Understanding Autoimmune Diseases Common in Women

Autoimmune diseases represent a complex and multifaceted group of conditions wherein the body's immune system mistakenly attacks its own tissues. These disorders predominantly affect women, with some estimates suggesting that nearly 80% of individuals with autoimmune diseases are female. This article delves into the nature of autoimmune diseases, focusing on lupus and rheumatoid arthritis, exploring their causes, symptoms, diagnosis, and treatment options, and highlighting their impact on women's health.

Overview of Autoimmune Diseases

The immune system is designed to protect the body from harmful pathogens such as bacteria, viruses, and fungi. However, in autoimmune diseases, the immune system loses its ability to distinguish between foreign invaders and the body's own cells. This malfunction leads to an immune response against healthy tissues, causing inflammation, tissue damage, and various symptoms depending on the organs affected.

Autoimmune diseases are characterized by a pathologic response to self- or autoantigens; these responses can be categorized as autoimmunity or auto-reactivity and underlie a wide range of clinical disorders. These disorders may be generalized, such as systemic rheumatic diseases like systemic lupus erythematosus, vasculitis, and others, or tissue- or organ-specific, such as endocrine and neurologic disorders, including autoimmune thyroiditis and multiple sclerosis, respectively, and other conditions. Autoimmune diseases can be acute or chronic and affect all organs and body systems. (Pisetsky, D. S., Schur, P. H., & Romain, P. L. 2020)

Why Do Autoimmune Diseases Predominantly Affect Women?

For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. Symptom severity, disease course, response to therapy, and overall survival may also differ between males and females with autoimmune diseases. Sex hormones have a crucial role in this sex bias, with estrogens being potent stimulators of autoimmunity and androgens playing a protective role. Accumulating evidence indicates that genetic, epigenetic, and environmental factors may also contribute to sex-related differences in risk and clinical course of autoimmune diseases. Women are also more likely to be diagnosed with these diseases during their reproductive years, suggesting that hormonal changes play a significant role. (Ortona, E. et al., 2016), (Ngo, S. T. et al., 2014)

Do you experience severe cramps, irregular periods, and other menstrual discomforts? We've got the solution for you!

Say goodbye to discomfort and hello to confidence with our personalized Menstrual Health program!

Lupus (Systemic Lupus Erythematosus)

Systemic lupus erythematosus (SLE; lupus) is a complex autoimmune disease with a chronic relapsing-remitting course and variable manifestations leading to a spectrum of diseases ranging from mild to life-threatening. The clinical onset of SLE derives from the interaction between genetic predisposition and environmental, immunological, and hormonal factors, with a strong predilection for women of childbearing age.

Causes and Risk Factors (Gergianaki, I. et al., 2018)

The exact cause of lupus remains unknown, but it is believed to result from a combination of genetic, environmental, and hormonal factors. Risk factors include:

• Genetics: Having a family history of lupus or other autoimmune diseases increases the risk.
• Gender: Women are more likely to develop lupus, especially during their childbearing years.
• Hormones: Estrogen is thought to play a role in the development of lupus, though the precise mechanism is unclear.
• Environmental Triggers: Infections, exposure to sunlight, and certain medications can trigger lupus flares in predisposed individuals.

Symptoms (Parks, C. G. et al., 2017)

Lupus symptoms can vary widely and may change over time. Common symptoms include:

• Fatigue: Persistent tiredness is a hallmark of lupus.
• Joint Pain and Swelling: Often affecting the hands, wrists, and knees.
• Skin Rash: A butterfly-shaped rash across the cheeks and nose is characteristic of lupus.
• Photosensitivity: Sensitivity to sunlight, leading to skin rashes or other symptoms.
• Fever: Low-grade fevers without an apparent cause.
• Kidney Problems: Lupus nephritis, an inflammation of the kidneys, can occur.
• Neurological Symptoms: Headaches, confusion, and seizures.

Diagnosis

Diagnosing lupus can be challenging due to its diverse symptoms and similarities to other conditions. Cutaneous manifestations occur in about 75% of patients with SLE in the course of the disease and are the first sign in a quarter of cases. Based on clinical and histological criteria, the skin lesions are divided into lupus erythematosus (LE)-specific and LE-non-specific manifestations. The most frequent LE-specific manifestation is the acute cutaneous lupus erythematosus (ACLE), which may occur as a butterfly rash or in the form of a generalized maculopapular exanthema. Patients with SLE present in many different ways and therefore may first encounter the medical system in several different clinics, including dermatology, nephrology, neurology, hematology, or rheumatology, in both adult and pediatric care settings. Screening tests for SLE are not always useful. The ANA test is present in a significant proportion of normal individuals and lacks specificity or prognostic value. Recognition of SLE manifestations requires a provider who is trained in its many guises, and specialized clinics for SLE care may best optimize treatment approaches. Physicians typically use a combination of medical history, physical examination, and laboratory tests, including:

• Antinuclear Antibody (ANA) Test: A positive ANA test indicates the presence of autoantibodies.
• Anti-dsDNA and Anti-Sm Antibodies: Specific autoantibodies often found in lupus patients.
• Complete Blood Count (CBC): To check for anemia, low white blood cell count, or low platelet count.
• Urinalysis: To detect kidney involvement.
• Biopsy: Skin or kidney biopsy may be performed in some cases. (Thong, B., & Olsen, N. J. (2017)

Treatment

While there is no cure for lupus, treatment focuses on managing symptoms and preventing flares.  Treatment of SLE poses significant challenges and is often based on clinical acumen. Nevertheless, in recent times several controlled trials and well-conducted observational studies have focused on novel treatments and also on the more efficient use of old, conventional drugs. Treatment options include:

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): For pain and inflammation.
• Corticosteroids: To reduce inflammation during flares.
• Immunosuppressants: Medications like azathioprine or mycophenolate mofetil to suppress the immune system.
• Biologic Agents: Belimumab, a monoclonal antibody, is used for treating lupus.
• Antimalarials: Antimalarials are among the oldest drugs for treating SLE. Following empirical use for years, the Canadian Hydroxychloroquine Study demonstrated in 1991 the efficacy of HCQ in preventing lupus flares. However, for many years the use of antimalarials was limited to patients with cutaneous and/or articular involvement, thus playing a marginal role in core lupus therapy. This scenario has changed substantially during the last 10 years. Hydroxychloroquine is commonly used to manage skin and joint symptoms. (Ruiz-Irastorza, G., & Bertsias, G. 2020), (Tanaka, Y. 2020)

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. It leads to chronic inflammation, causing pain, swelling, and eventually joint damage. Women are two to three times more likely to develop RA than men, and the disease often manifests between the ages of 30 and 60. (Radu, A. F., & Bungau, S. G. 2021)

Causes and Risk Factors (Radu, A. F., & Bungau, S. G. 2021)

Like lupus, the exact cause of RA is unknown, but it involves a combination of genetic, environmental, and hormonal factors. Risk factors include:

• Genetics: A family history of RA increases the risk. RA is a multifactorial disease caused by genetic, environmental, and stochastic factors. The genetic risk for RA that has been estimated by scientific studies is about 50%. The presence or absence of rheumatoid factor (RF) and ACPA can divide RA into two types (seropositive and seronegative) and there are also differences between the risk factors involved.
• Gender: Women are more likely to develop RA than men.
• Age: RA commonly begins between the ages of 30 and 60.
• Smoking: Smoking is a significant risk factor for developing RA. The harmful chemicals in tobacco products have been comprehensively evaluated and the results suggest that smoking delivers a specific signal. Smoking might be related to a genetic context with a specific role in triggering a particular subtype of RA
• Obesity: Excess weight can increase the risk of RA.

Symptoms (Jutley, G. S., 2017)

RA symptoms typically start gradually and can vary in severity. Common symptoms include:

• Joint Pain and Stiffness: Particularly in the mornings or after periods of inactivity.
• Swollen Joints: Especially in the hands, wrists, and feet.
• Fatigue: Persistent tiredness and a general feeling of malaise.
• Fever: Low-grade fevers may occur.
• Nodules: Firm lumps under the skin, often near the elbows.
• Decreased Range of Motion: Stiffness and reduced joint flexibility.

Diagnosis (Kourilovitch, M et al., 2014)

RA diagnosis is based on the classification criteria that involve four parameters: joint involvement, serology (rheumatoid factor and anti-cyclic citrullinated peptide -anti-CCP), levels of acute phase reactants, and the duration of the symptoms. This classification simplifies the categorization of patients with early RA, however, the diagnosis requires highly trained specialists who can differentiate early symptoms of RA from other pathology. Diagnosing RA involves a combination of clinical evaluation, imaging, and laboratory tests, including:

• Rheumatoid Factor (RF): An antibody found in many RA patients.
• Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibodies: More specific for RA.
• Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP): Indicators of inflammation.
• X-rays and MRI: To assess joint damage and inflammation.

Treatment (Bullock, J, et al., 2019), (Conigliaro, P. et al., 2019)

The goals of treatment for RA are to reduce joint inflammation and pain, maximize joint function, and prevent joint destruction and deformity. Treatment regimens consist of combinations of pharmaceuticals, weight-bearing exercise, educating patients about the disease, and rest. Treatments are generally customized to a patient’s needs and depend on their overall health. This includes factors such as disease progression, the joints involved, age, overall health, occupation, compliance, and education about the disease. Treatment options include:

• NSAIDs: For pain relief and inflammation reduction. The overall goal of first-line treatment is to relieve pain and decrease inflammation. Medications, considered to be fast-acting, are nonsteroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylate (Aspirin), naproxen (Naprosyn), ibuprofen (Advil and Motrin), and etodolac (Lodine). Aspirin is an effective anti-inflammatory for RA when used at high doses, due to the inhibition of prostaglandins. It is one of the oldest NSAIDs used for joint pain. Side effects of aspirin at high doses include tinnitus, hearing loss, and gastric intolerance. Other NSAIDs are newer on the market than aspirin and just as effective.
• Corticosteroids: Corticosteroids are a more potent anti-inflammatory medication than NSAIDs, but they come with greater side effects. For this reason, they are only indicated for a short period at low doses, during exacerbations or flares of RA. Intra-articular injections of corticosteroids can be used for the local symptoms of inflammation 
• Disease-Modifying Antirheumatic Drugs (DMARDs): Methotrexate is the most commonly used DMARD to slow disease progression. The overall goal of second-line treatment is to promote remission by slowing or stopping the progression of joint destruction and deformity. Medications are considered to be slow-acting because they take from weeks to months to be effective. Disease-modifying antirheumatic drugs (DMARDs) can also reduce the risk of developing lymphoma that can be associated with RA.
• Biologic Agents: Target specific parts of the immune system; examples include TNF inhibitors like etanercept and adalimumab.
• Physical Therapy: To maintain joint flexibility and strength.
• Surgery: In severe cases, joint replacement or repair may be necessary. Joint surgery in patients with RA reached a peak in the 1990s. However, a 2010 study showed decreased rates of joint surgery in RA patients 40–59 years of age. In contrast, patients older than 60 years had increased rates of surgery. Surgery is a last resort for the treatment of RA. Indications include intractable joint pain or functional decline due to joint destruction after all nonsurgical approaches have failed. At this point, the disease is considered “end-stage.” The goal of surgical management is to relieve pain for the patient and restore the function of the joints. A patient needing surgical treatment should be evaluated based on their customized needs because there are many different types of surgery.

Conclusion

Autoimmune diseases like lupus, rheumatoid arthritis, multiple sclerosis, Hashimoto's thyroiditis, and Sjögren's syndrome significantly impact women, who are disproportionately affected due to hormonal, genetic, and environmental factors. These conditions profoundly affect women's physical, emotional, and social well-being, particularly during their reproductive years.

Effective management involves understanding symptoms and treatment options, using medications, lifestyle changes, and coping strategies to improve quality of life. Recognizing gender-specific aspects is crucial for comprehensive care. Continued research offers hope for better treatments and, potentially, a cure. For women, staying informed, seeking medical care, and maintaining a healthy lifestyle are key to managing these diseases.

References

Pisetsky, D. S., Schur, P. H., & Romain, P. L. (2020). Overview of autoimmunity. Uptodate. com.

Ortona, E., Pierdominici, M., Maselli, A., Veroni, C., Aloisi, F., & Shoenfeld, Y. (2016). Sex-based differences in autoimmune diseases. Annali dell'Istituto superiore di sanita, 52(2), 205-212.

Ngo, S. T., Steyn, F. J., & McCombe, P. A. (2014). Gender differences in autoimmune disease. Frontiers in neuroendocrinology, 35(3), 347-369.

Gergianaki, I., Bortoluzzi, A., & Bertsias, G. (2018). Update on the epidemiology, risk factors, and disease outcomes of systemic lupus erythematosus. Best Practice & Research Clinical Rheumatology, 32(2), 188-205.

Parks, C. G., Santos, A. D. S. E., Barbhaiya, M., & Costenbader, K. H. (2017). Understanding the role of environmental factors in the development of systemic lupus erythematosus. Best practice & research Clinical rheumatology, 31(3), 306-320.

Thong, B., & Olsen, N. J. (2017). Systemic lupus erythematosus diagnosis and management. Rheumatology, 56(suppl_1), i3-i13.

Ruiz-Irastorza, G., & Bertsias, G. (2020). Treating systemic lupus erythematosus in the 21st century: new drugs and new perspectives on old drugs. Rheumatology, 59(Supplement_5), v69-v81.

Tanaka, Y. (2020). State‐of‐the‐art treatment of systemic lupus erythematosus. International journal of rheumatic diseases, 23(4), 465-471.

Radu, A. F., & Bungau, S. G. (2021). Management of rheumatoid arthritis: an overview. Cells, 10(11), 2857.

Jutley, G. S., Latif, Z. P., & Raza, K. (2017). Symptoms in individuals at risk of rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 31(1), 59-70.

Kourilovitch, M., Galarza-Maldonado, C., & Ortiz-Prado, E. (2014). Diagnosis and classification of rheumatoid arthritis. Journal of autoimmunity, 48, 26-30.

Bullock, J., Rizvi, S. A., Saleh, A. M., Ahmed, S. S., Do, D. P., Ansari, R. A., & Ahmed, J. (2019). Rheumatoid arthritis: a brief overview of the treatment. Medical Principles and Practice, 27(6), 501-507.

Conigliaro, P., Triggianese, P., De Martino, E., Fonti, G. L., Chimenti, M. S., Sunzini, F., ... & Perricone, R. (2019). Challenges in the treatment of rheumatoid arthritis. Autoimmunity reviews, 18(7), 706-713.