RARE DISEASE
Adult-onset Still disease
Adult-onset Still disease
Adult-onset Still disease
Synonyms: AOSD, Wissler-Fanconi syndrome
Synonyms: AOSD, Wissler-Fanconi syndrome
Synonyms: AOSD, Wissler-Fanconi syndrome
Drug discovery
3
drugs
With orphan designations
Overview
Adult-onset Still disease (AOSD) is a rare multisystem autoinflammatory disorder characterized by daily high-spiking fevers (>39°C), evanescent salmon-pink rash, arthralgia/arthritis, and systemic inflammation. Key biomarkers include neutrophilic leukocytosis, hyperferritinemia, and elevated inflammatory markers (CRP, ESR). Diagnosis requires exclusion of infections, malignancies, and other rheumatic diseases. Treatment escalates from NSAIDs/corticosteroids to biologic agents targeting IL-1/IL-6 pathways in refractory cases. Macrophage activation syndrome (MAS) is a life-threatening complication requiring urgent immunosuppression [1][3][17].
Therapies
First-line: High-dose corticosteroids (± NSAIDs for mild cases) [3][11][15].
Refractory/chronic cases: Methotrexate or biologics (IL-1 inhibitors [anakinra/canakinumab] > IL-6 inhibitors [tocilizumab] > TNF-α/JAK inhibitors) [3][13][17].
MAS management: Pulse methylprednisolone, cyclosporine, or IL-1/IFN-γ inhibitors [7][9].
Categories: rare renal diseases, rare systemic and rheumatological diseases, rare transplant-related disorders
Research Papers
812 drug discovery papers about Adult-onset Still disease, with 3 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
812 drug discovery papers about Adult-onset Still disease, with 3 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Adult-onset Still disease, including 1 approved therapy.
3 orphan drug designations for Adult-onset Still disease, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Camoteskimab | antibodies | FDA | 2024-02-14 | — | Apollo Therapeutics Inc. |
canakinumab | antibodies | FDA | 2017-07-31 | 2020-06-16 | Novartis Pharmaceuticals Corporation |
tadekinig alfa | proteins | FDA | 2017-07-03 | — | AB2 Bio Ltd |
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