Kawarabi: Administrative Structuring of a Multicenter Research Collaborative to Study Kawasaki Disease in the Arab Countries.

Kawasaki disease (KD), the leading cause of acquired heart disease in children in developed countries, merits conducting detailed studies in Arab countries. We introduce Kawarabi, as a multicenter research collaborative effort dedicated to improving diagnosis, care, and outcome of children and adults with KD in the Arab world. During the COVID-19 pandemic, there emerged a new multisystem inflammatory syndrome in children; a disease similar to KD. This highlighted the challenges that Arab physicians face in diagnosing and managing children with KD and KD-like illnesses. Kawarabi brings together experts in North America and Arab nations to study this family of diseases in a not-for-profit, voluntary scientific collaborative setting. Bylaws addressing the vision, objectives, structure, and governance of Kawarabi were established, and vetted by the 45 organizing members in 2021. An initial scientific publication showed evidence of a decreased level of awareness of the disease in the general population, as well as the lack of access to resources available for physicians caring for children with KD in Arab countries. Kawarabi has since held several educational webinars and an inaugural yearly meeting. The groundwork for future initiatives targeted at increasing awareness and understanding of the management and the long-term outcomes of children with KD in the region was established. Data on KD in the Arab world are lacking. Kawarabi is a multicenter research collaborative organization that has the unique resources, diversified ethnic makeup, and energy, to accomplish significant advances in our understanding and management of KD and its variants.

Efficacy of Anakinra Treatment in two Moroccan Patients With Mevalonate Kinase Deficiency.

Mevalonate kinase deficiency (MKD) is a rare hereditary autoinflammatory disease, with a widely variable clinical spectrum. It is characterized by febrile recurrent episodes and systemic inflammation. Data on therapeutic options for MKD are still limited and remain unknown in our country. We report Moroccan cases with MKD referred in our unit and treated with Anakinra, an interleukin-1 receptor antagonist. Through this study, we evaluate the efficacy of this bioagent, in our 2 MKD patients, in whom Anakinra has shown a complete clinical remission, with a remaining mild inflammation for one case, and normalization of growth with rare episodes of cervical adenopathies for the second case. Our experience provides an additional argument supporting the efficacy of Anakinra treatment, demonstrated previously but still lacks of objective data.

Access to Care and Therapy for Kawasaki Disease in the Arab Countries: A Kawasaki Disease Arab Initiative (Kawarabi) Multicenter Survey.

Kawasaki Disease (KD) is still the most common acquired heart disease in children below the age of five years; it has been well described in the developed world; however, data from the Arab world are limited to case reports or single-center case series. In an effort of optimizing KD research in the Arab world, a group of physicians and researchers established the KD Arab Initiative (Kawarabi) in 2021, and published the first survey, which showed disparities in the availability of intravenous immunoglobulin (IVIG); this had prompted Kawarabi to assess the access to care and therapy of KD patients in Arab countries. A 32 structured questions survey was conducted in thirteen Arab countries and addressed KD patients' access to healthcare in urban and rural settings. The survey results showed that access to care was uniform across large, mid-size cities and rural areas in 7/13 (54%) countries, while in 6/13 (46%) countries, it was in favor of large and mid-size cities over rural areas. The quality of medical services received by children with KD in large cities was rated as excellent in 6/13 or good in 7/13 countries compared to fair in 4/13 or poor in 4/13 countries in rural areas. Availability of IVIG was limited (23%) in mid-size cities and almost impossible (23%) in rural areas. The KD patients in mid-size cities and rural areas have limited access to standard healthcare in the Arab world. This survey laid the foundation for future Kawarabi endeavors to improve the care of children with KD.

Factors associated with poor prognosis of hip arthritis in juvenile idiopathic arthritis: Data from the JIR cohort.

OBJECTIVES: Hip involvement remains a predictor of severe juvenile idiopathic arthritis (JIA) course and carries a high risk of disability. This study aims to determine the factors of poor prognosis of hip involvement in patients with JIA and to assess the treatment response. METHODS: This is a multicenter observational cohort study. Patients were selected from the JIR Cohort database. Hip involvement was defined as clinically suspected and confirmed by an imaging tool. Follow-up data were collected during 5 years. RESULTS: Among the 2223 patients with JIA, 341(15%) patients had hip arthritis. Male gender, enthesitis-related arthritis, and North African origin were factors associated with hip arthritis. Hip inflammation was associated with disease activity parameters during the first year, particularly Physician Global Assessment, joint count, and inflammatory marks. Structural hip progression was associated with early onset of the disease, a longer time to diagnosis, geographic origin, and JIA subtypes. Anti-TNF therapy was found to be the only treatment able to effectively reduce structural damage progression. CONCLUSION: The early onset diagnostic delay, origin, and systemic subtype of JIA predict a poor prognosis of hip arthritis in children with JIA. The use of anti-TNF was associated with a better structural prognosis.

Spectrum of auto-inflammatory diseases in Morocco: a monocentric experience.

Objective: Auto-inflammatory diseases (AIDs) result from mutations in genes of the innate immune system leading to periodic multisystemic inflammation. We aimed to describe the clinical, biological and molecular features (when available) and outcomes of Moroccan patients with AIDs. Methods: Patient data were collected retrospectively and analysed over a 13-year period. Results: Among 30 patients, 60% had FMF, 16% mevalonate kinase deficiency (MKD) and 24% other AIDs. The mean age at first consultation was 6.9 years, and the mean diagnostic delay was 3 years. Consanguinity was reported in 16 cases. IgA vasculitis was associated with 33% of FMF patients, in whom the main clinical features were fever (88.8%), abdominal pain (100%), arthralgias (88.8%) and arthritis (50%), and the most frequent mutation was M694V (66%). All FMF patients were treated with colchicine. Most MKD patients were confirmed by elevated urinary mevalonic acid levels, and four of five MKD patients received targeted therapy. Chronic recurrent osteomyelitis patients were confirmed by radiological and histological analysis. Two cases of Marshall syndrome were diagnosed according to validated criteria. A case of familial pustular psoriasis was diagnosed based on histological analysis and a patient with Muckle-Wells syndrome by clinical features. The outcome was favourable in 76%, partial in 13%, and three deaths were reported. Conclusion: FMF and MKD are the most reported diseases. AIDs are probably underestimated because they are unknown to clinicians. The aim of this work is to raise awareness among paediatricians about AIDs and create a network for best practice.

Biotherapy in juvenile idiopathic arthritis Moroccan patients: a single-center experience.

In this study, we aimed to evaluate the clinicobiological findings and the biotherapy treatment response of Moroccan patients with juvenile idiopathic arthritis (JIA), and compare our results with those of populations of the same or different ethnicity. This retrospective cross-sectional study included patients aged 1-14 years, diagnosed between 2003 and 2018 with JIA according to the International League of Associations for Rheumatology (ILAR) 2004 revised criteria, who received biologics and who followed up during the year 2018 in the day hospital of our single-center tertiary pediatric rheumatology unit. Among 59 patients, 53% had systemic JIA, 29% seronegative polyarticular JIA, 8% arthritis-related enthesitis, 5% seropositive polyarticular JIA, 3% oligoarthritis and 2% psoriatic arthritis. Tocilizumab was the most prescribed biologic (34 patients), followed by Etanercept (25 patients), Adalimumab (6 patients), Anakinra (3 patients) and biosimilar Infliximab (3 patients). Eleven patients switched biologics. Erythrocyte sedimentation rate, number of active joints and the Juvenile Arthritis Disease Activity Score 27 (JADAS 27) decreased significantly at month three for 56 patients. These results were maintained at the last visit for 31 patients, while there was a slight worsening in 15 of them and no assessment in 13 patients due to lack of data. At the end of the evaluation, 39% of the patients were exclusively on biotherapy, while 61% were still on other disease-modifying antirheumatic drugs (DMARDs). Twenty-eight patients developed lymphopenia, 4 patients had elevated transaminases, 4 patients developed moderate infection, and 2 patients developed macrophage activation syndrome. To the best of our knowledge, this is the first Moroccan study on biotherapy in JIA. Our study population was characterized by a male predominance, a high frequency of the systemic form and a low percentage of positive antinuclear antibodies. We have shown that in the era of biologics, only 67.4% patients are nearly disease-free at the end of the study with a real risk of side effects. Although effective, biotherapy must be closely monitored because of potentially severe side effects, especially with Tocilizumab use.

Dilated cardiomyopathy: An unusual and severe condition in juvenile systemic lupus erythematosus.

BACKGROUND: Systemic juvenile lupus erythematosus can affect any organ including the heart. While pericarditis and endocarditis are the most common cardiac complications, dilated cardiomyopathy remains rare. We report the full recovery of dilated cardiomyopathy in a girl with juvenile lupus. CASE PRESENTATION: A 7-year-old girl presented with persistent fever, weight loss, alopecia, positive anti-lupus antibodies, and decreased complement. Examination found dyspnea, tachycardia, and hypotension. Chest X-ray revealed an enlarged cardiac silhouette, and echocardiography showed a left ventricular ejection fraction of 35%. After excluding other causes, systemic lupus erythematosus related dilated cardiomyopathy was selected. Heart failure treatment, Prednisone, and hydroxychloroquine were prescribed. On day three, she developed macrophage activation syndrome which responded to methylprednisolone boluses. Clinical and biological improvement was observed after 4 weeks, normalization of echocardiography after 4 months. CONCLUSION: A review of the literature confirmed the rare and severe nature of dilated cardiomyopathy in juvenile lupus emphasizing the importance of performing echocardiography at the slightest cardiac sign.

Epidemiology and demographics of juvenile idiopathic arthritis in Africa and Middle East.

Juvenile Idiopathic Arthritis (JIA) is a group of chronic heterogenous disorders that manifests as joint inflammation in patients aged <16 years. Globally, approximately 3 million children and young adults are suffering from JIA with prevalence rates consistently higher in girls. The region of Africa and Middle East constitute a diverse group of ethnicities, socioeconomic conditions, and climates which influence the prevalence of JIA. There are only a few studies published on epidemiology of JIA in the region. There is an evident paucity of adequate and latest data from the region. This review summarizes the available data on the prevalence of JIA and its subtypes in Africa and Middle East and discusses unmet needs for patients in this region. A total of 8 journal publications were identified concerning epidemiology and 42 articles describing JIA subtypes from Africa and Middle East were included. The prevalence of JIA in Africa and Middle East was observed to be towards the lower range of the global estimate. We observed that the most prevalent subtype in the region was oligoarticular arthritis. The incidence of uveitis and anti-nuclear antibody (ANA) positivity were found to be lower as compared to the incidence from other regions. There is a huge unmet medical need in the region for reliable epidemiological data, disease awareness, having regional and local treatment guidelines and timely diagnosis. Paucity of the pediatric rheumatologists and economic disparities also contribute to the challenges regarding the management of JIA.

Infectious adverse events in children with Juvenile Idiopathic Arthritis treated with Biological Agents in a real-life setting: Data from the JIRcohorte.

OBJECTIVES: The main objective of our study is to assess the infectious adverse events occurring in juvenile idiopathic arthritis (JIA) children treated with biological agents. METHODS: Patients were selected from the retrospective module of the JIRcohorte, data concerning the period between January 2001 and August 2015. All infectious adverse events (IAE) were retrieved. For every infectious side effect, the date, the severity, the need for a hospitalization, the type of pathogen and the affected organ were noted. Incidence rates were expressed in number of events per 100 person-years (100p-y), and OR were calculated. RESULTS: Six hundred seventy-seven patients with JIA were included in the study. A total of 3075.4 person-years of exposure were analyzed. One hundred eighty-four infectious events were described (6.0 events/100 p-y): 15.5/100 p-y with tocilizumab (TCZ), 9.6/100 p-y with Canakinumab (CAN), 7.4/100 p-y with abatacept (ABA), 6.9/100 p-y with Golimumab (GOL), 6.7/100 p-y with Anakinra (ANA), 6.3/100 p-y with Infliximab, 4.8/100 p-y with Etanercept, and 3.7/100 p-y with Adalimumab. Risk of developing an infection was significantly higher with IL-6 antagonists or IL-1 antagonists than with TNF-inhibitor. Forty point eight percent of the infectious adverse events (IAE) affected the upper respiratory tract or the Ear, nose and throat (ENT) system. Twelve infectious adverse events were described as severe or very severe (0.4/100p-y). No case of tuberculosis or death was reported. CONCLUSION: Infectious complications with biologics occurring in children treated for JIA are rare, and in most of the cases have a mild or moderate severity, affecting mainly the upper respiratory tract or the ENT.

Dilated cardiomyopathy: A rare and late complication of the hemolytic-uremic syndrome.

Hemolytic uremic syndrome (HUS) is a non-exceptional, progressive complication of acute gastroenteritis in children, especially secondary to Escherichia coli infection. It is responsible for significant morbidity and significant mortality (10% of deaths) because of acute renal failure which often complicates it. Dilated cardiomyopathy is a rare but critical extra renal manifestation of the HUS. This article highlights the importance of considering the diagnosis of associated cardiomyopathy in the acute phase of HUS and the following months. A five-year-old boy presented with HUS with acute renal failure requiring peritoneal dialysis for 24 days. No cardiac signs appeared during the acute phase of the disease. After dialysis and normalization of blood pressure, fluid, and electrolyte disturbance, severe dilated cardiomyopathy with cardiac failure appeared three months later without definite etiology. A review of the literature confirmed the rare and severe nature of cardiac lesions occurring in HUS. Dilated cardiomyopathy is a rare but important extra renal manifestation of the HUS and is best demonstrated by echocardiography. A cardiac manifestation should also be screened for in the acute phase of HUS and several months later. .

Consensus classification criteria for paediatric Behçet's disease from a prospective observational cohort: PEDBD.

BACKGROUND: We aimed to describe the main features of Behçet's disease (BD) in children in the largest prospective cohort to date and to propose a classification. METHODS: An international expert consensus group was formed to define a data set of minimal symptoms for the inclusion of patients. Patients were entered prospectively during 66 months. Experts classified patients on a consensus basis. The concordance of two international classifications was analysed in confirmed patients with BD. Comparisons of subgroups of patients helped define consensus criteria. BD-associated clinical manifestations were also investigated in three control diseases extracted from an independent data set (Eurofever). FINDINGS: In total, 42 centres from 12 countries included 230 patients; data for 219 (M/F ratio=1) could be analysed. The experts classified 156 patients (71.2%) as having confirmed BD. Males more often than females showed cutaneous, ocular and vascular symptoms and females more often genital aphthosis. Age at disease onset and skin and vascular involvement were lower for European than non-European children. Oral aphthosis was the presenting sign for 81% (179/219) of patients. The mean delay to the second symptom was 2.9±2.2 years. International classifications were not concordant with the expert classification. Our paediatric classification contains six categories, a minimum of three signs (each in a distinct category) defining paediatric BD. Three clinical signs discriminated our cohort from the Eurofever cohorts. INTERPRETATION: We present a comprehensive description of a large cohort of patients from both European and non-European countries and propose the first classification of paediatric BD for future therapeutic trials.