Juvenile Idiopathic Arthritis (jia)

Hala Etayari
Libyan board of pediatrics
Tripoli Children Hospital, Tripoli/Libya

First Created: 04/09/2001  Last Updated: 04/09/2001

Introduction

Juvenile idiopathic arthritis is the most common rheumatic condition found in children. Early diagnosis and treatment is a key point to prevent long term morbidity and multidisciplinary team is needed to achieve the best outcome. Therefore it is essential for the pediatrician to be familiar with the disease and the drugs used in its treatment to be able to know when to refer a patient to a rheumatologist and how to help in the management of the patients during periods of infection and recognize side effects of the treatment.

JIA - Background

Juvenile idiopathic arthritis (JIA) is a group of heterogeneous diseases sharing the presence of chronic arthritis (arthritis for more than 6 weeks) developing before the 16th birthday, of unknown cause, after the exclusion of other causes of chronic arthritis.

Collectively, this group constitutes the most common rheumatic condition in children.

The term JIA has replaced the previous nomenclature including "Juvenile rheumatoid arthritis" used in U.S.A and "Juvenile chronic arthritis" used in Europe.

The original classification of JIA has been revised several times. The International League of Associations for Rheumatology (ILAR) developed the most recent classification system which describes seven categories of JIA (Table 1) in 2001, resulting in further clarification of the various subsets, correction of prior incongruence, and improvement in clinical utility to the rheumatologist. Also, it provides an important framework for research in JIA as well as assisting with appropriate treatment and prediction of natural history.1

Exclusions:
The principle of this classification is that all categories of JIA are mutually exclusive. This principle is reflected in the list of possible exclusions for each category:

  • Psoriasis or a history of psoriasis in the patient or first-degree relative.
  • Arthritis in HLAB27 positive male beginning after the 6th birthday.
  • Ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, Reiter's syndrome, or acute anterior uveitis or history of one of these disorders in a first-degree relative.
  • The presence of IgM rheumatoid factor on at least 2 occasions at least 3 months apart.
  • The presence of systemic JIA manifestations

Table 1: ILAR classification of JIA

Category Diagnostic criteria
Systemic arthritis (sJIA) Fever of at least 2 weeks duration (daily for at least 3 days) and arthritis in one or more joints, plus one of the following:
  • Erythematous rash
  • Generalised lymph node enlargement
  • Hepatomegaly and/or splenomegaly
  • Serositis
Exclusions: a, b, c, d.
Oligoarthritis Arthritis affecting = four joints during the first 6 months of the disease. If after 6 months more than four joints are involved the term extended oligoarthritis is used
Exclusions: a, b, c, d, e.
Polyarthritis (rheumatoid factor negative)(seronegative) Arthritis affecting = five joints during the first 6 months of the disease with rheumatoid factor negative
Exclusions: a, b, c, d, e.
Polyarthritis (rheumatoid factor positive)(seropositive) Arthritis affecting = five joints during the first 6 months of disease with rheumatoid factor positive on at least two occasions at least 3 months apart
Exclusions: a, b, c, e.
Psoriatic arthritis (psJIA) Arthritis and psoriasis or arthritis and at least two of the following:
  • Dactylitis
  • Nail pitting or onycholysis
  • Psoriasis in a first degree relative
Exclusions: b, c, d, e.
Enthesitis related arthritis (ERA) Arthritis and enthesitis or arthritis or enthesitis with at least two of the following:
  • Presence/history of sacroiliac joint tenderness and/or inflammatory lumborsacral pain and HLA-B27 positive
  • Onset of arthritis in a male over 6 years of age
  • Acute (symptomatic) anterior uveitis
  • History of ankylosing spondylitis, enthesitis related arthritis, sacroiliitis with inflammatory bowel disease or acute anterior uveitis in a first degree relative
Exclusions: a, d, e.
Undifferentiated arthritis Arthritis that fulfils criteria in no category or in two or more of the above categories

JIA - Clinical Manifestations

Arthritis is defined as the presence of joint effusion with reduced range of motion, pain on movement, and/or the warmth of the joint. Joint pain generally is aching in quality, mild to moderate in severity, and occur with movement. Children differ in how they communicate pain according to developmental age. They may use the limb in a different way, refuse to use the limb, and put it in the resting position or they may be irritable.

Joint stiffness and gelling noticed mainly in morning or after a prolonged period of inactivity. The parents may notice that the child is slow to get moving or moving awkwardly after sleep or day time nap.

Patterns of joint involvement are often quite characteristic. Thus, the symmetrical involvement of large and small joints is typical of polyarticular disease. Arthritis predominantly affecting the joints of the lower extremity characterizes ERA. The presence of the hip joint disease is not uncommon in ERA but rarely occurs in oligoarticular JIA. Psoriatic arthritis tends to be somewhat asymmetrical and involves both large and small joints, sometimes including the distal interphalangeal joints.

Bone pain is not a characteristic of arthritis and should alert the examiner to the possibility of malignancy or infection involving bone.

Other than arthritis, clinical manifestations vary between subtypes. Constitutional symptoms like fatigue, anorexia, weight loss, and growth failure found more in systemic and polyarticular JIA.

Extra-articular manifestations:
Generalized growth abnormalities:
Linear growth is retarded during periods of active systemic disease. Mean weight for age and weight per height are significantly diminished in those with polyarticular disease. This occurs secondary to prolonged disease activity and cannot be explained by prolonged use of corticosteroids alone.

Localized growth abnormalities:
During early active disease, the development of the ossification centers is accelerated, apparently related to the hyperemia of inflammation and local production of growth factors. The result may be either overgrowth of the affected limb or, ultimately (though much less commonly), premature fusion of the involved physes, resulting in diminished length.

If arthritis occurs in one knee, this may result in leg length discrepancy.

Leg-length inequality may also result from pelvic rotation and scoliosis.

Micrognathia and/or retrognathia may result from growth disturbances of the mandible as a consequence of arthritis in the temporomandibular joint.

Skin and subcutaneous tissue:
One of the characteristic skin manifestations in sJIA is the evanescent rash that appears with fever. Some of the other skin manifestations include dark discoloration of the skin over the proximal interphalangeal joints which may indicate chronicity and the subcutaneous rheumatoid nodules. The most commonly occur over the proximal ulna and the Achilles tendon.

Asymmetrical lymphedema of the subcutaneous tissues of one or more extremities has been documented in several children with arthritis.

Ocular disease:
Uveitis is the most common extra-articular manifestation of JIA. It is presented most commonly as a chronic asymptomatic anterior uveitis.

Uveitis complications include posterior synechiae, band keratopathy, glaucoma, cataract, and macular edema. The reported frequency of occurrence of uveitis varied considerably from 2-20% and it varies also between JIA subtypes. It occurs in 15-20% of oligoarthritis patients and 5-10% of polyarthritis patients. It is rarely seen in sJIA.2-4

Because of the asymptomatic nature of the disease and its vision-threatening complications, regular screening by ophthalmology is required. The frequency of screening according to the American Academy of Pediatric guidelines is determined by the degree of risk and demonstrated in the following tables:

Table 2: Stratification of uveitis risk in JIA

Factor Low risk High risk
Gender Male Female
Age of onset of JIA >6 years <6 years
Type of JIA sJIA Oligoarticular JIA
Duration of JIA >4 years <4 years
ANA Negative Positive
Rheumatoid factor Present Absent

Table 3: American Academy of pediatrics recommendations screening

Level of risk Definition Screening frequency
High Oligoarticular or polyarticular JIA <6 years at onset ANA positive 3-4 monthly
Medium Oligo or polyarticular JIA >6 years at onset ANA negative 6 monthly
Low sJIA 12 monthly

JIA - Epidemiology

The true prevalence of JIA is not known, but approximately 1 in 1000 children worldwide are affected. The reported incidence and prevalence vary considerably in different regions. This variation may reflect differences in ethnicity, environmental factors, or immunogenic susceptibility, or may result from underreporting in some countries.3,5

Overall, more females than males are affected by JIA; however, the sex distribution varies by disease subtype, with a striking female predominance in the oligoarticular and polyarticular onset subtypes, an even distribution of sexes in the systemic onset subtype, and a male predominance in the enthesitis-related arthritis subtype.5

Certain subtypes have an age-specific peek incidence; however, it is unusual for JIA to be manifested before 6 months of age.2,3

Different proportions of JIA subtypes were reported from different countries. In the USA and Europe, the oligoarticular subtype is the commonest, while in India, South Africa, and Zambia ERA and seronegative oligoarticular JIA reported more.3

Etiology and Pathogenesis

JIA is characterized by a chronic inflammatory process involving the synovial membrane, bone, and cartilage. Histologically what is found in the infiltration of the synovium by lymphocytes, plasma cells, macrophages, and dendritic cells? Another prominent feature is the proliferation of fibroblasts and macrophage-like synoviocytes.

Th1 cells driven by the population of cytokine and chemokine producing T-cells are believed to mediate the inflammation in JIA.

The most important cytokines that play a role in JIA and targeted by the most recent drugs developed for the treatment are Tumor necrotizing factor-a (TNF-a), IL-1, and IL-6.

Antigen-driven T cells also play a central role in the pathogenesis of JIA.

Systemic onset JIA histologically can be classified as a subtype of JIA but pathologically better classified as an autoinflammatory syndrome.

What causes the inflammation in JIA is unknown, but it is believed to be multifactorial. Some of the factors that may play a role are:

  • Maternal smoking increase the risk of developing JIA.

  • Breast feeding decreases the risk of developing JIA.

  • Infections by many bacteria and viruses play a role in the initiation and the augmentation of the symptoms of JIA.

  • Vaccines may act as disease triggers.

  • Vitamin D deficiency also may play a role.

The causal relationship between JIA and environmental factors is obscure and requires more investigation.

Also, genetics play a role where several genetic loci have been proposed to be associated with susceptibility to and severity of JIA.


1. Petty R, Southwood T, Manners P, Baum J, Glass D, Goldenberg J, et al. ILAR criteria.pdf. J Rheumatol. 2004;2(31).
2. Boros C, Whitenhead B. Juvenile idiopathic arthritis.
3. Petty RE, Laxer RM, Lindsley CB, Wedderburn L, Cassidy JT. Textbook of pediatric rheumatology [Internet]. 2016 [cited 2016 May 9]. Available from: https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20120003493
4. Patel H, Goldstein D. Pediatric uveitis. Pediatr Clin North Am. 2003;50(1):125–36.
5. Huang J-L. New advances in juvenile idiopathic arthritis. Chang Gung Med J. 2012;35(1):1–14.
6. Naz S, Mushtaq A, Rehman S, Bari A, Maqsud A, Khan MZ, et al. Juvenile rheumatoid arthritis. J Coll Physicians Surg--Pak JCPSP. 2013 Jun;23(6):409–12.


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