Integrative Treatment Approaches for Juvenile Idiopathic Arthritis
Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis, is a nonspecific type of arthritis appearing before the age of 16 years and lasting at least 6 weeks.1,2 JIA is the most common chronic arthritis in children.2 Two peaks of onset have been described at 2 to 4 and 6 to 12 years of age,4 most often in Caucasian and female patients.5 In 2011, the American College of Rheumatology (ACR) updated their recommendations for pharmaceutical management of patients with JIA to include the following treatments alone or in combination: non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular glucocorticoid injections, methotrexate (MTX), sulfasalazine, tumor necrosis factor alpha (TNF-α) inhibitors (ie, etanercept [Enbrel] and adalimumab [Humira]), leflunomide, abatacept (Orencia), anakinra (Kineret), and systemic glucocorticoids.2
Because of concerns of adverse events, the ACR recommends that NSAID and MTX safety monitoring consist of baseline serum creatinine levels, urinalysis, complete blood count, and liver function testing with repeat lab measurements over time. TNF-α inhibitors also require yearly tuberculosis screening. Hepatitis B and C screening are recommended prior to MTX and TNF-α administration if the patient has risk factors for infection.2 Data on combining these pharmaceuticals and natural health products (NHPs) are sparse, so if the clinician decides to use some natural products with the above medications, the lab studies can help with safety monitoring of novel combinations.
Benefits/Risks of Pharmaceutical Therapy
Since most JIA patients will be on prescription medications to aleviate painful symptoms, it is important to understand the benefits and risks of treatments. In a double-blind placebo-controlled trial of early aggressive therapy, 85 patients with JIA were randomly assigned to two groups: 42 patients received a combination of MTX 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks; and 43 patients received MTX 0.5 mg/kg/week, etanercept-placebo, and prednisolone-placebo.
Results from the study found that a cohort of 85 JIA patients achieved clinically inactive disease status in 32% of patients by 6 months and in 66% by 12 months. Patients who were treated earlier during the course of the disease in both arms experienced a higher rate of JIA remission with these treatments. Despite the success of these treatments, both arms of the study reported severe to less severe adverse events, including significant transaminase elevations, peritonsillar abscess, worsened pre-existing herpes infection, pneumonia, psychotic episodes during steroid taper, and septic hip joints.6 Concerns regarding malignancy and infection are also important to consider for patients taking a biologic agent.7-10
Fifty percent or more of patients with JIA have the risk of ongoing arthritis as adults, which necessitates long-term support for those patients.11,12 Despite MTX use in 66% and NSAID use in 88% of the children surveyed with polyarticular arthritis, many still experienced pain and reduced function, resulting in missed school and social activities. Higher levels of anxiety correlated with higher pain and function complaints, so adequate pain control should include mind–body approaches at promoting a sense of calm.13
Integrative Rheumatology In JIA
The use of NHPs and complementary and alternative medicine (CAM) is common in JIA. Parental fear of medication side effects, pain relief, a desire to improve their child’s well being, longer disease duration and multiple illnesses in the child, parental CAM use, and parental perception of whether medications are helping or not have all been found to drive pediatric CAM use in JIA.14-17 To follow is a discussion of alternative therapies for JIA.
Clinicians have few guidelines on the judicious, safe, and effective use of NHPs and CAM modalities for improving JIA symptoms, with or without standard-of-care medications and exercise prescriptions. Clinical outcomes in JIA patients who used CAM and NHP therapies showed that outcomes were no better compared to non-users. However, CAM users were more adherent to conventional therapy compared to non-users.18-20
The most commonly used CAM therapies include dietary modification, NHPs, chiropractic care, relaxation techniques, homeopathy, prayer, massage, meditation, acupuncture, and naturopathy.15-17,21-23 This article will discuss the practical aspects of recommending a select group of these CAM therapies for the clinician managing the young patient with JIA. The following discussion provides a good sample of evidence-based recommendations, but does not include all possible therapies due to space constraints.
Anti-inflammatory Diet, Intestinal Permeability, and Autoimmune Disease
Increased intestinal permeability (IP) has been implicated in several autoimmune and inflammatory conditions like rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, celiac disease, type 1 diabetes, asthma, and inflammatory bowel disease.24,25 Mielants et al studied ileum biopsies of JIA patients and found a majority with histologic gut inflammation.26,27 Bacteria, antigenic fragments, and primed immune cells may migrate to joints from distant sites that originated in the "leaky gut," subsequently promoting synovitis.28 More research is needed to firmly establish this relationship. Based on ongoing research on IP and its role in autoimmune disease, there is potential in mitigating diseases like JIA with therapies that can reduce gut permeability.
Testing for Intestinal Hyperpermeability
The lactulose/mannitol test may help diagnose IP.29 Another possible non-invasive test for gut inflammation is the fecal calprotectin test, although more study is needed to validate its use.30-32 The lactulose/mannitol and fecal calprotectin tests are available commercially, and are often bundled with other tests aimed at identifying parasites, candida, and pathogenic bacteria as causes of gut dysfunction. Testing for IP may be skipped unless the patient requests the tests or the clinician needs test data for better compliance with recommendations.
The Elimination Diet
Certain food substances have been identified as negatively affecting the health of the small intestinal mucosa, whose functions include nutrient absorption, barrier function, metabolism, detoxification, immune modulation, and production of many biologically active compounds.33 Some food substances have been implicated in the production of advanced glycation end products (AGEs) and glycated lipids (ALEs). The production of AGEs and ALEs form free radicals that can exacerbate IP through inflammation. Certain foods higher in AGEs and ALEs include fructose, casein (dairy), gluten (wheat, barley, rye), tea, coffee, diet soda, roasted peanuts, and soybean products.34