Systemic lupus erythematosus overview

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Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Systemic lupus erythematosus from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Lupus and Quality of Life
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2] Raviteja Guddeti, M.B.B.S. [3]

Historical perspective

The word "lupus" means wolf in Latin, as the destructive injuries the disease caused brought to mind the bites of this animal. The history of lupus erythematosus can be divided into three periods: Classical, neoclassical, and modern periods. The classical history mostly refer to the ancient history, when there was no exact definition of the disease and its facts. During the neoclassical lupus era, scientists were investigating to find out the manifestations of lupus and tried to define the disease action. Modern history is mostly focused on the microscopical understanding of the disease and pathogenesis of SLE.

Classification

Lupus may be classified into several subtypes according to clinical features which include: systemic lupus erythematosus, cutaneous lupus erythematosus, drug-induced lupus, and neonatal lupus. Systemic lupus erythematosus (SLE) itself may be classified into several subtypes based on glomerulonephritis and dermatologic manifestations. SLE may be classified according to dermatologic manifestations into 4 subtypes: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE), and intermittent cutaneous lupus erythematosus (ICLE). SLE may be classified according to glomerulonephritis into 6 subtypes: minimal mesangial lupus nephritis (class I), mesangial proliferative lupus nephritis (class II), focal lupus nephritis (class III), diffuse lupus nephritis (class IV), lupus membranous nephropathy (class V), and advanced sclerosing lupus nephritis (class VI).

Pathophysiology

The pathophysiology of systemic lupus erythematosus involves the immune system. Other factors such as genetic factors, hormonal abnormalities, and environmental factors also play a role. The most important environmental factors involved in the pathogenesis of SLE include ultraviolet (UV) light and some infections. The most important genes involved in the pathogenesis of SLE include HLA-DR2, HLA-DR3, HLA class 3, C1q, and interferon (IFN) regulatory factor 5. The most prominent events involving immune abnormalities are related to persistent activation of B cells and plasma cells that make auto-antibodies during disease progression. The disease developmental process begins with the release of microparticles and proinflammatory cytokines from the cells that are undergoing apoptosis. Due to excess amount of apoptosis, the body is unable to clear these microparticles entirely, and these microparticles are presented to dendritic cells as antigens. Dendritic cells process these microparticles and mature, and present these as antigens to T-cells. T-cells, microparticles, and proinflammatory cytokines themselves trigger B-cell activation and autoantibody production. As a result, body tissues lose their self-tolerance. The most prominent events involving hormonal abnormalities are due to prolactin and estrogen. On microscopic histopathological analysis, apoptotic keratinocytes, vacuolization of the basement membrane, and dermal mucin deposition are characteristic findings of SLE dermatitis, and active or inactive endocapillary or extracapillary segmental glomerulonephritis are characteristic findings of lupus nephritis.

Causes

There are no established causes for systemic lupus erythematosus. Common causes of systemic lupus erythematosus include genetic predisposition, auto-immune diseases, and drugs. Less common causes of systemic lupus erythematosus include environmental factors and exposure to ultraviolet (UV) light.

Differentiating Systemic lupus erythematosus from other diseases

Systemic lupus erythematosus (SLE) must be differentiated from other diseases that cause skin rash, arthritis, positive autoimmune serology, weight loss, fevers and chronic pain, such as rheumatoid arthritis(RA), mixed connective tissue disease (MCTD), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis(PM), and other autoimmune diseases.

Epidemiology and Demographics

Worldwide, the prevalence of systemic lupus erythematosus is 60 per 100,000 persons. In North America, South America, Europe, and Asia, the incidence of systemic lupus erythematosus ranges from a low of 1 per 100,000 persons to a high of 20 per 100,000 persons with an average prevalence of 12 per 100,000 persons. The overall mortality rate of lupus is very high, estimated to have approximately 50,000 death of 100,000. Women are more commonly affected with systemic lupus erythematosus than men. Systemic lupus erythematosus flare ups are more prevalent in women. Systemic lupus erythematosus is more prevalent in the African race and Asian races.

Risk Factors

The most potent risk factor in the development of systemic lupus erythematosus is sex. Other risk factors include HLA genetic mutations, being African Americans, Asians, and non-Causcasian, and previous exposure to some special infections.

Screening

According to the United States Preventive Services Task Force, screening for systemic lupus erythematosus is not recommended.

Natural history, complications and prognosis

Natural History

Systemic lupus erythematosus (SLE) is an autoimmune disease. SLE involves many flare ups. SLE usually develops in the second and third decade of life, although it can present any age, and start with mild symptoms such as fatigue, fever, and skin rashes. Without treatment, the patient will develop symptoms of end organ damage, which will eventually lead to death in most patients. The disease course can be divided into 4 subcategories based on the course of the disease: developmental phase, preclinical phase, clinical phase, and comorbid complication phase.

Complications

Common complications of systemic lupus erythematosus include dermatitis, nephritis and arthritis. Most of these complications may happen as part of the disease chronic activity, and are the most important reason of the disabilities characteristics of the disease.

Prognosis

The prognosis of systemic lupus erythematosus ranges from a benign illness to an extremely rapid progressive disease that can lead to a fulminant organ failure and death. Without treatment, systemic lupus eryhtematosus will result in a very high mortality rate, with a report of more than 60% mortality rate during the mid-20th century. SLE is associated with a 10 year mortality of more than 50% among patients with nephritis. The presence of nephritis is associated with a particularly poor prognosis among patients with SLE. The increase in survival rate of patients and better prognosis may be due to increased disease recognition with more sensitive diagnostic tests, earlier diagnosis or treatment, the inclusion of milder cases, increasingly judicious therapy, and prompt treatment of complications. Although improvement in SLE diagnosis have led to better prognosis, the mortality rate among SLE patients is still 5 times more than normal population.

Diagnosis

Diagnostic criteria

Based on SLICC criteria, for an SLE diagnosis: Patient should have either at least 4 of 17 criteria, including at least 1 of the 11 clinical criteria and one of the six immunologic criteria (for each criterion, any bullet is considered as 1 clinical criteria), OR a biopsy-proven nephritis compatible with SLE in the presence of antinuclear antibodies (ANA) or anti-double-stranded DNA (dsDNA) antibodies.

History and Symptoms

A positive history of familial lupus, skin rashes (especially photosensitive skin rashes), arthritis, and fatigue may be suggestive of systemic lupus erythematosus. The most common symptoms of SLE include constituitional symptoms like Fatigue, Fever, Myalgia, and weight changes. Other organ specific symptoms mostly occur with disease progression. SLE may show a variety of symptoms in different organs according to its complications.

Physical Examination

In the earlier stages of the disease, the patients are more well-appearing while in the late stages of the disease, patients are ill with multi-organ involvement. The patient may show a wide range of skin manifestations including urticaria, bullous lesions, malar rash, and scarring alopecia. Patient may develop nasal and oral ulcers. Arthritis may lead to decrease range of motion, joint effusion, and arthralgia. Neurological manifestations include psychosis, cognitive impairment, and hallucinations may be present too. 

Laboratory Findings

Laboratory findings consistent with the diagnosis of systemic lupus erythematosus include autoantibodies elevation of ANA, anti-dsDNA antibody, anti-SM antibody and antiphospholipid antibodies, and decrease of complement levels. Non specific laboratory findings include mild pancytopenia, elevated levels of creatinine and proteinuria due to renal failure (secondary to nephritis), elevated levels of ESR and CRP as acute phase reactants, decreased level of complements, and positive direct coombs test.

Imaging Findings

Electrocardiographic findings

The most important and prevalent ECG findings associated with systemic lupus erythematosus (SLE) include sinus tachycardia, ST segment changes, and ventricular conduction disturbances. Other ECG findings are related to late complications of SLE and may range based on the complication. 

X ray

On X ray imaging, systemic lupus erythematosus (SLE) may be characterized by different features regarding the present complication. the most common characteristic findings of SLE in X ray include: thumb printing sign in the abdominal graphy, blunting of the costophrenic angle due to pleural effusion, cardiomegaly, hepatomegaly, osteoprosis, tenosinovitis, and other manifestations based on the complications. 

CT scan

On abdominal CT-scan, systemic lupus erythematosus (SLE) may be characterized by hepatosplenomegaly, pancreatic parenchymal enlargement, and ascites. On cardiac CT-scan, SLE may be characterized by enhancement of the thickened pericardium. On brain CT-scan, SLE may be characterized by brain atrophy, stroke patterns like cortical hypodensity, and increased attenuation of the cortex.

MRI

On abdominal MRI, systemic lupus erythematosus (SLE) may be characterized by hepatomegaly, pancreatic parenchymal enlargement, and hypervascularity of mesentery. On cardiac MRI, SLE may be characterized by mitral leaflet thickening, pericardial thickness, and pericardial effusions. On brain MRI, SLE may be characterized by white matter lesions, changes in blood circulation of the brain, and patchy areas of enhancement. On musculoskeletal MRI, SLE may be characterized by intramuscular edema, proliferative tenosynovitis, and bone marrow edema.

Ultrasound and echocardiography

On abdominal ultrasound, systemic lupus erythematosus (SLE) may present with hepatosplenomegaly, ascites, hyperecho-kidney tissue due to nephritis, and rarely cholecystitis. On synovial ultrasound, SLE may present with synovial effusions and synovitis. On SLE may present with decrease ejection fraction, cardiac wall motion abnormality, effusion pericarditis, and valve leaflet thickening.

Other imaging findings

Other imaging systems that can be used for diagnosis of systemic lupus erythematosus complications include: Fibreoptic bronchoscopy and double-contrast technique for gastritis evaluation. Another imaging technique that can be helpful in diagnosis of SLE complications especially early manifestaions is Technetium-99m scan. It can be used in different ways include bone scintigraphy and bone scans to evaluate early and late bone complications, and for early evaluation of other organ complications including cardiac, hepatobiliary, and pulmonary complications.

Other diagnostic studies

Other diagnostic tests that can be used for diagnosis of complications include barium swallow for stricture diagnosis, biopsies of kidneys and endometrium for further diagnosis of the degree of involvement, paracentesis to evaluate body effusions, and arthrocentesis to differentiate different causes of arthritis.

Treatment

Medical Therapy

The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. The treatment choice for systemic lupus erythematosus (SLE) is varied based on the severity of the disease and symptoms. Generally all the patients with any type of SLE manifestation should be treated with hydroxychloroquinedespite the level of their disease. Other pharmacologic medical therapies for SLE include glucocorticoids like oral prednisone or intravenous methylprednisolone, NSAIDs like celecoxib, and immunosuppressive therapy with either mycophenolate, cyclophosphamide, or rituximab particularly in severe cases. Cutaneous lupus eryhtematosus (CLE) if presented separately without any other system involvement can be treated with topical corticosteroids. Other organ related complications of SLE should be treated separately.

Surgery

Surgical intervention is not recommended for the management of systemic lupus erythematosus.

Prevention

Primary Prevention

There is no established method for prevention of systemic lupus erythematosus.

Secondary Prevention

Secondary prevention strategies following systemic lupus erythematosus include using aspirin, ACE inhibitors, and statins to reduce atherosclerotic diseases, and using cancer screenings.

References

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