Rheumatoid Arthritis (FL Autonomous Practice INITIAL Pharmacology)

Rheumatoid arthritis (RA), the most common autoimmune disease, is a chronic autoimmune disease that is systemic and progressive. This disease causes the lining of the joints to become inflamed, leading to bone erosion and permanent joint deformity. Uncontrolled inflammation damages soft tissue such as cartilage, which cushions joints and acts as the "shock absorber" in the body. The metacarpophalangeal (MCP), proximal interphalangeal (PIP), and thumb interphalangeal (IP) joints are most frequently involved. Tenosynovitis (inflammation and swelling of the tendon) causes reduced flexion and grip strength. Other areas of the body can be impacted, including the connective tissue, skin, eyes, heart, and lungs. It affects approximately 1.3 million adults in the United States and occurs in one percent of the population (Medline Plus, 2013). It is 2.5 times more common in people designated as female at birth (Cleveland Clinic, 2022).

"Body composition is frequently altered in patients with RA, with changes of increased body fat mass and reduced lean body mass (sarcopenia), even with a normal body mass index" (Matteson & Davis, 2022, para. 40). Rheumatoid arthritis negatively impacts the quality of life and self-image in that joints are often swollen and painful, making movement difficult. As the disease progresses, the pain is so severe and disabling that the ability to work is limited and often impossible. The Social Security Administration (SSA) identifies RA as a disability (Social Security Administration, 2022). "RA usually starts to develop between the ages of 30 and 60. In children and young people, it's called young-onset rheumatoid arthritis (YORA), and in older people (age 60 and above), it is called later-onset rheumatoid arthritis (LORA)" (Cleveland Clinic, 2022, para. 8).

Julie is a 54-year-old female who works in the accounting department of her local hospital. She smokes half a pack a day of cigarettes, is sedentary and eats a high-fat diet. There is a strong family history of rheumatoid arthritis. Her twin sister is in an assisted living facility as she can no longer manage daily living activities due to the excruciating joint pain she experiences. Julie visits her sister twice a week to play cards and has noticed increasing pain in the joints of her bilateral hands and toes. There is some noted swelling and redness in the MIP joints of her right hand. She has called her primary doctor and scheduled a visit due to the pain.

Rheumatoid arthritis likely results from both genetic and environmental factors. "The most significant genetic risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes, especially the HLA_DRB1 gene. The proteins from the HLA genes help the immune system distinguish the body's proteins from foreign proteins (such as viruses and bacteria)" (Medline Plus, 2013). Patients with schizophrenia have a one-third higher risk of rheumatoid arthritis than the general population (Sadock, Sadock, & Ruiz, 2017). The genetic risk in twin studies has been shown to be 60 percent, and "there is no difference in the overall genetic contribution to RA among variables of sex, age, age at onset, and disease severity" (Ishikawa & Terao, 2020, para. 5).

Environmental factors that impact the development of rheumatoid arthritis include smoking and alcohol intake. Other factors affecting RA development include birth weight, breastfeeding, socioeconomic status, and region of birth (Ishikawa-& Terao, 2020; Liao, Alfredsson, & Karlson, 2009). Smoking increases the risk of RA by 26 percent (Ishikawa-& Terao, 2020). Smoking also impacts the effect of DMARD treatment and thus can negatively impact the long-term outcomes of joint destruction and disability potential in patients who smoke (Ishikawa-& Terao, 2020).

Another environmental factor to consider is exposure to silica. Silica-induced inflammation and fibrosis can activate the innate immune system. This activation leads to cytokine production, pulmonary inflammation, adaptive immunity activation, tolerance breaking, and autoantibody production leading to tissue damage (Ishikawa-& Terao, 2020, para. 19).

While there is no definitive test for rheumatoid arthritis, there are ways that providers can accurately assess for and diagnose this disease. These include physical presentation, imaging, and biomarkers. Providers look for specific symptoms and decide which diagnostic test would be most appropriate.

A client with rheumatoid arthritis will likely present with fatigue, malaise, low-grade fever, weight loss, anemia, or anorexia, which are all early symptoms of RA. Stiffness of joints (especially after inactivity such as sleeping), paresthesia (tingling) of the hands and feet, or joint pain with swelling and warmth in the joint are common. Inflammatory arthritis will involve three or more joints (Baker, O'Dell & Romain, 2022). Involvement of the musculoskeletal system other than joints (occurs in approximately 40 percent of patients (Matteson & Davis, 2022).

On physical examination, the patient will have reduced or limited joint mobility. Deformities include the presence of rheumatoid nodules, which are subcutaneous, round, non-tender masses. Skin lesions may also be present and are caused by vasculitis. If the spinal cord is involved, the patient may have a positive Babinski's sign indicating compression of the vertebrae. Periodontal bone loss is also seen with lymphocytic infiltration of the salivary glands, which causes bone resorption (Matteson & Davis, 2022).

The goal of imaging the joints in patients with suspected rheumatoid arthritis is to rule out septic arthritis, identify soft tissue swelling, and discover early erosions of the joints. Radiography is inexpensive and provides for serial comparison of disease progression (Tsou, 2022). Percutaneous ultrasonography-guided aspiration may help localize and obtain samples of any fluid that can be found.

Image 1: Bilateral hand x-ray of a patient with Rheumatoid Arthritis.

According to the National Institute of Health, a biological marker (biomarker) is "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" (Biomarkers Definitions Working Group, 2001). By using biomarkers to identify the disease and the effectiveness of treatment, providers can identify patients at risk for RA and target those patients who are more likely to assume a more rapidly destructive form of the disease with early and aggressive interventions (Taylor & Deleuran, 2022). The primary biological marker used is the rheumatoid factor (RF). RF autoantibodies are found in approximately 80 percent of patients with RA. Citrullinated peptides (ACPA) have relatively high specificity for RA. If both are present, they are predictive of poor functional outcomes (Taylor & Deleuran, 2022). Other blood tests used to rule out and confirm the diagnosis include erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP). Both blood tests are typically elevated in RA (Baker, O'Dell & Romain, 2022).

Early interventions and aggressive treatment approaches are implemented to prevent joint damage and disability and improve quality of life. There is evidence that the course of disease activity in RA patients has become milder since the mid-1980s. Much of the improvement, particularly in the progression of joint damage, may be attributable to earlier and more widespread use of effective medications (Schur & Gibofsky, 2022, para. 11). The goal of treatment is to control synovitis and prevent joint injury (Cohen & Mikuls, 2022). The first line of treatment is disease-modifying antirheumatic drugs (DMARDs), a group of medications that suppress the immune system to control inflammation. The list below contains both conventional and targeted DMARDs (DMARDs, 2022):

• Azathioprine
• Baricitinib
• Cyclophosphamide – reserved for severe, treatment-resistant RA
• Cyclosporine
• Hydroxychloroquine – used to treat mild RA
• Leflunomide – used to treat moderate to severe RA
• Methotrexate – most commonly prescribed for RA
• Mycophenolate mofetil
• Sulfasalazine
• Tofacitinib – used in moderate to severe RA

DMARDs decrease pain and inflammation, prevent joint damage, and slow the progression of the disease but not without side effects. This drug category will suppress the immune system and thus increase the risk of both viral and bacterial infections. Other risk factors with these medications include nausea, vomiting, diarrhea, hair loss, and liver and pancreatic damage. Serious side effects can include infection, blood clots, and an increased risk of cancer. There is an increased risk of congenital disabilities for patients who are or become pregnant during treatment. They can also decrease sperm count in men who use DMARDs to manage their symptoms. 

Complications of therapy include generalized osteoporosis sequela to steroid use. Boney erosions and severe osteopenia increase the risk for atraumatic fractures. Long-term steroid use predisposes the patient to avascular necrosis.

Nonpharmacological interventions help delay progression and maintain quality of life. These include patient education about the disease and disease progression, appropriate use of rest, exercise, and nutritional counseling (Schur & Gibofsky, 2022). Teaching patients about their disease empowers them to understand what is happening in their bodies and what interventions will most effectively manage their symptoms and preserve joint function. Cognitive Behavioral Therapy (CBT) has significantly reduced self-reported pain, functional disability, disease activity, and low self-esteem (Schur & Gibofsky, 2022). Physical activity and appropriate rest preserve the range of motion and prevent deformities.

Physical therapy helps relieve pain, reduces inflammation, and preserves joint integrity and strength. "Patients should be evaluated and receive education and instruction by an expert in physical therapy to optimize strength and joint function without worsening pain and inflammation" (Schur & Gibofsky, 2022, para. 26). Physical therapy also uses targeting treatment options to maintain joint integrity through ultrasound, heat and cold therapy, rest, splinting, and relaxation techniques (Schur & Gibofsky, 2022).

Nutrition and diet therapy can also improve functioning. Diets rich in fish oil may result in decreased arachidonic acid metabolites and cytokines, with a concurrent decrease in symptoms" (Schur & Gibofsky, 2022, para. 34). Mediterranean diets, which encourage a high intake of fruits and vegetables, can decrease the risk of cardiovascular disease and overall inflammation. Elimination diets, where foods that cause inflammation are eliminated from the diet, have also been beneficial.

Research supports that more than 50 percent of all deaths worldwide can be attributed to inflammation-related disease conditions (Shields, Spahr & Slavich, 2020). Helping patients understand their diagnosis and available treatment options helps delay or reduce the risk of disability. Many people do not understand rheumatoid arthritis is a chronic and debilitating disease. Physical activity reduces disease, fatigue, and pain and improves overall psychological well-being (Schur & Gibofsky, 2022). The ability of psychosocial interventions to enhance immunity and improve immune-related health outcomes is grounded in research showing that immune system processes are influenced by social, neurocognitive, and behavioral factors (Slavic & Cole, 2013).

Reducing stress through meditation, eating healthy, exercising, and maintaining social interactions positively impacts and slows the progression of rheumatoid arthritis (Schur & Gibofsky, 2022; Shields, Spahr & Slavich, 2020; Slavic & Cole, 2013). Psychosocial factors modulate the immune system and help it adapt to stressful environments (Shields, Spahr & Slavich, 2020). Encouraging patients to incorporate and utilize these strategies will allow them to develop more robust coping mechanisms and help improve their quality of life for these patients.

Julie was seen by her nurse practitioner, and after a physical and radiographic exam, the nurse practitioner diagnosed Julie with rheumatoid arthritis. She was prescribed Methotrexate to decrease the inflammation and educated on her disease process. Smoking cessation education was provided along with a referral to physical therapy.

Rheumatoid arthritis is a chronic and debilitating disease that affects approximately 1.3 million adults in the United States and occurs in one percent of the population (Medline Plus, 2013). Current treatment modalities can positively impact the patient to help preserve joint function, mobility, and pain management. Key to positive outcomes include early intervention and aggressive treatment modalities.

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