Patients with established rheumatic disorders may develop complications of macrophage activation syndrome due to severe flares of the underlying disease (adult-onset Still\'s disease, SLE); however, in most other rheumatic disorders, MAS develops in association with identified viral or other infectious triggers. It is therefore important to pursue appropriate studies to identify potential infectious triggers in rheumatic disease patients who develop MAS. Management is best directed toward treatment of the triggering infections and combinations of high-dose corticosteroids, calcineurin inhibitors, and biologic therapies targeting IL-1 and/or IL-6 to suppress the associated cytokine storm.

Elevated liver enzymes are commonly observed among adult-onset Still\'s disease (AOSD), but severe acute liver failure is extremely rare. Although severe acute liver failure associated with AOSD poses a life-threatening condition, the appropriate treatment is unclear. Some case reports have demonstrated the efficacy of high-dose prednisolone (PSL) and cyclosporin A (CyA), although the adverse effects of CyA led certain patients to cease its use. Therefore, an alternative treatment option is crucial, and thus far, there have been no reports of tocilizumab (TCZ) being used for this severe phenotype. Here, we report the first case of successful treatment using TCZ as maintenance therapy for severe ALF associated with AOSD. Following initial treatment with high-dose PSL and CyA, our case was switched to TCZ due to CyA-related side effects including alopecia and tremors. Our case highlights TCZ as a potential option for maintenance therapy of this severe condition.

OBJECTIVE: Risk factors for adverse drug reactions (ADRs) associated with prophylactic sulfamethoxazole-trimethoprim (SMX/TMP) in patients with rheumatic and musculoskeletal diseases undergoing immunosuppressive therapy remain unclear, we aimed to identify the risk factors associated with ADRs.
METHODS: Consecutive patients with rheumatic and musculoskeletal diseases, who were admitted to Keio University Hospital and received prophylactic administration of SMX/TMP, were included. Data regarding ADRs to SMX/TMP were collected to identify associated risk factors using multivariable analysis.
RESULTS: Of 438 patients included in the analysis, 82 (18.7%) experienced ADRs. Patients in the ADRs group were significantly older, had chronic kidney disease, and exhibited lower lymphocyte and platelet counts, lower albumin levels, lower estimated glomerular filtration rates, higher aspartate aminotransferase levels, and higher ferritin levels than those in the non-ADR group. Regarding underlying rheumatic and musculoskeletal diseases, adult-onset Still\'s disease (ASD) was associated with a significantly higher incidence of ADRs (67%) than other diseases. Multivariable analysis identified the presence of ASD and low lymphocyte counts as independent risk factors for allergic ADRs, and older age and use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers for non-allergic ADRs.
CONCLUSIONS: Risk factors for ADRs associated with prophylactic SMX/TMP treatment in patients with rheumatic and musculoskeletal diseases were identified.

Aims/Background Adult-onset Still\'s disease (AOSD) shares similar clinical symptoms with sepsis. Thus, differentiating between AOSD and sepsis presents a great challenge while making diagnosis. This study aimed to analyse the changes in blood microbiota related to AOSD and sepsis using metagenomic next-generation sequencing (mNGS), identify potential biomarkers that distinguish AOSD from sepsis, and explore the diagnostic value of mNGS in differentiation between these two pathological conditions. Methods Clinical data of four AOSD patients and four sepsis patients treated in the Department of Rheumatology and Immunology, The Affiliated Hospital of Xuzhou Medical University between October 2021 and February 2022 were collected. The mNGS diagnostic records of these patients were analysed for microbial correlations in terms of species taxonomic structure and beta diversity by comparing blood microbiota between AOSD and sepsis. The biomarkers with the strongest capability in distinguishing the subgroups were screened using a random forest algorithm. Results There was no statistically significant differences between AOSD patients and sepsis controls in terms of gender and age (p > 0.05). A total of 91 operational taxonomic units (OTUs) were obtained. At the level of phylum, Proteobacteria, Ascomycota and Basidiomycota were present in high abundances in both groups (79.76%, 14.18% and 3.30% vs 54.03%, 32.77% and 5.81%). At the genus level, the abundances of Parainfluenzae, Aspergillus and Ralstonia were the top three highest in the AOSD group (73.88%, 10.92% and 5.48%), while Ralstonia, Aspergillus and Malassezia were ranked as the top three in the sepsis group in term of abundance (48.69%, 27.36% and 5.52%). In beta-diversity analysis, there were advances shown in visual principal coordinates analysis (PCoA) and non-metric multidimensional scaling (NMDS) between the AOSD group and sepsis group (p < 0.05), with little significant differences in the analysis of similarities (Anosim) (p > 0.05). Linear discriminant analysis effect size (LEfSe) showed that Mucoromycota, Saccharomycetes, Moraxellales, Mucorales, Xanthomonadales, Saccharomycetales, Acinetobacter, Stenotrophomonas, Yarrowia, Apophysomyces, Acinetobacter johnson, Yarrowia lipolytica, Apophysomyces variabilis and Stenotrophomonas maltophilia were more enriched in sepsis group (p < 0.05). The top five variables with the strongest capability in distinguishing between AOSD and sepsis were Acinetobacter johnsonii, Apophysomyces variabilis, Propionibacterium acnes, Stenotrophomonas maltophilia and Yarrowia lipolytica. Conclusion The blood microorganisms in AOSD were different from sepsis, and mNGS was potential to distinguish between AOSD and sepsis.

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.

Objective Adult-onset Still\'s disease (AOSD) is a rare orphan disease, the diagnosis of which remains challenging. This study aimed to identify additional clues for establishing early diagnosis beyond the existing criteria. Methods A retrospective longitudinal cohort study was conducted at two community hospitals in Japan between March 2012 and December 2022. The clinical characteristics and medical histories of patients with AOSD were extracted from the clinical records. The primary outcome was to identify the key manifestations of AOSD for an early diagnosis beyond the existing criteria. Results Twenty-one patients (mean age, 58 years) were included in the study. Fever was the first symptom in 13 out of 21 patients (62%). Six out of 21 patients (29%) presented with a pruritic rash only, while two out of 21 (10%) initially presented with a sore throat. All patients visited more than one medical institution. The median time to reach a correct diagnosis was 41 days (IQR 19-138). Nineteen out of 20 patients (95%) exhibited a pruritic rash, identified as persistent pruritic linear streaks, with a median duration of 21 days (IQR 12-64) before the diagnosis of AOSD as a cutaneous manifestation. Conclusions Persistent pruritic linear streaks were a key feature in the context of an early diagnosis of AOSD, offering an option for reconsidering and revising the existing classification criteria.

We investigated the phenotypic characteristics of human leukocyte antigen (HLA)-E-expressing macrophages, NKG2A/CD94 expression in T and natural killer (NK) cells, and their interactions in patients with adult-onset Still\'s disease (AOSD). Peripheral blood mononuclear cells from 22 patients with AOSD and 22 healthy controls (HC) were used. Isolated monocytes were cultured first with macrophage colony-stimulating factor to differentiate into M0 macrophages and subsequently with lipopolysaccharide/interferon-γ or interleukin-4 to differentiate into M1 or M2 macrophages, respectively. HLA-E and NKG2A/CD94 expression levels were evaluated using quantitative RT-PCR and flow cytometry. HLA-E expression in M0 and M2 macrophages was significantly higher in patients with AOSD than in HC, and was positively correlated with serum C-reactive protein levels and erythrocyte sedimentation rate. NKG2A/CD94 expression in CD4 + and CD8 + T cells was significantly higher in patients with AOSD than in HC, but that in NK cells was not significantly different. In patients with AOSD, NKG2A expression in CD4 + T cells positively correlated with HLA-E expression in M0, M1, and M2 macrophages. CD94 expression in CD8 + T cells inversely correlated with HLA-E expression in M1 and M2 macrophages. NKG2A and CD94 expression in NK cells inversely correlated with HLA-E expression in M0, M1, and M2 macrophages. No significant correlation was observed between HLA-E and NKG2A/CD94 expression in HC. Increased expression of HLA-E in macrophages and NKG2A/CD94 in T cells can be observed in the inflammatory condition of AOSD. HLA-E-expressing macrophages may be associated with NKG2A/CD94 expression in T and NK cells with different correlations.

An inflammatory condition known as adult-onset Still\'s disease (AOSD) is typified by quotidian (daily) fevers, arthritis, and a transient rash. This report details the case of a 21-year-old female patient who presented to our hospital with polyarthritis, a red rash, and a high-grade fever for more than three months. History was suggestive of AOSD, which was further proved by investigation and Yamaguchi criteria for AOSD. Steroids and methotrexate were started, to which the patient responded very well and thereafter.

BACKGROUND: Adult-onset Still\'s disease (AOSD) is a rare systemic inflammatory disorder characterized by fever, arthritis, skin rash, and systemic symptoms. The etiology of AOSD is unknown; however, it is thought to be related to immune dysregulation. Although a rare disease, AOSD can significantly impact reproductive health, particularly during pregnancy. This case study assesses the implications of pregnancy in a patient with AOSD, as well as the potential for heredity of the disease. Neonatal hemophagocytic lympho-histiocytosis (HLH) is a rare and life-threatening disorder characterized by hyperinflammation and uncontrolled activation of immune cells, leading to multiple organ dysfunction. This case report aimed to introduce neonatal HLH from a mother with AOSD.
METHODS: This case study presents a 29-year-old female with AOSD who became pregnant and gave birth to a premature infant who was diagnosed with neonatal HLH. AOSD can significantly impact pregnancy and childbirth, as it may become more severe during pregnancy, with an increased risk of fetal loss and preterm birth. The management of AOSD during pregnancy involves the use of nonsteroidal anti-inflammatory drugs and glucocorticoids, as well as immunosuppressive agents in severe cases. However, the use of immunosuppressive agents during pregnancy may be associated with potential risks to the fetus. The hereditary implications of AOSD are unclear; however, available evidence suggests that genetic factors may play a role in the disease development.
CONCLUSIONS: AOSD can have significant implications for pregnancy and childbirth, including an increased risk of fetal loss and preterm birth. Neonatal HLH, a complication of AOSD in pregnancy, requires prompt diagnosis and management. Women with AOSD who are considering pregnancy should discuss their options with their healthcare provider and develop a management plan that addresses the potential risks to both mother and fetus.

This case presents a 23-year-old male with a rare presentation of lupus as fever of unknown origin (FUO). The patient\'s clinical symptoms, examination findings, and laboratory results painted a complex picture that necessitated considering macrophage activation syndrome and adult-onset Still\'s disease but ultimately led to the diagnosis of systemic lupus erythematosus. The case emphasizes the importance of including lupus in the differential diagnosis of FUO given the associated risks and higher mortality rates in this demographic, especially in males. Understanding lupus prevalence and classification criteria aids in diagnosis, highlighting the importance of a systematic approach for FUO and emphasizing timely intervention for improved patient outcomes.