Rhupus syndrome in children: A multi-center retrospective cohort study and literature review.

OBJECTIVE: In this study, we aimed to evaluate the characteristics of pediatric rhupus patients including all the related series in the literature. METHODS: Thirty pediatric patients with rhupus syndrome from 12 different centers in Turkey were included in this study. The literature was also reviewed for pediatric patients with rhupus syndrome. RESULTS: The most prominent phenotype of these 30 patients was juvenile idiopathic arthritis (JIA) (60%) at the disease onset and SLE (73.3%) at the last visit. Major SLE-related organ involvements were skin (80%), hematological system (53.3%), and kidney (23.3%). Arthritis was polyarticular (73.3%), asymmetric (66.7%), and erosive (53.3%) in most patients. Hydroxychloroquine (100%), glucocorticoids (86.7%), and mycophenolate mofetil (46.7%) were mostly used for SLE, while glucocorticoids (76.6%), methotrexate (73.3%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (57.6%) were mainly preferred for JIA. Our literature search revealed 20 pediatric patients with rhupus syndrome (75% were RF positive). The most prominent phenotype was JIA (91.7%) at the disease onset and SLE (63.6%) at the last visit. Major SLE-related organ involvements were skin (66.7%), hematological system (58.3%), and kidney (58.3%). Arthritis was polyarticular (77.8%), asymmetric (63.6%), and erosive (83.3%) in most patients. Glucocorticoid (100%), hydroxychloroquine (76.9%), and azathioprine (46.2%) were mostly used for SLE, while methotrexate (76.9%) and NSAIDs (46.2%) were mainly preferred for the JIA phenotype. CONCLUSION: Our study is the largest cohort in the literature evaluating pediatric rhupus cases. Most of the pediatric patients had polyarticular, asymmetric, and erosive arthritis, as well as organ involvements associated with SLE, including the skin, hematological system, and kidney.

The risk of cardiovascular comorbidity in children with Behçet's disease.

OBJECTIVE: Patients with Behcet disease (BD) may experience long term morbidity caused by different forms of cardiovascular diseases. This study aimed to assess the risk for cardiovascular comorbidity in pediatric BD patients with and without vascular involvement, independent of the contribution of traditional risk factors. METHODS: Pediatric patients classified as BD according to the 2015 International Pediatric BD criteria were included in the study. Twenty-four-h ambulatory blood pressure monitoring (ABPM), transthoracic echocardiography, and carotid intima media thickness (cIMT) measurements were performed. Patients with an active disease and have other known risk factors for cardiovascular disease were not included in the study. RESULTS: Thirty-one children and adolescents with pediatric BD (16 female, 51.6%; F/M: 1.06) were enrolled in the study. Among all BD patients 10 patients (34.4%) had abnormal ABPM. Carotid IMT values, mean arterial pressure, systolic and diastolic blood pressure by ABPM and the prevalence of abnormal ABPM, non-dipping, and ambulatory hypertension were similar between patients with and without vascular involvement. The echocardiography measurements showed that BD patients with vascular involvement had significantly higher velocity and velocity time integral of the left ventricle outflow tract which may point out increased stiffness of the aorta. CONCLUSION: Pediatric BD patients with vascular involvement may tend to have more cardiovascular risk factors. However, cardiovascular assessment should be considered in all BD patients regardless of the involved systems. We suggest that ABPM may accurately define hypertension and cardiovascular risk in BD.

Plasma Proteomic Analysis Reveals the Potential Role of Lectin and Alternative Complement Pathways in IgA Vasculitis Pathogenesis.

BACKGROUND: IgA vasculitis (IgAV) is the most common form of childhood vasculitis. A better understanding of its pathophysiology is required to identify new potential biomarkers and treatment targets. OBJECTIVE: to assess the underlying molecular mechanisms in the pathogenesis of IgAV using an untargeted proteomics approach. METHODS: Thirty-seven IgAV patients and five healthy controls were enrolled. Plasma samples were collected on the day of diagnosis before any treatment was initiated. We used nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) to investigate the alterations in plasma proteomic profiles. For the bioinformatics analyses, databases including Uniprot, PANTHER, KEGG, Reactome, Cytoscape, and IntAct were used. RESULTS: Among the 418 proteins identified in the nLC-MS/MS analysis, 20 had significantly different expressions in IgAV patients. Among them, 15 were upregulated and 5 were downregulated. According to the KEGG pathway and function classification analysis, complement and coagulation cascades were the most enriched pathways. GO analyses showed that the differentially expressed proteins were mainly involved in defense/immunity proteins and the metabolite interconversion enzyme family. We also investigated molecular interactions in the identified 20 proteins of IgAV patients. We extracted 493 interactions from the IntAct database for the 20 proteins and used Cytoscape for the network analyses. CONCLUSION: Our results clearly suggest the role of the lectin and alternate complement pathways in IgAV. The proteins defined in the pathways of cell adhesion may serve as biomarkers. Further functional studies may lead the way to better understanding of the disease and new therapeutic options for IgAV treatment.

Pediatric mixed connective tissue disease versus other overlap syndromes: a retrospective multicenter cohort study.

Pediatric mixed connective tissue disease (MCTD) is a subgroup of overlap syndromes. We aimed to compare the characteristics and outcomes in children with MCTD and other overlap syndromes. All MCTD patients met either Kasukawa or Alarcon-Segovia and Villareal criteria. The patients with other overlap syndromes had the features of ≥ 2 autoimmune rheumatic diseases but did not meet MCTD diagnostic criteria. Thirty MCTD (F/M = 28/2) and thirty (F/M = 29/1) overlap patients were included (disease onset < 18 years). The most prominent phenotype at disease onset and the last visit was systemic lupus erythematosus (SLE) in the MCTD group; juvenile idiopathic arthritis and dermatomyositis/polymyositis, respectively, in the overlap group. At the last visit, systemic sclerosis (SSc) phenotype was more frequent among MCTD than overlap patients (60% vs. 33.3%; p = 0.038). The frequency of the predominant SLE phenotype had decreased (60% to 36.7%), while predominant SSc phenotype had increased (13.3% to 33.3%) during follow-up in MCTD patients. Weight loss (36.7% vs. 13.3%), digital ulcers (20% vs. 0), swollen hands (60% vs. 20%), Raynaud phenomenon (86.7% vs. 46.7%), hematologic involvement (70% vs. 26.7%), and anti-Sm positivity (29% vs. 3.3%) were more common, while Gottron papules (16.7% vs. 40%) were less frequent among MCTD than overlap patients (p < 0.05). A higher percentage of overlap patients achieved complete remission than MCTD patients (51.7% vs. 24.1%; p = 0.047). The disease phenotype and outcome differ between pediatric MCTD and other overlap syndromes where MCTD may be regarded as a more severe disease. Analyzing these patients could pave the way for early and effective treatment.

Evaluation of periodontal status and cytokine response in children with familial Mediterranean fever or systemic juvenile idiopathic arthritis.

OBJECTIVES: Familial Mediterranean fever (FMF) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases and anti-inflammatory agents are used in their treatment. This study evaluates the periodontal status and cytokine response in pediatric patients with FMF or sJIA. MATERIALS AND METHODS: Forty-eight FMF/sJIA patients were under treatment/control and in attack-free period; 20 systemically healthy children participated in the study. FMF/sJIA patients were divided into two subgroups based on the treatment they received: receiving anti-IL-1 therapy (anti-IL-1 ( +)) and not receiving anti-IL-1 therapy (anti-IL-1 ( -)). The clinical periodontal indices were recorded. Gingival crevicular fluid (GCF) and serum samples were collected. Cytokine levels (IL-1ß, IL-1α, TNF-α, IL-6, IL-8, IL-10, IL-17, IL-33) in GCF and serum were measured using ELISA kits. RESULTS: There was no significant difference between the groups in terms of GCF IL-1ß and IL-1α levels although, BoP and GI were significantly lower in the anti-IL-1 ( +) group compared to the control group. GCF IL-10 level was higher in the anti-IL-1 ( -) group than in the control group; GCF IL-8 levels were lower in both FMF/sJIA subgroups versus controls. There was no significant difference between serum cytokine levels of FMF/sJIA subgroups. CONCLUSIONS: Considering the significant decrease in GI, BoP, and GCF IL-8 levels in the anti-IL-1 ( +) group, it can be concluded that anti-IL-1 medications may suppress periodontal inflammation clinically and immunologically. CLINICAL RELEVANCE: Anti-IL agents are not currently used in periodontal therapy. However, this study demonstrated the positive effect of anti-IL-1 medications on periodontal inflammation in pediatric patients with FMF or sJIA.

The challenges in diagnosing pediatric primary antiphospholipid syndrome.

Pediatric primary antiphospholipid syndrome (APS) is a very rare disease with significant distinctions from the APS in adults. Herein, we present our experience in the diagnosis and treatment of six pediatric primary APS patients, who met the updated Sapporo criteria for the APS diagnosis. One of them was also diagnosed as having probable catastrophic APS (CAPS) due to the involvement of three different organ systems simultaneously. Besides vascular involvement, four patients had thrombocytopenia, one had psychiatric disorder, and one had chorea and valvular heart disease. All patients received immunosuppressive treatment along with long-term anticoagulation therapy. Specific neurologic and hematologic manifestations that are not part of the classification criteria can be seen in children with primary APS. Therefore, using the adult criteria for diagnosing pediatric APS may result in missed or delayed diagnoses in children.

Assessment of systemic and ocular inflammation in juvenile idiopathic arthritis via choroidal vascularity index.

We aimed to evaluate the retina and the choroid in children with juvenile idiopathic arthritis (JIA) employing optical coherence tomography (OCT). This cross-sectional study, carried out between June 2017-December 2019, included JIA patients with (JIAU; n = 28) and without (JIAN; n = 65) uveitis and age-matched healthy controls (HC) (n = 102). Laboratory and demographic information of the children were obtained from hospital records. Activity of the disease was evaluated by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Choroidal scans were obtained with spectral domain-OCT in enhanced-depth imaging (EDI)-OCT mode to assess choroidal thickness (ChT) at five locations (under the fovea, at 750 and 1500 µm nasal and temporal sections), luminal area (LA), stromal area (SA), total subfoveal choroidal area (TCA) and CVI (choroidal vascularity index). Central foveal thickness (CFT) and 1-mm diameter foveal thickness (FT) were calculated automatically through macular volume scan analysis. The choroid was significantly thicker in JIAU and JIAN patients than in HC at the subfoveal and at the 750N, 750T, 1500T points (p < 0.001, p = 0.009, p < 0.001, and p < 0.001, respectively). The CVI was lower in JIAU patients than in JIAN patients and HC (p = 0.02). Conversely, CFT was greater in JIAU patients as compared to the JIAN patients and HC (p = 0.02). Changes in chorioretinal OCT parameters in the absence of uveitis in JIA patients may reflect subclinical choroidal inflammation in these patients. Ophthalmologic examination, including choroidal imaging in a larger cohort, may clarify this aspect.

Spinal involvement in juvenile idiopathic arthritis: what do we miss without imaging?

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. Enthesitis-related arthritis (ERA) has been one of the most controversial subtypes of JIA with a higher risk of axial involvement.  Our aim was to assess the frequency and spectrum of MRI findings of spine involvement in patients with JIA and determine if the axial involvement is always clinically symptomatic in patients with positive MRI findings. In this retrospective cross-sectional observational study we included known or suspected JIA patients who underwent spinal MRI examination between 2015 and 2017 and followed up in the Pediatric Rheumatology outpatient clinic. The demographic and clinical data were reviewed from the medical charts and electronic records. All patients were grouped as clinically symptomatic and asymptomatic for spinal involvement and MRI findings were re-evaluated for presence of inflammatory and erosive lesions. Of the 72 JIA patients, 57 (79.2%) were diagnosed with ERA, and 15 (20.8%) with non-ERA subtypes of JIA. Overall, 49 (68%) patients with JIA had positive spinal MRI findings (inflammatory and/or erosive lesions). Twenty-seven (47%) ERA patients were clinically symptomatic for spine involvement and among them, 19 (70.3%) had positive spinal MRI findings. Although 30 ERA (53%) patients were clinically asymptomatic, 23 of them (77%) had positive spinal MRI findings, as well. Eleven (73%) patients diagnosed with non-ERA JIA subtypes were clinically symptomatic for spine involvement at the time of MRI. Among them, four (36.3%) had inflammatory and/or erosive lesions on spine MRI. Four (26%) non-ERA patients were clinically asymptomatic for spine involvement, but three (75%) of them showed positive findings on spinal MRI. Inflammatory and/or erosive lesions of the thoracolumbar spine could exist in patients with JIA, regardless of the presence of symptoms. Not only because the significant proportion of ERA patients show asymptomatic axial involvement but also the presence of axial involvement in patients who were classified as non-ERA depending on current ILAR classification underlines the necessity of using MRI for accurate classification of patients with JIA.

Long-term renal survival of paediatric patients with lupus nephritis.

BACKGROUND: Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN). MATERIALS AND METHODS: This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up. RESULTS: The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4-15.8]. The median follow-up duration was 43.1 months (IQR 24.3-69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome. CONCLUSIONS: Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.

The pyrin inflammasome aggravates inflammatory cell migration in patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by pathogenic variants of the MEFV gene, which encodes pyrin. Leukocyte migration to serosal sites is a key event during inflammation in FMF. The pyrin inflammasome is a multiprotein complex involved in inflammation. Here, we aimed to determine the relationship between inflammatory cell migration and the pyrin inflammasome in FMF patients. METHODS: Monocytes were isolated from blood samples collected from patients with FMF, healthy controls, and a patient with cryopyrin-associated periodic syndrome (CAPS), which served as a disease control. Inflammasome proteins were analyzed under inflammasome activation and inhibition by western blotting. Cell migration assays were performed with the isolated primary monocytes as well as THP-1 monocytes and THP-1-derived macrophages. RESULTS: When the pyrin inflammasome was suppressed, migration of monocytes from FMF patients was significantly decreased compared to the migration of monocytes from the CAPS patient and healthy controls. Cell line experiments showed a relationship between pyrin inflammasome activation and cell migration. CONCLUSIONS: These findings suggest that the increased cell migration in FMF is due to the presence of more active pyrin inflammasome. This study contributes to our understanding of the role of pyrin in inflammatory cell migration through inflammasome formation. IMPACT: The pyrin inflammasome may play a role in inflammatory cell migration. FMF patients show a pyrin inflammasome-dependent increase in inflammatory cell migration. Correlations between the pyrin inflammasome and cell migration were observed in both THP-1 monocytes and THP-1-derived macrophages.

Galectin-3: a new biomarker for differentiating periodic fever, adenitis, pharyngitis, aphthous stomatitis (PFAPA) syndrome from familial Mediterranean fever?

Differentiating PFAPA (periodic fever, aphthosis, pharyngitis, and adenitis) syndrome from familial Mediterranean fever (FMF) could be challenging in some cases. Galectin-3 is a lectin with regulatory functions in apoptosis and inflammation. We aimed to test whether galectin-3 could be a biomarker for differentiating PFAPA syndrome from FMF. Patients with PFAPA syndrome, FMF, cryopyrin-associated periodic syndrome (CAPS), and streptococcal pharyngitis, and healthy controls were included in this study. Serum galectin-3 levels were measured using enzyme-linked immunosorbent assay. Eighty-seven patients (36 with PFAPA, 39 with FMF, 8 with CAPS, 4 with streptococcal pharyngitis), and 17 healthy controls were included. Blood samples were drawn during attacks from 20 PFAPA and 7 FMF patients and attack-free periods from 22 PFAPA, 35 FMF, and 8 CAPS patients. The median serum galectin-3 level in the PFAPA-attack group (1.025 ng/ml) was significantly lower than the levels in healthy control (2.367 ng/ml), streptococcal pharyngitis (3.021 ng/ml), FMF attack (2.402 ng/ml), and FMF-attack-free groups (2.797 ng/ml) (p = 0.006, 0.03, 0.01, and < 0.001, respectively). PFAPA-attack-free group had lower galectin-3 levels than the FMF-attack-free group (1.794 vs. 2.797 ng/ml, respectively; p = 0.01). Galectin-3 levels did not differ significantly between CAPS and attack-free PFAPA patients (1.439 ng/ml vs. 1.794 ng/ml, respectively; p = 0.63). In our study, for the first time, we defined galectin-3 as a promising biomarker that differs between PFAPA and FMF patients during both disease flares and attack-free periods. Further studies with high number of patients could validate its role as a biomarker.

Comparison of IVIG resistance predictive models in Kawasaki disease.

BACKGROUND: We aimed to compare the ten different scores (by Kobayashi, Egami, Harada, Formosa, Sano, Piram et al., Wu et al., Yang et al., Tan et al., and Kanai et al.) to assess their performance in predicting IVIG resistance in Turkish children. METHODS: Complete and incomplete KD patients diagnosed with KD at Hacettepe University between June 2007 and September 2019 were evaluated retrospectively. RESULTS: A total of 129 patients, 79 boys (61.2%), with a median age 36 (IQR 19.5-57.0) months were evaluated. Sixteen patients (12.4%) had IVIG resistance. Sensitivity was low for all the ten scores. Tan, Sano, and Egami predictive models had the highest specificity (97.3, 89.4, 86.7%, respectively). Almost all scoring systems distinguished the group of patients with low risk for IVIG resistance but could not differentiate IVIG-resistant patients. Multivariate analysis for the laboratory features showed that platelet count <300 × 109/L and GGT serum levels were independent risk factors for IVIG resistance (OR: 3.896; 95% CI: 1.054-14.404; p = 0.042 and OR: 1.008; 95% CI: 1.001-1.015; p = 0.050). CONCLUSIONS: The current scoring systems had a low sensitivity for predicting the risk for IVIG resistance in Turkish children. On the other hand, increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance. IMPACT: Intravenous immunoglobulin (IVIG) resistance may be observed in 10-20% of patients diagnosed with Kawasaki disease. Coronary artery involvement is more frequent in IVIG-resistant patients. It is important to predict the patients who might develop IVIG resistance to improve prognosis. The performance of the IVIG resistance predictive models in Kawasaki disease in our population is limited due to the low sensitivity.

Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement (p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-ß2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings (p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-ß2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER.

BACKGROUND: Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort. METHODS: This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey. RESULTS: Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)-negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09-10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor-alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention. CONCLUSIONS: Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.

A case report of intracranial hypertension and aseptic meningitis: anti-tumor necrosis factor associated or juvenile idiopathic arthritis related.

BACKGROUND: The adverse effects of tumor necrosis factor alpha inhibitors (TNFi) are well characterized but rare adverse events are increasing day by day. CASE: We presented an 18-year-old girl with rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA) who developed fever, headache, and nausea after the second dose of adalimumab. In addition to her suspicious complaints for meningitis, she had bilateral papilledema and partial abducens nerve palsy. Leptomeningeal contrast enhancement was noted in magnetic resonance imaging (MRI) of the brain. Brain MRI venography was normal. The cerebrospinal fluid (CSF) opening pressure was high but CSF analysis was normal. She was diagnosed with non-infectious subacute meningitis. Since brain biopsy was not performed, no definite distinction could be made between TNFi related aseptic meningitis or cerebral involvement of JIA. Due to the onset of neurological complaints after initiation of adalimumab treatment and rare cerebral involvement in JIA, the drug-associated aseptic meningitis was likely to be responsible in our patient. Adalimumab was discontinued and methylprednisolone followed by methotrexate treatment were initiated. Her symptoms resolved and control brain MRI was normal. CONCLUSION: Pediatric rheumatologists should be aware of this potentially severe side effect of anti-TNF treatment.