Performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for antineutrophil cytoplasmic antibody-associated vasculitis in previously diagnosed adult patients from Türkiye.

Objectives: This study aimed to evaluate the applicability of the new 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria in Turkish adult patients previously diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients and methods: One hundred sixty-four patients (96 males, 68 females; mean age: 49.6±14.4 years; range, 18 to 87 years) diagnosed with AAV by experienced rheumatologists between July 2016 and May 2022 were included in this retrospective cross-sectional study and reclassified based on the 1990 ACR criteria, the European Medicines Agency (EMEA) algorithm, and the 2022 ACR/EULAR criteria. For external validation, 83 patients (48 males, 35 females; mean age: 47.3±17.5 years; range, 19 to 81 years) diagnosed with immunoglobulin (Ig)A vasculitis were included. Results: One hundred twenty-six (76.8%) patients had granulomatosis with polyangiitis (GPA), 13 (7.9%) patients had eosinophilic granulomatosis with polyangiitis (EGPA), and 25 (15.2%) patients had microscopic polyangiitis (MPA). According to the criteria, the number of unclassified patients was nine (5.5%) for both the 2022 ACR/EULAR AAV classification criteria and the EMEA algorithm. The new criteria had an almost perfect agreement with the clinician's diagnosis (Cohen's kappa coefficient [κ]=0.858 for GPA, κ=0.820 for EGPA, and κ=0.847 for MPA). The kappa statistics for agreement of 2022 ACR/EULAR classification criteria with the EMEA algorithm were found 0.794 for GPA, 0.820 for EGPA, and 0.700 for MPA. None of the 83 patients diagnosed with IgA vasculitis could be classified as GPA, EGPA, or MPA using the new ACR/EULAR AAV classification criteria. Conclusion: The 2022 ACR/EULAR classification criteria for AAV showed substantial or perfect agreement with the clinical diagnosis and the EMEA algorithm.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Coronavirus Disease 2019 Outcomes in Amyloid A Protein Amyloidosis Secondary to Rheumatic Conditions and Signs of Post- Coronavirus Disease 2019 Proteinuria Progression.

BACKGROUND: We aimed to investigate coronavirus diease 2019 (COVID-19) outcomes in patients with amyloid A protein (AA) amyloidosis secondary to rheumatic diseases and discuss factors associated with disease course. METHODS: A retrospective cohort was formed from adult patients with a diagnosis of AA amyloidosis. In patients with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) test, rates of hospitalization, intensive care unit admission and mortality due to COVID-19 were collected from medical records. Data regarding to demographics, comorbidities, laboratory tests, medical treatments, adherence to previous treatments during COVID-19 and treatment administered for COVID-19 were collected from hospital databases and patient reviews. RESULTS: In 96 patients with AA amyloidosis, 16 had COVID-19 with a positive PCR. Ten (62.5%) patients were hospitalized, 2 (12.5%) were admitted to ICU, 1 (6.25%) was died. Hospitalized patients tended to be older. Comorbidities seemed to be more frequent in hospitalized patients. None of the patients had rapid progression to end-stage renal disease post-COVID-19. Seven patients had pre-COVID-19 and post-COVID-19 proteinuria levels. Three had notable increase in proteinuria after COVID-19 in 2 of which amyloidosis treatment was revised accordingly. CONCLUSION: Despite high rates of hospitalization in AA amyloidosis patients, mortality was observed only in 1 patient. Progression of proteinuria requiring treatment adjustment may be an issue in these patients. Cite this article as: Güven SC, Erden A, Küçük H, et al. Coronavirus disease 2019 outcomes in amyloid A protein amyloidosis secondary to rheumatic conditions and signs of post-coronavirus disease 2019 proteinuria progression. Eur J Rheumatol. Published online April 4, 2024. DOI:10.5152/eurjrheum.2024.23050.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Investigation of the value of hematological biomarkers in the clinical differential diagnosis of IgG4-RD.

BACKGROUND: IgG4- related disease (IgG4- RD) is a systemic fibroinflammatory disease whose pathogenesis has not been completely elucidated. Due to the novelty and complexity of the diagnostic criteria, it is difficult to distinguish from the diseases included in the differential diagnosis without tissue biopsy. This study aimed to discover new biomarkers that can help for disease diagnosis and its differential diagnosis by reviewing the relationships between neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). METHODS: Thirty IgG4- RD, 38 granulomatous polyangiitis (GPA), and 46 sarcoidosis patients presenting to the Rheumatology Clinic meeting the criteria of 2019 American College of Rheumatology, 2012 International Chapel Hill and 1999 American Thoracic Society meeting, respectively, and 27 healthy control subjects were included. We collected data on complete blood count with automated differential values including NLR, PLR, SII, and SIRI. RESULTS: The SII and PLR values were significantly higher in patients with IgG4-RD compared to healthy controls, (SII median (minmax) 572 (102-5583) vs. 434 (172-897), PLR median (min-max) 130 (56.8-546) vs. 104 (57.5- 253) p < 0.001). SII value was found to have a significant positive correlation with CRP in IgG4-RD disease (r = 0.371; p = 0.043). While SII, SIRI, NLR, PLR parameters were not significant between the IgG4-RD and sarcoidosis groups, SII, SIRI, NLR, PLR were significantly higher in patients with GPA than in IgG4-RD patients (p < 0.001). DISCUSSION: This is the first study to review the SII, SIRI, NLR, and PLR in IgG4-RD. The obtained results suggest that the SII could beused as a new tool, for differential diagnosis and activity of the IgG4-RD.

Cancer incidence in familial Mediterranean fever patients: a retrospective analysis from central Anatolia.

Although chronic inflammation has been associated with increased cancer risk in various disease including hepatitis or inflammatory bowel disease, a lower incidence of cancer has been reported recently in familial Mediterranean fever (FMF) which is an auto-inflammatory disease with persistent inflammation. We have assessed cancer incidence among FMF patients with or without amyloidosis to investigate this hypothesis. We performed a retrospective review of FMF patients, diagnosed and treated in Hacettepe University hospitals between 2001 and 2018. We identified patients from the hospital medical records using the ICD-10 code for FMF. We collected data on demographic and clinical features, drug history, the presence of amyloidosis and subsequent diagnosis of cancer. The expected cancer incidence was estimated using age- and gender-specific standardized incidence rates (SIRs) in comparison with the general Turkish population according to Turkish National Cancer Registry data at 2014. Total of 3899 FMF patients (120 patients had also amyloidosis) were included. Median age was 22 and 56% were females. Thirty-eight patients were diagnosed with cancer during 100,283 person-years of follow-up. The most common cancer was breast cancer in females (7/28 patients) and leukemia (2/10 patients) in males. The overall cancer incidence among patients with FMF was significantly lower in both males {SIR 0.42 [95% confidence interval; (CI) 0.21-0.75], p = 0.019} and females [SIR 065 (95% CI 0.44-0.93), p = 0.002]. The overall cancer incidence among patients with FMF and amyloidosis was [SIR 1.21 (95% CI 0.49-2.52), p = 0.73] without gender difference. Cancer incidence was significantly lower in FMF patients compared with the general Turkish population. We found no increased cancer incidence in FMF patients having amyloidosis. Possible underlying mechanisms need to be explained.