Systemic Lupus Erythematosus (SLE) Treatment & Management

Updated: Jun 16, 2022
  • Author: Christie M Bartels, MD, MS; Chief Editor: Herbert S Diamond, MD  more...
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Approach Considerations

Management of systemic lupus erythematosus (SLE) often depends on disease severity and disease manifestations, [8] although hydroxychloroquine has a central role for long-term treatment in all SLE patients. The LUMINA (Lupus in Minorities: Nature versus Nurture) study and other trials have offered evidence of a decrease in flares and prolonged life in patients given hydroxychloroquine, making it the cornerstone of SLE management. [115]

In general, cutaneous manifestations, musculoskeletal manifestations, and serositis represent milder disease, which may wax and wane with disease activity. These are often controlled with nonsteroidal anti-inflammatory drugs (NSAIDS) or low-potency immunosuppression medications beyond hydroxychloroquine and/or short courses of corticosteroids. More prolonged steroid use is generally reserved for patients with involvement of vital organs. For example, central nervous system involvement and diffuse proliferative kidney disease must be recognized as more severe disease manifestations, and these are often treated with more aggressive immunosuppression. Evidence suggests a relative undertreatment of SLE patients with end-stage renal disease (ESRD), because the extent of lupus activity may be underestimated. [116]

Assessing response and defining remission

A number of instruments instruments have been devised for the standardized assessment of disease activity in SLE; however, none can be considered the "gold standard". [117] From the clinician’s perspective, an assessment of disease activity that represents the ideal treatment target for SLE has not yet been found. From the patient’s perspective, improvement in fatigue, joint pain, and quality of life appear to be the ideal treatment goals. [118]

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), which consists of 24 weighted clinical and laboratory variables of nine organ systems, was developed and introduced in 1985 as a clinical index for the assessment of lupus disease activity in the preceding 10 days. [117] A modification of the SLEDAI, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), was introduced in 2002. The SLEDAI-2K allows consideration of persistent active alopecia, mucous membrane ulcers, rash, and proteinuria—disease features that the original SLEDAI considered only as new or recurrent. See the SLEDAI-2K calculator.

A newer approach, the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS), includes 17 clinical and laboratory features (see the SLE-DAS calculator) and has demonstrated higher sensitivity to change as compared with the SLEDAI-2K. [118]

The SLE Responder Index (SRI) is a tool that was developed following phase II trials and is composed of the following scores [119] :

  • SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus: National Assessment– Systemic Lupus Erythematosus Disease Activity Index)
  • BILAG (British Isles Lupus Assessment Group)
  • PGA (physician global assessment)

SRI response is defined by the following [119] :

  • A 4-point or greater reduction in the SELENA-SLEDAI score
  • No new BILAG A or no more than 1 new BILAG B domain score
  • No deterioration from baseline in the PGA by 0.3 or more points.

European League Against Rheumatism (EULAR) definitions of treatment goals in SLE are as follows [74] :

  • Complete remission - Absence of clinical activity with no use of glucocorticoids or immunosuppressive drugs
  • Low disease activity - SLEDAI score ≤3 with antimalarial therapy, or SLEDAI ≤4, PGA ≤1 with glucocorticoids at ≤7.5 mg of prednisone equivalent and well-tolerated immunosuppresisive agents
  • Partial renal remission - Reduction in proteinuria by ≥ 50% to subnephrotic levels and serum creatinine within 10% from baseline by 6–12 months
  • Complete renal remission - Proteinuria < 500 mg/24 hours and serum creatinine within 10% from baseline

EULAR recommendations

EULAR released recommendations for the treatment of SLE in 2008 and updated them in 2019. [67, 74] EULAR recommends that treatment in SLE aim at remission, or at low disease activity in all organ systems if remission cannot be achieved. Specific medication recommendations include the following:

  • Hydroxychloroquine is recommended for all patients with SLE.
  • Glucocorticoids can provide rapid symptom relief, but the medium- to long-term aim should be to minimize the daily dose to ≤7.5 mg/day prednisone equivalent or to discontinue them.
  • Subsequent initiation of immunosuppressive drugs facilitates more rapid tapering of glucocorticoids and may prevent disease flares. The choice of agent depends on prevailing disease manifestation(s), patient age and childbearing potential, safety concerns, and cost.

EULAR recommendations regarding immunosuppressive drugs for SLE are as follows:

  • Consider methotrexate and azathioprine in patients with poor symptom control with glucocorticoids and hydroxychloroquine, or when hydroxychloroquine alone is unlikely to be sufficient.
  • Mycophenolate mofetil (MMF) is a potent immunosuppressant with efficacy in renal and non-renal SLE (but not in neuropsychiatric lupus), but its teratogenic potential and higher cost limit its recommendation in women of reproductive age with non-renal manifestations.
  • Cyclophosphamide can be considered in organ-threatening disease (especially renal, cardiopulmonary, or neuropsychiatric) and as rescue therapy in patients with non–major organ manifestations refractory to other agents. Due to its gonadotoxic effects, it should be used with caution in women and men of fertile age; concomitant use of gonadotropin-releasing hormone (GnRH) analogues  is recommended in premenopausal patients.

EULAR recommendations regarding biologic agents for SLE are as follows:

  • Consider belimumab in patients with extrarenal disease inadequately controlled by first-line treatments.
  • Off-label use of rituximab may be considered in patients with severe renal or extrarenal (mainly hematologic and neuropsychiatric) disease refractory to multiple other agents.

EULAR recommendations for specific SLE manifestations are as follows:

  • Skin disease - First-line treatment includes topical agents (glucocorticoids and/or calcineurin inhibitors) and antimalarials (preferably hydroxychloroquine); the addition of systemic glucocorticoids may be considered, with the starting dose dependent on the severity of skin involvement.
  • Neuropsychiatric disease - Consider glucocorticoids and/or immunosuppressive agents if the underlying pathophysiologic mechanism is presumed to be inflammatory; if antiphospholipid antibodies are present, anticoagulant/antithrombotic treatment is favored; if the mechanism is uncertain, or both mechanisms appear to coexist, combined immunosuppressive therapy and anticoagulant/antithrombotic therapy may be considered.

  • Hematologic disease - First-line treatment of significant lupus thrombocytopenia (platelet count below 30,000/mm3) is with moderate to high doses of glucocorticoids in combination with a steroid-sparing immunosuppressive agent (azathioprine, MMF, or cyclosporine; the last having the least potential for myelotoxicity). Initial therapy with pulses of intravenous methylprednisolone for 1–3 days is encouraged. Intravenous immunoglobulin (IVIG) may be considered in the acute phase.

  • Lupus nephritis - Treatment consists of an initial induction phase followed by a more prolonged maintenance phase. MMF and (preferably low dose) cyclophosphamide are the immunosuppressive agents of choice for induction treatment. MMF plus high-dose cyclophosphamide may be considered for patients with severe lupus nephritis at increased risk for progression to end-stage renal disease. Maintenance treatment is with MMF or azathioprine, with the choice depending on the agent used for induction and on patient characteristics, including age, race, and wish for pregnancy; rituximab may be considered in refractory or relapsing disease. Calcineurin inhibitors may be considered as second-line agents for induction or maintenance therapy, mainly in membranous lupus nephritis, podocytopathy, or in proliferative disease with refractory nephrotic syndrome despite standard-of-care within 3–6 months; in refractory cases, calcineurin inhibitors may be cobined with MMF

American College of Rheumatology guidelines

In 2009, an American College of Rheumatology (ACR) Task Force generated a quality indicator set. [120] In 2012, the ACR published “ Guidelines for the Screening, Diagnosis, Treatment and Monitoring of Lupus Nephritis in Adults,” as well as an evidence report for lupus nephritis. In 2020, the ACR published a Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases, which includes recommendations tailored to patients with SLE. [121] These and other guidelines are available at the ACR's Clinical Practice Guidelines Web site.

Adjunctive therapies

Vitamin D insufficiency and deficiency are more common in patients with SLE than in the general population. [122] Vitamin D supplementation may decrease disease activity and improve fatigue. [123, 124] In addition, supplementation may improve endothelial function, which may reduce cardiovascular disease. [125, 126, 127]

No diet-based treatment of SLE has been proven effective. Patients with SLE should be reminded that activity may need to be modified as tolerated. Specifically, stress and physical illness may precipitate SLE flares. Additionally, persons with SLE should wear sunscreen and protective clothing or avoid sun exposure to limit photosensitive rash or disease flares.


The multisystemic nature of SLE often requires involvement of consultants, depending on the organ system involved. Consultation with any of the following specialists may be necessary:

  • Rheumatologist
  • Infectious disease specialist
  • Neurologist
  • Pulmonologist
  • Cardiologist
  • Gastroenterologist
  • Nephrologist
  • Dermatologist
  • Hematologist
  • High-risk obstetrician

Biologic DMARD Therapy


The monoclonal antibody belimumab (Benlysta), a B-lymphocyte stimulator–specific inhibitor, has been found to reduce disease activity and possibly decrease the number of severe flares and steroid use in patients with SLE when used in combination with standard therapy. [128] In  2011, the US Food and Drug Administration (FDA) approved the use of belimumab in combination with standard therapies (including steroids, nonbiologic DMARDS [eg, hydroxychloroquine, azathioprine, methotrexate]) to treat active autoantibody-positive SLE. [129]  In 2017, a subcutaneous (SC) formulation was approved that allows patients to self-administer a once-weekly dose. [130]

Patients of African-American or African descent did not show significant responses to belimumab in phase III post-hoc analysis, but those studies were not powered to assess for this effect; in a phase II trial, Blacks had a greater treatment response. These results indicate that the benefits of belimumab in SLE patients remain inconclusive and that further investigation is needed. Patients with severe active lupus nephritis or CNS lupus or patients previously treated with other biologics or cyclophosphamide have been excluded from participation in early trials.

A multinational phase III study (BLISS-52) that evaluated the efficacy and safety of intravenous (IV) belimumab, in 867 patients with a minimum SELENA-SLEDAI score of 6, reported that patients given belimumab had significantly higher SRI scores at 52 weeks than did those given placebo. [131] All groups had similar rates of adverse events.

Similarly, a phase III trial of 819 SLE patients who were positive for either antinuclear antibody or anti–double-stranded DNA at baseline screening found that belimumab at 10 mg/kg plus standard therapy resulted in a significantly greater SRI score (43.2%) than placebo (33.5%) at 1 year (those who received IV belimumab 1 mg/kg plus standard therapy had a 40.6% response rate). [132] Overall, the addition of belimumab to standard therapy reduced SLE disease activity and severe flares, and the medication was well tolerated. [132]

Approval for SC belimumab was based on the BLISS-SC phase III study (n=839), which documented reduction in disease activity at week 52 in patients receiving belimumab plus standard of care, compared with those receiving placebo plus standard of care. SRI response with belimumab versus placebo was 61.4% vs 48.4%, respectively (P = 0.0006). In the belimumab group, both time to and risk of severe flare were improved (median 171 days vs 118 days; P = 0.0004), and more patients were able to reduce their corticosteroid dosage by ≥25% (to ≤7.5 mg/day) during weeks 40-52 (18.2% vs 11.9%; P = 0.0732), compared with placebo. [133]


B-cell depletion with rituximab (Rituxan) has been used successfully for rheumatoid arthritis, but studies have shown mixed results for the treatment of SLE. An open study using rituximab showed positive results as rescue therapy for patients with active SLE that was unresponsive to standard immunosuppressant therapy. [134]

There have also been case reports of patients with severe refractory SLE in which off-label use of rituximab showed benefits with tolerable safety profiles. [135, 136, 137] For example, in a retrospective study of 115 patients with severe or refractory SLE, 40% of patients had a complete response and 27% had a partial response, as measured by BILAG scores recorded 6 months after the first rituximab treatment. [138]

However, three placebo-controlled studies, including the Exploratory Phase II/III SLE Evaluation of Rituximab [EXPLORER] trial and the Lupus Nephritis Assessment with Rituximab [LUNAR] trial, [139, 140] failed to show an overall significant response. Despite the negative results in these trials, rituximab continues to be used to treat patients with severe SLE disease that is refractory to standard therapy.

Pharmacologic agents targeting specific pathways such as cytokines and complement, as well as combinations of rituximab with costimulatory inhibition with anti-CD40L or CTLA-4Ig, may prove to be more effective in treating SLE. [141]


SLE has been associated with high serum levels and increased type 1 interferon (IFN) gene signature. Anifrolumab is a human IgGk monoclonal antibody that binds to the type 1 IFN receptor and inhibits activity of all type 1 IFNs. The blockade of the type 1 IFN receptor inhibits IFN-responsive gene expression as well as downstream inflammatory and immunological processes. In August 2021, the FDA approved anifrolumabb (Saphnelo) for the treatment of moderate-to-severe SLE.

Approval was based on combined data from the TULIP-1 and TULIP-2 phase III trials and the MUSE phase II trial. The TULIP-1 trial randomized 457 patients with moderate-to-severe SLE to receive anifrolumab 150 mg IV, 300 mg IV, or placebo every 4 weeks, in addition to standard therapy. The primary endpoint was not reached. However, certain secondary endpoints (eg, reduction in oral corticosteroid dose, CLASI responses, British Isles Lupus Assessment Group [BILAG]–based Composite Lupus Assessment [BICLA] responses) suggest clinical benefit of anifrolumab compared with placebo. [142]

The randomized TULIP-2 trial used these secondary endpoints for its primary endpoint, which measured response to treatment with BICLA. The anifrolumab group had a higher BICLA response (47.8%) than did the placebo group (31.5%). Response to anifrolumab was superior to placebo in patients with high and low IFN gene signature (48% vs 30.7% in high-signature patients, 46.7% vs 35.5% in low-signature patients). The occurrence of herpes zoster was higher in the anifrolumab group than with placebo. [143]

Like the TULIP-1 trial, the MUSE trial compared 2 doses of anifrolumab (300 mg or 1000 mg) with placebo. Anifrolumab substantially reduced disease activity compared with placebo across primary and secondary endpoints in patients with moderate-to-severe SLE. [144]


Emergency Department Management

Acute emergencies in patients with systemic lupus erythematosus (SLE) include the following:

  • Severe neurologic involvement
  • Systemic vasculitis
  • Profound thrombocytopenia with a thrombotic thrombocytopenia (TTP)–like syndrome
  • Rapidly progressive glomerulonephritis
  • Diffuse alveolar hemorrhage [145]

These conditions may be treated with high-dose intravenous steroids and cytotoxic therapy such as cyclophosphamide. Strokes, acute myocardial infarctions, and pulmonary emboli occurring as complications of SLE are managed in the same way as they are in patients without SLE. In patients who present with fever, it may be necessary to limit immunosuppression to steroids and to empirically treat for an infection until culture results have been received.

In rare cases, diffuse alveolar hemorrhage may require plasma exchange, or profound steroid-refractory thrombocytopenia may require therapy with intravenous immunoglobulin (IVIG). Catastrophic antiphospholipid antibody syndrome also requires aggressive acute management.

For more information, see the Medscape article Antiphospholipid Syndrome.



Fever in patients with systemic lupus erythematosus (SLE) is grounds for hospital admission because of the difficulty of distinguishing a disease flare from infection in these immunocompromised hosts. Patients with SLE are often complement deficient and functionally asplenic; therefore, they are at particular risk for infections with encapsulated organisms. For example, meningococcemia in young females with lupus may be catastrophic.

Although it is known that chronically low complement levels and functional asplenia may result in a low level of susceptibility to infection, it is not known to what degree. [146, 147] Overall, it is likely that the primary reason patients with SLE die of infections is immunosuppressive medications.Stress-dose steroid protocols should be used in patients who are receiving maintenance corticosteroids when they are admitted with infectious or perioperative stress.

Central nervous system lupus with depressed consciousness or alveolar hemorrhage may prompt transfer to an intensive care unit and consideration of protective intubation. Thrombotic thrombocytopenic purpura and catastrophic antiphospholipid antibody syndrome should prompt transfer to a center capable of offering plasma exchange therapy.

For more information, see the Medscape articles Neurologic Manifestations of Systemic Lupus Erythematosus and Thrombotic Thrombocytopenic Purpura.


Lupus Nephritis

The 2012 American College of Rheumatology (ACR) guidelines for lupus nephritis recommend that treatment of this condition be largely based on classification by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) histologic criteria (see Biopsies and Histologic Features). [106]

Lupus nephritis is managed with a combination of glucocorticoids [148] and immunosuppressive agents to slow the progression to end-stage renal disease (ESRD), along with maintaining normal blood pressure levels (ie, target of ≤130/80 mm Hg). [74, 106] In general, individuals with class I or II lupus nephritis do not need management with immunosuppression. [106]

Patients with class III or IV disease, as well as those with a combination of class V and class III or IV disease, generally undergo aggressive therapy with glucocorticoid drugs and immunosuppressants. [106] Immunosuppressive therapy consists of induction and maintenance therapy. Induction therapy involves potent immunosuppressive drugs (eg, mycophenolate mofetil, cyclophosphamide) to achieve remission; these drugs are generally used for 3 months to 1 year, with an average of 6 months’ treatment having been shown to be more efficacious and safer than long-term therapy. [149]

A large randomized trial that compared induction therapy consisting of oral mycophenolate mofetil with cyclophosphamide therapy in patients with lupus nephritis showed that mycophenolate mofetil was not inferior to cyclophosphamide. [150] The investigators suggested that mycophenolate mofetil was associated with both a trend toward greater complete remissions and a greater safety profile. [150] This study’s findings were confirmed with the large, international Aspreva Lupus Management Study (ALMS) trial. [151]

Once remission is achieved, start maintenance therapy with azathioprine or mycophenolate mofetil (ie, use less potent agents relative to long-term cyclophosphamide). The ALMS maintenance trial also found that mycophenolate mofetil was superior to azathioprine in the maintenance of the renal response to treatment and in the prevention of relapse in patients with lupus nephritis. [152] In the MAINTAIN trial, there was a trend toward fewer renal flares in patients receiving mycophenolate mofetil than in those receiving azathioprine [153] ; however, these results did not reach statistical significance.

When Griffiths et al compared the corticosteroid-sparing effect of cyclosporine with azathioprine in patients with severe SLE, they concluded that azathioprine may be considered first-line therapy, whereas cyclosporine requires close monitoring of blood pressure and serum creatinine. However, the investigators noted that in patients who are unable to tolerate azathioprine, cyclosporine may be considered. [154]

Unfortunately, significant side effects are associated with cyclophosphamide-based regimens, which have proven long-term efficacy. In refractory cases (lack of treatment response by 6 months), consider intensifying therapy with mycophenolate mofetil. [74]

Argolini et al retrospectively compared the efficacy and safety of azathioprine, mycophenolate mofetil, and cyclosporine in long-term maintenance therapy of lupus nephritis. The study included 106 patients followed for eight years. Although

In patients with SLE and nephritis who progress to end-stage renal disease, dialysis and transplantation may be required; these treatments have rates of long-term patient and graft survival that are similar to those observed in patients without diabetes and SLE. [74] However, transplantation is considered the treatment of choice because of improved survival rates. [74]

For more information, see Lupus Nephritis.

Adjunctive therapy

Unless contraindicated, hydroxychloroquine should be used as adjunctive therapy in lupus nephritis because of the potential for reduction in rates of disease flare; damage accrual, including kidney damage; and risk of thrombotic events. [106]

Administer angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to all patients with lupus nephritis (except pregnant women) who have proteinuria of 0.5 g or more per 24 hours (or equivalent by protein/creatinine ratios on spot urine tests). [106] This treatment has been reported to not only reduce proteinuria by about 30% but also significantly delay the doubling of serum creatinine and the progression to ESRD (in patients with nondiabetic chronic renal disease). [155]

Statin therapy is recommended in patients with low-density lipoprotein cholesterol (LDL-C) levels greater than 100 mg/dL because both renal dysfunction alone and SLE alone are independent risk factors for accelerated atherosclerosis. [106]


Antiphospholipid Syndrome

In patients with systemic lupus erythematosus (SLE), the presence of antiphospholipid antibodies is common; depending on the assay, these antibodies have been reported in up to 30-50% of SLE patients. [156] Therefore, it is important to evaluate these patients for risk factors for thrombosis, such as use of estrogen-containing drugs, being a smoker, immobility, previous surgery, and the presence of severe infection or sepsis. [74] The European League Against Rheumatism (EULAR) has noted that low-dose aspirin in individuals with SLE and antiphospholipid antibodies is potentially useful for primary prevention of thrombosis and pregnancy loss. [74]

Secondary prevention of thrombosis in nonpregnant patients with SLE and thrombosis associated with antiphospholipid syndrome can be managed with long-term use of oral anticoagulants. [74] In pregnant patients with SLE and antiphospholipid syndrome, unfractionated or low-molecular-weight heparin and aspirin may reduce the risk of pregnancy loss.

For additional information, see Antiphospholipid Syndrome and Systemic Lupus Erythematosus and Pregnancy.


SLE in Pregnancy

Fertility rates in women with systemic lupus erythematosus (SLE) may be similar to those in the general population. However, the incidence of spontaneous abortion, premature labor, early preeclampsia/eclampsia, fetal growth restriction, and intrauterine death are somewhat higher in women with SLE, [74, 157] especially in those with SSA(Ro)/SSB(La) antibodies, antiphospholipid antibodies, [98] or lupus nephritis. [155] One study suggested that women with SLE have fewer live births than the general population. [158] In this study, decreased live births were associated with exposure to cyclophosphamide and high SLE disease activity.

SLE can also flare during or after pregnancy. Whether flares of SLE are more frequent during pregnancy is controversial. The flares do not seem to be exceedingly more serious than those in nonpregnant patients, although pregnancy outcomes are generally more likely to be complicated. Increased rates of hypertension during pregnancy, premature delivery, unplanned cesarean delivery, postpartum hemorrhage, and maternal venous thromboembolism are all more frequent in women with SLE.

To minimize complications in pregnancy, SLE ideally should be well controlled for at least 4-6 months before conception. Obstetricians who handle high-risk pregnancies should optimally offer pregnancy planning consultation and monitor all pregnancies in patients with SLE. Suggestions for treatment of SLE during pregnancy are also included in the European League Against Rheumatism (EULAR) recommendations. High-dose aspirin and NSAIDs should be avoided in later pregnancy.

The EULAR recommendations indicate that in pregnant women with SLE, prednisolone, azathioprine, hydroxychloroquine (unnecessary discontinuation of hydroxychloroquine during pregnancy may result in lupus flares), and low-dose aspirin may be used. [74] Prednisone, prednisolone, and methylprednisolone are the corticosteroids of choice during pregnancy because of their minimal placental transfer. However, mycophenolate mofetil, cyclophosphamide, and methotrexate are strictly contraindicated. [74]

The ACR strongly suggests counseling women with SLE who are considering pregnancy regarding the improved maternal and fetal outcomes associated with entering pregnancy with quiescent/low activity disease. [121] Testing recommendations include the following:

  • Test for anti‐Ro/SSA and anti‐La/SSB once before or early in pregnancy, as determining the status of these autoantibodies improves counseling regarding pregnancy and fetal risk (strong recommendation) 
  • In women with SLE who are considering pregnancy or are pregnant, test for LAC, aCL, and anti‐β 2GPI antibodies once before or early in pregnancy; do not repeat these tests during pregnancy (strong recommendation)
  • During pregnancy, monitor SLE disease activity with clinical history, examination, and laboratory tests at least once per trimester (strong suggestion)

The ACR guideline recommends that all women with SLE take hydroxychloroquine (HCQ) during pregnancy, if possible. If a patient is already taking HCQ, continuing it during pregnancy is strongly recommended; if she is not taking HCQ, starting it if there is no contraindication is conditionally recommended. The ACR also conditionally recommends treating SLE patients with low‐dose aspirin (81 or 100 mg daily), beginning in the first trimester.

Neonatal lupus erythematosus (NLE) can develop in the babies of mothers with antibodies to SSA/Ro. Neonates with NLE can present with rash around 4-6 weeks of life, elevated liver function test results, thrombocytopenia around 1-2 weeks of life, neutropenia, and hydrocephalus. [159] NLE can also manifest as a congenital atrioventricular conduction block, [160] with as many as 1-5% of pregnancies in mothers with anti- SSA/SSB antibodies leading to heart block, rising to a 6-25% risk for subsequent pregnancies after one affected child is born. [161]

In pregnant women with anti‐Ro/SSA and/or anti‐La/SSB antibodies, the ACR conditionally recommends serial fetal echocardiography, starting between 16 and 18 weeks and continuing through week 26. For women with a history of an infant with complete heart block (CHB) or NLE, the ACR conditionally recommends performing fetal echocardiography weekly; screening can be less frequent than weekly in women without such a history, but a recommended interval has not been determined.

The ACR conditionally recommends treating all women who are positive for anti‐Ro/SSA and/or anti‐La/SSB antibodies with HCQ during pregnancy, to reduce the risk of fetal CHB. For pregnant women with anti‐Ro/SSA and/or anti‐La/SSB antibodies and fetal first‐ or second‐degree heart block shown on echocardiography, the ACR conditionally recommends treatment with oral dexamethasone 4 mg daily. If CHB (without other cardiac inflammation) is present, the ACR conditionally recommends against treating with dexamethasone. [121]

For additional information, see Systemic Lupus Erythematosus and Pregnancy and Neonatal and Pediatric Lupus Erythematosus.



Patients with SLE should be educated to avoid triggers for flare. Persons with SLE should avoid ultraviolet light and sun exposure to minimize worsening of symptoms from photosensitivity. Diet modification should be based on the disease activity. A balanced diet is important, but patients with SLE and hyperlipidemia, for example, should be placed on a low-fat diet. Many patients with SLE have low levels of vitamin D because of less sun exposure; therefore, these patients should take vitamin D supplements. Exercise is important in SLE patients to avoid rapid muscle loss, bone demineralization, and fatigue. Smoking should also be avoided.

Antimalarial therapy (hydroxychloroquine) has been shown to prevent disease flares and to decrease mortality. [115] In contrast, high rates of sulfa allergy and anecdotal reports of disease flares have led to avoidance of sulfa-based medications in patients with SLE.

Contraception and family planning are important considerations given the risks of disease flare with exogenous estrogens and pregnancy and with the teratogenic risks of some SLE drugs. Estrogen therapies have typically been avoided to prevent disease flares; progesterone-only contraception is more often considered. [162] However, studies have suggested that oral estrogen-containing contraceptives may not be associated with disease flares or thrombosis risk in patients with mild lupus without antiphospholipid antibodies. [58, 163]

Preventive measures are necessary to minimize the risks of steroid-induced osteoporosis and accelerated atherosclerotic disease. [164] The American College of Rheumatology (ACR) Guidelines for the prevention of glucocorticoid-induced osteoporosis suggest the use of traditional measures (eg, calcium, vitamin D) and the consideration of prophylactic bisphosphonate therapy.

The ACR Quality of Care statement [165] recommends annual cardiovascular disease risk assessment; some researchers suggest that the cardiovascular risk for SLE is similar to that for diabetes mellitus. The 10-year coronary event rate is 13-15% in patients with active SLE, which is comparable to the 10-year event rate of 18.8% in patients with known coronary artery disease. [166] African American patients with SLE may be particularly vulnerable to premature cardiovascular disease and related death. [167]

Angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers may be useful in patients with kidney disease. Aggressive blood pressure and lipid goals may help prevent CAD or kidney disease progression. [166]

The European League Against Rheumatism (EULAR) vaccination recommendations for rheumatic diseases, including lupus, advocate baseline assessment and delivery of nonlive vaccines during stable disease. [168] Particularly important is immunization against encapsulated organisms, such as meningococcal vaccine, pneumococcal vaccine, and routine Haemophilus influenzae childhood vaccination. Annual influenza vaccine is also encouraged.


Long-Term Monitoring

Periodic follow-up and laboratory testing, including complete blood counts with differential, creatinine, and urinalyses, are imperative for detecting signs and symptoms of new organ-system involvement and for monitoring response and adverse reactions to therapies. At least quarterly visits are recommended in most cases. [169] Periodic complement levels and dsDNA titers may be used as adjuncts to clinical evaluation for detecting lupus flares.

Opportunistic infections can develop, most often in patients receiving chronic immunosuppressive therapy. Another less-common complication is osteonecrosis, especially of the hips and knees after prolonged high-dose corticosteroid usage. More commonly, premature atherosclerotic disease and myocardial infarction are indolent complications of chronic inflammation and steroids.


Vitamin D

Studies from around the world have documented a higher prevalence of vitamin D insufficiency and deficiency in patients with SLE, compared with the general population, especially in conjunction with obesity. [122, 170, 171, 172, 173, 124] Studies from Australia, [170] France, [173] the Mediterranean region, [123] and Taiwan [172] —but not from Mexico [171] —have shown an association between serum vitamin D levels and SLE disease activity.

Limited evidence suggests that supplementation may be clinically beneficial in SLE patients with low levels of vitamin D. In Mediterranean patients,  female patients who were not receiving supplemental vitamin D showed more fatigue and received more oral corticosteroids than those with normal levels of vitamin D. [123] In Australian patients, an increase in serum vitamin D levels was associated with reduced disease activity over time. [170]

A randomized, double-blind, placebo-controlled trial in 40 patients with juvenile-onset SLE suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in these patients. Compared with the placebo group, patients receiving oral cholecalciferol 50,000 IU/week demonstrated significant improvement in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (P = 0.010) and European Consensus Lupus Activity Measurement (ECLAM) scores (P = 0.006), along with a reduction of fatigue related to social life, as measured by the Kids Fatigue Severity Scale (K-FSS) score (P = 0.008). [124]

Endothelial dysfunction and increased risk of cardiovascular disease occur in SLE. [125] In vitro and clinical studies have demonstrated a beneficial effect of vitamin D supplementation on endothelial function in SLE. [126, 127]