Systemic Lupus Erythematosus (SLE): Symptoms, Causes, Effects, Diagnosis, Treatment, Complications and Outlook

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systemic lupus erythematosus

1Overview

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves different organs. Its clinical course is varied. The diagnosis of SLE is based on characteristic findings of the kidneys, central nervous system, skin, and joints. Serological parameters are also used as an aid to diagnosis, such as antinuclear antibodies (ANA). The diagnosis of SLE should not be taken lightly, because of the increased risk for complications due to the disease.

The peak age of onset of SLE among young women is in the late teens, and then again in the early 40s. The disease has a female to male ratio of 9:1. In the European Union, the annual incidence of SLE ranges between 3.3 cases per 100,000 people to 4.8 cases per 100,000 individuals. In the United States, the annual incidence of SLE is approximately 1.8-7.6 cases per 100,000 individuals. The incidence of the disease may be increasing.

2Symptoms

The symptoms of SLE vary widely, but there is always skin involvement. Joints are also involved, as about 90% of patients with SLE present with arthralgia. Usually, however, there is no overt arthritis in patients. Some patients may have deformed joints, but they are associated with hypertrophy.

Clinically significant muscular involvement has been reported in 30-50% of patients with SLE. However, muscle weakness and myalgia may be due to other complications.

Cutaneous lesions occur in up to 85% of patients with SLE. The characteristic butterfly rash can be observed. It is erythematous, blotchy, and found over malaria bones and the across the nose bridge. Lesions such as discoid lesions and maculopapular rashes also occur. Other symptoms include dilated capillaries at the base of the nail, bullies lesions, and genital and nasal ulceration.

Many of the cutaneous symptoms are made worse by exposure to ultraviolet light. Indeed, many flare-ups of SLE are connected with exposure to sunlight.

SLE may also manifest neurologically. Neurological manifestations include seizures and psychosis.

Aside from these, SLE may also manifest as a hematologic disorder, where the patient develops immune-mediated hemolytic anemia, thrombocytopenia, and lymphopenia.

3Causes

The causes of SLE remain unclear, however, it has been postulated that the concept of apoptosis is relevant to how the immune system recognizes intracellular antigens. Autoantigens are released by apoptotic and necrotic cells. In SLE, defects in the clearance of apoptotic cells have been described which may lead to the dysfunctional uptake by macrophages. These present intracellular antigens to T and B cells, thus furthering the immune process.

The most striking recent studies have demonstrated the role of autoantibodies before the clinical symptoms of SLE are apparent. Antinuclear antibodies (ANA) occurred in these patients earlier than anti-DNA antibodies. Aside from these, a significant number of patients have increased titers of anti-DNA antibodies just before diagnosis.
The potential of anti-DNA antibodies for pathogenicity is unclear.

Several animal models and experiments have shown that these anti-DNA antibodies have the capacity to produce renal lesions in severe combined immunodeficiency (SCID).

Cytokine patterns may also be important in the pathogenesis of SLE. Recent studies have shown that patients with SLE have an overexpression of type I interferon pathway. Common interferon regulatory factor 5 has been identified as an important genetic risk factor for SLE.

Genetic susceptibility to SLE is inherited as a trial that is complex and studies have shown that several genes are implicated. Clinically, it is widely accepted that SLE is typified by elevated erythrocyte sedimentation rates. However, their C-reactive proteins remain normal. 

4Effect on the Body

The effect of SLE on the body varies widely, in part due to the multisystem involvement that is associated with the disease. SLE has systemic manifestations. These include fever, weight loss, anemia, fatigue, and myalgia/arthralgias. The fever is usually low-grade.
The patient may also experience photosensitivity. Psychologically, fatigue accompanied by loss of appetite will lead to weight loss. The mouth and the nose can have ulcers, which may be painful. The face displays a butterfly rash over the cheeks and on the bridge of the nose. Muscle aches are also common. Arthritis is also observed in patients with SLE.
The patient’s lungs may be inflamed and the tissue surrounding the heart, or the pericardium, may be inflamed as well. Poor oxygen circulation can be observed in the fingers and toes.

Musculoskeletal effects can also be seen. Polyarthritis involves various joints, such as knees, fingers, wrists, and hands. However, erosions on joints upon x-ray are rare. Myalgias may also be observed but these do not come with frank myositis.

Discoid lupus erythematosus (DLE) presents with a systemic rash. On the other hand,
sub-active cutaneous lupus erythematosus (SCLE) presents with circular discoid lesions on the scalp and face. The rashes in SLE are photosensitive and are exacerbated by exposure to sunlight and UV light.

Lupus nephritis is another effect on the body, which manifests as nephrotic syndrome.
This may be accompanied by secondary hypertension and accelerated atherosclerosis.

Nervous system manifestations include headaches, seizures, psychosis, and myelopathy. 

5Diagnosis

The clinical diagnosis of SLE depends on a thorough examination of the patient, investigation of organs, and laboratory tests. Symptoms of SLE often occur intermittently over a number of months or years. Oral ulcers, Reynaud’s phenomenon, hair fall, arthralgia, photosensitive rashes, and headaches may point to a diagnosis of SLE.

The clinical examination of all organ systems includes the performance of routine analysis and blood pressure measurement. Simple investigations may yield information that is significant. For instance, an elevated erythrocyte sedimentation rate (ESR) accompanied by a normal C-reactive protein is a strong indicator of SLE. Blood count abnormalities, such as anemia, neutropenia, and thrombocytopenia are also common. Serological investigations should include examinations for ANA, but these are highly sensitive yet unspecific.
Thus, investigations for the diagnosis of SLE involve many tests and a trained clinician will be able to differentiate SLE from other syndromes that have similar presentations. 

6Treatment

The goals of therapy for SLE are to primarily stop inflammation in the organs and to prevent or limit organ damage. In addition, the clinician must keep in mind that there are potential toxicities associated with immunosuppressive therapy. The current therapy for SLE includes corticosteroids, cyclophosphamide, methotrexate, azathioprine, and belimumab.

Although these therapeutic interventions have proven to be successful, they come with risks. Immunosuppressive therapy confers an increased risk for cancer, infection, and infertility. Corticosteroids, on the other hand, also have their own risks. These include infections, diabetes, osteoporosis, mood disturbances, hypertension, and lipid abnormalities.

Other studies suggest that antimalarial agents are effective as treatments for SLE.
The action of antimalarials is based on the inhibition of several receptors that mediate immunity. Hydroxychloroquine and chloroquine are approved for the treatment of SLE. Apart from their efficacy against arthritis and skin lesions, antimalarials are able to prevent relapse, are associated with fewer disease flares, and reduce the damage that comes with the course of the disease.

Glucocorticoids are the treatment of choice for skin lesions on SLE. Class IV glucocorticoids, such as clobetasol, can be applied to the soles, scalp, and palms. In other areas of the body, class II and class III glucocorticoids are recommended. Due to the adverse effects that come with glucocorticoids, they should not be administered long-term and only used intermittently.

Immunosuppressives such as methotrexate, mycophenolate, and azathioprine are recommended if antimalarials are not enough. Methotrexate, in particular, may have a good effect on the joints and skin lesions.

For patients with lupus nephritis, mycophenolate mofetil and intravenous cyclophosphamide are recommended.

7Complications of SLE

Chronic damage is observed in patients with SLE. Chronic damage, in this case, is defined as long-standing damage that has been there since the onset of SLE. Renal and/or pulmonary damage within a year after diagnosis is complications of the disease.
These are associated with an increased risk for dialysis in patients.
The increased risk of death for those with early damage, defined as occurring within 2 years after diagnosis, is increased.

Coronary artery disease is another common complication of SLE.
The risk of coronary artery disease increases with age, longer disease duration, hypertension, longer steroid use, obesity, diabetes, and post-menopausal status.

Osteoporotic fractures are common in patients with SLE. It is also the most preventable form of skeletal damage. Individuals with SLE self-report that they had at least one fracture since they were diagnosed.

8Outlook

The outlook for patients with SLE depends on the duration of the disease and the time of diagnosis. Patients with SLE generally do well with anti-malarial drugs, which addresses some of the inflammatory problems associated with the disease. However, for patients with multi-organ system involvement, the outlook is less bright. Multi-organ system involvement will increase the risk of dialysis, infections, and eventually early mortality and morbidity. Aside from these, cardiac involvement in patients with SLE also contributes to morbidity and mortality. The risk factors for the disease also contributes to the development of adverse outcomes for those with SLE.