Systemic Lupus Erythematosus

History of Systemic Lupus Erythematosus

Lupus was first described in 1833 by Biett and his student Cazenave. The term lupus is Latin for “wolf” and describes the facial rash seen in affected patients due to its apparent resemblance to a wolf bite. The facial rash first described in 1833 was initially termed erythema centrifugum. The butterfly distribution, a commonly used descriptive term today, was described in 1846.

In 1872, Kaposi proposed that systemic lupus erythematosus was not solely a dermatologic condition. He observed that affected patients frequently had associated fever, weight loss, subcutaneous nodules, lymphadenopathy, anemia, arthritis with synovial hypertrophy of small and large joints, and central nervous system involvement. The presence of systemic lupus was confirmed in 1904 by Osler and Jadassohn. 

Major breakthroughs came in 1948 when Hargraves and colleagues discovered lupus erythematosus cells in the bone marrow of afflicted patients. Following this discovery, new diagnostic avenues in the field of immunology for the detection of systemic lupus erythematosus, or SLE, were opened. Shortly after, in the 1950s, two important immunologic markers were discovered: presence of ANA and the biologic false-positive venereal disease research laboratory/rapid plasma reagin (VDRL/RPR) test. Moore demonstrated that systemic lupus erythematosus developed in 7% of patients with chronic false-positive tests for syphilis and that a further 30% had symptoms consistent with collagen disease. 

In 1894, Payne reported that quinine provided benefit for lupus and that the addition of salicylates potentiated the palliative effects. In the mid-20th century, Hench demonstrated that use of corticosteroids was effective. Today, antimalarials and corticosteroids remain stalwarts in the treatment of systemic lupus erythematosus.¹

Epidemiology

The age-standardized prevalence of systemic lupus erythematosus in the US population is about 70 to 180 cases per 100,000.²  Prevalence varies by sex and ethnicity. Age-standardized prevalence rates are highest in African Americans (111-261 per 100,000)^2,3 and Hispanic Americans (94-138 per 100,000)^3,4 and lowest among Caucasians (43-65 per 100,000)^3,5 Interestingly, while most African Americans originated from West Africa, SLE prevalence in this region is low, suggesting that environmental factors may play a role in pathogenesis.⁶ 

SLE affects females more than males in all age groups. In prepuberal children, the female-to-male ratio is 3:1. During childbearing years, the ratio increases to between 7:1 and 15:1.^7,8 Prevalence in postmenopausal women is 8 times higher compared with age-matched males.⁷

African American women represent the most burdened population in the United States with incidence rates up to 406 per 100,000.⁸ This pattern is evidence for 2 underlying contributors to systemic lupus erythematosus pathogenesis, which is multifactorial. First, increased incidence in prepuberal females indicates that genetic factors related to the X chromosome are at play. Second, the hormonal effects of estrogen are associated with an increased risk for systemic lupus erythematosus.⁹ 

Indeed, predisposing variants to the IRAK1, and TLR7 genes located on the X chromosome have been identified.¹⁰ Theoretically, females have the potential to harbor 2 copies of these predisposing variants and are therefore more likely to develop systemic lupus erythematosus. Likewise, patients with Klinefelter syndrome (XXY) are male and can potentially harbor 2 copies of these variants and prevalence in this population is 14-fold compared to XY males in the general population, a phenomenon referred to as the gene-dose effect.¹¹

Etiology and Risk Factors

The precise etiology of systemic lupus erythematosus remains obscure but appears to be multifactorial with genetic, hormonal, immunological, and environmental factors being major contributors to disease pathogenesis. Factors that favor a genetic predisposition are the increased risk for disease development in patients with first degree relatives with SLE and increased incidence rates in identical twins.¹⁴ The effects of estrogen, geography, and ethnicity also play a role (see Epidemiology). 

The hallmark of systemic lupus erythematosus is the production of autoantibodies against nuclear components of cells, or antinuclear antibodies (ANAs), including anti-dsDNA, anti-Smith, anti-Ro, and anti-LA antibodies. These antibodies can target any organ in the body. Additionally, antiphospholipid antibody formation is common in systemic lupus erythematosus, including antiphospholipid (aPL) antibodies and anti-cardiolipin antibodies.¹⁴

Autoantibody production and formation of immune complexes lead to all of the clinical manifestations of systemic lupus erythematosus. IC deposition leads to inflammation through complement activation and tissue damage that can occur anywhere in the body and involve any organ.¹⁴ 

Environmental factors know to trigger flares in patients with an established diagnosis of systemic lupus erythematosus are sunlight (ultraviolet light), cigarette smoking, infection, vaccines (rare and many case reports are anecdotal), vitamin D deficiency, exogenous estrogen, select conventional drugs, biologic agents, pesticides and phthalates.¹⁵

Systemic Lupus Erythematosus Prognosis

Life expectancy with systemic lupus erythematosus has improved considerably over the past few decades. However, despite improvements in disease recognition and early treatment, patients still have mortality rates 3 to 5 times higher than the general population.¹⁶ SLE was among the leading causes of death in young women in the United States from 2000 to 2015.

During this time, SLE was the No. 1 cause of death among chronic inflammatory diseases, ranking higher than diabetes mellitus, HIV, chronic lower respiratory disease, nephritis, pneumonitis, and liver disease in women ages 15 to 24 years.¹⁷

Systemic lupus erythematosus carries a high degree of morbidity. In 2021, one European survey reported that half of patients note significant negative impacts on educational studies, 57% attribute systemic lupus erythematosus to career difficulty, and 18% report sexual disturbances.¹³

Causes of death in systemic lupus erythematosus are infections due to immunosuppression, renal failure, and cardiovascular disease.¹⁸ Cardiovascular disease is the leading cause of death among patients with long-standing or late-onset SLE.¹⁹

Predictors of negative outcomes include renal disease, hypertension, male sex, young age, older age at presentation, low socioeconomic status, African American, positive antiphospholipid antibodies, and high overall disease activity.^15,18-21

Systemic Lupus Erythematosus Presentation

Physical Examination Findings

The clinical presentation of systemic lupus erythematosus is directly related to autoantibody formation and IC deposition. Lupus is an autoimmune disease so it is not surprising that constitutional symptoms characteristic of rheumatic disease are common in systemic lupus erythematosus patients. Constitutional symptoms are common in SLE and are seen in >90% of patients. They may include fatigue, fever, and weight loss. ²⁰ Arthralgias, myalgias, lymphopenia, headache, and loss of appetite may also be present.²¹

The approach to patients with these nonspecific complaints is sometimes challenging. Fever may be due to infection, headaches are common in all populations, and the differential diagnosis for joint pain is extensive. The presence of a malar rash makes diagnosis easier; however, not every patient will present with classical signs and symptoms.

Additionally, the patterns of arthritis, arthralgias, and myalgias associated with systemic lupus erythematosus can help distinguish them from other entities. Arthritis and arthralgias are common initial symptoms and are experienced by 80% to 90% of patients. It is usually a nonerosive, nondeforming, migratory, symmetrical polyarthralgia affecting the small joints of the hands, wrists, and knees. Morning stiffness may be present but typically lasts minutes unlike rheumatoid arthritis (RA) which lasts hours and is associated with deformity in the long term.²¹ Myalgias in systemic lupus erythematosus are usually not accompanied by muscle weakness.  

It is essential to recognize that many autoimmune diseases, eg, polymyositis, RA, psoriatic arthritis, Sjögren’s syndrome, and systemic lupus erythematosus, share many of the same features. Understanding this allows for a healthy suspicion for rheumatic disease and send for screening laboratory tests for biomarkers of autoimmunity (see diagnosis).

Mucocutaneous Involvement

Mucocutaneous involvement is seen in most patients and manifests as a malar rash resembling the wings of a butterfly. Approximately 70% to 80% of patients with systemic lupus erythematosus will develop dermatologic manifestations.

The malar rash is exacerbated by sunlight and presents as erythema over the cheeks and nose that spares the nasolabial folds. This lesion may appear as an inflammatory lesion consisting of disc-shaped plaques with follicular plugging that tends to scar. This type is referred to as a discoid rash—a pathognomonic feature of systemic lupus erythematosus. Examination of the oral mucosa may reveal buccal and nasal ulcers that are not painful, unlike those seen in oral herpes simplex.²¹

Additional manifestations include patchy alopecia (14%-50%) and Raynaud’s phenomenon (50%).²² Some cutaneous manifestations are attributed to underlying vasculitis, which can take many forms. Examples are palpable purpura, petechiae, papulonodular lesions, livedo reticularis, panniculitis, splinter hemorrhages, and superficial ulcerations.²³

Cardiopulmonary Involvement

Cardiac complications are seen in half of systemic lupus erythematosus patients. The most common is pericarditis; however, conduction deficits, valvular damage, coronary artery involvement, and myocarditis may be present.²⁵ Approximately one quarter of patients will develop symptomatic pericarditis with or without effusion at some point during their disease course.²⁶

There are no unique distinguishing features of SLE-associated pericarditis. Physicians can expect to encounter patients presenting with tachycardia, substernal or precordial chest discomfort, dyspnea, and positional pain as chief complaints. On examination, a friction rub may be auscultated, and common ECG findings are PR depression and diffuse ST-segment elevation. An echocardiogram would reveal a thickened pericardium with or without effusion. Isolated pericarditis in systemic lupus erythematosus patients is seldom and is associated with pleuritis in most patients.²⁶

Myocarditis is rare in systemic lupus erythematosus; however, when present it can be potentially fatal. Patients can present with symptoms of heart failure, including resting tachycardia, dyspnea with associated chest discomfort, and fever. Global hypokinesis on echocardiogram in patients without evidence of coronary artery disease (CAD) supports the diagnosis. Patients with cardiomyopathy almost always require additional cardiac work-up to exclude other underlying causes, including an evaluation for underlying CAD.²⁶

Atherosclerosis is accelerated in systemic lupus erythematosus patients through mechanisms that are not completely understood. Theories include excessive oxidative stress,²⁷ dysfunctional proinflammatory HDL cholesterol,²⁸ high levels of type 1 interferon,²⁹ antiphospholipid antibodies,³⁰ and increased neutrophil extracellular trap formation.³¹

Traditional modifiable and non-modifiable risk factors, such as smoking, hypertension, diabetes, and metabolic syndrome, are common in patients with systemic lupus erythematosus and further augment coronary risk. Furthermore, recall that treatment with glucocorticoids is associated with weight gain and hyperglycemia. Accelerated atherosclerosis is responsible for premature CAD and females are at highest risk. There have been extreme case reports of myocardial infections in systemic lupus erythematosus patients as young as 5 years old.²⁶

Libman-Sacks endocarditis is a sterile, verrucous, valvular disease seen in 11%-74% of patients. IC deposition is thought to be the main pathogenic factor. It is usually clinically silent; however, it can be a source of embolic formation. It most frequently affects the mitral valve and is only clinically evident in 1%-18% of patients. It is detected with transesophageal echocardiography.²⁶

Infants born to mothers with systemic lupus erythematosus can develop neonatal lupus, a condition in which the cardiac conduction system is damaged by maternal anti-Ro/SS-A autoantibodies that cross the placenta. Infants with neonatal lupus develop complete heart block, which requires pacing for survival. Complete heart block in the fetus is associated with fetal myocarditis.²⁶

Renal Involvement

Lupus nephritis (LN) is present in most patients with systemic lupus erythematosus. Half of patients will develop clinically evident disease and 10% will develop end-stage kidney disease (ESKD).^32,33 LN is 6 times more prevalent in women compared to men and is twice as prevalent in African American women compared to Caucasian women.³⁴ LN is an IC-mediated glomerular disease that damages the glomerulus through compliment activation at the site of deposition. 

The most common presenting sign of LN is proteinuria.³³ Since patients with systemic lupus erythematosus almost always have some degree of kidney involvement, blood and urine tests are frequently monitored for signs of kidney disease. Other manifestations of LN are microscopic hematuria with or without red cell casts, kidney function impairment, nephrotic-range proteinuria or nephrotic syndrome, and hypertension. LN is classified based on histopathologic findings obtained from kidney biopsy and is divided into six categories (see Tables 1 and 2).³⁵ 

Table 1. WHO Classification of Lupus Nephritis Based on Histopathologic Findings³⁶

LN Class	Histopathologic Findings
I: Minimal Mesangial LN	Glomeruli appear normal on light microscopy. Immunofluorescence shows IC deposits in the mesangial space.
II: Mesangial Proliferative LN	Purely mesangial hypercellularity of any degree or mesangial matrix expansion by light microscopy, with mesangial immune deposits. May be a few isolated subepithelial or subendothelial deposits visible by immunofluorescence or electron microscopy, but not by light microscopy.
III: Focal LN	Active or inactive focal, segmental, or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits, with or without mesangial alterations. Subclasses: IIIA: Active lesions: focal proliferative lupus nephritis; IIIA/C: Active and chronic lesions: focal proliferative and sclerosing lupus nephritis; IIIC: Chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritis.
IV: Diffuse LN	Active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis involving ≥50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations. This class is divided into diffuse segmental (IV-S) lupus nephritis when ≥50% of the involved glomeruli have segmental lesions, and diffuse global (IV-G) lupus nephritis when ≥50% of the involved glomeruli have global lesions. Segmental is defined as a glomerular lesion that involves less than half of the glomerular tuft. This class includes cases with diffuse wire loop deposits but with little or no glomerular proliferation.
V: Lupus membranous nephropathy	Global or segmental subepithelial immune deposits or their morphologic sequelae by light microscopy and by immunofluorescence or electron microscopy, with or without mesangial alterations.
VI: Advanced sclerosing nephropathy	≥90% of glomeruli globally sclerosed without residual activity.

Table 2. Histologic Classification of LN, Clinical Findings, and Implications^{35, 36}

LN Class	Clinical Findings	Comments
I: Minimal Mesangial LN	None	Rarely diagnosed since kidney biopsy is not typically performed in patients with normal urine analysis, normal creatinine, and mild-to-absent proteinuria. Earliest and mildest form of glomerular involvement.
II: Mesangial Proliferative LN	Microscopic hematuria and/or proteinuria.	Therapy not required unless progression occurs. Prognosis is excellent.
III: Focal LN	Hematuria, proteinuria +/- hypertension, +/- nephrotic syndrome, decreased GFR	Requires immunosuppressive therapy given in 2 phases. Initial therapy is with potent anti-inflammatory and immunosuppressive drugs like mycophenolate and cyclophosphamide. Once a renal response is achieved, less aggressive subsequent immunosuppressive therapy is given for a prolonged period to prevent relapse. Poor prognosis.
IV: Diffuse LN	Nephrotic syndrome, hypertension, decreased GFR	Treatment is similar for Class III and IV LN. Poorest prognosis.
V: Lupus membranous nephropathy	Nephrotic syndrome, hypertension, normal to elevated creatinine, microscopic hematuria	Immunosuppressive therapy considered for patients with nephrotic syndrome, persistent proteinuria >3.5g/day, rising serum creatinine, mixed membranous and proliferative disease on biopsy. Treatment options are mycophenolate + corticosteroids, cyclophosphamide, or calcineurin inhibitors.
VI: Advanced Sclerosing LN	EDKD, relatively bland urine sediment.	This is the advanced stage of class III-V LN characterized by global sclerosis of ≥90% of glomeruli. Active glomerulonephritis not usually observed.

Neuropsychiatric Involvement

Approximately 20%-40% of patients will develop neuropsychiatric symptoms.³⁷ Clinical neuropsychiatric syndromes associated with systemic lupus erythematosus are as follows:

• Stroke: Risk is 1.5-3 times higher than in the general population and affects up to 19% of patients.³⁸
• Seizures: Affects up to 11.5% of patients.³⁹ Presence of antiphospholipid antibodies, active disease, and glucocorticoid treatment are associated risk factors. 
• Altered mental status: Includes psychosis and acute confusional state. This is a medical emergency. 
• Cognitive impairment: Usually appears later in disease course. Often described using vague terms like feeling “foggy.”
• Depression and anxiety disorders: Prevalence of major depressive disorder is 24% and anxiety disorder is 37%.⁴⁰

Systemic Lupus Erythematosus Diagnosis

Diagnosis of systemic lupus erythematosus is the work of experienced clinicians with adequate experience in the field. Several guidelines have been developed in the past for the diagnosis of systemic lupus erythematosus, but their sensitivity and specificity are suboptimal. The most recent criteria for the diagnosis and classification of systemic lupus erythematosus are endorsed by both the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) (See Table 3). EULAR/ACR criteria have a sensitivity of 96.1% and a specificity of 93.4%.⁴¹ Diagnostic workup for SLE is detailed in Table 4. 

Indications for kidney biopsy are outlined by the joint European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) guidelines.⁴² Kidney biopsy is obtained in SLE patients with:

• Glomerular hematuria with or without cellular casts
• Proteinuria >0.5g/24hrs or spot urine protein-to-creatine ratio >500 mg/g
• Unexplained decrease in glomerular filtration rate (GFR)

Treatment is guided by histologic subtype and is therefore an important procedure for determining a treatment roadmap. Additionally, clinical findings do not always accurately reflect the degree of glomerular involvement.  

Laboratory Testing

If SLE is suspected, the first step is to obtain ANA titers. This is an entry criterion for perusing an systemic lupus erythematosus diagnosis. If ANA is positive, proceed to the diagnostic workup (Table 4) and score patients accordingly using the EULAR/ACR criteria (Table 3). If a patient is ANA-negative, order complement levels and antiphospholipid (aPL)-antibodies. Low complement levels and/or positive antiphospholipid antibodies could be used as an alternative entry criterion.³⁷ These tests can all be ordered initially in anticipation of a possible negative ANA titer. Institutional guidelines may vary. 

For patients who do not meet the threshold for diagnosis (≥10 points), systemic lupus erythematosus is not excluded. In this instance, the presence of photosensitivity, immunological, and clinical features can be used by experts to make a diagnosis.⁴¹

Table 3. EULAR/ACR Criteria for the Diagnosis of systemic lupus erythematosus

Entry Criteria: ANA at a titer of ≥1:80 on HEp-2 cells or an equivalent positive test (ever). If ANA-negative: Low complement levels and/or positive antiphospholipid antibodies are used as an alternative entry criterion.
Additional Criteria: Do not count a criterion if there is a more likely explanation than systemic lupus erythematosus. Occurrence of a criterion on ≥1 occasion is sufficient. Criteria need not occur simultaneously. Within each domain (eg, mucocutaneous, complement proteins), only the highest-weighted criterion is counted toward the total score if more than 1 is present.
Domain	Score
Constitutional: Fever	2
Hematologic — Leukopenia — Thrombocytopenia — Autoimmune hemolysis	3 4 4
Neuropsychiatric — Delirium — Psychosis — Seizure	2 3 5
Mucocutaneous — Alopecia — Oral Ulcers — SCLE/DLE — ACLE	2 2 4 6
Serosal –Effusion — Acute pericarditis	5 6
Musculoskeletal: — Joint involvement	6
Renal — Proteinuria — Class II/V — Class III/IV	4 8 10
Antiphospholipid antibodies  — Anticardiolipin antibodies — Anti-β2GP1 antibodies — Lupus anticoagulant	2 2 2
Complements — Low C3 or C4 — Low C3 and C4	3  4
SLE-specific antibodies — Anti-Sm — Anti-dsDNA	6 6
Score of ≥10 + ≥1 clinical domains + entry criteria met? Classify as SLE

Table 4. Diagnostic Work-up for SLE

Diagnostic Test	Rationale
CBC	Anemia, thrombocytopenia, and leukopenia are common hematologic manifestations.
BUN, creatinine, and urine protein to creatinine ratio	Most patients have kidney involvement.
Urine analysis	To detect hematuria, casts, proteinuria, and/or pyuria.
C3/C4 or CH50 complement levels	Hypocomplementemia is common to IC deposition and complement activation and consumption.
Serum protein electrophoresis	May reveal hypergammaglobulinemia (seen in systemic inflammation).
ESR, CRP	Non-specific markers of inflammation.
SLE-specific antibodies (Anti-dsDNA or Anti-Smith antibody)	Highly specific for SLE.
Antiphospholipid antibodies (LA, IgG and IgM aCL, IgG and IgM anti-β2GP1 antibodies)	Common autoantibodies in SLE.
ANA antibodies	Entry criterion for diagnosis.

Differential Diagnosis

The differential diagnosis is broad due to its wide array of clinical manifestations and multisystem involvement. Below are some possible considerations:²⁰

• Other autoimmune diseases: Rheumatoid arthritis (RA) is characterized by polyarticular inflammatory arthritis and may present with extra-articular manifestations that may resemble systemic lupus erythematosus. Positive ANA, Anti-Ro, and Anti-La may also be seen in RA. 
• Drug-induced SLE (DIL): Characterized by resolution of symptoms after the offending agent has been discontinued. Drugs known to cause DIL include hydralazine, procainamide, anti-TNF agents, interferon-alpha, minocycline, isoniazid, rifampin, phenytoin, penicillamine, quinidine, phenytoin, methyldopa, chlorpromazine, carbamazepine, ethosuximide, propylthiouracil, and sulfasalazine.⁴³
• Infections: Infection with Parvovirus B19 can cause fever, rash, inflammatory arthritis, and cytopenias. Hepatitis B and C is also associated with arthalgias or inflammatory arthritis. ANA and RF positivity have been reported with Parvovirus B19, Hepatitis B and C infection. HIV can cause fatigue, cytopenias, fever and oral ulcers. Infectious endocarditis may mimic cardiac manifestations of systemic lupus erythematosus.
• Malignancy: Lymphomas especially Non-Hodgkin’s lymphoma can present with fatigue, fever, cytopenias, weight loss, lymphadenopathy and a positive ANA. Cancer should be ruled out in the elderly in the presence of new onset lupus-like symptoms.

Management of Systemic Lupus Erythematosus

Treatment goals for systemic lupus erythematosus include long-term patient survival, prevention of organ damage, and optimization of health-related quality of life (HQL). Aims of therapy are remission or at least low disease activity and prevention of flares.³⁷ Disease activity is measured using the SLE Disease Activity Index (SLEDAI) and a value of ≤4 is considered low disease activity (see Table 5). It can be determined through a combination of physical examination findings and laboratory tests.

Table 5. SLE Disease Activity Index 200 (SLEDAI-2K)⁴⁴

Nonpharmacologic

Exercise, and psychological interventions may improve fatigue, quality of life and depression in patients with systemic lupus erythematosus. Examples of psychological interventions include Mind-Body Practices, Mindfulness-based stress reduction, Tai Chi, and Yoga; however, stronger clinical studies are required to fully support these therapies as adjuncts to treatment.⁴⁵
Ultraviolet radiation is a well-documented environmental trigger for cutaneous manifestations of systemic lupus erythematosus. The use of sunscreen is highly effective for the prevention of cutaneous lesions.⁴⁶

Pharmacologic

To determine which treatment tier to initiate, an assessment of disease activity is needed. Disease activity is measured using the Physician Global Assessment and the SLEDAI-2K index. It is recommended that the PGA be filled out before SLEDAI-2K assessment.⁴² The EULAR recommendations are as follows:

Mild disease: SLEDAI 1-4

• HCQ + ≤7.5mg/day glucocorticoids PO/IV (prednisone or equivalent). 
• Add methotrexate or azathioprine if refractory.

Moderate disease: SLEDAI 5-10

• HCQ + glucocorticoid PO/IV + immunomodulatory agent (methotrexate, azathioprine, or calcineurin inhibitor). 
• Refractory disease: add belimumab (first line) or mycophenolate mofetil.

Severe disease: SLEDAI >10

• HCQ + glucocorticoid PO/IV + mycophenolate OR cyclosporin. IV pulses of methylprednisolone are usually used for patients with severe disease. Dosage ranges from 250-1000 mg/day. 
• Add Rituximab for refractory disease.

Kidney Involvement

Targets for management of lupus nephritis (LN) is complete response defined as proteinuria <0.5-0.7 g/24 hours with near-normal GFR by 12 months. This can be extended in patients with baseline nephrotic-range proteinuria.⁴²

Immunosuppressive agents, administered in combination with glucocorticoids, are recommended in class III and IV LN (target dose: 1-2 g/day, or mycophenolic acid [MPA] at equivalent dose) with a calcineurin inhibitor (CNI), especially tacrolimus (TAC), is an alternative, particularly in patients with nephrotic-range proteinuria.

Monitoring for Systemic Lupus Erythematosus Side Effects

Patients with systemic lupus erythematosus require chronic pharmacotherapy and must be monitored for adverse events related to these medications. Consider the following:⁴⁷

1. Patients taking azathioprine should be monitored for myelosuppression, hepatotoxicity, and lymphoproliferative disorders, and require a complete blood count (CBC)and metabolic panel every three months. 
2. Patients taking cyclophosphamide should be monitored for myelosuppression, malignancy, immunosuppression, and hemorrhagic cystitis and require a CBC and basic metabolic panel every 3 months. 
3. Fasting glucose and lipids should be monitored every 3-6 months for patients taking long-term glucocorticoids. Additionally, bone mineral density should be monitored once a year. 
4. An ophthalmologic examination should be performed every 6-12 months on patients taking HCQ to assess for macular damage. 
5. Methotrexate therapy is associated with hepatic fibrosis, myelosuppression, and pulmonary fibrosis. Monitoring with a CBC and complete metabolic panel every 3 months is required.
6. Patient’s taking mycophenolate require CBC and complete metabolic panel every 3 months to monitor for myelosuppression and infection.  
7. CBC and renal testing should be done annually to assess for GI bleeding, liver disease and kidney disease associated with chronic NSAID use. 
8. Patients taking Rituximab should undergo CBC every 2-4 months.

Complications of Systemic Lupus Erythematosus

Disease-related complications include accelerated atherosclerosis, ESKD, neurologic deficits, and skin scarring and alopecia. Pregnancy-related complications are fetal loss, pre-eclampsia and eclampsia, congenital heart block and neonatal lupus. There is an increased incidence of major depression and anxiety in lupus patients.⁴³

Patient Education

The EULAR journal Annals of the Rheumatic Diseases (ARD) provides short research summaries for patients and non-clinicians written in plain language in a consistently structured format and checked for accuracy and readability by expert rheumatologists and people from EULAR’s patient research partner network.

The Lupus Foundation of America is a good educational resource for patients and consists of chapters, offices, and support groups in communities throughout the United States. Its goals are to conduct activities to increase awareness of lupus, provide educational programs, support groups and services, rally support for those who are affected by lupus and advocate on their behalf, and raise money to support research and educational programs so everyone affected by lupus can have an improved quality of life.

FAQs 

What causes systemic lupus erythematosus?

The precise etiology of systemic lupus erythematosus remains obscure but appears to be multifactorial with genetic, hormonal, immunological, and environmental factors being major contributors to disease pathogenesis. Formation of antinuclear antibodies (ANA), immune complex (IC) formation, IC deposition, and complement activation are the drivers of inflammation and tissue damage.

Does systemic lupus erythematosus affect one group of people more than others?

Lupus affects more women than men and affects African American individuals disproportionately.

What is the life expectancy of someone with systemic lupus erythematosus?

The life expectancy of individuals with systemic lupus erythematosus has improved considerably over the past few decades. However, despite improvements in disease recognition and early treatment, patients still have mortality rates 3 to 5 times higher than the general population.

What are the main clinical features?

The most iconic manifestation is malar rash, also known as butterfly rash, though not all patients will present with dermatologic findings. Other common manifestations include fever, arthritis, arthralgias, oral ulcers, pericarditis, pleuritis, nephrotic syndrome, and neurological manifestations.

How is systemic lupus erythematosus diagnosed?

A diagnosis is made based on physical findings and laboratory testing. The presence of ANA, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) criteria help guide diagnosis.

What are the complications of systemic lupus erythematosus?

Disease-related complications include accelerated atherosclerosis, end-stage kidney disease (ESKD), neurologic deficits, and scarring of skin. Pregnancy-related complications are fetal loss, pre-eclampsia and eclampsia, congenital heart block, and neonatal lupus. There is an increased incidence of major depression and anxiety in patients with SLE.

How is systemic lupus erythematosus treated?

SLE treatment is determined by disease activity. Most patients will receive hydroxychloroquine. Flares are treated with immunosuppressive drugs like corticosteroids, and long-term management involves the use of immunomodulatory agents like methotrexate, azathioprine, and calcineurin inhibitors.

Systemic lupus erythematosus ICD 10 Codes

Here are ICD 10 codes relevant to systemic lupus erythematosus, specified or otherwise:

L93	Lupus erythematosus
L93.0	Discoid lupus erythematosus
L93.1	Subacute cutaneous lupus erythematosus
L93.2	Other local lupus erythematosus

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