Juvenile idiopathic arthritis (JIA) is the term given to a group of conditions that result in joint inflammation in children before the age of 16 years. It is an autoimmune condition caused by the formation of autoantibodies that target the synovial membranes of the affected joints. This is the most common rheumatic condition to affect children.

JIA affects the synovial membranes of joints, leading to stiffness, pain, and restriction of movement of the swollen, red joint. The child may not use the limb affected. In addition, fever and other systemic symptoms, including loss of weight and the appearance of a rash over the involved joint, are other possible clinical features.

JIA is a chronic condition, and periods of remission alternate with flares. Such chronic nature of this condition carries with it the potential to cause several complications, as well as those produced by the potent medications used to control it.

Complications of JIA affecting joints and eyes

Over two-thirds of children with JIA continue to have joint and eye involvement in adult life. Joint pain can lead to a poor functional outcome over the long term. This means the child may be unable to participate freely in play, school activities, as well as in other social interactions. This could result in both psychological and physical distress.

Markers of future joint damage include:

• Severe arthritis within the first two years of onset, with initial involvement of more than 1 joint, involvement of at least one joint in the upper limb, or an ESR above 100 mm/hr predicted progression of joint destruction in pauci-articular forms
• fever and multiple joint involvement within the first six months in the systemic forms
• multiple joint involvement with positivity for rheumatoid factor predicted significant adult disability
• Sacro-iliitis in psoriatic JIA patients who were male and HLA-B27-positive
• Involvement of the leg, especially the tarsals and the knee, predicted sacroiliitis in enthesitis-related JIA

Uveitis (i.e. an inflammation of the uvea, which represents the middle layer of the eye) is a long-term complication which is associated with cataract, glaucoma and band keratopathy, and which has only 36% remission rates. Markers of other complications can include a family history of psoriasis in oligoarticular JIA that is associated with chronic uveitis, and secondary amyloidosis (4%) linked to systemic JIA.

Macrophage Activation Syndrome

Macrophage activation syndrome (MAS) is a feature of systemic JIA, and may be present in either clinical or subclinical form in almost all patients who have active forms of this subset of JIA. MAS is considered an acquired variant of hemophagocytic lymphohistiocytosis. It is characterized by the persistent fever, pancytopenia, coagulopathy and organ dysfunction in the form of brain and liver deficits.

The presence of foamy macrophages and hemophagocytosis (a term used to describe the phagocytosis of blood cells by macrophages) is a distinctive feature on biopsy. Serum albumin is low, while ferritin, liver enzymes, and triglyceride levels usually go up.

MAS may occur as part of the rheumatic process, or be a reaction to the use of some therapeutics, such as the biologics. It may also be a response to an infection, or a switch between drugs.

Other Complications of JIA

Pulmonary complications  may occur in over 80% of patients who have systemic JIA and are often fatal. Symptoms include shortness of breath, dyspnea on exertion, clubbing and cough.  The pulmonary manifestations comprise mainly of pulmonary arterial hypertension (64%), interstitial lung disease (28%), alveolar proteinosis (20%) and lipoid pneumonia. Complications like pleuritis, pericarditis and growth failure can also ensue.

Complications due to treatment mainly encompass three broad categories:

• Steroid-associated complications (osteoporosis in 40% of cases, pathologic fractures in 8% of cases, cataracts in 24% of cases, avascular necrosis in 12% of cases, and a propensity for serious infections)
• Drug-related toxicity (liver and bone marrow suppression, oral ulcerations and infections)
• Biologics-related toxicity (immunosuppression leading to reactivation of tuberculosis and other infections, demyelinating disease, drug-induced lupus and leukocytoclastic vasculitis)

Infections may occur during the course of disease or while being treated with immunosuppressive drugs or steroids. The most severe infections include sepsis, salmonella and adenoviral gastroenteritis, pneumonia, Clostridium difficile enteritis, typhilits and ascariasis.

Potential rare complications are psychosis, myositis, transient ischemic attack, thrombotic thrombocytopenic purpura and dyslipidemia. Also, it has to be emphasized that children with JIA have a higher rate of development of cancers, i.e. an increased risk of malignancy.

When talking about mortality, it is known that the risk of death is highest in systemic JIA , mostly due to the presence of MAS and infections. Nevertheless, the current use of biologics has led to an improvement in the short- and long-term prognosis of this condition.

Reviewed by Catherine Shaffer, M.Sc. and Tomislav Meštrović, MD, PhD