Publications by authors named "Yelda Bilginer"

109 Publications

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

Lupus 2021 May 6:9612033211014271. Epub 2021 May 6.

Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

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 ( = 0.04,  = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Smith (anti-Sm) antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings ( = 0.001 for anti-cardiolipin antibody positivity and  < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia ( = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority ( = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 0.249; 95%CI: 0.126-0.490;  < 0.001 and OR: 1.136; 95%CI: 1.065-1.212;  < 0.001).

Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.
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http://dx.doi.org/10.1177/09612033211014271DOI Listing
May 2021

Systematic review of childhood-onset polyarteritis nodosa and DADA2.

Semin Arthritis Rheum 2021 Apr 19;51(3):559-564. Epub 2021 Apr 19.

Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, and Hacettepe University Vasculitis Research Center, Ankara, 06100, Turkey. Electronic address:

Background: Diagnosis of childhood polyarteritis nodosa (PAN) has become challenging after the definition of deficiency of adenosine deaminase 2 (DADA2). We aimed to define the differential features of pediatric PAN and DADA2 patients in our center and in the literature.

Methods: The charts of pediatric PAN and DADA2 patients followed at the Pediatric Rheumatology Unit of Hacettepe University between 2010-2020 were analyzed. A systematic literature review was conducted for articles regarding pediatric PAN or DADA2.

Results: Thirty-four pediatric PAN and 18 pediatric DADA2 patients were included. The age at onset was younger, parental consanguinity, livedo reticularis, neurologic involvement (especially strokes), lymphopenia, and hypogammaglobulinemia were more frequent, while thrombocytosis and panniculitis were less frequent in DADA2 patients. The primary treatment was anti-tumor necrosis factor (anti-TNF) in DADA2. For induction treatment, all systemic PAN patients received corticosteroids, and cyclophosphamide (n=11) or mycophenolate mofetil (MMF) (n = 3). Cyclophosphamide was replaced with MMF in nine once remission was confirmed with PVAS. In the literature, 28 articles describing 613 pediatric PAN patients and 26 articles describing 207 pediatric DADA2 patients were identified. Neurologic, gastrointestinal, and cardiac involvements were more frequent in DADA2, while constitutional symptoms and testis involvement were more common in PAN.

Conclusion: In a child with PAN-like phenotype, DADA2 should be considered in the presence of young age at disease onset, parental consanguinity, strokes, lymphopenia, and lack of thrombocytosis during active disease. Anti-TNF treatment is indicated for vasculitic DADA2. Cyclophosphamide could be switched to MMF when remission is confirmed with PVAS in severe PAN.
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http://dx.doi.org/10.1016/j.semarthrit.2021.04.009DOI Listing
April 2021

LONG TERM RENAL SURVIVAL OF PEDIATRIC PATIENTS WITH LUPUS NEPHRITIS.

Nephrol Dial Transplant 2021 Apr 7. Epub 2021 Apr 7.

Department of Pediatrics, Division of Nephrology, Hacettepe University Faculty of Medicine Ankara, Turkey.

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, short- and long-term renal outcomes of pediatric 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 2000-2020. 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 (IQR : 10.4-15.8) years. The median follow-up duration was 43.1 (IQR : 24.3-69.3) months. Of the 102 SLE patients, 53 patients (52%) had lupus nephritis (LN). The most frequent histopathological class was class IV LN (54.7%), followed by class III LN (22.6%). The proportion of patients who achieved either complete or partial remission were 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 6th month 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 the proliferative LN (Class III and IV), the vast majority of class IV patients (%79) received CYC as induction threapy. There was no difference between the response rates in any treatment regimens at 12th month (p = 0.56). In the multivariate analysis; male gender, requiring dialysis at the time of LN diagnosis, failure to achieve remission at 6th and at 12 th months were found to be associated with poor renal outcome.

Conclusion: Our study demonstrated that male gender, failure to achieve remission at 6th and at 12 th months, and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore, appropriate and agressive management of pediatric LN is essential to achieve and maintain remisson.
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http://dx.doi.org/10.1093/ndt/gfab152DOI Listing
April 2021

Comparison of IVIG resistance predictive models in Kawasaki disease.

Pediatr Res 2021 Mar 22. Epub 2021 Mar 22.

Division of Pediatric Rheumatology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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 × 10/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.
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http://dx.doi.org/10.1038/s41390-021-01459-wDOI Listing
March 2021

Plasma checkpoint protein levels and galectin-9 in juvenile systemic lupus erythematosus.

Lupus 2021 May 10;30(6):998-1004. Epub 2021 Mar 10.

Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University, Ankara, Turkey.

SLE is a disease of the adaptive immune system where T lymphocyte dysfunction has an important role as well. We assessed the plasma levels of checkpoint receptors expressed on T cells, along with Galectin-9 to reflect type-1 IFN activity and IL-2Rα in childhood SLE patients. Forty-nine children with SLE and15 healthy controls were included. SLEDAI scores were evaluated at the time of sampling. CD25 (IL-2Rα), 4-1BB, B7.2 (CD86), TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG- 3, Galectin-9 levels were studied by cytometric bead-based multiplex assay panel. Galectin-9 and PD-L1 were significantly higher in SLE patients. Other checkpoint proteins and IL-2Rα were also higher but did not reach statistical significance. There were significant correlations between SLEDAI and IL-2Rα, Galectin-9 and PDL1. There were three clinical clusters: Cluster 1 included patients with no major organ involvement, cluster 2 had predominantly haematological involvement(n=16) and cluster 3 (n=11) had predominantly renal involvement. Checkpoint proteins were not different among these three clusters. Our data supports that Galectin 9 and IL-2Rα are good markers for disease activity in childhood SLE. We need larger series to evaluate differences between disease clusters in SLE. We failed to show a significant correlation with checkpoint proteins and SLEDAI except for PDL1.
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http://dx.doi.org/10.1177/09612033211002275DOI Listing
May 2021

Genetic disorders with symptoms mimicking rheumatologic diseases: A single-center retrospective study.

Eur J Med Genet 2021 Apr 2;64(4):104185. Epub 2021 Mar 2.

Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey. Electronic address:

Musculoskeletal symptoms may be due to noninflammatory causes, including genetic disorders. We aimed to examine the final genetic diagnosis in patients who presented with musculoskeletal complaints to the rheumatology department. Patients who presented to the Department of Pediatric Rheumatology and were referred to the pediatric genetic department between January 2015 and May 2019 were evaluated retrospectively. A total of 60 patients, 19 boys (31.66%), with a mean age of 12.46 ± 1.41 years were included in the study. The total consanguinity rate was 25%. The most common (29.5%) cause of referral to the pediatric genetic department was the presence of skeletal anomalies (such as camptodactyly, clinodactyly, and short stature) with accompanying joint findings. Approximately one-third of the patients (n: 19) were diagnosed and followed up by the pediatric genetics department. The diagnoses of patients were as follows: camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome (n: 3); trichorhinophalangeal syndrome (n: 1); progressive pseudorheumatoid dysplasia (n: 2); LIG4 syndrome (n: 1); H syndrome (n: 1); spondyloenchondrodysplasia (SPENCD) (n: 3); and nonspecific connective tissue disorders (n: 8). In the differential diagnosis of patients who are referred to the Department of Pediatric Rheumatology with complaints of the musculoskeletal system, genetic disorders should also be considered.
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http://dx.doi.org/10.1016/j.ejmg.2021.104185DOI Listing
April 2021

Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean.

Clin Rheumatol 2021 Feb 12. Epub 2021 Feb 12.

Faculty of Medicine, Department of Pediatrics, Division of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.

Objective: We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country.

Methods: Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study.

Results: A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral.

Conclusion: Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases. Key Points • MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe/critical pediatric cases with COVID-19. • Higher CRP and low total WBC count are the independent predictors for the diagnosis of MIS-C. • MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19.
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http://dx.doi.org/10.1007/s10067-021-05631-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879406PMC
February 2021

Penile involvement of immunoglobulin a vasculitis/Henoch-Schönlein purpura.

J Pediatr Urol 2021 Jan 22. Epub 2021 Jan 22.

Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. Electronic address:

Background: Immunoglobulin A vasculitis/Henoch-Schönlein purpura (IgAV/HSP) is a leukocytoclasia vasculitis of childhood, predominantly affecting the skin, joints, gastrointestinal tract, and kidneys. The involvement of the penis is rare.

Objective: We aimed to describe this rare manifestation of IgAV/HSP and to review the previous studies, including similar cases.

Methods: Clinical data were reviewed for two children of penile involvement of IgAV/HSP in our hospital. More clinical cases were retrieved from the databases of PubMed/MEDLINE and Scopus from database inception to February 1, 2020.

Results: We presented two boys aged three and five years both of whom had penile lesions after presenting with the typical rash of IgAV/HSP on lower extremities. The penile lesions improved entirely in a few days without treatment in one and with corticosteroid treatment in the other. The literature review revealed 12 articles describing 20 patients with penile involvement of IgAV/HSP. The penile findings were edema, erythema, ecchymosis, purpuric rash, edema, color change, stiffness of the shaft or prepuce, and tenderness. Penile lesions appeared before the purpuric rash of IgAV/HSP in three of 22 patients. The penile involvement could make the diagnosis challenging especially if the penile lesions appear before the typical rash of the disease. The lesions improved entirely in the short term in all patients; in five without treatment in fifteen after corticosteroid or immunosuppressive drug treatment.

Conclusions: It is important to raise awareness about this rare manifestation among health care providers. It is not clear whether corticosteroid treatment should be initiated for treatment since it seems as a self-limited feature. Treatment with corticosteroids could be considered in the treatment of selected cases especially with systemic involvement.
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http://dx.doi.org/10.1016/j.jpurol.2021.01.012DOI Listing
January 2021

Clinical features, muscle biopsy scores, myositis specific antibody profiles and outcome in juvenile dermatomyositis.

Semin Arthritis Rheum 2021 Feb 22;51(1):95-100. Epub 2020 Dec 22.

Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University, Ankara 06100, Turkey. Electronic address:

Introduction: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy of childhood.

Objective: To analyze clinical features, paraclinical examinations, MSAs, treatment response and long-term outcome in a JDM cohort METHODS: 58 patients (35F, 23 M) from a tertiary referral center in the last two decades are included.

Results: Mean age at onset was 8.1 ± 4.3, with a mean follow-up period of 5.66±3.59 years. Dermatological manifestations (91%) and muscle weakness (76%) were the key diagnostic elements. Elevated serum creatine kinase levels (86%), electromyography (23/25), muscle MRI (12/15), and muscle biopsy (n = 35) were compatible with the diagnosis. Out of 46 patients tested, 34 (76%) had autoantibodies, with NXP2 (21.7%), followed by TIF1g (17.4%), MDA5 (8.7%), and Mi-2 (8.7%). Presence of TIF1g and NXP2 indicated a severe course; and Ku a much severe course compared to previous studies. Corticosteroids (100%) combined with methotrexate (93%) was the initial treatment. Biological disease modifying anti-rheumatic drugs (DMARDs) were used in 22% of the cohort. Calcinosis (36%) was the most common long-term complication, associated with disease onset ≤6 years, higher muscle biopsy scores and MDA5 positivity. Complete remission was achieved in 65.5% of the patients in a median 24 (IQR 11.8-42.5) months with a relapse rate of 26.3%. 43.9% of NXP2 and 33.3% of TIF-1 g positive patients had a relapse. Course was monophasic (31%), polyphasic (17.2%), chronic (51.8%) without mortality.

Conclusion: Integration of clinical features with laboratory and biopsy findings may help to predict prognosis and guide treatment in JDM. In our cohort calcinosis was associated with age, MDA5 autoantibodies, and muscle biopsy scores.
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http://dx.doi.org/10.1016/j.semarthrit.2020.10.007DOI Listing
February 2021

Validation of the EULAR/ACR 2017 idiopathic inflammatory myopathy classification criteria in juvenile dermatomyositis patients.

Clin Exp Rheumatol 2020 Dec 4. Epub 2020 Dec 4.

Division of Paediatric Rheumatology, Department of Paediatrics, Hacettepe University, Ankara, Turkey.

Objectives: In 2017, a new set of criteria was proposed by EULAR/ACR to classify idiopathic inflammatory myopathies. Our aim was to validate the EULAR/ACR 2017 classification criteria in juvenile dermatomyositis (JDM) patients.

Methods: This study was carried out at Hacettepe University Children's Hospital Department of Paediatrics, Divisions of Rheumatology, Neurology and Paediatric Pathology Unit. Control patients included inborn errors of metabolism presenting with myopathy and/or rhabdomyolysis, idiopathic rhabdomyolysis, dystrophinopathies, neuromyotonia and systemic rheumatic disorders. Patients' data were collected retrospectively from patient files.

Results: Fifty-eight JDM patients (60.3% female) and 40 controls (32.5% female) were included in this study. When the probability cut-off was set at 55% as recommended, the sensitivity/specificity of the new criteria to diagnose JDM were 96.5%/85% in the total cohort, 95.8%/84.6% without the muscle biopsy data and 97%/85.7% with biopsy data. With the ROC curve analysis, the optimal probability cut-off for the whole cohort was found to be >62%; providing a sensitivity/specificity of 96.6% (95% CI: 88.1% to 99.6)/90% (95% CI: 76.3% to 97.2%), and >68.5% for the patients with muscle biopsy providing sensitivity/specificity of 97% (84.7-99.9%)/100% (76.8-100%), respectively. The new EULAR/ACR criteria were the most sensitive, however, the least specific compared to the Tanimoto criteria (sensitivity/specificity 64%/97.5%) and Bohan-Peter criteria (sensitivity/ specificity 74.1%/92.5%).

Conclusions: The new EULAR/ACR criteria performed favourably in our JDM cohort especially with the probability cut-off of >62%.
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December 2020

Performances of the "MS-score" And "HScore" in the diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis patients.

Rheumatol Int 2021 Jan 19;41(1):87-93. Epub 2020 Nov 19.

Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Macrophage activation syndrome (MAS) is a devastating complication of systemic JIA (sJIA), seen in approximately 10-25% of the sJIA patients. A number of criteria have been proposed to differentiate between activation of sJIA and MAS, including HScore and the recently proposed MS-score. This is the first study comparing the performances of MS-score and HScore for the diagnosis of MAS in sJIA patients. Systemic JIA patients followed at Hacettepe University Pediatric Rheumatology Unit were included in the study. Clinical features and laboratory findings at the time when the disease was most active or patients were diagnosed with MAS were recorded retrospectively. HScore and MS-score were calculated and the diagnostic performance for MAS was compared by receiver operating characteristic (ROC) curve analysis. Seventy-one sJIA patients were included (23 MAS, 48 activation). There was no difference in age of onset (median 4.7 vs. 5.0 years) and gender (73.9% vs. 54.2%) between patients who had MAS and sJIA activation. Median MS-score and HScore were higher in the MAS group. ROC curve analysis revealed that the HScore performed slightly better in diagnosing MAS, compared with the MS-score (AUC = 0.965 and 0.901 for HScore and MS-score respectively, P < 0.001). In our cohort, the optimal cut-off for the MS score was ≥ - 1.64 (sensitivity: 91.3%; specificity: 83.8%) and for the HScore it was ≥ 162.5 (sensitivity: 91.3%; specificity: 90.2%). HScore performed slightly better than MS-score for the diagnosis of MAS in our cohort.
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http://dx.doi.org/10.1007/s00296-020-04750-xDOI Listing
January 2021

The Performances of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 Classification Criteria in Pediatric Systemic Lupus Erythematosus.

J Rheumatol 2020 Nov 15. Epub 2020 Nov 15.

E.D. Batu, MD, MSc, U. Kaya Akca, MD, E. Sağ, MD, S. Demir, MD, Y. Bilginer, MD, MSc, S. Ozen, MD, MSc, Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara; A. Pac Kısaarslan, MD, S. Özdemir Çiçek, MD, H. Poyrazoglu, MD, Department of Pediatrics, Division of Rheumatology, Erciyes University Faculty of Medicine, Kayseri; F. Demir, MD, B. Sozeri, MD, Department of Pediatrics, Division of Rheumatology, Ümraniye Training and Research Center, University of Health Sciences, Istanbul, Turkey. The authors declare no conflict of interest. Address correspondence to Dr. S Özen, Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. Email: Accepted for publication November 5, 2020.

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, and European League Against Rheumatism (EULAR)/ACR 2019 SLE classification criteria are formed based on data mainly from adult patients. We aimed to test the performances of the SLE classification criteria among pediatric patients with SLE.

Methods: Pediatric patients with SLE (n = 262; 80.9% female) were included from 3 different centers in Turkey. As controls, 174 children (60.9% female) with other diseases who had ANA (antinuclear antibody) test results were included. The gold standard for SLE diagnosis was expert opinion.

Results: The sensitivities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 68.7%, 95.4%, and 91.6%, respectively. The specificities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 94.8%, 89.7%, and 88.5%, respectively. Eighteen patients with SLE met the SLICC 2012 but not the EULAR/ACR 2019 criteria. Among these, hematologic involvement was prominent (n = 13; 72.2%). Eight patients with SLE fulfilled the EULAR/ACR 2019 but not the SLICC 2012 criteria. Among these, joint involvement was prominent (n = 6; 75%).

Conclusion: To our knowledge, this is the largest cohort study of pediatric SLE to test the performances of all 3 classification criteria. The SLICC 2012 criteria yielded the best sensitivity, whereas the ACR 1997 criteria had the best specificity. SLICC 2012 criteria performed better than EULAR/ACR 2019 criteria. Separation of different hematological manifestations in the SLICC 2012 criteria might have contributed to the higher performance of this criteria set.
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http://dx.doi.org/10.3899/jrheum.200871DOI Listing
November 2020

Inflammatory milieu of muscle biopsies in juvenile dermatomyositis.

Rheumatol Int 2021 Jan 26;41(1):77-85. Epub 2020 Oct 26.

Pediatric Pathology Unit, Department of Pediatrics, Hacettepe University, Ankara, Turkey.

Juvenile dermatomyositis (JDM) is an inflammatory myopathy which causes severe morbidity and high mortality if untreated. In this study, we aimed to define the T-helper cell profile in the muscle biopsies of JDM patients. Muscle biopsies of twenty-six patients (50% female) were included in the study. Immunohistochemical expression of CD3, CD20, CD138, CD68, IL-17, Foxp3, IFN-ɣ, IFN-alpha and IL-4 was studied and muscle biopsies were scored using the JDM muscle biopsy scoring tool. Inflammatory cells were in small clusters in perimysium and perivascular area or scattered throughout the endomysium in most biopsies; however in 2 biopsies, lymphoid follicle-like big clusters were observed, and in one, there was a very dense and diffuse inflammatory infiltration nearly destroying all the muscle architecture. Seventy-three per cent of the biopsies had T cells, 88% had B cells, 57% had plasma cells, and all had macrophages. As for T-helper cell subtypes, 80% of the biopsies were Th1 positive, 92% Th17 positive and 30% Treg positive. No IL-4 positive inflammatory cell was detected, and only 2 biopsies showed IFN-alpha positivity. The mean JDM biopsy score was 17.6, meaning moderate to severe muscular involvement. Visual analogue score of the pathologist was strongly correlated with histopathological features. B cells, macrophages, plasma cells and T cells constitute the inflammatory milieu of the JDM muscle biopsies. As for T cells, JDM is a disease mainly related with Th1 and Th17 T-helper cell subtypes and to some extend Treg. Th2 cells are not involved in the pathogenesis.
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http://dx.doi.org/10.1007/s00296-020-04735-wDOI Listing
January 2021

Predictive biomarkers of IgA vasculitis with nephritis by metabolomic analysis.

Semin Arthritis Rheum 2020 12 19;50(6):1238-1244. Epub 2020 Sep 19.

Hacettepe University Faculty of Medicine, Department of Pediatric Rheumatology, Ankara, Turkey. Electronic address:

Background: IgA vasculitis (IgAV) is the most common vasculitis of childhood. Renal involvement defines late morbidity of the disease. A better understanding of the pathophysiology of the progression to kidney disease and predictive biomarkers are required for better management of IgAV and its nephritis (IgAVN).

Objectives: An untargeted metabolomics approach was performed to reveal the underlying molecular mechanism of disease pathogenesis and to define potential biomarkers from plasma samples from IgAV and IgAVN patients.

Methods: Forty-five active IgAV patients (H) and six healthy controls (C) were enrolled in the study. Plasma samples were collected on the same day of diagnosis and before any immunosuppressive treatment was initiated. At the time of diagnosis and sample collection, none of the patients had renal involvement. We used Quadrupole Time of Flight Mass Spectrometry (Q-TOF LC/MS) to investigate the alterations in plasma metabolomic profiles. Three separate pools were created: healthy controls (group C), active IgAV patients who did not develop renal involvement (group H), and patients who developed IgAVN at follow up (group N). Peak picking, grouping, and comparison parts were performed via XCMS (https://xcmsonline.scripps.edu/) software.

Results: At follow-up, IgAVN developed in 6 out of 45 IgAV patients. The median time of renal involvement development is 23 days (range 5-45 days). Of these, 3 had nephritic proteinuria, one had nephrotic proteinuria, and 2 had microscopic hematuria. There were no significant differences in gender, age, clinical manifestations, and laboratory findings between the six patients who developed renal involvement and those who did not. In multivariate analysis, there was no significant association between any of the defined demographic and clinical characteristics (male sex, gastrointestinal system involvement, joint involvement, CRP, WBC, PLT) and the occurrence of renal involvement. Totally 2618 peaks were detected for group H, N, and C. Among them, 355 peaks were found to be statistically significant and reliable (p<0.05), and 155 of these peaks were found to be changed (fold change >1.5) between the groups C and H, and 66 peaks were found to be changed (fold change >1.5) between the groups H and N. The number of the peaks on the intersection of the peaks found to be different between the groups (C and H) and (H and N) was 39. Based on putative identification results, 15 putatively identified metabolites matched with 11 peaks were presented as biomarker candidates after careful evaluation with a clinical perspective.

Conclusion: We suggest that DHAP (18:0), prostaglandin D2/I2, porphobilinogen, 5-methyltetrahydrofolic acid, and N-Acetyl-4-O-acetylneuraminic acid/N-Acetyl-7-O-acetylneuraminic acid may serve as biomarkers for predicting kidney disease. Future studies with larger groups of IgAV patients are needed to validate the identified metabolic profile.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.006DOI Listing
December 2020

Burden of illness in hereditary periodic fevers: a multinational observational patient diary study.

Clin Exp Rheumatol 2020 Sep-Oct;38 Suppl 127(5):26-34. Epub 2020 Sep 30.

Medicine F, Sheba Medical Centre, Tel-Hashomer, Ramat-Gan, Israel.

Objectives: This study aimed to characterise the burden of illness of patients with inadequately controlled hereditary periodic fevers (HPFs), during and outside of flares. It was focused on the burden to the patients and also considered the wider impact on their caregivers and families.

Methods: The target population was patients or caregivers of patients with clinically/genetically confirmed colchicine resistant FMF (crFMF), mevalonate kinase deficiency/hyperimmunoglobinaemia D with periodic fever syndrome (MKD/HIDS) or TRAPS, who were expected to flare at least once in a 6-month period based on patient history. Disease burden was captured during and between flares using an electronic diary (e-diary) with questions on patient functioning, emotional/social well-being and pain, using validated instruments.

Results: HPF-related symptoms such as fever, joint, muscle or bone pain and tiredness and fatigue were reported by patients both during and outside of a flare. The SF-10 Health Survey (SF-10v2) (paediatric patients) and SF-12 Health Survey (SF-12v2) (adult patients) showed that flares negatively impacted patients' psychosocial and physical health. Negative effect of on-flare status on health utility index score assessed by the Short-Form Six-Dimension (SF-6D) was significant only for crFMF patients. Furthermore, the Sheehan Disability Score (SDSv3) showing the on-flare status resulted in significant functional impairment in all 3 disease cohorts through assessment of impact on work/school, social and family life.

Conclusions: crFMF, MKD/HIDS and TRAPS negatively affected the quality of life (QoL) of adult and paediatric patients, including their physical, mental, psychosocial health, and social functioning. There remains, however, a high number of unmet needs for these patients to reduce their disease burden.
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December 2020

Is Takayasu's arteritis more severe in children?

Clin Exp Rheumatol 2020 Sep 16. Epub 2020 Sep 16.

Hacettepe University Vasculitis Center, and Division of Paediatric Rheumatology, Department of Paediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Objectives: Takayasu's arteritis (TAK) is a chronic vasculitis, affecting predominantly the aorta and/or its major branches. The aim of this study was to compare the differences between childhood and adult onset TAK.

Methods: We retrospectively evaluated 179 TAK patients followed between August 2005 and July 2019. Demographic characteristics, laboratory features, disease activity, echocardiographic data at diagnosis and treatment regimens in the disease course were compared between the paediatric and adult onset patients.

Results: Twenty-five paediatric-onset (<18 years of age at diagnosis) and 154 adult-onset patients (≥18 years of age at diagnosis) were enrolled. The mean age at diagnosis for children and adults were 13.6±4 and 35.6±13, respectively. Paediatric onset TAK patients had more intense inflammation at the time of diagnosis reflected in their clinical findings. Acute phase reactants were high in all paediatric patients and significantly higher in patients with paediatric-onset TAK (p=0.006 and p=0.005, respectively). Abdominal predominant disease was more common in the paediatric group, in contrast, focal disease and aortic arch predominant disease were more common in the adult group. Ascending aortic dilatation, left ventricular hypertrophy and moderate-severe aortic insufficiency were more frequent in echocardiography findings of paediatric onset TAK patients. In comorbidities, hypertension was more common in paediatric TAK patients during follow-up, whereas cerebrovascular disease was more common in adult patients.

Conclusions: Our paediatric onset TAK patients presented with a more severe inflammation and more widespread vascular involvement. Multicentre studies from different geographic areas are needed to verify our observation and understand the underlying causes.
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September 2020

Kawasaki-like disease in children with COVID-19.

Rheumatol Int 2020 12 16;40(12):2105-2115. Epub 2020 Sep 16.

Division of Pediatric Rheumatology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we investigated children with typical and atypical Kawasaki disease (KD) likely to be associated with COVID-19. We have reported four children with Kawasaki-like disease probably associated with COVID-19. The clinical features were consistent with incomplete KD in three patients. SARS-CoV-2 RT-PCR was positive in one and the serology was positive in one patient with negative RT-PCR. Corticosteroids, anakinra, intravenous immunoglobulin (IVIG), and acetylsalicylic acid were used in the treatment. Three patients recovered after the treatment while one patient died. The literature review revealed 36 articles describing 320 children with Kawasaki-like disease associated with COVID-19. SARS-CoV-2 RT-PCR was negative in 120 (65.5%) of 183 patients while the serology was positive in 130 (83.8%) of 155 patients. The therapeutic options have included IVIG, acetylsalicylic acid, tocilizumab, anakinra, enoxaparin, and methylprednisolone. Pediatric COVID-19 cases may present with atypical/incomplete Kawasaki-like disease. Thus, pediatricians need to be aware of such atypical presentations resembling KD for early diagnosis of COVID-19.
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http://dx.doi.org/10.1007/s00296-020-04701-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492688PMC
December 2020

COVID-19 in paediatric rheumatology patients treated with b/tsDMARDs: a cross-sectional patient survey study.

Ann Rheum Dis 2020 Jul 6. Epub 2020 Jul 6.

Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey

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http://dx.doi.org/10.1136/annrheumdis-2020-218341DOI Listing
July 2020

Whole exome sequencing in unclassified autoinflammatory diseases: more monogenic diseases in the pipeline?

Rheumatology (Oxford) 2021 02;60(2):607-616

Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.

Objective: Autoinflammatory diseases (AIDs) are characterized by recurrent sterile systemic inflammation attacks. More than half of the patients remain genetically undiagnosed with next-generation sequencing panels for common AIDs. In this study, we aimed to define phenotype-genotype correlations in a cohort of unclassified AID patients via whole exome sequencing (WES).

Methods: Patients with features of AIDs were included in this study followed in the Department of Pediatric Rheumatology at Hacettepe University. They were first screened for MEFV with Sanger sequencing and then WES performed for the patients with clinically insignificant results. Pre-analysis of WES data was done by considering the 13 most common AID-related genes. Further bioinformatic analysis was performed if the patient remained genetically undiagnosed.

Results: The median age at disease onset was 1.2 years (range 0.2-16) and at the time of study recruitment was 14 years (range 3.5-17). In our cohort, WES provided a definite or probable disease-causing variant in 4 of 11 patients (36%). Heterozygous mutations for two of these genes were previously associated with neurological defects (ADAM17, TBK1), also homozygous ADAM17 mutations were observed in one family with neonatal inflammatory skin and bowel disease. Besides, two genes (LIG4, RAG1) were associated with immunodeficiency although the patients had presented with inflammatory features. Finally, for one patient, we associated a strong candidate gene (NLRC3) with autoinflammatory features.

Conclusion: WES strategy is cost-effective and provides substantial results for a selected group of undefined AID patients. Our results will contribute to the spectrum of unclassified AIDs.
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http://dx.doi.org/10.1093/rheumatology/keaa165DOI Listing
February 2021

Colchicine and Leukopenia: Clinical Implications.

J Pediatr 2020 09 13;224:166-170.e1. Epub 2020 May 13.

Division of Pediatric Rheumatology, Department of Pediatrics, Ankara, Turkey. Electronic address:

Colchicine is the mainstay of treatment for familial Mediterranean fever. We investigated the frequency of leukopenia in 213 patients with familial Mediterranean fever treated with standard doses of colchicine (0.5-2.0 mg/day). We found that 23 patients (10.8%) had reversible leukopenia, 3 moderate, and none severe and that their rate of infections was not increased.
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http://dx.doi.org/10.1016/j.jpeds.2020.03.065DOI Listing
September 2020

Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry.

Rheumatology (Oxford) 2020 11;59(11):3324-3329

Department of Paediatrics, Division of Paediatric Rheumatology.

Objectives: FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry.

Methods: HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents.

Results: Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions.

Conclusion: Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.
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http://dx.doi.org/10.1093/rheumatology/keaa121DOI Listing
November 2020

Choroidal vascularity index as a biomarker of systemic inflammation in childhood Polyarteritis Nodosa and adenosine deaminase-2 deficiency.

Pediatr Rheumatol Online J 2020 Apr 3;18(1):29. Epub 2020 Apr 3.

Department of Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey.

Background/purpose: To assess EDI-OCT (enhanced depth imaging optical coherence tomography) of choroid for inflammatory signs in children with polyarteritis nodosa (PAN) and adenosine deaminase-2 deficiency (DADA-2).

Methods: In this cross-sectional study conducted between June 2017 and September 2018, we evaluated children diagnosed with PAN (n = 11) and DADA-2 (n = 4) and an age- and sex-matched control group (n = 15). Demographic and laboratory data were retrospectively analyzed from patient charts. Disease activity was assessed using the pediatric vasculitis activity score (PVAS). Choroidal images were obtained with spectral domain-OCT to measure choroidal thickness (ChT) at 5 points (750 and 1500 μm from the foveal center in the temporal and nasal quadrants and beneath the fovea), and to calculate the total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), and the choroidal vascularity index (CVI).

Results: The median (min-max) age was 8 (4-16) years in PAN patients, 6 (5-16) years in DADA-2 patients and 8 (8-10) years in control group at the OCT visit (p = 0.214). The ChT at 3 points and the TCA, LA, and SA were higher in children with both PAN and DADA-2 patients compared to those of the control group (p < 0.0001, p = 0.049, p = 0.007, p = 0.007, p = 0.006, p = 0.033, respectively). The CVI was similar in both groups. No association was observed between the OCT findings, PVAS, and the erythrocyte sedimentation rate, and serum leukocyte and C-reactive protein levels.

Conclusion: Similar CVI scores were obtained from PAN and DADA2 patients under treatment and from healthy controls. Increased subfoveal ChT without any other signs of ocular involvement may suggest choroidal thickening as a sign of mild subclinical inflammation.
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http://dx.doi.org/10.1186/s12969-020-0417-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118843PMC
April 2020

Characteristics of pediatric Behçet's disease in Turkey and Israel: A cross-sectional cohort comparison.

Semin Arthritis Rheum 2020 06 4;50(3):515-520. Epub 2020 Feb 4.

Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. Electronic address:

Background: Behçet's disease (BD) is a variable vessel vasculitis which is rare in children.

Objective: We aimed to compare the main characteristics of pediatric BD patients from Turkey versus Israel.

Methods: Three centers from Turkey and two centers from Israel participated in this study. The BD diagnosis was before 16 years of age and based on expert opinion. Disease activity was assessed with BD current activity form (BDCAF).

Results: A total of 205 patients were included (165 from Turkey; 40 from Israel). HLA-B51 positivity (68.3% vs. 46.2%, p = 0.028), male gender (52% vs. 30%, p = 0.012), and skin involvement (55.2% vs. 22.5%, p<0.001) were more frequent among patients from Turkey compared to patients from Israel. Tests of pathergy and HLA-B51 were more frequently performed in patients from Turkey than patients from Israel (93.3% vs. 32.5%, p<0.001 and 97.6% vs. 65%, p<0.001; respectively). For BD classification in the whole group, International Criteria for BD (ICBD) had the highest sensitivity (73.2%), followed by pediatric BD (PED-BD) (47.8%), and The International Study Group (ISG) (42%) criteria sets. The most commonly prescribed drug was colchicine in the whole group (96.6%). Significantly more patients were treated with corticosteroids (50% vs. 28.5%, p = 0.006), methotrexate (17.5% vs. 3%, p = 0.002), and nonsteroidal anti-inflammatory drugs (12.5% vs. 1.8%, p = 0.007) in Israel than in Turkey. The median BDCAF values were higher at the first visit for patients from Turkey compared to those in Israel (4 vs. 2, p<0.001).

Conclusion: This is the largest cohort of pediatric BD reported to date. The disease characteristics significantly differ among pediatric BD patients from Turkey and Israel, which may be due to different ethnicity and environmental factors.
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http://dx.doi.org/10.1016/j.semarthrit.2020.01.013DOI Listing
June 2020

Tocilizumab treatment in juvenile idiopathic arthritis patients: A single center experience.

Turk J Pediatr 2019 ;61(2):180-185

Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Demir S, Sönmez HE, Arslanoğlu-Aydın E, Özen S, Bilginer Y. Tocilizumab treatment in juvenile idiopathic arthritis patients: A single center experience. Turk J Pediatr 2019; 61: 180-185. Tocilizumab is a monoclonal antibody against interleukin-6 that has recently emerged as an alternative treatment modality for juvenile idiopathic arthritis (JIA). In the present study, we aimed to discuss the clinical and laboratory findings and treatment response of JIA cases to tocilizumab therapy. This retrospective study included 20 JIA patients aged between 0-18 years who were followed up from 2014 to 2016 and received tocilizumab treatment in our clinic. Treatment response could be not evaluated in two patients since they developed anaphylactic reactions due to tocilizumab. Of the remaining 18 patients, seven of them (38.9%) had polyarticular JIA, and eleven (61.1%) had systemic JIA. Platelet counts, erythrocyte sedimentation rate and C-Reactive protein (CRP) levels, active joint counts, and Juvenile Arthritis Disease Activity Score 71 (JADAS71) were significantly decreased at the third month in both polyarticular and systemic JIA, while there were not any significant differences between the third and sixth months. All of the patients with polyarticular JIA had low disease activity at six months. Eight patients with systemic JIA had an inactive disease at six months, whereas the remaining three patients had high levels of CRP without presence of any clinical symptoms. Steroid treatment was terminated at the sixth month in all patients except for three patients who continued to receive 0.05-0.25 mg/kg steroid treatment. Two patients developed thrombocytopenia, one patient developed macrophage activation syndrome, and one patient had elevated transaminases due to tocilizumab treatment. Previous studies have shown that tocilizumab treatment is well-tolerated, effective, and safe for use in JIA patients. In the present study, we also demonstrated the efficacy of tocilizumab treatment in JIA patients from our clinic.
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http://dx.doi.org/10.24953/turkjped.2019.02.005DOI Listing
August 2020

Chronic recurrent multifocal osteomyelitis in children: a single center experience over five years.

Turk J Pediatr 2019 ;61(3):386-391

Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Sağ E, Sönmez HE, Demir S, Bilginer Y, Ergen FB, Aydıngöz Ü, Özen S. Chronic recurrent multifocal osteomyelitis in children: a single center experience over five years. Turk J Pediatr 2019; 61: 386-391. Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease characterized by sterile bone inflammation. It is an orphan disease with many unclear aspects in terms of diagnosis, treatment and follow-up. The aim of this study was to report our experience of pediatric CRMO patients. Children who were diagnosed with CRMO, and were followed-up between January 2008 and January 2017, were included in this study. There were 15 CRMO patients (8M/7F) with a median age at diagnosis of 9.0 years (range: 0.6-15.0). Bone pain was the most common presenting symptom. All of the patients had multifocal bone lesions. Vertebrae (66.7%) and femur (66.7%) were the most commonly affected bones. Eight of the patients also had sacroiliitis; however, only one of them was HLA-B27 positive. Whole-body magnetic resonance imaging (MRI) was used as a diagnostic tool in 13 patients revealing bone marrow edema (84.6%), osteitis (69.2%), and periosteal reaction (61.5%). All patients were initially treated with non-steroidal anti-inflammatory drugs (NSAIDs), however, disease-modifying anti-rheumatic drugs, anti-TNF agents or pamidronate were added to therapy due to inadequate treatment response. Clinical remission was achieved in 12 patients (1 with NSAIDs, 3 with methotrexate, 1 with pamidronate and 7 with an anti-TNF agent). During the follow-up period, relapses were observed in four patients who presented with pain and/or a newly formed bone lesion on MRI. Eventually, however, all of these patients also reached remission. CRMO is a chronic disease which may have a progressive or relapsing-remitting course. Improvement of the knowledge about this rare disease may help to enlighten the unknowns of the disease.
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http://dx.doi.org/10.24953/turkjped.2019.03.010DOI Listing
August 2020

Desensitisation overcomes rituximab- and tocilizumab-related immediate hypersensitivity in childhood.

Clin Exp Rheumatol 2020 May-Jun;38(3):552-557. Epub 2019 Nov 20.

Division of Rheumatology, Department of Paediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Objectives: Biologic drugs (BD) have been game-changers in rheumatic diseases; however, severe hypersensitivity reactions concerning anaphylaxis may limit their use. Desensitisation is a crucial option that is safe and effective to maintain patients on the preferred drug. Herein we report 84 Rapid Drug Desensitisation (RDD) procedures with rituximab and tocilizumab in children with rheumatic diseases.

Methods: The study was conducted as a retrospective chart review of patients who received tocilizumab or rituximab therapy between January 2010 and December 2018. The results of RDD with tocilizumab and rituximab were documented.

Results: The study group consisted of 53 patients (11.6±4.5 years, 67.9% female) with rheumatic disease who had used tocilizumab (64.1%, 1007 infusions) or rituximab (35.8%, 73 infusions). Five patients (14.7%) had experienced anaphylaxis with tocilizumab and two patients (10.5%) with rituximab. Anaphylaxis was grade II in four cases whereas it was grade III in the remaining three children. Skin testing with the culprit BD performed in five children yielded positive results. We performed 65 RDDs with tocilizumab in 3 patients and 19 RDDs with rituximab in two patients. No reactions were recorded in 97.6% of the procedures. We observed one anaphylaxis during the 5th RDD of tocilizumab. After modifying the protocol, this patient continued tocilizumab RDD uneventfully.

Conclusions: RDD is a groundbreaking innovation which ensures giving the full target doses while protecting the patient against severe hypersensitivity reactions (HSRs) and anaphylaxis. As BD use increases in childhood, management of HSRs to BD will become more complicated, necessitating an increased need for RDD in clinical practice.
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September 2020

Pleural effusion as an atypical presentation of Kawasaki disease: a case report and review of the literature.

J Med Case Rep 2019 Nov 25;13(1):344. Epub 2019 Nov 25.

Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey.

Background: Kawasaki disease is an acute, febrile vasculitis of childhood that affects medium-sized arteries, predominantly the coronary arteries. It is a multisystem disease; therefore, it may present with non-cardiac findings of disease.

Case Presentation: Here, we report the case of 7-year-old Turkish girl who presented with symptoms of fever, chest pain, and vomiting, who was diagnosed as having Kawasaki disease. We also present a literature review on pulmonary involvement due to Kawasaki disease.

Conclusion: Pediatricians should consider the diagnosis of Kawasaki disease in the presence of pneumonia and pleural effusion that is nonresponsive to antibiotic therapy. This will prevent delay in diagnosis and the adverse consequences of the disease.
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http://dx.doi.org/10.1186/s13256-019-2284-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876070PMC
November 2019

A clinical score to guide in decision making for monogenic type I IFNopathies.

Pediatr Res 2020 03 22;87(4):745-752. Epub 2019 Oct 22.

Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Objective: To develop a set of clinical criteria that identifies patients with a potential autoinflammatory IFNopathy.

Methods: Based on a literature review, a set of clinical criteria identifying genetically confirmed monogenic IFNopathies was selected. For validation, the clinical score was assessed in healthy controls (HCs) and 18 disease controls, including 2 known autoimmune IFNopathies, juvenile systemic lupus erythematosus (JSLE, n = 4) and dermatomyositis (JDM, n = 4); adenosine deaminase 2 deficiency (DADA2, n = 4); and oligoarticular juvenile idiopathic arthritis (oJIA, n = 6). We assessed an IFN score (IRG-S) in whole blood by NanoString using a previously published 28-gene-IRG-S and a reduced 6-gene-IRG-S.

Results: The 12 patients with a possible IFNopathy had higher clinical scores (3-5) than the patients with sJLE, JDM, DADA2, and oJIA and in HCs. Both the 28-IRG-S and 6-IRG-S were significantly higher in the autoinflammatory IFNopathy patients compared to HCs and oJIA and DADA2 patients but not different from patients with JSLE and JDM. Subsequently, genetic analysis revealed mutations in genes previously reported in genes related to the IFN pathway in 9 of the 12 patients.

Conclusion: We developed a clinical score to identify patients with possible autoinflammatory IFNopathies. A clinical score was associated with a high IRG-S and may serve to identify patients with an autoinflammatory IFNopathy.
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http://dx.doi.org/10.1038/s41390-019-0614-2DOI Listing
March 2020