Despite advances in treatment, mortality among SLE patients remains high with significant geographic variations. Gender, race, and ethnicity significantly affect SLE incidence, prevalence, damage accrual, and mortality. In , data from the Michigan 1 and Georgia 2 Lupus Registries were published and provided a valuable insight into the incidence and prevalence of systemic lupus erythematosus SLE in the United States in a population predominantly composed of Caucasians and African Americans Table 1.
The number of Hispanic and Asian patients in these three registries was small, so the CDC supported the creation of two similar lupus registries in California and New York. Both studies reported a higher prevalence and incidence rate of SLE in women compared with men, and in African Americans compared to Caucasians, similar to the data reported from Michigan and Georgia.
The diverse population allowed estimation of incidence and prevalence among Hispanics and Asians, who had a higher incidence and prevalence of SLE compared to Caucasians, but lower than African Americans table 1.
The diverse populations included in these two registries allowed the first reliable estimation of incidence and prevalence among the Hispanic and Asian population in the United States. Ungprasert et al. They demonstrated a higher incidence of SLE when using SLICC criteria 58 cases compared to ACR criteria 44 cases , mostly due to cases of isolated lupus nephritis, serologic abnormalities, and non-scarring alopecia. Furst et al. The incidence and prevalence of SLE was similar to previous estimates table 1.
Other than the recently published data from the Michigan Lupus Epidemiology and Surveillance Registry 8 which described a 2. Al Dhanhani et al. The age-standardized incidence over the four-year period was 8. The incidence rates described were similar to the ones reported in the Michigan Lupus Epidemiology and Surveillance Registry for the Arab population 7.
In Europe, Schneider et al. The estimated incidence rates of SLE were at the lower end of other estimates from comparable European countries, with the incidence rate for German women being less than half of the French rate Otsa et al. The reported SLE incidence in Estonia was lower than in countries with similar prevalence, presumably due to the use of a lower age limit of 20 years as a study inclusion criterion.
In southern Sweden, Ingvarsson et al. The prevalence of SLE increased slowly over the same period. Sex-specific incidence rates of SLE and of lupus nephritis peaked later in life among men than among women. The first estimates of SLE incidence and prevalence on the island of Crete were reported 15 table 2.
While the incidence of SLE and lupus nephritis remained stable over the study period — , prevalence increased. There was regional variation in both incidence and prevalence. People of Afro-Caribbean ethnicity had the highest incidence and prevalence. In a systematic review of worldwide incidence and prevalence of SLE 17 , the highest estimates of incidence and prevalence of SLE were in North America Women were more frequently affected than men for every age and ethnic group.
People of African ethnicity had the highest incidence and prevalence of SLE, whereas those with Caucasian had the lowest incidence and prevalence. There appeared to be an increasing trend of SLE prevalence with time.
After an initial decrease between and , SLE mortality increased annually for 24 years, followed by a sustained decrease for 14 years starting in On the other hand, all-cause mortality decreased throughout the study period.
Residence in the Northeast conferred the lowest mortality risk regardless of sex or ethnicity. Costenbader et al. In a general population based study in the United Kingdom, SLE patients were shown to have nearly double the premature mortality risk of their peers Lee et al.
All-cause standard mortality rates were increased 2. The risk of mortality was significantly increased for mortality due to renal disease SMR 4. A study from Denmark 22 identified hospitalized patients with SLE over a period of 36 years and coupled them with their relatives through the Civil Registration System followed by identification of twins using the Danish twin registry.
In a separate publication 23 , same authors reported a lower SLE twin concordance in Denmark than previously reported. Among seven monozygotic, eight same-sex dizygotic and five opposite-sex dizygotic twin pairs, one monozygotic and one dizygotic same-sex pair were concordant for SLE. This corresponded to proband and pairwise concordance rates of Men also had more cardiovascular comorbidities and were hospitalized more frequently. Men were more likely to lose weight, have lupus nephritis, lymphadenopathy, splenomegaly, and pulmonary fibrosis.
A prospective single-center cohort in South Korea followed children and adults with SLE over a period of 14 years Immunosuppressants were used more frequently by children with SLE. The standardized mortality rate in pediatric SLE was Several studies examined the malignancy risk among SLE patients. A retrospective nested case-control study 26 which included patients in Taiwan analyzed the risk of malignancy among SLE patients on azathioprine, cyclophosphamide, methotrexate, hydroxychloroquine and glucocorticoids.
A total of patients developed a malignancy. Diagnosis of SLE can be challenging and while several classification criteria have been posed, their utility in the clinical setting is still a matter of debate. Management of SLE is dictated by organ system involvement, and despite several agents shown to be efficacious in the treatment of SLE, the disease still poses significant morbidity and mortality risk in patients.
SLE is a multifactorial disease with unknown exact etiology, however, several genetic, immunological, endocrine, and environmental factors play a role in the etiopathogenesis of SLE. Familial segregation and high concordance rates in identical twins suggest a strong genetic contribution in SLE, although there is no obvious pattern of inheritance.
This suggests an association with genes on the X-chromosome, however, despite several studies, the exact genes have not been identified.
Female sex and hormonal influence is a significant risk factor for SLE. Estrogens and prolactin promote autoimmunity and increase the B-cell activation factor production and modulate lymphocyte and pDC activation. The use of estrogen-containing contraceptives and postmenopausal hormone replacement therapy can cause flares in patients with SLE and have been associated with a higher incidence of SLE.
Elevated levels of prolactin are seen in patients with SLE. Androgens, on the other hand, are considered protective. Several environmental triggers of SLE have been identified. Several drugs have been implicated in causing a lupus-like phenomenon by causing demethylation of DNA and alteration of self-antigens. Ultraviolet rays and sun exposure leads to increased cell apoptosis and is one of the well-known triggers for SLE.
Several viral infections have been implicated, the underlying mechanism thought to be molecular mimicry. Smoking is also thought to be a risk, with a dose-response.
Varying prevalence and incidence rates of SLE have been reported, with differences mostly attributes to the population differences. The Georgia and Michigan lupus registries reported prevalence of African-Americans have the highest rates, and rates are higher among Asian and Hispanic populations compared to Caucasians.
The disease tends to have an earlier age of onset and is more severe in African-Americans. SLE predominantly affects women of childbearing age, with female to male ratio of 9 to 1.
The risk, however, decreases after menopause in women although still is twice as compared to men. Studies have indicated that although rare, lupus in men tends to be more severe. Age plays an important role in SLE, and although the disease is more common in childbearing age in women, it has been well reported in the pediatric and elderly population. SLE is more severe in children while in the elderly, it tends to be more insidious onset and has more pulmonary involvement and serositis and less Raynaud's, malar rash, nephritis, and neuropsychiatric complications.
A break in the tolerance in genetically susceptible individuals, on exposure to environmental factors, leads to the activation of autoimmunity. Cell damage caused by infectious and other environmental factors exposes the immune system to self-antigens leading to activation of T and B cells which become self-sustained by a chronic self-aimed immune response. Cytokine release, complement activation, and autoantibody production then lead to organ damage.
Both innate and adaptive immune systems play a role in the pathogenesis of SLE. The innate immune system activation is either Toll-like receptor TLR dependent, or independent.
Neutrophils, on activation by various factors such as cytokines, activated platelets and vascular endothelial cells systematically release their nuclear aggregates in the extracellular environment.
These nuclear aggregates can then promote Interferon-alpha production by the dendritic cells, mediate thrombosis and vascular damage and serve as self-antigens for T-lymphocytes. T-lymphocytes and B-lymphocytes play a significant role in the pathogenesis of SLE. Apoptotic and damaged cell-derived antigens are presented to T-cells by antigen-presenting cells. T-cells in SLE display a distorted gene expression leading to the production of several cytokines. These T-cells produce less IL-2, which leads to altered regulatory T-cell production.
T-cells lead to the activation of autoreactive B-cells by CD40L and cytokine production, which leads to autoantibody production, which is a hallmark of SLE. Toll-like receptors on interaction with DNA and RNA lead to activation of these B-cells, and the nucleic acid and protein-containing intranuclear complexes are the most prominent antigens leading to B-cel activation.
These autoantibodies are pathogenic and cause organ damage by immune complex deposition, complement, and neutrophil activation, and altering cell function leading to apoptosis and cytokine production. Further, the autoreactive B-cells in SLE which are stimulated by self-antigens, are not readily eliminated due to a deficiency of the process involved in the functional neutralization of autoreactive B cells.
The B-cells can also serve as antigen-presenting cells and can activate T-cells by presenting internalized soluble antigens to T-cells. This creates a loop where both B and T cells activate each other, both leading to more autoimmunity.
Tissue pathology is SLE can demonstrate a variety of aberrant immunologic mechanisms including immune complex formation, autoantibody formation, and immunologically mediated tissue injury. LE body or hematoxylin body is a hallmark of SLE pathology.
It is a homogeneous globular mass of nuclear material that stains bluish-purple with hematoxylin. It can be observed in the lungs, kidneys, spleen, heart, lymph nodes, and serous and synovial membranes. Pathology from skin lesions in SLE demonstrates immune complex formation leading to tissue damage, vascular and perivascular inflammation and chronic mononuclear cell infiltration.
Acute lesions demonstrate fibrinoid necrosis at the dermo-epidermal junction and the dermis along with liquefactive degeneration of the epidermis and perivascular inflammatory cell infiltration with a T-cell predominance. Chronic lesions can also demonstrate hyperkeratosis and follicular plugging. Immunofluorescence demonstrates deposition of IgG, IgA, and IgM immunoglobulins and complement components along the dermal-epidermal junction.
Immune complex deposition with an inflammatory response is the most common lesion, although it may be seen without significant inflammatory response as well. Small and large vessel necrotizing vasculitis with fibrinoid necrosis is less common but can be seen and can be differentiated from other vasculitides by immune complex deposition in the vessel wall.
Thrombotic microangiopathy can be seen in patients with SLE and antiphospholipid antibody syndrome. Central nervous system pathology in SLE reveals small intracranial vessel involvement with thrombotic lesions with or without perivascular inflammation and endothelial proliferation. Necrotizing vasculitis can be seen rarely. Thromboembolism from Libman-Sacks endocarditis has been seen as well. Cardiac pathology may include valvular involvement leading to Libman-Sacks endocarditis which is sterile verrucous endocarditis.
It tends to involve the mitral valve most commonly with vegetations seen on the forward flow side of the valve.
Pathology reveals platelet thrombi, necrotic cell debris, proteinaceous deposits, and mononuclear cells. Pericarditis with fibrinous exudate is common and pathology reveals fibrinoid necrosis and perivascular infiltration with mononuclear cells. Myocarditis can be seen as well. SLE poses a very high risk for atherosclerotic coronary artery disease, and vasculitis, immune complex deposition in addition to corticosteroid use and hypertension are thought to be contributory.
Lymphadenopathy is common in SLE, and pathology may reveal follicular hyperplasia with giant cells, plasma cells infiltration of the interfollicular zones, and necrosis of the paracortical T-cell zones. LE bodies may be rarely seen. The necrotic vessel wall shows immunoglobulin and Complement C3 deposition.
Splenomegaly is also common in SLE, with pathology showing the classic onionskin lesion with has multiple concentric rings of perivascular collagen.
Follicular hyperplasia and periarterial fibrosis are common. Interstitial pneumonitis, alveolitis, alveolar wall injury, and edema and hemorrhage are commonly seen in these patients.
Immunoglobulin and complement deposition is seen in the vessel wall. Medial hypertrophy and intimal fibrosis involving the branches of the pulmonary artery lead to pulmonary hypertension in SLE. Again, immunoglobulin and complement deposition can be seen in the vessel wall.
Lupus nephritis can involve the glomeruli, interstitium, tubules and the vessels with immune complex deposition in all four compartments. The World Health Organization classification criteria for lupus nephritis [7] describes 6 classes of lupus nephritis all with distinct pathological features and significant differences in clinical outcomes.
This has lead to a different treatment approach for each class and knowing the class of lupus nephritis before initiating treatment is vital.
SLE is a multisystem disease with several phenotypes, and clinical features may vary from a very mild disease with only mucocutaneous involvement, to a very severe life-threatening disease with multiorgan involvement. All organ systems can be involved in SLE. An autoantibody profile can sometimes be helpful in predicting the disease course and clinical features.
Several studies have indicated the development of serological abnormalities several years before the onset of clinical lupus.
This is termed as pre-clinical lupus, where a patient may have serological abnormalities consistent with SLE and may have some clinical features, but still does not meet the criteria for SLE. There is evidence that a significant percentage of these patients with pre-clinical lupus that include those with incomplete lupus, or undifferentiated connective tissue disease may transition to clinical lupus and fulfill the SLE criteria later in life. Fatigue, malaise, fever, anorexia and weight loss are common.
Further, SLE is a very rare cause of fever of unknown origin. Lupus specific lesions include 1. Acute cutaneous lupus erythematosus ACLE , which includes localized, malar and generalized, 2. Subacute cutaneous lupus erythematosus SCLE , which includes annular and papulosquamous, and 3.
Acute cutaneous lupus erythematosus ACLE may be localized or generalized. The hallmark ACLE lesion is the malar rash or the butterfly rash, which is an erythematous raised pruritic rash involving the cheeks and nasal bridge. The rash may be macular or papular and spares the nasolabial folds photoprotected. It usually has an acute onset, but may last several weeks, and may cause induration and scaling.
The malar rash may also fluctuate with lupus disease activity. Other rashes in this location that must be differentiated from ACLE malar rash include rosacea, erysipelas, seborrheic dermatitis, and perioral dermatitis. Generalized ACLE leads to widespread maculopapular or macular rash in a photosensitive pattern.
ACLE lesions usually heal without scarring. Subacute cutaneous lupus erythematosus SCLE rash is a photosensitive, widespread, nonscarring, nonindurated rash.
SCLE lesions may last several months but usually, heal without scarring. SCLE can also be caused by some drugs such as hydrochlorothiazide. DLE may occur with or without SLE, and can be either localized only head and neck or generalized above and below the neck.
The lesions are disk-shaped erythematous papules or plaques with adherent scaling and central clearing. DLE heals with scarring, and when present on the scalp, can be associated with permanent alopecia. Mucosal DLE lesions can be seen in the oral cavity, and these tend to be painful erythematous round lesions with white radiating hyperkeratotic striae.
Hypertrophic DLE may mimic squamous cell carcinoma histologically. Lupus panniculitis can occur above the waist and is less likely to be associated with SLE. The lesions result in depressed areas, and when associated with DLE lesions overlying them, are known as lupus profundus. Chilblains lupus presents with erythematous tender plaques on fingers and toes.
Lupus tumidus lesions are erythematous edematous smooth plaques without epidermal involvement. Oral and nasal ulcers are common in SLE, and acutely, often are painless. They may present as gradual onset erythema, macule, petechiae, erosions or ulcers involving any part of the oral cavity with most common locations being the hard palate, the buccal mucosa, and the vermilion border. These patients also experience worsening of their systemic symptoms on sun exposure.
These include cutaneous vasculitis leukocytoclastic or urticarial , vasculopathy livedo reticularis, superficial thrombophlebitis, Raynaud's phenomenon, erythromelalgia, periungual telangiectasia , sclerodactyly, rheumatoid nodules, calcinosis cutis, bullous lesions, urticaria, erythema multiforme, acanthosis nigricans, lichen planus, and leg ulcers. Lupus arthritis is typically a non-erosive, symmetrical inflammatory polyarthritis affecting predominantly the small joints of the hands, knees, and wrists, although any joint can be involved.
Jaccoud arthropathy is the result of the joint capsule and ligament laxity leading to non-erosive deformities of the hands including ulnar deviation and subluxation of the metacarpophalangeal joints, that may mimic rheumatoid arthritis.
Usually, these deformities are reducible, although rarely, they may become fixed. Rheumatoid nodules have been reported in patients with SLE. Other causes of anemia in SLE may include iron deficiency anemia, coomb's positive autoimmune hemolytic anemia, red blood cell aplasia and microangiopathic hemolytic anemia which may be associated with antiphospholipid antibody syndrome.
Leukopenia secondary to neutropenia or lymphopenia is also very frequent and can be severe. Pancytopenia is not infrequent and may occasionally be associated with myelofibrosis. Soft non-tender lymphadenopathy is common in SLE, although rare cases of histiocytic necrotizing lymphadenitis have been reported Kikuchi-Fujimoto disease.
Splenomegaly is common in SLE, while splenic atrophy and asplenism have been reported. Other CNS manifestations include aseptic meningitis, demyelinating syndrome including optic neuritis and myelitis, movement disorders such as chorea and cognitive dysfunction. Patients with SLE are also at high risk for ischemic strokes. Psychiatric manifestations are especially difficult to diagnose and manage and may range from depression and anxiety to frank psychosis.
Lupus nephritis is a well-known and common complication of SLE. The involvement may range from mild subnephrotic proteinuria to diffuse progressive glomerulonephritis leading to chronic kidney damage. Lupus nephritis usually occurs early in the course of SLE. New-onset hypertension, hematuria, proteinuria, lower extremity edema, and elevation in creatinine shall raise suspicion for lupus nephritis.
A biopsy is crucial in staging the lupus nephritis and ruling out other causes. The six classes of lupus nephritis are mentioned in the histopathology section of this article. The treatment of lupus nephritis is dictated by the biopsy findings and prognosis varies for each class with an excellent prognosis for classes I and II, and poor outcomes with classes III and IV.
Class V usually carries a favorable prognosis except for complications of nephritis syndrome such as thromboembolism which are common in this class. Other renal manifestations may include thrombotic microangiopathy, interstitial nephritis, lupus vasculopathy, vasculitis, and arteriolosclerosis. However, other adults may experience SLE flares more frequently throughout their life. Other symptoms can include sun sensitivity, oral ulcers, arthritis, lung problems, heart problems, kidney problems, seizures, psychosis, and blood cell and immunological abnormalities.
Learn more about lupus triggers and how to control your symptoms on the Managing Lupus page. Early diagnosis and effective treatments can help reduce the damaging effects of SLE and improve the chance to have better function and quality of life.
Poor access to care, late diagnosis, less effective treatments, and poor adherence to therapeutic regimens may increase the damaging effects of SLE, causing more complications and an increased risk of death. These limitations experienced by people with SLE can impact their quality of life, especially if they experience fatigue. Fatigue is the most common symptom negatively affecting the quality of life of people with SLE. Adherence to treatment regimens is often a problem, especially among young women of childbearing age 15 to 44 years.
Because SLE treatment may require the use of strong immunosuppressive medications that can have serious side effects, female patients must stop taking the medication before and during pregnancy to protect unborn children from harm. Women with lupus can safely get pregnant and most will have normal pregnancies and healthy babies. SLE is diagnosed by a health care provider using symptom assessments, physical examination, X-rays, and lab tests. SLE may be difficult to diagnose because its early signs and symptoms are not specific and can look like signs and symptoms of other diseases.
Because diagnosis can be challenging, it is important to see a doctor specializing in rheumatology for a final diagnosis. SLE can affect people of all ages, including children. However, women of childbearing ages—15 to 44 years—are at greatest risk of developing SLE. Most people with SLE do not have family members with the disease; however, some people with SLE do have a family history of the disease.
Men and women with an immediate family member with SLE have only a slightly higher risk for the disease. Treating SLE often requires a team approach because of the number of organs that can be affected.
SLE treatment consists primarily of immunosuppressive drugs that inhibit activity of the immune system. Hydroxychloroquine and corticosteroids e. Incidence and prevalence are terms commonly used to describe how many people have a disease or condition.
CDC uses the latest available data for important research questions. Recent national estimates of prevalence and incidence are not available for SLE.
SLE is relatively uncommon, is difficult to diagnose, and is not a reportable disease, so it is expensive to capture all diagnosed cases reliably for epidemiologic studies. There are no recent studies to determine if SLE prevalence or incidence are changing over time. See the Lupus Studies page for more information.
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