Systemic Lupus Erythematosus - an overview (2023)

Systemic lupus erythematosus (SLE) is defined by 11 diagnostic criteria, reflecting major clinical features such as mucocutaneous, articular, serosal, renal, and neurologic affections and associated laboratory, hematologic, and immunologic findings.

From: Reference Module in Biomedical Sciences, 2014

Related terms:

  • Lupus Nephritis
  • Serositis
  • Autoimmune Disease
  • Antibody
  • Protein
  • Autoantibody
  • Rheumatoid Arthritis
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Systemic Lupus Erythematosus

Robert M. Kliegman MD, in Nelson Textbook of Pediatrics, 2020


Treatment of SLE is tailored to the individual and is based on specific disease manifestations and medication tolerability. For all patients, sunscreen and avoidance of prolonged direct sun exposure and other UV light may help control disease and should be reinforced at every visit with the patient.Hydroxychloroquine is recommended for all individuals with SLE when tolerated. In addition to treating mild SLE manifestations such as rash and mild arthritis, hydroxychloroquine prevents SLE flares, improves lipid profiles, and may improve mortality and renal outcomes. Potential toxicities include retinal deposition and subsequent vision impairment; therefore, annual ophthalmology exams are recommended for patients taking hydroxychloroquine, including automated visual field testing as well as spectral-domain optical coherence tomography (SD-OCT). Given that risk factors for ocular toxicity include duration of use and dose, hydroxychloroquine in SLE should never be prescribed at doses >6.5 mg/kg (maximum 400 mg daily), and newer ophthalmology guidelines recommend limiting maintenance dosing to 4-5 mg/kg.

Corticosteroids are a treatment mainstay for significant manifestations of SLE and work quickly to improve acute deterioration; side effects often limit patient adherence, especially in adolescence, and potential toxicities are worrisome. It is important to limit dose and length of exposure to corticosteroids whenever possible. Potential consequences of corticosteroid therapy include growth disturbance, weight gain, striae, acne, hyperglycemia, hypertension, cataracts, avascular necrosis, and osteoporosis. The optimal dosing of corticosteroids in children and adolescents with SLE remains unknown; severe disease is often treated with high doses of intravenous (IV) methylprednisolone (e.g., 30 mg/kg/day to a maximum of 1,000 mg/day for 3 days, sometimes followed by a period of weekly pulses) and/or high doses of oral prednisone (1-2 mg/kg/day). As disease manifestations improve, corticosteroid dosages are gradually tapered over months. For most patients it is necessary to introduce a steroid-sparing immunosuppressive medication to limit cumulative steroid exposure.

Steroid-sparing immunosuppressive agents for the treatment of pediatric SLE include methotrexate, leflunomide, azathioprine, mycophenolate mofetil (MMF), tacrolimus, cyclophosphamide, rituximab, and belimumab. Methotrexate, leflunomide, and azathioprine are often used to treat persistent moderate disease, including arthritis, significant cutaneous or hematologic involvement, and pleural disease. Cyclophosphamide, MMF, and azathioprine are appropriate for the treatment of lupus nephritis, whereas MMF and rituximab are often used for significant hematologic manifestations, including severe leukopenia, hemolytic anemia, or thrombocytopenia.

Cyclophosphamide, usually administered intravenously, is reserved for the most severe, potentially life-threatening SLE manifestations, such as renal, neurologic, and cardiopulmonary disease. Although cyclophosphamide is highly effective in controlling disease, the potential toxicities are significant, including cytopenias, infection, hemorrhagic cystitis, premature gonadal failure, and increased risk of future malignancy. Attention to adequate hydration can attenuate the risk of hemorrhagic cystitis. Fortunately, young girls are at much lower risk of gonadal failure than older women, and the use of gonadotropin-releasing hormone agonists, such as leuprolide acetate, may help prevent gonadal failure.

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Systemic Lupus Erythematosus

Yun Deng, ... Betty P Tsao, in Emery and Rimoin's Principles and Practice of Medical Genetics (Sixth Edition), 2013

77.1 Introduction

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by autoantibody production, immune complex deposition, and heterogeneous clinical manifestations. Epidemiologic studies on the sibling risk ratio, familial aggregation of SLE and the disease concordance rate in monozygotic twins support a strong genetic contribution to the development of SLE (1). The inheritance of SLE is complex, following a polygenic model that common variations in a number of genes are involved, each contributing modestly to disease risk (2). As a genetically complex disease, SLE typically exhibits genetic heterogeneity, which has been demonstrated by genetic association analyses stratified by specific clinical features and ethnic backgrounds. In addition, epistasis, that is, interactions between genes or between genes and environmental factors, should be considered as potentially important determinants of disease risk.

Numerous genetic studies on SLE have been performed. Before 2007, the main approaches to explore genes predisposing to disease risk are (1) targeted and genome-wide linkage studies using multiplex families and (2) candidate gene association studies, usually performed using unrelated cases and ethnically matched control individuals. In the past four years (2007–2011), genome-wide association (GWA) studies that represent an important step beyond the two aforementioned methods have revolutionized the search for genetic influences on SLE susceptibility with more than 30 disease-associated loci identified and confirmed in large datasets. Efforts in delineating functional variants underlying SLE-associated signals and rare variants that may have strong impact in risks for SLE are underway. Results from these studies will help elucidate the molecular mechanisms and cellular pathways modulated by robust genetic associations with SLE, and should provide new targets for more focused therapies.

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Systemic Lupus Erythematosus

Fred F. Ferri MD, FACP, in Ferri's Clinical Advisor 2022, 2022

General Rx

There are only four FDA-approved SLE medications: Aspirin, steroids, hydroxychloroquine (1955), and belimumab (2011).

Treatment should be targeted toward the involved organ(s).

Limited and defined courses of corticosteroids are useful for a variety of SLE symptoms. Steroid therapy should be restricted to acute or subacute control of symptoms, due to the increased cardiovascular risk and increased organ damage associated with chronic steroid use.

Consider checking G6PD in certain ethnic groups more predisposed to antimalarial- induced hemolytic anemia.

Hydroxychloroquine has best evidence for reducing flares, organ damage, lipids, thrombosis; improving survival; augmenting action of mycophenolate mofetil (MMF) in lupus nephritis; and preventing seizures. Currently recommend not to exceed dose of 5 mg/kg/day to decrease risk of retinal toxicity.

Methotrexate and azathioprine are used as steroid-sparing agents. Indications include cutaneous and joint involvement.

Joint pain and mild serositis are generally well controlled with NSAIDs or low-dose corticosteroids. Hydroxychloroquine and methotrexate are also effective for arthritis. Belimumab does well for joint and cutaneous manifestations. Leflunomide and rituximabmay be considered for refractory arthritis. Treatment approach for musculoskeletal features of SLE is summarized inTable 5.

Cutaneous manifestations:


Topical or intradermal corticosteroids are helpful for individual discoid lesions, especially in the scalp.

(Video) Systemic lupus erythematosus (SLE) - causes, symptoms, diagnosis & pathology


Hydroxychloroquine alone or in combination with quinacrine and/or chloroquine can be considered for refractory skin disease.


Refractory cases may be treated with belimumab, MMF, dapsone, or combination treatment.


Table 6 summarizes general management of cutaneous lesions in SLE.

Hematologic manifestations:


Corticosteroids are first-line therapy.Table E7 summarizes the treatment and main hematologic features of SLE.


Azathioprine can be used for thrombocytopenia or hemolytic anemia. Check for TPMT genetic mutation before the first use.


Intravenous immunoglobulin (IVIG) or rituximab may be considered for severe leukopenia, autoimmune hemolytic anemia, or autoimmune thrombocytopenia.

Central nervous system manifestations:


Headaches are treated symptomatically. Most headaches will not be SLE-related and should be treated according to underlying cause.


Anticonvulsants and antipsychotics may be indicated.


Standard therapy for other neuropsychiatric SLE symptoms is not established.

Renal disease: The histologic classification of lupus nephritis according to the International Society of Nephrology/Renal Pathology Society is summarized inTable E8. Severity of lupus nephritis is described inTable E9. Treatment recommendations for lupus nephritis are summarized inTable E10. (Class III, IV or IV/V with cellular crescents lupus nephritis; seeTable E11). INDUCTION: 6-mo treatment

The typical treatment induction period is 6 mo. The use of intravenous cyclophosphamide (CYC) with corticosteroids given at monthly intervals is more effective in preserving renal function than is treatment with glucocorticoids alone. Low-dose “Euro-Lupus” protocol may be equally efficacious and less toxic for certain populations (e.g., Caucasians, Blacks) than high-dose regimen. MMF is considered equivalent to CYC based on high-quality studies, with better tolerability and fertility profile. MMF may be preferred in African Americans and Hispanics. MMF and azathioprine are good options for maintenance treatment.

There is interest in and positive data for use of calcineurin inhibitors, such as tacrolimus, for treatment of LN. Newer and possibly less toxic voclosporin has entered phase III trial and when added to MMF showed better results in renal responses compared with MMF alone.

Severe nonrenal organ disease:


Evidence from systematic randomized controlled trials for nonrenal lupus treatment is comparatively limited.


High-dose intravenous CYC is used as induction treatment. Azathioprine or MMF may be used as maintenance.


IVIG may be considered in severe disease especially when concomitant infection is present.


Plasmapheresis or plasma exchange may be considered in critical situations: First-line therapy in Guillain-Barré syndrome, TTP, second line for SLE-related hemolytic anemia, cerebritis, and DAH. Infectious complications are common.

Therapy targeting B cells:


Rituximab: Anti-CD 20 monoclonal antibody. Randomized controlled trials for rituximab as an adjunct induction agent were negative in terms of both renal and nonrenal outcomes but were felt to be limited by study design. Some observational studies have shown efficacy in those who have failed other regimens.


Epratuzumab: An anti-CD 22 agent. Studies initially showed positive data, but in July 2015 both phase III trials for SLE failed to meet their primary endpoint and this medication is no longer studied.


Belimumab: Decreases activation of B cells. When used in addition to standard therapy, patients on belimumab showed improvement in cutaneous and musculoskeletal disease. Belimumab-treated patients had decreased SLE activity, a reduced time to disease flare, and lower glucocorticoid exposure. Safety data were good. Patients with central nervous system or serious kidney disease were excluded. There is interest in adding belimumab to standard lupus nephritis regimen, but data from BLISS-LN are not yet available.


Abatacept: Downregulates T cell activation. Data is limited regarding improvement in arthritis, fatigue, sleep if added to routine therapy. Negative data as adjunct agent for lupus arthritis when added to MMF or CYC. Abatacept data provided evidence that low-dose cyclophosphomide may be as effective as high-dose cyclophosphomide in Blacks (ACCESS trial).


Interferon therapy: Interferon α (INFα) has been linked to increased disease activity in SLE. INFα blocking therapies are in phase II clinical trials. Sifalimumab, a monoclonal antibody against INFα, reduced moderate to severe mucocutaneous involvement in SLE and decreased active joint count and fatigue scores in preliminary data analysis. Development of sifalimumab has been terminated in favor of anifrolumab, a similar INFα blocking agent. The TULIP-1 study of that molecule did not meet response criteria based on score used in BLISS trial. TULIP-2 used BICLA as response measure and showed statistically significant improvement compared to placebo. The phase III trial is ongoing.


There is continuous interest in studying B cell- and interferon-based treatment, but no FDA approved treatment, other than above, is currently used clinically.


Novel potential targeted treatment approaches may include blocking IL17, IL12/23, and JAK inhibitors (early data for 4-mg baricitinib showed positive results). Research remains very active and ongoing to find new therapeutic targets.

Recommended assessment and monitoring of patients with SLE with nonrenal, non–central nervous system manifestations are summarized inBox 1.

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The Digestive Involvement in Systemic Autoimmune Diseases

M. Vilardell-Tarrés, ... J. Ordi-Ros, in Handbook of Systemic Autoimmune Diseases, 2017

1 Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a broad range of clinical manifestations. It is characterized by an immune system dysregulation resulting in the production of various autoantibodies and is considered a multifactorial disease with evidence of genetic susceptibility [1]. SLE affects several organ systems and leads to significant morbidity and mortality. Gastrointestinal (GI) manifestations caused by the disease per se or aggressive treatment regimens are not rare in SLE patients [2], but are seldom reported, likely being masked by other, more salient clinical features such as renal or central nervous system abnormalities. The incidence of GI symptoms attributable to the disease itself varies widely, ranging from 1.3% to 27.5% in the literature. Chronic intestinal pseudoobstruction (CIPO), protein-losing gastroenteropathy, and intestinal vasculitis are the most common identifiable SLE-related GI manifestations [3], which seem to occur more commonly in Asian populations. No specific autoantibodies associated with SLE-related gastroenteropathy have been identified to date. In this chapter, we describe the GI manifestations occurring in SLE patients. The liver manifestations of the disease are beyond the scope of this chapter and will be reviewed elsewhere.

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Systemic Lupus Erythematosus

Lee Goldman MD, in Goldman-Cecil Medicine, 2020

(Video) Lupus - Disease Overview

Renal System

Kidney involvement in SLE (Chapter 113) is common, with 74% of patients being affected at some time in the course of disease, and is a poor prognostic indicator. Renal pathology is generally attributed to the deposition of circulating immune complexes or in situ formation of these complexes in glomeruli and results in the activation of complement and subsequent recruitment of inflammatory cells. In addition to glomerular inflammation, necrosis, and scarring, renal pathology is characterized by vascular lesions, including thrombotic microangiopathy and extraglomerular vasculitis. Tubulointerstitial disease, including infiltration of the interstitium with mononuclear cells, tubular atrophy, and interstitial fibrosis, is increasingly recognized as associated with a poor prognosis for persistent nephritis and renal survival.17 Hypertension may be a consequence of significant renal involvement.

Most cases of lupus nephritis present a complex immunopathologic picture, but in general, the pattern of renal disease reflects the site of deposition of immunoglobulins and the quality of the effector mechanisms they induce. Mesangial deposition of immunoglobulin induces mesangial cell proliferation and is associated with microscopic hematuria and mild proteinuria (Fig. 250-3). Subendothelial deposition of immune complexes results in proliferative and exudative inflammation, together with hematuria, mild to moderate proteinuria, and reduced glomerular filtration rate. Subepithelial deposition of immune complexes adjacent to podocytes and along the glomerular basement membrane can result in membranous nephritis with nephrotic-range proteinuria. In addition, antiphospholipid antibodies may support the development of thrombotic or inflammatory vascular lesions within or external to glomeruli.

A World Health Organization classification of lupus nephritis lesions was first published in 1975, with subsequent revisions. These classifications were reviewed and rigorously reexamined in the revised International Society of Nephrology and Renal Pathology Society classification criteria for lupus glomerulonephritis (GN) published in 2004, with additional review in 2018.18 (Table 113-7 inChapter 113, and alsoE-Table 250-2). Class I and II GN involves mesangial deposition of immune complexes (class I without and class II with mesangial hypercellularity); class III describes focal GN involving less than 50% of total glomeruli; class IV includes diffuse GN involving 50% or more of glomeruli; class V designates membranous lupus nephritis; and class VI is characterized by advanced sclerotic lesions. Classes III and IV have subdivisions for active and sclerotic lesions, and class IV currently also has subdivisions for segmental and global involvement. Recent recommendations from these societies include elimination of the IV-S and IV-G subdivisions and replacement of the active and chronic designations for class III/IV lesions with application of activity and chronicity indices for all classes. They also suggest eliminating the term “endocapillary proliferation” and are considering a more appropriate definition of endocapillary hypercellularity. Validation of candidate revised classification criteria is planned by these groups. Pathologic diagnosis should include descriptions of tubulointerstitial and vascular disease as well as glomerular involvement. Several renal pathologic lesions seen in SLE patients that are not encompassed in the classification scheme for lupus GN include lupus podocytopathy, collapsing glomerulopathy, and thrombotic microangiopathy, the latter often associated with antiphospholipid syndrome.

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Physiology and Immune System Dysfunction

Grainne Murphy, David Isenberg, in Encyclopedia of Immunobiology, 2016


Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disorder with a diverse presentation and clinical course. It is most prevalent in females of childbearing age with a female:male ratio of 9:1 in this population. The prevalence of SLE is also higher in certain ethnicities, reflected in prevalence rates of ∼40/100000 persons in Northern European cohorts in comparison with rates of 200/100000 persons in studies of patients of African-American descent (Johnson etal., 1995). In addition to the higher disease frequency in this population, patients of Afro-Caribbean and Hispanic origin have also been observed to have an adverse clinical course. Recent studies also support the need for closer monitoring in patients with a juvenile onset of disease and males with SLE, both phenotypic factors that portend the potential for an adverse clinical course (Amaral etal., 2014).

Despite marked improvements in the therapeutics of SLE, there remains a significantly increased mortality in patients diagnosed with SLE. While in the 1970s a standardized mortality rate (SMR, which defines how many persons, per thousand of the population, will die in a given year)of 12.6 was noted in one large study of a cohort with SLE, reassessment of the same population within the last decade reported an SMR of 3.46 (Bernatsky etal., 2006). Although this indicates significant therapeutic advances, it should be highlighted that SLE is a condition that tends to affect a young female population making this statistic all the more clinically relevant. Further understanding of the pathophysiology of the disease with the ultimate goal of identifying unique therapeutic targets is required to further improve the prognosis of individuals withSLE.

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Systemic Lupus Erythematosus

Anastasiia Rind, David A Isenberg, in Reference Module in Biomedical Sciences, 2021

1 Introduction

Systemic lupus erythematosus (SLE) is a chronic, multisystemic, autoimmune disease with a highly heterogeneous pattern of clinical and serological manifestations. It is found in approximately 9–10 times as many women as men. It usual occurs in women during the child bearing years. It is more common, and often more severe, in black, hispanic and Chinese populations compared to caucasians. The disease may commence with one or two symptoms, however, multi-organ involvement is characteristic of SLE. Clinical manifestations vary significantly in different patients and in different periods of the disease. Although the individual's form of the disease is often established in a given patient during the 5years after diagnosis, great long term vigilance is required, as additional features (even renal disease) may appear after more than 10years. In the past four decades, major efforts have been made to define disease activity and damage, using standardized scales. These tools are essential to get international agreement about disease progression and prognosis especially in the era of new biological treatment.

The aetiopathogenesis of SLE is complex and involves an interplay of environmental, hormonal and immunological factors, although precisely how these interactions come about and the invariable, but subtle differences between individuals, remains obscure. A key factor in lupus development is the failure of the efficient removal of dead/dying cells. This normal process is known as apoptosis (the program of cell death) and inefficient removal of “cell debris” results in the undue persistence of nuclear fragments. This process ultimately leads to the development of the antinuclear antibodies, which characterize this disease, together with a reduction in complement levels and patterns of interferon expression.

The outlook for patients with SLE is much better than 50years ago with a current prognosis of about 85% 15year survival. However, the mortality rate remains too high, especially as many SLE patients are under 40. Common causes of death in SLE patients include infection, atherosclerosis and cancer. Death from severe active disease per se is now very uncommon. Morbidity is another major concern for SLE patients. As well as profound fatigue (almost universal among patients), fever and lymphadenopathy, which must be distinguished from infection and malignancy respectively, are often prominent. Longer term problems include atherosclerosis, which is increased in SLE, osteoporosis and avascular necrosis both linked to the corticosteroids widely used to treat the disease, and other concomitant autoimmune diseases (present in approximately one third of SLE patients).

The current conventional therapies notably hydroxychloroquine, corticosteroids and immunosuppressives together with adjunctive drugs (e.g., anti-hypertensives, statins and vitamins D) and some major interventions such as dialysis and transplantation, have lead to the improved prognosis for SLE patients. However, analogous to the improved outlook for patients with diseases like rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis brought about by the biologic drugs, many attempts have been made to treat SLE with these newer approaches. In contrast to the great successes seen in these other conditions, SLE has proved a much “tougher proposition.” Indeed to date, only benlysta (which blocks a B cell activating factor) and B cell depletion (induced by anti CD20 monoclonals like rituximab and its biosimilars) have receive any kind of formal approval. However, many other attempts to block molecules involved in the immune response are on going. Linked to this, is an appreciation that much of the damage (i.e., permanent change) observed in SLE is due to the excessive use of corticosteroids. Thus, there are major attempts, also on going, to try and reduce the amounts of corticosteroids used to treat SLE patients. This article will now describe the clinical features, serological abnormalities, key pathological aspects, current and possible future treatment of SLE in some detail.

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Systemic Lupus Erythematosus

Thomas J.A. Lehman MD, in Pediatric Clinical Advisor (Second Edition), 2007

Basic Information


Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that results from widespread immune complex deposition and secondary tissue injury. It is characterized by the presence of antinuclear antibodies (ANAs) and multiple organ system involvement. Any organ system may be affected by SLE, but the skin, joints, and kidneys are most commonly involved.




ICD‐9‐CM Code

710.0Systemic lupus erythematosus

Epidemiology & Demographics

The frequency of SLE varies by age, race, and sex.

It most commonly affects females between the ages of 15 and 25 years.

(Video) Systemic Lupus Erythematosus Nursing SLE NCLEX Review: Pathophysiology, Symptoms, Treatment

Incidence is as high as 30 cases per 100,000 Asian teens.

Incidence is estimated at 4 cases per 100,000 whites.

Hispanic and black girls have intermediate incidences.

Older and younger individuals and males are also affected. The incidence among boys is roughly one fourth of that for girls of the same race.

Positive test results for ANAs are found in approximately one third of first‐degree relatives.

Actual disease occurs in only about 1 of 50 first‐degree relatives.

Clinical Presentation


Fever, malaise, and weight loss are the most common presenting findings.

In teenagers who have unintentional weight loss or chronic fatigue, SLE should be included in the differential diagnosis.

Less commonly, SLE may have an explosive onset, manifesting with the following:

Seizures and diffuse neurologic symptoms

Nephritis or nephrotic syndrome



Profound leukopenia or thrombocytopenia

Any combination of above systems

Physical Examination

Because SLE involves multiple organ systems, the physician must carefully evaluate every organ system.

Children with SLE are often chronically ill and withdrawn appearing.

They may be depressed.

They may have undiagnosed arthritis.

They often do not want to be touched.

Hypertension may be present if there is renal involvement.

Most patients with SLE have a mild, nonspecific facial rash.

Only one in three children have a recognized malar rash with a butterfly distribution.

Bruises may be present if there is thrombocytopenia or abnormal clotting due to the lupus anticoagulant.

Alopecia is a common finding, but it may manifest with any chronic illness.

Ophthalmologic findings are uncommon. If central nervous system vasculitis is present, cotton‐wool exudates or other evidence of vasculitis may be found on funduscopic examination.

The hard palate often has areas of irritation and redness. This may be helpful when the family dismisses the facial rash as being caused by cosmetics or other topical agents.

Chest and cardiac examination findings may be normal.

SLE is a polyserositis, and the patient may have physical examination findings of pleural or pericardial effusions.

Be suspicious if the patient is tachypneic.

Children with lupus can have pulmonary emboli (more common in those with anticardiolipin antibodies or lupus anticoagulant).

Examine the abdomen.

Hepatosplenomegaly may be present in advanced cases.

Children may have diffuse, nonfocal tenderness from polyserositis.

Most children with active SLE have mild arthritis but may not be aware of it.

Tenderness when you squeeze their hands or feet

Knee effusions

Pitting edema suggests nephrotic syndrome.


The cause of SLE is unknown.

It occurs with increased frequency in first‐degree family members of affected individuals and is thought to have a genetic component, but it often occurs without any family history of disease.

Genetic absence of immunoglobulin A (IgA) and absent C4 complement occur more often than expected among children with SLE.

It is hypothesized that one or more immunoregulatory defects allow degeneration of a normal immune response into polyclonal B‐cell activation.

This results in production of antibodies to a wide variety of antigens unrelated to the initial immune response.

(Video) Systemic Lupus Erythematosus - A Clinical Overview for Medical Students

These antibodies lead to immune complex deposition and tissue damage.

The organ system involvement in a given individual is determined by the combination of his or her genetic background and the antigens his or her immune system has previously been exposed to.

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Systemic Lupus Erythematosus

Dandan Wang, Lingyun Sun, in A Roadmap to Non-Hematopoietic Stem Cell-based Therapeutics, 2019

1 SLE Is a Chronic Autoimmune Disease With Challenging Therapies

Systemic lupus erythematosus (SLE) is a heterogeneous chronic multisystem autoimmune inflammatory disorder with a prevalence of 40–70 out of 100,000 people. It is believed that genetic predisposition and environmental factors (e.g.,UV exposure, infection, and stress), or a combination of the two, may contribute to the development of SLE [1]. Despite the different initiating factors involved, the final pathway leads to aberrations in immune cells, including Tcells, B cells, and monocytic lineage cells that result in Tcell deficiencies, polyclonal B cell activation, autoantibody production, and immune complex formation [2].

The initial flare of SLE can be controlled by conventional immunosuppressive therapy. However, a definitive cure is rarely achieved and lifelong immunosuppression is often required. Positive response to therapy ranges from20% to 100% at 6months, depending on the criteria used to define improvement, the extent of visceral damage, and the patient's ethnic origin and socioeconomic profile. First-line validated standard therapies, used to induce remission in the first 6–9months of a disease flare, are efficacious and well tolerated and combine corticosteroids with either (1) cyclophosphamide (CYC), using the classic National Institutes of Health regimen or the Eurolupus regimen with lower doses for shorter periods of time (3months) [3,4] or (2) mycophenolate mofetil (MMF) [5].

Despite a paucity of validated therapeutic targets and inability to conclusively demonstrate efficacy, monoclonal antibodies (e.g., rituximab) against T or B cell receptors (e.g., CD20) or adhesion molecules and costimulatory signals involved in T or B cell interactions have been used to treat the renal and extrarenal manifestations of SLE [6]. In 2011, belimumab, a monoclonal antibody against B cell-activating factor (BAFF) (also known as B-lymphocyte stimulator [Blys]) was the first targeted therapy that demonstrated efficacy in mild to moderate SLE in a randomized clinical trial [7]. Despite early diagnosis and treatment with immunosuppressive agents, as well as tight control of hypertension and infection, there is still a subgroup of SLE patients that don't respond to treatment and have a 10-year mortality of 10% [8]. In addition, early death from rapidly progressive atherosclerosis in SLE suggests that the subclinical inflammatory disease promotes endothelial damage and plaque formation and prolonged treatment with corticosteroids and immunosuppressive drugs leads to further damage beyond the SLE itself.

Treatment of drug-resistant SLE with allogeneic/autologous hematopoietic stem cell transplantation (HSCT) was the first application of stem cell–based therapy for lupus. In 1997, Marmont etal. in Genova, Italy, performed the first autologous HSCT for SLE [9] using a peripheral CD34+ stem cell source after mobilization with CYC and granulocyte colony stimulating factor. Since that time, phase 1/2 prospective and retrospective studies have demonstrated a very favorable and prolonged clinical response with autologous HSCT in severely affected lupus patients [10]. Five-year follow-up data from 50 patients in the Center for International Blood and Marrow Transplant Research (CIBMTR) database showed an overall survival of 84%, probability of disease-free survival of 50%, and treatment-related mortality of 4% [11]. More recently, data from the European Group for Blood and Marrow Transplantation (EBMT) showed that 5-year overall survival was 81±8% and disease-free survival was 29±9%, with a nonrelapse mortality of 15±7% [12], suggesting that HSCT for lupus patients was a satisfactory and efficacious therapy. However, the biggest challenge for autologous HSCT is the high rate of disease relapse and the serious side effects of the conditioning therapy [13]. Jayne etal. reported that although 66% of patients achieved clinical remission by 6months, 32% of these patients subsequently relapsed, and transplant-related mortality (TRM) was 12% at 1year [14]. Unlike autologous HSCT, allogeneic HSCT appears to offer curative potential in that the auto-aggressive “old” immune system is replaced by a “new” one [15]. EBMT data contained two SLE patients who underwent allogeneic HSCT; however, one patient died of infection at 2.9months and the other patient's disease progressed after being followed for 3years. The clinical use of HSCT for severe autoimmune disease has been limited as TRM remains at about 20% [16] and the risk of graft versus host disease is high [17]. Clearly, a more effective and less toxic treatment regimen for SLE patients is urgently needed.

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Systemic Lupus Erythematosus

Benjamin Rhodes, Timothy J. Vyse, in Genomic and Personalized Medicine (Second Edition), 2013

Classification and Clinical Features

Systemic lupus erythematosus (SLE or lupus) is a potentially fatal systemic autoimmune disease that predominantly affects women of childbearing age (Bertoli and Alarcon, 2007). Although the pathogenesis of SLE remains poorly understood, there is clearly widespread immune dysfunction encompassing both the innate and adaptive immune pathways. The immunological hallmark of SLE is the production of high-affinity autoantibodies directed against ubiquitous intracellular antigens, particularly double-stranded DNA and nucleoprotein complexes (Rahman and Isenberg, 2008). The clinical features of lupus are notoriously heterogeneous, with symptoms related to immune-mediated dysfunction of the kidney, skin, central nervous system, blood, and other organs. Accelerated cardiovascular disease is an important late-stage complication (Elliott et al., 2007; Urowitz et al., 1976).

This diversity of clinical presentation raises issues of how to define SLE cases for the purposes of enrollment into research studies. At present, the 1982 American College of Rheumatology (ACR) criteria are almost universally used (Table 80.1) (Tan et al., 1982). Later, we will discuss how use of the ACR criteria impacts upon the interpretation and utility of genetic studies. The key issue is that lupus is so clinically heterogeneous that patients fulfilling the ACR criteria may be very different in terms of their disease manifestations; indeed it is theoretically possible for lupus patients to share no clinical features at all. The implication of this is that SLE may also be genetically heterogeneous, with some genes associated with disease in general and others associated with specific clinical sub-phenotypes.

Table 80.1. The 1982 revised ACR criteria for the diagnosis of lupus

Classification criterionDetails
Malar rashThe “butterfly rash” of SLE
Discoid rashRaised erythematosus plaques. May scar
PhotosensitivitySkin rash as unusual response to sunlight
Oral ulcersUsually painless
ArthritisNon-erosive in >2 peripheral joints
SerositisPleuritis or pericarditis
Renal disorderPersistent proteinuria or cellular casts
Neurological disorderSeizures or psychosis
Hematological disorderHemolytic anemia or other cytopenia
Anti-nuclear antibodiesIn the absence of “drug-induced” lupus
Other immunological disordere.g., anti-dsDNA or anti-Sm antibodies

SLE diagnosed for the purposes of clinical study if >4 criteria present. dsDNA, double stranded DNA; Sm, smooth muscle; ACR, American College of Rheumatology.

Adapted from Tan et al., 1982.

Although considerable progress has been made in the management of lupus over the last 10 years (recent estimates suggest an 80–90% 10-year survival rate), it remains an incurable disease (Ramsey-Goldman and Gladman, 2007). The current therapeutic options of corticosteroids, small-molecule immunosuppressants, and even targeted biological agents all really fail to address fundamental disease mechanisms in SLE. As a consequence, treatment regimens remain suboptimal both in terms of therapeutic efficacy and unwanted side effects.

Perhaps the key motivation for studying lupus genetics is that it has the potential to highlight fundamental disease pathways that are part of the causative pathogenic process – pathways that will then be amenable to therapeutic intervention. However, we are also aware that demonstrable immunological dysfunction precedes the development of clinical lupus, often by many years, and it is during this window of opportunity that we perhaps have the best chances of intervening with targeted therapeutics to prevent the onset of overt disease (Arbuckle et al., 2003). The identification of genetic variants contributing to disease susceptibility may also eventually allow us to identify individuals who are at high risk of developing the disease and who can therefore be targeted for preventative, or pre-clinical treatment strategies. Whether we can utilize our genetic knowledge further, to predict disease manifestations or to guide therapeutic decisions, is more speculative and dependent on further research (Rhodes and Vyse, 2010).

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(Video) Systemic Lupus Erythematosus - CRASH! Medical Review Series


What triggers systemic lupus erythematosus? ›

Sunlight (UVB) is considered a definite SLE trigger. Additional possible SLE triggers include colds and other infections, fatigue, stress, smoking, chemicals, and certain drugs. Some research suggests an association between Epstein-Barr virus (EBV), the cause of mononucleosis, and increased risk for lupus.

What are daily struggles with lupus? ›

Having lupus can make everyday life challenging. When your lupus is active, symptoms like joint stiffness, pain, fatigue, confusion, or depression can make simple tasks difficult — and sometimes impossible. Since these symptoms aren't visible, the people around you may have trouble understanding how you feel.

What is the difference between lupus and systemic lupus erythematosus? ›

Systemic lupus erythematosus (SLE) is the most common and most serious type of lupus. SLE affects all parts of the body. Cutaneous lupus erythematosus, which affects only the skin. Drug-induced lupus, a short-term type of lupus caused by certain medicines.

What are the 4 stages of lupus? ›

Stages of lupus nephritis
  • Class I: Minimal mesangial lupus nephritis.
  • Class II: Mesangial proliferative lupus nephritis.
  • Class III: Focal lupus nephritis (active and chronic, proliferative and sclerosing)
  • Class IV: Diffuse lupus nephritis (active and chronic, proliferative and sclerosing, segmental and global)

What is the life expectancy with lupus? ›

With close follow-up and treatment, 80-90% of people with lupus can expect to live a normal life span.

What should you not do if you have lupus? ›

5 Things to Avoid if You Have Lupus
  1. (1) Sunlight. People with lupus should avoid the sun, since sunlight can cause rashes and flares. ...
  2. (2) Bactrim and Septra (sulfamethoxazole and trimethoprim) Bactrim and Septra are antibiotics that contain sulfamethoxazole and trimethoprim. ...
  3. (3) Garlic. ...
  4. (4) Alfalfa Sprouts. ...
  5. (5) Echinacea.

What is the most common body organ affected from lupus? ›

Kidneys About one half of people with lupus experience kidney involvement, and the kidney has become the most extensively studied organ affected by lupus. Lungs About 50% of people with SLE will experience lung involvement during the course of their disease.

What is the most common complication of lupus? ›

Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus. Brain and central nervous system. If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures.

Does lupus affect your behavior? ›

Mood swings and personality changes.

People with lupus may experience unpredictable changes in moods and personality traits. This can include feelings of anger and irritability. These may be related to the disease process or, in some cases, the use of corticosteroid medications.

What happens if lupus goes untreated? ›

If left untreated, it can put you at risk of developing life-threatening problems such as a heart attack or stroke.

How does lupus make you feel? ›

You may experience pain and stiffness, with or without swelling. This affects most people with lupus. Common areas for muscle pain and swelling include the neck, thighs, shoulders, and upper arms. Fever.

Does lupus qualify for disability? ›

For Social Security's purposes, lupus qualifies as a disability when it meets these conditions: It involves two or more organs or body systems. It includes at least two major signs or symptoms, such as severe fatigue, fever, malaise, and involuntary weight loss.

What blood tests show lupus? ›

Antinuclear antibody (ANA) test.

A positive test for the presence of these antibodies — produced by your immune system — indicates a stimulated immune system. While most people with lupus have a positive ANA test, most people with a positive ANA do not have lupus.

Is lupus a serious diagnosis? ›

The seriousness of SLE can range from mild to life-threatening. The disease should be treated by a doctor or a team of doctors who specialize in care of SLE patients. People with lupus that get proper medical care, preventive care, and education can significantly improve function and quality of life.

What are the 11 markers for lupus? ›

The 11 Signs of Lupus: What You Need to Know
  • A butterfly-shaped rash across both sides of the face.
  • Raised, red skin patches.
  • Sensitivity to light.
  • Ulcers in the mouth or nose.
  • Arthritis plus swelling or tenderness in two or more joints.
  • Seizures or other nervous system problems.
  • Excessive protein in urine.
Oct 24, 2019

Is living with lupus hard? ›

Living with lupus can be hard, but a positive outlook is important. You can do several things to help you live with lupus. A good place to start managing your lupus is to work with your doctor and take your medications as directed. At times, you may feel sadness and anger.

Does lupus progressively get worse? ›

Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening.

Can you drink alcohol with lupus? ›

Most people with lupus who are old enough to drink alcohol can do so in moderation. Be aware, however, that alcohol can change the way the body uses or metabolizes certain medications, rushing them into the bloodstream. This can intensify both the good and not-so-good effects of medications.

How do you calm a lupus flare up? ›

Treating a lupus flare
  1. Rest and sleep. This might mean taking some time off of work or asking for help around the house. ...
  2. Focus on your mental health and stress levels. There are stress management resources out there to help.
  3. Lean on your support system. ...
  4. Take medications as directed.
Jan 12, 2022

Do you need rest with lupus? ›

Get Enough Rest to Prevent Fatigue

If you have lupus you may need even more sleep. “It's important to develop good sleeping habits,” says Jolly. “It can really make the difference in getting a good night's sleep.”

What pain medication is prescribed for lupus? ›

Non-steroidal anti-inflammatories (NSAIDs)

They're the most common treatment for typical lupus symptoms like fever and joint pain.

How does lupus affect your bowels? ›

Lupus can slow the digestive process, and this can cause a wide variety of GI issues. Digestive problems may be the direct result of an attack by the immune system or from medications to treat lupus. These digestive difficulties include nausea, vomiting, diarrhea, or constipation.

What does lupus do to the brain? ›

Lupus and the central nervous system

Symptoms include: Confusion and trouble concentrating (sometimes called lupus brain fog) Seizures (sudden, unusual movements or behavior) Stroke (blocked blood flow in the brain that causes brain cells to die)

What is the most common treatment for lupus? ›

Corticosteroids (prednisone) may help reduce swelling, tenderness, and pain. In high doses, they can calm the immune system. Corticosteroids, sometimes just called “steroids,” come in different forms: pills, a shot, or a cream to apply to the skin. Lupus symptoms usually respond very quickly to these powerful drugs.

What is the leading cause of death in lupus patients? ›

As death from kidney disease has declined, heart attacks and related cardiovascular diseases have emerged as leading causes of early mortality in people with lupus. The reasons for accelerated heart disease have not been precisely delineated, but it is clear that multiple factors contribute.

What is lupus hair? ›

But some people with lupus develop round (discoid) lesions on the scalp. Because these discoid lesions scar your hair follicles, they do cause permanent hair loss. Lupus can also cause the scalp hair along your hairline to become fragile and break off easily, leaving you with a ragged appearance known as lupus hair.

Does lupus cause sleep problems? ›

Lupus and sleep disorders

Unfortunately, 61% of those with lupus claim that they do not feel refreshed after a night of sleep. Typically, those with lupus have sleep problems that may include any or all of the following: restless sleep. poor sleep quality.

Is lupus triggered by stress? ›

Stress weakens the immune system and increases the risk of developing psychological conditions like depression and anxiety disorder. According to the Lupus Foundation of America and the Center of Disease Control (CDC), emotional stress may act as a trigger to set off lupus or bring on a flare.

Does lupus make you gain weight? ›

Weight changes — Lupus can sometimes cause weight loss or weight gain. Weight loss may be unintentional and due to decreased appetite or problems with the digestive system (see 'Digestive system' below). It can also be a side effect of some medications used to treat lupus.

What vitamins should I avoid with lupus? ›

People with lupus should avoid certain supplements, including echinacea, spirulina, and vitamin E. These supplements may increase the immune system response and trigger lupus symptoms. It is also helpful to avoid excess sun exposure, salt, and alfalfa sprouts, which may also make symptoms worse.

How do rheumatologists diagnose lupus? ›

If your doctor suspects you have lupus based on your symptoms, a series of blood tests will be done in order to confirm the diagnosis. The most important blood screening test is ANA. If ANA is negative, you don't have lupus. However, if ANA is positive, you might have lupus and will need more specific tests.

How long can you have lupus without knowing? ›

On average, it takes nearly six years for people with lupus to be diagnosed, from the time they first notice their lupus symptoms.

How much does disability pay for lupus? ›

Some lupus victims may be able to work but if this isn't possible Social Security disability benefits (SSDI) can help you pay your medical bills. The Maximum SSDI benefit each month is $3,627 in 2023. If you are approved for SSDI, then you may be eligible for federal Medicare benefits.

Can you drive with lupus? ›

Lupus can indirectly cause other health problems that interfere with driving a vehicle. I have severe neck pain that started when I was stuck in bed for months due to fatigue and joint pain. This neck pain has prevented me from driving more often than anything else.

What are the early signs of lupus in females? ›

With that said, anyone with lupus can be affected by the following symptoms:
  • Joint swelling, pain, and stiffness. ...
  • A butterfly-shaped face rash. ...
  • Unusually high sensitivity to sunlight. ...
  • Fever. ...
  • Chest pain. ...
  • Hair loss. ...
  • Mouth sores. ...
  • Kidney problems.
Jan 21, 2022

What level of ANA indicates lupus? ›

The initial requirement of the criteria for lupus diagnosis is a positive ANA test with a titer of at least 80. The numerical value of the titer refers to the ratio of blood serum being evaluated to a dilution agent.

Why is lupus so hard to diagnose? ›

Lupus is a disease that is known for being difficult to diagnose because the symptoms are different from person to person, they mimic the symptoms of many other diseases, and they can come and go. It can sometimes take several years to receive an official diagnosis.

Would lupus show up on a CBC? ›

Many people with systemic lupus have abnormal CBCs. White blood cell counts can be low (leukopenia) due to lupus, immunosuppressive therapy, or the presence of a virus. High WBC counts may signal infection but also occur when individuals are on corticosteroids such as prednisone.

What are the most severe symptoms of lupus? ›

The most common lupus symptoms (which are the same for men and women) are: Extreme fatigue (feeling tired all the time) Pain or swelling in the joints. Swelling in the hands, feet, or around the eyes.

Can you suddenly develop lupus? ›

It can occur suddenly or appear after exposure to sunlight. Sometimes the rash appears just before a flare-up. Lupus can also cause non-itchy lesions in other areas of the body.

Who is most likely to get lupus? ›

Anyone can get lupus; however, women get the disease about nine times more often than men. Most often it happens in people between ages 15 and 45 years, but lupus can occur in childhood or later in life as well.

What is the number one symptom of lupus? ›

The most common lupus symptoms (which are the same for men and women) are: Extreme fatigue (feeling tired all the time) Pain or swelling in the joints. Swelling in the hands, feet, or around the eyes.

What blood type is prone to lupus? ›

Since antigens play a major role in how lupus works, studies checked if the blood groups with antigens (A, B, and AB) are a risk factor. One study⁸ demonstrated that people with B+ blood type might have a higher risk of developing lupus.

Does lupus show up in blood work? ›

No one test can diagnose lupus. The combination of blood and urine tests, signs and symptoms, and physical examination findings leads to the diagnosis.

What tests confirm lupus? ›

Blood and urine tests.

The antinuclear antibody (ANA) test can show if your immune system is more likely to make the autoantibodies of lupus. Most people with lupus test positive for ANA.

What is lupus pain like? ›

Muscle and joint pain.

You may experience pain and stiffness, with or without swelling. This affects most people with lupus. Common areas for muscle pain and swelling include the neck, thighs, shoulders, and upper arms.

What does lupus do to a person? ›

If you have lupus, you might experience joint pain, skin sensitivities and rashes, and issues with internal organs (brain, lungs, kidneys and heart). Many of your symptoms might come and go in waves — often called flare-ups. At times, symptoms of lupus might be mild or not noticeable (meaning they're in remission).

Is lupus a big deal? ›

Lupus flares can be mild to serious, and they do not follow a pattern. However, with treatment, many people with lupus can manage the disease. Anyone can get lupus, but women are more likely to get the disease than men are.


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