Principles in the Management of Patients with Rheumatic Disease

The Team

Expertise should be the cornerstone of care for children with rheumatic diseases. Accurate diagnosis is the first step. Rheumatic diseases may be acute and explosive in onset, or they may evolve over a period of months and years. They can affect one or many organ systems. Rheumatic diseases may mimic several other inflammatory and noninflammatory diseases, and it may be difficult to make an accurate diagnosis initially. Even life-threatening complications and functional disabilities may have to be managed prior to accurate diagnosis, and great skill and patience are required to support the families in managing their problems in the face of uncertainties with diagnosis and prognosis.

Comprehensive treatment centers should be based in tertiary care academic centers. The treatment team ( Fig. 11.1 ) should consist of a pediatric rheumatologist, a nurse specialist, physical and occupational therapists, a social worker, and a psychologist, all working as a team with the child’s primary care physician. Consultations with an orthopedic surgeon, ophthalmologist, nutritionist, geneticist, nephrologist, neurologist, dermatologist, dentist, and other subspecialists should be available when required. Team care is expensive and not required for every child; however, these services should be available when needed ( Fig. 11.1 ). Service for patients who reside at a great distance from a pediatric rheumatology center is facilitated by good communication with adult rheumatologists or pediatricians who reside in the patients’ community or connection via telemedicine or outreach clinics. Appropriate training in basic rheumatology and examination techniques for community health care workers, pediatricians, and general practitioners at outreach sites can help foster trust and facilitate effective communication. Specially trained nurses have fulfilled the contact function effectively in many pediatric rheumatology centers.

Nutrition and Diet

Nutritional abnormalities affect a significant number of children with rheumatic diseases. ^, Factors that contribute to these abnormalities include metabolic effects of inflammation, physical activity, caloric intake, and the effects and side effects of drugs used to treat these diseases. The fact that fasting can have an antiinflammatory effect and that rare patients develop transient arthritis caused by certain foods (e.g., gluten-containing foods) has promoted interest in the relationship between diet and arthritis. Additionally, microbiome studies suggest there is likely a link between the microbiome and JIA pathogenesis, but further studies are needed to clarify the relationship. ^,

Patients and parents are also influenced by the publicity for nutrition and diet because scientific medicine cannot promise a cure for rheumatic diseases. Therefore the following questions are often raised: Can specific food items aggravate or precipitate symptoms of arthritis? If so, what food items should be avoided in the diet? What are the roles of dietary supplements, special diets, and elimination diets?

The physician’s main goal should be to control inflammation as rapidly as possible and thus minimize the nutritional abnormalities. The child should be maintained on a well-balanced, healthy diet with adequate vitamins and minerals and should be encouraged to be as physically active as possible. The physician also must counsel parents on the proper role of nutrition and educate them about fad diets, restrictive diets, and dietary supplements.

Physicians must educate parents that there are currently no specific, evidence-based dietary recommendations for the treatment of rheumatic diseases. There are no data to recommend an elimination or antiinflammatory diet, although rare patients may exhibit altered immune response or allergy to items such as milk or gluten. Moreover, special diets should be tried only under strict medical supervision, as there is danger of precipitating malnutrition and deficiency diseases. Megavitamins and macrobiotic diets should be avoided as well as a result of the risk of adverse effects.

Evidence-based advice should include supplemental calcium and vitamin D (particularly for children on glucocorticoid therapy), folic acid for children on methotrexate, and supplemental iron with or without vitamin C for children with anemia of chronic illness. ^,

In previous decades, the main dietary focus for patients with arthritis was increasing caloric consumption. However, as new therapies have been developed, the number of patients with insufficient caloric intake has declined. Today, childhood obesity is becoming an important issue in children with rheumatic disease. Increased body weight adds increased stress on the weight-bearing joints, which can lead to arthralgia. An individualized weight management plan and consultation with a dietitian may be indicated for some patients or those on chronic glucocorticoids. Programs that include exercise along with dietary restriction are more likely to be successful. Obesity is often seen in other family members, and success is found with family participation.

Children with rheumatic diseases on chronic glucocorticoid therapy are at increased risk for accelerated atherosclerosis. Additionally, children with chronic inflammatory diseases are at increased risk for dyslipidemia and cardiovascular disease. Children should be screened for additional risk factors, and screening should include a family history of early coronary heart disease, assessment of the amount and type of physical activity, measurement of blood pressure, body mass index, fasting blood sugar, and a lipid profile. Evaluation and screening may require referral to a dietitian or other specialists for further management.

Immunization

Immunizations play an important role in health and health maintenance of children. There are two major questions related to immunization and rheumatic diseases: (1) Is there any relationship between immunization and onset or exacerbation of rheumatic diseases? (2) What are the recommendations for children with rheumatic diseases who are on immunosuppression?

Although some earlier reports suggest that immunization may exacerbate or initiate rheumatic disease, more recent studies do not support this association. Studies in adults and children who received immune modulators and biologics showed no exacerbation of the underlying diseases after immunization with inactivated influenza virus and pneumococcal vaccines. ^, Current recommendations indicate nonlive vaccines appear to be safe in children with rheumatic disease while using glucocorticoids (≤2 mg/kg/day), methotrexate (≤25 mg weekly), other disease-modifying antirheumatic drugs (DMARDs) and biologics. Additionally, the immunogenicity of vaccines has been shown to be appropriate despite reduced responses when on methotrexate (>15 mg/m ² /week) and glucocorticoids (>2 mg/kg/day). Rituximab, cyclophosphamide, and azathioprine have been shown to greatly reduce responses to vaccines indicating the need to consider vaccination prior to therapy. Tumor necrosis factor (TNF) inhibitors did not reduce immunogenicity of vaccines. Adherence to national vaccination guidelines for live-attenuated vaccines is recommended unless patients are on high-dose DMARDs, high-dose glucocorticoids, or biological agents. However, vaccination can be considered on a case-to-case basis, weighing the risk of infections against the hypothetical risk of inducing infections by vaccination.

Although there are variations in response between patients on methotrexate compared with those on TNF inhibitors, there is overall good response to immunization with influenza vaccine, and it appears that the benefits of annual immunization of children with rheumatic diseases far outweighs any risk in most situations. ^, Studies also indicate that patients taking glucocorticoids and immunosuppressive drugs respond to influenza, ^, measles-mumps-rubella (MMR), meningococcal, human papillomavirus (HPV), and pneumococcal vaccines with adequate antibody titers. Children with SLE, asplenia, and complement deficiencies should receive pneumococcal vaccines (pneumococcal conjugate [PCV13] and polysaccharide [PPSV23]), and meningococcal vaccine (meningococcal conjugate [MCV]). Some evidence indicates that HPV infection is more common among patients with SLE. Additionally, there are reports of venous thromboembolic events associated with the quadrivalent HPV vaccine particularly in those with antiphospholipid antibody syndrome. However, the HPV vaccine has demonstrated safety and efficacy and is recommended for adolescent males and females prior to 25 years of age. Finally, immunizations should not give a false sense of security because immunity is not guaranteed, particularly in patients on high-dose glucocorticoids and potent immunosuppressive treatments. If antibody titers are low, vaccine boosters may be beneficial.

Ideally, children should receive all routine recommended immunizations before the start of immunosuppressive therapies. It is best to advise families to adhere to the regular schedule of immunizations while cautioning them about the rare possibility of disease flare. The following are a few special circumstances, exceptions, and precautions:

• 1.

  Active disease: Children with severe, active rheumatic disease should defer immunizations until the disease is at a more stable, less active, or inactive state; however, this can be determined on a case-by-case basis weighing risks and benefits of immunization.

• 2.

  Varicella-zoster (VZV): Varicella can be a major problem for children receiving immunosuppressive therapy. For all children, a suggested management strategy for the prevention of disease is given in Box 11.3 . Ideally, the antibody level against VZV should be known before the start of therapy. Varicella is a live virus vaccine that is generally contraindicated in children taking high-dose glucocorticoids (2 mg/kg/day of prednisone or its equivalent to a total of 20 mg/day of prednisone or equivalent for children who weigh more than 10 kg) for longer than 14 days. For children receiving smaller doses, the risk/benefit ratio must be assessed. Salicylate should not be used for at least 6 weeks after varicella vaccine administration. The potential for Reye syndrome in children treated with salicylates in association with varicella and influenza has been widely documented.

  BOX 11.3

  Varicella Prevention Strategy for Children Taking Glucocorticoids, Immunosuppressives, and Biological Agents

  • Document successful vaccination in the past; measure serum antibody level.

  • If seronegative (susceptible), immunize with varicella vaccine 3 weeks before starting therapy.

  • Susceptible children exposed to varicella should receive varicella-zoster immunoglobulin within 72 hours after exposure.

  • If chickenpox develops, treat with oral or parenteral acyclovir depending on severity and spread. Stop biologic and disease-modifying antirheumatic drug temporarily but continue glucocorticoids.

• 3.

  Children on immunosuppressive therapy:

  • a.

    Children undergoing immunosuppressive therapy, including high-dose glucocorticoid therapy, should not receive any live virus or bacterial vaccines. If high-dose glucocorticoids and cytotoxic drugs have been stopped, live vaccines may be given after a minimum of 3 months. It is also important to remember that the nasal spray vaccine for influenza contains live virus and is therefore contraindicated in immunocompromised patients and their contacts. Only the inactivated form of the influenza vaccine should be used. Recommendations made by the Committee on Infectious Diseases of the American Academy of Pediatrics should be followed for children. The British Society of Rheumatology recommends the use of influenza A, meningococcus C, Haemophilus b, hepatitis B, and tetanus toxoid, but warns that the response may be suboptimal.

  • b.

    Children on immunosuppressive therapy are at increased risk for infection. Fortunately, most infections are minor, but risk for opportunistic infections and varicella appear most commonly with anti-TNF use. ^, Other less common infections include mycobacteria, histoplasmosis, Aspergillus species, Candida , hepatitis B, Epstein–Barr virus, and herpes simplex virus. Prior to initiation of anti-TNF therapy, patients should be screened for latent tuberculosis and hepatitis B immunity.

• 4.

  Intravenous immunoglobulin (IVIg): The effectiveness of live vaccines may decrease if administered 2 weeks prior to IVIg administration. MMR and varicella vaccines should be administered 8 months after IVIg. Additionally, if MMR and varicella are administered 14 days prior to IVIg, they should be repeated 8 months after IVIg.