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Introduction: This retrospective cohort study aimed to describe the articular manifestations in Saudi children with X-linked hypophosphatemic rickets (XLHR). Materials and Methods: The medical records of children with XLHR were retrospectively reviewed. The diagnosis of XLHR was confirmed biochemically by low serum phosphorus and elevated alkaline phosphatase, radiologically by the evidence of active rickets and genetically by phosphate-regulating gene with homology to endopeptidases (PHEX) gene mutations. Results: Twenty-two patients with XLHR (10.8 years + 4.9) were enrolled. All children were followed at King Faisal Specialist Hospital & Research Center for a mean duration of 8.7 years (+3.7). Clinically, all patients had disproportionate short stature (-2.5 standard deviation +1.3) with varying degrees of skeletal deformities, including genu varum in 68%, genu valgum in 18%, coxa vara in 14%, bowing of tabia in 32%, and history of fractures in 32% of children. Hearing impairment was noted in two children. Biochemically, all patients showed increased urinary phosphate loss with hypophosphatemia 0.67 mmol/l (+0.15) and elevated serum alkaline phosphatase levels 522 IU/l (+133). Genetically, hemizygous PHEX mutation (C746F) was reported in seven patients. Radiologically, four children had osteoarthritis and three had enthesopathies. Four patients craniosynostosis. All children were on oral inorganic phosphate salts (50–70 mg/kg/day), combined with 1,25(OH)2D3 (alfacalcidol or calcitriol, 30–40 ng/kg/day). Conclusion: Patients with XLHR frequently present with varying degrees of joint deformities that are not completely resolved with either medical or surgical treatment. Long-term skeletal complications of XLHR that present in adults are less common in children and adolescents.

Monogenic lupus is a rare inherited entity, which has been increasingly recognized over the past decade. Monogenic lupus demonstrates heterogeneity in etiopathogenesis, phenotypes, and outcome compared to sporadic systemic lupus erythematous (SLE). Its distinctive features include early-onset disease, atypical manifestations of underlying diseases such as immunodeficiency, immune dysregulation, and refractory disease course. The term “monogenic lupus” has been used internationally to collectively describe a group of patients presenting with SLE or SLE-like symptoms with a proven underlying pathogenic variant. It has been considered a form of SLE irrespective of the differences observed. To date, there is no standardized definition or criteria to identify monogenic lupus. Therefore, this review highlights the differences between monogenic lupus and sporadic SLE to discuss the challenges related to the current nomenclature and unmet needs in the diagnosis of monogenic lupus. A considerable number of underlying pathogenic variants have recently been uncovered, leading to various pathways’ involvement with significant overlap. This allows us to propose a new definition for monogenic lupus which can be considered as a construct rather than a disease or syndrome.

To evaluate the application of the EULAR/ACR-2019 criteria to monogenic lupus patients and compare its performance against the SLICC-2012 criteria.In a multicenter retrospective cohort study, consecutive patients with monogenic lupus from three tertiary lupus clinics were enrolled. The diagnosis of monogenic lupus was based on the expert physician's opinion or fulfilling the SLICC-2012 criteria. All enrolled patients had genetic variants. A control group of sporadic childhood SLE (cSLE) and non-SLE patients, were included. A descriptive data analysis was conducted, and the EULAR/ACR-2019 and SLICC-2012 criteria were applied to both groups.Forty-nine patients with monogenic lupus with a median age at diagnosis of 6.0 (IQR 3.0-10.8) years and 104 controls (55 patients with cSLE and 49 non-lupus patients with a median age at diagnosis of 10.0 and 5.0 respectively) were included. Forty-four (89.8%) patients with monogenic lupus fulfilled the EULAR/ACR-2019 with a mean score of 22.3±8.9. The most frequent domains were immunologic (93.9%), musculoskeletal and renal (each 57.1%), and mucocutaneous (55.1%). Fifty-four (98.2%) cSLE patients and six (12.2%) non-lupus patients met the EULAR/ACR-2019 criteria with a mean score of 22.5±9.2 and 8.5±5.2, respectively. The sensitivity of the EULAR/ACR-2019 criteria in monogenic lupus was 89.9% (95% CI: 78.3-90.2), while the specificity was 87.6% (95% CI: 75.2-88.7).This is the first and largest cohort of monogenic lupus patients testing the performance of the 2019-EULAR/ACR criteria. It efficiently classifies monogenic lupus patients, irrespective of the underlying genetic variants. Further studies are needed before these criteria are adopted worldwide. Key Points • Typically, patients with monogenic lupus have early onset severe disease, especially with mucocutaneous manifestations and a strong family history of SLE. • Monogenic lupus is a distinctive entity and might differ from the sporadic childhood SLE. • Our study includes a large multinational cohort of monogenic lupus with heterogeneous phenotypic features and underlying genetic variants. • Our study demonstrates that the EULAR/ACR-2019 criteria efficiently classified monogenic lupus patients, irrespective of the diversity of the underlying genetic variants.

Objectives To evaluate the impact of family history of autoimmune diseases (FHADs) on the clinical characteristics and outcome of juvenile idiopathic arthritis (JIA). Methods We retrospectively reviewed children with JIA seen in 7 pediatric rheumatology clinics from 6 Arab countries. All included patients met the International League of Associations for Rheumatology classification criteria for JIA and had a disease duration greater than 1 year. Data were collected at the last follow-up visit and comprised clinical findings, including FHADs. Disease activity and disease damage were assessed by Juvenile Arthritis Multidimensional Assessment Report, and juvenile arthritis damage index (JADI) respectively. Disease activity was categorized as remission off treatment, remission on treatment, or active disease. Results A total of 349 (224 females) JIA patients with a disease duration of 5 (interquartile range 2.9-7.5) years were included. The most frequent JIA categories were polyarticular JIA and oligoarticular JIA, followed by systemic JIA. There were 189 patients with FHADs and 160 patients without FHADs. The most frequent FHADs were diabetes mellitus (21.2%), JIA (18.5%), rheumatoid arthritis (12.7%). Among patients with FHADs, 140/189 (74.1%) achieved clinical remission, while 131/160 (81.9%) patients without FHDs had clinical remission (odds ratio [OR] = 1.2, 95% CI 0.97-1.5). Rate of consanguinity, enthesitis-related arthritis (ERA) and psoriatic arthritis were higher in patients with FHADs (OR = 0.6, 95% CI 0.4-0.9 and OR = 1.2, 95% CI 1.1-1.4). Also, articular JADI correlated significantly with presence of FHADs (OR = 1.1, 95% CI 1.0-1.1). Conclusion This study shows that autoimmune diseases cluster within families of patients with JIA with a high proportion of ERA and psoriatic arthritis. JIA patients with FHADs are likely to have more disease damage.

The type II transmembrane protein fibrinogen-like protein 2 (FGL2) plays critical roles in hemostasis and immune regulation. The C-terminal immunoregulatory domain of FGL2 can be secreted and is a mediator of regulatory T (Treg) cell suppression. Fgl2Our aim was to identify the genetic underpinning and immune function in a patient with childhood onset of leukocytoclastic vasculitis, systemic inflammation, and autoantibodies.Whole-exome sequencing was performed on patient genomic DNA. FGL2 protein expression was examined in HEK293 transfected cells by immunoblotting and in PBMCs by flow cytometry. T follicular helper cells and Treg cells were examined by flow cytometry. Treg cell suppression of T-cell proliferation was assessed in vitro.The patient had a homozygous mutation in FGL2 (c.614_617del:p.V205fs), which led to the expression of a truncated FGL2 protein that preserves the N-terminal domain but lacks the C-terminal immunoregulatory domain. The patient had an increased percentage of circulating T follicular helper and Treg cells. The patient's Treg cells had impaired in vitro suppressive ability that was rescued by the addition of full-length FGL2. Unlike full-length FGL2, the truncated FGL2We identified a homozygous mutation in FGL2 in a patient with immune dysregulation and impaired Treg cell function. Soluble FGL2 rescued the Treg cell defect, suggesting that it may provide a useful therapy for the patient.

Objective To report the cumulative articular and extraarticular damage in Arab children with juvenile idiopathic arthritis (JIA) and to identify variables that correlate with disease damage. Methods We conducted a multicenter, cross-sectional study among 14 pediatric rheumatology centers from 7 Arab countries. JIA patients who met the International League of Associations for Rheumatology classification criteria and had a disease duration of >1 year were enrolled. Disease activity status was assessed using the Juvenile Arthritis Multidimensional Assessment Report. Disease damage was assessed by the Juvenile Arthritis Damage Index, articular (JADI-A) and extraarticular (JADI-E). Results A total of 702 (471 female) JIA patients with a median age of 11.3 years (interquartile range [IQR] 8.0-14.0 years) were studied. Median age at disease onset was 5 years (IQR 2.0-9.0 years) and the median disease duration was 4 years (IQR 2.0-7.0 years). The most frequent JIA categories were oligoarticular JIA (34.9%), polyarticular JIA (29.5%), and systemic JIA (24.5%). Clinical remission was achieved in 73.9% of patients. At the last clinic visit, 193 patients experienced joint damage, with a mean ± SD JADI-A score of 1.7 ± 4.5, while 156 patients had extraarticular damage, with a mean ± SD JADI-E score of 0.5 ± 1.1. Patients with enthesitis-related arthritis had the highest JADI-A score. JADI-A correlated significantly with the presence of a family history of JIA. JADI-A and JADI-E had a significant correlation with long disease duration. Conclusion Cumulative damage was common in this Arab JIA cohort, and consanguinity and JIA in a sibling were frequent findings and were associated with a greater cumulative damage.

Background The classification and pathogenic basis of juvenile idiopathic arthritis (JIA) are a subject of some controversy. Essentially, JIA is an exclusion diagnosis that represents a phenotypically heterogeneous group of arthritis of unknown origin. Familial aggregation of JIA supports the concept of genetic influence in the pathogenesis of JIA. Objective To present the spectrum of laccase domain-containing 1 (LACC1)-associated juvenile arthritis with clinical, biochemical, and molecular genetic data of a cohort of 43 patients, including 11 previously unpublished cases. Methods We studied 11 patients with different categories of juvenile idiopathic arthritis from 5 consanguineous families, all from Saudi Arabia, except 2 patients who were of Jordanian ethnicity. Whole-exome sequencing was used to identify the disease-causing variant of LACC1. We also reviewed the clinical spectrum and molecular genetic data of previously published cases of LACC1-associated juvenile arthritis. Results This study describes 43 (29 females, 14 males) patients from consanguineous multiplex families. Most of the included patients were of Arab origin with 86% having early onset disease. The most frequent categories were systemic (19 patients) and rheumatoid factor-negative polyarticular (19 patients). Thirty-seven (86%) had progressive erosive arthritis and 10 (23.3%) had persistent limb lymphedema. None of the patients had features of macrophage activation syndrome. Genetic analysis confirmed LACC1 variant in all patients; 22 patients had common founder mutation (LACC1: c.850T > C,p.C284R), while the others showed different LACC1 variants. All patients were treated aggressively with methotrexate and sequential biologic agents. Most of them showed a poor response to treatment. Conclusion This report expands the pathogenic variants of LACC1 and the clinical spectrum associated with this genetic subset of juvenile arthritis. The predominance of autosomal-recessive inheritance and strong genetic evidence allowed us to propose LACC1-associated juvenile arthritis as a distinct disorder.

The objective of the study was to report the safety and potential therapeutic effect of belimumab in monogenic systemic lupus erythematosus (SLE). Consecutive children with monogenic SLE treated with belimumab were evaluated retrospectively. Response parameters assessment was completed at the time of initiation of belimumab, at 6 months, and last follow-up visit. Response parameters comprised physician global assessment (physician GA) and parent global assessment (parent GA), global disease activity as measured by SLE disease activity index (SLEDAI), and daily glucocorticoids dose. Undesirable events affecting patients during treatment were also collected. Six children with monogenic SLE proved by genetic testing (five patients with C1q deficiency and one patient with deoxyribonuclease II (DNase II) deficiency), failed glucocorticoids and sequential immunosuppressive medications. Belimumab was added to glucocorticoids and current immunosuppressive medications. The main indications for belimumab initiation were mucocutaneous disease, arthritis, and inability to taper glucocorticoids. All patients tolerated belimumab infusion. No serious events were reported. However, one patient was lost to follow-up and died because of sepsis. Compared to the baseline values, there was an improvement in physician GA, parent GA, and SLEDAI, and a notable reduction in the need of daily corticosteroids. However, there were no significant changes in the complement and ds-DNA antibody levels. Belimumab can be considered as an adjunctive therapeutic option for patients with refractory monogenic SLE. Further follow-up and more patients needed to confirm this finding and a larger prospective study is required for more definitive conclusions.

Objective: To assess the usefulness of serum ferritin and soluble interleukin-2 receptor (sIL-2r) levels as markers of disease activity in childhood systemic lupus erythematosus (cSLE) and their role in screen for subclinical macrophage activation syndrome (MAS). Patients and methods: This is a cross-sectional analysis of prospectively collected data. Consecutive children who met the Systemic Lupus International Collaborating Clinics (SLICC) criteria were enrolled between June 2015 and June 2017. All patients interviewed and assessed for disease activity using SLE disease activity index (SLEDAI). Biochemical and serological tests including markers of disease activity and MAS were measured by standard laboratory procedure. Results: A total of 31 (25 female; 6 male) consecutive cSLE patients with a mean age of 10.6 (±3.2) years were included. The most frequent manifestations were mucocutaneous and musculoskeletal (84%) followed by hematological (64.5%) then renal involvement (58%). Twenty-two patients had active disease (SLEDAI ≥ 4), with a mean of 9.8. Mean serum ferritin and sIL-2r were 555 (±1860) and 2789 (±1299) respectively. Both correlated significantly with leucocyte, platelet count, transferrin, C3 and SLEDAI (p

Introduction Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease associated with autoimmune diseases. The aim of the study is to assessed the frequency of celiac disease (CD) in adults and children with SLE (aSLE and cSLE, respectively) and compare them with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) patients; the study also explored the clinical impact of CD serologic markers on SLE disease activity and severity. Methods This was a cross-sectional study. Patients with SLE who had regular follow-up in rheumatology clinics were evaluated for laboratory and clinical variables using serology and the SLE Disease Activity Index (SLEDAI). To assess the occurrence of CD serology in cSLE and aSLE and the clinical impact of CD serologic markers on SLE, patients were tested for antigliadin (AGA), anti-endomysium (EmA) and anti-tissue transglutaminase (tTG) antibodies. RA and JIA patients were included for comparison. Duodenal biopsy was conducted in patients who exhibited CD markers. Results The CD marker was found in 29 (11.6%) of the 250 patients. AGA was present in seven aSLE patients and tTG in two (11.1%). Among cSLE patients, the autoantibody was present in 17.6% (AGA in four, tTG in two, and EmA in three). For RA patients, five had AGA and tTG and one had EmA, with an overall positivity of 9.7%. Five JIA patients had AGA (four with EmA and five with tTG) with overall positivity of 10.9%; the serum IgA level was normal in all patients except one. Duodenal endoscopic biopsy was performed in patients with positive CD markers (two declined). Histologic confirmation of CD was reported in one RA and one JIA patient but in none of the SLE patients. There was no correlation between the presence of CD markers and autoantibodies in SLE. Conclusion CD antibodies did not influence SLE activity. Thus, SLE patients may not need to be screened for CD antibodies.

Genetic defect of phosphatase and tensin homolog (PTEN) gene might play a role in B cell hyperactivity and result in the development of systemic lupus erythematosus (SLE), while transaldolase deficiency has a spectrum of clinical features including autoimmune endocrinopathy. Herein, we identified a novel phenotype in a girl presenting with clinical and laboratory findings consistent with SLE. Exome sequencing identified pathogenic heterozygous variant in PTEN gene (NM_000314: exon 6: c.518G > C: p. R173P) and homozygous variant in TALDO1 gene (NM_006755: exon 6: c.793C del: p. Q265f). Our report highlights the association of PTEN mutation and autoimmunity and the possibility that transaldolase deficiency may be indirectly involved in the development of SLE.

Juvenile Idiopathic Arthritis (JIA) is a group of chronic heterogenous disorders that manifests as joint inflammation in patients aged

To define the spectrum and phenotypic characteristics of systemic autoinflammatory diseases (SAIDs) other than familial Mediterranean fever (FMF) in Arab children and to delineate diagnostic evaluation. Data retrospectively collected on patients with clinical and/or genetically proven SAIDs other than FMF at 10 tertiary Arab pediatric rheumatology clinics from 1990 to 2018. The collected data comprised the clinical findings and diagnostic evaluation including genetic testing, the provided treatment and the accrual damage related to SAIDs. A total of 144 patients (93 female) with a median age at onset of 2.5 (range 0.1-12) years were enrolled. The initial diagnosis was inaccurate in 49.3%. Consanguinity rate among parents was 74.6%. The median time-to-diagnosis for all SAIDs was 2.5 (range 0.1-10) years. There were 104 patients (72.2%) with a confirmed diagnosis and 40 patients with suspected SAIDs. Seventy-two had monogenic and 66 patients with multifactorial SAIDs while six patients had undifferentiated SAIDs. The most frequent monogenic SAIDs were LACC1 mediated monogenic disorders (n = 23) followed by CAPS (12), TRAPS (12), HIDS (12), and Majeed's syndrome (6). The most frequent multifactorial SAIDs was CRMO (34), followed by PFAPA (18), and early onset sarcoidosis (EOS) (14). Genetic analysis was performed in 69 patients; 50 patients had genetically confirmed disease. Corticosteroid used for 93 patients while biologic agents for 96 patients. Overall, growth failure was the most frequent accrual damage (36%), followed by cognitive impairment (13%). There were three deaths because of infection. This study shows a heterogenous spectrum of SAIDs with a high number of genetically confirmed monogenic diseases; notably, LACC1 associated diseases. Hopefully, this work will be the first step for a prospective registry for SAIDs in Arab countries.

The objective of this study is to assess the usefulness of the stand-alone renal SLICC criterion in patients with childhood systemic lupus erythematosus (cSLE) and report their disease course, treatment response, and outcome. This study included children who were followed regularly in our lupus clinic with proved full house glomerular immune deposits nephritis and antinuclear (ANA), or anti-double-stranded DNA (dsDNA). They were compared with patients who diagnosed with cSLE with and without biopsy proven nephritis, based on Systemic Lupus International Collaborating (SLICC). The comparative group selected by systematic sampling from our cSLE database; the first patient was chosen randomly, and the subsequent patients chosen at intervals of three. The two groups were compared in respect to demographic data, clinical and laboratory findings, and disease course including response to treatment and outcome using urine protein/creatinine ratio, eGFR, and urine sediments. A total of 37 patients were assessed, six patients met the stand-alone renal SLICC criterion, 18 patients had cSLE with biopsy proven nephritis, and 13 cSLE patients without biopsy proven nephritis. Age of onset and time to diagnosis were comparable. However, patients with stand-alone renal criterion had significantly higher baseline serum creatinine, urine protein/creatinine ratio, and lower ANA titer (p 0.05). Furthermore, none of the patients had other lupus manifestations. Four patients showed partial response to treatment. Two patients had renal impairment and one patient developed end-stage renal disease. Patients with full house glomerular immune deposits nephritis and ANA, or anti-dsDNA reflect a different disease spectrum with severe renal manifestations and worse outcome. Further large prospective study is required to revisit the validity of the stand-alone renal SLICC criterion in cSLE. KEY POINTS : • There is no definite diagnostic tool for SLE. Furthermore, to date there are no specific classification criteria for cSLE. • It seems that patients who met the stand-alone renal SLICC criterion might represent a distinct disease spectrum with severe renal involvement.

Objective: To report the outcome of children with rheumatic diseases admitted to pediatric intensive care unit (PICU) in a tertiary hospital. Methods: Database from PICU and pediatric rheumatology section used to retrieve all candidate patients admitted to PICU from June 2000 to December 2017. Medical records of all enrolled patients reviewed for diagnosis, organ involvement, reason of PICU admission, the length of stay, and outcome. Results: Twenty-five patients (17 female, 8 male) with total of 41 admissions identified. The median PICU stay was 13.5 days (range, 3–24). The most frequent diagnoses were systemic lupus erythematosus (SLE) (48%), followed by systemic vasculitis (16%). Most admissions were from the medical ward (68.3%), while 24.4% from the emergency room. The main reason of PICU admission was a disease flare or related complications (48.8%), followed by infection (34.2%). Fifty one percent of the admissions were due to respiratory dysfunction, 46% required non-invasive respiratory support while 38% was in need for mechanical ventilation. During PICU stay, anti-microbial agents used 90.3%, immunosuppressive treatment adjustment 75.6%, anti-hypertensive 24.4% and vasopressors 12.2%. Twelve patients (48%) fully recovered and 40% partially recovered while three patients died during their PICU stay. The causes of death were macrophage activation syndrome complicated by sepsis in two patients and advanced pulmonary hypertension in one patient. Conclusion: Our data showed that children with rheumatic diseases, particularly SLE, are mostly admitted to PICU with serious disease exacerbation or severe infection. To improve the outcome, early diagnosis of critical condition and proper intervention are fundamental in reducing mortality. Keywords: Pediatric intensive care, Childhood rheumatic diseases, Systemic lupus erythematosus, Outcome

Purpose of review We describe the clinical and genetic findings in four patients from a single family who presented with refractory psoriatic arthritis and were hemizygous in the forkhead box protein 3 (FOXP3) gene (c.1222G>A). Recent findings We report four siblings with hemizygous mutation in the FOXP3 gene (c.1222G>A) who presented with type 1 diabetes mellitus and psoriatic arthritis poorly responsive to treatment. Our findings expand the phenotype spectrum of FOXP3 mutations. Immune dysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutations in FOXP3 gene, which lead to early onset of constellation of autoimmune manifestations. This report highlights the influence of immune dysregulation in juvenile arthritis.

Background Systemic juvenile idiopathic arthritis (sJIA) is a diagnosis of exclusion. The complex nature and clinical variety of the disease, as well as the vast clinical variation of disease presentation, may lead to difficulties in disease detection and subsequent delays in treatment. Aim To provide a consensus guidance on the management of newly diagnosed sJIA patients among pediatric rheumatologists in Arab countries. Methods This work was conducted in two phases. The first phase utilized an electronic survey sent through an email invitation to all pediatric rheumatologists in Arab countries. In the second phase, a Task Force of ten expert pediatric rheumatologists from Arab countries met through a series of virtual meetings. Results obtained in phase one were prioritized using a nominal group and Delphi-like techniques in phase two. Results Seven overarching principles and a set of recommendations were approved by the Task Force to form the final consensus. Conclusion This is the first consensus on a clinical approach for pediatric rheumatic diseases among Arab pediatric rheumatologists. It is presented as a guidance on the clinical approach to sJIA that requires further evidence, and future updates are anticipated.

Objectives To report the phenotypic, genetic findings and outcome of children with lupus manifestations associated with primary immunodeficiency diseases (PIDs). Methods Data are retrospectively collected on patients with lupus manifestations and PIDs seen between 1998 and 2019. Data comprised the clinical findings and genetic testing, the response to treatment and the accrual damage related to SLE. Results A total of 39 patients (22 female) were reviewed. Thirty-four patients had lupus manifestations and six patients with SLE-like manifestations. Genetic analysis was performed in 25 patients. Complement deficiency was the most frequent PIDs; 26 patients were C1q deficient, three patients had C3 deficiency, two patients had C4 deficiency and one patient with heterozygous C8b variant. The other seven patients had different PIDs genetic defects that include SCID caused by PNP deficiency, CGD, CVID (PIK3CD), IL-2RB mutation, DNase II deficiency, STAT1 mutation, ISG15 mutation and Griscelli syndrome type 3. Mucocutaneous lesions, arthritis and lung involvement were the main clinical features. 84.1% experienced recurrent infections. The mean accrual damage was 2.7 ± 2.2. There were five deaths because of infection. Conclusion This study suggests that patients with lupus manifestations and early onset disease, family history of SLE or recurrent infections should undergo immunological work-up and genetic testing to rule out PIDs.

Mucopolysaccharidosis (MPS) is a group of rare disorders that are characterized by intracellular accumulation of glycosaminoglycans with subsequent cellular and organ dysfunction. In the Middle East, especially Saudi Arabia, higher prevalence of MPS type I was observed compared to reported rates from European countries and the United States (U.S). The present work was developed as a part of the Saudi MPS Group’s efforts to address the current situation of MPS type I in Saudi Arabia and to reach a national consensus in the management of MPS type I. The first “Management of MPS Type I Advisory Board” meeting was held in Riyadh on May 2, 2019, to reflect the expert opinions regarding different aspects of MPS type I and develop this manuscript; eight consultants from different specialties (medical genetics, pediatric rheumatology, and pediatric endocrinology), representing six Saudi institutions, in addition to a global expert in genetics participated in the meeting.

Genetic defect of phosphatase and tensin homolog (PTEN) gene might play a role in B cell hyperactivity and result in the development of systemic lupus erythematosus (SLE), while transaldolase deficiency has a spectrum of clinical features including autoimmune endocrinopathy. Herein, we identified a novel phenotype in a girl presenting with clinical and laboratory findings consistent with SLE. Exome sequencing identified pathogenic heterozygous variant in PTEN gene (NM_000314: exon 6: c.518G C: p. R173P) and homozygous variant in TALDO1 gene (NM_006755: exon 6: c.793C del: p. Q265f). Our report highlights the association of PTEN mutation and autoimmunity and the possibility that transaldolase deficiency may be indirectly involved in the development of SLE.

Purine nucleoside phosphorylase (PNP) deficiency accounts for about 4% of severe combined immunodeficiency diseases. PNP deficiency is a variable disease with recurrent infections and neurodevelopmental delay. Autoimmunity and malignancy can still occur in one-third of patients. Case report. An 8-year-old Saudi female who was apparently healthy presented at the age of 7 years with confirmed systemic lupus erythematosus (SLE) and lupus nephritis that were poorly controlled with conventional therapy. She also had frequent sinopulmonary and varicella infections. Preliminary immunological workup showed severe lymphopenia and depressed lymphocyte proliferation assay. The uric acid was within normal levels at 179 μmol/L (normal range, 150 to 350 μmol/L) 6 weeks after blood transfusion. Genetic study revealed a homozygous missense mutation c.265G>A in the PNP gene, resulting in a substitution of glutamic acid to lysine at amino acid 89 of the encoded protein (E89K). The PNP serum level was 798 nmol/h/mg (normal level 1354 ± 561 nmol/h/mg) 6 weeks after blood transfusion. Hematopoietic stem cell transplantation (HSCT) was planned from a matched unrelated donor; however, she developed an EBV and varicella meningoencephalitis. Atypical malignant cells suggestive of lymphoma were discovered, likely induced by EBV, and suspicious lesions were shown on brain MRI and PET scan. Unfortunately, she passed away before HSCT due to multiorgan failure. This report emphasizes the challenges in recognizing PNP deficiency in a patient suffering from SLE.

Made available in DSpace on 2021-06-25T10:38:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Healthway Objective. To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. Methods. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. Results. A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. Conclusion. The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively. UOC Clinica Pediatrica e Reumatologia IRCCS Istituto Giannina Gaslini Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili (DiNOGMI) Università degli Studi di Genova Dipartimento di Epidemiologia e Biostatistica IRCCS Istituto Giannina Gaslini Faculty of Medicine Ain Shams University Pediatric Rheumatology Division Institute of Child Health Section of Pediatric Rheumatology SRCC Children's Hospital Rheumatology Division Pediatric Department Faculty of Medicine Ramathibodi Hospital Mahidol University Pediatric Rheumatology Clinic R G Kar Medical College Division of Rheumatology IRCCS Ospedale Pediatrico Bambino Gesù Division of Pediatric Rheumatology Institute of Child Health Sir Ganga Ram Hospital Faculty of Medicine Benha University Faculty of Medicine Alexandria University Faculty of Medicine Tanta University Faculty of Medicine Cairo University Pediatric Rheumatology Division Adolescent Health Care Unit Universidade do Estado do Rio de Janeiro Department of Internal Medicine Universidade Federal do Rio de Janeiro Servicio de Inmunología y Reumatología Hospital de Pediatría Garrahan Department of Clinical Sciences and Community Health University of Milan Division of Rheumatology University Hospital Meyer Rheumatology Division National Medical Research Center of Children's Health Sechenov First Moscow State Medical University Department of Immunology Rheumatology and Allergy Queen Rania Children's Hospital Saint-Petersburg State Pediatric Medical University UOC Pediatria a Media Intensità di Cure Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Rheumatology Department Faculty of Medicine Suez Canal University Department of Pediatrics King Faisal Specialist Hospital and Research Center Dipartimento Promise G. D'Alessandro Università degli Studi di Palermo Pediatric Department Hospital das Clínicas Botucatu Medicine University UNESP UOC Pediatria Servizio di Immuno-Reumatologia Pediatrica Azienda Ospedaliera Universitaria Gaetano Martino Messina UO Nefrologia e Reumatologia Pediatrica Azienda Ospedaliera Universitaria Gaetano Martino Department of Pediatrics School of Medicine Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Pediatric Unit Ospedale Vito Fazzi Pediatric Unit AON SS Antonio e Biagio e Cesare Arrigo Children's Hospital Pediatric Department Hospital das Clínicas Botucatu Medicine University UNESP

Juvenile idiopathic arthritis (JIA) is the most common chronic childhood arthritis; unfortunately, no diagnostic tool is available. Genetic disorders with musculoskeletal involvement that mimic chronic polyarthritis should be considered in the differential diagnostics of JIA. Normal inflammatory markers and characteristic radiological features are able to distinguish these disorders from JIA. Timely diagnosis of these disorders is crucial to offer the family proper genetic counseling and avoid inappropriate therapy. This review highlights selected noninflammatory disorders that often present with articular manifestations and that are often mislabeled as JIA. The focus is on the clinical, biochemical, and imaging features of these disorders.

Objective To report the clinical and genetic features of the first cases of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome in an Arab population and to compare them with patients of C1q deficient systemic lupus erythematosus (SLE). Materials and Methods This is a retrospective case series of patients with CANDLE syndrome and C1q deficient SLE seen at a single tertiary hospital. Medical records were reviewed for demographic data, clinical and laboratory features, histopathology and imaging findings, and response to therapeutic intervention. Descriptive data were summarized. Results Three patients from unrelated families fulfilled the clinical manifestations of CANDLE syndrome. The disease onset was within the first 4 months of age. Two patients had uncommon features including uveitis, pulmonary involvement, aseptic meningitis and global delay. Skin biopsy showed heterogeneous findings. Genomic DNA screening was homozygous for mutation in PSMB8, (NM_004159.4:c.212C>T, p.T71M) in one patient and inconclusive for the other two patients. The comparison group was three patients with familial C1q deficient SLE from three unrelated families, who were born to consanguineous parents with at least one affected sibling. They presented with extensive mucocutaneous lesions, discoid rash and scarring alopecia. They required frequent admissions due to infections. Conclusion This is the first report of CANDLE syndrome in an Arab population; our patients had heterogeneous phenotypic and genetic features with overlap manifestations with C1q deficient SLE. Both are monogenic interferonopathies. However, C1q deficient SLE had more systemic inflammatory disease.

This study describes the disease characteristics and outcome of Arab children with juvenile dermatomyositis (JDM) and compares the findings with other ethnicities. We retrospectively reviewed the hospital registries of the participating hospitals for children with JDM seen between 1990 and 2016 in three Arab countries. All patients fulfilled Bohan and Peter criteria for JDM, diagnosed before 14 years of age and were of Arab ethnicity. Clinical and laboratory features as well as the long-term outcomes including accrual disease damage were collected at the last follow-up visit. A total of 92 JDM patients (58 girls) were included. Mean age at the onset was 6 ± 3 years, with a mean follow-up duration of 5 ± 4.4 years. Forty-three patients (46.7%) had polycyclic disease course, 34 (36.9%) had a monocyclic course, while 15 (16.3%) had a continuous progressive course. Forty-five patients (48.9%) had arthritis, 14 (15.2%) patients had an upper airway and dysphagia, and 10 patients (10.9%) had lung involvement. Eight patients (8.7%) were admitted to the intensive care unit (ICU), 4 of them required mechanical ventilation. Methotrexate had been the most frequently used immunosuppressive drug (86%) and rituximab was used in eight patients. Additionally, 31 patients received IVIG. Most of the patients achieved a complete clinical response, but 16 ended up with permanent skin changes and 12 had a residual muscle weakness. Twenty-seven patients developed calcinosis. There were two deaths due to infection during the follow-up period. We report the largest phenotypic data on Arab children with JDM. Our patients have similar characteristics to previously described cohorts. Majority of the patients remained with inactive disease.

Objective To describe the physical, social, educational and employment status and clinical outcomes of patients with juvenile idiopathic arthritis (JIA) from multiplex families. Methods All familial JIA patients were treated and had regular follow-up between 1990 and 2015 at King Faisal Specialist Hospital and Research Center (KFSH-RC), Riyadh, were included. Demographic data, disease duration, active arthritis and articular and extra-articular damage at last follow-up visit were reviewed. Additionally, social, educational and employment history were obtained via personal or phone interviews. Results Twenty-three patients (20 females) belonging to 10 families were included. The mean age was 14.6 (±9) years with mean disease duration of 11.4 (±9) years and mean follow-up duration of 10.5 (±6). Fourteen patients had systemic JIA while eight patients had polyarticular subtype, and one patient had psoriatic arthritis. All patients received concomitant treatment. Twenty-one patients commenced biologic agents; treatment switched to another agent in all of them because of inadequate response. Most patients had progressive disease course. Twelve patients had active polyarthritis and 22 patients showed evidence of articular damage. All patients had raised inflammatory markers. Eighteen patients had short stature and 11 patients had delayed puberty. Two patients had lower limb lymphedema and one patient had a single kidney with refractory hypertension. Three patients underwent hip arthroplasty. Seventeen patients had satisfactory educational achievement and four patients were in employment. Two patients died due to infection. Conclusion Our results showed the largest familial clusters of JIA in the Middle East. Patients with familial JIA had refractory disease with progressive disease course.

Rheumatic fever is a rare yet serious condition develop as a consequence of throat infection caused by Streptococcus pyogenes. It is the leading cause for rheumatic heart disease. Rheumatic heart disease is a worldwide public health concern. It is a chronic condition that results in carditis, irreversible valve damage and heart failure in children and young adults living in low-income countries. The age of onset peaks between 5 and 15 years. Approximately, 3% of patients with untreated acute streptococcal sore throats develop rheumatic fever. Rheumatic fever and rheumatic heart disease can be prevented with appropriate antibiotics administration to prevent the progression of valve damage. The current use of primary and secondary prevention antibiotics in Saudi Arabia is not known. Therefore, this clinical practice guideline is developed, based on the best available evidence, to promote appropriate antibiotics secondary prophylaxis use for prevention of rheumatic heart disease.

Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is an autosomal recessive disorder caused by mutations inConsecutive patients with CACP syndrome were prospectively evaluated at the enrollment and 3 months after the right knee injection with yttrium-90. The outcome variables were patient/parent and physician's global assessment measured by a 3-point scale, right knee swelling and range of motion on a 3-point scale, in addition to magnetic resonance imaging (MRI) assessment of the right knee for bone, cartilage, fluid, synovial hypertrophy and soft tissue changes.Six (three boys, three girls) patients with a mean age of 12 years and mean follow-up duration of 8.5 years completed a single right knee intra-articular yttrium-90 injection with 5 mCi. The procedure was well tolerated without adverse events apart from mild and transient joint pain in two patients. There was a minimal radioisotope leakage to soft tissue in two patients. During the 3-month follow-up interval, there was no improvement in the outcome variables. Patients and parents did not notice favorable therapeutic effects and global physician assessment was unsatisfactory. There was no difference in knee joint swelling or range of motion. Furthermore, MRI findings were unchanged. However, there was a minimal increase in synovial fluid post injection.Yttrium-90 radiosynovectomy seems to be a safe and well tolerated procedure, however, it did not show a beneficial therapeutic effect in arthropathy of CACP syndrome with the given dosage and interval. Studies including a larger number of patients and probably repeated injections are needed to derive satisfactory results about the effectiveness of yttrium-90 in CACP syndrome patients.Amaç: Kamptodaktili-artropati-koksa vara-perikardit (CACP) sendromu eklem ve tendon yüzeylerinin ana lubrikanı olan proteoglikan 4’ü kodlayan PRG4 genindeki mutasyonlara bağlı bir otozomal resesif hastalıktır. Eklemde efüzyon ve sinovyal hipertrofi ile karakterize non-enflamatuvar bir artropatidir. Henüz bu hastalığın etkin bir tedavisi yoktur. Amacımız CACP sendromlu hastaların artropatisinde yttrium-90 radyosinovektominin etkinliğini araştırmaktır. Yöntem: CACP sendromu tanısı alan ardışık hastalar tanı anında ve sağ dize yttrium-90 enjeksiyonu uygulanmasından 3 ay sonra prospektif olarak değerlendirildiler. Sonuç değişkenleri 3-puanlı skala üzerinden hasta/ebeveyn ve doktor genel değerlendirmesi, 3-puanlı skala üzerinden sağ diz ödemi ve hareket aralığı ve kemik, kıkırdak, sıvı, sinovyal hipertrofi ve yumuşak doku değişiklikleri açısından sağ diz manyetik rezonans görüntülemesi (MRG) idi. Bulgular: Ortalama yaşı 12, ortalama takip süreleri 8,5 yıl olan altı hastaya (üç erkek, üç kız) tek sefer sağ dize 5 mCi intra-artiküler yttrium-90 enjeksiyonu uygulandı. İşlem iki hastada hafif ve geçici eklem ağrısı dışında herhangi bir komplikasyon olmadan iyi tolere edildi. İki hastada yumuşak dokuya minimal radyoizotop kaçağı oldu. Üç aylık takip süresince sonuç değerlerinde iyileşme olmadı. Hastalar ve ebeveynleri olumlu terapötik etki fark etmediler ve genel doktor değerlendirmesi tatmin edici değildi. Diz eklemi ödemi ve hareket aralığında değişiklik yoktu. MRG bulguları değişmedi, ancak enjeksiyon sonrası sinovyal sıvıda minimal artış saptandı. Sonuç: Yttrium-90 radyosinovektomi güvenli ve iyi tolere edilen bir işlem olarak görülmektedir, ancak verilen doz ve sürede CACP sendromlu hastaların artropatisinde yararlı bir terapötik etki göstermemiştir. Daha fazla hasta içeren ve muhtemelen tekrarlayan enjeksiyonların uygulandığı çalışmalar yttrium-90’ın CACP sendromlu hastalardaki etkinliği ile ilgili gerekli sonuçları sağlayabilir.

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

Objective: The objective of the study is to report the compliance with childhood-onset systemic lupus erythematosus-quality indicators (cSLE-QIs) in a Saudi Tertiary Childhood Lupus Clinic. Methods: In this cross-sectional, observational study, charts of patients with cSLE followed regularly between January 2010 and December 2019 at King Faisal Specialist Hospital and Research center, Riyadh, were reviewed. Data were collected at the last follow-up visit comprising the compliance with the quality of medical care of patient with cSLE using cSLE-QIs, which capturing diagnostic testing, lupus nephritis, medication, bone health, ophthalmological assessment, vaccination, and transition. Pregnancy domain and smoking cessation were not measured in this study. Results: A total of 66 (58 females) cSLE patients were assessed. The median age at disease onset was 10 (interquartile range [IQR]: 7.0–11.0) years, and the median disease duration was 4 (IQR: 3.0–6.0) years. Most of the patients had nephritis (69.7%), while cardiovascular and neuropsychiatric features were 37.7% and 18.8%, respectively. The adherence with cSLE-QIs differed markedly; performance of diagnostic testing, medication management including corticosteroid weaning, and bone health was high while the compliance with flu vaccine, eye screening, photoprotection, and education about cardiovascular risk was lower. There was a noticeable variability between the international childhood lupus clinics. Conclusion: Providing cSLE patients with a high quality of health care is challenging without the proper guidance. Hopefully, these findings will enhance the adherence to cSLE-QIs and increase the likelihood of the desired outcome.

Background and objectives: To examine the frequency of endocrinopathies in children with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). Design and setting: A cross-sectional study. Patients and methods: A study was conducted in Saudi children with SLE and JIA who were seen at King Faisal Specialist Hospital and Research Centre, Riyadh, between September 2013 and April 2015. All enrolled patients completed the clinical evaluation, which included information about family history of autoimmune disease, growth parameters and tanner stage, as well as the following assessments: vitamin D profile (parathyroid hormone and 25-OH vitamin D levels), TSH, FT4 and total T3, thyroglobulin antibodies, thyroperoxidase antibodies, random blood sugar, HbA1C, IGF1, IGFBP-3, LH, and FSH. Results: A total of 42 patients, 22 with JIA and 20 with SLE, were included in the study. The mean participant age was 12.2 ± 5.3 years with a mean disease duration of 3.2 ± 3.4 years. Female gender was predominant (17 SLE, 13 JIA) in the patient population. Fifteen patients (35.7%) presented with a family history of autoimmune disease. The most frequently detected endocrinopathies were vitamin D insufficiency (35%) and thyroid disease (31%). Eight JIA patients and 7 SLE patients exhibited low vitamin D levels; 10 patients presented with hyperparathyroidism. Thyroid dysfunction was observed in 13 patients (8 SLE, 5 JIA), and 2 patients were found to be euthyroid (normal TSH, FT4) with positive thyroid autoantibodies. Furthermore, 7 patients presented with subclinical hypothyroidism (high TSH, normal FT4), and 4 patients presented with overt hypothyroidism (high TSH, low FT4). Seven patients (4 SLE and 3 JIA) presented with short stature due to growth hormone insufficiency (low IGF1, IGFBP-3). Two patients exhibited delayed puberty accompanied by low LH levels. Diabetes mellitus was more frequently observed in patients with JIA (4 patients) than in patients with SLE (1 patient). Conclusion: Our findings demonstrated that coexistence of endocrinopathies is not uncommon in children diagnosed with JIA and SLE. Abnormal thyroid function occurs frequently and at a similar rate in children diagnosed with SLE and JIA. Thus, screening for endocrinopathies, namely thyroid disease, during the assessment of childhood SLE and JIA is worth consideration.

Background: Conduction disturbances other than heart block related to neonatal lupus are rarely explored and reported in children with systemic lupus erythematosus (SLE). Objective: To report the electrocardiographic (ECG) abnormalities in children with SLE and assess whether anti-Ro/SSA antibodies and hydroxychloroquine are associated with the rhythm disturbances. Methods: This cross-sectional retrospective study comprised patients with SLE who had regular follow-up in the Pediatric Lupus Clinic at King Faisal Specialist Hospital and Research Center-Riyadh. All enrolled patients were evaluated with regard to demographics, age at disease onset, disease duration, clinical and laboratory variables including autoantibodies, disease activity using SLEDAI disease activity index, and medications. An expert pediatric cardiologist reviewed the ECG findings of all enrolled patients independently without knowing the clinical status of the patients. Results: A total of 41 (35 females, 6 males) unselected patients with SLE with a mean age of 12.8 (2.5) years and mean follow-up duration of 4 (3) years completed the evaluation. The most frequent manifestations were renal disease (65.8%), followed by musculoskeletal (46.3%), hematological (41.5%), and cardiac involvement (19.5%). Thirty-two had active disease (SLEDAI >4), and the mean of SLEDAI was 9.2 (6.2). ECG abnormalities were seen in 12 patients (29.3%); these changes included ST-T changes (9.8%), right bundle branch block (7.3%), 4 prolonged QT interval (9.8%), and low QRS voltage (2.4%). Thirty-seven (90.3%) patients were on hydroxychloroquine, and 9 patients (22%) had positive anti-Ro/SSA antibodies. ECG abnormalities were associated significantly with anti-Ro/SSA antibodies (P

Background: Children with lupus nephritis particularly, diffuse proliferative and membranous glomerulonephritis, may necessitate potent immunosuppressive medications and occasionally combined therapy. Objective: To report the beneficial effects of tacrolimus (TAC) in children with refractory lupus nephritis from a single tertiary pediatric rheumatology clinic. Methods: This is a retrospective case series of children with refractory lupus nephritis treated with TAC after failure of aggressive immunosuppressive treatment. All patients were evaluated at the time of initiation of TAC and at last follow-up visit by assessing the following response parameters: cSLE Disease Activity Index (SLEDAI), urine protein/creatinine ratio, urine sediments, serum albumin, complement (C3 and C4), anti-double-stranded DNA (dsDNA) antibody levels, and renal function assessed by glomerular filtration rate (eGFR). Results: Three children (two girls and one boy) with lupus nephritis and persistent nephrotic-range proteinuria failed prednisone treatment as well as sequential treatment of cyclophosphamide, mycophenolate mofetil (MMF), and rituximab. When TAC was administered along with MMF and prednisone, all patients showed improvement in response parameters, namely, SLEDAI, serum albumin, and proteinuria, and prednisone doses were significantly weaned off and discontinued in two patients. However, eGFR remained stable during the treatment period. TAC was well tolerated, and no adverse effects were observed. Conclusion: TAC combined with MMF can be considered as an alternative therapeutic option for children with refractory lupus nephritis particularly those with persistent nephrotic-range proteinuria. Keywords: Systemic lupus erythematosus, Tacrolimus, Lupus nephritis, Nephrotic syndrome

Made available in DSpace on 2018-12-11T16:53:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01 Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA. Clinica Pediatrica e Reumatologia Università degli Studi di Genova Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Department of Pediatrics Asklepios Klinik Sankt Augustin Department of Pediatric and Adolescents Medicine University Hospital of Cologne Division od Rheumatology University of Toronto Hospital for Sick Children Division of Rheumatology Cincinnati Children's Hospital Medical Center University of Cincinnati Department of Paediatric Immunology Wilhelmina Children's Hospital University Medical Center Utrecht University of Utrecht Rheumatology Unit Department of General Medicine Royal Children's Hospital Murdoch Children's Research Institute Department of Pediatric Rheumatology King Faisal Specialist Hospital and Research Center Alfaisal University Division of Pediatric Rheumatology Hospital Sant Joan de Déu Universitat de Barcelona Department of Allergology Rheumatology and Clinical Immunology University Medical Center Ljubljana Medical Faculty University of Ljubljana Division of Rheumatology Western University Children's Hospital London Health Sciences Centre Institute of Translational Medicine University of Liverpool Alder Hey Children's NHS Foundation Trust Rheumatology Department Hospital General de México Eduardo Liceaga Pediatric Rheumatology Azienda Ospedaliero Universitaria Meyer Division of Rheumatology Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù Pediatric Rheumatology and Immunology University of Muenster Department of Pediatrics Nippon Medical School Institute of Clinical Medicine Children's Hospital Helsinki University Hospital Paris-Descartes University IMAGINE Institute RAISE 22 National Reference Centre Necker-Enfants Malades Hospital Assistance Publique Hopitaux de Paris Clinica Pediatrica e Reumatologia Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini Servicio de Inmunología y Reumatología Hospital de Pediatría Garrahan Reumatologia Pediátrica São Paulo State University (UNESP) Department of Rheumatology ISIC Superspeciality Hospital Sir Ganga Ram Hospital Red Cross War Memorial Children's Hospital University of Cape Town Pediatric Rheumatology Seattle Children's Hospital and Research Center University of Washington Pediatric Rheumatology Unit Department of Pediatrics Meir Medical Center Tel Aviv University Sackler School of Medicine Division of Rheumatology Department of Medicine3 Medical University of Vienna Reumatologia Pediátrica São Paulo State University (UNESP)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Arabic language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic and clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 100 JIA patients (27.0% systemic JIA, 23.0% oligoarticular, 25.0% RF negative polyarthritis, and 25.0% other categories) and 100 healthy children, were enrolled in one paediatric rheumatology centre. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed satisfactory psychometric performances. In conclusion, the Arabic version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research.

Objectives: Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by sterile bone osteolytic lesions. The aim of this study was to evaluate the demographic data and clinical, instrumental and therapeutic features at baseline in a large series of CNO/CRMO patients enrolled in the Eurofever registry.Methods: A web-based registry collected retrospective data on patients affected by CRMO/CNO. Both paediatric and adult centres were involved.Results: Complete baseline information on 486 patients was available (176 male, 310 female). The mean age of onset was 9.9 years. Adult onset (>18 years of age) was observed in 31 (6.3%) patients. The mean time from disease onset to final diagnosis was 1 year (range 0-15). MRI was performed at baseline in 426 patients (88%), revealing a mean number of 4.1 lesions. More frequent manifestations not directly related to bone involvement were myalgia (12%), mucocutaneous manifestations (5% acne, 5% palmoplantar pustulosis, 4% psoriasis, 3% papulopustular lesions, 2% urticarial rash) and gastrointestinal symptoms (8%). A total of 361 patients have been treated with NSAIDs, 112 with glucocorticoids, 61 with bisphosphonates, 58 with MTX, 47 with SSZ, 26 with anti-TNF and 4 with anakinra, with a variable response.Conclusion: This is the largest reported case series of CNO patients, showing that the range of associated clinical manifestations is rather heterogeneous. The study confirms that the disease usually presents with an early teenage onset, but it may also occur in adults, even in the absence of mucocutaneous manifestations.

IntroductionAutoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting.MethodsThe ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an ‘observer-nested-within-subject’ design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach’s alpha.ResultsThe ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items.ConclusionThe ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.