Consensus clinical approach for a newly diagnosed systemic juvenile idiopathic arthritis among members of the pediatric rheumatology Arab group.

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.

Familial aggregation of juvenile idiopathic arthritis with other autoimmune diseases: Impact on clinical characteristics, disease activity status and disease damage.

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.

Cumulative Damage in Juvenile Idiopathic Arthritis: A Multicenter Study From the Pediatric Rheumatology Arab Group.

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.

The Arabic version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

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.

Phenotypic characteristics and outcome of juvenile dermatomyositis in Arab children.

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.

Cardiovascular complications in paediatric-onset systemic lupus erythematosus in Saudi Arabian patients.

OBJECTIVES: To assess the prevalence and types of cardiovascular complications in Saudi patients with paediatric-onset systemic lupus erythematosus (pSLE). METHODS: Retrospective record review of pSLE patients following from January 2014 to September 2015 at the rheumatology clinic of King Abdul-Aziz University Hospital, Jeddah. Laboratory data such as C-reactive protein (CRP), antinuclear antibodies (ANA), anti-double stranded DNA antibody (anti-dsDNA), C3 and C4 complements, were collected. Cardiac evaluation included chest x-ray, electrocardiogram (ECG), and echocardiography, along with estimation of SLE activity by calculating the SLE Disease Activity Index (SLEDAI) score according to SELENA modification. RESULTS: Forty-six cases of pSLE were included (91.3% females, mean±SD age at diagnosis=10.53±2.28 years). Prevalence of cardiac manifestations was 47.8%; the most frequent of which were valvular heart diseases diagnosed in 16 (34.8%) cases, followed by pericarditis in 6 (13%) cases. Of the 16 valvular diseases, tricuspid and pulmonary valves were involved in 9 and 8 cases, respectively. Cardiac involvement was silent in 36.4% and occurred as an initial presenting symptom of SLE in 9.1% cases. Biologically, patients with cardiac involvement had higher levels of CRP and anti dsDNA, and lower levels of complement C3 compared to patients with no cardiac involvement; while high SLE activity was the only significant predictor for cardiac involvement (beta=0.654; p=0.020). CONCLUSIONS: Cardiac complications are common in Saudi children with pSLE and are asymptomatic in 1 out of 3 times. They are predicted by high SLE activity and associate with high anti-dsDNA and CRP and low C3 levels.

The Pattern of Juvenile Idiopathic Arthritis in a Single Tertiary Center in Saudi Arabia.

Introduction. Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children. Our aim is to describe demographic, clinical, and laboratory characteristics and treatment of JIA patients followed up in Pediatric Rheumatology clinic in a tertiary center in Saudi Arabia. Methods. Medical records of all patients who are followed up between January 2007 and January 2015 were retrospectively reviewed. Data were collected about demographic, clinical, and laboratory features and treatment. Results. Total patients were 82, males were 31 (37.8%), and mean age of JIA onset was 7.1 ± 3.6 yr. Mean follow-up duration was 2.67±1.6 yr. Systemic onset JIA (SoJIA) was the commonest (36.5%), followed by polyarticular in 29.2% and oligoarticular in 28%. Large and small joints are involved in 76 (92%) and 30 (36.6%), respectively. Main extra-articular feature was fever in 34 (41.4%). Uveitis was diagnosed in 7 (8.5%) and in 5 (21.7%) of oligoarticular JIA. Anemia was found in 49 (59.7%), high ESR in 45 (54.8%), and leukocytosis and thrombocytosis in 33 (40.2%). Positive ANA was found in 30 (36.5%) mainly in oligoarticular subtype as 12 (52%) patients (out of 23) had this positive test. 9 patients (10.9%) required NSAIDs only, 6 patients (7.3%) required NSAIDs and intra-articular steroids only, and 19 (23%) required NSAIDs, methotrexate, steroids, and biologics. Conclusion. SoJIA is the most common JIA subtype in our study. A population based rather than a single center study will give more details about JIA characteristics in Saudi Arabia.

Familial aggregation of Crohn's disease and necrotizing sarcoid-like granulomatous disease.

Granulomatous inflammatory diseases are disorders of an undetermined etiology, affecting different organs and having a diverse clinical course. Familial aggregation of these disorders is being reported increasingly, most commonly familial Crohn's disease. We described the coexistence of Crohn's disease and necrotizing sarcoid-like granulomatous disease in two siblings from a first-degree consanguineous Saudi family. The first child presented with recurrent abdominal pain associated with bloody stool and arthritis, whereas the second child presented with fever of unknown origin and lymphadenopathy as well as hepatomegaly without gastrointestinal tract disease. They are phenotypically different; however, they share a novel risk locus and allele. This report supports the heritability and familial aggregation of granulomatous inflammatory diseases and suggests that one causal mutation underlies both Crohn's disease and necrotizing sarcoid-like granulomatous disease.

Oligoarticular juvenile idiopathic arthritis among Saudi children.

BACKGROUND AND OBJECTIVES: Oligoarticular juvenile idiopathic arthritis (JIA) is the most frequent chronic inflammatory rheumatic condition in children. We aimed to describe the clinical and serological profile of Saudi patients with oligoarticular JIA. DESIGN AND SETTINGS: Hospital-based retrospective chart review of all children diagnosed with oligoarticular JIA and followed up at King Abdulaziz University Hospital between 1998 and 2012. PATIENTS AND METHODS: We reviewed the medical files of children with oligoarticular JIA and recorded the gender, age at presentation and diagnosis, clinical presentation, laboratory and radiological investigations, treatment administered, and disease complications. Descriptive statistics was performed using SPSS (version 20, SPSS Inc., Chicago, IL, USA). RESULTS: We enrolled 37 patients with JIA, of which 24 (64.9%) were girls. The mean age of the patients at presentation was 6.9 years, while the mean age at diagnosis was 7.2 years. A total of 31 patients (83.8%) presented with joint pain, and 36 (97.3%) had a swelling; 19 patients (51.4%) had a high erythrocyte sedimentation rate (ESR) at first presentation (mean, 41.8 [25.4] mm/h). ANA was positive in 15 patients (40.5%). The following treatments were administered: naproxen in 37 patients (100%), intra-articular corticosteroids in 12 cases (32.4%), methotrexate in 14 patients (37.8%), and adalimumab in 5 patients (13.5%). During follow-up, the following were documented: limited range of motion (n=15; 40.5%), deformity (n=5.4%), contracture (n=1; 2.7%), leg-length discrepancy (n=9; 24.3%), and anemia (n=7; 18.9%). CONCLUSION: Oligoarticular JIA is more frequent in females, and it shows a predilection for the knees. Initially, many patients presented with high ESRs, and they were antinuclear antibody positive. Early diagnosis and aggressive treatment resulted in a low rate of arthritis and extra-articular manifestations in our cohort.

Clinical and laboratory variables of childhood systemic lupus erythematosus in western province of Saudi Arabia.

To study the demographic, clinical, laboratory features, treatment and outcome of childhood systemic lupus erythematosus (SLE) in western province of Saudi Arabia. Children with SLE who were diagnosed at King Abdulaziz University Hospital, Jeddah, between March 1998 and October 2008 were included. Charts of all patients were reviewed retrospectively for clinical and laboratory features, treatment and outcome. There were 28 girls and 2 boys, with a mean age of 10.5 years (range 5-18). The female:male ratio was 14:1. Constitutional symptoms represent significant symptoms. Hematological manifestations were the most frequent finding (86.7%) at the time of diagnosis followed by arthritis and nephritis (73.3%). The malar rash represents the most common skin manifestation (46.7%). Discoid lupus was very rare. Neurological symptoms were seen in 30%, while cardiac and pulmonary involvement was uncommon. All patients had positive ANA and 90% of them had high anti-ds DNA. All patients were treated with steroids and hydroxychloroquine and 26 patients received immunosuppressive therapy. Three patients died due to severe infection; massive brain infraction and severe lung disease (one in each). Twenty-seven patients are alive in stable condition. Clinical manifestations and laboratory abnormalities were similar to previously reported series. This report confirms that SLE has comparable findings among children from different ethnicities.

Neonatal screening of glucose-6-phosphate dehydrogenase deficiency in Yanbu, Saudi Arabia.

OBJECTIVE: To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the population tested, and to evaluate the prevalence of neonatal jaundice in newborns with G6PD deficiency. METHODS: Cord blood of all babies born between October 1996 and October 1998 at the Royal Commission Medical Center in Yanbu, Saudi Arabia, was screened for G6PD deficiency by fluorescent spot test. The results of screening of cord blood samples were reported to the physician in charge, and also placed on the files of the babies and their mothers. These babies were observed for 72 h and discharged if no jaundice developed. RESULTS: During this two-year period, 2,505 neonatal cord blood samples from 1,278 boys and 1,227 girls were screened for G6PD. There were 50 positive results for G6PD deficiency (39 boys and 11 girls), and the prevalence was estimated to be around 2%. The sex-specific prevalence for boys was 3.05%, and for girls 0.9%. Male to female ratio was 3:1. Neonatal jaundice developed in six (12%) babies, five male and one female. All were treated with phototherapy and discharged within one week of birth. CONCLUSION: The prevalence of G6PD is relatively high in Yanbu. Routine neonatal screening in areas with a high prevalence of G6PD in Saudi Arabia is justifiable.

Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis.

OBJECTIVE: To determine whether levels of soluble tumor necrosis factor receptor 55 (sTNFR55), sTNFR75, and interleukin 1 receptor antagonist (IL-1Ra) can differentiate different subtypes of juvenile rheumatoid arthritis (JRA), and to determine if the levels of these proteins correlate with disease activity. METHODS: Serum sTNFR (55 and 75) and IL-1Ra levels were measured by ELISA in 34 patients with JRA and these values were correlated with disease subtype and activity. RESULTS: Serum sTNFR55 levels were significantly elevated in patients with systemic onset JRA (SoJRA) (mean +/- 2 SD, 2.9 +/- 1.8 ng/ml) (p < or = 0.05) compared to rheumatoid factor positive (RF+) polyarticular JRA (2.1 +/- 0.6), RF-polyarticular JRA (1.5 +/- 0.6), and pauciarticular JRA (1.4 +/- 0.4). There was a trend for elevation of sTNFR75 levels in patients with SoJRA compared to other subtypes (p = 0.08). More patients had elevated levels of sTNFR75 than sTNFR55 (15 vs 7). This was true for all subsets (SoJRA 7 vs 5; polyarticular JRA 4 vs 2; and pauciarticular JRA 4 vs 0). In contrast to sTNFR, IL-1Ra levels were significantly elevated in RF+ polyarticular JRA compared to the other subgroups (p < or = 0.001). We found statistically significant Pearson correlations between (1) sTNFR75 and hemoglobin concentration: and (2) IL-1Ra and number of active joints and number of joints with effusions. CONCLUSION: The increased serum level of sTNF receptors in SoJRA suggests that TNF is likely more important than IL-1 in systemic inflammation and in particular in SoJRA. Conversely, IL-1 is likely more important in the inflammatory arthritis of JRA and in particular in the pathogenesis of RF+ polyarticular JRA. Our results suggest that cytokines have differing roles in JRA subtypes and likely reflect JRA subtype heterogeneity.

Pattern of clinical features of Kawasaki disease.

OBJECTIVE: To study the pattern of clinical features, complications, and outcome of Kawasaki disease among Saudi children. METHODS: Medical records and referral letters of all children (1997 through to 2001) diagnosed with Kawasaki disease were reviewed. This study was carried out at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. Collected data included clinical features, laboratory results, echocardiogram findings, therapy, complications and outcome. RESULTS: Thirteen children (10 boys, 3 girls) were reviewed, age range from 0.3 to 7 years (mean 3.4 years). Nine patients met 5 out of 6 criteria for the diagnoses of Kawasaki disease and 4 met 4 out of 6 criteria and coronary aneurysm. Thirteen patients had fever and skin rash for more than 5 days, 12 had extremity and oral mucus changes, 9 had bilateral conjunctivitis, and 7 had cervical lymph node enlargement. Other associated clinical features include diarrhea, and aseptic meningitis in 3 patients, ischemia of the fingers and toes in 2, arthritis in 2, arthralgia in one, seizure and pneumonia in one. Hepatosplenomegaly, pancytopenia and elevated liver enzymes in one, hepatomegaly and normal liver enzymes in 2 patients. Cardiac complication seen in 4 patients (30%), all of them were boys, 3 had coronary artery aneurysm (4-7 mm) and one had giant aneurysm (9mm), one of the 3 patients had axillary and subclavian artery aneurysm as well. Two out 4 patients were treated with intravenous immunoglobulin and aspirin within 10 days of illness and one was treated on day 21 and one was treated with aspirin alone. Aneurysmal changes persisted in 3 patients and resolved in one patient who was treated early. Extra-cardiac complications include reaction to intravenous immunoglobulin, coagulopathy, thrombocytopenia, hemophagocytic syndrome and ischemia of peripheral extremities. CONCLUSION: Our observation showed a high percentage (30%) of coronary aneurysm and unusual complications, this is most likely due to delay in the diagnosis and initiation of treatment.