Juvenille Rheumatoid Arthritis (JRA)

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Juvenile Rheumatoid Arthritis (JRA) is among the most common childhood diseases in the United States. It affects approximately 150 out of every 100,000 children(Hommel, Chaney, Wagner, and Jarvis, 2006). It is found predominantly in females with a 3:1 ratio (Brunner et al., 2006). Marked by chronic inflammation of the joints and extra-articular tissue, the course of the disease is erratic. The patient suffers through a series of remissions, as the disease goes through lapses and relapses (Hommel, Chaney, Wagner, and Jarvis, 2006, Cakmak, and Bolukbas, 2005). The episodic nature of the disease creates complicated situations for the child, inhibiting the child’s participation in some activities. Being restrained from activity, both pleasurable and necessary, can result in the development of social problems later in life (Hommel, Chaney, Wagner, and Jarvis, 2006).

Arthritic joints.jpg

History

This genetic disease was first documented and defined as Juvenile Rheumatoid Arthritis in the beginning of 16th Century. From that point on, it has been recognized as JRA in the United States and in most European countries, although the parameters defining the disease have shifted throughout the years (Cakmak, and Bolukbas, 2005). However, there has been an international movement to make a transition from JRA to JIA, or Juvenile Idiopathic Arthritis (Passo, 2006). This change in nomenclature is an attempt to include more types of arthritis, such as psoriatic arthritis and spondyoarthropathies which are not currently part of the JRA spectrum, as well as creating a more detailed classification system of the current JRA subtypes, pauciarticular, polyarticular, and systemic JRA (Passo, 2006).

Diagnosis/Symptoms

When diagnosing JRA, clinicians must consider a few criteria. First, the onset of juvenile arthritis must be before the age of 16 (Cakmak, and Bolukbas, 2005). However, peak onset age ranges are from the ages of 2 to 4 (Özdal, Vianna, and Deschênes, 2006), and is rarely diagnosed before 6 months of age (Cakmak, and Bolukbas, 2005).

The second standard that must be met is the presence of arthritis, defined as inflammation of the joint. Arthritis then must be present in at least one joint. If arthritis is not present in at least one joint, then two of the following conditions must be present: a) limitation in range of motion, b) tenderness or pain with joint movement or, c) increased fever.

Third, the symptoms of the disease must have persisted for the previous six weeks or longer. Following the initial onset and the persistence of symptoms for the first six weeks the doctor observes the patient’s symptoms for the remainder of what equates to a six month period. The final diagnosis is based on the clinical observation of the number of involved joints within the six months, and if systemic disease is present (Brunner et al., 2006, Sawyer et al., 2005). From this data, the doctor can then determine which of the three subcategories the patient falls in.

The final piece of information included in diagnosis is the ability of the doctor to place the patient’s symptoms within one of the classified subtypes of JRA.

Subtypes of Juvenile Rheumatoid Arthritis

1. Pauciarticular (Oligoarticular)
• affecting less than five joints
• contains 50-70% of all JRA patients, making it the most common subtype
• most research of the treatments and therapy options due to its frequency, has the best prognosis and responds very well to treatment

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Active pauciarticular arthritis. Notice the swelling above the knee

2. Polyarticular
• can by identified by five or more joints being affected
• has the worst functional outcome of all subtypes (Foster, 2002).
• more than 50% of these patients have undergone at least one joint replacement (Nigrovic, and White, 2006).

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Active polyarticular arthritis. Notice the swelling of only certain finger joints

3. Systemic JRA (Still's Disease)
• marked by a systemic inflammatory reaction, such as fevers, rashes, and other systemic problems (Nigrovic, and White, 2006) such as height impairment, metabolic abnormalities, and uveitis (Simon, Prieur, and Czernichow, 2000, Özdal, Vianna, and Deschênes, 2005).
• associated with long term treatment with steroids and immunosuppressive drugs(Feldman, Weglage, Roth, Foell, and Frosch, 2005).

Treatment, Therapy, and Rehabilitation

As with any chronic pathology, the patients’ goal of treatment and therapy include achieving symptom control. With JRA, the optimal goal consists of decreased chronic joint pain, increase function, and avoidance of erosive joint damage by means of suppressing the inflammatory process (Carrasco, Smith, and Lovell, 2004, Ilowite, 2002). If JRA is allowed to run rampant and is not treated as early as possible, it may lead to functional deficiency in the musculoskeletal system or blindness (Cakmak, and Bolukbas, 2005). When beginning treatment of JRA, one must consider the components of treatment which include education, medical treatment, and exercise.

First and foremost, education is the single most important aspect of treatment, as demonstrated in the quote, “An ounce of prevention is worth a pound in cure” (Cakmak, and Bolukbas, 2005). This holds true with JRA patients, because without understanding the importance of early and effective treatment, it becomes futile.

In terms of medical treatment, the drug therapy’s objective is to decrease inflammation and stop the progression of the disease (Wolf, 2002). To accomplish this goal, researchers have identified three categories of drugs. These categories include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs) (Wolf, 2002).


NSAIDS:
• Include aspirin and ibuprofen.
• First line of therapy.
• Unable to stop the progression of disease(Wolf, 2002).

Glucocorticoids:
• Include cortisone and prednisone.
• Commonly associated with a number of side-effects.
• Unable to stop the progression of JRA.
• Used in patients that NSAIDs have failed.
• Not to use for an extended period of time, as it can aggravate diabetes, glaucoma, and cataracts or cause weakness and hypertension (Wolf, 2002).

DMARDs:
• Inhibit the disease from progressing and has been shown to reverse the pathological damage caused by the arthritis.
• By inhibiting the immune response, DMARDs can control synovitis and erosive changes during the active stages of JRA.
• Risks and effectiveness not fully understood

As previously stated, JRA patients have some difficulty participating in physical activities and tend to limit involvement as much as possible. However, this inactivity has proven to be detrimental to the patients in the long run. The American College of Rheumatology recommends muscle strengthening and aerobic conditioning programs for management of JRA symptoms (Myer et al., 2005). Patients that shared in these forms of training and even participated in impact sports showed greater improvement in functional ability and patient satisfaction, as opposed to the standard care patients (Myer et al., 2005). Heat can be used to reduce the rigidity of joints as well as increasing the flexibility in the joint capsule, or cold can be used as an analgesic and as a vasoconstrictor. Massage is another form of therapy, used to relieve pain and prevent adhesions in the subcutaneous tissue. Finally, electrical stimulation and ultrasound can be used in cases of excessive muscle atrophy (Cakmak, and Bolukbas, 2005). Some therapeutic exercises a patient can use include aquatic exercising, positioning, passive ROM exercises, and isometric exercises (Lovell et al., 1987-1994).

Mechanism and Complications

JRA is known for the effects it has on the musculoskeletal system, and complaints are common and are reported by up to 30% of children and adolescents (Foster, 2002). Among the musculoskeletal problems that develop with JRA, the trademark issue is the chronic inflammation of the joints. Although the pathogenesis of this autoimmune disease is not fully understood, certain physiological causes of the inflammatory response can provide some insight. As the disease enters into the chronic phase of the inflammatory response, the synovium is penetrated by inflammatory cells. The synovium then becomes hyperplastic when proliferation of the synovial fibroblasts occurs. As a result, it leads to the destruction of articular cartilage and bone (Chikanza, 2002). As a result of the chronic inflammatory state, the erosion of the cartilage and bone lead to the other increasingly frequent symptom of growth-related deformities (Simon, Prieur, and Czernichow, 2000). Other orthopedic problems that arise as a result should be considered. Some examples would be shortening of limbs, decreased femoral head size, and deformed ankles and feet (Nigrovic, and White, 2006). With the destruction of the joints as a result of the active inflammation, joint replacements such as total knee arthroplasty are likely to be needed, especially in the more severe cases (Palmer et al., 2005).

Of nonarticular complications, development of chronic anterior uveitis is the most serious symptom, occurring in 10-20% of patients (Kotaniemi, Kautianen, Karma, and Aho, 2001). Most children with JRA develop uveitis within the first seven years of onset (Kotaniemi, Kautianen, Karma, and Aho, 2001). Consequently, it has been recommended that patients are examined by an ophthalmologist every two to six months for the first seven years (Kotaniemi, Kautianen, Karma, and Aho, 2001).

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An eye with anterior uveitis

Of all systemic diseases, JRA is the most common cause of pediatric anterior uveitis in Europe and North America (Carvounis, Herman, Cha, and Burke, 2006), amounting to nearly 80% of all cases being associated (Özdal, Vianna, and Deschênes, 2005). In cases of uveitis that are directly linked to JRA are typically insidious, bilateral, and chronic (Kotaniemi, Kautianen, Karma, and Aho, 2001). Some factors that lend to the development of JRA- associated uveitis are patients with pauciarticular type JRA, having an early onset of arthritis, being positive for antinuclear antibodies, negativity of rheumatoid factor, and being of the female gender, as it has been documented that two thirds patients with JRA-associated uveitis are female (Kotaniemi, Kautianen, Karma, and Aho, 2001). When JRA patients develop uveitis, it has been seen to result in visual loss in up to 58% of the cases, depending on the severity of the inflammation. Although early detection and aggressive treatment has proven to have a good prognosis (Özdal, Vianna, and Deschênes, 2005), 20% or more of JRA associated uveitis patients will have some degree of ocular injury. Some potential injuries include cataracts, glaucoma, and partial loss of vision (Nigrovic, and White, 2006). However, as opposed to reports form the 1970s to the 1980s, there has been a decrease in reported complications throughout the years.

Psychological Effects

The psychosocial repercussions of having JRA can be devastating in children if left uncontrolled. JRA patients experience unpleasant symptoms such as pain, fatigue, disfigurement, disability, swelling and limited range of motion (Takken, Net, and Helders, 2002). As the disease begins to change the patient’s body to a state outside the social norm, it can become difficult to deal with. Social pressure to look as everyone else does, will wear on the patient as they realize they do not look that way. This harsh realization leads to the eventual break down of the patient’s quality of life (Nigrovic, and White, 2006).

As a child develops symptoms of JRA, they are more likely to self-limit the physical activity (Myer et al., 2005, Hommel, Chaney, Wagner, and Jarvis, 2006). Although these children enjoy leading a very active lifestyle, limitation of pleasurable and even necessary activities occurs because of the physical pain and functional disability associated with JRA. When children must restrain themselves in usual activities at home and school, both places of important social influence, it presents a possible social challenge (Minden, 2006).

As JRA follows an irregular course, so does the psychological state of the patient. JRA has periods of lapses and relapses that are unpredictable and spontaneous, resulting in more than 20% experiencing a period of depression sometime in late adolescence or early adulthood (Nigrovic, and White, 2006). Although body image issues are prevalent in most adolescents, over 50% of JRA patients have reported having body image issues, with some part of the physical deformities to blame (Nigrovic, and White, 2006). Adult patients tend to stay single longer and have reported to having social issues in the work place. A reason for this could be that 25% report some form of vocational discrimination as a result of the patient’s inability to painlessly and quickly perform simple tasks, such as typing on a computer. This discrimination lends to the high unemployment of JRA patients, at a climbing rate of 25-40% (Nigrovic, and White, 2006).

Current Research

Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis
One study is looking to determine a uniform method of treatment. Since treatment for Poly JRA is usually treated by a gradual increase of a wide range of medications, this study is looking to test the early treatment of one aggressive medication. This is hoping to have an increase in the remission of the disease for children. Based upon other studies done with adult Rheumatoid Arthritis, there appears to be an early window of opportunity where aggressive drug treatment seems to be beneficial in the long run. They are currently testing methotrexate as an aggressive drug treatment, and trying to see if aggressively treated early enough the disease will be more likely to go into remission. This study is currently recruiting subjects.[1]

Safety and Efficacy of Measles, Mumps, Rubella Vacinnation in Juvenile Idiopathic Arthritis
Another current study is investigating the safety and effectiveness of the MMR booster vaccination in children 4-8 years of age with Juvenile Idiopathic Arthritis. Earlier studies have determined that there was no increase in disease activity after children with JIA were immunized with dead vaccines. It has been determined that the live weakened Measles, Mumps, Rubella vaccination had caused no increase in disease activity either. But, it is unknown whether the MMR vaccination is effective in children with JIA because of immunosuppressive therapy that they are receiving for their disease that may diminish the immune response they have to the vaccination. Once the vaccination is administered, a 12 month follow-up period will determine disease activity and side-effects that will determine the safety of the vaccination in these patients. The effectiveness of the vaccine will also be studied by determining antibody levels and functions against the vaccine in the blood. This study is currently recruiting subjects.[1]

Safety and Efficacy of a Tumor Necrosis Factor Receptor Fusion Protein on Uveitis
A study is also currently recruiting participants in order to investigate the safety and effectiveness of Enbrel (a tumor necrosis factor receptor fusion protein- TNFR:Fc), a drug to treat the eye inflammation called uveitis in patients with Juvenile Rheumatoid Arthritis. Other studies showed that TNFR:Fc reduced joint pain and swelling in adults and it was approved by the Food and Drug Administration for that use. This study will help determine whether TNFR:Fc can also help patients with eye inflammation even though that is not what it was approved for. Participants will be injected twice a week for up to a year with TNFR:Fc. Follow-up exams and evaluations will be done in order to determine side effects of the medicine as well as its affect on uveitis. The participants will be between the ages of 2 and 18.[1]

To read more current studies visit this site for clinical trials [1] Current Research Studies

References

Brunner, Hermine I., Taylor, Janalee, Britto, Maria T., Corcoran, Melinda S., Kramer, Sandy L., Melson, Paula L., Kotagal, Uma R., Graham, T. Brent, Passo, Murray H. (2006). Differences in diseased outcomes between medicaid and privately insured children: possible health disparities in juvenile rheumatoid arthritis. Arthritis & Rheumatism. 55: 3, 378-384.

Cakmak, Aysegul, Bolukbas, Nalan. (2005). Juvenile rheumatoid arthritis: physical therapy and rehabilitation. Southern Medicine Journal. 98: 2, 212-216

Carrasco, Ruy, Smith, Judith A., Lovell, David. (2004). Biologic agents for the treatment of juvenile rheumatoid arthritis. Pediatr Drugs. 6: 3, 137-146.

Carvounis, Peter E., Herman, David C., Cha, Stephen, Burke, James P. (2006). Incidence and outcomes of uveitis in juvenile rheumatoid arthritis, a synthesis of the literature. Graefe’s Arch Clin Exp Ophthalmol. 244: 281-290.

Chikanza, Ian C. (2002). Juvenile rheumatoid arthritis: Theraputic perspectives. Pediatr Drugs. 4 (5):335-348.

Feldmann, Reinhold, Weglage, Josef, Roth, Johannes, Foell, Dirk, Frosch, Michael. (2005). Systemic juvenile arthritis: Cognitive function and social adjustment. American Neurological Association. 58: 605-609.

Foster, Helen E. (2002). Chronic Arthritis in children and adolescents. Children and Adolescents. 34-38.

Hommel, Kevin A. Chaney, John M., Wagner, Janelle L., Jarvis, James N. (2006). Learned helplessness in children and adolescents with juvenile rheumatic disease. Journal of Psychosomatic Research. 60:73-81.

Kotaniemi, Kaisu, Kautianen, Hannu, Karma, Anni, Aho, Kimmo. (2001). Occurrence of uveitis in recently diagnosed juvenile chronic arthritis. American Academy of Ophthalmology. 108: 2071-2075.

Lovell, David J., Reiff, Andreas, Jones, Olcay Y., Schneider, Rayfel, Nocton, James, Stein, Leonard D., Gedalia, Abraham, Ilowite, Norman T., Wallace, Carol A., Whitmore, James B., White, Barbara, Giannini, Edward H. (2006). Long- term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis & Rheumatism. 54: 6, 1987-1994.

Minden, Kristen. (2006). What are the costs of childhood-onset rheumatic disease? Best Practice & Research Clinical Rheumatology. 20: 2, 223-240.

Myer, Gregory D., Brunner, Hermine I., Melson, Paula G., Paterno, Mark V., Ford, Kevin R., Hewett, Timothy E. (2005). Specialized neuromuscular training to improve neuromuscular function and biomechanics in a patient with quiescent juvenile rheumatoid arthritis. Physical Therapy. 85: 8, 791-802.

Nigrovic, Peter A., White, Patience H. (2006). Care of the adult with juvenile rheumatoid arthritis. Arthritis and Rheumatism. 55: 2, 208-216.

Özdal, Pinar Ç., Vianna, Raul N.G., Deschênes, Jean. (2005). Visual outcomes of juvenile rheumatoid arthritis-associated uveitis in adults. Ocular Immunology and Inflammation. 13: 33-38.

Palmer, David H., Mulhall, Kevin J., Thompson, Corey A., Severson, Erik P., Santos, Edward R.G., Saleh, Khaled J. (2005). Total knee arthroplasty in juvenile rheumatoid arthritis. The Journal of Bone and Joint Surgery. 87-A: 7, 1510- 1514.

Passo, Murray. (2006). Emerging therapies in juvenile rheumatoid/idiopathic susceptibility to JRA/JIA: Complementing general autoimmune and arthritis traits. Genes and Immunity. 7: 1-10.

Simon, Dominique, Prieur, Anne-Marie, Czernichow, Paul. (2000). Treatment of juvenile rheumatoid arthritis with growth hormone. Hormone Research. 53: 82-86.

Takken, Tim, Net, Janjaap van der, Helders, Paul J.M. (2002). Aerobic exercise testing in juvenile rheumatoid arthritis patients. Clinical Exercise Physiology. 4: 1, 38-43.

Wolf, Steven L., ed. Pharmacology in Rehabilitation. 3rd ed. Philadelphia : F.A. Davis Company, 2002.



Additional Information:

[2] KidsHealth.org

[3] MedlinePlus

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