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The article presents a case study of a 51-year-old man who initially presented with dysphnea, cough, and fatigue, later developing a rash after antibiotic treatment, raising concerns of Stevens-Johnson syndrome. Topics discussed include the differential diagnosis of pneumonia and exanthematous drug eruptions, the role of laboratory findings in diagnosis, and the challenges in distinguishing between infectious and drug-related rashes.

Objectives: To define groups and characterize differences in the prognosis of patients with adult-onset Still's disease (AOSD). Methods: We performed a retrospective cohort study. Patients with AOSD were grouped using hierarchical unsupervised cluster analysis according to age, sex, clinical features, and laboratory data. The primary endpoints were overall survival and drug-free remission rate. Results: A total of 153 patients with AOSD were placed into four clusters. Those in Cluster 1 had a young onset, tended to be female, and had fewer complications and moderate ferritin concentrations. Those in Cluster 2 had a young onset and had more complications and higher ferritin concentrations. Those in Cluster 3 had a young onset, tended to be male, and had no lymphadenopathy and fewer complications. Those in Cluster 4 had an older onset, tended to be female, and had more complications and higher ferritin concentrations. Overall survival tended to be lower (P = .0539) in Cluster 4, and drug-free remission was higher in Clusters 1, 2, and 3 [hazard ratios (HRs) 2.19, 3.37, and 3.62 vs. Cluster 4, respectively]. Conclusions: Four groups of AOSD that have distinct clinical manifestations, ferritin concentrations, severity, and drug-free remission rate were identified, which were lowest in Cluster 4. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the performance of radionuclide-labeled fibroblast activation protein inhibitors (Al18F-NOTA-FAPI-04) PET/CT in patients with autoimmune rheumatic diseases (ARDs) and compare it with fluorine-18 (18F) labeled fluorodeoxyglucose (FDG) imaging. Methods: Fifty-eight participants with ARDs were prospectively enrolled from April 2022 to February 2024 and underwent dual-tracer PET/CT imaging. For both 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT, imaging findings were interpreted and compared. The clinical significance was compared between18F-FDG PET/CT and Al18F-NOTA-FAPI-04 PET/CT imaging. Results: 18F-FDG imaging was positive in 53 out of 58 cases (91.4%) while Al18F-NOTA-FAPI-04 imaging was positive in 55 out of 58 cases (94.8%). Overall positive rate of Al18F-NOTA-FAPI-04 imaging was as high as 18F-FDG imaging (P = 0.625). 18F-FDG imaging detected more lesions in lymph node, spleen, and bone marrow. Al18F-NOTA-FAPI-04 imaging detected more lesions in the lung, muscle, and tendon/ligament. There was no statistical difference of composing ratio of grades of clinical significance between two imaging modalities (χ2 = 2.875, P = 0.238). The superior rate of Al18F-NOTA-FAPI-04 PET/CT imaging was higher than 18F-FDG imaging (P = 0.020). In subgroup of adult-onset Still's disease, 18F-FDG imaging showed better performance than Al18F-NOTA-FAPI-04 imaging. In most of the other subgroup of ARDs, Al18F-NOTA-FAPI-04 PET/CT imaging overperformed 18F-FDG imaging. Conclusion: Both 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging have excellent sensitivity in ARDs. The detection capabilities of two tracers varied according to the involving organs of ARDs. In most of ARDs except adult-onset Still's disease, Al18F-NOTA-FAPI-04 PET/CT imaging overperformed 18F-FDG imaging. Key Points • 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging have excellent sensitivity in diagnosing of ARDs. • 18F-FDG PET/CT imaging detected more lesions in lymph node, spleen, and bone marrow. • 18F-NOTA-FAPI-04 PET/CT imaging detected more lesions in the lung, muscle, and tendon/ligament. • 18F-NOTA-FAPI-04 PET/CT imaging overperformed18F-FDG in most subgroups of ARDs. [ABSTRACT FROM AUTHOR]

Objective: To develop the Still's Disease Activity Score (SDAS). Methods: We used data from the prospective adult-onset Still's disease cohort study and evaluated the disease activity. An expert group selected the most frequent, reproducible, and objective variables significantly modified in statistical analysis when comparing patients in the active group and in the remission group. These criteria were weighted to design the Still's Disease Activity Score (SDAS). The Delphi method was used to appreciate the level of disease activity. Total SDAS was calculated for each patient and compared to final consensus experts. Results: At the diagnosis, all patients had an active disease (n = 80), while 48 patients were in remission at 6 months. The SDAS criteria were weighted as follows: fever ≥ 38.5 °C (1 point), rash (1 point), joint involvement (arthralgia: 1 point, swollen joints count "SJC": 1–3 SJC: 2 points, ≥ 4 SJC: 3 points), physician global assessment VAS ≥ 5/10 or a raise in physician VAS ≥ 2/10 (3 points), patient VAS ≥ 5 or a raise in patient VAS ≥ 2/10 (1 point), and CRP (> 10 mg/l: 1 point, ≥ 100 mg/l: 2 points). At 6 months, the consensus was achieved for 76 (95%) patients with 40 in remission (0–1 point), 8 in low disease activity (2–3 points), 16 in moderate disease activity (4–7 points), and 12 in severe disease activity (≥ 8 points). Conclusion: The Still's Disease Activity Score is a valid and sensitive assessment of the disease activity and the therapeutic response in Still's disease, despite its heterogeneous manifestations and patterns with systemic and articular forms. Key Points • The Still's Disease Activity Score (SDAS) is a good simple tool to assess the activity of the disease in a stable state for a week. • The SDAS is developed specifically for Still's disease without the need for an application or a calculator to calculate SDAS in routine clinical practice. • SDAS is a composite score classifying the disease activity in remission, low disease activity, moderate disease activity, and severe disease activity despite its heterogeneous patterns (systemic and articular forms). • The SDAS is a valid, reliable, and sensitive score and can be useful to guide the therapeutic strategy in clinical practice and in research. [ABSTRACT FROM AUTHOR]

Objective: Adult‐onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D‐dimer, C‐reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D‐dimer); interleukin‐1/interleukin‐6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25). Methods: This was a single‐center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included. Results: There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 μg/L vs. 29 020 μg/L, p =.01) while D‐dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, p =.3). CRP was higher (median 168 mg/L vs. 71 mg/L, p <.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, p =.004) in AOSD compared to HLH. The combined ROC curve using CRP >130 mg/L and sCD25< 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93–0.97) with sensitivity 91% and specificity 93%. Conclusions: These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted. [ABSTRACT FROM AUTHOR]

Historically inflammation against self was considered autoimmune which stems back to the seminal observations by Ehrlich who described serum factors, now known to be autoantibodies produced by B lineage cells that mediate “horror autotoxicus”. The 20th century elucidation of B- and T-cell adaptive immune responses cemented the understanding of the key role of adaptive immune responses in mediating pathology against self. However, Mechnikov shared the Nobel Prize for the discovery of phagocytosis, the most rudimentary aspect of innate immunity. Fast forward some 100 years and an immunogenetic understanding of innate immunity led to the categorising of innate immunopathology under the umbrella term ‘auto inflammation’ and terminology such as “horror autoinflammaticus” to highlight the schism from the classical adaptive immune understanding of autoimmunity. These concepts lead to calls for a two-tiered classification of inflammation against self, but just as innate and adaptive immunity are functionally integrated, so is immunopathology in many settings and the concept of an autoimmune to autoinflammation continuum emerged with overlaps between both. Herein we describe several historically designated disorders of adaptive immunity where innate immunity is key, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) where the immunopathology phenotype is strongly linked to major histocompatibility complex (MHC) class II associations and responds to drugs that target T-cells. We also consider MHC-I-opathies including psoriasis and Behcet's disease(BD) that are increasingly viewed as archetype CD8 T-cell related disorders. We also briefly review the key role of barrier dysfunction in eczema and ulcerative colitis (UC) where innate tissue permeability barrier dysfunction and microbial dysbiosis contributes to prominent adaptive immune pathological mechanisms. We also highlight the emerging roles of intermediate populations of lymphocytes including gamma delta (gd) and mucosal-associated invariant T (MAIT) cells that represent a blend of adaptive immune plasticity and innate immune rapid responders that may also determine site specific patterns of inflammation. [ABSTRACT FROM AUTHOR]

Graves' disease is the leading cause of autoimmune hyperthyroidism. Thyroid hormones are an essential element of the endocrine system, playing a pivotal role in the body's development, especially important in children with intensified growth. Disturbance within thyroid tissue certainly affected the whole body. Nowadays, numerous research studies indicate different factors contributing to the onset of the disease; however, the exact pathomechanism of Graves' disease is still not fully understood, especially in the context of immune-related processes. Th1, Th17, and Th22 effector lymphocytes were found to be crucial participants in the disease outcome, as well as in autoimmune diseases. Here, our study aimed at assessing selected effector T lymphocytes, Th1, Th17, and Th22, in newly diagnosed pediatric Graves' disease patients, together with their association with thyroid-related parameters and the potential outcome of disease management. We indicated significant increases in the frequencies and absolute numbers of selected effector lymphocytes in Graves' disease patients. In addition, their mutual ratios, as well as Th1/Th17, Th/Th22, and Th17/Th22, seem to be significant in those diseases. Notably, low Th17/Th22 ratio values were distinguished as potential prognostic factors for normalizing TSH levels in response to methimazole treatment. To sum up, our research determines the crucial contribution of Th1, Th17, and Th22 cells in the pathogenesis of Graves' disease. Moreover, the mentioned subset of T cells is highly likely to play a substantial role in the potential prediction of therapy outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Adult-onset Still's disease is a rare systemic autoinflammatory disease. We present a case of a young man with a constellation of symptoms and myopericarditis as a complication of this disease. Case: A 36-year-old Hispanic man with no significant past medical history developed a quotidian fever pattern following an upper respiratory tract infection. He initially presented with chest pain concerning for myocardial infarction and underwent cardiac catheterization, which revealed non-obstructive coronary artery disease. He was found to have myopericarditis, significant neutrophilic leukocytosis, and hyperferritinemia. He improved on high-dose corticosteroids but developed steroid-induced psychosis, and 4 months from symptom onset, he finally received tocilizumab, which eventually induced remission without adverse reactions. Discussion: Adult-onset Still's disease should be considered in a patient with fevers of undetermined origin. Due to its multisystemic involvement, adult-onset Still's disease is often a diagnosis arrived at after an extensive cardiac, hematologic, malignant, and infectious workup. Imaging, laboratory testing, and bone marrow biopsy were necessary to rule out alternative etiologies of this patient's presentation. Steroids are the mainstay of treatment because they are easily affordable, although the high risk of adverse effects makes them less desirable. Interleukin-1 inhibitors (anakinra or canakinumab) and interleukin-6 inhibitor tocilizumab are the steroid-sparing biologic agents of choice but are cost-prohibitive. Conclusion: Adult-onset Still's disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 40-year-old man who presented with symptoms of fevers, sore throat, fatigue, weakness, and joint pains. After ruling out common respiratory viruses and streptococcus infection, further examination revealed musculoskeletal findings and elevated inflammatory markers, suggesting a possible rheumatologic cause. The patient was diagnosed with adult-onset Still's disease, a rare inflammatory condition characterized by fevers, rash, and joint pain. Treatment options discussed include nonsteroidal anti-inflammatory drugs, biologic agents, disease-modifying antirheumatic drugs, and interleukin inhibitors. The article emphasizes the need for effective immunomodulatory therapy and further research in this area. [Extracted from the article]

Objective: Rare coexistence of disease or pathology. Background: Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder with a highly variable clinical presentation. Pulmonary complications of AOSD most commonly include pleural effusion and transient pulmonary infiltrates. In extremely rare cases, pulmonary arterial hypertension (PAH) develops as a complication. We present the case of a 49-year-old woman with adult-onset Still's disease presenting with fever, dyspnea, and pleuritic chest pain who was diagnosed with PAH. Case Report: A 49-year-old woman with a history of adult-onset Still's disease presented to the Emergency Department due to 1 week of fever, dyspnea, and pleuritic chest pain. Imaging, cardiac, immunologic, and infectious workups were performed and detected elevated inflammatory markers. She then underwent right-heart catheterization, which revealed high pulmonary artery pressure (PAP) and mean PAP at 43/18 mmHg and 27 mmHg, respectively. The patient was stabilized and discharged for further management of heart failure with preserved ejection fraction, and group 1 pulmonary arterial hypertension secondary to Still's disease. Conclusions: Pulmonary complications of adult-onset Still's disease, such as PAH, are rare but potentially life-threatening. The treatment of PAH in adult-onset Still's disease involves the use of pulmonary vasodilators, immunosuppressive therapy, and regular monitoring to assess the prognosis of PAH. Our case report highlights the importance of considering PAH in patients with adult-onset Still's disease who present with dyspnea, fatigue, and chest pain. Increased clinician awareness of this extremely rare complication of AOSD can assist with rapid identification and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background and Objective: Adult-onset Still's disease (AOSD) is a recognized autoinflammatory disorder of unknown etiology. The standard initial management for AOSD includes conventional corticosteroids and disease-modifying antirheumatic drugs. In cases that are resistant to these treatments, additional therapeutic options such as immunosuppressants, biologics, and other alternative treatments may be considered. Yet, a significant proportion of patients remain unresponsive to these therapeutic interventions. Herein, a case is reported involving a patient with AOSD who had persistent pruritic lesions that did not respond to conventional therapy, but were alleviated with Janus kinase inhibitors (JAKi), namely baricitinib and upadacitinib. The objective is to expand the number of refractory AOSD cases treated with JAKi in clinical practice. Another aim is to offer potentially effective therapeutic options for AOSD patients who experience persistent pruritus. Methods: A case was reported involving AOSD characterized by persistent pruritic lesions that failed to respond to conventional treatment, but showed favorable outcomes with JAKi therapy. An analysis of the PubMed literature was performed to assess the medication's efficacy and explore possible mechanisms. Results: The present case study is one of the few documented instances exploring the use of JAKi for treating AOSD, aligning with previously published research. After initiating JAKi therapy, the patient exhibited significant improvement in symptoms, most notably a reduction in persistent pruritus. Additionally, there was a substantial decrease in the patient's glucocorticoid dosage. Aside from minor renal function anomalies, no adverse reactions were observed. Conclusions: The present case illustrates that JAKi can provide rapid and sustained clinical improvement in patients with AOSD, especially those who have not responded to conventional treatment, and they have the ability to alleviate persistent itching. Further investigation is needed to ascertain the precise mechanism. [ABSTRACT FROM AUTHOR]

A recent study published in the Journal of Internal Medicine explores the use of IL-1β/DNA complex levels as a diagnostic tool for distinguishing autoinflammatory disorders from autoimmune and infectious diseases. The researchers developed a novel ELISA assay to measure the amount of IL-1β bound to extracellular DNA in plasma samples. They found that circulating IL-1β/DNA complex levels were significantly higher in patients with autoinflammatory disorders compared to those with autoimmune rheumatic diseases, acute infections, and healthy individuals. The assay also showed promise in evaluating treatment response in patients receiving IL-1 inhibitors. Further studies are needed to validate the diagnostic and prognostic utility of this assay in diverse inflammatory disorders. [Extracted from the article]

Introduction: Adult-onset Still's disease (AOSD) is a rare chronic autoinflammatory condition characterized by a spiking fever, arthritis, a rash, hepatosplenomegaly, lymphadenopathy, leucocytosis, and hyperferritinemia. It is sometimes accompanied by life-threatening complications like macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH). Treatment options for AOSD include glucocorticoids (GCs), immunosuppressive drugs, biological medications, and Janus kinase (JAK) inhibitors. The features that differentiate MAS/HLH from AOSD are: in MAS/HLH, a different type of fever, which is persistent, a sharp decrease in the number of leukocytes and thrombocytes, a further increase in the level of transaminases and ferritin, significant hepatosplenomegaly, lymphadenopathy, symptoms of the central nervous system (CNS), disseminated intravascular coagulation (DIC) and hemophagocytosis in the bone marrow. This study aimed to evaluate the course of AOSD, which results in MAS/HLD. Patients and methods: Nine AOSD patients, four of whom developed MAS/HLH, were treated at the Rheumatology Clinic in the Central Clinical Hospital of the Ministry of Interior Affairs from 1 January 2015 to 15 March 2020 and at the Rheumatology Clinic in the National Institute of Geriatric, Rheumatology and Rehabilitation from 1 September 2021 to 1 March 2024. Medical history, clinical data, demographic data, laboratory data, imaging data, Hscore, and treatment data were collected. Results: All the patients with MAS and an Hscore above 150 recovered. Discussion: MAS/HLH requires rapid diagnosis as well as treatment with methylprednisolone pulses, cyclosporine A, and etoposide. When comparing patients who developed MAS/HLH with those who did not, possible risk factors were identified: the presence of pregnancy (two cases) and an aggressive course of AOSD. The Hscore is a useful tool for identifying patients with MAS/HLH. [ABSTRACT FROM AUTHOR]

Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory condition with onset in childhood. It is sporadic, but elements of its stereotypical innate immune responses are likely genetically encoded by both common variants with small effect sizes and rare variants with larger effects. Genomic investigations have defined the unique genetic architecture of sJIA. Identification of the class II HLA locus as the strongest sJIA risk factor for the first time brought attention to T lymphocytes and adaptive immune mechanisms in sJIA. The importance of the human leukocyte antigen (HLA) locus was reinforced by recognition that HLA-DRB1*15 alleles are strongly associated with development of drug reactions and sJIA-associated lung disease (sJIA-LD). At the IL1RN locus, genetic variation relates to both risk of sJIA and may also predict non-response to anakinra. Finally, rare genetic variants may have critical roles in disease complications, such as homozygous LACC1 mutations in families with an sJIA-like illness, and hemophagocytic lymphohistiocytosis (HLH) gene variants in some children with macrophage activation syndrome (MAS). Genetic and genomic analysis of sJIA holds great promise for both basic discovery of the course and complications of sJIA, and may help guide personalized medicine and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

This document is a case report discussing a patient who presented with symptoms of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition associated with COVID-19. The patient experienced persistent fever, rash, gastrointestinal symptoms, and neurocognitive dysfunction. They were initially diagnosed with Still's Disease but did not respond to treatment. The patient was eventually diagnosed with MIS-C based on the CDC criteria and treated with intravenous immunoglobulin (IVIG) and methylprednisolone. The symptoms improved with treatment. The authors acknowledge the patient and her parents for giving permission to publish the details of the case. [Extracted from the article]

Atopic dermatitis and psoriasis are prevalent inflammatory skin conditions that significantly impact the quality of life of patients, with diverse treatment options available. Despite advances in understanding their underlying mechanisms, recent research highlights the significance of interleukins IL-18 and IL-37, in Th1, Th2, and Th17 inflammatory responses, closely associated with the pathogenesis of psoriasis and atopic dermatitis. Hence, IL-18 and IL-37 could potentially become therapeutic targets. This narrative review synthesizes knowledge on these interleukins, their roles in atopic dermatitis and psoriasis, and emerging treatment strategies. Findings of a literature search up to 30 May 2024, underscore a research gap in IL-37-targeted therapies. Conversely, IL-18-focused treatments have demonstrated promise in adult-onset Still's Disease, warranting further exploration for their potential efficacy in psoriasis and atopic dermatitis. [ABSTRACT FROM AUTHOR]

The objectives of the study were to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler's syndrome (SchS) according to a multicenter Russian cohort. An observational retrospective study for a 10-year period (2012–2022) involved 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis (eight women and nine men). The diagnosis of all of them corresponded to the Strasbourg diagnostic criteria. The age of patients ranged from 25 to 81 years (Me 53[46; 56]). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46[39; 54]), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5[3; 6]), in three patients it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDs (CAPS, TRAPS, and HIDS) were excluded from all patients at the prehospital stage. The referral diagnosis for all of them was Still 's disease in adults. Clinical manifestations of the disease in all patients included fatigue, lethargy, fatigue, rash, and fever. In all patients, skin elements were urticular and were accompanied by itching in 6 (37.5%) patients. Bone pain was observed in 12 (70.6%) patients; arthralgias, in 16 (94.1%); arthritis, in 9 (52.9%); myalgia, in 7 (41.2%); and weight loss, in 4 (23.5%). Lymphadenopathy was detected in 6 (35.3%) patients; enlarged liver, in 6 (35.3%); pericarditis, in 4 (23.5%); angioedema, in 6 (35.3); redness and dryness in the eyes, in 3 (17.6%); sore throat, in 2 (11.8%); abdominal pain, in 1 (5.9%), distal polyneuropathy, in 2 (11.8%); paraesthesia, in 1 (5.9%); and chondritis of the auricles, in 1 (5.9%). Monoclonal gammopathy was detected in all patients with a secretion level of 2.9–15.1 g/L: IgMk (n = 10, 64.7%), less often IgMλ (n = 2), IgGk (n = 2), IgGλ (n = 1), and IgAλ (n = 1). Ben-Jones protein was not detected in any of them. All patients had an increased level of ESR and CRP. Before inclusion in the study, 16 patients received GCs (94.1%) with a temporary effect that disappeared with dose reduction or cancellation. Seven patients received cDMARDs, including methotrexate (5), hydroxychloroquine (2), and cyclophosphamide (1). All patients received NSAIDs and antihistamines, as well as biologics, including the anti-B-cell drug rituximab (1), monoclonal ABs to IgE omalizumab (2, 1 without effect and 1 with partial effect), IL-1i canakinumab (n = 10, 58.8%) subcutaneously once every 8 weeks, and anakinra (n = 4, 23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3 patients. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1i, 10 out of 11 (90.9%) patients received a complete response in terms of the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In one patient, a partial response to the administration of anakinra was detected; however, after switching to canakinumab, the effect of treatment was finally lost. One patient received IL-6i for 8 months with an incomplete effect and a positive dynamics after switching to anakinra. Thus, anakinra was initially prescribed to four patients and changed to canakinumab in two of them; canakinumab was started as the first drug in seven patients. Treatment with anakinra was continued in two patients; with canakinumab, in nine patients. In one patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation; however, subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born by the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAEs were noted. SchS is a rare multifactorial/non-monogenic AID that should be differentiated from a number of rheumatic diseases and other AIDs. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1i is a highly effective and safe option in the treatment of such patients. [ABSTRACT FROM AUTHOR]

Background: Caspase-1 is a crucial component in the inflammasome activation cascade. This study evaluated the potential of serum caspase-1 level as an inflammatory biomarker in patients with adult-onset Still's disease (AOSD). Methods: The study included 51 consecutive patients diagnosed with AOSD based on the Yamaguchi criteria, 66 patients with rheumatoid arthritis (RA) as disease control, and 36 healthy controls (HCs). Serum caspase-1 concentrations were measured using enzyme-linked immunosorbent assay. The serum 69 cytokine levels were analyzed using a multisuspension cytokine array in patients with AOSD, and a cluster analysis of each cytokine was performed to determine specific molecular networks. Results: Patients with AOSD had significantly increased serum caspase-1 levels versus patients with RA (p < 0.001) and HCs (p < 0.001). Additionally, serum caspase-1 demonstrated significant positive correlations with AOSD disease activity score (Pouchot score, r = 0.59, p < 0.001) and serum ferritin (r = 0.54, p < 0.001). Furthermore, among patients with AOSD, significant correlations existed between serum caspase-1 and inflammatory cytokines, including interleukin-18. Immunoblot analysis detected the cleaved form of caspase-1 (p20) in the serum of untreated patients with AOSD, not in those from patients with inactive AOSD receiving immunosuppressive treatments. Conclusions: Caspase-1 is a useful biomarker for AOSD diagnosis and monitoring. Caspase-1 activation could be correlated with the inflammatory component of AOSD, specifically through proinflammatory cytokine induction via inflammasome activation cascades. [ABSTRACT FROM AUTHOR]

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of α‐synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self‐induced aggregation of α‐synuclein into amyloid‐type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII‐induced α‐synuclein aggregation. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 53-year-old man with adult-onset Still's disease who developed streptococcal toxic shock syndrome (STSS) due to Streptococcus dysgalactiae subsp. equisimilis (SDSE) while receiving treatment with tocilizumab (TCZ), an anti-IL-6 receptor antibody. The article discusses the potential modifying effect of TCZ on the immune response and the pathophysiology of SDSE infection, which may have led to retroperitoneal panniculitis and atypical STSS. The case highlights the importance of considering the risk of infectious complications in patients receiving TCZ therapy. [Extracted from the article]

This article discusses the relationship between the timing of tocilizumab (TCZ) introduction and its glucocorticoid-sparing effects on adult-onset Still's disease (AOSD). A retrospective observational study was conducted on AOSD patients who received TCZ and high-dose glucocorticoids for remission-induction therapy. The study found that early introduction of TCZ within 3 weeks of initiating glucocorticoid treatment effectively reduced the glucocorticoid dose requirement without increasing adverse events or the risk of macrophage activation syndrome. However, further research is needed to determine the efficacy of early TCZ introduction in AOSD treatment. [Extracted from the article]

Adult-onset Still's disease (AOSD) is a multigenic autoinflammatory disease with a severe systemic involvement. Because of the rarity of the disease, most published cohorts are multicentric. The aim of this report is to describe a monocentric cohort of AOSD patients, reporting clinical features and response to therapy in a long follow-up. Thirty-eight patients, attending the Clinical Immunology Unit and fulfilling Yamaguchi, Fautrel, or Daghor-Abbaci classification criteria for AOSD, were recruited for this study. In all patients, clinical and serological data were collected at diagnosis and every 6 months thereafter. The Pouchot score was calculated at every visit. Fever, arthromyalgia, and skin rash were the most frequent manifestations, followed by lymphadenopathy, sore throat, arthritis, splenomegaly, hepatic involvement, pleuropericarditis, and weight loss. As far as the disease course is concerned, 25% presented a monocyclic and 35% a polycyclic pattern, and 40% developed chronic articular involvement. Severe complications were observed at disease onset in 21% of the patients. All of the patients were treated with steroids; 74% also received conventional synthetic disease-modifying anti-rheumatic drugs (methotrexate in most cases) and 71% biological disease-modifying anti-rheumatic drugs (interleukin-1 inhibitors in most cases). Therapeutic switching for lack/loss of efficacy or adverse drug reactions was necessary in 66%. The analysis of this cohort confirms that AOSD is a complex, severe, and heterogeneous disease. However, despite long-term treatment and comorbidities, therapies are effective and well tolerated. The therapeutic armamentarium now available allows long-lasting remission with low immunosuppression to be achieved in most patients. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case details adult‐onset Still's disease (AOSD) onset post‐human papillomavirus (HPV) vaccination and acute gastroenteritis. The timing of HPV vaccine and vaccine‐autoimmune disease literature may potentially confound the well‐established link between infections and AOSD onset. [ABSTRACT FROM AUTHOR]

Objective: We aimed to review the literature on the clinical presentation, renal pathology, treatment, and outcome of renal manifestations in adult-onset Still's disease (AOSD). Methods: We used PRISMA guidelines for our systematic review and included all English-language original articles from inception till September 15, 2023, on AOSD and kidney involvement in any form. Data on patient demographics, diagnostic criteria, clinical presentation, renal pathology, treatment employed including dialysis, outcome, cause of death were collected and analyzed. Results: The median age at the diagnosis of renal issues was 37, with a higher prevalence among females (58.1%). Among the cases, 28 experienced renal problems after being diagnosed with AOSD, 12 had simultaneous diagnoses of renal issues and AOSD, and in 4 cases, renal problems appeared before AOSD diagnosis. Out of the 44 cases, 36 underwent renal biopsy, revealing various pathology findings including AA amyloidosis (25%), collapsing glomerulopathy (11.4%), thrombotic microangiopathy (TMA) (11.4%), IgA nephropathy (9.1%), minimal change disease (6.8%), and others. Some cases were clinically diagnosed with TMA, proximal tubular dysfunction, or macrophage activation syndrome-related acute kidney injury. Treatment approaches varied, but glucocorticoids were commonly used. Renal involvement was associated with increased mortality and morbidity, with 6 out of 44 patients passing away, 4 progressing to end-stage renal disease (ESRD), and data on 2 cases' outcomes not available. Conclusion: Renal manifestations in AOSD are diverse but rarely studied owing to the rarity of the disease. Studies with larger data would be essential to study further on the pathogenesis and implications. [ABSTRACT FROM AUTHOR]

This article, "Parkinson's disease: Still waiting for a cure," offers a unique perspective on living with Parkinson's disease. The author, who has Young Onset Parkinson's Disease, reflects on their experiences in regulatory and scientific meetings, the impact of the patient voice in drug development, and the challenges of living with a progressive disease. They emphasize the importance of a patient-centric approach in research and drug development, highlighting the need for disease-modifying interventions and the use of biomarkers in clinical trials. The author calls for urgency in the research process and emphasizes the importance of collaboration and data sharing. Overall, the article provides hope for the future of Parkinson's disease research and drug development. [Extracted from the article]

The article titled "VEXAS Syndrome: Clinical Case Series From a Canadian Cohort" provides a case series of VEXAS syndrome, an autoinflammatory condition caused by a somatic mutation in the UBA1 gene. The study describes six patients with a median age of disease onset at 67.5 years, all experiencing constitutional symptoms and dermatological findings. The article suggests considering VEXAS syndrome in treatment-resistant relapsing polychondritis and highlights its presence in a female patient with Turner syndrome. The text also discusses a case of VEXAS syndrome with multiple complications and provides a table summarizing pharmacotherapy options. The authors express gratitude to healthcare professionals for confirming somatic variants associated with VEXAS syndrome. [Extracted from the article]

We use this study to analyze the trends in in-hospital length of stay, total hospital charges, and mortality among adult patients with a primary diagnosis of adult-onset still's disease (AOSD). We used the 2016–2019 National Inpatient Sample (NIS) database to conduct a retrospective study on adult AOSD patients (≥18 years old). We analyzed data on baseline patient and hospital characteristics and determined trends in in-hospital mortality, length of stay (LOS), and total hospital charges (TOTCHG). Univariate and multivariate linear and logistic regression analyses were performed to identify factors that independently affected these outcomes. Among the 1615 AOSD hospitalizations, the mean LOS was 7.34 days and the mean TOTCHG was 68,415.31 USD. Macrophage activating syndrome (MAS), disseminated intravascular coagulation (DIC), and a large hospital size were shown to statistically increase the LOS and TOTCHG, while a Native American background was shown to statistically decrease both. The mean in-hospital mortality was 0.929%, with age being the only independent predictor. Our findings reveal an increase in the economic burden of AOSD hospitalizations despite declining admissions and mortality rates. Complications, like MAS and DIC, were found to significantly contribute to this burden despite treatment advancements. Our study indicates the importance of investigating new strategies to prevent these complications. [ABSTRACT FROM AUTHOR]

Background: Kikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical lymphadenopathy. It can mimic many sinister diseases such as lymphoma, tuberculosis, and systemic lupus erythematosus. Aseptic meningitis due to Kikuchi disease is extremely rare, and majority were reported from Japan. There have been no published cases of aseptic meningitis due to Kikuchi disease in Sri Lanka. Case presentation: A 29 years old Sri Lankan female presented with a prolonged fever for three weeks with an associated headache for five days duration. She developed painful cervical lymphadenopathy during the hospital stay. She has been previously well and had been vaccinated against COVID-19 six weeks before. Her lumbar puncture showed lymphocytic pleocytosis with marginally elevated protein levels and reduced ratio of serum to CSF sugar. Lymph node biopsy was consistent with necrotizing lymphadenitis. She was subsequently diagnosed with Kikuchi disease complicated with aseptic meningitis. She responded to corticosteroids well and had an uneventful recovery. Conclusion: Kikuchi disease is a rare self-limiting disorder that can be complicated with aseptic meningitis on infrequent occasions. Other conditions such as tuberculosis, lymphoma, systemic lupus erythematosus, and adult-onset Still's disease should be considered as differential diagnoses. Knowledge of Kikuchi disease and its complications will prevent unnecessary investigations which delay the early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude between patients with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS; a form of secondary HLH) in systemic juvenile idiopathic arthritis (sJIA). Therefore, this study aimed to develop a population pharmacokinetic model for emapalumab across a patient population with a wide range of total (free and emapalumab-bound) IFNγ levels using observations from patients with primary HLH or MAS in sJIA in clinical trials. Methods: Pharmacokinetic data were pooled (n = 58; 2709 observations) from studies enrolling patients administered emapalumab for primary HLH or MAS in sJIA. Patients with primary HLH were administered emapalumab 1 mg/kg (potentially increasing to 3, 6, and up to 10 mg/kg based on clinical response) every 3 days. Patients with MAS in sJIA were administered emapalumab 6 mg/kg, followed by 3 mg/kg every 3 days until day 15 and twice weekly until day 28. An earlier population PK model was re-parameterized using this data. Results: The final model for emapalumab comprised a 2-compartment model with first-order elimination. Emapalumab clearance remains constant when the total IFNγ concentration (free and emapalumab-bound) is < ~ 10,000 pg/ml but increases proportionally to total IFNγ concentration above this threshold. Emapalumab clearance was estimated to be 0.00218, 0.00308, 0.00623 and 0.01718 l/h at total serum IFNγ concentrations of 103, 104, 105 and 106 pg/ml, respectively, with corresponding terminal half-lives of 19.2, 13.8, 7.18 and 3.12 days for a 1-year-old patient weighing 10 kg with primary HLH. The median terminal half-life for emapalumab in patients with MAS in sJIA was estimated to be 24.0 (range, 6.13–32.4) days, which is similar to observations in healthy volunteers. Conclusions: Emapalumab pharmacokinetics in patients with primary HLH and MAS in sJIA were described by a two-compartment model with fixed allometric exponents and an age-related effect. Differences in total IFNγ levels between patients with primary HLH and MAS may affect emapalumab pharmacokinetics, suggesting that each indication may require different dosing to rapidly control hyperinflammation. Trial registration: Clinicaltrials.gov identifiers: NCT01818492, NCT03311854 and NCT02069899. Plain Language Summary: Patients with a rare condition called hemophagocytic lymphohistiocytosis (HLH) produce excessive amounts of a molecule called interferon-gamma. Excessive interferon-gamma causes extreme (or hyper) inflammation, which can be fatal. A drug called emapalumab can be used to block the action of interferon-gamma. However, we need to understand how the concentration of emapalumab in the blood changes over time to ensure that the correct dose is administered when attempting to control interferon-gamma-driven hyperinflammation in patients with HLH. Because HLH is a rare condition, data from a small number of patients were used to create a mathematical model that predicts emapalumab concentrations in the blood at various times after it is administered. Importantly, the amount of interferon-gamma observed in patients with different types of HLH is highly variable, which can alter how quickly emapalumab is removed from the blood. The higher interferon-gamma levels go above a certain threshold, the faster emapalumab is removed. In particular, interferon-gamma levels generally only exceed this threshold in patients with a familial or genetic form of HLH (primary HLH). Interferon-gamma levels in patients with a type of HLH called macrophage activation syndrome, which can occur in patients with systemic juvenile idiopathic arthritis (sJIA), do not usually cross the threshold associated with faster removal of emapalumab. This means that higher dosing may be required for patients with primary HLH compared with patients who have macrophage activation syndrome in sJIA to expedite control of hyperinflammation because of differences in the rate at which emapalumab is removed from the blood. [ABSTRACT FROM AUTHOR]

Objectives Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. Methods The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Results Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. Conclusion In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline. [ABSTRACT FROM AUTHOR]

Background: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. Methodology: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. Results: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. Conclusions: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the potential use of soluble programmed death 1 (sPD-1) as a biomarker for predicting mortality in patients with adult-onset Still's disease (AOSD). AOSD is a systemic inflammatory disease with a varied clinical course, and currently, there are no established biomarkers for predicting prognosis. The study included 69 patients with AOSD and found that higher levels of sPD-1 were associated with worse survival outcomes. The authors suggest that sPD-1 could be a valuable indicator for mortality in patients with AOSD. However, further research is needed to confirm the usefulness of sPD-1 levels as an indicator of diagnosis and disease activity in AOSD patients. [Extracted from the article]

This article explores the potential connection between adult-onset Still's disease (AOSD) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. It presents a case study of a patient who developed SAPHO syndrome after being diagnosed with AOSD. The article suggests that the immune system abnormalities and genetic susceptibility associated with these diseases may contribute to their coexistence. However, more research is needed to fully understand the relationship between AOSD and SAPHO syndrome. The article concludes by emphasizing the need for further investigation into the potential association and genetic basis of these conditions. [Extracted from the article]

The article discusses Still's disease, also known as systemic juvenile idiopathic arthritis (SJIA), which is a complex autoimmune disorder affecting individuals of all ages. Recent advancements in research and treatment have led to more precise diagnostic tools and personalized treatment strategies, improving outcomes for patients. The use of anti-inflammatory medications and biologic therapies has reshaped the treatment landscape, offering hope for those with SJIA and adult-onset Still's disease (AOSD). Collaboration between pediatric and adult rheumatologists is crucial in providing comprehensive care and developing innovative treatment approaches. The principles of precision medicine, personalized care, and collaboration guide efforts to enhance the management of Still's disease and improve the lives of affected patients. [Extracted from the article]

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001-0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease. [ABSTRACT FROM AUTHOR]

Background: Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing. Case presentation: A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml). Conclusion: Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches. [ABSTRACT FROM AUTHOR]

Macrophage activation syndrome (MAS) is a rare complication of autoimmune inflammatory rheumatic diseases (AIIRD) characterized by a progressive and lifethreatening condition with features including cytokine storm and hemophagocytosis. Predisposing factors are typically associated with microbial infections, genetic factors (distinct from typical genetically related hemophagocytic lymphohistiocytosis (HLH)), and inappropriate immune system overactivation. Clinical features include unremitting fever, generalized rash, hepatosplenomegaly, lymphadenopathy, anemia, worsening liver function, and neurological involvement. MAS can occur in various AIIRDs, including but not limited to systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), systemic lupus erythematosus (SLE), Kawasaki disease (KD), juvenile dermatomyositis (JDM), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), etc. Although progress has been made in understanding the pathogenesis and treatment of MAS, it is important to recognize the differences between different diseases and the various treatment options available. This article summarizes the cell types and cytokines involved in MAS-related diseases, the heterogeneity, and treatment options, while also comparing it to genetically related HLH. [ABSTRACT FROM AUTHOR]

Background: Autoinflammation with cytokine dysregulation may be implicated in the pathophysiology of adult-onset Still's disease (AOSD); however, the relationship between galectins and cytokines in patients with active AOSD remains unknown. We aimed to examine the relationship between circulating cytokines/chemokines and galectin-3 (Gal-3) or its ligand, Mac-2 binding protein glycosylation isomer (M2BPGi), in Japanese patients with AOSD. Methods: We recruited 44 consecutive patients diagnosed with AOSD according to the Yamaguchi criteria, 50 patients with rheumatoid arthritis (RA) as disease controls, and 27 healthy participants. Serum M2BPGi levels were directly measured using a HISCL M2BPGi reagent kit and an automatic immunoanalyzer (HISCL-5000). Serum Gal-3 concentrations were measured by enzyme-linked immunosorbent assay. The serum levels of 69 cytokines were analyzed in patients with AOSD using a multi-suspension cytokine array. We performed a cluster analysis of each cytokine expressed in patients with AOSD to identify specific molecular networks. Results: Significant increases in the serum concentrations of Gal-3 and M2BPGi were found in the serum of patients with AOSD compared with patients with RA and healthy participants (both p <0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p <0.001) and serum ferritin levels. However, no significant correlations were observed between serum M2BPGi levels and AOSD disease activity scores (Pouchot score, r = 0.32, p = 0.06) or serum ferritin levels. Furthermore, significant correlations were observed between the serum levels of Gal-3 and various inflammatory cytokines, including interleukin-18, in patients with AOSD. Immunosuppressive treatment in patients with AOSD significantly reduced serum Gal-3 and M2BPGi levels (p = 0.03 and 0.004, respectively). Conclusions: Although both Gal-3 and M2BPGi were elevated in patients with AOSD, only Gal-3 was a useful biomarker for predicting disease activity in AOSD. Our findings suggest that circulating Gal-3 reflects the inflammatory component of AOSD, which corresponds to proinflammatory cytokine induction through inflammasome activation cascades. [ABSTRACT FROM AUTHOR]

The European Journal of Rheumatology is an open access journal that covers various aspects of rheumatology. It publishes original articles, reviews, case-based reviews, and letters to the editor. The journal is aimed at academicians, practitioners, specialists, and students in the field of rheumatology. The document provides a schedule of sessions and presentations at a conference on autoimmune diseases, covering topics such as COVID-19, lupus, vasculitis, and novel approaches to handling autoimmune diseases. It also contains summaries of presentations on topics related to autoimmune diseases, including myositis, post-COVID syndrome, uveitis, and genetic predisposition to autoimmunity. The document discusses cell therapy, novel therapies, and the impact of environmental factors on autoimmune diseases. It explores the potential of CAR-T cell therapy, mesenchymal stromal cell transplantation, cannabis, therapeutic peptides, and RNA gene expression in the treatment and management of autoimmune diseases. The document also highlights the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), finding that SLE patients have an increased risk of severe COVID-19 and higher mortality rates. The document contains summaries of various research studies and discussions related to autoimmune diseases, covering topics such as inflammatory signals in myeloid cells, cardiovascular risk profile of rheumatoid arthritis patients, and immunonutritional status of patients with systemic lupus erythematosus. It also explores subjects such as autoantib [Extracted from the article]

This document is a collection of abstracts from the Australasian Journal of Dermatology. The articles cover a range of topics, including the diagnosis of bacterial skin infections, the economic viability of genotyping in epilepsy patients, and the diagnosis of fungal infections. Other articles discuss the complications of certain skin conditions, such as Stevens-Johnson Syndrome and toxic epidermal necrolysis, and the potential association between a COVID-19 vaccine and toxic epidermal necrolysis. The document also includes case studies and discussions on the treatment of different dermatological conditions, such as morphoea and lymphomatoid papulosis. Additionally, there are articles on the impact of bariatric surgery on dermatology drugs, the treatment of livedoid vasculopathy, and the role of interleukin-17 in pyoderma gangrenosum. [Extracted from the article]

The investigation of the prediction of disease population is a noticeable exploration topic in the field of sciences. As a type of neurological disease, the incidence and prevalence of Parkinson's disease are still difficult to accurately study. In this paper, a method is proposed to forecast the number of incident cases (NumIn), incidence rate (InRa), the number of prevalent cases (NumPr), and prevalence rate (PrRa) of Parkinson's disease in ten countries selected. Using past data on the incidence rate, the number of prevalent cases, and the prevalence rate from 1990 to 2019, three types of fractal interpolations with different fractal dimensions are constructed for reconstructing the past data, where the vertical scaling factors are determined by the method proposed in this article. Then, the Long Short-Term Memory (LSTM) model is employed to forecast the values of NumIn, InRa, NumPr, and PrRa with Parkinson's disease in 2020. Meanwhile, the autoregressive integrated moving average model is used to predict the values compared with the LSTM model. The evaluation metrics employed for error calculation include the root mean square error and the coefficient of determination (R 2). According to the proposed optimal criteria, the best predicted results are the average of three types of prediction values based on the LSTM model by analyzing and comparing eight predicted results. [ABSTRACT FROM AUTHOR]

The given text provides concise summaries of various medical case reports and studies, covering a wide range of topics. These summaries offer valuable insights into rare medical conditions and their management, emphasizing the importance of early diagnosis and treatment. [Extracted from the article]

Background: Adult‐onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated. Methods: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co‐occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis. Results: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p =.829. Conclusions: A majority of patients with AOSD‐associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk‐stratify high‐risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD‐associated TMA. [ABSTRACT FROM AUTHOR]

Introduction: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear. Methods: We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineural hearing loss from a cohort intended to study preclinical phases of Alzheimer's disease. Participants are volunteers over 55 years without cognitive impairment. We correlated the results of an objective auditory evaluation with brain amyloid and p-tau181 levels and with the outcomes of a comprehensive neuropsychological assessment. Results: Fifty-five subjects at different stages of the Alzheimer's disease continuum were evaluated. There were no statistically significant correlations between amyloid-β and p-tau levels and any of the objective auditory measures. A weak but significant correlation was found between amyloid-β values and the Hearing Handicap Inventory for the Elderly. The neuropsychological domains more correlated to hearing loss were executive function and processing speed. Discussion: Age-related hearing loss is not linked to any pathological markers of Alzheimer's disease nor to neuropsychological domains typically affected in this disease. The Hearing Handicap Inventory for the Elderly has an important component of subjectivity and further studies are needed to explore its relationship with amyloid-β levels. [ABSTRACT FROM AUTHOR]

Aim: This study addresses the challenge of predicting the course of Adult‐onset Still's disease (AoSD), a rare systemic autoinflammatory disorder of unknown origin. Precise prediction is crucial for effective clinical management, especially in the absence of specific laboratory indicators. Methods: We assessed the effectiveness of combining traditional biomarkers with the k‐medoids unsupervised clustering algorithm in forecasting the various clinical courses of AoSD—monocyclic, polycyclic, or chronic articular. This approach represents an innovative strategy in predicting the disease's course. Results: The analysis led to the identification of distinct patient profiles based on accessible biomarkers. Specifically, patients with elevated ferritin levels at diagnosis were more likely to experience a monocyclic disease course, while those with lower erythrocyte sedimentation rate could present with any of the clinical courses, monocyclic, polycyclic, or chronic articular, during follow‐up. Conclusion: The study demonstrates the potential of integrating traditional biomarkers with unsupervised clustering algorithms in understanding the heterogeneity of AoSD. These findings suggest new avenues for developing personalized treatment strategies, though further validation in larger, prospective studies is necessary. [ABSTRACT FROM AUTHOR]

The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition that lacks a universally accepted diagnostic test. The clinical presentation comprises symptoms such as fever, rash, joint pain, sore throat, swelling of lymph nodes, and enlargement of the liver and spleen. The diagnostic criteria developed by Yamaguchi and Fautrel are commonly employed because of their great sensitivity and specificity. However, there are cases in which individuals may not meet these criteria but still demonstrate symptoms of AOSD. In this case, we report an elderly patient who has been diagnosed with AOSD but does not meet the criteria for any of these criteria. We discussed the factors contributing to impaired sensitivity and put forth various suggestions to enhance the sensitivity of these criteria. [ABSTRACT FROM AUTHOR]