small molecules

2026-08-01 | Shared bone marrow-spleen-lymph node hypermetabolic phenotype on 18F-FDG PET/CT in AOSD and undiagnosed FUO is associated with distinct glucocorticoid trajectories.

To characterize the bone marrow-spleen-lymph node hypermetabolic phenotype (BSL-HMP) identified by 18F-FDG PET/CT in patients with fever of unknown origin (FUO) and to explore whether imaging-defined inflammatory burden was associated with subsequent treatment intensity. This single-center retrospective cohort study included FUO patients who attended the Department of Rheumatology and Immunology at the Third Affiliated Hospital of Soochow University between January 2020 and January 2025, underwent 18F-FDG PET/CT, and exhibited BSL-HMP. After systematic exclusion of known diseases, patients were divided into an AOSD group and a FUO group that did not meet the Yamaguchi criteria at baseline, and differences between the two groups were compared. Exploratory unsupervised phenotyping of PET/CT features was performed using weighted Gower distance combined with PAM clustering. A mixed-effects model for repeated measures (MMRM) was further applied to analyze longitudinal changes in glucocorticoid dose across different clusters. An exploratory PET/CT-based model was additionally developed and internally evaluated to characterize cluster membership. A total of 95 patients were included, comprising 40 patients with AOSD and 55 patients with FUO. Although the FUO group showed PET/CT features broadly similar to those of the AOSD group, they had overall lower inflammatory marker levels and less frequent rash and sore throat. During follow-up, 8 patients in the FUO group eventually received an alternative definite diagnosis, while 47 remained undiagnosed. Unsupervised clustering classified the patients into high- and low-inflammatory-burden groups, with 80% of AOSD patients and 42% of FUO patients assigned to the high-inflammatory-burden group. Glucocorticoid dose trajectories differed significantly between clusters in the unadjusted MMRM (group-by-time interaction, P = 0.007) and after adjustment for age, sex, baseline diagnosis, C-reactive protein, and ferritin levels (P = 0.005). The difference remained significant after additional adjustment for baseline glucocorticoid dose (P = 0.029). DMARD use was also more frequent in the high-burden cluster (P = 0.011). BSL-HMP is a shared, nonspecific systemic inflammatory imaging phenotype. Among patients exhibiting this phenotype, PET/CT-based phenotyping identified different inflammatory burdens associated with subsequent glucocorticoid dose trajectories and DMARD use. These exploratory and hypothesis-generating findings suggest that PET/CT-derived inflammatory burden may help characterize patient heterogeneity, although further validation in independent prospective cohorts is warranted.

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2026-07-12 | Successful salvage treatment with baricitinib for macrophage activation syndrome complicating adult-onset Still's disease during interleukin-6 inhibition: a case report and literature review.

Adult-onset Still's disease is a systemic autoinflammatory disorder, and macrophage activation syndrome is a life-threatening hyperinflammatory complication. Interleukin-1 and interleukin-6 inhibitors have improved outcomes in refractory adult-onset Still's disease, but optimal management of macrophage activation syndrome, particularly when it develops during biologic therapy, remains uncertain. We report a case of a 49-year-old woman with articular-predominant adult-onset Still's disease who developed fulminant macrophage activation syndrome while receiving high-dose glucocorticoids, tacrolimus and the interleukin-6 receptor inhibitor tocilizumab. At the onset of macrophage activation syndrome, she had persistent fever, cytopenia, hyperferritinemia and liver dysfunction, and bone marrow examination revealed hemophagocytosis. Macrophage activation syndrome persisted despite two courses of intravenous methylprednisolone pulse therapy and continuation of tocilizumab. Tocilizumab was discontinued, and treatment was switched to the oral Janus kinase 1/2 inhibitor baricitinib in combination with glucocorticoids and tacrolimus. After this change, the patient experienced rapid defervescence, marked improvement in blood counts and ferritin levels, and sustained control of articular and systemic disease activity. Glucocorticoids were successfully tapered without relapse, and the patient remained in remission for more than two years without serious infections. To contextualize this case, we reviewed published reports on Janus kinase inhibition in adult-onset Still's disease, including cases complicated by macrophage activation syndrome. Multi-cytokine blockade through Janus kinase 1/2 inhibition, targeting overlapping interleukin-6, interferon-gamma and granulocyte-macrophage colony-stimulating factor pathways, may simultaneously suppress macrophage activation and systemic inflammation. This case highlights the potential of baricitinib as a therapeutic option for refractory adult-onset Still's disease-associated macrophage activation syndrome during interleukin-6 inhibition.

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2026-06-25 | What are the treatment options for managing adult-onset Still's disease?

The treatment of adult-onset Still's disease involves glucocorticoids, biological DMARDs like IL-1 and IL-6 inhibitors, and JAK inhibitors for refractory cases. The approach should be individualized, incorporating the latest evidence to manage the condition effectively while minimizing adverse effects.

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2026-06-18 | Adult-Onset Still's Disease in a Patient with Macrophage Activation Syndrome and Pre-Disseminated Intravascular Coagulation: A Case Report and Literature Review.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory condition characterized by high spiking fevers, arthralgia, typical rash, and systemic inflammation. Life-threatening complications, such as macrophage activation syndrome (MAS) and disseminated intravascular coagulation (DIC), may arise. Prompt recognition and intensive management are crucial for patient survival. This report presents a case of AOSD complicated by MAS and pre-DIC, accompanied by a review of the relevant literature. A 22-year-old male presented with recurrent high-grade fever, generalized red rash, lymphadenopathy, splenomegaly, and knee arthralgia. He met the Yamaguchi criteria for AOSD and the Ravelli criteria for MAS, and was diagnosed with pre-DIC using the Chinese Diagnostic Scoring System for DIC (CDSS). Following diagnosis, the patient received a comprehensive medical regimen that included glucocorticoids, the JAK inhibitor tofacitinib, infusion of fresh frozen plasma, and supportive care, resulting in clinical improvement. At the 8-month follow-up evaluation, the patient's condition remained stable without any signs of progression. This case underscores the critical importance of early identification of MAS and pre-DIC in AOSD, and demonstrates that aggressive immunosuppressive and supportive therapy, implemented within a multidisciplinary framework, is essential to prevent progression to overt DIC and multi-organ failure.

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2026-06-11 | Clozapine-associated systemic inflammatory reaction with adult-onset Still's disease-like features and marked interleukin-18 elevation in a patient with schizophrenia: a case report.

Clozapine can trigger early inflammatory adverse reactions ranging from transient fever to organ-dominant syndromes. It remains unclear whether this spectrum can also present as a systemic adult-onset Still's disease (AOSD)-like phenotype. A 54-year-old Japanese woman with long-standing treatment-resistant schizophrenia, psychogenic polydipsia with water intoxication, and overweight/obesity underwent olanzapine-to-clozapine cross-titration. Under the standard Japanese Clozaril Patient Monitoring Service procedure, clozapine was increased to 75 mg/day by day 23. Psychosis improved, but on day 27 she developed spike fever to 39.2 °C and fever-associated arthralgia. Infection was initially suspected, and empiric piperacillin/tazobactam was started while clozapine was continued because no neutropenia, marked eosinophilia, or severe organ-dominant reaction was evident. During days 27-30, no infectious focus was identified, and an evening spike-fever pattern with arthralgia and sore throat increased suspicion for clozapine-associated inflammation. Ferritin and interleukin-18 (IL-18), an autoinflammatory cytokine associated with Still's disease, were measured after a Still-like phenotype was suspected. Clozapine was discontinued on day 35. However, the syndrome evolved with recurrent fever up to 40.2 °C, evanescent rash, edema/hypoxemia, neutrophil-predominant inflammation, hypoalbuminemia, ferritin elevation, and serial IL-18 increase from 470 pg/mL on day 33 to 1,160 pg/mL on day 49. Infection, established autoimmune disease, drug reaction with eosinophilia and systemic symptoms, and neuroleptic malignant syndrome were not favored. Overt myocarditis was not supported by normal troponin/creatine kinase and nonspecific electrocardiographic findings, but echocardiography was not performed. She fulfilled Yamaguchi and Fautrel classification criteria for AOSD-like illness. Consequently, hydrocortisone and supportive care were used, and no further spike fever occurred after day 49. This case expands the clozapine inflammatory spectrum to a systemic AOSD-like phenotype with marked serial IL-18 elevation. When spike fever with systemic inflammation emerges during clozapine titration, early temporary interruption of clozapine should be considered, and persistent Still-like inflammation after discontinuation may warrant anti-inflammatory supportive treatment, including corticosteroids in selected cases.

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proteins

2026-08-12 | Trained immunity in autoinflammatory diseases: Cellular reprogramming across the monogenic-polygenic spectrum.

Trained immunity, an innate immunological memory induced by epigenetic and metabolic reprogramming, has changed the paradigm of host defense and pathogenesis of chronic inflammatory disease. Unlike adaptive immunological memory, trained immunity is characterized by the ability of innate immune cells and their progenitors to respond more robustly or differently to subsequent stimulations and contributes to chronic inflammatory conditions. Emerging data suggests that this process might be essential in autoinflammatory and immune-mediated inflammatory illnesses by enhancing sterile inflammation, decreasing activation thresholds, and boosting disease chronicity. This narrative review summarizes the existing evidence relating trained immunity to monogenic and polygenic autoinflammatory diseases. The greatest evidence in monogenic disease is for mevalonate kinase deficiency, where dysregulated mevalonate metabolism directly overlaps with conventional trained immunity pathways. Moderate evidence exists for familial Mediterranean fever, cryopyrin-associated periodic syndromes, and tumor necrosis factor receptor-associated periodic syndrome. For other rare hereditary autoinflammatory diseases, data are still inadequate. There is convincing evidence for a role of trained immunity in polygenic disorders like gout, atherosclerosis, obesity-associated "metaflammation", and type 2 diabetes and increasing evidence in Behçet's disease, adult-onset Still's disease, psoriasis, hidradenitis suppurativa, inflammatory bowel disease, and related inflammatory spectrum disorders. A major conceptual finding is that autoinflammatory illnesses may be a dynamic interplay between hereditary susceptibility and dysfunctional innate immune memory, rather than isolated static inflammatory abnormalities. However, information gaps still exist in reprogramming at the progenitor level, disease-specific epigenetic markers, and the reversibility of trained states. Understanding these systems may allow the development of therapeutic techniques to de-train abnormal innate immunological memory and obtain resilience for diseases.

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2026-08-02 | Adult-Onset Still's Disease Presenting as Fever of Unknown Origin: A Case Report.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder that should be considered in patients presenting with fever of unknown origin (FUO). Diagnosis is challenging due to overlapping features with infectious, autoimmune, and hematological conditions. We report the case of a 19-year-old female presenting with a six-day history of persistent fever, later developing an evanescent rash and migratory polyarthralgia. Laboratory findings included cytopenias, elevated inflammatory markers, and markedly elevated ferritin levels. After ruling out infectious, autoimmune, and neoplastic etiologies, AOSD was diagnosed based on the Yamaguchi classification criteria. Initial treatment with corticosteroids led to partial clinical improvement, but persistent articular symptoms required escalation to anakinra, resulting in complete remission. This case reinforces that AOSD should be considered in the differential diagnosis of FUO, particularly in the presence of quotidian fever, rash, polyarthralgia, and marked hyperferritinemia. Early recognition and appropriate treatment, including biological therapy, are essential to control disease activity and prevent complications.

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2026-06-29 | A case of adult-onset Still disease complicated by macrophage activation syndrome and toxic epidermal necrolysis.

A 56-year-old woman with 1-year recurrent fever, rash, joint swelling (acute exacerbation) was diagnosed with adult-onset Still disease (AOSD) per 1992 Yamaguchi criteria. She initially improved with methylprednisolone, tocilizumab, methotrexate, and iguratimod but relapsed after discontinuing methylprednisolone. Twenty-four hours after first Re Du Ning injection, she developed progressive rash (extensive polymorphic erythema, bullae, and >30% body surface epidermal detachment), high fever, organ impairment, and coagulopathy and was diagnosed with AOSD complicated by macrophage activation syndrome (2004 haemophagocytic lymphohistiocytosis guidelines), toxic epidermal necrolysis, myocardial injury, hepatic impairment, and disseminated intravascular coagulation. Treatment included dexamethasone, methylprednisolone, plasma exchange, cyclosporine, anakinra, ganciclovir, voriconazole, intravenous immunoglobulin, and supportive care, leading to marked improvement in lesions. This case highlights rare AOSD complications and anakinra's efficacy.

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2026-05-23 | Still's disease in pregnancy complicated by anakinra-related hepatotoxicity and rescued by intravenous immunoglobulin: a case-based review.

Still's disease (SD) in pregnancy is a rare autoinflammatory disorder presenting considerable diagnostic and therapeutic challenges. Balancing maternal disease control with foetal safety is essential, and evidence supporting biologic therapies - particularly interleukin-1 (IL-1) blockade - during gestation remains scarce. A 34-year-old primigravida developed de novo SD at 27 weeks' gestation with high-grade fever, evanescent maculopapular rash, polyarthralgia, neutrophilic leucocytosis, and hyperferritinaemia (peak 27,967 ng/mL; CRP 342 mg/L; WCC 18.1 × 10⁹/L; ALT 69 IU/L). Intravenous methylprednisolone, oral prednisolone, and subcutaneous anakinra (100 mg daily) achieved disease control, but anakinra was complicated by suspected drug-induced liver injury (ALT 1138 IU/L) with biochemical improvement after withdrawal. Intravenous immunoglobulin (IVIg; 0.4 g/kg/day for 5 days) was administered as rescue therapy. Caesarean delivery at 34 weeks resulted in a healthy neonate. Postpartum control was achieved with tocilizumab, which the patient self-discontinued after two years, remaining in drug-free remission. A CABARET-compliant search of PubMed/MEDLINE, EMBASE and DOAJ (to May 2026) identified 23 publications describing 29 pregnancies; only five referenced anakinra with two cases of new antenatal exposure with no complications, underscoring the paucity of evidence for IL-1 blockade in pregnancy. SD in pregnancy demands prompt multidisciplinary assessment, exclusion of mimics (Haemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS), Haemolysis, Elevated Liver Enzymes, Low Platelets Syndrome (HELLP), sepsis, intrahepatic cholestasis of pregnancy), and vigilant monitoring for treatment-related toxicity. This case documents suspected anakinra-related hepatotoxicity and supports IVIg as a potential rescue option, with tocilizumab as a viable postpartum strategy.

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2026-05-11 | A Diagnosis of Exclusion: Unraveling Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder characterized by quotidian fevers, arthralgia, transient rash, and elevated inflammatory markers, often leading to diagnostic delay due to overlap with infectious, autoimmune, and malignant conditions. We present the case of a 60-year-old Latina woman who developed daily fevers, polyarthralgia, rash, and hypoxemic respiratory failure. Despite broad-spectrum antibiotics, her symptoms persisted, and extensive infectious and hematologic evaluations were unrevealing. A diagnosis of AOSD was established based on the Yamaguchi criteria and markedly elevated ferritin. The patient responded to corticosteroids but later developed macrophage activation syndrome (MAS), requiring anakinra in addition to high-dose steroids. This case highlights the diagnostic challenges of AOSD in older adults, the potential for atypical systemic manifestations such as pulmonary nodules and anasarca, and the importance of early cytokine-directed therapy to prevent life-threatening complications.

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cell therapies

2026-03-07 | Adjunctive Therapeutic Plasma Exchange in Refractory Adult-Onset Still's Disease Complicated by Secondary Macrophage Activation Syndrome: A Single-Center Experience.

Adult-onset Still's disease (AOSD) complicated by macrophage activation syndrome (MAS) carries substantial mortality. The role of therapeutic plasma exchange (TPE) remains uncertain. We retrospectively analyzed patients with AOSD-MAS treated with TPE at a single-center. All five patients had arthralgia, a salmon-pink rash, extreme hyperferritinemia, and multiorgan dysfunction including liver dysfunction. Prior to TPE, all patients received pulse glucocorticoids; three also received calcineurin inhibitors and one tocilizumab. TPE was initiated at a median of 12.0 days after diagnosis; the patients underwent a median of six sessions without major adverse events. Following TPE, fever and rash resolved; C-reactive protein (CRP), ferritin, and liver enzyme levels decreased without further corticosteroid escalation during and immediately after TPE. At 1 month, four patients achieved CRP < 1.0 mg/dL, four recovered with tapered immunosuppression. One patient died from cytomegalovirus infection despite MAS improvement. Adjunctive TPE was associated with rapid clinical and biochemical improvement.

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2025-01-07 | Management of Adult-Onset Still's Disease Patients in Intensive Care Unit: a Case Report

Background: Adult-onset Still's disease (AOSD) is a rare inflammatory disorder characterized by the classic triad of fever, arthritis, and evanescent rash. AOSD is a multi-systemic disorder with unclear etiology. Glucocorticoids are the first line treatment for AOSD, and disease-modifying anti-rheumatic drugs (DMARDs) are often used in some patients with a poor response to glucocorticoids. Parenchymal lung involvement in AOSD is rare (only 5% of AOSD), one of them is acute respiratory distress syndrome (ARDS), where ARDS is the most severe complication. Management of such conditions in the intensive care unit (ICU) is crucial.Case: A 25-year-old woman came with unresolved fever for one week which was preceded by joint pain and reddish spots on the skin. The patient was diagnosed as AOSD complicated with ARDS due to pneumonia which kept the patient in the ICU for 24 days.Discussion: AOSD is a multigenic auto-inflammatory disorder involving the innate and adaptive immune systems. Based on Yamaguchi's criteria, the patient was diagnosed with AOSD where there was a high fever that lasted more than a week, arthritis, salmon rash, leucocytosis, sore throat, splenomegaly, alanine aminotransferase (ALT) abnormalities, and negative antinuclear antibodies (ANA) test. The first-line therapy given was methylprednisolone, doses were tapered gradually. As the patient didn't respond to therapy, she was then given immunosuppressive therapies such as cyclosporine, hydroxychloroquine and underwent therapeutic plasma exchange (TPE). The patients responded to treatments and showed good laboratory results.Conclusion: This case report describes a patient with AOSD that was diagnosed based on clinical manifestations and Yamaguchi criteria. The patient improved clinically with high dose administration of corticosteroids, immunosuppressive agents, and TPE. Making a correct diagnosis and starting an appropriate treatment as soon as feasible is crucial in this case as the patient suffers complications.

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2022-07-08 | Efficacy of plasma exchange on top of standard immunosuppressive therapy in adult autoimmune inflammatory rheumatic diseases-associated macrophage activation syndrome, a single center real-world analysis.

There is a lack of documented real-world evidence about the efficacy of current therapeutics for autoimmune inflammatory rheumatic diseases (AIIRD)-associated adult macrophage activation syndrome (MAS). To analyze the efficacy of different treatments, especially plasma exchange (PE), in AIIRD-associated MAS. Among 5775 patients with AIIRD in Tongji Hospital from 2014 to 2020, 62 AIIRD-associated MAS cases were collected. Unadjusted logistic regression, least absolute shrinkage and selection operator (LASSO), and inverse probability of treatment weight (IPTW) analyses were used to characterize the clinical features and potential factors related to the prognosis. Paired t-test was used to compared the changes of inflammatory indicators before and after PE treatment. The baseline data was defined as the data collected at the onset of MAS, and all of the 62 patients were diagnosed as AIIRD before MAS onset. The prevalance rate of MAS in AIIRD was 1.1%, and the most common types of AIIRD were systemic lupus erythematosus (45.2%) and adult-onset Still's disease (33.9%). All 62 MAS patients received glucocorticoids, 87.1% patients used at least one immunosuppressive agent, and 54.8% received PE. LASSO regression indicates a positive effect of PE on the basis of variables. After PE treatment, serum levels of multiple inflammatory cytokines were rapidly reduced, accompanied by improvements in clinical symptoms and laboratory indecies including ferritin, lactate dehydrogenase, and C-reactive protein. LASSO regression indicates that PE treatment was associated with a marked reduction of mortality (from 53.6% to 11.8%), with a hazard ratio (HR) of 0.148 (p < 0.001) after adjustment for confounding factors using IPTW analysis. With the background therapy of glucocorticoids and immunosuppressive agents, PE is an effective approach to rapidly clear inflammatory cytokines and reduce mortality of AIIRD-associated MAS. This study provided real-world information on the efficacy of PE in AIIRD-associated MAS.

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2021-06-25 | The utility of liver transplantation to treat acute liver failure caused by adult-onset Still's disease: case reports.

Adult-onset Still's disease (AOSD) is an inflammatory condition commonly complicated by mild liver dysfunction. However, severe liver failure is rarely reported. We report three cases of severe acute hepatic failure (ALF) associated with AOSD. We encountered three cases of acute liver failure (ALF) with encephalopathy. Case 1 was a 75-year-old female, who was started on a steroid (prednisolone, PSL) to treat AOSD; this was gradually tapered. Two months later, severe ALF developed. She died despite an increase in the PSL dose and artificial liver support. Case 2 was a 26-year-old-female taking PSL 30 mg/day to treat subacute thyroiditis. PSL was tapered, and she received methyl PSL pulse therapy and artificial liver support, but this did not cure the ALF. Liver transplantation (LT) was performed 25 days later. Three years later, the same symptoms were observed and we diagnosed AOSD. Case 3 was a 56-year-old-female who met the AOSD criteria. PSL 50 mg/day was started and then tapered. Methyl PSL pulse therapy was prescribed to treat hemophagocytic syndrome, but she required LT on hospital day 13. In AOSD cases, ALF is rarely complicated; urgent LT should be considered only for patients with AOSD-related severe ALF.

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2018-12-11 | Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders.

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult-onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down-modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.

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antibodies

2026-08-06 | Refractory Relapsing-Remitting Adult-Onset Still's Disease in an Adolescent Female: A Rare Case Report.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory condition that presents with symptoms such as episodic fevers, a transient rash, inflammatory arthritis, and significant systemic inflammation. Diseases that have a relapsing-remitting clinical course can be challenging to diagnose and treat. We present a case of an 18 year old female with multiple flares over several years requiring stepwise escalation from conventional disease-modifying antirheumatic drugs (DMARDs) to targeted biologic therapy, highlighting the challenges of achieving durable remission. Our patient presented with recurrent episodes of high-grade fever (up to 40°C), evanescent salmon-pink rash, bilateral symmetrical inflammatory polyarthritis involving the wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP) joints, and knees with mild splenomegaly. After ruling out infectious, malignant, and other autoimmune diseases via biochemical, serological, autoimmune testing and biopsy, she was diagnosed with AOSD on the basis of the Yamaguchi criteria. Despite receiving treatment with corticosteroids and conventional disease-modifying antirheumatic drugs (DMARDs), including methotrexate, she suffered from multiple relapses, indicating a polycyclic disease pattern. The introduction of biologic therapy with tocilizumab provided temporary remission. However, her flares returned during the tapering of steroids, necessitating an increase in the dosage and the use of pulse corticosteroid therapy during the current admission. This case report illustrates the relapsing-remitting nature of AOSD. Escalation to IL-6 receptor inhibition (tocilizumab) is required in DMARDs refractory relapsing AOSD, with dose optimization to achieve sustained remission of disease activity of our patient.

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2026-08-05 | Real-world therapeutic strategies in active adult-onset Still’s disease: clinical insights from the GIRRCS-AOSD study group

Objectives To evaluate the therapeutic management of patients with active adult-onset Still’s disease (AOSD) in a multicentre real-world setting and to provide and compare current real-world treatment strategies with existing recent international recommendations. Methods From January 2022 to December 2023, 173 consecutive patients with active AOSD attending centres participating in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD research study group were prospectively enrolled. Demographic, clinical, and laboratory data were collected, and therapeutic strategies prescribed by the treating physicians were systematically recorded. Factors associated with the administration of biologic disease-modifying antirheumatic drugs (bDMARDs), including IL-1 and IL-6 inhibitors, were analysed. Results Glucocorticoids were administered in 97.7% of patients. Conventional synthetic DMARDs were prescribed in 58.8% of cases, mainly methotrexate and cyclosporin A. Overall, 43.3% of patients received bDMARDs, predominantly IL-1 and IL-6 inhibitors. Specifically, 33.5% were treated with IL-1 inhibitors, 5.8% with IL-6 inhibitors, and 4.0% with tumour necrosis factor inhibitors. After three months of treatment, 86.7% of patients achieved clinical inactive disease as assessed by the treating physician. Comparing recorded treatment strategies with international recommendations, no compliance was found regarding the use of glucocorticoids, which are recommended to be markedly limited or avoided, and early administration of bDMARDs, which were administered within 3 months in a minority of patients. Conclusions This multicentre real-world study outlines current therapeutic approaches for patients with active AOSD and highlights a gap between international treatment recommendations and clinical practice, underscoring the need for further studies to optimize patient management.

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2026-07-21 | Adult-onset Still's disease presenting with periorbital erythematous rash and progressive interstitial lung disease.

A man in his 80s with chronic obstructive pulmonary disease presented with fever, arthralgia and periorbital erythema resembling a heliotrope rash, accompanied by progressive interstitial lung disease (ILD). Laboratory investigations revealed neutrophilic leucocytosis and markedly elevated C-reactive protein, ferritin and Krebs von den Lungen-6. Dermatomyositis, particularly clinically amyopathic dermatomyositis, was considered in the differential diagnosis; however, myositis-specific autoantibodies were negative and histopathological findings supported a diagnosis of adult-onset Still's disease (AOSD). Despite the high-dose corticosteroids and ciclosporin, lung disease progressed to respiratory failure. Treatment with tocilizumab led to clinical and radiological remission with normalisation of inflammatory markers.This case highlights that AOSD can present with rapidly progressive ILD and closely mimic dermatomyositis, underscoring the importance of careful differential diagnosis and timely cytokine-targeted therapy.

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2026-07-02 | Clinical Features and Outcome Measures Across Still Disease (Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still Disease) Cohorts Worldwide: A Systematic Literature Review.

J Rheumatol 2026; doi: 10.3899/jrheum.2025-0822 The following text should be added to the acknowledgment: "The contributions of the National Institutes of Health (NIH) authors are considered works of the US government. The findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services." This correction applies to the December 1 2025 First Release and February 2026 print issue. The online version has been corrected.

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2026-06-27 | Achievement of intermediate treatment targets for Still's disease under tocilizumab treatment: a post-hoc analysis of the phase III trial.

To evaluate the intermediate treatment targets for Still's disease proposed by EULAR/PReS recently, we conducted this post-hoc analysis of the Phase III trial of tocilizumab and its long-term extension to assess the achievement probability of these targets with tocilizumab. Additionally, we assessed the associations of the intermediate treatment targets with long-term outcomes, including glucocorticoid-free clinically inactive disease (CID) and recurrence. Given the predefined glucocorticoid tapering schedule, we also evaluated the achievement of CID irrespective of glucocorticoid dosage when assessing treatment targets at Months 3 and 6. Twenty-one patients were followed for a median of 39.8 months. The week 4 target was achieved in 57.1%, while 47.6% and 38.1% achieved CID at months 3 and 6, respectively. At the final visit, 57.1% and 28.6% achieved CID and glucocorticoid-free CID, respectively. Achievement of the week 4 target and CID at month 6 was associated with subsequent glucocorticoid-free CID (50% vs. 0%, p = 0.01; 62.5% vs. 7.7%, p = 0.01). Month 6 CID achievers had higher baseline swollen joint counts and lower interferon-γ levels. In conclusion, achievement of intermediate treatment targets was associated with long-term CID, suggesting that these targets may also be useful in treatment with tocilizumab. UMIN000012987, UMIN000018414.

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other

2026-03-08 | Is a variant of uncertain significance always 'insignificant'? A systematic review on PRF1 A91V in Hemophagocytic Lymphohistocytosis and comparative analysis with Still's disease.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disorder that may arise secondary to rheumatic diseases such as Still’s disease, where macrophage activation syndrome (MAS) represents its clinical counterpart. The pathogenic significance of the PRF1 A91V variant remains uncertain, although functional data suggest partial perforin dysfunction and a possible contribution to late-onset or atypical HLH. This study aimed to clarify the clinical implications of the PRF1 A91V variant through a systematic review of published HLH and MAS cases and a comparative analysis with a single-center Still’s disease cohort. RESULTS: A total of 20 studies, including 38 individual HLH or MAS cases carrying the PRF1 A91V variant, were identified. The median age at diagnosis was 22 years, and 18.4% of patients were homozygous. Fever (82.6%), splenomegaly (57.9%), and hepatomegaly (36.8%) were the most frequent clinical findings. Anemia (57.1%) and thrombocytopenia (85.7%) were the predominant laboratory abnormalities, accompanied by marked hyperferritinemia (median 9319 ng/mL). Compared with 43 active Still’s disease cases, PRF1-mutated HLH patients showed significantly higher rates of cytopenias, hepatomegaly, and central nervous system involvement, together with substantially elevated ferritin levels (9,193 vs 800 ng/mL, p = 0.0023), whereas C-reactive protein levels were comparable. Receiver-operating characteristic analysis identified a ferritin cutoff of 7000 ng/mL (sensitivity 63.2%, specificity 84.6%) as the optimal discriminator for PRF1 A91V positivity. In multivariate regression, ferritin ≥ 7,000 ng/mL remained the only independent predictor (OR 17.3, 95% CI 2.0–146.3, p = 0.009). CONCLUSIONS: Patients carrying the PRF1 A91V variant represent a distinct subgroup within the spectrum of hyperinflammatory syndromes. Extreme hyperferritinemia combined with cytopenias should raise suspicion for perforin-related HLH rather than cytokine-driven MAS or classic Still’s disease. Recognition of this variant as a risk-modifying allele may guide early genetic testing and therapeutic decisions, including consideration of advanced interventions in selected cases.

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2025-06-01 | POS1430 GENETIC LANDSCAPE OF ADULT-ONSET STILL'S DISEASE WITH MACROPHAGE ACTIVATION SYNDROME: IDENTIFYING KEY RISK LOCI FOR DISEASE MECHANISMS AND PERSONALIZED TREATMENT

Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are severe, life-threatening systemic hyperinflammatory syndromes. They can arise from genetic defects as well as various triggers, including infections, malignancies, and autoimmune diseases. MAS is most recognised and best studied in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Currently, research on the underlying pathogenesis of MAS and its treatment options remains insufficient. Recently, the field of genomics has garnered increasing attention. The objective of this study is to identify the genetic variants associated with AOSD-MAS susceptibility and to elucidate their connections to specific target genes. Such insights are critical for advancing the clinical translation of genetic discoveries, thereby enhancing the accuracy of diagnostic genetic screenings and informing personalized therapeutic strategies. In this study, we performed whole-exome sequencing (WES) on a cohort of AOSD patients to identify potential genetic variations, followed by Sanger sequencing for validation. RNA sequencing (RNA-seq) was conducted to explore gene expression profiles. Statistical analyses were carried out using Fisher's exact test (two-sided) to assess associations, and survival analysis was employed to evaluate outcomes. This study investigated the genetic predisposition of AOSD-MAS, highlighting the critical involvement of known causative genes for primary HLH (pHLH-KG) and the candidate genes in AOSD-MAS. Among the 72 AOSD-MAS patients, 19 individuals (19/72, 26.39%) harbored mutations in pHLH-KG genes, including LYST, PRF1, STX11, UNC13D, NLRC4, STXBP2, AP3B1, CTPS1, RASGRP1, NCKAP1L, and RC3H1. Gene level comparisons demonstrated that ADGRE2, TGFB1, C6, IKZF3, MPO, POLD1, LIFR, IL15RA, and FANCC were significantly enriched in AOSD-MAS compared to AOSD without MAS (AOSD-nMAS), with notable differences (log2OR > 1 or infinite, p-value < 0.05). At the variant level, significant differences were observed for LYST p.I2666N, STX11 p.A125V, POLA1 p.V539M, LRBA p.E88A, ERCC4 p.G912R, and ADGRE2 p.C29Y (p-value < 0.05). These findings strongly suggest that ADGRE2 plays a pivotal role in the pathogenesis of AOSD-MAS. Additionally, we also conducted gene-phenotype correlation analysis, which revealed that CSF2RB and MECOM were significantly more prominent in refractory AOSD-MAS. In conclusion, the potential synergistic interactions among these genes may contribute critically to the development of AOSD-MAS. Our study identified mutations in known HLH-associated genes as well as new candidate genes in AOSD-MAS through WES. Gene-phenotype correlation analysis revealed differences in gene profiles across different clinical phenotypes, providing insights for the precision therapies for AOSD-MAS. NIL. NIL. None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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2023-06-05 | Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

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2020-02-14 | Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease

Adult-onset Still’s disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5′-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P=1.20×10 -8 , OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n=82, median: 9.31 pg/mL), particularly in the cases with activity score≥6 (n=42, 10.94 pg/mL), compared to the healthy donors (n=68, 5.31 pg/mL) (P<0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P<0.0001) or AT genotype (11.61 pg/mL) (P=0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD.

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