Arthritis Nursing CE Course

eight as a mechanical factor contributes to the development of OA, but the presence in non-weight bearing joints of obese patients has resulted in an expanded understanding.  Adipose tissue is an endocrine organ that secretes chemical mediators, including cytokines, adipokines, chemokines, and lipids, which act systemically and locally.  The cytokines interleukin-6 (IL-6) and IL-8 in serum and synovial fluid of OA patients are increased. While the specific process is not known, these cytokines increase inflammation as well as increase tissue breakdown and decrease tissue repair, especially in the synovial tissue. The discovery of leptin, an inflammatory molecule produced by adipose tissue, led to the additional finding of changes in immune cells that indicate that obesity may result in a slight but chronic level of systemic inflammation.  Along with leptin, the other adipokines (adiponectin, resistin, and visfatin) are implicated in rheumatoid arthritis, diabetes, and inflammatory bowel disease. The cytokines activate nociceptive (general) pain receptors, and reports of generalized and musculoskeletal pain increase with leptin and body mass index (BMI) in women. Each of these contributes to the patient’s experience of pain with OA (Capezuti, Malone, Gardner, Khan, & Baumann, 2018; Urban & Little, 2018). 

OA Risks and Protective Factors

Risk factors for OA include aging, estrogen deficiency, genetics, mechanical overload, metabolic factors, and previous trauma (Deveza & Loeser, 2018.) Among the non-modifiable risk factors, aging is the most common with estimates that up to 85% of those over 65 have radiographic changes. The interplay of genes and aging contribute to the increase in OA. Both oxidative-stress and “senescence-associated secretory phenotype” are recognized as a foundation for understanding aging as a risk for OA. Senescence-associated secretory phonotype typically reinforces senescence in an autoimmune type manner and heightens inflammation with adverse effects to the tissues microenvironment (Coppe, Desprez, Krtolica & Campisi, 2014). Genetics contributes through inherited connective tissue disorders or systemic disorders, including acromegaly and metabolic syndrome. Defects in the collagen II gene influence joint formation and production of lubricin, which physiologically supports structures and promotes smooth joint function. Joint malalignment is a risk factor for knee OA progression (Goldman & Schafer, 2016). The shape of the bone and the joint are genetic factors, and the influence of this is illustrated by the finding that having a parent with a history of total knee replacement increases the risk for both pain and physiologic change in the knee (Allen & Golightly, 2015). One of the genetic factors is exhibited in patients with distal interphalangeal joint involvement noted by Heberden nodes (Cash & Glass, 2017; Goldman & Schafer, 2016). Women have a higher prevalence, greater reported pain, and more disability from OA (Arthritis Foundation, 2018; Cash & Glass, 2017).  Krishnasamy, Hall & Robbins (2018) find that fat filtration of the skeletal muscle is increased in women, which is associated with both pain and structural evidence of knee OA.  The weakened muscle is less able to provide support to the joint. Exercises that promote strength and length, such as swimming and bicycling, are encouraged specifically for this reason (Cash & Glass, 2017). Risk factors for individuals also include extremely high bone density, smoking, and history of low-birth-weight or prematurity at birth (Allen & Golightly, 2015). 

Obesity is the most common modifiable risk factor for OA.  Obesity increases the risk of OA three times and also predisposes obese individuals to a more rapid progression of the disease (Allen & Golightly, 2015).  Primary prevention includes a balance of nutrition and activity to maintain a healthy weight, which promotes bone health as well as preventing joint damage.  In patients who are already obese, Skou, Pedersen, Abbott, Patterson & Barton (2018) report that a 5% weight loss can improve function and decrease symptoms of OA.   The low-grade chronic inflammation that occurs with obesity contributes to the development of cardiovascular disease, type 2 diabetes, and dementia, which then compound the immobility (Skou et al., 2018).   

The impact of nutrition on OA is currently being researched.  Findings reviewed by Allen and Golightly (2015) included the Osteoarthritis Initiative Study, which found that women with a greater milk intake had less joint space narrowing, which is associated with OA.  A deficiency of vitamin D is associated with OA, but current data does not support vitamin D supplementation to prevent or treat OA.  Another study found that low vitamin K1 intake in older adults correlated with greater progression of pathologic changes of OA over three years (Allen & Golightly, 2015).  

The greatest risk factor for early-onset OA is a joint injury. Occupations which include squatting, bending, and lifting increase knee involvement whereas work with tools which are high impact and rapid vibration, such as pneumatic drills, increase wrist and hand OA (Goldman & Schafer, 2016)  Adolescent sports result in 2.5 million knee injuries each year and immediate medical attention is advised.  Initial interventions of rest/ice/compression/elevation (RICE) and ibuprofen (Motrin, Advil) followed by early exercise and long-term physical therapy can prevent ongoing knee pain and disability. Exercises that both strengthen and stretch the muscles supporting the knee are recommended to begin within 24 – 48 hours of a minor injury. Some simple prevention measures for knee injuries include:

1. Warm-up: before intense exercise or sports, take the time to walk and perform slow, gentle stretches.
2. Knee exercise: include stairs, bikes, and leg exercises with weights as part of overall fitness.
3. Work to gradually increase the intensity of exercise rather than making sudden changes.
4. Wear good shoes: assure good shock absorption and traction along with the correct fit.
5. Use devices to protect and aid the knee, especially during sports.
6. Wear seatbelts at all times (Davis, 2017). 

The presence of OA is also a risk factor for other diseases.  The presence of symptomatic OA predicts the development of cardiovascular disease, and the number of joints that have decreased function is correlated to onset (Corsi et al., 2018).  

OA Signs and Symptoms

The outstanding symptom of OA is joint pain in one or more joints. Some patients experience acute episodes while others have almost constant pain, including pain that can disturb sleep. The pain level varies from mild to severe. Pain can increase with activity, especially with repetition or load-bearing activity. Stiffness occurs after periods of rest or inactivity, such as sleeping, but usually resolves within 30 minutes (Goldman & Schafer, 2016). Crepitus, a grating sound, may occur and has been found to occur earlier than pain in some patients (Lo, Strayhorn, Price, Eaton, & McAlindon, 2017). Symptoms unique to spinal arthritis are caused by pressure on spinal nerves. Low back pain is the “hallmark of lumbosacral spine OA”. The patient may experience pain, numbness and tingling in the extremities with spinal OA (Schlenk & Shi, 2019, p. 24).

Specific joints exhibit more unique symptoms.  Knee OA may be identifiable by the resulting deformity:  medial compartment OA may lead to a bow-legged (varus) deformity while lateral compartment leads to a knock-kneed (valgus) deformity (Allen & Golightly, 2015).  Patellofemoral tends to exhibit pain that increases when going down stairs. Synovial (Baker’s) cysts, bursitis, or meniscal damage may cause knee instability and pain.  Groin pain, which may radiate to the knee, is typical of hip arthritis. Hip movement is limited, beginning with internal rotation and eventually limitation in all directions. The patient may have asymmetry from changes in leg length. Pain and swelling, along with the limitation of movement, are found in the thumb when the carpometacarpal joint is affected. The most common site for OA in the feet is the base of the big toe, where bunions occur along with the pain. Degenerative disk disease may occur along with OA in the spine and result in spinal stenosis, neck pain, or back pain (Goldman & Schafer, 2016). Loss of function is commonly experienced by the patient.  Studies that include gait speed and chair stands (the ability to rise to a standing position from a chair without the use of the arms) find that these skills decline as symptoms of OA progress (Corsi et al., 2018).

OA Diagnosis

The patient’s reports of joint pain and loss of function are the primary diagnostic tools for OA. Physical assessment is not “sufficiently sensitive” but remains a major diagnostic tool in OA. Ultrasound and magnetic resonance imaging (MRI) can detect synovitis while high-sensitivity c-reactive protein (hs-CRP) and IL-6, along with novel systemic markers, can detect systemic inflammatory processes (Deveza & Loeser, 2018).  Additional laboratory tests such as sedimentation rate, complete blood count, and a metabolic panel may be used in some patients to rule out other diseases. There is no definitive laboratory test at this time that is used to diagnose OA specifically. A synovial fluid sample may also be obtained and examined for the presence of microbes, white blood cells, or crystals. While joint radiography and MRI are the two most common tests, there is not a direct relationship between the results of the tests and the level of pain and discomfort experienced by the patient. Radiographic changes include osteophytes, narrowed joint space, and sclerosis of the bone beneath the cartilage. Ultrasound has been used to determine local synovitis but not significantly for diagnosis. MRI gives the greatest detail of the structural changes but is used predominately for research rather than clinical diagnosis due to economic reasons (Goldman & Schafer, 2016). Inflammation of the infrapatellar fat pad increases signal intensity on MRI and has been linked to increased pain as well as lesions on the bone marrow and breakdown of cartilage within the knee (Urban & Little, 2018).    

OA Treatment and Management

Treatment guidelines for OA have changed in recent years.  All guidelines include pharmacologic and non-pharmacologic measures. Older guidelines called for acetaminophen (Tylenol) to be used first for analgesia. Newer guidelines question the use of acetaminophen (Tylenol) due to its liver risk along with a lack of anti-inflammatory effects.  While most promote exercise as the first intervention, pain relief is a priority for the patient during an exacerbation. Modifications such as footwear with thick, soft soles and no heels, splints, and canes can support the joint for more comfort (Cash & Glass, 2017).  Medication is used for all levels of pain, but surgery is the final intervention that may be used (Goldman & Schafer, 2016). 

Acetaminophen (Tylenol) is used for analgesia in OA patients at elevated risk for bleeding, gastric ulceration, or renal impairment.  Acetaminophen (Tylenol) rarely has adverse effects at therapeutic levels, but daily use as required by OA increases the risk of hypertension.  It is also associated with an increased risk of asthma.  Stevens-Johnson syndrome and toxic epidermal necrolysis are medical emergencies that can occur with acetaminophen (Tylenol) use requiring education of the patient to seek medical treatment immediately for a painful rash or blisters on the skin. Liver function impairment is a primary concern with acetaminophen (Tylenol). A daily maximum of 2000 mg is recommended for patients with alcohol use rather than the usual 4000 mg daily maximum.  Patients using acetaminophen (Tylenol) regularly require an awareness of combination medications such as hydrocodone/acetaminophen (Vicodin, Lortab), which may contribute to the daily total (Burchum & Rosenthal, 2019). 

Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively with OA for both pain relief and to decrease the inflammation in the joint.  The first generation NSAIDs include aspirin (Bayer), ibuprofen (Motrin, Advil), and naproxen (Naprosyn), all of which inhibit both COX-1 and COX-2 enzymes. Cyclooxygenase leads to prostaglandin formation that is caused by inflammation and results in pain. The greatest risk with this group of medications is gastric ulceration.  Patients who use these drugs for long-term treatment of OA are frequently prescribed proton pump inhibitors, histamine-2 receptor antagonists, or H-2 blockers, or misoprostol (Cytotec).  Other recommendations to decrease the risk of gastric ulceration include taking the medications with food and assuring the dose is taken with a full glass of water, which is especially important with aspirin (Bayer) as the particles directly cause damage to stomach lining (Burchum & Rosenthal, 2019).  The topical NSAIDs, ketoprofen (Orudis) and diclofenac (Voltaren), are available in gel formulations, which can be effective in pain relief without the adverse gastrointestinal effects of systemic formulations (Derry, Conaghan, Da Silva, Wiffen, & Moore, 2019). Second-generation NSAIDs only inhibit COX-2, which decreases the risk of gastric ulceration. Celecoxib (Celebrex) is currently the only drug available. The caution is that there remains a risk of renal impairment and an increased risk for stroke and myocardial infarction (MI). A progressive approach to the treatment of musculoskeletal pain should begin with non-pharmacologic measures, and then utilization of acetaminophen (Tylenol) or aspirin (Bayer), other NSAIDs, and as a “last resort” a COX-2 inhibitor (Burcham & Rosenthal, 2019). Tramadol (Ultram) has been researched for analgesia in OA, but a literature review by Toupin-April et al. (2019), reports minimal improvement in pain or function. They found only a small number of people who showed significant improvement, although it may still be used for short-term exacerbations (Toupin-April et al., 2019). 

 Alternative and complementary treatments are frequently used for OA.  Cash & Glass (2017) mention the use of Tai Chi as an alternative therapy that provides motion without joint stress.  Topical application of capsaicin cream requires wearing gloves during application and warning that it may cause a burning sensation at the application site.  Immediate handwashing is necessary to prevent unintended application to other tissue (Schlenk & Shi, 2019). Systematic reviews and meta-analyses have found the use of chondroitin sulfate and glucosamine sulfate not to be consistently beneficial for knee OA (Capezuti et al., 2018).  

Injections into the joint are often used to treat severe pain.  Corticosteroid injections, most commonly triamcinolone acetonide (Kenalog-10) or methylprednisolone (Depo-Medrol) mixed with 1% or 2% lidocaine, are limited to three to four times a year at three-month intervals.  The nurse should caution the patient that the pain may increase in the first 24 to 48 hours after an injection before the pain begins to decrease (Cash & Glass, 2018).  A meta-analysis on the effects of corticosteroid injection for hip and knee OA indicated that the best outcomes are seen in patients experiencing severe pain rather than moderate pain, but the benefits are short term (Deveza & Loeser, 2018).   The American Academy of Orthopedic Surgeons 2013 practice guidelines make no recommendation for, or against, intra-articular corticosteroid injections but include a strong recommendation against using hyaluronic acid for knee OA based on lack of evidence for clinical improvement.  The rate of use of corticosteroid injections remains the same but is increased in patients less than 50 years of age. A specific caution is that corticosteroid injections increase risk for post-surgical infection if administered within a few months prior to total knee arthroplasty. Hyaluronic acid injections have decreased overall but are used more by primary care physicians (Bedard et al., 2018; Zelman, 2019).  

Exercise is both preventative and therapeutic for OA. Whether education and self-management or physical therapy are implemented, it provides benefits without the high cost or adverse effects of medication and surgery. Skou et al. (2018) report that exercise is two to three times more effective at pain relief for knee OA than acetaminophen (Tylenol). Patients may prefer exercise to pharmacologic treatment to avoid the adverse effects of medication. Emphasis has been on strengthening the quadriceps but work to strengthen the hamstrings can decrease knee OA symptoms as well. The quadriceps work to extend the knee, and its strength is used both for stability and shock absorption during mobility (Krishnasamy et al., 2018).  A specific exercise for this purpose is the seated leg raise. While seated in a chair with feet on the floor, the patient raises one leg at a time parallel to the floor, holds for 30 seconds, then lowers the foot slowly while keeping the other foot flat on the floor. The recommended frequency for this exercise is 10 repetitions on each side twice a day (Harvard Men’s Health Watch, 2018).  A review of randomized controlled trials of land-based exercises includes aerobic, resistance, and performance activities. Walking can begin on a treadmill for a softer surface with an eventual goal of at least 6000 steps per day.  Nordic poles can distribute some weight away from the knees during walking.  The physiologic effect of activity on OA also extends to decreases in other associated disorders, including cardiovascular disease, type 2 diabetes, depression, and Alzheimer’s disease (Skou et al., 2018).  

Surgical intervention is a common treatment as OA severity increases, especially with a loss of function. A review of the evidence does not support surgical intervention for patients experiencing mild to moderate symptoms (Palmer et al., 2019). Arthroscopic surgery is not generally recommended except in patients who experience “locking” or other severe mechanical disruptions of function as other treatments are comparable in terms of outcomes (Capezuti et al., 2018).  The most common surgical intervention is total joint replacement with the knee and hip as the most common sites, respectively.  Surgical intervention is recommended when pain is severe, and there is a loss of function as well as radiographic evidence of physiologic progression.  Postoperatively, patients usually experience less pain and improved mobility, with over 95% of joint replacements lasting over 20 years (Capezuti et al., 2018). 

OA-Related Evidence-Based Practice and Implications for Nursing

Nurses encounter patients at risk for or experiencing OA in most settings. Table 1: Nursing Care for OA Patients, highlights assessment and some interventions to consider in a variety of clinical settings. In Ignatavicius’ (2019) concept-based approach to nursing, OA is an exemplar for the concept of mobility. Within the framework of concept-based nursing, arthritis impacts comfort; health, wellness and illness; inflammation; and mobility.  The patient’s ability to perform activities of daily living (ADLs) is critical to wellness. The physiologic consequences of immobility are all experienced by patients with OA and require assessment and intervention by the nurse.  These are listed as: “pressure injuries, disuse osteoporosis, constipation, weight loss or gain, muscle atrophy, atelectasis/hypostatic pneumonia, venous thromboembolism, urinary system calculi, depression, changes in sleep-wake cycle and sensory deprivation.” Other concepts that the nurse needs to incorporate into planning care include comfort, inflammation, and safety (Ignatavicius, 2019, p. 291).

Table 1: Nursing Care for OA Patients

CLINICAL PRACTICE AREA	ASSESSMENT	INTERVENTION
Clinic setting (the most common location for encounters with OA patients.)	Patient’s preferred activity. Daily activity level. Weight and height. Gait: observe for posture and symmetry of movement. Muscle strength and joint range of motion. Occupational risk:  Does the patient’s job require lifting, squatting, bending, or repetitive activity. The onset of unilateral joint pain. The onset of crepitus  Co-morbidities: DM II, CVD, Depression Joint specific discomfort and limitation: exemplar: thumb arthritis	Teach the patient to self-manage activity by exploration and incorporation of preferred activities (Schlenk & Shi, 2019). Teach to include weight-bearing activity within daily routine with a goal of 6000 – 10000 steps (Skou et al., 2018). Promote the maintenance of recommended weight or reduction for obese patients (Lewis, Bucher, Heitkemper & Harding, 2019). Refer for further evaluation if malalignment, bow-legged, or knock-kneed, as these increase risk for more rapid progression of OA (Goldman & Schafer, 2016). Implement 0-5 scale (5 = normal, 0 none) for both measures. Implement specific measures to support joint (i.e., medially-directed patellar taping for the knee, Schlenck & Shi, 2019) Teach the patient to use supports, i.e., knee brace or back support. Assure proper placement.  Refer to PT for specific exercises for strengthening and proper positioning. (Skou et al., 2018) Teach that interventions can prevent progression and relieve pain rather than OA being inevitable progression and constant pain (Goldman & Schafer, 2016). Teach that occasional sounds in joints are expected but to report if frequency increases (Lo et al., 2017). Identify factors that may decrease activity levels and plan holistically for the individual patient to maximize function and prevent complications (Schlenk & Shi, 2019). Gentle exercise and application of ice and heat for five to ten minutes (note decrease time for smaller joint) on the thumb provides direct comfort. (Mayo Clinical Health Letter, 2018).
Perioperative	Level of use of NSAIDs. Postoperative mobility.	Teach: Discontinue aspirin/NSAIDs one week prior to procedures with risk for bleeding. For low-risk surgeries, no discontinuation is needed. (Burcham & Rosenthal, 2019). Plan early and progressive ambulation for all surgeries (Lewis et al., 2017).
Obstetrics	OTC use of NSAIDs.	Teach that NSAIDs interfere with prostaglandin formation and increase the risk of patent ductus,  thus suggest no NSAIDs during the last trimester (Burcham & Rosenthal, 2019).
Pediatrics	Participation in sports or intense activity. Use of seat belts.	Encourage the utilization of joint support measures (i.e., knee support for basketball) to decrease long-term injury risk (Schlenk & Shi, 2019). Teach seat belt use to prevent skeletal injuries, specifically knee injuries caused by bracing during motor vehicle accidents.
Home Health	Environmental safety. Utilization of supportive mobility devices.	Perform fall risk assessment and implement measures to minimize tripping hazards inside the home (Pechar, 2020). Teach and evaluate the effectiveness of canes and walkers, where indicated.
Rehabilitation	Pain level and mobility after joint replacement.	Assist in progressive distance and duration of ambulation.  Promote the use of assistive devices such as zipper pullers and long-handled shoehorns (Schenck & Shi, 2019).
Geriatrics	Pain level after resting and during moderate activity. Activities of daily living.	Encourage participation in individual and group activities to improve mobility (Schub & Schiebel, 2017b). Implement adjunct measures such as plate guard to promote independence and delegate tasks to staff as needed for maximal function (Schlenk & Shi, 2019).
Adult acute medical-surgical	Joint mobility with PROM and AROM. Nutritional needs  Assess nursing implication for OTC and prescribed medications.	Ambulate patient. Perform range-of-motion if that patient is unable to perform independently every 2 hours (Ignatavicius, 2019).  Collaborate with a dietitian to plan for a high-fiber, high-protein diet to promote elimination and decrease muscle loss during immobility (Ignatavicius, 2019). Identify medication interactions and follow-up as needed i.e., additive effects with warfarin (Burcham & Rosenthal, 2019).

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic, progressive autoimmune disease that affects approximately 1% of the population (Carafaro., 2020). A new diagnosis of RA occurs in 3 in 10,000 people each year (Balderama & Schub, 2018). Onset is most commonly during ages 30 – 60 but can occur earlier or later.   Women are approximately three times more likely than men to have RA (Arthritis Foundation, 2018).  All races can have RA, but the highest rates are in Native Americans at 5 – 6% (Balderama & Schub, 2018). Until recently, the average lifespan for people with RA was decreased by 10 – 20 years (NIH, 2018). Even with improvements from current therapy, lifespan expectation remains three to seven years less than the average (Craven, 2016).  In the first 10 years after a diagnosis of RA, 40% of people cannot continue to function in their job (Balderama & Schub, 2018).  

RA Pathophysiology

Rheumatoid arthritis involves both systemic and localized changes.  Within the joints, there is long-term synovitis and pannus formation.  Synovitis involves the recruitment of a variety of immune cells, including neutrophils and T helper cells, which are then activated to release monocytes, macrophages, and fibroblasts within the joint. This leads to synovial hypertrophy and chronic joint inflammation. The cytokines which contribute to this process include IL-1, IL-6, and tumor necrosis factor (TNF) (Dong, Fu, Ji, Li, & Gu, 2018; Lewis et al., 2017). The formation of pannus, a vascular granulation tissue that destroys normal joint structures, is a pathologic change unique to RA (Carafaro., 2020). Pannus is an invasive synovial tissue that breaks down the cartilage and the bone beneath it. Inflammatory cysts form initially within the bone, and later erosion of the bone occurs (Ostrowska, Maslinski, Prochorec-Sobieszek, Nieciecki & Sudol-Szoprinska, 2018). Fibroblast-like synoviocytes (FLS) act directly to destroy joint structures as well as releasing chemicals to cause further destruction (You, Koh, Leng, Kim & Bucala, 2018). Interleukin-9 and its receptor have been recently identified as a regulator of pannus formation (Raychaudhuri, Abria, Maverakis & Raychaudhuri, 2018).

Systemically, evidence suggests that changes in the regulation of the immune process occur years before symptoms (You et al., 2018). The immunologic nature of RA is based on the adaptive immune system.  The activation of T-cells in RA cause T-cell proliferation and secretion of cytokines including tissue necrosis factor (TNF) which act to promote inflammation and joint destruction.  In humoral adaptive immunity, B lymphocytes for antibodies but in RA they promote production of autoantibodies including rheumatoid factors (RF) and anti-cyclic citrullinated peptide (including anti-CCP).  B-cells present antigens to the T lymphocytes, direct cellular interactions and promote cytokine production.(The drug rituximab (Rituxin) eliminates  circulating B-cells but does not eliminate all autoantibody formation). Neutrophils increase within the joints in RA and produce prostaglandins (which are known to cause pain) and chemicals that increase the effects of proteases and depolymerize hyaluronic acid (a lubricant in the joint) resulting in joint damage. Microphages produce the proinflammatory cytokines including TNF, IL–1, IL-6, IL-8 and  granulocyte-macrophage colony-stimulating factor(GMCSF).These cytokines damage the joint but also generate acute phase response proteins (such as C-reactive proteins) and produce prostaglandins, leukotrienes, nitric oxide that have local and systemic effects. Synovial fibroblasts secrete interleukins and GMCSF.  Chondrocytes, activated by IL-1 and TNF, secrete proteolytic enzymes destroying the joint cartilage that is evidenced as narrowed joint spaces on x-ray. The most important cytokines are TNF, IL-1 and IL-6 which activate cells within the joint (paracrine), systemically (endocrine), and activation within the same cell (autocrine). The cytokines cause systemic symptoms of fatigue, fever and cachexia, as well as local structural and chemical joint changes. Other soluble mediators include prostaglandins, leukotrienes (which affects vascular permeability), matrix metalloproteinases (degrade cartilage), kinins (potent agents of pain) and substance P (vasoactive, proinflammatory peptide) (John’s Hopkins Arthritis Center, 2019). 

RA Risks and Protective Factors

A combination of genetics and environmental factors participate in the development of RA.  The specific genetic risk factors identified are the presence of human leukocyte antigen (HLA-DRB₁) alleles (Carafaro, 2020) HLA -DR₄, PRPN22, and PAD14 genes (Barous, 2018; Balderama & Schub, 2018). Genetic factors comprise roughly 50% of the risk for the development of RA (Balderama & Schub, 2018). An environmental trigger is suspected to be microbiologic, although no specific organism has been identified. Some of the organisms suspected include Mycoplasma organisms, Epstein-Barr virus, and rubella viruses (Caple & Parks-Chapman, 2017). A bacteria found in periodontal disease, Porphyromonas gingivalis, causes protein citrullination is suspected to precede RA in some patients. (John’s Hopkins Arthritis Center, 2019).

 Rheumatoid arthritis occurs most often in women and has increased incidence with aging.  Most patients report a recent systemic illness or trauma. A family history of RA is also a risk (Balderama & Schub, 2018; Cash & Glass, 2017). Smoking, high caffeine intake, and oral contraception increase the risk, especially in people with genetic risks.  Occupational exposure to dust and silica also increases the risk of RA (Carafaro, 2020). Obesity and birth weight greater than 4 kg are also risk factors (Balderama & Schub, 2018). Overweight or obesity is present in 60% of RA patients and frequently exists at the initial diagnosis of RA (Feng et al., 2019).  A commonality identified is that an environmental stressor causes cellular changes in barrier tissues that initiate the immunologic response (McInnes & Schett, 2011). 

The risk for RA is reduced during the first five years postpartum, but 35 – 52% of patients with RA who are pregnant have symptoms while 39 -90% have a postpartum flare (Scheibel & Uribe, 2018; Schub, 2018a). Alcohol consumption has been found to reduce the risk of RA (Balderama & Schub, 2018). Vitamin D intake, through both food and sunlight exposure, has been found to be inversely related to the severity of symptoms and decrease prevalence (Aslam, John, Bhatti, Jahangir & Kamboh, 2019).

The systemic nature of RA impacts cardiovascular, cerebrovascular, cognitive, liver, lung, muscle, bone, skin, adipose, and brain function.  Anti-inflammatory treatment can prevent the early onset of osteoporosis in RA patients. Lymphoma is a risk for patients, with greater disease activity increasing the risk. Another risk is lung cancer related to fibrotic lung changes in smokers and non-smokers.  The joint changes in the cervical spine can cause spinal cord compression and thus become a life-threatening complication (Balderama & Schaub, 2018; March & Schub, 2018).A specific risk in health care with cervical spine involvement is that it may be asymptomatic, therefore, medical personnel should be aware that extension of the neck, such as during intubation, can cause spinal cord injury (Kontzias, 2018b). The leading cause of death in RA is cardiovascular disease (Balderama & Schub, 2018).  

RA Signs and Symptoms

The characteristic findings in RA include chronic, symmetrical joint swelling and stiffness, which indicates joint destruction.  Joint stiffness after sleep or other inactivity typically lasts for more than 60 minutes (Craven, 2016).  The joints of the appendicular skeleton are most commonly affected, but the cervical spine may also be involved (Carafaro, 2020). Typically, joints are painful, tender to touch, edematous, and there may be deformity with further progression of the disease.  Most people with RA experience “flares” with increased pain along with increased systemic symptoms such as cardiopulmonary, renal, and immune symptoms.  Significant disability accompanies this pain and dysfunction with need for supportive devices to prevent falls (Balderama & Schub, 2018). The most common joints affected first are in the hand with significant deformities as the disease progresses. The proximal interphalangeal (PIP) joints and metacarpophalangeal (MCP) joints in the hand and the metatarsophalangeal (MTP) joints in the foot are common sites for early joint involvement (Lewis et al., 2017). Ulnar deviation occurs early, and observation of the fingers bent toward the side of the hand opposite the thumb. Patients exhibit pitting edema in the hands that resemble a boxing glove.  Monitoring grip strength is an assessment of disease progression (Cash & Glass, 2017.) Figure 1 (below) illustrates the common joints of the hand that may be involved.

The typical onset of RA is gradual, and the patient may experience tiredness, loss of energy, and possibly anorexia with weight loss prior to joint symptoms (Lewis et al., 2017). In older adults (over age 60), the onset is more sudden, occurs equally in men and women, and is more likely to involve large joints such as the shoulder; thus, some consider it a distinct clinical entity (Schub & Schiebel, 2017b). Some patients experience rheumatoid nodules, non-tender round masses that occur in pressure areas of the skin. Complications can occur if damage or infection of the nodule occurs. Blindness can result if the nodule is in the sclera. Nodules can occur in muscles, including the heart, resulting in altered muscle function (Lewis et al., 2017).  Rheumatoid nodules indicate poor prognosis (Caple & Parks-Chapman, 2017).  Other complications include Sjogren’s syndrome, which causes dry mouth and dry eyes; Felty syndrome, causing low white blood cell count; and splenomegaly, enlarged spleen (Lewis et al., 2017).  

 RA affects mental health as well as physical health. Some mental health behaviors identified as significant by March and Schub (2018) include changes in personality, pain behaviors, level of self-efficacy, level of perceived helplessness, and cognitive distortion. Chronic pain, deformity, and loss of function contribute to the risk for suicidal ideation. The most effective intervention has been cognitive behavioral therapy along with exercise (March & Scheibel, 2018) RA patients who averaged the recommended 150 minutes of moderate exercise per week had better word retrieval. Fewer memory complaints were found in patients taking anti-TNF biologics (Delzell, 2018).

RA Diagnosis

Diagnostics for RA reflect the local and systemic aspects of the disease process with no single diagnostic test considered definitive. Medical history and examination contribute to the diagnosis. Radiologic tests include conventional x-ray, MRI, and CT. While conventional x-ray is not significantly diagnostic as a single tool and joint changes are not always noted early, it may be helpful to obtain baseline radiographs to track disease progression.  MRI and CT can identify joint damage in early RA and are used specifically for cervical-spine involvement to identify cord compression (March & Schub, 2018).  Cervical spine ultrasound may be used to evaluate secondary changes of tenosynovitis and effusions (Caple & Parks-Chapman, 2017).  MRI can be used to see bone marrow edema, as well as evidence of inflammatory infiltrates, which can be found early in the disease and indicate the likelihood of rapid disease progression.  Both MRI and ultrasound can detect synovitis, cysts, hyaline cartilage defects, bone marrow edema, and bone erosions. MRI may be useful in detecting damage to the cartilage prior to symptoms and evaluation of intra- and extra-articular fat tissue changes that accompany synovitis (Ostrowska et al., 2018).

Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) are detectable in some patients prior to disease development. This ACPA is the laboratory test most specific to RA, previously known as anti-CCP (citrullinated peptide antibodies) (Craven, 2016). Earlier diagnosis and treatment can be made based on an elevation of ACPA (Lewis et al.,2017). Rheumatoid factor (RF) is elevated in 80% of people with RA at some time and increases during exacerbations.  The inflammatory process of the disease elevates both the ESR (erythrocyte sedimentation rate) and the hs-CRP, which correlates with the progression of joint damage on x-ray.  Antinuclear antibody (ANA) is elevated in 20-30% of RA patients.  The most general laboratory test, the CBC, gives information about anemia and inflammation status that may guide therapeutic interventions (Caple & Parks-Chapman, 2017). Joint fluid may be examined for WBCs ranging from 2,000 – 50,000/mm³ as well as the presence of MMP-3 (matrix metalloproteinase-3), an enzyme which is known to breakdown connective tissue encoded by the MMP-3 gene (Lewis et al., 2017; March & Schub, 2018; National Center for Biotechnology Information, 2019).

The diagnosis of RA currently uses a scoring system devised in 2010 by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR).  A score of six or greater on a ten-point scale is diagnostic of RA.  The four categories are the number of joints involved (zero to five possible), serum RF level (zero to three possible), acute phase reactants which include either CRP or ESR (zero to one possible), and duration of symptoms (zero to one possible) (Lewis et al., 2017). The Short Form Score for Assessment of Chronic Rheumatic Affections of the Hands (SF-SACRAH) evaluates the progression of RA focusing on the hands, a primary location for functional alterations in RA (Caple & Parks-Chapman, 2017). 

The Health Assessment Questionnaire (HAQ) is used to determine the psychological impact of the disease on the patient.  This rating scale assesses Activities of Daily Living and instrumental ADLs (ADLs), which are the skills that support independent living such as meal preparation and maintaining a house (March & Schub, 2018).  

RA Treatment and Management

Medication is the primary treatment for RA.  The first-line medications are disease-modifying antirheumatic drugs (DMARDs), which include methotrexate (Rheumatrex, MTX), hydroxychloroquine (Plaquenil), leflunomide (Arava), and sulfasalazine (Azulfidine).  Early treatment with these medications can slow disease progression by suppressing the immune response, thus decreasing inflammation (Schiebel & Uribe, 2018). DMARDs have a slow onset, sometimes weeks to months, and NSAIDs or corticosteroids may be given concurrently to treat current pain and inflammation (Burchum & Rosenthal, 2019).  The 2015 ACR guidelines establish criteria for the implementation of drug therapy. This approach is known as “treat to target”. The target is remission or low-level symptoms. For patients with early RA, defined as less than six months, who have low disease activity, the first recommendation is a DMARD, preferably methotrexate (Rheumatrex, MTX). A DMARD is also recommended if disease activity is moderate or high with early diagnoses, although no specific drug is recommended.  If disease activity increases or continues, a combination of DMARDs or the addition of a tissue necrosis factor inhibitor (TNFI) or non-TNF biologic is recommended. If disease activity remains moderate to high, a TNFI may be used alone or with MTX, but tofacitinib (Xeljanz) is not recommended.   Patients who have had symptoms for over six months have a similar progression of treatment recommendation.  If moderate to high activity remains, combination therapy can include DMARDS, TNFI, a non-TNF biologic, or tofacitinib (Xeljanz). Combination therapies may be used progressively until symptoms decline. Treat to target matches the biologic activity of the drug to the biologic activity of the RA. Low-dose corticosteroids may be added to combination therapy if disease activity remains high.  Short-term corticosteroids, such as prednisolone (Prednisone), at the lowest effective dose are used to treat flares in RA patients.  For patients who meet the goal of low disease activity or remission, it is recommended to taper but continue RA medication (Singh et al., 2015). The use of targeted biologic medications for patients who are not responsive to DMARDs has improved symptom relief with fewer side effects.  These drugs have also been useful in the treatment of pediatric patients (NIH, 2018). Table 2 (below) lists the most common medications as well as associated nursing implications. 

Table 2: Common Medications for the Treatment of RA

Nonbiologic DMARDs (Disease-Modifying Antirheumatic Drugs): These medications slow disease progression and/or delay onset.  Less associated risk and cost than biologics.
Methotrexate (Rheumatrex, MTX) (preferred)	Monitor CBC, liver, and kidney function. Teratogenic, contraindicated in pregnancy, or when planning pregnancy – both female and male. Folic acid (<5mg/week) to decrease GI and hepatic side effects (Uribe, 2018). Available as auto-injector or oral weekly dose.
Hydroxychloroquine (Plaquenil)	Usually in combination with MTX. Long-term outcomes improved by early use. The full effect may take three to six months. Retinal damage resulting in blindness can occur. This is dosage-related and can occur after the medication is stopped. Ophthalmologic exam prior to treatment and every six months. Educate the patient to report visual changes immediately.
Sulfasalazine (Azulfidine)	The specific benefit is the slowing of joint deterioration.  Contraindicated in patients with sulfa allergy. GI distress can be decreased with divided doses and the use of enteric-coated form. Monitor liver function and CBC to detect hepatitis and bone marrow suppression, which can occur but rare.
leflunomide (Arava)	Common adverse effects include rash, reversible alopecia, diarrhea, and respiratory infection. Serious adverse effects include severe hypertension, pancytopenia, hepatotoxicity, and Stevens-Johnson syndrome. Monitor liver function monthly, counsel patients to report symptoms of liver failure and contraindicated in patients with liver disease. Contraindicated in pregnancy, with a protocol to clear using cholestyramine must be implemented for planned pregnancy – both male and female.
Penicillamine, Gold Salts, Azathioprine, Cyclosporine, Minocycline, Protein A	Used infrequently but may be used as last resort if other medications are not effective. A higher risk of toxicity, thus require complete and focused assessment when utilized.
Biologic DMARDs:  These medications interfere with the immunologic response with the goal of decreased RA  symptoms. A significant associated cost and risk of infection and/or cancer.
Tissue Necrosis Factor Inhibitors (TNFIs): Interfere with TNF to prevent the release of chemical and immunologic factors that damage joints in RA (and other inflammatory disorders). The medications are each a unique monoclonal antibody that binds to TNF.
Etanercept (Enbrel)	First-line drug when the use of biologics is indicated. Binds with TNF to prevent it from binding with cell receptors. Injection site symptoms may last several days. Risks for fungal infections, opportunistic infections, hepatitis B reactivation, and especially TB – requires TB testing before and monitoring during treatment. Avoid administration with a concurrent disease with infection risk i.e., diabetes. Live virus vaccines are contraindicated. Serious adverse effects include severe allergic reactions, heart failure, cancer (especially lymphoma in younger patients), blood disorders, liver failure, and demyelinating nervous system disorders.  Withhold one week prior to surgery
Adalimumab (Humira)	Only indicated for use in adults. Withhold two weeks prior to surgery. See etanercept (Enbrel) for precautions and adverse effects.
Golimumab (Simponi)	Only used in combination with MTX. Injection site as well as upper respiratory tract infections more common. Withhold before surgery at the recommendation of provider. See etanercept (Enbrel) for precautions and adverse effects.
Infliximab (Remicade)	Administration of antihistamines, acetaminophen and/or corticosteroids as well as decreasing the infusion rate can reduce infusion reaction.  Stop infusion if anaphylaxis occurs.  Withhold 6 – 8 weeks prior to surgery. See etanercept (Enbrel) for precautions and adverse effects.
Certolizumab pegol (Cimzia)	Specific side effects include upper respiratory tract infections, urinary tract infections, and arthralgia. Withhold two weeks prior to surgery.   See etanercept (Enbrel) for precautions and adverse effects.
Non-TNFI biologics
Rituximab (Rituxan)	A monoclonal antibody that reduces B lymphocytes by binding with CD20 on the B cell. Indicated when one or more TNF antagonists have not been effective. Infusion reaction can be severe with onset in 30 to 120 minutes, including angioedema, cardiogenic shock, myocardial infarction, and bronchospasm.  Antihistamine, acetaminophen (Tylenol), and corticosteroids should be given prior to administration.  Corticosteroids, epinephrine, bronchodilators, and oxygen should be immediately available during administration to be used for adverse events. Risks include Hepatitis B or reactivation of John Cunningham (JC) virus in the brain of patients treated for non-Hodgkin’s lymphoma, causing progressive multifocal leukoencephalopathy.
Abatacept (Orencia)	T-cell activation inhibitor. Increases risk for infections and cancer. Specific infection risks include upper respiratory infection, pneumonia, cellulitis, bronchitis, diverticulitis, and urinary tract infections. Not used in combination with TNF inhibitors or anakinra May cause a decreased response to all vaccines and live vaccines contraindicated.
Tocilizumab (Actemra)	An IL-6 receptor antagonist that is administered IV. It can be combined with MTX, but not with TNF inhibitors, other DMARDs, or other immunosuppressant medications. Adverse effects include serious infections and perforation of the colon, especially in patients with diverticulitis and liver damage. Monitor for increased cholesterol, decreased platelets, and decreased neutrophil count. Decreases drug levels and effectiveness of oral contraceptives, warfarin (Coumadin), proton pump inhibitors, and HMG-CoA reductase inhibitors used to lower cholesterol.
Anakinra (Kineret)	Blocks receptors for IL-1. Indicated when one or more non-biologic DMARDs have not been effective. Risk for serious infections and contraindicated if active infection is present. Not to be combined with TNF inhibitors.
Corticosteroids: anti-inflammatory action decreases symptoms until DMARDs effective and added during flares (Burchaum, 2019)
Prednisone (Deltasone) Prednisolone (Prelone)	A dosage sufficient to control symptoms with five to seven-day taper. Potential side effects include gastric ulceration, osteoporosis, and adrenal suppression.
(Burcham & Rosenthal, 2019; Singh et al., 2015)

Both RA and its medications require the incorporation of nutrition as part of management.  Protein and calcium are the major nutrients necessary in RA.  The list of vital vitamins and minerals includes vitamins C, D, B6, B12, and E as well as folic acid, calcium, magnesium, zinc, and selenium.  Avoidance of allergen-related foods, both generally and specific to the individual, is a common recommendation.  A variety of specialty diets, including intermittent fasting, vegetarian, elemental, Mediterranean, and low-fat, have been used, but there is no specific diet recommended for all RA patients at this time. The functional challenge of meal preparation and grocery shopping for the patient also needs to be considered. The disease frequently results in nutritional deficiency and weight loss (Marcel, 2017). Corticosteroid use and decreased activity levels may result in weight gain that can complicate joint symptoms and affect body image (Lewis et al., 2017).

Surgery is used in RA treatment to both prevent damage and to restore function.  Surgeries to prevent damage include synovectomy and partial arthrodesis. Total joint replacements, osteotomy, resection arthroplasty, radiosynoviorthesis, tendon repairs, and arthrodesis may be used to reconstruct or fuse the joint after damage affects function.  Lower limb function to maintain mobility has the highest surgical priority as well as the most severely affected joints. The immune status of the patient increases the risk of postoperative infection. Joint infection risk increases in both hip and knee periprosthetic joint surgery by 57%.  When TNF inhibitors are stopped preoperatively, the risk for infection of the surgical site decreases by 38%. General recommendations include withholding biologic medications before joint replacement surgery and restarting with evidence of wound healing.  The patient can remain on nonbiologic DMARDs perioperatively. Surgery for internal joint fixation is complicated by osteopenia. Friable skin and minor vasculitis may result in poor wound healing. Surgery is contraindicated in patients with active infection and other diseases that are uncontrolled (Schub, 2018b). 

The systemic aspects of RA require a multifaceted approach that includes a large interprofessional team which may include the nurse, the primary healthcare provider, occupational and physical therapists, social workers, as well as specialists in rheumatology, infectious disease, cardiology, pulmonology, ophthalmology, orthopedics, and mental health. In rehabilitation, stretching and strengthening exercises of the hand can improve motions necessary to perform ADLs.  Splinting is beneficial early, and the amount of support needed progresses with the disease based on routine re-evaluation (March & Scheibel, 2018). Treatment may include transcutaneous electrical nerve stimulation (TENS), especially for older patients or those with pain unrelieved by other measures. Behavior modification, cognitive behavioral therapy, and relaxation exercises may also be beneficial (Schub & Schiebel, 2017a). 

RA-Related Evidence-Based Nursing Practice and Implications for Nursing

Nursing assessment of function and patient perspective, in addition to objective and subjective data, is essential with the RA patient. Joint implications for RA require careful assessment and individualized planning. Chronic pain that is rated moderate to severe is a predominant symptom in over half of RA patients requiring ongoing pain assessment including type, intensity, duration and location (Key & Smith, 2018).  Joint deformity affects body image, and this change in appearance is closely associated with depression (March & Schub, 2018). Falls are a major risk related to deformity, pain, weakness from anemia, and joint instability necessitating fall risk assessment increasing in frequency as the disease progresses (Balderama & Schub, 2018).  At diagnosis, 50% of patients have foot involvement, and 80-90% of those with chronic RA experience foot deformities and pain.  Referrals and implementation of specific shoes and orthotics promote mobility and general health (Barous, 2018). Functional ability can be assessed using the HAQ Disability Index to guide planning based on the ability to perform ADLs, including arising, dressing, hygiene, eating, reach, grip, walking, and activities (March & Schub, 2018).

Most RA patients are at home, and thus interventions are focused on self-management. The medication regimen is complex, and education needs to convey confidence in the approach while informing the patient of the risk and actions necessary to be safe while taking their medications. It is important to plan sufficient time for patient education to provide emotional support as well as the content. Behavioral interventions that give specific, measurable goals are more effective than general information (Schub & Scheibel, 2017).  Self-efficacy and adherence to the medication regimen improve with acceptance of an RA diagnosis and the understanding of the need for a strict administration schedule for DMARDs and biologics. Health care educators can promote autonomy by teaching the patient to adjust NSAIDs and corticosteroids to address changes in symptoms, especially pain, that occur during flares. The nurse can suggest medication reminders from family or devices and use of convenient locations, pill organizers, and establishment of a schedule for the appropriate intervals (Oshotse, Zulling, Bosworth, Tu, & Lin, 2018). Smoking cessation for all patients is recommended, especially female patients who are prescribed corticosteroids to prevent bone loss (Cash & Glass, 2017). Single-tablet dosing can be implemented more consistently by the patient and should be a consideration for older adults (Schub & Scheibel, 2017).

Non-pharmacologic pain relief measures should also be implemented. The application of heat and cold improves both comfort and mobility (Schub & Scheibel, 2017). During flares, cold gives comfort. Either ice or small bags of frozen vegetables can be manipulated to adapt to joint contours. Heat, especially moist heat such as paraffin or warm baths, can decrease stiffness. The time limit for cold is 15 minutes, and for heat 20 minutes (Lewis et al., 2017).  Repositioning with pillows can provide comfort, but caution must be implemented as prolonged flexion can prevent mobility when stiffening occurs (Balderama & Schub, 2018).

Exercise for RA patients include both general activity and therapeutic exercise and is usually directed by the physical therapist. As new exercises are added, supervision to assure joint position and safe muscle movement is necessary. ROM exercises help maintain joint mobility and may need to be performed by the nurse if the patient is in an acute care setting. Low-impact exercise, such as water aerobics and walking, are recommended, but high-intensity exercise is discouraged (Lewis et al., 2017). Fall risk may be high and is often related to pain, impaired gait, deformity, and fatigue, so implementation of safety measures should be taught, and their implementation assessed (Schub & Scheibel, 2017).

Early and continued patient education are vital to achieving the maximum function of the patient with RA. Many resources are available through the Arthritis Foundation (www.arthritis.org). One-on-one education is the preference for most information, but group formats have been used for self-management techniques and exercise (Schub & Scheibel, 2017). The education and assessment of the implementation of mobility aids and assistive devices such as large-handled eating utensils assist with independence. Identification of the need for a referral to physical or occupational therapy, mental health clinician, or social worker based on the changing needs of the patient promotes wellness (Balderama & Schub, 2018).   Paul-Savoie, Bourgault, Potvin, Gosselin, and Lafrenaye (2018) found that patient-centered care that includes the four dimensions (patient-as-person, biopsychosocial perspective, sharing power and responsibility, and therapeutic alliance) along with clinical empathy is essential for the nurse to improve assessment and anticipatory guidance. Implementation of this concept allows the nurse to address the physical, mental health, social, and personal education needs to help the patient meet the challenges of living with RA (Paul-Savoie et al., 2018).

Gout    

Gout is a disorder of elevated serum uric acid.  The three most common causes of gout are decreased renal excretion of uric acid (which can be from diuretics), decreased glomerular filtration rate, or alcohol intake. Some patients have increased production of urate that occurs with hematologic conditions and conditions which increase cellular proliferation and cell death, such as cytotoxic cancer therapy and radiations therapy.  Increased dietary intake of purine foods can initiate an attack. The urate forms monosodium urate crystals that deposit in the avascular joint tissue, such as the tendons and ligaments. Acute gouty arthritis is frequently the first indication of the presence of the systemic hyperuricemia.  The classic onset of the disease includes redness, warmth and swelling with extreme pain in the metatarsophalangeal joint of the great toe (known as podagra). These symptoms typically begin at night. Other commonly affected joints include the instep, ankle, knee, wrist and elbow.  The hip, shoulder, sacroiliac, sternoclavicular joint or cervical spine joints are affected but rarely.  Triggers for gouty arthritis include increased intake of purine-rich food, alcohol, trauma, pneumonia or other infections, surgery, thiazide diuretics and hypouricemic medications including allopurinol (Zyloprim), febuxostat (Uloric), and nitroglycerine (Nitro-dur).  As the disease progresses, attacks may involve multiple joints simultaneously.  Instead of resolution in a few days, which is common in early attacks, the duration may be up to three weeks. Frequency of attacks also increase. Tophi, firm yellow or white nodules, can form at joints or in the kidneys in patients who have had acute gouty arthritis (Edwards, 2018).

Gout is most common in men between the ages of 40 and 50, especially African American men (Lewis et al., 2017). Incidence increases in women after menopause (Lewis et al., 2017; NIH, 2019a). While multiple genes have been identified to have roles in the development of gout, two have the greatest influence.  Genetic changes in SLC2A9 cause increase reabsorption of urate and decreased release in urine.  Genetic changes in ABCG2 decrease the release of urate in the bowel (Genetics Home Reference, 2019a).  Presence of podagra or recurrent instep inflammation are diagnostic symptoms and changes can be found on x-ray and ultrasound. The most specific diagnostic test is synovial fluid analysis with confirmation of gout indicated by findings of 2,000 – 100,000 WBCs/µL, polymorphonuclear WBCs, and identification of needle-shaped urate crystals (Edwards, 2018). A 24 hour urine specimen for uric acid can assist in differentiating whether the cause is decreased renal excretion or overproduction of uric acid (Lewis et al., 2017). Most people with gout have chronic kidney disease, hypertension, or obesity. It has not been established whether these conditions are a complication of gout or gout is a complication of these disorders (Edwards, 2018).  

Treatment of acute attacks includes NSAIDs for pain relief and early initiation of oral colchicine (Colcrys).  Corticosteroids may be used and are tapered after complete resolution of the attack.  If a patient is unable to take corticosteroids, colchicine, and/or NSAIDS, an interleukin-1 antagonist, such as anakinra (Kineret) may be given for an acute attack until resolution occurs. Gout is a chronic disease and treatment focuses on prevention of attacks and physiologic damage.  The objective goal of medical treatment is to lower the serum uric acid levels to less than 6.0 mg/dL.  Allopurinol (Zyloprim) continues to be used for maintenance but febuxostat (Uloric) is a more potent (and much more expensive) alternative for patients who do not tolerate allopurinol (Zyloprim).  In patients with decreased uric acid excretion, Probenecid (Benemid) may be used but normal renal function is critical to safely initiate this therapy.  Tophi may be removed surgically to improve comfort and joint function.  Lithotripsy may be necessary if uric renal stones form.  Diet recommendations are to avoid high purine foods such as dried beans, gravy, mushrooms, organ meats and some canned fish.  Alcohol, especially beer (whether alcoholic or non-alcoholic) should also be avoided.  Low-fat dairy products are encouraged. One of the most important measures is the need for the patient to have a fluid intake of three or more liters of fluid a day (Edwards, 2018).  

Sjogren’s Syndrome

Sjogren’s syndrome is an autoimmune disorder that primarily affects tear and saliva production. It is considered arthritis because the connective tissue of joints may also be affected. RA increases the risk for Sjogren’s syndrome (Genetic and Rare Diseases Information Center [GARD], 2016). There is a genetic susceptibility that requires a trigger thought to be microbial. The genetic tendency increases the incidence of autoimmune disease, but not Sjogren’s syndrome specifically. Sjorgren may affect the kidneys, blood vessels, lungs, liver, pancreas, and brain. It is more common in women and usually occurs after age 40.  Life expectancy is not directly affected by Sjogren’s, but it is associated with RA, systemic lupus erythematosus (SLE), primary biliary cirrhosis, and increased risk for lymphoma. Treatment includes moisture replacement for the eyes and mouth, NSAIDs, corticosteroids, and immunosuppressants. Eye drops and/or ointments are applied frequently to maintain moisture. Oral care includes brushing after every meal, semi-annual dental visits for the detection of dental decay, reporting white/red patches or burning in the mouth, as well as interventions to maintain moisture. Alcohol-based mouthwash and foaming toothpaste are avoided to prevent drying of oral tissues.  Hoarseness can be decreased by sipping water, using sugar-free candy or gum, and humming or laughing, which bring the vocal cords together. Medications should be reviewed for drying effects, such as antihistamines, decongestants, diuretics, antihypertensives, and psychiatric medications (NIH, 2016c). 

Palindromic Rheumatism (Hench-Rosenberg syndrome, Hench’s syndrome)

This rare disease is a form of arthritis with recurrent joint inflammation involving one or several joints that occurs episodically for hours or days.  During an episode of joint pain, stiffness and redness occur and may be accompanied by fever or other systemic symptoms (GARD, 2017). The attacks resolve spontaneously in one to three days and resemble gout in severity (Edwards, 2018). The person may eventually develop an autoimmune disorder such as RA or lupus.  The presence of ACPA antibodies increases the risk of RA. NSAIDs and DMARDs are effective, and hydroxychloroquine (Plaquenil) is the most effective at controlling episodes and decreasing the risk of progression to RA (GARD, 2017).

Adult-Onset Still’s Disease (AOSD)

AOSD is a rare inflammatory disorder that involves several joints resulting in stiffness for several hours in the morning.  It causes fever, frequently accompanied by a rash, with a typical afternoon onset. Abdominal pain, pleurisy, swollen lymph nodes, and weight loss may occur, and severe progression can include inflammation of the heart and lungs.  Specific blood test results seen in AOSD patients include increased levels of WBC, CRP, ESR, ferritin, fibrinogen, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Treatment includes NSAIDs, corticosteroids, nonbiologic, or biologic DMARDs.  Theories of the etiology of AOSD include hypersensitivity, autoimmunity, and a microbial trigger in some combination (GARD, 2018). Chronic polyarthritis develops in approximately 60-70% of AOSD patients (Yoo, 2017).

Reactive Arthritis (Post-infectious arthritis; Post-infectious reactive arthropathy)

This rare arthritis is a sequela that occurs weeks to months after an infection in another location in the body, usually genitourinary or gastrointestinal. The characteristic joint inflammation is at the insertion of the tendon into the bone (entheses). While joint inflammation in one to many joints can be the only symptom, conjunctivitis and urethritis may also occur. The patient may also have skin involvement with small, superficial ulcers on oral mucosa or the glans penis. Hyperkeratotic, crusted vesicles on the palms and/or soles, or around the nails are characteristic. Patient history usually reflects recent diarrhea or dysuria. Reactive arthritis after a urinary infection usually affects men ages 20 to 40 and is commonly associated with Chlamydia trachomatis.  The gastrointestinal infections that initiate reactive arthritis are foodborne, including Shigella, Salmonella, Yersinia, or Campylobacter. Reactive arthritis usually lasts from three to four months and can resolve, recur, or develop into a chronic disease. When the disease is chronic or recurrent, joint inflammation and deformity may include the spine and sacroiliac joint. Antibiotics are prescribed, and NSAIDs, especially indomethacin (Indocin), and corticosteroids are given for the joint symptoms (Kontzias, 2018a). 

Systemic Scleroderma (Systemic sclerosis)

This is an autoimmune disorder in which fibrosis or hardening occurs in the skin and other tissue from an overproduction of collagen. The earliest symptom, with onset weeks to years before fibrosis, is Raynaud phenomenon in which exposure to cold, or other stress, causes the patient’s hands to turn white or blue. Along with this, the patient’s hands may be puffy or swollen, and the skin on the hands and face may be thickened and eventually develop open sores. The patient may develop calcinosis, which causes painful bumps under the skin and telangiectasia, where enlarged blood vessels become visible under the skin. Heartburn, dysphagia, and hypertension indicate the progression of fibrotic effects that may include the esophagus, heart, lungs, and kidneys. In the gastrointestinal system, peristalsis is decreased, preventing the movement of food. Other connective tissue disorders, including RA and SLE, are found in 15 – 25% of systemic scleroderma patients. It is four times more common in women. Genetic changes in HLA and other genes, along with environmental factors, have been identified in the etiology of the disease. Some cases occur without a genetic history, while others have known inheritance (Genetics Home Reference, 2019b).

Polymyalgia Rheumatica

The focus of pain and stiffness in this arthritis-related disease occurs in the neck, shoulders, and hips.  Onset is usually gradual but can be sudden and may be accompanied by fever, fatigue, and weight loss. It occurs most often over age 50, peaking between the ages of 70 – 80.  Women are more likely to develop the disorder. While it can last for years, it typically resolves within a year.  Giant cell arteritis, which is the inflammation of arteries on each side of the head, is an associated risk.  Treatment includes NSAIDs or corticosteroids with dosing that eliminates the symptoms and is continued to maintain symptomatic control (NIH, 2016b).

Psoriatic Arthritis

Psoriatic arthritis occurs in patients with the skin disease psoriasis, which causes scaly patches on the skin. Onset is usually between the age of 30 and 50 (NIH, 2017a).  Significant joint inflammation occurs at the entheses. This damage occurs most often at the Achilles tendon, plantar fascia, and greater trochanter of the femur. MRI can differentiate this extrasynovial involvement from the predominately synovial inflammation of RA (Liu, Horng-Ming, Liu & Chen, 2014). The joints most commonly affected are the wrists, distal joints of the fingers or toes, knees, ankles, and lower back. Joint tenderness and stiffness may be sporadic, and redness and warmth may occur at the joint. Pain and stiffness are noted in the neck and lower back. The patient may report foot pain with tenderness along the heel and bottom of the foot. The fingers may swell to resemble sausages. Nails may separate from the nail bed or have pitting. Fatigue is common, and eye infections, including conjunctivitis, occur more often (NIH, 2017a). Skin and joint psoriasis are exacerbated by emotional stress. Treatment includes corticosteroids, NSAIDs, or non-biologic and biologic DMARDs. Intra-articular injections of corticosteroids may be used if only one or a few joints are involved (Liu et al., 2014).  

Ankylosing Spondylitis

The spine is the primary location of ankylosing spondylitis (AS). Joint pain occurs along the spine and at the junction with the pelvis. Back pain may be sporadic or constant. Other joints that may be affected are the shoulders, ribs, hips, knees, and feet (NIH, 2016a). AS is more common in males. Onset at a young age and early lumbar spine limitations are related to a poor prognosis. Assessment findings may include abnormal deep tendon reflexes secondary to spinal cord compression. Photophobia and eye pain may be experienced. Aortic regurgitation, arrhythmia, and enthesitis (inflammation at the junction between bone and tendons/ligaments) may occur (GARD, 2015). The bowel is more frequently affected, but in rare instances, the heart and lungs may also be affected. Stiffening of the spine and rib cage may cause difficulty breathing. AS occurs twice as often in men than women. The genes that are known to be related to AS include HLA-B27, IL23R, and ERAP1, but the disease is thought to require an unknown environmental factor or trigger. Primary treatments include medicine, exercise, and diet, but surgery (spinal fusion) may be needed to maintain function. NSAIDs, corticosteroids, DMARDs, and biologics may be used. Exercise is critical, and stretching, strengthening, and maintaining joint motion are key goals. Exercise requires HCP direction and should begin gradually and safely. A diet to maintain nutrients and healthy weight is recommended, and omega-3 fatty acids in tuna, salmon, flaxseed, and walnuts may be beneficial (NIH, 2016a).

Juvenile Arthritis

Age of onset prior to age 18 is a key feature of juvenile arthritis. It is a rheumatic disease with classic arthritis symptoms of pain, swelling, stiffness, and loss of joint mobility with increased limitation after rest. Limping in the morning and excessive clumsiness may be observed as the primary initial symptom.  Systemic symptoms include high fever, skin rash, and swollen lymph nodes, especially in the neck. Inflammation of the eyes is a severe risk and regular eye exams are needed. Genetic and environmental factors contribute to the autoimmune response.  Diagnostic test results are similar to RA. The disease may increase or decrease bone growth and may result in slowed overall growth, asymmetric growth of limbs, or a change in the shape of the chin. The goal of exercise is to decrease inflammation and pain. During flares, the patient should avoid intense activity. Some activity is encouraged, and swimming is the exercise of choice during flares.  Patient education should focus on promoting growth and development with an awareness of the psychological, social, and educational impact of long-term disease (NIH, 2015) 

Arthritis Future Research and Directions

Research is ongoing to improve treatment for all forms of arthritis. Most research specifically focuses on OA and RA, but that information is then used to impact the less common disorders. 

The incidence of OA is expected to increase, but advances in treatment are expected.  Allen and Golightly (2015) highlight some of the emerging areas of research to include metabolic pathways, vitamins, joint shape, bone density, limb length inequality, muscle strength and mass, and early structural damage.  Deveza and Loeser (2018) propose that future research in OA will be more useful through using a phenotyping system that narrows the focus, thus potentially improving outcomes.  Phenotypes may be based on the mechanistic subgroup, prognosis, or response to therapy.  Currently, most research includes people with or without structural changes, one or more joints affected, history of injury, or a variety of co-morbid conditions. The focus would support more promising interventions specific to individual patients rather than grouping across a variety of the populations studied. Urban and Little (2018) predict that future therapies can improve treatment of both injury and age-related OA by modification of the inflammatory process while meanwhile identifying the need for more research into the specific biochemical changes of aging and injury that result in OA. More information is necessary to determine the ideal exercise as well as the intensity and frequency of exercise for prevention and treatment (Krishnasamy et al., 2018). The identification of evidence-based interventions that improve the lives of OA patients and control co-morbid conditions are needed (Sandoval-Rosario et al., 2018). One of the goals of future medical treatment is to identify medications that will slow the progression of OA rather than merely treat the symptoms (Goldman & Schafer, 2016). One of these is research into using binding agents with hyaluronic acid and improving localization of injection to maximize the potential for regeneration of lubrication within the joint (Faust et al., 2018).  

Much of the current research and predictably future research focuses on the immunologic and biochemical basis of RA. The relationship of gut microbes and RA are a newer area of study and new-onset, untreated RA patients were found to have a higher rate of Prevotella copri, an organism previously found to increase inflammation in animal research. RA patients have significantly less bifidobacteria but more Bacterioides, Porphyromonas, Prevotella groups of bacteria (Wu et al., 2016). New findings on the neuropathology of pain may produce treatments for the chronic pain of RA (NIH, 2018). Dong et al. (2018) looked specifically at the effects and interrelationships of IL-4 and the IL-4-receptor on T-cell and B-cell activity, and mast cells as well as IL-4 effects on VEGF (vascular endothelial growth factor) and TGF-beta1 (transforming growth factor beta) both of which participate in synovitis. One of the areas of investigation that is beginning is the relationship between increased levels of leptin and patients with RA (Caple & Parks-Chapman, 2017). As more information emerges about the action of cytokines and immune system cells, the influence of cellular regulation on RA is expected to impact treatment options.  The aggressive activity of fibroblast-like synoviocytes (FLS) is similar to oncologic cells in damage and growth. The similarity of cancer growth and RA progression is being researched and may yield an understanding of both diseases (You et al., 2018).  Exploration of the increased cancer risks with RA and the medications used to treat it may also expand treatment options (Balderama & Schub, 2017). NIH (2017b) predicts that more autoantibodies will be identified to aid in early treatment. Recent recognition that early, aggressive treatment of RA can stop disease progression and minimize effects on the patient have given hope for future treatment (Balderama & Schub, 2018).  

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