Assignment instruction

Scientific Literature Review on an autoimmune condition. For Assignment 4, you are to write a draft of the final paper that will be submitted for Assignment 5. 

Assignment 5 is to write a 10 to 15-page Scientific Literature Review (2,500 to 3,750 words, not including title page and reference pages) in APA format on one autoimmune condition as listed below. Create your topic statement on an RA.

Organize your Scientific Literature Review in the following format:

There are four main parts of your Scientific Literature Review paper: the introduction, main body, conclusion, and reference page(s). An abstract in APA format, 7th edition, is not required. For a general description of the process, please see the following:

  • Introduction is the first part and may be the most important part of the paper as it provides the reader with the intent. It should state the main point or thesis statement that will be discussed. It is an overview of the topic along with the objectives of the literature review.
  • The main body of the scientific literature review contains the bulk of information that supports the paper’s thesis statement. It is the critical analysis and evaluation of topically relevant research/data and is often presented with subheadings to organize the content.
  • The conclusion summarizes the key points of your review and tie this in with the thesis statement in the introduction. The breakdown of the word count of the Introduction, Main Body and Conclusion should be:

    Introduction=10%
    Main Body= 80-85%
    Conclusion=5-10%
  • Reference pages include all your references and must include at least ten peer-reviewed sources. The references must be cited in APA format and each one must have been cited in-text where the information was used (as per APA format 7.0)

HERE IS A ROUGH OUTLINE WITH THE SOURCES I WOULD LIKE FOR YOU TO USE

Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, causing inflammation, pain, swelling, and, over time, joint damage and deformities.

RA occurs when the body’s immune system mistakenly attacks its tissues, particularly the synovial membrane, which lines the joints. This leads to an inflammatory response extending beyond the joints, affecting other systems such as the lungs, heart, and blood vessels (Chauhan et al., 2023).

Prevalence in the U.S.

Statistics from 2022 show approximately 1.3 million people in the United States are living with rheumatoid arthritis, with the condition affecting women more frequently than men (at a ratio of about 3:1). The typical age of onset is between 40 and 60 years, but RA can occur at any age. The prevalence of RA continues to increase due to factors such as environmental triggers, genetics, and lifestyle choices that exacerbate autoimmune reactions (Elgaddal et al., 2024).

Symptoms of RA

Rheumatoid arthritis manifests with a range of symptoms, including:

  • Joint pain and swelling (most commonly in the hands, wrists, knees, and feet)
  • Morning stiffness lasting more than 30 minutes
  • Fatigue
  • Low-grade fever
  • Symmetrical joint involvement (affecting both sides of the body)
  • Joint deformity (in advanced stages)
  • Rheumatoid nodules (lumps of tissue under the skin)
  • Systemic symptoms affecting the lungs, heart, or eyes (Chauhan et al., 2023).

Triggers Associated with RA

RA is influenced by both genetic predisposition and environmental triggers. Some common triggers include:

  • Infections: Viral or bacterial infections may activate the immune system, potentially triggering RA in susceptible individuals.
  • Smoking: Cigarette smoking is a well-documented risk factor for the development of RA and can also worsen disease progression.
  • Environmental Toxins: Exposure to pollutants and chemicals (such as silica dust) has been linked to an increased risk of RA.
  • Hormonal Changes: RA is more common in women, particularly during times of hormonal shifts, such as pregnancy or menopause, possibly due to fluctuations in estrogen.
  • Chronic Stress: Persistent stress can exacerbate RA symptoms by increasing systemic inflammation and immune dysregulation.
  • Dietary Factors: A diet high in inflammatory foods (e.g., processed sugars, red meat, trans fats) may contribute to RA flare-ups, while food sensitivities (e.g., gluten, dairy) can act as triggers for some individuals (Chauhan et al., 2023).

Cytokines Involved in Rheumatoid Arthritis
Once triggered, the immune system in individuals with RA becomes overactive, producing specific pro-inflammatory cytokines that drive inflammation and joint destruction. Here are some of the critical cytokines involved:

Here’s a breakdown of the key cytokines involved in Rheumatoid Arthritis (RA), categorized by their roles in inflammation and immune modulation:

Pro-inflammatory Cytokines (Promote Inflammation in RA)

  1. Tumor Necrosis Factor-alpha (TNF-α):
    • TNF-α is one of the most significant cytokines in RA.
    • It promotes inflammation, stimulates the production of other inflammatory cytokines, and contributes to joint damage.
    • TNF-α increases the activity of osteoclasts, leading to bone erosion.
  2. Interleukin-1 (IL-1):
    • IL-1 plays a crucial role in promoting synovial inflammation and cartilage destruction.
    • It enhances the breakdown of cartilage and stimulates the production of other pro-inflammatory cytokines.
  3. Interleukin-6 (IL-6):
    • IL-6 contributes to the systemic effects of RA, including fatigue, anemia, and increased pain.
    • It drives the acute-phase response and promotes B cell activation and autoantibody production, such as rheumatoid factor (RF).
  4. Interleukin-17 (IL-17):
    • Produced by Th17 cells, IL-17 promotes neutrophil recruitment to inflamed joints.
    • It contributes to the chronic inflammation seen in RA by increasing the production of matrix metalloproteinases (MMPs), which degrade cartilage and tissue.
  5. Interleukin-23 (IL-23):
    • IL-23 is involved in the differentiation and maintenance of Th17 cells.
    • It amplifies the pro-inflammatory response by promoting the secretion of IL-17.

Anti-inflammatory Cytokines (Counteract Inflammation)

  1. Interleukin-10 (IL-10):
    • IL-10 is produced by regulatory T cells (Tregs) and plays an immunosuppressive role.
    • It inhibits the production of pro-inflammatory cytokines like TNF-α and IL-1, helping to balance immune responses.
  2. Interleukin-4 (IL-4):
    • IL-4 promotes Th2 cell differentiation, reducing Th1 and Th17 cell activity.
    • It helps counteract the pro-inflammatory effects of TNF-α and IL-1, though its role in RA is less dominant compared to other cytokines.

Cytokines Involved in Joint Destruction

  1. Interleukin-8 (IL-8):
    • IL-8 attracts neutrophils to the site of inflammation, contributing to synovial inflammation and joint damage.
  2. Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF):
    • GM-CSF promotes the differentiation of macrophages and neutrophils, enhancing the inflammatory response.
    • It plays a role in perpetuating the inflammatory cycle in RA.

Summary of Cytokine Interactions in RA:

  • TNF-α, IL-1, IL-6, IL-17, and IL-23 are the major pro-inflammatory cytokines driving the chronic inflammation and joint destruction in RA.
  • IL-10 and IL-4 act as anti-inflammatory cytokines, attempting to reduce excessive immune activation, though their effects are often overwhelmed in RA.
  • Targeting these cytokines, particularly TNF-α and IL-6, has become the foundation of biologic therapies in treating RA.

Understanding these cytokine interactions is key in both conventional and integrative approaches to managing RA, aiming to reduce inflammation, prevent joint damage, and promote immune balance.

Conventional Standard of Care

The standard treatment for RA aims to reduce inflammation, control symptoms, and prevent joint damage. Critical components of conventional RA management include:

  1. Disease-modifying antirheumatic Drugs (DMARDs) are the cornerstone of RA treatment. They slow disease progression and prevent joint damage. Common DMARDs include methotrexate, leflunomide, and sulfasalazine.
  2. Biologics: These are advanced medications that target specific components of the immune system, such as tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab) and interleukin-6 (IL-6) inhibitors (tocilizumab).
  3. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): These are used to manage pain and inflammation in RA, though they do not slow disease progression. Common NSAIDs include ibuprofen and naproxen.
  4. Corticosteroids: Steroids such as prednisone are sometimes used to reduce inflammation quickly during RA flare-ups, though long-term use is discouraged due to potential side effects. (Chauhan et al., 2023).

Surgery

Advanced stages of severe joint and bone damage require surgery to prevent further destruction (Trieb & Hofstaetter, 2009). Surgical options comprise:

  • Synovectomy: Remove diseased synovium (lining of the joint).
  • Arthroscopic Surgery: Remove loose cartilage and repair tears.
  • Osteotomy: Cut the bone (only seldom used).
  • Joint Replacement Surgery (Arthroplasty) is the surgical reconstruction or replacement of the joint. It is usually done in patients over 50 years old with severe disease progression.
  • Arthrodesis or fusion: This procedure fuses two bones, significantly reducing mobility, but also decreasing pain, and increasing joint stability.

Integrative Health Modalities for RA

Integrative approaches can be used alongside conventional treatments to support overall well-being, reduce inflammation, and potentially induce remission in RA. These approaches focus on diet, lifestyle changes, physical activity, stress management, and sleep.

1. Nutrition (Diet), Botanicals, and Supplements

A pro-inflammatory diet can exacerbate RA symptoms, while an anti-inflammatory diet may help reduce inflammation and alleviate pain.

  • Mediterranean Diet: High in omega-3 fatty acids (fatty fish, flaxseed, chia seeds), fruits, vegetables, and whole grains, this diet has been shown to reduce inflammation in people with RA (Nikiphorou & Philippou, 2023).
  • Omega-3 Fatty Acids supplementation reduces joint pain and stiffness in RA by decreasing inflammatory cytokines like IL-6 and TNF-alpha (Gioxari et al., 2018).
  • Curcumin: The active component in turmeric has potent anti-inflammatory properties that may help reduce RA symptoms. Studies have shown that curcumin can inhibit NF-kB, a protein complex that plays a role in inflammation (Peng et al., 2021).
  • Boswellia Serrata: This botanical, also known as Indian frankincense, has been used to reduce inflammation and pain in RA patients by inhibiting 5-lipoxygenase, an enzyme involved in the inflammatory pathway (Kumar et al., 2019; Siddiqui, 2011).
  • Ginger essential oil contains gingerols and shogaols, which help to reduce inflammation and pain by inhibiting the expression of inflammatory cytokines. These compounds effectively reduce inflammation in patients with rheumatoid arthritis (Funk et al., 2016).
  • Vitamin D’s Role: Low vitamin D levels are linked to increased RA activity; it may be a potential biomarker for RA progression.
  • Study Findings:
    • Vitamin D supplementation improved DAS28 (disease activity), TJC (tender joint count), and ESR (inflammation marker).
    • No significant effects on VAS (pain), SJC (swollen joints), CRP, or PTH.
    • Higher doses (>50,000 IU) and longer duration (>12 weeks) showed greater benefits, particularly in reducing pain and inflammation.
    • Mechanism: Regulates inflammation via Toll-like receptors and Th17 cells, supporting both innate and adaptive immunity (Guan et al., 2020).
  • Probiotics (Lactobacillus, Bifidobacterium, and Streptococci) may modulate RA progression by affecting the gut microbiota. Emerging studies suggest probiotics could improve RA symptoms, reduce inflammation, and enhance health outcomes. Probiotic-rich foods like yogurt, kefir, and fermented vegetables may support the immune system and reduce inflammation (Bungau et al., 2021).

2. Lifestyle Changes

Making intentional changes in daily habits can help manage RA symptoms:

  • Avoid Smoking: Smoking is a known risk factor for RA and can worsen symptoms and disease progression. Quitting smoking is essential for reducing inflammation (Chang et al., 2014).
  • Reduce Exposure to Environmental Toxins: The environment is critical in developing rheumatic musculoskeletal diseases (RMDs), including RA. Chronic exposure to air pollution has been linked to immune system damage, triggering autoimmunity and autoantibody production. A strong connection exists between the lungs and synovial tissue in RA development. Recent evidence also shows that acute exposure to toxic inhalants can trigger RA flares (Adami, 2022).

3. Physical Activity

While rest is necessary during RA flare-ups, regular low-impact exercise can improve joint mobility, reduce stiffness, and strengthen muscles, which helps support affected joints.

  • Exercise is effective in reversing cachexia (muscle wasting) and significantly improving physical function in RA patients without worsening disease activity.
  • Regular aerobic and resistance exercise may also lower cardiovascular risk, which is higher in RA patients.
  • All RA patients should be encouraged to include exercise in their routine care.
  • Swimming and aqua aerobics are excellent forms of exercise for individuals with RA, as they are gentle on the joints while promoting cardiovascular health.
  • Yoga and Tai Chi improve flexibility, reduce stiffness, and support mental health (Cooney et al., 2011).

4. Stress Management

Chronic stress is a known trigger for autoimmune flare-ups, and managing stress is crucial for people with RA.

  • Meditation: Regular meditation can reduce stress hormones like cortisol, lower inflammation, and enhance emotional resilience (Parker et al., 1995).
  • Acupuncture: Acupuncture can help reduce pain and improve the quality of life in individuals with RA by promoting energy flow (qi) and reducing inflammatory responses (Li et al., 2022).
  • Aromatherapy: Using essential oils like lavender, frankincense, or eucalyptus may help reduce stress and inflammation when used in diffusers or massage therapy (Gok Metin & Ozdemir, 2016).

5. Sleep Management

Sleep is vital for managing inflammation and promoting healing, but RA can interfere with sleep quality due to pain and discomfort (Grabovac et al., 2018).

  • Reducing Screen Time: Limiting screen time, especially before bed, helps regulate the body’s circadian rhythms and promotes deeper sleep.
  • Journaling: Writing down thoughts or worries before bed can help clear the mind and reduce sleep-disrupting anxiety.
  • Aromatherapy: Incorporating essential oils like lavender into bedtime can promote relaxation and improve sleep quality.

Conclusion

Rheumatoid arthritis is a complex autoimmune disease with various symptoms and triggers. Conventional treatments, including DMARDs and biologics, are the standard for managing RA, but integrating holistic approaches can offer additional relief and help manage the condition more effectively. By incorporating anti-inflammatory nutrition, lifestyle changes, physical activity, stress management, and sleep hygiene, individuals with RA can improve their quality of life and potentially induce periods of remission. This integrative approach can help balance the immune system, reduce inflammation, and alleviate the symptoms of this chronic disease.

References

Adami G. (2022). Mining the pathogenesis of rheumatoid arthritis, the leading role of the environment. RMD open, 8(2), e002807. https://doi.org/10.1136/rmdopen-2022-002807

Cooney, J. K., Law, R. J., Matschke, V., Lemmey, A. B., Moore, J. P., Ahmad, Y., Jones, J. G., Maddison, P., & Thom, J. M. (2011). Benefits of exercise in rheumatoid arthritis. Journal of aging research, 2011, 681640. https://doi.org/10.4061/2011/681640

Bungau, S. G., Behl, T., Singh, A., Sehgal, A., Singh, S., Chigurupati, S., Vijayabalan, S., Das, S., & Palanimuthu, V. R. (2021). Targeting probiotics in rheumatoid arthritis. Nutrients, 13(10), 3376. https://doi.org/10.3390/nu13103376

Chang, K., Yang, S. M., Kim, S. H., Han, K. H., Park, S. J., & Shin, J. I. (2014). Smoking and rheumatoid arthritis. International journal of molecular sciences, 15(12), 22279–22295. https://doi.org/10.3390/ijms151222279

Chauhan, K., Jandu, J. S., Brent, L. H., & Al-Dhahir, M. A. (2023, May 25). Rheumatoid arthritis. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK441999/

Elgaddal, N., Kramarow, E., Weeks, J., & Reuben, C. (2024). Arthritis in adults age 18 and older: United States, 2022. Centers For Disease Control And Prevention (CDC). https://doi.org/10.15620/cdc:145594

Funk, J. L., Frye, J. B., Oyarzo, J. N., Chen, J., Zhang, H., & Timmermann, B. N. (2016). Anti-inflammatory effects of the essential oils of ginger (Zingiber officinale Roscoe) in experimental rheumatoid arthritis. PharmaNutrition, 4(3), 123–131. https://doi.org/10.1016/j.phanu.2016.02.004

Gioxari, A., Kaliora, A. C., Marantidou, F., & Panagiotakos, D. P. (2018). Intake of ω-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: A systematic review and meta-analysis. Nutrition (Burbank, Los Angeles County, Calif.), 45, 114–124.e4. https://doi.org/10.1016/j.nut.2017.06.023

Gok Metin, Z., & Ozdemir, L. (2016). The effects of aromatherapy massage and reflexology on pain and fatigue in patients with rheumatoid arthritis: A randomized controlled trial. Pain management nursing: official journal of the American Society of Pain Management Nurses, 17(2), 140–149. https://doi.org/10.1016/j.pmn.2016.01.004

Grabovac, I., Haider, S., Berner, C., Lamprecht, T., Fenzl, K. H., Erlacher, L., Quittan, M., & Dorner, T. E. (2018). Sleep quality in patients with rheumatoid arthritis and associations with pain, disability, disease duration, and activity. Journal of Clinical Medicine, 7(10), 336. https://doi.org/10.3390/jcm7100336

Guan, Y., Hao, Y., Guan, Y., Bu, H., & Wang, H. (2020). The effect of vitamin D supplementation on rheumatoid arthritis patients: A systematic review and meta-analysis. Frontiers in Medicine, 7. https://doi.org/10.3389/fmed.2020.596007

Kumar, R., Singh, S., Saksena, A. K., Pal, R., Jaiswal, R., & Kumar, R. (2019). Effect of Boswellia serrata extract on acute inflammatory parameters and tumor necrosis factor-α in complete Freund’s adjuvant-induced animal model of rheumatoid arthritis. International journal of applied & basic medical research, 9(2), 100–106. https://doi.org/10.4103/ijabmr.IJABMR_248_18

Li, H., Man, S., Zhang, L., Hu, L., & Song, H. (2022). Clinical efficacy of acupuncture for the treatment of rheumatoid arthritis: meta-analysis of randomized clinical trials. Evidence-based complementary and alternative medicine: eCAM, 2022, 5264977. https://doi.org/10.1155/2022/5264977

Nikiphorou, E., & Philippou, E. (2023). Nutrition and its role in prevention and management of rheumatoid arthritis. Autoimmunity reviews, 22(7), 103333. https://doi.org/10.1016/j.autrev.2023.103333

Parker, J. C., Smarr, K. L., Buckelew, S. P., Stucky‐ropp, R. C., Hewett, J. E., Johnson, J. C., Wright, G. E., Irvin, W. S., & Walker, S. E. (1995b). Effects of stress management on clinical outcomes in rheumatoid arthritis. Arthritis & Rheumatism, 38(12), 1807–1818. https://doi.org/10.1002/art.1780381214

Peng, Y., Ao, M., Dong, B., Jiang, Y., Yu, L., Chen, Z., Hu, C., & Xu, R. (2021). Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures. Drug design, development and therapy, 15, 4503–4525. https://doi.org/10.2147/DDDT.S327378

Siddiqui M. Z. (2011). Boswellia serrata, a potential antiinflammatory agent: An overview. Indian journal of pharmaceutical sciences, 73(3), 255–261. https://doi.org/10.4103/0250-474X.93507

Trieb, K., & Hofstaetter, S. G. (2009). Treatment strategies in surgery for rheumatoid arthritis. European Journal of Radiology, 71(2), 204–210. https://doi.org/10.1016/j.ejrad.2009.04.050

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