Inflammatory comorbidities in the largest pediatric Familial Mediterranean fever cohort: a multicenter retrospective study of Pediatric Rheumatology Academy (PeRA)-Research Group (RG).

AIM: The aim of this study was to investigate the frequency and type of FMF-associated inflammatory diseases in a large FMF pediatric patients and to compare them to those FMF patients without concomitant inflammatory diseases. MATERIALS AND METHODS: Familial Mediterranean fever patients enrolled in the Pediatric Rheumatology Academy (PeRA)-Research Group (RG) were included. The patients were divided into two groups according to concomitant inflammatory disease as FMF patients who had a concomitant inflammatory disease (group 1) and FMF patients who did not have a concomitant inflammatory disease (group 1). The clinical findings and treatments were compared between the two groups. RESULTS: The study group comprised 3475 patients with FMF. There were 294 patients (8.5%) in group 1 and 3181 patients (91.5%) in group 2. Juvenile idiopathic arthritis (n = 136) was the most common accompanying inflammatory disease. Arthritis, M694V homozygosity, and the need for biological therapy were more frequently observed in Group 1 (p < 0.05). Fever and abdominal pain were more frequently detected in Group 2 (p < 0.05). FMF patients with concomitant inflammatory diseas more frequently demonstrated colchicine resistance. There were no significant differences in the median attack frequency, chest pain, amyloidosis, erysipelas-like erythema, or family history of FMF between the two patient groups. CONCLUSION: To the best of our knowledge, this is the largest pediatric cohort reviewed to date. FMF patients may have different clinical profiles and colchicine responses if they have with concomitant inflammatory diseases. Key points • FMF is associated with some inflammatory comorbidities diseases. • To the best of our knowledge, this is the largest cohort evlauated pediatric FMF associated inflammatory comorbidities diseases reviewed to date.

Pediatric Behçet's disease: Experience of a single tertiary center.

Objectives: The aim of this study was to examine the clinical and phenotypic features of pediatric Behçet's disease (PEDBD) in our clinic and present the rates of fulfilling the diagnostic criteria. Patients and methods: Thirty-four patients (20 males, 14 females; mean age: 16.0±2.1 years; range, 10 to 18 years) diagnosed with PEDBD between January 2010 and December 2019 were retrospectively evaluated. Patients were reclassified according to 1990 International Study Group (ISG) criteria, 2014 International Criteria for Behçet's Disease (ICBD), and PEDBD criteria. Results: The mean age at diagnosis was 12.6±3.1 years, the median diagnosis delay time was 12.0 (range, 4.5 to 27.0) months, and the mean age at symptom onset was 10.8±2.9 years. The mean follow-up period was 31.9±20.9 months. Oral aphthous ulcer was observed in 33 (97.1%), genital ulcer in 16 (47.0%), ocular involvement in 15 (44.1%), skin lesion in 11 (32.3%), joint involvement in nine (26.4%), both vascular and neurological involvement in six (17.6%) patients. The pathergy test was positive in 11 (37.8%) patients, and human leukocyte antigen (HLA)-B51 was positive in 11 (78.5%) of 14 patients. The rates of patients meeting the criteria for ISG, ICBD, and PEDBD were 52.9%, 82.4%, and 50.0%, respectively. Conclusion: Pathergy and HLA-B51 can be used as supportive findings in patients who do not meet the diagnostic criteria. However, expert opinion is still the gold standard in diagnosis.

How common is remission in rheumatoid factor-positive juvenile idiopathic arthritis patients? The multicenter Pediatric Rheumatology Academy (PeRA) research group experience.

OBJECTIVE: Rheumatoid factor (RF)-positive polyarthritis is the least common type of juvenile idiopathic arthritis (JIA). Functional disability in RF-positive polyarthritis patients is much more severe than in patients with other subtypes; but data on this subtype alone is limited. This study aimed to analyze clinical features, long-term follow-up, treatment response, and remission status in a large multicenter cohort of RF-positive polyarthritis patients. METHODS: This retrospective study included RF-positive polyarthritis patients that were followed up for ≥ 6 months between 2017 and 2022 by the Pediatric Rheumatology Academy (PeRA)-Research Group (RG). Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts. JIA treatments and duration of treatment were also recorded. The patients were divided into 2 groups based on methotrexate (MTX) response, as follows: group 1: MTX responsive, group 2: MTX unresponsive. Clinical and laboratory findings were compared between the 2 groups. RESULTS: The study included 56 (45 female and 11 male) patients. The median age at onset of RF-positive polyarthritis was 13.2 years [(interquartile range) (IQR): 9.0-15.0 years] and the median duration of follow-up was 41.5 months (IQR: 19.5-75.7 months). Symmetrical arthritis affecting the metacarpophalangeal and proximal interphalangeal joints of the hands was commonly observed. Subcutaneous MTX was the preferred initial treatment; however, it was ineffective in 39 (69.6%) of the patients. Of 25 patients followed for 24 months, 56% still had active disease at 24 months. CONCLUSION: During 2 years of treatment, 44% of RF-positive polyarthritis patients have inactive disease, and they should be considered as a distinct and important clinical entity requiring aggressive and early treatment.

Remission rates and risk factors for relapse in pediatric morphea: a multicenter retrospective study of Pediatric Rheumatology Academy (PeRA)-Research Group (RG).

AIM: Morphea, also known as localized scleroderma, is an immune-mediated disease and the most common form of scleroderma in children. It is a localized sclerosing disease of the skin, but can also involve such adjacent tissues as the fascia, muscle, bone, and underlying tissues. This multicenter study aimed to evaluate Turkish pediatric morphea patients, regarding demographics, treatments, and response to treatment. MATERIALS AND METHODS: The study was performed by the Pediatric Rheumatology Academy and included pediatric morphea patients from 6 Turkish pediatric rheumatology centers who were followed up for ≥6 months. Demographic, clinical, and laboratory findings and treatment modalities were analyzed. The patients were divided into 3 groups according to treatment response, as follows: group 1: topical treatment response, group 2: methotrexate response, and group 3: methotrexate resistance. Clinical findings were compared between the 3 groups. RESULTS: The study included 76 patients, of which 53 (69.7%) were female. Mean age at diagnosis of morphea was 9.7 ± 4.3 years and mean duration of follow-up was 3.2 ± 2.9 years. Linear morphea was the most common form, accounting for 43.4% (n = 33) of the patients. Extracutaneous features were noted in 17 patients (22.4%) and anti-nuclear antibody positivity was noted in 32 (42.1%). In all, 14.4% of the patients received topical treatment only, whereas 86.6% received both topical and systemic treatment. The methotrexate response rate was 76.9% in the patients that received systemic immunosuppressive therapy. The overall relapse rate while under treatment was 19.7%. CONCLUSION: In this study, most of the pediatric morphea patients responded well to methotrexate. Bilateral lesions were more common in the methotrexate-resistant group. Multiple involvement, and bilateral lesions, were more common in relapsed patients than in non-relapsed patients. Key points • Most of the pediatric morphea patients respond well to MTX. • Multiple involvement, and bilateral involvement, were more common in relapsed patients than in non-relapsed patients. • Presence of extracutaneous findings in patients increased relapse rate 5.7 times.

Investigating Wrist Joint Position Sense and Hand Functions in Children With Polyarticular Juvenile Idiopathic Arthritis With Wrist Involvement.

Comparing the wrist joint position sense and hand functions between children with juvenile idiopathic arthritis (JIA) and healthy controls, and determining possible relationships between these parameters in children with JIA were the aims of this study. Twenty children with polyarticular JIA with wrist involvement (JIAWrist+), 20 children with other subtypes of JIA without wrist involvement (JIAWrist-), and 20 healthy controls were included. Wrist joint position sense was evaluated by measuring joint repositioning error. Hand functions were assessed by using the Purdue Pegboard test, hand grip strength, pinch strength, and Duruoz Hand Index. Joint position sense and hand functions were diminished in the JIAWrist+ group compared with healthy control group (P < .05). Few moderate relationships were detected between hand functions and wrist joint position sense (P < .05). Improving proprioceptive acuity by appropriate training methods may have a role in enhancing hand functions.

Erratum to `Tuberculosis risk in the biologic era: tuberculin skin test conversion rates in children with rheumatologic diseases` [Turk J Pediatr 2021; 63: 978-985].

This article is corrected. DOI: 10.24953/turkjped.2021.06.005.

Tuberculosis risk in the biologic era: tuberculin skin test conversion rates in children with rheumatologic diseases.

BACKGROUND: The widespread use of biological treatments has increased the frequency of opportunistic infections such as tuberculosis (TB). The primary objective of our study was to determine the rate of tuberculin skin test (TST) conversion during biological therapy. The secondary objective was to monitor the side effects related to isoniazid (INH) prophylaxis, in the selected subgroup. METHODS: Children with rheumatologic diseases receiving treatment with tumor necrosis factor-alpha (TNF-α) inhibitors, and tocilizumab and canakinumab were included in the study. If baseline screening was negative, TST was performed annually after initiation of biologic therapy. TST conversion was accepted as an increase of at least 6 mm and becoming positive or an increase of 10 mm or more, even in the absence of positivity. RESULTS: 121 patients (female n: 63, 52%) were included in the study. The mean follow-up period was 26.10±14.8 months. 85 of the patients were using TNF-α inhibitors and 18 tocilizumab, and 18 canakinumab. Forty patients had positive TST before biological agents and received chemoprophylaxis with INH. The rate of TST conversion among the 3 biological agents was not statistically significant (20.4% of TNF-α inhibitors, 25% of canakinumab and 33.3% of tocilizumab users). All patients with LTBI received INH prophylaxis, and none of them had active TB. CONCLUSIONS: There was no statistically significant difference among the three biological agents, regarding the seroconversion rates. Patients receiving tocilizumab and canakinumab should also be screened for TB during follow-up. INH related side effects are rare.

Paediatric Behçet's disease with sinus venous thrombosis: experience from three centres in Turkey.

OBJECTIVES: To report our experiences of the juvenile Behçet's disease (BD) patients with cerebral venous sinus thrombosis (CVST) and to review previous studies reporting the clinical characteristics and outcomes of juvenile BD with CVST. METHODS: Clinical characteristics and outcomes of paediatric patients with CVST who met the Paediatric Behçet's Disease (PEDBD) classification criteria for juvenile BD from 3 referral centres in Turkey were reviewed retrospectively. A systematic review of literature of all published data was conducted. RESULTS: The study group consisted of 12 juvenile BD patients with CVST. At the time of CVST diagnosis, the most common symptom was headache (100%), followed by vomiting (25%), blurred vision (16.7%), and disturbances in eye movements (16.7%). Six (50%) patients presented with CVST. Transverse sinus was the most frequently affected sinus (9/12, 75%) followed by superior sagittal sinus. The mean (±2SD) BDCAF at the CVST diagnosis was 6 (±3.8). Four children (33.3%) had another venous thrombosis apart from CVST. All patients received pulse methylprednisolone for three consecutive days continued with oral prednisolone. Steroid treatment was tapered and discontinued minimum in six months. Eleven patients received azathioprine concomitant to steroid treatment at the time of CVST. All the patients received anticoagulant therapy concomitantly. Only one patient who did not receive azathioprine relapsed. Median follow-up period was 4 years (IQR: 2-5.4). In the literature review, we identified nine articles, describing 35 pediatric CVST patients associated with BD. Thirty patients achieved remission, while five patients had residual neurologic deficit. CONCLUSIONS: Neuroimaging is very important in the diagnosis of NBD. We suggest that treatment with immunosuppressants and steroid treatment is essential to decrease the adverse events of corticosteroids in the pediatric population and decrease relapses. Further multicenter studies with prospective follow-up may guide us in better management of these patients.

Correction to: Evaluation of the effects of miRNAs in familial Mediterranean fever.

The name of the last author of this article was incorrectly presented as "Cogulu Ozgur" this should have been "Ozgur Cogulu".

Evaluation of the effects of miRNAs in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an inherited autoinflammatory disorder that can result in attacks with accompanying recurrent episodes of fever, serositis, and skin rash. MiRNAs are demonstrated to be associated with a number of other diseases; however, no comprehensive study has revealed its association with FMF disease. The aim is to investigate the role of microRNAs in FMF. We included 51 patients with genetically diagnosed FMF who had clinical symptoms and 49 healthy volunteers. Fifteen miRNAs that were found to be associated with autoinflammatory diseases and have a part in immune response were evaluated. The expression levels of 11 miRNAs (miR-125a, miR-132, miR-146a, miR-155, miR-15a, miR-16, miR-181a, miR-21, miR-223, miR-26a, and miR-34a) in the patient group were significantly low, compared with the control group (p < 0.05). The patient group was analyzed and compared within itself, and the expression levels of 5 miRNAs (miR-132, miR-15a, miR-181a, miR-23b, miR-26a) in the patients who took colchicine seemed to have increased and levels of 5 miRNAs (miR-146a, miR-15a, miR-16, miR-26a, miR-34a) in the patients who took colchicine were significantly lower (p < 0.05). Furthermore, the attack patients were compared with the control group, and their expression levels of 4 miRNAs (miR-132, miR-15a, miR-21, miR-34a) were significantly lower (p < 0.05). Levels of 9 miRNAs (miR-132, miR-146a, miR-15a, miR-16, miR-181a, miR-21, miR-223, miR-26a, miR-34a) in non-attack patients decreased significantly (p < 0.05). Our study demonstrates that miRNAs could be effective in the pathogenesis of FMF.

The Publication Rates of Pediatric Rheumatology Abstracts Presented in European League Against Rheumatism 2009 Congress.

OBJECTIVES: This study aims to evaluate the publication rates and features of the abstracts related to pediatric rheumatology presented in European League against Rheumatism 2009 congress. PATIENTS AND METHODS: A systematic search was performed to find full-text publications of abstracts related to pediatric rheumatology in European League against Rheumatism 2009 congress. Full-text publication rate, the elapsed time between presentation and full-text publication, type of the disease in the studies, distribution of abstracts and full-texts according to countries, journals, and presentation types were investigated. RESULTS: Totally 220 abstracts were detected related to pediatric rheumatology. Twenty-two of them had only the title, authors' names, and institution of origin, but no abstract. Therefore, a total number of 198 abstracts were evaluated. Eighty-six (43.4%) abstracts were found to be accepted as full-text articles. The elapsed time between presentation and full text publication was median 19 months (range 0 to 64 months). While 12 orally presented abstracts (34%) became full-text articles, this rate was 45% (74 abstracts) for poster presentations. There was no significant difference in the elapsed time to reach full-text publication and impact factors between presentation types (p=0.832 and p=0.053, respectively). CONCLUSION: The full-text publication rates were within similar ranges when compared to other reports in rheumatology field. It seems that even though European League against Rheumatism is a general rheumatology congress, it takes an important place in pediatric rheumatology field as well.