Global Issues in Pediatric Rheumatology

Juvenile Idiopathic Arthritis

The pooled prevalence of JIA in Caucasians is 32.6 (31.3 to 33.9) per 100,000. In India a prevalence of 48 per 100,000 based on a school survey was found. The recent estimated number of children living with JIA is highest in India (397,283), followed by China (264,792), Nigeria (88,257), and Indonesia (72,341). These estimates are based on a population less than 16 years of age in that country and the prevalence of SLE taken as 1 in 10,000 and that of JIA as 1 in 1000.

Though the prevalences of JIA are similar, there are significant differences in the relative frequencies of different categories of JIA in different parts of the world. A recent study conducted in 130 centers in 49 countries and 5 continents found that countries in regions with limited resources like Asia, Africa, and South America had a higher prevalence of systemic JIA (sJIA) compared with Europe and North America. Enthesitis-related arthritis (ERA) was reportedly the most common diagnosis in Southeast Asia and exceeded that in other regions of the world, whereas in Europe and North America, oligoarthritis was the most common category of JIA. These data suggest that the categories of JIA that are more linked to environment and may be autoinflammatory in nature are more frequent in developing countries.

Uveitis is the most common extraarticular manifestation of JIA and it is associated with significant morbidity. This complication has a much lower reported prevalence in less-resourced (5% to 6%) compared with developed countries (11% to 19%). This could be partly related to the lower prevalence of oligoarticular disease in less-resourced countries or to less rigorous screening for asymptomatic uveitis.

Further, the time to diagnosis is longer in less-resourced countries. This may be due to lack of access to health care, poverty, easy availability of drugs without prescriptions leading to self-medication in the early part of disease when symptoms are mild, and faith in alternative systems of medicine. In addition, fever in a child is commonly thought to be the result of infection; thus it is not unusual to see a child with sJIA receive multiple courses of antibiotics despite having a classic fever and rash. sJIA is also often misdiagnosed initially as acute rheumatic fever as disorders present with fever, rash, arthritis, and may have cardiac involvement. Similarly, children with ERA are often thought to have tuberculosis (TB) of the knee or hip and receive anti-TB treatment or have synovial biopsies before a correct diagnosis is made. Leprosy can present with asymmetrical arthritis and needs to be considered in the differential diagnosis of JIA in endemic areas.

Lack of access to biologics is especially critical in sJIA, and lack of access to biologics is especially critical in sJIA as patients not responding to corticosteroids and/or methotrexate have very few alternatives; although interleukin (IL)-1 or IL-6 blocking biologics are available, they are very expensive and beyond reach for most families. Only one-quarter of children with JIA in less-resourced countries received biologics in contrast to nearly 40% in developed countries in the epidemiology, treatment, and outcome of childhood arthritis throughout the world (EPOCA) study. Systemic amyloidosis in sJIA, now rarely seen in developed world still occurs in the developing world because of persistent disease activity. The EPOCA study found an inverse correlation between gross domestic product (GDP) and disease activity. Lower GDP was also associated with greater articular and extraarticular damage in JIA. To improve outcomes globally, health must be accessible to all. Management recommendations for less-resourced countries, such as the juvenile arthritis management in less-resourced countries (JAMLess), may contribute to improved care and outcomes for patients.

Systemic Lupus Erythematosus

In Taiwan, the incidence of SLE was found to be 4.87 per 100,000 and prevalence was 97.5 per 100,000. In addition it was noted that the incidence rate had reduced by 4.2% per year from 2003 to 2008. In a multicenter study from India the prevalence of SLE was 10 per 100,000, which is much lower than from Taiwan. The recent estimated number of children living with SLE is highest in India (39,728), followed by China (26,479), Nigeria (8826), and Indonesia (7234).

Late diagnosis and misdiagnosing rheumatic diseases as infections are common issues, even for SLE. A recent study in Africa found multiple factors leading to delay in diagnosis of SLE in children including lack of knowledge about SLE in the community, financial issues, and social stigma attached to illness, along with lack of trained medical staff.

Asians and Africans with SLE have a higher prevalence of nephritis than Caucasians. The survival rates of SLE and lupus nephritis are at least 5% to 10% lower than in the developed world in the short term. ^, The rate of end-stage renal disease and the need for transplant is much higher. ^, Several studies also show poorer outcome compared with Caucasians. This is probably related to the increased burden of infectious complications and lack of access to renal replacement therapy.

Juvenile Dermatomyositis

No prevalence or incidence data are available for juvenile dermatomyositis (JDM) in less-resourced countries. Children with JDM often have arthritis and may be misdiagnosed as having JIA. An appropriate muscle examination may not be performed in busy clinics. In adolescents, multifocal pyomyositis can mimic inflammatory myositis. Because of a delay in diagnosis, contractures and calcinosis are reported more often from the developing world. ^,

Vasculitis

Immunoglobulin (Ig)A vasculitis (Henoch–Schönlein purpura) and Kawasaki disease are increasingly recognized in the less-resourced countries. Takayasu arteritis (TA), a large vessel vasculitis seen uncommonly in the West, is seen much more frequently in southern Africa, Asia, and South America. In a recent Brazilian study, about one-quarter of patients with TA had been misdiagnosed as coarctation of aorta, acute rheumatic fever, JIA, or spondyloarthropathy because of lack of awareness of TA. In India TA is the most common cause of renovascular hypertension. In a recent study from China, among 101 children with TA common findings included hypertension, blood pressure discrepancy, and vascular bruits. Almost one-quarter of children had congestive heart failure or limb claudication.

Though leprosy has been eradicated from most parts of the world, it is still seen often in India and Brazil. In a study from Brazil, 21.4% children developed lepra reaction. The lepra reaction in leprosy can simulate vasculitis as a result of the presence of fever, rash, arthritis, swollen hand and feet syndrome, and neuropathy. Rickettsial infections also need to considered in the differential of vasculitis in less-resourced countries, especially in children residing in or returning from tick-endemic areas.

Acute Rheumatic Fever

A systematic review estimated that around 336,000 children aged 5 to 14 years develop acute rheumatic fever every year and most of them reside in low-income countries.

In the developing world, large family size leading to overcrowding and poverty contribute to high rates of acute rheumatic fever. Patients are often diagnosed only when they develop rheumatic heart disease and its complications. In addition infectious diseases like dengue, chikungunya, and Ross River virus can simulate acute rheumatic fever and thus need to be excluded. However with wider availability of echocardiography and updated diagnostic criteria, the diagnosis is being made earlier.