Rheumato

Background/Objectives: Autoimmune rheumatic diseases (AIRDs) are complex, heterogeneous, and relapsing–remitting conditions in which early diagnosis, flare prediction, and individualized therapy remain major unmet needs. This review aims to synthesize recent progress in AI-driven, biomarker-based precision medicine, integrating advances in imaging, multi-omics, and digital health to enhance diagnosis, risk stratification, and therapeutic decision-making in AIRD. Methods: A comprehensive synthesis of 2020–2025 literature was conducted across PubMed, Scopus, and preprint databases, focusing on studies applying artificial intelligence, machine learning, and multimodal biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, spondyloarthritis, and related autoimmune diseases. The review emphasizes methodological rigor (TRIPOD+AI, PROBAST+AI, CONSORT-AI/SPIRIT-AI), implementation infrastructures (ACR RISE registry, federated learning), and equity frameworks to ensure generalizable, safe, and ethically governed translation into clinical practice. Results: Emerging evidence demonstrates that AI-integrated imaging enables automated quantification of synovitis, erosions, and vascular inflammation; multi-omics stratification reveals interferon- and B-cell-related molecular programs predictive of therapeutic response; and digital biomarkers from wearables and smartphones extend monitoring beyond the clinic, capturing early flare signatures. Registry-based AI pipelines and federated collaboration now allow multicenter model training without compromising patient privacy. Across diseases, predictive frameworks for biologic and Janus kinase (JAK) inhibitor response show growing discriminatory performance, though prospective and equity-aware validation remain limited. Conclusions: AI-enabled fusion of imaging, molecular, and digital biomarkers is reshaping the diagnostic and therapeutic landscape of AIRD. Standardized validation, interoperability, and governance frameworks are essential to transition these tools from research to real-world precision rheumatology. The convergence of registries, federated learning, and transparent reporting standards marks a pivotal step toward pragmatic, equitable, and continuously learning systems of care. Full article

Introduction: In hemoglobinopathies, the amount of globin synthesis in hemoglobin (Hb) or its structure is altered. Clinical features are related to the rate and kind of structural aberrations. The heterozygous form of the Lepore syndrome resembles minor thalassemia both clinically and hematologically. On electrophoresis, abnormal Hb Lepore fractions are found at a rate of 5–15%, with a mildly higher percentage of HbF and lower HbA. In general, Hb Lepore heterozygotes are asymptomatic. Case presentation: A 32-year-old male was admitted to our hospital with complaints of pain and swelling in multiple large joints and high-grade fever for 11 days. His past history was unremarkable; one of his sisters had the β-thalassemia trait. On physical examination, he was moderately anemic, with mild hepatomegaly and normal spleen; both knees and ankles were tender and swollen. Laboratory showed mild microcytic hypochromic anemia with variables similar to the thalassemia trait and signs of inflammation with very high CRP, serum ferritin, and leukocytosis. Blood sugars were increased. Hb electrophoresis showed an abnormal pattern with mild elevation in HbS, normal Hb F, mild reduction in HbA, and high HbA2, compatible with heterozygosity for the Hb Lepore beta chain variant. He was initially diagnosed with diabetes (treated with insulin) and sepsis from unknown origin, but fever and joint pains did not respond to NSAIDs or antibiotics. He had very good response on high-dose methylprednisolone. Undifferentiated arthritis was diagnosed in the patient with Hb Lepore, and he was treated with oral prednisolone and sulfasalazine (SSZ). At follow up, the patient was doing well. He refused further investigations and did not allow testing on his family members. In summary: Hb Lepore is a rare hemoglobinopathy linked to thalassemia, which may manifest with musculoskeletal problems. Our patient with the Hb Lepore trait presented with undifferentiated polyarthritis and fever, but in our case, a causal relationship remains unclear. This is one of the first adult cases of Hb Lepore in Bangladesh and the first with arthritis of unknown origin. The prevalence of Hb Lepore in Bangladesh is unknown. Full article

Background: Chimeric Antigen Receptor T-cell (CAR-T) cell therapy has revolutionized cancer treatment and is now being explored as a novel approach to treat refractory autoimmune diseases by targeting autoreactive immune components, especially B cells. Objective: Our aim was to provide a narrative review of the current evidence, mechanisms, efficacy, safety, and future directions of CAR-T cell therapy in autoimmune diseases. Methods: A structured literature search was conducted in MEDLINE via PubMed using keywords such as “CAR-T”, “chimeric antigen receptor T-cell”, “autoimmune diseases”, “lupus”, “rheumatoid arthritis”, “multiple sclerosis”, and “vasculitis”. Studies on CAR-T mechanisms, efficacy, safety, and clinical outcomes were included. Results: CAR-T cell therapies, especially CD19-directed constructs, demonstrated sustained drug-free remission in all patients across early SLE case series (n = 5–7), with normalization of serological markers and improved renal outcomes. Emerging preclinical and early clinical data in rheumatoid arthritis, multiple sclerosis, ANCA-associated vasculitis, juvenile autoimmune diseases, and idiopathic inflammatory myopathies also report clinical improvement and biomarker normalization. Reported adverse events in autoimmune cohorts were limited to mild cytokine release syndrome in a minority of cases, with no severe neurotoxicity or life-threatening infections, suggesting a more favorable safety profile compared to oncology settings. In parallel, next-generation innovations—including dual-target CARs, CAR-Tregs, and molecular safety switches—are advancing toward clinical translation. Conclusions: CAR-T cell therapy is emerging as a transformative strategy for autoimmune disease management, especially in refractory cases. Although initial outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key challenges. Future research should focus on optimizing cell targets, minimizing off-target effects, and improving affordability. Full article

Background/Objectives: Sjögren’s disease (SjD) flares are incompletely understood. The patient perspective is critical to closing this gap. This retrospective social media listening (SML) study characterized the flare lexicon within the online Reddit SjD community using novel machine learning and natural language processing. Methods: Documents (posts/comments) were analyzed from the subreddit group “r/Sjogrens” (October 2012 to August 2023). Outcomes were as follows: (1) Frequency of documents mentioning flare, and contexts in which flare was mentioned; (2) clinical concepts associated with flare (analyzed using co-occurrence and pointwise mutual information [PMI]); (3) proportion of flare vs. non-flare documents relevant to SYMPTOMS or TESTING (compared using a two-proportion z-test); and (4) primary emotions mentioned in flare documents. Results: Of 59,266 documents with 5025 authors, flare was mentioned 3330 times (4.4% of documents from 19.1% of authors). Flare was discussed as a symptom (1423 instances), disease (13), or with no clinical category (1890). Flare-associated clinical concepts (co-occurrence > 100 and PMI² > 3) included SYMPTOMS (pain, fatigue, dryness of eye, xerostomia, arthralgia, stress) and BODY PARTS (eye, mouth, joints, whole body). More flare vs. non-flare documents mentioned a SYMPTOM, whereas fewer mentioned a TEST (p < 0.001 for both). Within flare documents, 36.5% expressed emotions, primarily fear (40.5% of primary emotions), happiness (17.8%), sadness (15.7%), and anger (15.5%). Conclusions: The SjD community discusses flare frequently and in context with symptoms, specifically pain, eye and mouth dryness, and fatigue. Flare conversations frequently involve negative emotions. Additional research is required to clarify the patient experience of flare, its clinical parameters, and implications. Full article

Aim of the study: This paper focuses on the correlation of nicotine use with chronic lumbar back pain (CLBP). Methods: This is a cross-sectional observational study involving smoker and non-smoker patients with a diagnosis of chronic low back pain (CLBP), recruited during their initial neurosurgical consultation at the Neurosurgery Clinic over a period of 6 months. All patients were followed for a minimum of 3 months after the start of conservative therapy. Age, sex, smoking habits, and the presence of any comorbidities were noted. Pain severity and discomfort were evaluated using the Numeric Rating Scale (NRS), the DN4 questionnaire, and the Oswestry Disability Index (ODI). Based on imaging (MRI of the lumbosacral spine), diagnoses of disc herniation or vertebral lumbar stenosis were documented. Statistical analysis was performed using IBM SPSS Statistics software (Version 30). A p-value of less than 0.05 was considered statistically significant. Results: Improvement on the CLBP, NRS, and DN4 scales after the same conservative therapy was better in Patients with non-smoking habits improved more on the CLBP, NRS and DN4 scales when compared to smokers (NRS scale 0.001 and DN4 scale 0.027). Conclusions: Patients with smoking habitudes affected by lumbar disk her-niation and stenosis and undergoing conservative therapy had worse pain scores Full article

Living with inflammatory arthritis can have a significant impact; early identification, diagnosis and treatment has been shown to improve outcomes. The clinician working in settings where people with undiagnosed inflammatory arthritis may present for assessment has a crucial role in early identification and onwards referral. Inflammatory arthritis varies in its presentation with respect to gender. Rheumatoid arthritis tends to affect females more than males; historically, Axial Spondyloarthropathy was felt to predominately affect males but the distribution is now known to be equal between men and women. Psoriatic arthritis also affects males and females without obvious sex prevalence. Objectives: To investigate, through a narrative literature review, the early clinical manifestations of inflammatory arthritis, focusing on sex differences and key signs which primary care clinicians should recognise. Methods: A narrative literature review was undertaken with regards to presentation of three commonly seen inflammatory arthritis conditions: Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis. Studies describing differences in presentation of these conditions between the sexes were selected for this descriptive analysis. Results: Overall, when compared to males, females endure a longer time to diagnosis, and experience increased disease activity, elevated levels of pain and poorer response to medication. Conclusions: Understanding the difference in presentation of inflammatory arthritis between sexes can accelerate diagnosis and improve treatment. Full article

Background/Objectives: Chronic medical conditions are comorbid with psychological disorders, often attributed to the weight of managing persistent demands associated with debilitating illness. Lifestyle adjustments, physical pain, and costs of health care can impose impairment of functioning, exacerbated by the onset of a chronic disease. While cause-and-effect directionality is difficult to ascertain, it is widely assumed that psychological stress can exacerbate the ability of patients to manage chronic medical conditions. Methods: The current study examined a novel model comprising five psychological factors which might explain variations in patients’ level of adherence, satisfaction, and quality of life. The sample consisted primarily of 124 low-income, female Hispanic patients, who were patients diagnosed with rheumatic and endocrine medical diagnoses. Results: Psychological distress and the lingering psychological effects of the COVID-19 pandemic were negatively associated with patient adherence, satisfaction, and quality of life, and that patients’ reports of the working alliances with their doctors moderated (i.e., significantly lessened) the negative association between the lingering impact of the COVID-19 pandemic and their satisfaction with care. Patients’ self-efficacy, resilience, and working alliance were all positively and significantly associated with adherence, satisfaction, and QOL. The association between working alliance and satisfaction represents a very large effect (r = 0.77, p < 0.001). Path analysis found a direct effect between psychological distress (stand. est. = 0.28, p = 0.05) and treatment adherence and a direct effect between COVID-19 impact and adherence (stand. est. = −0.19, p = 0.05). Conclusions: This study provides evidence of the role that both psychological stress and psychological strengths play in the experience of receiving medical care for low-income patients with rheumatic and endocrine conditions. Psychological stress inhibits adherence, and the physician–patient working alliance moderates the negative correlation between COVID impact and treatment satisfaction. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE. Full article

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health. Full article

Background/Objectives: This review analyzes the effects of invasive and non-invasive methods of knee joint unloading on knee loading, employing a biomechanical model to evaluate their impact. Methods: PubMed, Web of Science, Cochrane, and Scopus were searched up to 15 May 2024 to identify eligible clinical studies evaluating Joint Space Width, Cartilage Thickness, the Western Ontario and McMaster Universities Osteoarthritis Index, the Knee Injury and Osteoarthritis Outcome Score system, Gait velocity, Peak Knee Adduction Moment, time to return to sports and to work, ground reaction force, and the visual analogue scale pain score. A second search was conducted to select a biomechanical model that could be parametrized, including the modifications that each treatment would impose on the knee joint and was capable of estimate joint loading to compare the effectiveness of each method. Results: Analyzing 28 studies (1652 participants), including 16 randomized clinical trials, revealed significant improvements mainly when performing knee joint distraction surgery, increasing Joint Space Width even after removal, and high tibial osteotomy, which realigns the knee but does not reduce loading. Implantable shock absorbers are also an attractive option as they partially unload the knee but require further investigation. Non-invasive methods improve biomechanical indicators of knee joint loading; however, they lack quantitative analysis of cartilage volume or Joint Space Width. Conclusions: Current evidence indicates a clear advantage in knee joint unloading methods, emphasizing the importance of adapted therapy. However, more extensive research, particularly using non-invasive approaches, is required to further understand the underlying knee joint loading mechanisms and advance the state of the art. Full article

Statins are effective drugs for lowering cholesterol and reducing cardiovascular risk. Rarely, they can trigger autoimmune myopathies like immune-mediated necrotizing myopathy (IMNM), associated with anti-HMGCR antibodies. This condition may persist after statin discontinuation and requires immunosuppressive treatment. Despite these rare side effects, the benefits of statins outweigh the risks for most patients. Full article

Objectives: This study aimed to compare hip abductor muscle composition and its age-related alterations between female patients with unilateral and bilateral osteoarthritis (OA) of the hip. Methods: This study enrolled 57 and 43 female patients with unilateral and bilateral advanced OA, respectively. Muscle composition of the glutei medius and minimus and the upper portion of the gluteus maximus was evaluated by computed tomography for planning unilateral total hip arthroplasty. The cross-sectional area ratio of the individual composition to the total muscle was calculated. Correlation coefficients were calculated to determine associations between age and muscle composition variables. Results: Comparison of hip abductor muscle composition between the affected and the contralateral sides in unilateral OA patients showed increased fatty infiltration in the muscles around the affected joint. Comparison of the composition around bilateral OA between the joint scheduled for operation and the contralateral joint demonstrated enhanced fatty infiltration in the glutei medius and minimus but no increase in the gluteus maximus around the operation-scheduled joint. Comparison of muscle composition between unilateral and bilateral OA demonstrated similar fatty infiltration around the operation-scheduled joint whereas there was increased fatty infiltration around the contralateral joint of bilateral OA. Significant association was found between age and hip abductor muscle composition around both sides of unilateral OA. However, there was no association between age and hip abductor muscle composition around both sides of bilateral OA. Conclusions: There were significant differences in hip abductor muscle composition and its age-related alterations between female patients with unilateral and bilateral OA. Full article

Hemophilia is an X-linked genetic disorder that predominantly affects males, with females typically serving as asymptomatic carriers. Hemophilia A results from a deficiency or dysfunction of coagulation factor VIII, while a deficiency in factor IX causes hemophilia B. A less common condition, factor XI deficiency (formerly hemophilia C), is categorized as a rare bleeding disorder. The severity of hemophilia is classified based on the activity concentration of factors VIII and IX: severe (<1 IU/dL), moderate (1–5 IU/dL), and mild (6–<40 IU/dL). One of the most prevalent complications of hemophilia is hemarthrosis, bleeding into joint cavities, which, if unrecognized or untreated, can lead to hemophilic arthropathy. The pathophysiology of hemophilic arthropathy involves two key mechanisms: the accumulation of iron from blood in synovial joints, which cannot be cleared due to repeated bleeding, and the inflammatory response, resulting in synovial hyperplasia and the progressive destruction of cartilage and bone. Hemophilic arthropathy significantly impairs quality of life, causing chronic pain, joint deformities, and sometimes requiring surgical intervention. This thesis will examine the pathophysiology and management strategies for hemophilic arthropathy. Full article

Background: Although the Profile of Mood States has been proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to measure emotional functioning in chronic pain patients, it has not yet been validated in these patients. Objective: To confirm the factor structure and internal consistency of the Shortened Version of the Profile of Mood States (37 items) in patients with chronic pain. Methods: A confirmatory factor analysis (CFA) was conducted to test the theoretical structure of six factors that result in a Total Mood Disturbance episode: Tension–Anxiety (six items), Depression–Dejection (eight items), Anger–Hostility (seven items), Vigor–Activity (six items), Fatigue–Inertia (five items), and Confusion–Bewilderment (five items). Participants: A total of 588 patients with chronic pain from Spanish primary care health and community centers completed the questionnaire. Results: The factors presented adequate reliability coefficients, McDonald’s Omega (ω) between 0.77 and 0.91, and appropriate average discrimination indexes (D), ranging from 0.35 to 0.67. The Total Mood Disturbance yielded excellent results, ω = 0.95, D = 0.61. The original structure was confirmed, ECVI = 4.361 (saturated ECVI = 2.395; independent ECVI = 21.855); RMSEA = 0.070, 90% CI [0.067, 0.072]; GFI = 0.974; AGFI = 0.971; CFI = 0.853; NFI = 0.812; and NNFI = 0.843. Conclusions: The Shortened Version of the Profile of Mood States has been proven to be a valid and reliable measure of emotional functioning in chronic pain patients. Full article

Rheumatoid arthritis (RA) is an immune-mediated chronic and long-term condition that can lead to severe joint damage and disability. It has been shown that doctor–patient interaction and communication can have a significant impact on faster patient diagnosis and treatment outcomes. Primary care (PC) is the first level of patient contact with doctors and the health system. Communication between them is often ineffective, leading to delays in diagnosis, care, and the use of disease-modifying antirheumatic drugs (DMARDs). The protocols and standards for the treatment of RA are well established by all rheumatology organizations. All of them recommend early initiation of DMARDs, which leads to better long-term outcomes. There are some recommendations that would lead to better optimization of recognition, management, and referral practices. Early diagnosis, effective communication between general practitioners and specialists, and patient education about possible targeted therapies and biological products, as well as subsequent monitoring of therapies and screening for risk factors and comorbidities, will improve patient health and optimize costs. We aimed to offer strategies and possibilities for integrating and optimizing primary care and specialized therapies in RA because proper management will reduce the severity of the disease and even reduce mortality from chronic diseases such as RA. Full article

Muscle function and pathology are complex subjects; the medical fields involved in their diagnosis and treatment represent rheumatology, physiatry and metabolic disease, among others. While we, rheumatologists, concentrate our efforts predominantly on inflammatory varieties and those associated with medications (e.g., corticosteroid and statin use), we are often the “turn to” gatekeepers for the identification of the diagnostic category represented by a patient’s symptomatology. The broad base of rheumatologic training prepares us for the recognition of endocrinologically derived myopathy. This subject and fundamentally biochemically derived myopathies form the basis for this review. Full article

The SARS-CoV-2 virus can cause hyperstimulation of the immune system, sometimes leading to the production of various autoantibodies and increased levels of interferons and interleukins in blood plasma. Background/Objectives: Only a few studies are currently focusing on the dynamics of immunological indices after any transferred infectious disease encountered by an organism for the first time. The attention of researchers and clinicians is captured by the dynamics of antibody titers and immunologic markers (interferons and interleukins), as well as the correlation of immunologic indices with changes in the symptomatology of long COVID. This paper discusses the association of antibodies against various autoantigens with rheumatological and neurological manifestations of COVID-19. Our study patient was a 36-year-old man diagnosed with polyneuropathy, which developed after COVID-19. We conducted a dynamic follow-up of the patient for two years. Methods: The blood plasma samples collected were analyzed by ELISA for different autoantigens, IFN-γ, and a variety of interleukins. Results: An association between rheumatologic and neurologic markers in patients with long COVID symptoms was considered. Antibody titers for myelin basic protein (MBP), double-stranded DNA (dsDNA), single-stranded DNA (dsDNA), and IFN-γ, IL-1, IL-6, and IL-10 levels significantly increased during the posthospital period when the patient reported persistent symptoms of long COVID, with complaints decreasing after the symptoms were resolved. Conclusions: The findings of this study shed light on the dynamic alterations of immunological factors, and elucidate the mechanism by which SARS-CoV-2 infection disrupts immunotolerance and eventually restores equilibrium, leading to the rheumatological pathology. Significantly, the notable rise in antibody titers for various autoantigens was transient and did not lead to the progression of autoimmune pathology. Full article

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a complex pathogenesis, primarily affecting women. SLE is associated with the presence of autoantibodies, chronic inflammation, and multi-organ dysfunction. Increasing evidence suggests that SLE is linked to a higher risk of malignancies, compared to the general population, though the mechanism behind this phenomenon remains unclear. Malignant tumors are the fourth most common cause of death in SLE patients. SLE is associated with an elevated risk of hematological cancers, as well as cancers of the lungs, thyroid, liver, and bile ducts. The aim of this paper is to review the latest literature on the pathogenesis, epidemiology, and risk factors for malignancies in SLE patients. The mechanisms of oncogenesis in SLE are still not fully understood, and the pathophysiology includes such risk factors as chronic inflammation, immune disorders, therapies used, overlap syndromes of connective tissue diseases, viral infections, and traditional cancer risk factors. Evaluating these factors and understanding the process of oncogenesis are crucial for prevention. Systemic lupus erythematosus may be an independent risk factor for the development of malignancies. It is important to raise awareness among SLE patients about the increased risk of malignancies. Further research is needed to establish guidelines for prevention, including screening recommendations. Full article

Early diagnosis and therapy in axial spondyloarthritis, axSpA, is known to reduce long-term morbidity. However, the time from symptom onset to diagnosis is typically delayed by several years, and this situation has not improved in recent years despite greater clinical awareness and better imaging. This narrative review discusses the underlying causes for axSpA diagnostic delay. It is proposed that to reduce axSpA diagnostic delay, a better understanding of the axSpA subclinical inflammatory process is required, together with machine learning-enabled inflammation/repair biomarkers such as lipocalin 2 and lipocalin 2-matrix metalloprotease 9, developed through extensive clinical domain knowledge. Full article