OBJECTIVES:To assess the long-term outcomes and prognostic factors of patients presenting with all-cause mixed cryoglobulinaemia vasculitis (CryoVas). METHODS:A European multicentre cohort study (EuroCryo) of 1294 patients presenting with all-cause CryoVas. RESULTS:The main aetiology for CryoVas was Hepatitis C Virus ( HCV) with 469 (36%) cases, followed by essential forms (n = 344, 26%) and autoimmune conditions (n = 302, 23%), with Sjögren's disease being the most common (n = 268, 21%). Over a median follow-up of 2.8 years, a total of 558 CryoVas patients experienced 661 severe events, notably 221 relapses, 52 severe infections and 45 lymphomas. The multivariable model for event-free survival retained a post-2014 diagnosis, male sex, older age, low C4 levels, positive Rheumatoid Factor and higher baseline creatinine levels as poor prognostic factors; HCV aetiology was protective. Factors associated with the occurrence of lymphoma were a post-2014 diagnosis, autoimmune aetiology, fever, fatigue and low C4 levels. CONCLUSION:HCV was for long considered a poor prognosis factor in CryoVas, and now those secondary to autoimmune conditions seem to evolve with a more severe course, notably carrying a higher lymphoma risk.

OBJECTIVE:Sjögren disease (SjD) is a systemic autoimmune disease characterized by increased risk of B-cell non-Hodgkin lymphoma. Although cryoglobulinemia and serum monoclonal component (MC) are well-recognized paraproteinemias in SjD, no large-scale study has directly compared their isolated and combined impact on phenotype and lymphoproliferative risk. METHODS:A retrospective, multicenter, cross-sectional study was conducted within the Italian GRISS registry. Patients with SjD were stratified into four groups: isolated monoclonal gammopathy (MC-alone), isolated cryoglobulinemia (CRYO-alone), both (MC+CRYO), or neither (controls). Demographics, lymphoma history, ever-documented ClinESSDAI domains, and laboratory lymphoproliferative risk-related markers were analyzed. Primary and secondary outcomes assessed lymphoma diagnosis and the distribution of laboratory lymphoproliferative risk-related markers and ClinESSDAI domains across groups, with associations tested using logistic regression adjusted for confounders. RESULTS:1202 SjD patients were enrolled: 58 (4.83%) in the MC-alone, 32 (2.66%) in the CRYO-alone, 35 (2.91%) in the MC+CRYO, and 1077 (89.60%) controls. Compared with controls, only the MC+CRYO group showed significant association with lymphoma (OR 6.30, 95%CI 2.66-14.92; p < 0.001), while MC-alone and CRYO-alone were not associated. Cryoglobulinemia, alone or combined with MC, correlated with laboratory lymphoproliferative risk-related markers such as rheumatoid factor (p < 0.001) and low C4 (p < 0.001), and with ClinESSDAI vasculitic features (cutaneous [p < 0.001], renal [p < 0.05], PNS [p < 0.001]). The MC+CRYO group additionally displayed a lymphoproliferative phenotype correlating with constitutional (p < 0.05), glandular (p < 0.05), hematological (p < 0.001), and lymphadenopathy (p < 0.001) domains. CONCLUSION:Cryoglobulinemia in SjD associates with vasculitic disease activity, whereas the coexistence of serum MC and cryoglobulins identifies a distinct, high-risk subset characterized by advanced B-cell expansion and increased lymphoma susceptibility.

ObjectiveBehçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages.MethodsData were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications.ResultsIn total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%).ConclusionMajor aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.

OBJECTIVES:To investigate cutaneous manifestations in Still's disease patients, evaluating any correlation with ethnic origin, age at disease onset, disease patterns, occurrence of macrophage activation syndrome (MAS) and systemic activity scores. METHODS:Data were retrospectively drawn from the International AutoInflammatory Disease Alliance (AIDA) Network Registry dedicated to Still's disease. RESULTS:A total of 518 patients (41.3% males) were enrolled. Salmon-coloured evanescent skin rash (n = 304, 63.9%), macules (n = 40, 7.7%), urticarial eruptions (n = 31, 5.9%), erythema (n = 27, 5.2%) and persistent pruritic papules and plaques (PPPP) (n = 25, 4.8%) accounted for the most frequent skin manifestations observed in Still's disease. Overall, atypical skin rash were described in 110 (21.2%) patients. Salmon-coloured evanescent skin rash and pruritus were more common among patients aged <16 years compared with patients aged 16-60 (P = 0.002 and P = 0.008, respectively). Pruritus was significantly more frequent among White than among Arab patients (P = 0.008) and in polycyclic vs monocyclic course (P = 0.049). Hispanics showed a significantly higher rate of atypical skin manifestations compared with Arabs (P = 0.036) and White (P = 0.036). Also, macules were more frequent among Hispanics than White (P = 0.027), while PPPP was more frequent among Hispanics than Arabs (P = 0.023) and White (P = 0.002). Salmon-coloured evanescent skin rash was significantly more frequent among patients with a systemic activity score ≥7 (P < 0.001). CONCLUSION:The present study enhances dermatologists' awareness of the diverse cutaneous lesions that may represent heterogeneous manifestations of Still's disease, shedding new light on the difference related to the age at disease onset, the patients' ethnic origin and the severity of the disease.

ObjectiveDry eye disease (DED) has been described in axial spondyloarthritis (axSpA), but patterns of tear fluid and ocular surface involvement remain incompletely characterized. This study aims to evaluate tear film instability and tear production in axSpA and explore the heterogeneity of DED manifestations.MethodsAxial spondyloarthritis patients and healthy controls underwent non-invasive tear break-up time (niTBUT), Schirmer test, and Ocular Surface Disease Index (OSDI)- 6 evaluation. Group differences were assessed using niTBUT thresholds (<10 s and <5 s).ResultsMean niTBUT was significantly lower in axSpA patients than controls (7.85 ± 5.63 vs. 10.61 ± 5.27 s; p < 0.001); niTBUT <5 s, but not <10 s, differentiated groups (p = 0.003 and p = 0.105, respectively). ROC analysis identified an optimal niTBUT cut-off of 5.15 s. Schirmer values also discriminated axSpA patients from controls, with an optimal threshold of 4.5 mm. Agreement between niTBUT and Schirmer classification was weak (Cohen κ = 0.18). OSDI-6 scores were not significantly associated with pathological niTBUT. The niTBUT values were significantly associated with patients’ age, but the diagnosis of axSpA accounted for the main determinant of niTBUT <5 s (likelihood ratio test, p = 0.026).ConclusionWithin the present cohort, a niTBUT <5 s showed greater discriminative performance than the conventional 10-s cut-off and may identify a subgroup of axSpA patients with more severe tear film instability. Aging contributes to tear film instability, but axSpA independently contributes to severe niTBUT impairment. Tear film instability and reduced tear secretion are both involved in DED affecting axSpA patients.

OBJECTIVES:Neurological involvement in Sjögren's disease (neuro-SjD), reported by up to 20% of patients, represents a highly relevant extra-glandular manifestation. Owing to the clinical complexity, frequent diagnostic delay and the poor response to treatment, neuro-SjD remains a major unmet need. This study aimed to better understand the burden of neuro-SjD from the patient perspective, focusing on the overall care journey. METHODS:An anonymous multilingual survey was co-developed by patient research partners and rheumatologists and distributed via patient associations. RESULTS:A total of 4050 valid responses from SjD patients across 60 countries were collected and analysed. All respondents reported at least one of the symptoms listed in the survey, with each symptom having a medium-to-severe impact in at least half of the patients. A formal diagnosis of neuro-SjD most often made by a neurologist was reported by 21.6% of symptomatic patients. Among those diagnosed, only 21% received pharmacological therapies and just 23% of them reported significant or complete symptom improvement. Overall, satisfaction with neuro-SjD care was poor, with half of the respondents feeling that healthcare providers underestimated their neurological symptoms. CONCLUSION:Our findings suggest that the prevalence of neurological symptoms in SjD is likely underestimated and highlight neuro-SjD as a major unmet need. We advocate for raising awareness and prompting research in this area, facilitating the diagnosis and correct attribution of these debilitating manifestations to support timely diagnosis, accurate symptom attribution and ultimately identifying effective treatment strategies to improve the quality of life of people living with SjD.

OBJECTIVES:In clinical practice, standardised reporting of nailfold videocapillaroscopy (NVC) findings is lacking, making the interpretation and comparison of results difficult. We aimed to achieve a national consensus on how to describe NVC findings in routine clinical practice. METHODS:A web-based Delphi consensus study was conducted among members of the Study Group on Capillaroscopy and Microcirculation in Rheumatic Diseases of the Italian Society of Rheumatology (CAPSIR). The study was based on items derived from a previous systematic review and international consensus by the EULAR Study Group on Microcirculation in Rheumatic Diseases (SG_MC/RD). RESULTS:A total of 40 items were proposed during the Delphi process, which was completed by 52 participants from different Italian regions. An agreement was reached on 23 items covering different aspects of the NVC examination: general aspects (2 items), description of the fingers examined (3 items), possible confounding factors (2 items), device description (2 items), image quality (1 item) and details of the NVC examination (13 items). Sixteen of these were considered mandatory for inclusion in the NVC practice report, and 7 were considered optional. CONCLUSIONS:The proposed NVC checklist covers 23 relevant issues in clinical practice, including 16 mandatory items grouped into five categories. This national consensus will improve the reproducibility and generalisability of NVC reporting in daily clinical practice. Furthermore, the outcomes of this NVC consensus process will inform the next European web-based Delphi consensus study, to be conducted among the member countries of the EULAR SG_MC/RD.

Objectives To evaluate whether early canakinumab initiation may provide treatment advantages in Still’s disease (SD) patients, particularly in terms of therapy discontinuation due to long-term disease remission, glucocorticoid sparing effect, and increase in the frequency of monocyclic disease course rather than a polycyclic or chronic articular pattern. Methods SD patients treated with canakinumab were grouped according to time between disease onset and canakinumab initiation (≤3 months vs. >3 months). Patients were enrolled from the international AutoInflammatory Disease Alliance (AIDA) Network registry for SD. Results Overall, 190 patients were enrolled, 35 (19%) treated with canakinumab within three months from SD onset and 155 (82%) starting canakinumab later. Glucocorticoids use decreased more rapidly in patients receiving canakinumab within 3 months from SD onset than among patients treated later, with reductions of 50% vs 6% at month 3 (p=0.0001), and 75% vs 32% at month 6 (p=0.004). In logistic regression analysis, canakinumab initiation within 3 months from disease onset was significantly associated with treatment discontinuation due to long-term remission (OR 4.83, 95% CI 1.08-23.19; p=0.04). A monocyclic course occurred in 49% of patients starting canakinumab ≤3 months versus 8% starting later (p<0.0001). Starting canakinumab within 3 months from disease onset was significantly associated with a monocyclic disease course compared with the chronic-articular (RRR 4.43, 95% CI 1.12-17.60; p=0.034) and polycyclic courses (RRR 8.97, 95% CI 1.29-62.3; p=0.03). Conclusions Early canakinumab initiation is associated with treatment discontinuation due to long-term remission and appears linked to a greater frequency of a monocyclic disease course.

OBJECTIVES:Immunoglobulin (Ig)G4-related disease (IgG4-RD) can affect any organ, but coronary artery involvement (CAI) is a potentially life-threatening manifestation of this disease. In this scoping review, we critically appraised the literature on IgG4-related CAI, aiming to explore clinical, radiological and histopathological characteristics as well as treatment strategies and prognosis. METHODS:A comprehensive search was performed on January 02, 2025 in PubMed® to identify studies describing individuals with IgG4-related CAI, including both coronaritis (true arteritis of the coronary vessel wall) and periarteritis (peri-coronary involvement), and considering case reports, case series, retrospective cohort studies and observational studies. Two reviewers independently conducted the revision of literature under the guidance of the methodologist to identify eligible studies. Data extraction included clinical presentation, imaging findings, histopathology, treatment, and outcomes. Given the heterogeneity of the studies, descriptive statistical analysis was used whenever possible to summarise the data. RESULTS:Out of 964 screened references, 143 articles met the above-mentioned inclusion criteria. Most CAI cases were included in case reports (90.2 %), 7 % in case series and 2.8 % in retrospective cohort studies or observational studies. CAI predominantly affected males in the sixth decade of life and frequently coexisted with aortic and large vessel involvement. All segments of the coronary arterial tree could be involved, even the smallest branches. Images detected by various methods revealed several types of lesions: stenosis, wall-thickening, aneurysm, ectasia, pseudotumor, pseudoaneurysm, dissection, and soft tissue masses. Increase serum IgG4 levels and increased inflammatory markers were reported. Histopathology was consistent with IgG4-RD in all coronary samples obtained. Glucocorticoid therapy, alone or combined with immunosuppressants and/or surgical interventions, was the most commonly reported treatment. Rituximab seemed to be an effective therapy for IgG4-related CAI even without associated glucocorticoids. Despite treatment, relapse and progression of coronary lesions were noted in some cases. CONCLUSIONS:Early identification and multidisciplinary management og IgG4-related CAI are crucial to reduce morbidity and mortality. Available data on the response to various treatments are limited, as dedicated coronary artery imaging was not consistently obtained soon enough after treatment to assess response. In addition, long-term follow-up was not available for all patients. Further studies are required to understand the real prevalence, natural history, optimal diagnostic strategies, and therapeutic approaches for this serious condition.

OBJECTIVES:The progression of Behçet's disease (BD) from a mucocutaneous-limited form to major organ involvement (MOI) represents a significant challenge. This study aims to identify patients without MOI at BD onset who are at increased risk of developing MOI in later stages. METHODS:Patients' data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. RESULTS:A total of 328 patients with exclusively mucocutaneous manifestations at BD onset were enrolled. Of these, 82 patients (25%) developed MOI over the entire follow-up period. Patients with minor oral aphthosis and no major oral aphthosis exhibited a reduced risk of developing MOI, with an odds ratio (OR) of 0.41 [95% confidence interval (95%CI): 0.22-0.79, P = 0.008]. Conversely, patients with both major and minor oral aphthosis had a significantly higher risk of developing MOI, with an OR of 12.76 (95%CI: 1.44-113, P = 0.02). Moreover, the development of MOI was associated with major oral aphthosis plus genital aphthosis (OR: 2.49, 95%CI: 1.1-5.6, P = 0.03), major oral aphthosis plus pseudofolliculitis (OR: 2.9, 95%CI: 1.15-7.4, P = 0.02) and major oral aphthosis plus both genital aphthosis and pseudofolliculitis (OR: 3.73, 95%CI: 1.22-11.4, P = 0.02). A positive family history for BD was associated with MOI (OR: 2.85, 95%CI: 1.08-7.58, P = 0.03). CONCLUSION:A positive family history and the presence of major oral aphthosis combined with minor oral aphthosis, genital aphthosis or pseudofolliculitis are associated with MOI development in patients with mucocutaneous BD at onset.

ObjectivesThis study aims to explore the application of machine learning techniques in assessing macrophage activation syndrome (MAS) in Still’s disease.MethodsA multicenter, observational, prospective study was conducted, including patients with Still’s disease enrolled in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) AOSD Study Group and the AutoInflammatory Disease Alliance (AIDA) Network Still’s Disease Registry.ResultsA total of 737 patients (age: 35.5 ± 17.8, male sex: 44.7%) with Still’s disease were assessed; 11.4% were affected by MAS, and 3% had a poor prognosis. First, random forest imputation was applied to the original dataset. Subsequently, a machine-learning-driven assessment was developed to explore MAS occurrence. Collectively, regression models, an exploration decision tree, and a random forest were applied, suggesting the importance of ferritin, age, C-reactive protein (CRP), and systemic score. A logistic regression model accounting for data leakage concerns was then generated using these variables, and missing values were imputed using random forest imputation. This analysis supported the role of the selected variables, which were further combined across different clinical scenarios to estimate the probability of MAS. The highest risk of MAS was estimated for patients simultaneously characterized by age ≥ 45 years, ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and a systemic score ≥ 7, corresponding to a 34.7% probability of MAS, as well as for those characterized by ferritin ≥ 4,178.10 ng/mL, CRP ≥ 27.15 mg/L, and systemic score ≥ 7, corresponding to a 33.5% probability of MAS.ConclusionsA machine-learning-driven prediction of MAS was explored in Still’s disease, highlighting the importance of age of onset, hyperferritinaemia, increased CRP, and multiorgan involvement. A combination of these features may suggest a clinician-friendly algorithm for stratifying the probability of MAS during Still’s disease.

OBJECTIVES:Refractory manifestations of Behçet's disease (BD) are commonly treated with TNF-α inhibitors; however, a subset of patients do not respond or are intolerant, prompting the need for alternative therapies. This study aimed to assess the real-life use, efficacy, and safety of non-TNF targeted biologic agents in BD. METHODS:Data were retrieved from the International AutoInflammatory Disease Alliance (AIDA) Network Registry for BD. Patients who received any biologic agent other than TNF-α inhibitors at any point during follow-up were included in the study. Clinical and demographic characteristics, prior treatments, and treatment responses at the 3-, 6- and 12-month follow-ups were collected. RESULTS:In total, 65 patients (36 female/29 male) with a mean age of 45.8 ± 13.3 years were included in the sample population for this study. Anakinra was the most frequently used agent (n = 31), with 34.7% of patients with mucocutaneous, 73.3% with musculoskeletal, and 77.7% with ocular involvement showing a partial or complete response. Canakinumab (n = 11) was effective in mucocutaneous, musculoskeletal and ocular involvement, including in some patients previously unresponsive to anakinra. Tocilizumab (n = 15) showed favourable outcomes in ocular and neurological involvement (a complete response in 5 of 6 patients), while 40% experienced worsening or no response in mucocutaneous manifestations. Secukinumab and ixekizumab were effective in patients with mucocutaneous-articular phenotypes, especially those with axial SpA. Ustekinumab (n = 3) and rituximab (n = 5) also demonstrated clinical improvement in selected refractory cases. No new major safety concerns were reported across the treatment groups. CONCLUSION:Biologics targeting IL-1, IL-6, IL-17 and the IL-12/23 pathways may offer therapeutic alternatives in BD patients unresponsive to TNF-α inhibitors. The treatment efficacy varied across phenotypes, highlighting the need for individualized treatment decisions.

ObjectiveThe primary aim of this study was to assess, in Still’s disease, whether the employment of canakinumab at a strictly on-label dose may increase the likelihood of treatment discontinuation due to study-defined long-term remission (LTR), compared with patients receiving lower doses.MethodsPatients were drawn from the international Autoinflammatory Disease Alliance (AIDA) Network registry dedicated to Still’s disease and stratified based on the starting canakinumab dose: the on-label group received either 300 mg every 4 weeks or 150 mg every 4 weeks (corresponding to 4 mg/kg), while the underdosed group received 150 mg every 4 weeks (corresponding to a dose not exceeding 3.5 mg/kg). Bayesian regression models were implemented to estimate the probability of achieving long-term remission with subsequent canakinumab withdrawal in the two groups, as well as the mean differences in probabilities and posterior probabilities indicating whether the on-label group was superior in achieving the endpoint.ResultsIn total, 131 patients (16.7%) were enrolled, 81 (61.8%) receiving the on-label posology and 50 (38.2%) the underdosed posology. The estimated marginal posterior probability of canakinumab discontinuation due to LTR was 19% (CrI 7.5%–34.6%) in the on-label group and 3.9% (CrI 0.7%–15.2%) in the underdosed group, yielding a mean difference of 15.1% (CrI 1.4%–31.4%) and a posterior probability of 98.4%. This difference remained credible, with posterior probabilities ranging from 97.9% to 99.6%, irrespective of disease course or age at disease onset.ConclusionOn-label canakinumab dosing appears to increase the likelihood of study-defined LTR with subsequent treatment discontinuation, compared with underdosed treatment strategies.

OBJECTIVES:To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and spondyloarthritis (SpA). METHODS:All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) identified potential cases of coexisting SpA and sarcoidosis. Inclusion criteria were the fulfilment of the current classification criteria both for SpA (ASAS) and sarcoidosis (WASOG). RESULTS:We identified twenty-three patients (14 females and 9 males) with a mean age of 44 years at diagnosis of SpA and of 45 years at diagnosis of sarcoidosis. Most of the patients fulfilled the ASAS criteria for axial SpA. In 8 patients, sarcoidosis was diagnosed after SpA, in 9 patients sarcoidosis preceded SpA and in 6 patients the diagnoses were concurrent. Within these groups, the HLA*B-27 haplotype was detected in 5 (62%), 2/8 (25%) and 3 (50%) of patients respectively. A median of 2 years (range 1-19) occurred between the diagnosis of the two diseases in the first 2 groups. Lung, skin, and extra-thoracic lymph nodes were the most frequent sarcoidosis manifestations in all 3 groups. CONCLUSIONS:We have characterised 23 patients who fulfilled the current classification criteria for both SpA and sarcoidosis. Therefore, sarcoidosis may coexist with SpA like other systemic autoimmune diseases, and this may be explained by shared pathogenic mechanisms. Since Th17 cells are leading actors in the pathogenesis of both SpA and sarcoidosis, these cells may be the missing link connecting the two diseases.

Bone marrow fibrosis is frequently observed in patients with haematological malignancies including myeloproliferative neoplasm (MPNs). The most common cause of BMF is the BCR-ABL-negative MPN primary myelofibrosis (PMF) however, BMF may also be caused by a variety of non-neoplastic disorders such as infections, endocrine diseases and autoimmune diseases (ADs). Autoimmune myelofibrosis (AIMF) is a type of BMF associated with either a fully blown AD (secondary AIMF) or serological signs of autoimmunity without an overt AD (primary AIMF). Although isolated case reports and case series have been published, AIMF remains a poorly recognized disorder. Therefore, we performed a scoping review and critically appraised the literature on AIMF pathogenesis, diagnosis and treatment with a particular focus on similarities and differences between AIMF and PMF.

Thymic tumors are rare in the general population, and to the best of our knowledge, no cases of thymoma have been described in patients with rheumatic diseases treated with tumor necrosis factor (TNF)-α inhibitors, except for the case of a patient receiving infliximab for Crohn's disease (CD) who developed a B2 thymoma. We describe a 60-year-old Caucasian male with radiographic axial spondyloarthritis (r-axSpA) and CD who developed an AB-type thymoma without myasthenia gravis after 18 years of treatment with TNF-α inhibitors. The patient had received the same molecule since the r-axSpA/CD diagnosis and changed it 6 months before the diagnosis of thymoma due to a disease flare. At the time of the drug switch, no mediastinal mass was present on the chest X-ray. The thymoma was surgically removed, and no additional therapy was needed. Treatment with TNF-α inhibitors was reintroduced after surgery. This case raises some important questions that remain open and deserve to be addressed in the future, such as the association between immunosuppressive therapy and thymoma and the controversial relationship between TNF-α inhibitors and myasthenia gravis.

Objectives:To detect factors capable of predicting the development of macular edema (ME) throughout the disease course in patients affected by non-infectious uveitis (NIU). Methods:Predictive factors leading to the development of ME were analyzed through regression analysis. The functional impact of ME on best corrected visual acuity (BCVA) was also examined. Results:A total of 1,160 NIU patients (1,857 eyes) were analyzed. ME was observed in 148 (12.76%), affecting 211 eyes. It was significantly more frequent in patients with non-anterior NIU (p < 0.0001, RR = 4.01), retinal vasculitis (p < 0.0001), and other structural complications (p = 0.0005). Gender, HLA-B*27 and/or HLA-B*51 positivity, and ethnicity did not show any significant impact on the prevalence of ME (p = 0.635, p = 0.372, p = 0.193, respectively). Four variables were associated with ME development during NIU course: the non-anterior anatomical pattern (p < 0.0001, OR = 4.01), the presence of retinal vasculitis (p = 0.028, OR = 1.68), complications other than ME (p = 0.044, OR = 1.51) and immunosuppressive treatment (p = 0.010, OR 1.69) while the diagnosis of Behçet disease-related uveitis was less likely to be associated with ME development (p = 0.24, OR 0.545). Mean ± SD BCVA was significantly lower in eyes with ME (0.82 ± 0.30) compared to eyes without ME (0.71 ± 0.33). Conclusion:ME can develop across all NIU types, but is more likely in cases involving the posterior segment and retinal vasculitis. Regular and focused monitoring is recommended for these high-risk patients. The study also highlights the limited predictive value of demographic and HLA-related factors, helping refine clinical risk stratification and predictive modeling in NIU.

Behçet’s disease (BD) frequently arises with exclusively mucocutaneous involvement, but some patients will develop major organ involvement, including ocular inflammation. This study aims to assess the patients’ demographic and clinical characteristics that may be associated with the development of ocular involvement in patients with BD with exclusively mucocutaneous involvement in the early stages. Patients’ data were collected in the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. A total of 328 patients with BD were enrolled, 36 (11