Rheumatoid Arthritis

Introduction

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of idiopathic inflammatory arthritis affecting children younger than 16 and lasting 6 weeks or longer. The terminology of chronic arthritis in children has evolved from juvenile chronic arthritis and juvenile rheumatoid arthritis to JIA since 1995. According to the consensus conference of the International League of Associations for Rheumatology in 2001, there are 7 JIA categories: a) oligoarthritis; b) rheumatoid factor (RF) positive polyarthritis; c) RF negative polyarthritis; d) systemic arthritis; e) psoriatic arthritis; f) enthesitis-related arthritis; g) undifferentiated arthritis.[1] These subtypes have distinct phenotypes, genetic predispositions, pathophysiology, laboratory findings, disease course, and prognosis. Although chronic arthritis is mandatory for all subtypes, the extraarticular and the systemic manifestations characterized every specific subtype. Recently, a new preliminary data-driven classification for JIA is proposed and being formally validated by the Pediatric Rheumatology International Trial Organization.[2]

Etiology

The cause and trigger of chronic arthritis in JIA remain unclear. Abnormal immune responses triggered by the interactions between environmental factors in a genetically susceptible individual are speculative. Some environmental factors such as antibiotic exposure and C-section deliveries are potential risks; however, breastfeeding and household siblings are possible protectives.[3] The roles of microorganisms such as Parvovirus B19, Epstein-Barr virus, enteric bacteria, Chlamydophila pneumoniae, and streptococcal infections are still inconclusive.[4]

Epidemiology

JIA is the most common rheumatic disease reported in children of the Western world. The incidence and prevalence are varied among 1.6 to 23 new cases for 100,000 children, and 3.8 to 400 cases per 100,000 children depending upon study designs, disease categories, and geographical areas.[9] In a US and Canada study, the incidence of JIA is 0.041 to 0.061 per 1000 children.[10] The Utah Population Database provides the prevalence of 1.2 per 1000 in white populations.[6] The relative risk of JIA in siblings varies from 15 to 30, similar to the relative risk of type 1 diabetes.[6]

The frequencies of different subtypes are 50% to 60% for oligoarthritis, 11% to 28% for RF negative polyarthritis, 2% to 7% for RF positive polyarthritis, 10% to 20% for systemic arthritis, 2% to 15% for psoriatic arthritis, 1% to 7% for enthesitis-related arthritis.[11] Specific subtypes are more common in some geographical regions. RF-negative polyarthritis is more common in North America; oligoarthritis is more common in southern Europe. Systemic arthritis and enthesitis-related arthritis are more common in southeast Asia. Uveitis is highest in northern Europe and southern Europe, but it is lowest in Latin America, Africa, the Middle East, and Southeast Asia.[12] Most JIA subtypes occur predominantly in females except enthesitis-related arthritis mainly affects males, and systemic JIA affects men and women equally.[13]

History and Physical

The disease course of JIA is highly unpredictable: in some patients is observed a self-limiting disease while in others, there is an unremitting disease with a high risk of joint destruction.[21] The JIA has the general pattern of inflammatory joint disease (synovitis, joint effusion, soft tissue swelling, osteopenia, bone edema, and erosions) with some additional elements related to developmental age, such as epiphyseal growth disturbances, premature physeal fusion, and limb length inequality.[22]

The thorough history taking, including the age of onset, the affected joints, the duration of arthritis, the associated symptoms or diseases, and physical and MSK examinations are essential for diagnosis and classification of JIA. A diagnosis of JIA is considered in any children younger than 16 years with arthritis for at least six weeks and exclusion of other causes of chronic arthritis.

Treatment / Management

Treatment of JIA requires anti-inflammatory and immunomodulatory drugs and physical therapy, and eventually, surgery, nutritional support, and psychosocial support may be needed. The choice of pharmacological treatment depends on the disease subtypes, disease severity and damage, associated disease, and family acceptance. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of initial symptomatic treatment for all subtypes. The NSAID use in JIA has decreased over time with modern aggressive treatment, including methotrexate and biologics. Physical therapy emphasizes range of motion with minimal stress on joints. Swimming is often a good option. Patients should participate in moderate fitness, flexibility, and strengthening exercises.

Differential Diagnosis

The differential diagnosis of chronic arthritis is broad, depending on the clinical presentation and the JIA subtypes. Since JIA is a diagnosis of exclusion, any patients with a positive review of the system should be considered for possible diseases. The following differential diagnosis should be considered:

A) Oligoarthritis need to exclude post-streptococcal reactive arthritis, Lyme arthritis, acute rheumatic fever, reactive arthritis, toxic synovitis, septic arthritis, pyomyositis, steroid-induced osteonecrosis, sickle cell disease, hemophilia, scurvy, osteomyelitis, chronic nonbacterial osteomyelitis (CNO), sports injury, non-accidental injury, pigmented villonodular synovitis, osteoid osteoma, bone tumors, neuroblastoma, leukemia, and lymphoma.

B) Polyarthritis need to exclude post-streptococcal reactive arthritis, Lyme arthritis, acute rheumatic fever, reactive arthritis, scurvy, CNO or chronic recurrent multifocal osteomyelitis, non-accidental injury, systemic lupus erythematosus (SLE), Mixed connective tissue disease, Sjögren syndrome, scleroderma, sarcoidosis, Blau syndrome, arthritis associated with inflammatory bowel diseases, Farber disease, benign hypermobility joint syndrome and amplified musculoskeletal pain syndrome

C) Systemic arthritis need to exclude infections (mycoplasma, cat scratch disease, bacterial endocarditis, Lyme disease), acute rheumatic fever, syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome), autoinflammatory syndromes, systemic vasculitis (polyarteritis nodosa, Kawasaki disease), inflammatory bowel disease, malignancy (leukemia, lymphoma, neuroblastoma), Castleman disease

D) Enthesitis-related arthritis. Apophysitis (especially Osgood-Schlatter, Sever disease), inflammatory bowel diseases, chronic recurrent multifocal osteomyelitis, amplified musculoskeletal pain syndrome.

Arthralgias are common early in the course of sJIA, but arthritis is not always prominent. Any number of joints may be involved when arthritis becomes apparent. Disease in the wrists, knees, and ankles is most typical. Hands, hips, cervical spine, and temporomandibular joints are also sometimes affected, unlike the oligoarticular and polyarticular subtypes of JIA Arthralgias are common early in the course of sJIA, but arthritis is not always prominent. Any number of joints may be involved when arthritis becomes apparent. Disease in the wrists, knees, and ankles is most typical, but the hands, hips, cervical spine, and temporomandibular joints are also sometimes affected. Unlike the oligoarticular and polyarticular subtypes of JIA. Musculoskeletal complaints in children with joint pain are common in general practice and increase significantly after ten years of age in general practice.[23] The most common presentation of musculoskeletal complaints is joint pain and soft tissue pain (65%), and the most common cause of all ages of children is trauma (45%).[24]