Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis in children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan's syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Assessment of quality of life and physical activity in patients with oligoarticular juvenile idiopathic arthritis in remission.

The purpose of this study was to evaluate physical activity (PA) and health-related quality of life (HRQOL) in children with oligoarticular juvenile idiopathic arthritis (JIA) in remission in comparison with healthy peers and to determine the disease-related factors affecting PA levels. This study was conducted with 50 oligoarticular JIA patients in remission and 50 healthy peers between 9 and 14 years. Demographic and clinical characteristics, laboratory parameters, and treatments were noted from electronic medical records. HRQOL was assessed with the Pediatric Quality of Life Inventory (PedsQL). PA was evaluated with the Physical Activity Questionnaire for Children (PAQ-C). Oligoarticular JIA patients had significantly lower self-reported median PedsQL scores in the domains of school functioning and social functioning compared to the control group (67.5 (10) vs. 75 (25), p = 0.001 and 70 (15) vs. 85 (26.3), p < 0.001, respectively). The median PAQ-C score was 2.6 (1.1) in patients with JIA and 3 (0.9) in their healthy peers (p = 0.02). The PAQ-C score was 2.8 (1.2) in patients < 8 years at the disease onset and 2.3 (1) in those aged ≥ 8 years (p = 0.022). There was no significant difference in the number of affected joints, type of affected joint, MTX and biologic agent treatment, and remission with or without drugs with the total score of the PedsQL and PAQ-C. All PedsQL domains were positively correlated with the PAQ-C.  Conclusion: Oligoarticular JIA patients demonstrated lower PA and HRQOL scores compared to healthy controls despite favorable disease control. What is Known: • Oligoarticular JIA has fewer functional limitations and disabilities compared to other JIA subtypes. • As JIA can affect all aspects of a child's life, there is a need to improve the quality of life related to the disease. What is New: • It should be considered that patients with oligoarticular JIA may show lower PA and HRQOL scores compared to healthy controls despite favorable disease control. • Since there may be a relationship between PA and HRQOL, factors that may affect PA should be investigated to provide a holistic approach to JIA treatment.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

The purpose of this study was to compare the demographic and clinical characteristics of the groups with and without bDMARDs added to the treatment of persistent oligoarticular juvenile idiopathic arthritis (JIA) patients on methotrexate (MTX) and also to determine the predictors of adding bDMARDs to treatment. This study included 86 oligoarticular JIA patients on MTX. Patients were divided into two groups receiving MTX (n = 69) and MTX plus bDMARD (n = 17). Predictors of adding bDMARDs were investigated by comparing demographic, clinical features and laboratory findings. Gender, age at diagnosis, time elapsed from the onset of symptoms to diagnosis, and disease duration, the number and distribution of affected joint at the time of diagnosis were similar in both groups. The mean JADAS10 at the time of diagnosis were 18.8 ± 4.2 and 19.5 ± 6.4 in the MTX and MTX plus bDMARDs groups, respectively (p = 0.68). JADAS10 at 3rd and 6th month were significantly higher in patients on MTX plus bDMARDs (p = 0.001, p = 0.004, respectively). In multivariate analysis, the risk of adding bDMARD was shown to increase 1.24-fold (p = 0.004, 95% CI: 1.07-1.43) for each point increase on the JADAS 10 at 3rd months. The number (p = 0.64) or type (p = 0.18) of joint involvement at disease onset were not predictors of adding a bDMARD. CONCLUSION: JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. WHAT IS KNOWN: • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. WHAT IS NEW: • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6 months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Evaluation of pediatric rheumatologists' approach to rituximab use: a questionnaire study.

Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration. CONCLUSIONS: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. WHAT IS KNOWN: • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. WHAT IS NEW: • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

Sacroiliitis in familial Mediterranean fever: A rare joint involvement of the disease.

AIM: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease characterised by recurrent episodes of fever and polyserositis. Sacroiliac joint involvement is rare in FMF patients. The purpose of this study was to evaluate the demographic, clinical, laboratory and imaging findings of patients with FMF who developed sacroiliitis. METHODS: The files of paediatric patients aged 0-18 years who were followed up with a diagnosis of FMF were retrospectively reviewed. FMF patients with evidence of sacroiliitis on magnetic resonance imaging (MRI) were included in the study. RESULTS: Among 1062 FMF patients, 22 (12 males; median age 8.5) (2.1%) of them were found to have sacroiliitis. FMF was diagnosed before sacroiliitis in nine (40.9%) patients and after in 13 (59.1%) patients. The most common symptom in patients with sacroiliitis was low back pain (n = 21, 95.5%). In MEFV gene analysis, M694V was found in 16 (72.7%) patients and was the most common mutation. MRI showed evidence of sacroiliitis in all patients. All patients were using colchicine. Patients with FMF-associated sacroiliitis, remission was achieved with non-steroidal anti-inflammatory drugs in 12 (54.5%), conventional disease-modifying antirheumatic drugs in six (27.3%) and tumour necrosis factor inhibitor treatment in four (31.8%). Four (31.8%) patients experienced sacroiliitis when colchicine incompatible and four (31.8%) patients experienced sacroiliitis while using biologic agents for colchicine-resistant FMF. CONCLUSIONS: FMF-associated sacroiliitis should be considered especially in patients with M694V mutation if they have symptoms such as low back pain. Colchicine-resistant FMF patients should be evaluated for sacroiliitis symptoms at each visit.

Assessment of quality of life, school performance, and physical activity in adolescents with Familial Mediterranean fever.

OBJECTIVES: The aim of this study is to evaluate differences in school performance, school attendance, quality of life, and physical activity in adolescents with Familial Mediterranean fever (FMF) compared to healthy controls. METHODS: One hundred and twenty-nine patients with FMF and 154 healthy controls between 13 and 18 years were included in the study. Demographic, school performance (according to grade point average), school absenteeism, and type and frequency of exercise were recorded. Quality of life was evaluated with the Pediatric Quality of Life Inventory (PedsQL) 4.0. RESULTS: The mean age of FMF patients was 15.1 ± 2.7 years, and 69 patients (53.5%) were female. School performance was significantly higher in the control group compared to FMF patients (P < 0.001). In the control group, there were significantly higher participants who engaged in professional sports (P < 0.001). Patients with FMF had significantly lower self-reported PedsQL scores in school functioning, physical, and psychosocial health domains compared to those in the control group (P = 0.001, P < 0.001, and P = 0.028, respectively). CONCLUSIONS: FMF patients demonstrated lower school performance and quality-of-life scores compared to healthy controls. In addition to improving symptoms in chronic diseases, it is important to evaluate and improve the quality of life of patients in routine practice and to ensure psychosocial well-being.

Predictors of disease course in systemic juvenile idiopathic arthritis.

PURPOSE: To identify potential predictors of the disease course of systemic juvenile idiopathic arthritis (sJIA) at the time of diagnosis. METHODS: This retrospective observational study was conducted in patients diagnosed with sJIA in our hospital between April 2009 and October 2023. The relationship between the disease course of sJIA patients and demographic, clinical, laboratory findings and complications were analyzed. RESULTS: Of the 51 patients diagnosed with sJIA, 26 (51%) patients had monocyclic, 7 (13.7%) polycyclic and 18 (35.2%) persistent disease course. 3 (5.8%) patients had a persistent disease course with persistent arthritis developed flares with systemic manifestations during follow-up. The presence of arthritis, polyarticular involvement, and hip involvement at the time of diagnosis were associated with persistent disease course (p=0.009, p=0.003, p=0.003). Serositis and higher white blood cell and neutrophil counts at the time of diagnosis were associated with a monocyclic disease course (p=0.034, p=0.002, p=0.008). However, no significant correlation was found between macrophage activation syndrome (MAS) and disease course (p=1). CONCLUSIONS: Systemic JIA patients with polyarthritis and hip involvement at disease onset may develop a persistent course. Although MAS is an important complication of sJIA, its effect on the course of the disease was not found in this study.

Association of Pediatric Vasculitis Activity Score with immunoglobulin A vasculitis with nephritis.

BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most serious complication affecting long-term prognosis. Understanding the risk factors and markers for the development of IgAVN is essential. The aim of this study is to identify IgAVN-associated factors and to evaluate the usability of Pediatric Vasculitis Activity Score (PVAS) at diagnosis as an early marker for the development of IgAVN. METHODS: We conducted a retrospective case-control study of 314 patients divided into two groups: those with nephritis (IgAVN) and without nephritis (non-IgAVN). The groups were compared in terms of clinical symptoms, laboratory values, and PVAS values. RESULTS: In total, 18.5% of the patients had IgAVN; they were older than the non-IgAVN patients (median age was 8.8, p < 0.05). Arthritis/arthralgia, abdominal pain, and intestinal bleeding were more common, systolic and diastolic BP were higher in IgAVN (p < 0.05). CRP, serum creatinine, and urine protein/Cr, PVAS were higher, while serum albumin was lower in IgAVN (p < 0.05). The receiver operator characteristic curve (ROC) analysis showed that IgAV patients with a determined cut-off PVAS value greater than 3 had 70.7% sensitivity in predicting whether or not they would develop IgAVN. Logistic regression analysis found that PVAS > 3 and low serum albumin at the time of diagnosis were independent risk factors for IgAVN. CONCLUSION: Our study revealed that PVAS > 3 at diagnosis is an independent predictor of IgAVN. Patients with PVAS > 3 should be followed more closely to ensure early diagnosis and management of IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Predictors of relapse in patients with oligoarticular juvenile idiopathic arthritis in remission off medication.

The aim of this study was to evaluate the predictors of relapse in patients with oligoarticular juvenile idiopathic arthritis (oJIA) who achieved clinical remission off medication. This retrospective observational study was conducted between June 2009 and July 2022 in 126 patients with oJIA who achieved remission off medication. The relationships between relapse status and demographic, clinical and laboratory findings, and treatment details were evaluated using electronic medical records. Of the 126 oJIA patients who achieved remission off medication, 85 (67.5%) were female. Relapse occurred in 31 patients (24.6%) with remission off medication after a median of 18 months (IQR 7-26). No statistically significant relationship was found between gender, age at diagnosis, oJIA subtype, number of joints, ANA, ESR, CRP level, initial Juvenile Arthritis Disease Activity Score and relapse in oJIA patients who achieved remission off medication (p = 0.66, p = 0.25, p = 1, p = 0.54, p = 0.29, p = 0.59, p = 0.95 and p = 0.52, respectively). There was a statistically significant relationship between the number of intraarticular corticosteroid injections (IACIs) and relapse (p = 0.01). Patients who underwent IACI 2-3 times had more relapses than those who never underwent IACI and those who underwent IACI only once (p = 0.01, p = 0.02, respectively). A relationship was found between the length of follow-up and relapse in patients with oJIA who achieved remission off medication (p = 0.035).    Conclusion: In oJIA patients who achieve remission off medication, the probability of relapse increases in patients who need ≥ 2 IACI during the period until remission. The length of follow-up period is associated with the probability of relapse. What is Known: • Approximately one-fourth of oJIA patients who are in remission off medication have relapse. • There is a need for markers that can predict the risk of relapse in oJIA patients who achieve remission on or off medication. What is New: • The possibility of relapse should be considered in patients with oJIA who need ≥ 2 IACIs until achieving remission off medication. • The relapse rate may increase as the follow-up period prolongs in patients who achieve remission off medication.

A case series of intracardiac thrombi and vascular involvement in pediatric Behçet's disease.

To evaluate the general characteristics of pediatric Behçet's disease (BD) patients with thrombus and to present the clinical features, treatment responses and prognosis of patients with intracardiac thrombus. The clinical characteristics and outcomes of 15 patients with thrombus among 85 pediatric BD patients followed in the Department of Pediatric Rheumatology were evaluated retrospectively. Of the 15 BD patients with thrombus, 12 (80%) were male, 3 (20%) were female. The mean age at diagnosis was 12.9 ± 1.1 years. Thrombus was present at the time of diagnosis in 12 patients (80%), while thrombus developed in three patients within the first three months after diagnosis. The most common site of thrombus was the central nervous system (n = 9, 60%), followed by deep vein thrombus (n = 6, 40%) and pulmonary artery thrombus (n = 4, 26.6%). Three male patients (20%) developed intracardiac thrombus. The overall intracardiac thrombus rate in the 85 patients was 3.5%. Two of the three patients had thrombus in the right, and one had thrombus in the left heart cavity. In addition to steroids, 2 of the 3 patients received cyclophosphamide, while the patient with thrombus localized in the left heart cavity was given infliximab. In the follow-up, the two patients with thrombus in the right heart cavity were switched to infliximab because of resistance to cyclophosphamide. Complete resolution was observed in 2 of the 3 patients on infliximab; a significant reduction in the thrombus of the other patient was achieved. Intracardiac thrombus is a rare presentation of cardiac involvement in BD. It is usually observed in males and in the right heart. Although steroids and immunosuppressive agents such as cyclophosphamide are recommended as first-line treatment, favorable outcomes can be achieved with anti-TNFs in resistant cases.