outcome of pregnancy as well as better prognosis of disease.