Systemic Lupus Erythematosus: Epidemiology and Pathophysiology

Systemic Lupus Erythematous (SLE) is a complex chronic autoimmune disease that affects multiple organ systems (Bengtsson & Ronnblom, 2016). In SLE many autoantibodies are created causing multiple organ systems to be affected and resulting in the inflammatory responses evident in the clinical manifestation of the disease (Bengtsson & Ronnblom, 2016). Due to the complexity of SLE and the involvement of multiple organ systems, it can be quite difficult to identify. Signs and symptoms of the disease widely vary in patients based upon the organ systems that are involved in individual cases, making diagnostic reasoning critically important in differentiating SLE from other diseases is may mimic.

Epidemiology

Systemic Lupus Erythematous (SLE) is known as an autoimmune disease, characterized by inflammation to multiple organ systems, thus creating many different antibodies. Prevalence of SLE in the United States is difficult to determine based on the magnitude of multiple organs affected, presenting a variety of different clinical manifestations. SLE has been described as heterogeneous disease for this reason. Less than ten in every 100,000 persons has SLE, as it is a rare disease (Yeoh, Dias, & Isenberg, 2018). SLE has been diagnosed in people of all ages, races, and ethnicities, but has prominence in women of childbearing years (Falasinnu, Chaichian, & Simard, 2017). African American women have a higher prevalence of SLE than Caucasian women (Jordan, Thompson, Dunlap-Thomas, Lim, & Drenard, 2019).  The age and ethnicity of the onset of symptoms plays a great role in the severity of the disease. Children diagnosed with SLE are more likely to experience greater complications associated to more aggressive progression of the disease, when compared to later diagnosis in adults (Cildag,S., Kara, Cakir, Cildag, M.B., & Senturk, 2019).

Pathophysiology

SLE is a complicated autoimmune disease that involves the impaired clearance of apoptotic cellular material, formation of immune complexes (ICs), dysfunction of the innate and adaptive immune systems, and inflammatory reactions involving all organ systems (Fava & Petri, 2019). SLE has a number of factors that lead to the onset of the disease. It is believed that genetics and environmental factors both have a role in the development of SLE in addition to immune and hormonal factors (Fava & Petri, 2019). Environmental factors in connection with SLE include Ultraviolet light, smoking, drugs (sulfamethoxazole), viral infections (Epstein-Barr virus), stress, and exposure to certain chemicals (mercury) all have a role in the development of SLE (Fava & Petri, 2019). 

Once the onset of SLE occurs as a result of epigenetics a cascade of immune dysfunction occurs resulting in multiple organ inflammation and dysfunction. The development of antibodies against nuclear antigens such as DNA and RNA results in the formation of antinuclear antibodies (ANAs) and anti-DNA autoantibodies (Banasik & Copstead, 2019). The ANAs and anti-DNA autoantibodies incite a cyclic reaction in which they interact with DNA and nuclear components from damaged cells in the body, resulting in an inflammatory response causing further cell damage and more antigen-antibody ICs are formed (Banasik & Copstead, 2019). The ICs are responsible for initiating the inflammatory responses in multiple organ systems that cause the clinical manifestations of the disease (Banasik & Copstead, 2019). 

Clinical Presentation

SLE patients typically do not present in the same clinical way as one another. Due to the relationship of the disease and the plethora of organs affected, clinical presentation varies from patient to patient. The organs that create characteristic manifestations include the kidneys, heart, skin, joints, nervous system, GI tract and lungs. Most often objective manifestation associated with SLE is a butterfly rash on the bridge of the nose and cheeks, also known as a malar rash (Yoeh, et al., 2018). Arthralgia with synovitis and symmetrical polyarthritis are prevalent in 70-90% of all cases of SLE at some point or another; alopecia, renal disease with proteinuria and valvular dysfunctions are present in 50-70% of patients with SLE (Yeoh, et al., 2018). Fatigue and pleurisy are often subjective manifestations of SLE. Photosensitivity is also a clinical manifestation of SLE.  As the disease progresses the clinical manifestations worsen, each case has exacerbations and remission periods and are graded based on the severity of presentation from mild to severe.

Diagnostic Reasoning

Diagnosis for SLE remains challenging for many providers, due to many organs presenting manifestations. SLE may initially present as other diseases and can sometimes be misdiagnosed or have a delayed diagnosis (Cildag, et al., 2019). Not all organs are affected at the same time and each patient may present with different symptoms at different stages of their disease. Diagnosis depends on clinical presentation as well as laboratory results. The Systemic Lupus International Collaborating Clinics (SLICC) developed criteria for diagnosing SLE. There are clinical criteria, with acute and chronic subparts, containing eleven criteria. Ranging from cutaneous, to neurological and circulatory involvement. Then the immunological criteria containing six sub criteria including an ANA which has high indication of SLE. The SLICC states that a patient must present with a total of four of the criteria, with one presentation being clinical and one being immunological to be diagnosed as having SLE (Yoeh, et al., 2018).

Diagnostic tools utilized in SLE vary depending on the patient's presentation, clinical and immunological criteria. Magnetic resonance imaging and ultrasound can help to identify soft tissue complications related to tendons and joint capsule involvement. Urinalysis will help determine proteinuria, which can lead to a renal biopsy for definitive diagnosis and cerebral spinal fluid analysis assists in confirming SLE (Fava et al., 2019).

Differential Diagnosis

The complexity of SLE and the multiple systems involved make it challenging to correctly diagnosis and can lead to misdiagnosis. Dermatomyositis (DM) is a disease to consider as a differential diagnosis when assessing a patient due to the similarity in presentation of photosensitivity with a rash, greater prevalence in women and systemic involvement. Serology plays in important role is distinguishing between SLE and DM. DeWane, Waldman and Lu stated that DM has specific antibodies known as myositis-specific antibodies (MSAs), including anti-Mi2, anti-MDA5, anti-NXP2, anti-TIFI, and anti-SAE (2019). None of which will be positive in SLE.

Fibromyalgia is a chronic pain syndrome with unknown etiology. Although fibromyalgia presents as generalized musculoskeletal pain, weakness, and fatigue similar to clinical manifestations of SLE there are no diagnostic labs or radiographic findings to support a diagnosis of fibromyalgia (Banasik & Copstead, 2019). The involvement of additional organ systems in addition to an elevated ANA lab value will not be present in fibromyalgia, unlike SLE, thus differentiating the two (Yoeh et al., 2018).

Similar to SLE, rheumatoid arthritis (RA) is an autoimmune disease affecting the systemic inflammatory response. Despite the similarities in RA and SLE, positive rheumatoid factor (RF), elevated C-reactive protein (CRP), and elevated erythrocyte sedimentation rate (ESR) would be expected laboratory findings in RA but not in SLE (Banasik & Copstead, 2019). Alternatively, multiple organ system involvement would not be expected in RA.

References

• Banasik, J., & Copstead, L. (2019). Pathophysiology (6th ed.). St. Louis, Missouri: Elsevier.
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• Cildag, S., Kara, Y., Cakir, E., Cildag, M. B., & Senturk, T. (2019). Comparison of clinical and laboratory findings in patients with Systemic Lupus Erythematosus with regard to age at onset. The Eurasian Journal of Medicine, 51(1), . doi:10.5152/eurasionjmed.2018.18022
• DeWane, M. E., Waldman, R., & Lu, J. (2019). Dermatomyositis part 1: Clinical features and pathogenesis. Journal of American Academy of Dermatology, , . doi:10.1016/
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• Fava, A., & Petri, M. (2019). Systemic lupus erythematosus: Diagnosis and clinical management. Journal of Autoimmunity, 96(2019), 1-13. doi.org/10.1016/j.jaut.2018.11.001
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• Yeoh, S. A., Dias, S. S., & Isenberg, D. A. (2018). Advances in systemic lupus erythematosus. Medicine, 46(2), 84-92. doi:10.1016/j.mpmed.2017.11.1010