Search

Background: Uveitis, the most common extra- articular manifestation in juvenile idiopathic arthritis (JIA), occurs in 10-20% of patients. Although prognosis of uveitis within JIA (JIA- U) improved, complications still cause severe impairment of visual function in 25-33% of children that affects their psychophysical and psychosocial development and quality of life (QoL). Objectives: To study the QoL and it’s dimensions in children suffering from JIA-U as well as to investigate is there any difference in childhood’s and parent’s perception of disease between the group of children with JIA- U and children with JIA without uveitis. Methods: The study included 42 children with JIA and their parents. Patients were divided into two groups. The first consisted of 21 children with JIA-U and the second of 21 children with JIA and no uveitis. Both groups of patients and their parents filled the Juvenile Arthritis Multidimensional Assessment Report questionnaire (JAMAR) for monitoring and assessing the health status of children with JIA. The variables used to test differences were: QoL, functional ability, pain level, disease activity estimation, and current emotional state of the child. The significance of differences between groups of children and parents was verified by the independent-samples t-test. The Pearson correlation coefficient was used for measurement of the strength of the linear relationship between variables. Results: There were no statistically significant differences in the JIA-U group and the control group in either of the examined variables. Although there is a tendency of higher scores in children with JIA- U, which indicates their worse functioning, higher pain intensity and worse current emotional state, these differences were not statistically significant. Two groups did not differ significantly in the assessment of their own overall functional ability, which was associated with experienced pain intensity. Stronger pain intensity was associated with dysfunction (r = 0.642, p

Introduction: Biallelic pathogenic variants in TRNT1 gene, coding for the enzyme transfer RNA nucleotidyltransferase 1, cause TRNT1 deficiency with various clinical manifestations of autoinflammation, autoimmunity and immunodeficiency, including the syndrome of congenital sideroblastic anaemia with immunodeficiency, periodic fevers and developmental delay (SIFD). Objectives: Authors present a case of a child with recurrent fevers and epilepsy with de novo heterozygous mutation in TRNT1 gene of uncertain role in disease pathogenesis, successfully treated with TNFα inhibitor. Methods: Retrospective analysis of patient medical data and genomic testing using whole exome sequencing (WES). Results: Three months old female infant was referred to our Department with right-sided hemiconvulsions and dysrhythmic EEG changes treated with valproic acid. Subsequently, she had seizures on several occasions successfully treated with diazepam. Since 11 months of age, the child has had periodic protracted febrile episodes. Seven months after the onset of fever, she developed intermittent erythema accompanied with swelling of both hands, feet, knees and face. Subsequently, episodes of fever recurred in an irregular rhythm. The patient has been showing signs of progressive fatigue and severe facial erythema unrelated to febrility. Her physical exam was unremarkable apart from occasional facial erythema. Laboratory findings were normal, except for the long-lasting microcytic anemia (the lowest hemoglobin was 85 g/L) and elevated C-reactive protein and erythrocyte sedimentation rate during the febrile episodes. Comprehensive laboratory, microbiological and immunological examination failed to establish underlying diagnosis. Bone marrow examinations were normal. The frequent and prolonged febrile episodes were successfully treated with short- term methylprednisolone, however this treatment failed to prevent the occurrence of new episodes. To ameliorate fevers, TNFα inhibitor (etanercept) was consequently introduced in therapy at 5 years of age. Over the four month period after the initiation of TNFα inhibitor, the child had no further febrile episodes or seizures and there was an improvement in appetite and general condition. It is planned to reduce the dose of antiepileptics. Genomic testing using trio WES identified a de novo heterozygous TRNT1 variant, NM_182916.2 (TRNT1_v001): c.448C>T, p.(R150C), predicted to be pathogenic with high CADD score. Previous cases of TRNT1 deficiency have been described with bialellic TRNT1 pathogenic variants and analyses are underway to elucidate whether this finding could establish the underlying diagnosis. At present we hypothesize that this could be a case of unidentified second intronic TRNT1 variant or that this TRNT1 variant could have a dominant negative effect. In this respect, it should be noted that in our patient we have identified some but not other features of SIFD. Conclusion: Clinical manifestations associated with TRNT1 deficiency have a broad spectrum with significant clinical heterogeneity, which makes it difficult for rapid clinical recognition. Although the WES is as a powerful tool for the diagnosis of clinically unrecognized genetic conditions, there are still unresolved cases that pose a challenge in routine clinical practice.

Introduction: Henoch-Schönlein purpura nephritis (HSPN) is the most severe complication of Henoch- Schönlein purpura (HSP) that can occur at any time of the disease process and includes isolated microscopic or macroscopic hematuria, mild or heavy proteinuria with or without nephrotic syndrome, renal failure and hypertension. Objectives: To determine a possible prognostic factor for earlier HSPN onset, to explore indications for kidney biopsy according to urine analysis and the correlation between 24-h urinary protein levels and biopsy findings, as well as biopsy findings and patient outcome. Methods: The cross-sectional study included all children with HSPN diagnosed by EULAR/PRES/PRINTO criteria from 2009 to 2017 at 5 tertiary care centres in Croatia. Results: Out of 540 patients diagnosed with HSP, 91 children who developed HSPN (16.85%) were included. The patient population with HSPN included 52 boys (57.14%) and 39 girls (42.86%). Median (range) age of HSP diagnosis was 8 years (1.5-17.5) and from the HSP diagnosis to HSPN onset was 1.5 (0- 60) months. Median (range) follow-up time was 44 (4-167) months. Nephritis was present in 18.68% of cases at the HSP onset. No statistically significant difference or correlation was found between the time of HSP diagnosis to HSPN onset and gender, age, purpura distribution, joint and gastrointestinal involvement. Kidney biopsy was done in 26 patients (28.57%). Among them, 3 patients had isolated persistent hematuria, 3 had isolated proteinuria and 20 patients had both hematuria and proteinuria. Median (range) 24-h urinary protein levels in patients who underwent biopsy was 1.28 (0-7.46) g/dU. The leading indication for biopsy was simultaneous hematuria and proteinuria (p1g/dU. No significant difference was found in patient outcome for different biopsy findings (p=0.214). Conclusion: Simultaneous hematuria and proteinuria was a statistically significant factor for kidney biopsy. However, while isolated proteinuria was not the sole determining factor, excessive levels of 24-h urinary proteins should be taken in consideration. Due to the small number of patients and no uniform classification generally used in grading biopsy findings, a statistically significant difference in regard to outcome could not be confirmed, indicating the need for both in future research.

Background Although clinical symptoms and immunological findings are common in both children and adults with systemic lupus erythematosus (SLE), children generally have a more severe clinical presentation at the time of diagnosis with a larger number of affected organs, a much more aggressive clinical course and greater chance of developing organ damage over time. Objectives To compare the SLEDAI-2K disease activity index in patients with SLE at the time of diagnosis with SLEDAI-2K in the same patients in adulthood and to compare of the SLICC/ACR damage index (SDI) in patients with cSLE at the last follow up in childhood with SLICC/ACR of the same patients in adulthood. Methods This retrospective study included children who were diagnosed with cSLE, according to the ACR 1997 and SLICC 2012 criteria, in the period from 1991–2016 at the Referral Centre for Paediatric and Adolescent Rheumatology Republic of Croatia, Department of Paediatrics, University Hospital Centre Zagreb and who by the end of March 2017 reached the age of majority at 18 and continued their treatment at the Department of Internal Medicine, University Hospital Centre Zagreb. Results Out of 95 children with cSLE, 48 patients (42 females and 6 males) who attained the age of majority, were included in the study. Mean age at the time of diagnosis was 13.5 years (range 6–18), and the mean disease duration was 11 years. Mean SLEDAI- 2K was 19, 25 (range 0–42) in childhood and 7125 (range 0– 30) in adulthood. In adulthood, thirty-two patients (66.67%) showed improvement, three (6.25%) disease progression, six (12.5%) had the same disease activity and seven patients (14.58%) were in remission. 13 children (27%) had organ damage at the last follow up with mean SDI 0.43 (0–6) and 20 patients in adulthood (41, 67%) had organ damage with SDI 0.75 (0–6). Cataract, erosive arthritis and avascular necrosis were the most common organ damage in both groups. The most common presenting symptoms in childhood were musculoskeletal (predominantly arthritis) occurring in 34 children (70.83%), mucocutaneous (rash) noted in 31 (64.58%) and fever in 21 patients (43.75%). Of different laboratory tests the most common were positive antinuclear antibodies (ANA) screen (95.83%) and hypocomplementaemia (75%). Proteinuria was noticed in 26 children (54.17%). Similarly, in adulthood the most common symptoms were arthritis in 10 (20.83%) and rash in 8 patients (16.67%). Alopecia, headaches and visual disturbances were represented with 12.5% each. ANA screen was positive in 27 patients (56.25%) and hypocomplementaemia present in 22 patients (45.83%). Conclusions At the time of diagnosis in childhood, disease activity is very high while in adulthood there is a significant decrease in disease activity. Higher disease activity in childhood is related to the development of the organ damage in adulthood.

Background: Raynaud’s phenomenon (RP) is a condition characterized by periodical vasospasm in response to cold temperatures or emotional stress exposure. To distinguish between primary and secondary RP, clinical examination, laboratory fi ndings, nailfold capillaroscopy (NC) and computerized color telethermography (CCTT) are necessary. Objectives: To analyze RP features in children in correlation with the most frequently associated laboratory tests, CCTT and NC. Methods: Th is study included children clinically recognized as RP in the period from 2011–2017 at the Referral Center for Pediatric and Adolescent Rheumatology Republic of Croatia. Laboratory data included serum level of IgG, C3, C4, CH50, RF, presence of ANA and ANCAs. Results: CCTT, performed in 188 patients, classifi cated 15 as primary RP, 57 as secondary RP, while in 47 no classifi cation could be made. Among patients classifi cated as secondary RP on CCTT, the most of them, 14 (24.6%), were diagnosed with juvenile idiopathic arthritis (JIA). Th ere were 5 patients (8.8%) with systemic sclerosis (SSc), 2 (3.5%) with mixed connective tissue disease (MCTD), 1 (1.7%) with systemic lupus erythematosus, 11 (19.3%) with undiff erentiated connective tissue disease (UCTD), whilst 24 (42.1%) had no evident other disease. Th e appearance of abnormal capillaroscopic pattern was found in 17 out of 89 patients and nonspecifi c capillaroscopic alterations were noticed in 27. Among patients with the appearance of abnormal capillaroscopic pattern, 5 (29.4%) were diagnosed with SSc, 3 (17.6%) with JIA, 2 (11.8%) with MCTD, 1 (5.9%) with dermatomyositis, 2 (11.8%) with UCTD, whilst 4 (23.5%) had no evident rheumatic disease. All patients with RP diagnosed with SSc and MCTD had both the appearance of abnormal capillaroscopic pattern and CCTT fi ndings consistent with secondary RP. No statistically signifi cant diff erence between NC and CCTT in predicting the diagnosis of secondary RP was determined (McNemar’s test, χ2 = 0.042, p = 0.838) nor was there signifi cant diff erence between NC and CCTT in regard to the results of laboratory fi ndings (χ2 = 1.042, p = 0.307). Conclusions: We found that nailfold capillaroscopy and CCTT were equally eff ective in the diagnosis of secondary RP in children. Th ere was no diff erence between them in regard to the results of immunological laboratory fi ndings distinctive with secondary RP.

Introduction: Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic, chronic autoimmune disease occurring in children and adolescents under 18, presenting heterogeneously, with the course of the disease often more severe than in adults, and the activity of the disease widely being evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI 2K) and damage by the SLICC/ACR damage index (SDI). Objectives: To compare and explore the correlation between the SLEDAI-2K disease activity index at the time of diagnosis and the SLICC/ACR damage index (SDI) of patients at their last follow up, to examine the quantity of organ damage in regard to patients’ characteristics and disease duration and to predict the risk of organ damage occurrence in time. Methods: The retrospective study included children treated for cSLE in the period from January 1991 to September 2017 at Department of Pediatrics, University Hospital Center Zagreb. The follow up data of patients after the age of majority at 18 and who were under care of the Department of Internal Medicine, University Hospital Center Zagreb was also included. All children were diagnosed according to the ACR 1997 and SLICC 2012 criteria. Data analysis was done using R environment for statistical computing. Results: The disease development of 93 children (74 females and 19 males) with cSLE was examined in this study. The median (range) follow up time was 7 (0.5-24) years and the median (range) age at diagnosis was 13 (5-19) years. Two patients have died during the examined period. Mean (SD) SLEDAI- 2K was 18.3 (9.0) at the disease onset. 35 children (38 %) had organ damage at the last follow up with the median (range) SDI 0 (0-7). The first organ systems damaged in affected patients were renal (28%), musculoskeletal (22%), ocular (19%), neuropsychiatric (17%), cardiovascular (11%) and peripheral vascular (2.8%), but with no significant statistical difference regarding the type of organ damage. Kendall rank correlation coefficient was used to evaluate the relationship between SLEDAI-2K at the disease onset and SDI, determining a positive correlation which was statistically significant (τb = 0.252, p = 0.003). However, no significant correlation was determined between the duration of the disease and SDI (τb = 0.042, p = 0.628) or follow up period and SDI (τb = 0.111, p = 0.191) nor was there significant difference of SDI in regard to gender (Asymptotic Wilcoxon- Mann-Whitney Test, p= 0.574). Using Kaplan-Meier method we estimated the decrease in ratio of patients without organ damage since diagnosis or the occurrence of the first symptoms. Since the estimated ratio of patients with organ damage at the endpoint was less than 50%, we could not estimate the time required for damage development in 50% of patients. However, we are 95% sure that the damage is not happening in the first 9 or 10 years after diagnosis or the occurrence of the first symptoms, respectively. Conclusion: The high correlation detected between SLEDAI-2K and SDI indicated that the presentation of the cSLE at onset can be prognostic of the course and long-term prognosis of lupus. Our findings suggest that it is unlikely that organ damage will occur in 50% of patients in the first nine years of the disease course.

Background: Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease with the course often more severe than in adults, and the activity of the disease widely being evaluated by SLE Disease Activity Index (SLEDAI 2K) and damage by the SLICC/ACR damage index (SDI). Objectives: To explore the correlation between the SLEDAI-2K disease activity index at the time of diagnosis and the SLICC/ACR damage index of patients at their last follow up and to predict the risk of organ damage occurrence in time. Methods: The retrospective study included children treated for cSLE from January 1991 to September 2017 at Department of Pediatrics, UHC Zagreb. All children were diagnosed according to the ACR 1997 and SLICC 2012 criteria. Results: The disease development of 93 children (74 females) with cSLE was examined in this study. The median (range) follow up time was 7 (0.5–24) years and the median (range) age at diagnosis was 13 (5–19) years. Mean (SD) SLEDAI-2K was 18.3 (9.0) at the disease onset. 35 children (38 %) had organ damage at the last follow up with the median (range) SDI 0 (0–7). Th e first organ systems damaged in affected patients were renal (28%), musculoskeletal (22%), ocular (19%), neuropsychiatric (17%), cardiovascular (11%) and peripheral vascular (2.8%). A statistically signifi cant positive correlation was found between SLEDAI-2K at the disease onset and SDI (τb = 0.252, p = 0.003). No significant correlation was determined between the duration of the disease (τb = 0.042, p = 0.628) or follow up period (τb = 0.111, p = 0.191) and SDI, nor in SDI in regard to gender (p= 0.574). Using Kaplan-Meier method we estimated the decrease in ratio of patients without organ damage since diagnosis or the occurrence of the first symptoms. Since the estimated ratio of patients with organ damage at the endpoint was less than 50%, we could not estimate the time required for damage development in 50% of patients. However, we are 95% sure that the damage is not happening in the first 9 years aft er diagnosis. Conclusions: The high correlation detected between SLEDAI-2K and SDI indicated that the presentation of the cSLE at onset can be prognostic of the course and long-term prognosis of lupus. Our findings suggest that it is unlikely that organ damage will occur in 50% of patients in the first nine years of the disease course. References: 1. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002; 29:288–91.

The aim of this study was to present our experience in rituximab therapy in patients with childhood-onset systemic lupus erythematosus, lupus nephritis, and ANCA-associated vasculitis. We conducted a retrospective clinical chart review of all patients treated with rituximab in the time period from January 2009 to December 2015. Eight patients (3 boys and 5 girls) aged 8 to 15 at the onset of disease were treated with rituximab. Remission of disease was accomplished in 4 patients with childhood- onset systemic lupus erythematosus and lupus nephritis, a partial improvement was achieved in 1 patient with childhoodonset systemic lupus erythematosus and lupus nephritis as well as in 2 patients with vasculitis, while in one patient with vasculitis treatment with rituximab showed no effect and the patient died due to Candida sepsis. Reduction of corticosteroid doses was enabled by rituximab treatment. Rituximab appeared to be a safe and efficient therapeutic option in severe cases of childhood- onset systemic lupus erythematosus or ANCA-associated vasculitis that failed to respond to conventional therapy or as a rescue therapy in life-threatening conditions.

The two most common entities among generally rare but under-diagnosed autoinflammatory bone disorders are chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Due to their similarities, many authors consider CRMO to be a subtype of SAPHO syndrome. The aim of this study was to compare clinical, laboratory, and imaging features and outcomes of patients with CRMO and SAPHO. The analysis of the data from 6 children with CRMO (four girls and two boys, age 3.5-14 years) and of 6 children (6 boys, age 13.5-17.5 years) with SAPHO syndrome was performed. The initiating symptoms in all patients with CRMO were bone pain with multifocal bone lesions. There were no skin manifestations. Five out of six patients achieved control with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, while one patient required disease-modifying antirheumatic drugs (DMARDs). The initiating symptom in five patients with SAPHO syndrome were severe acne, while in one patient acne occurred two years after the disease onset. Two patients typically developed inflamed sternoclavicular joints and sternum, while the others showed changes affecting other skeletal regions. Three patients achieved control with NSAIDs and corticosteroids, the others required DMARDs and TNFα inhibitors. In comparison with patients with CRMO, patients with SAPHO suffered more frequent and longer lasting exacerbations. In conclusion, CRMO and SAPHO syndrome have an array of common characteristics, but also a number of differences. Nevertheless, further investigation into the etiopathogenesis is required to establish a definite relationship between CRMO and SAPHO.