# Advancing Precision Medicine in Adult-Onset Still’s Disease: Insights into Biomarkers, Therapies, and COVID-19 Impacts

**Authors:** Debashis Priyadarshan Sahoo

PMC · DOI: 10.31138/mjr.020525.ahr · 2025-07-11

## TL;DR

This paper reviews biomarkers and therapies for adult-onset Still’s disease, a rare inflammatory condition, and discusses challenges in diagnosis and treatment, especially during the COVID-19 pandemic.

## Contribution

The paper introduces novel biomarkers like gasdermin D and emerging therapies such as IL-18 binding protein for precision medicine in AOSD.

## Key findings

- Biologic therapies achieve remission in 80–90% of systemic AOSD cases.
- SARS-CoV-2 infection and vaccination can trigger AOSD flares, requiring adaptive management.
- Gasdermin D is proposed as a novel biomarker for AOSD.

## Abstract

Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disorder characterized by spiking fevers, arthralgia, and a transient salmon-pink rash, with an incidence of 0.16–0.4 per 100,000. AOSD shares overlapping clinical and immunological features with systemic juvenile idiopathic arthritis (sJIA), supporting a disease continuum and shared treatment approaches. The COVID-19 pandemic has impacted AOSD care, with SARS-CoV-2 infection and vaccination occasionally triggering disease flares, necessitating adaptive management strategies. Driven by innate immune dysregulation and overproduction of proinflammatory cytokines (IL-1, IL-6, IL-18), AOSD presents in systemic and articular phenotypes, with severe complications like macrophage activation syndrome (MAS), fulminant hepatitis, and parenchymal lung disease. Diagnosis, based on Yamaguchi or Fautrel criteria and biomarkers (ferritin, IL-18), is challenging due to nonspecific symptoms. Biologic therapies (anakinra, canakinumab, tocilizumab) achieve remission in 80–90% of systemic cases. This review synthesises diagnostic challenges, novel biomarkers (e.g., gasdermin D), and emerging therapies (e.g., IL-18 binding protein), emphasising precision medicine and future research needs.

## Linked entities

- **Proteins:** IL1A (interleukin 1 alpha), IL6 (interleukin 6), IL18 (interleukin 18)
- **Diseases:** Adult-onset Still’s disease (MONDO:0019355), systemic juvenile idiopathic arthritis (MONDO:0019434), macrophage activation syndrome (MONDO:0015545), SARS-CoV-2 (MONDO:0100096)

## Full-text entities

- **Genes:** S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, GSDMD (gasdermin D) [NCBI Gene 79792] {aka DF5L, DFNA5L, FKSG10, GSDMDC1}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL18BP (interleukin 18 binding protein) [NCBI Gene 10068] {aka FVH, IL18BPa}, HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123] {aka DRB1, HLA-DR1B, HLA-DRB, SS1}, IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554] {aka CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NLRC3 (NLR family CARD domain containing 3) [NCBI Gene 197358] {aka CLR16.2, NOD3}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}
- **Diseases:** ARDS (MESH:D012128), Sore throat (MESH:D010612), urticarial dermatosis (MESH:D012871), allergic reactions (MESH:D004342), articular damage (MESH:D012213), FUO (MESH:D005335), articular disease (MESH:D057072), DRESS (MESH:D063926), Chlamydia trachomatis (MESH:D002690), Arthritis (MESH:D001168), Fever (MESH:D005334), systemic disease (MESH:D034721), vasculitis (MESH:D014657), Lymphadenopathy (MESH:D008206), cardiac symptoms (MESH:D006331), lung disease (MESH:D008171), SpA (MESH:D013167), Onset (MESH:D000067562), Neurological Complications (MESH:D002493), inflammation (MESH:D007249), endocarditis (MESH:D004696), urticaria (MESH:D014581), anaphylactic reactions (MESH:D000707), diabetes (MESH:D003920), opacities (MESH:D003318), cardiac tamponade (MESH:D002305), Gastrointestinal lesions (MESH:D005767), Viral infections (MESH:D014777), influenza (MESH:D007251), -COVID (MESH:D000086382), persistent infectious fevers (MESH:D000094025), death (MESH:D003643), ground (MESH:D007815), AOSD (MESH:D016706), axial (MESH:C537791), joint damage (MESH:D007592), PsA (MESH:D015535), Complications (MESH:D008107), DIAGNOSTIC (MESH:D005119), Abnormal liver function (MESH:D056486), chest pain (MESH:D002637), Acute Hepatitis (MESH:D017114), hyperinflammatory syndrome (MESH:D013577), abdominal pain (MESH:D015746), dysregulation (MESH:D021081), Hyperferritinemia (MESH:D000085583), fatigue (MESH:D005221), hepatitis B (MESH:D006509), RA (MESH:D001172), Flares (MESH:D000067251), Arthralgia (MESH:D018771), ulcers (MESH:D014456), sepsis (MESH:D018805), infectious (MESH:D003141), aseptic meningitis (MESH:D008582), coagulopathy (MESH:D001778), HLH (MESH:D051359), malignancies (MESH:D009369), osteoporosis (MESH:D010024), Cushing's syndrome (MESH:D003480)
- **Chemicals:** Methotrexate (MESH:D008727), Prednisone (MESH:D011241), Ruxolitinib (MESH:C540383), Tocilizumab (MESH:C502936), tofacitinib (MESH:C479163), Steroid (MESH:D013256), oxygen (MESH:D010100), Azathioprine (MESH:D001379), cyclosporin A (MESH:D016572), bDMARDs (-), Canakinumab (MESH:C541220), naproxen (MESH:D009288), Etoposide (MESH:D005047), methylprednisolone (MESH:D008775), Emapalumab (MESH:C000644327), ibuprofen (MESH:D007052)
- **Species:** Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12835927/full.md

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Source: https://tomesphere.com/paper/PMC12835927