Of all cases, 70 to 90% occur in women (usually of child-bearing age). Systemic lupus erythematosus (SLE) is more common and severe among Black and Asian patients than among White patients. It can affect patients of any age, including neonates. In some countries, the prevalence of SLE rivals that of rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more . SLE may be precipitated by currently unknown environmental triggers that cause autoimmune reactions in genetically predisposed people. Some drugs (eg, hydralazine, procainamide, isoniazid, anti-tumor necrosis factor [TNF] drugs) cause a reversible lupus-like syndrome.
Symptoms and Signs of SLE
Clinical findings vary greatly. SLE may develop abruptly with fever or insidiously over months or years with episodes of arthralgias and malaise. Vascular headaches, epilepsy, or psychoses may be initial findings. Manifestations referable to any organ system may appear. Periodic exacerbations (flares) may occur.
Joint symptoms, ranging from intermittent arthralgias to acute polyarthritis, occur in about 90% of patients and may precede other manifestations by years. Most lupus polyarthritis is nondestructive and nondeforming. However, in long-standing disease, deformities without bone erosions may develop (eg, the metacarpophalangeal and interphalangeal joints may rarely develop reducible ulnar drift or swan-neck deformities Swan-Neck Deformity A swan-neck deformity consists of hyperextension of the proximal interphalangeal (PIP) joint, flexion of the distal interphalangeal (DIP) joint, and sometimes flexion of the metacarpophalangeal... read more without bony or cartilaginous erosions [Jaccoud arthritis]). As in many other chronic diseases, the prevalence of fibromyalgia is increased, which may cause diagnostic confusion in patients with periarticular and generalized pain and fatigue.
Skin and mucous membrane manifestations
Skin lesions include malar butterfly erythema (flat or raised) that generally spares the nasolabial folds. The absence of papules and pustules and presence of skin atrophy help distinguish SLE from rosacea Rosacea Rosacea is a chronic inflammatory disorder characterized by facial flushing, telangiectasias, erythema, papules, pustules, and, in severe cases, rhinophyma. Diagnosis is based on the characteristic... read more . A variety of other erythematous, firm, maculopapular lesions can occur elsewhere, including exposed areas of the face and neck, upper chest, and elbows. Skin blistering and ulceration are rare, although recurrent ulcers on mucous membranes (particularly the central portion of the hard palate near the junction of the hard and soft palate, the buccal and gum mucosa, and the anterior nasal septum) are common (sometimes called mucosal lupus); findings can sometimes mimic toxic epidermal necrolysis.
Generalized or focal alopecia Alopecia Alopecia is defined as loss of hair from the body. Hair loss is often a cause of great concern to the patient for cosmetic and psychologic reasons, but it can also be an important sign of systemic... read more is common during active phases of SLE. Panniculitis Panniculitis Panniculitis describes inflammation of the subcutaneous fat that can result from multiple causes. Diagnosis is by clinical evaluation and biopsy. Treatment depends on the cause. (See also Erythema... read more can cause subcutaneous nodular lesions (sometimes called lupus panniculitis or profundus). Vasculitic skin lesions may include mottled erythema on the palms and fingers, periungual erythema, nail-fold infarcts, urticaria, and palpable purpura. Petechiae may develop secondary to thrombocytopenia. Photosensitivity occurs in some patients.
Lupus erythematosus tumidus is characterized by pink to violaceous urticarial nonscarring plaques and/or nodules, some annular, in light-exposed areas.
Chilblain lupus is characterized by tender, bright red to reddish blue nodules on the toes, fingers, nose, or ears that occur in cold weather. Some patients with SLE have features of lichen planus Lichen Planus Lichen planus is a recurrent, pruritic, inflammatory eruption characterized by small, discrete, polygonal, flat-topped, violaceous papules that may coalesce into rough scaly plaques, often accompanied... read more .
Raynaud syndrome Raynaud Syndrome Raynaud syndrome is vasospasm of parts of the hand in response to cold or emotional stress, causing reversible discomfort and color changes (pallor, cyanosis, erythema, or a combination) in... read more due to vasospasm in the fingers and toes causes characteristic blanching and cyanosis.
Cardiopulmonary symptoms commonly include recurrent pleurisy, with or without pleural effusion. Pneumonitis is rare, although minor impairments in pulmonary function are common. Diffuse alveolar hemorrhage Diffuse Alveolar Hemorrhage Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis... read more occasionally occurs. Prognosis has traditionally been poor. Other complications include pulmonary emboli, pulmonary hypertension, and shrinking lung syndrome. Cardiac complications include pericarditis Pericarditis Pericarditis is inflammation of the pericardium, often with fluid accumulation in the pericardial space. Pericarditis may be caused by many disorders (eg, infection, myocardial infarction, trauma... read more (most commonly) and myocarditis Myocarditis Myocarditis is inflammation of the myocardium with necrosis of cardiac myocytes. Myocarditis may be caused by many disorders (eg, infection, cardiotoxins, drugs, and systemic disorders such... read more . Serious, rare complications are coronary artery vasculitis, valvular involvement, and Libman-Sacks endocarditis. Accelerated atherosclerosis Atherosclerosis Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more is an increasing cause of morbidity and mortality. Congenital heart block can develop in neonates whose mother has the antibodies against Ro (SSA) or La (SSB).
Generalized adenopathy is common, particularly among children, young adults, and Black people; however, mediastinal adenopathy is not common. Splenomegaly Splenomegaly Splenomegaly is abnormal enlargement of the spleen. (See also Overview of the Spleen.) Splenomegaly is almost always secondary to other disorders. Causes of splenomegaly are myriad, as are the... read more occurs in 10% of patients.
Neurologic symptoms can result from involvement of any part of the central or peripheral nervous system or meninges. Mild cognitive impairment is common. There may also be headaches, personality changes, ischemic stroke, subarachnoid hemorrhage, seizures, psychoses, aseptic meningitis, peripheral and cranial neuropathies, transverse myelitis, choreoathetosis, or cerebellar dysfunction.
Renal involvement can develop at any time and may be the only manifestation of SLE (see Lupus Nephritis Lupus Nephritis Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Clinical findings include hematuria, nephrotic-range proteinuria, and, in advanced stages, azotemia. Diagnosis... read more ). It may be benign and asymptomatic or progressive and fatal. Renal lesions can range in severity from a focal, usually benign, glomerulitis to a diffuse, potentially fatal, membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis is a heterogeneous group of disorders that share mixed nephritic and nephrotic features and microscopic findings. They mostly affect children. Cause... read more . Common manifestations include proteinuria (most often), an abnormal urinary sediment manifested by red blood cell casts and leukocytes, hypertension, and edema. Early lupus glomerulonephritis may be misdiagnosed as asymptomatic urinary tract infection.
Obstetric manifestations include early and late fetal loss. In patients with antiphospholipid antibodies, the risk of recurrent miscarriages is increased. Pregnancy can be successful (see SLE in Pregnancy Systemic Lupus Erythematosus in Pregnancy Autoimmune disorders are 5 times more common among women, and incidence tends to peak during reproductive years. Thus, these disorders commonly occur in pregnant women. Antiphospholipid antibody... read more ), particularly after 6 to 12 months of remission, but SLE flares are common during pregnancy and especially during the postpartum period. Pregnancy should be timed for when disease is in remission. During pregnancy, the patient should be monitored closely for any disease flare or thrombotic events by a multidisciplinary team that includes an obstetrician who specializes in high-risk pregnancies. Women who are SSA antibody-positive should have weekly fetal ultrasonography between week 18 and week 26 to assess for congenital heart block.
Hematologic manifestations include anemia (anemia of chronic disease Anemia of Chronic Disease The anemia of chronic disease is a multifactorial anemia. Diagnosis generally requires the presence of a chronic inflammatory condition, such as infection, autoimmune disease, kidney disease... read more , autoimmune hemolytic anemia Autoimmune Hemolytic Anemia Autoimmune hemolytic anemia is caused by autoantibodies that react with red blood cells at temperatures ≥ 37° C (warm antibody hemolytic anemia) or < 37° C (cold agglutinin disease). Hemolysis... read more ), leukopenia (usually lymphocytopenia Lymphocytopenia Lymphocytopenia is a total lymphocyte count of < 1000/mcL ( 1 × 109/L) in adults or < 3000/mcL (< 3 × 109/L) in children < 2 years. Sequelae include opportunistic... read more , with < 1500 cells/mcL), and thrombocytopenia (usually mild but sometimes life-threatening autoimmune thrombocytopenia Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more ). Recurrent arterial or venous thrombosis, thrombocytopenia, and a high probability of obstetric complications occur in patients with antiphospholipid antibodies. Thromboses probably account for many of the complications of SLE, including obstetric complications. Macrophage activation syndrome can occur.
Gastrointestinal manifestations can result from bowel vasculitis or impaired bowel motility. In addition, pancreatitis can rarely result from SLE. Manifestations may include abdominal pain resulting from serositis, nausea, vomiting, manifestations of bowel perforation, and pseudo-obstruction. SLE rarely causes parenchymal liver disease.
Diagnosis of SLE
SLE should be suspected in patients, particularly young women, with any of the symptoms and signs. However, early-stage SLE can mimic other connective (or nonconnective) tissue disorders, including rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more if arthritic symptoms predominate. Mixed connective tissue disease Mixed Connective Tissue Disease (MCTD) Mixed connective tissue disease is an uncommon, specifically defined syndrome characterized by clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with very... read more can mimic SLE but also may involve features of systemic sclerosis Systemic Sclerosis Systemic sclerosis is a rare chronic disease of unknown cause characterized by diffuse fibrosis and vascular abnormalities in the skin, joints, and internal organs (especially the esophagus... read more , rheumatoid-like polyarthritis, and polymyositis Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more . Infections (eg, bacterial endocarditis, histoplasmosis) can mimic SLE and may develop as a result of treatment-caused immunosuppression. Disorders such as sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more and paraneoplastic syndromes Paraneoplastic Syndromes Paraneoplastic syndromes are symptoms that occur at sites distant from a tumor or its metastasis. Although the pathogenesis remains unclear, these symptoms may be secondary to substances secreted... read more can also mimic SLE.
Laboratory testing may differentiate SLE from other connective tissue disorders. Routine testing should include the following:
Antinuclear antibodies (ANA) and anti–double-stranded (ds) DNA (anti-dsDNA)
Complete blood count (CBC)
Chemistry profile including renal and liver enzymes
In clinical practice, some clinicians rely on the classification criteria for SLE developed by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR; see table ). Patients are eligible for these criteria only if they have a positive ANA ≥ 1:80. The 2019 EULAR/ACR classification criteria include clinical and immunologic domains, and each criterion is assigned a weight of 2 to 10. If the patient's score is 10 or more, and at least one clinical criterion is fulfilled, disease is classified as SLE. However, a positive ANA does not indicate a diagnosis of lupus. A positive ANA test in the presence of fatigue and generalized myofascial pain without other clinical or laboratory findings is rarely significant.
The fluorescent test for ANA is the best initial test for SLE in patients who have compatible symptoms and signs; positive ANA tests (usually in high titer: > 1:80) occur in > 98% of people with SLE. However, positive ANA tests can also occur in rheumatoid arthritis, other connective tissue disorders, autoimmune thyroid disease, cancers, and even in the general population. The false-positive rate varies from about 3% with ANA titers of 1:320 to about 30% for ANA titers of 1:40 among healthy controls. Drugs such as hydralazine, procainamide, and tumor necrosis factor-alpha antagonists can produce positive ANA results as well as a lupus-like syndrome; the ANA eventually becomes negative if the drug is stopped. Positive ANA should prompt more specific testing such as anti-dsDNA antibodies; high titers of anti-dsDNA are highly specific for SLE but occur in < 70% of people with SLE.
Other ANA and anticytoplasmic antibodies
The ANA test is very sensitive, but it is not specific for SLE; thus, evidence of other autoantibodies is used to aid in diagnosis. They include Ro (SSA), La (SSB), Smith (Sm), ribonucleoprotein (RNP), and dsDNA. Ro is predominantly cytoplasmic; anti-Ro antibodies are occasionally present in ANA-negative SLE patients presenting with chronic cutaneous lupus. Anti-Ro is the causal antibody for neonatal lupus and congenital heart block. Anti-Sm is highly specific for SLE but, like anti-dsDNA, is not sensitive. Anti-RNP occurs in patients with SLE, mixed connective tissue disease, and occasionally other systemic autoimmune disorders and systemic sclerosis.
Other blood tests
Leukopenia Overview of Leukopenias Leukopenia is a reduction in the circulating white blood cell (WBC) count to < 4000/mcL (9/L). It is usually characterized by a reduced number of circulating neutrophils, although... read more (usually lymphopenia) is common. Hemolytic anemia Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span... read more may occur, but low hemoglobin and red blood cell counts are more often due to the anemia of chronic disease Anemia of Chronic Disease The anemia of chronic disease is a multifactorial anemia. Diagnosis generally requires the presence of a chronic inflammatory condition, such as infection, autoimmune disease, kidney disease... read more . Thrombocytopenia in SLE may be difficult or impossible to differentiate from idiopathic thrombocytopenic purpura except that patients have other features of SLE and/or SLE-specific antibodies (anti-dsDNA or anti-Sm). False-positive serologic tests for syphilis occur in 5 to 10% of SLE patients. These test results may be associated with the lupus anticoagulant and a prolonged partial thromboplastin time (PTT). Abnormal values in one or more of these assays suggest the presence of antiphospholipid antibodies (eg, anticardiolipin antibodies), which should then be measured directly by enzyme-linked immunosorbent assay (ELISA). Antiphospholipid antibodies are associated with arterial or venous thrombosis, thrombocytopenia, and, during pregnancy, spontaneous abortion or late fetal death but may be present in asymptomatic patients.
Other tests help monitor disease severity and determine the need for treatment. Serum complement levels (C3, C4) are often depressed in active disease and are usually lowest in patients with active nephritis. Erythrocyte sedimentation rate (ESR) is elevated frequently during active disease. C-reactive protein levels are not necessarily elevated; high levels raise the concern for infection and/or serositis.
Screening for renal involvement begins with urinalysis. Red blood cell (RBC) and/or white blood cell casts suggest active nephritis Lupus Nephritis Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Clinical findings include hematuria, nephrotic-range proteinuria, and, in advanced stages, azotemia. Diagnosis... read more . Urinalysis should be done at regular intervals (eg, every 3 to 6 months), even for patients in apparent remission, because kidney disease is usually asymptomatic. Proteinuria can be estimated by the urine protein/creatinine ratio or measured in a 24-hour urine collection. Renal biopsy is indicated in patients whose protein excretion is > 500 mg/day and who have hematuria (thought to be glomerular) or RBC casts and is helpful in evaluating the status of renal disease (ie, active inflammation vs postinflammatory scarring) and in guiding therapy. Patients with chronic renal insufficiency and mostly sclerotic glomeruli are not likely to benefit from aggressive immunosuppressive therapy.
Prognosis for SLE
The course is usually chronic, relapsing, and unpredictable. Remissions may last for years. If the initial acute phase is controlled, even if very severe (eg, with cerebral thrombosis or severe nephritis), the long-term prognosis is usually good. The 10-year survival in most developed countries is > 95%. Improved prognosis is in part due to earlier diagnosis and more effective therapies. Complications include infection from immunosuppression or osteoporosis from long-term corticosteroid use. Increased risk of coronary artery disease can contribute to premature death.
Treatment of SLE
Hydroxychloroquine (an antimalarial) for all patients with SLE
Nonsteroidal anti-inflammatory drugs (NSAIDs) in addition to antimalarials for mild disease
Corticosteroids, immunosuppressants, and antimalarials for severe disease
To simplify therapy, SLE should be classified as mild to moderate (eg, fever, arthritis, pleurisy, pericarditis, rash) or severe (eg, hemolytic anemia, severe thrombocytopenic purpura, massive pleural and pericardial involvement, diffuse alveolar hemorrhage or pneumonitis, nephritis, acute vasculitis of the extremities or gastrointestinal tract, florid central nervous system [CNS] involvement).
The antimalarial drug hydroxychloroquine is indicated for all patients with SLE regardless of disease severity because it decreases disease flares and decreases mortality (1 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ); however, hydroxychloroquine is not used in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic defect common in people with African ancestry that can result in hemolysis after acute illnesses or intake of oxidant... read more because it can cause hemolysis.
(See also recommendations for the management of SLE from the European League Against Rheumatism [EULAR].)
Mild to moderate disease
Arthralgias are usually controlled with NSAIDs. However, chronic NSAID use is discouraged because of gastrointestinal adverse effects (eg, peptic ulcer disease) and potential coronary and renal toxicity (eg, interstitial nephritis, papillary necrosis). Topical agents (corticosteroids, tacrolimus) can be used for skin disease, usually under the guidance of dermatology.
Antimalarials, such as hydroxychloroquine, are useful for joint and skin manifestations. Hydroxychloroquine reduces the frequency of SLE flares and decreases mortality, and is therefore used in virtually all patients with SLE. Dose is 5 mg/kg of actual body weight orally once a day. Baseline ophthalmologic examination should be done before starting therapy to exclude maculopathy because chronic hydroxychloroquine use increases the risk of toxic maculopathy. Ophthalmologic screening should be done yearly after the drug has been used for 5 years to assess for retinal toxicity. Alternatives include oral chloroquine 250 mg once a day and oral quinacrine 50 to 100 mg once a day. (See also recommendations on screening for chloroquine and hydroxychloroquine retinopathy.) Hydroxychloroquine can rarely cause skeletal or cardiac muscle toxicity.
Methotrexate (15 to 20 mg orally or subcutaneously once a week), azathioprine (2 mg/kg orally once a day), or mycophenolate mofetil (1 to 1.5 grams orally twice a day) can be added to hydroxychloroquine in patients with uncontrolled mild to moderate disease who would otherwise be candidates for a course of corticosteroids. The ultimate goal is to maintain disease remission either without the need for corticosteroids or with only the lowest dose possible.
Belimumab (10 mg/kg IV every 2 weeks for 3 doses, then 10 mg/kg IV once a month or 200 mg subcutaneously once a week) should be considered if patients have uncontrolled disease or frequent flares, particularly for joint, skin, or nonsevere hematologic manifestations (2 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ). It can be used in addition to hydroxychloroquine and in combination with other drugs depending on the specific system involved and severity of disease.
Treatment includes induction therapy to control acute severe manifestations followed by maintenance therapy. Corticosteroids are first-line therapy. A combination of a corticosteroid and other immunosuppressants is typically used in active severe disease (ie, lupus nephritis with impaired renal function or CNS involvement).
The complication for which there is the strongest evidence for treatment efficacy is lupus nephritis Lupus Nephritis Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Clinical findings include hematuria, nephrotic-range proteinuria, and, in advanced stages, azotemia. Diagnosis... read more . Methylprednisolone 1 g by slow (1-hour) IV infusion on 3 successive days is often the initial treatment, although trial evidence for this pulse corticosteroid therapy is lacking. Then, oral prednisone given in doses of 0.5 to 1 mg/kg once a day (usually 40 to 60 mg once a day) is initiated and the dose is adjusted according to the manifestation of SLE. Corticosteroids should be tapered as soon as allowed by the disease, usually within 6 months, to limit adverse effects. Cyclophosphamide (see table ) or mycophenolate mofetil (3 g a day orally in 2 doses) is also used for induction therapy along with corticosteroids.
Recently, adding belimumab in a dose of 10 mg/kg IV monthly to corticosteroids and mycophenolate or corticosteroids and cyclophosphamide has been shown to lead to a better renal response and complete renal response at 6 months compared to corticosteroids and mycophenolate or corticosteroids and cyclophosphamide alone (3 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ). Vocloscorin in a dose of 23.7 mg orally twice a day in combination with mycophenolate mofetil and a rapidly tapered course of corticosteroid has been shown to lead to better renal outcomes at one year than corticosteroids and mycophenolate mofetil alone (4 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ). Both belimumab and voclosporin are now often being used to treat lupus nephritis (class III, IV, V), but clear guidelines for their use are not yet available (5 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ). Classification of lupus nephritis is based on histologic findings on renal biopsy (see table ).
Cyclophosphamide use for more than 6 months is discouraged because of potential toxicities, including increased risk of cancer. Once disease control is achieved, patients are transitioned to either mycophenolate mofetil (1 to 1.5 g orally 2 times a day) or azathioprine (0.5 to 1.5 mg/kg orally twice a day) for maintenance. Women of childbearing age for whom cyclophosphamide is being considered should be informed about the risk of gonadal toxicity and offered a fertility consult for ovarian protection or egg harvesting when possible.
In CNS lupus, including transverse myelitis Acute Transverse Myelitis Acute transverse myelitis is acute inflammation of gray and white matter in one or more adjacent spinal cord segments, usually thoracic. Causes include multiple sclerosis, neuromyelitis optica... read more , treatment recommendations are based on anecdotal evidence, and options include IV cyclophosphamide or IV rituximab (eg, 1 g on day 1 and day 15 given at 6-month intervals) in addition to a corticosteroid.
First-line therapy for thrombocytopenia and hemolytic anemia includes moderate- or high-dose corticosteroids (typically prednisone, 1 mg/kg orally once a day, maximum 80 mg a day) along with an immunosuppressant (azathioprine 2 mg/kg orally once a day or mycophenolate mofetil 1 g orally every 12 hours). IV immune globulin 400 mg/kg once a day for 5 consecutive days or 1 g/kg once a day for 2 days may be useful, particularly if high-dose corticosteroids are contraindicated (eg, in patients with active infection). Rituximab is an alternative option for refractory cases (2 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ).
Patients with end-stage renal disease can undergo kidney transplantation, as an alternative to dialysis, with a successful outcome, especially if their disease has been in remission.
Improvement of severe SLE often takes 4 to 12 weeks. Thrombosis or embolism of cerebral, pulmonary, or placental vessels requires short-term treatment with heparin and longer treatment with warfarin. If the diagnosis of antiphospholipid syndrome is confirmed, lifelong therapy (usually warfarin) is usually indicated. The initial target international normalized ratio is usually 2 to 3.
A new drug anifrolumab (IgG1κ monoclonal antibody to type I interferon receptor), at a dose of 300 mg IV every 4 weeks, may be added to standard therapy for the management of moderate to severe systemic lupus erythematosus, particularly in those with severe skin disease. However, patients with active and severe neuropsychiatric or renal disease were not included in the pivotal trial (6 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ).
Chronic disease should be treated with the lowest dose of corticosteroids (eg, oral prednisone ≤ 7.5 mg once a day or its equivalent) and other drugs that control inflammation (eg, antimalarials, immunosuppressants [mycophenolate mofetil or azathioprine]) to maintain remission (2 Treatment references Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more ). Treatment should be guided by clinical features primarily, although anti-dsDNA antibody titers or serum complement levels may be followed, particularly if they have correlated with disease activity in the past. However, anti-dsDNA antibody titers or serum complement levels may not parallel nonrenal disease flares. Other pertinent blood and urine tests may be used to assess specific organ involvement.
Calcium, vitamin D, and bisphosphonate therapy (see prevention of osteoporosis Prevention Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more ) should be considered in patients taking corticosteroids long term.
If combination immunosuppressive therapy is used, patients should be given prophylaxis for opportunistic infections, such as Pneumocystis jirovecii (see prevention of Pneumocystis jirovecii pneumonia Prevention Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more ), and vaccines against common infections (eg, streptococcal pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , influenza Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more , COVID-19 COVID-19 Vaccine COVID-19 vaccines provide protection against COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Vaccination is the most effective strategy to prevent severe illness and death... read more ).
Coexisting medical conditions and pregnancy
All patients should be closely monitored for atherosclerosis, and cardiovascular risk reduction is a key part of management (see treatment of atherosclerosis Treatment Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more ). Long-term anticoagulation is vital in patients with antiphospholipid antibodies and history of thrombosis (see also Anticoagulants Anticoagulants Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ).
Pregnant women should remain on hydroxychloroquine throughout their pregnancy, and low-dose aspirin is recommended as well. When clinical antiphospholipid syndrome is present, as manifested by prior thrombotic events, full anticoagulation therapy with low molecular weight or unfractionated heparin is advised. If the pregnant woman has positive antiphospholipid syndrome antibodies and prior late-stage fetal loss or recurrent 1st trimester miscarriages, prophylactic low molecular weight or unfractionated heparin can be considered during pregnancy and 6 weeks postpartum. When the patient has positive serologies but no prior obstetric or thrombotic events, recommendations are less clear. Co-management by a hematologist, an obstetrician, and a rheumatologist should be considered when managing these patients.
Mycophenolate mofetil is teratogenic. Because of this teratogenicity and the known poor outcomes related to active SLE during pregnancy, women should ideally conceive after their disease has been in remission for 6 months or longer. If the patient needs to remain on immunosuppression (eg, ongoing maintenance therapy for lupus nephritis), mycophenolate mofetil is usually switched to azathioprine at least 6 months prior to conceiving.
1. Alarcón GS, McGwin G, Bertoli AM, et al: Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: Data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 66(9):1168–1172, 2007. doi: 10.1136/ard.2006.068676
2. Fanouriakis A, Kostopoulou M, Alunno A, et al: 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 78(6):736-745, 2019. doi:10.1136/annrheumdis-2019-215089
3. Furie R, Rovin BH, Houssiau F, et al: Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 383(12):1117-1128, 2020. doi:10.1056/NEJMoa2001180
4. Rovin BH, Teng YKO, Ginzler EM, et al: Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.Lancet 397(10289):2070-2080, 2021. doi:10.1016/S0140-6736(21)00578-X. Erratum in: Lancet 397(10289):2048, 2021.
5. Bajema IM, Wilhelmus S, Alpers CE, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int 93(4):789-796, 2018. doi:10.1016/j.kint.2017.11.023
6. Morand EF, Furie R, Tanaka Y, et al: Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med 382(3):211-221, 2020. doi:10.1056/NEJMoa1912196
Joint and skin manifestations are classic in SLE, but the disorder can affect various organ systems, such as the skin, heart and lungs, lymphoid tissue, kidneys, and gastrointestinal, hematologic, reproductive, and nervous systems.
The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria can be used to confirm the diagnosis of SLE.
Among tests, use the highly sensitive ANA for screening, but use more specific autoantibodies (eg, anti-dsDNA, anti-Sm) for confirmation.
Evaluate all patients for kidney involvement.
Treat all patients with hydroxychloroquine and, for mild disease, NSAIDs as needed.
Use corticosteroids for moderate or severe SLE and an immunosuppressant for active lupus nephritis, CNS lupus, skin manifestations that do not respond to hydroxychloroquine, diffuse alveolar hemorrhage, vasculitis, recurrent serositis, or cardiac manifestations.
Use corticosteroids at the lowest possible dose and other drugs that control inflammation to maintain remission.
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Variant Forms of Lupus
Discoid lupus erythematosus (DLE)
DLE, also sometimes called chronic cutaneous lupus erythematosus, is a set of skin changes that can occur as part of lupus, with or without systemic involvement. Skin lesions begin as erythematous plaques and progress to atrophic scars. They cluster in light-exposed areas of the skin, such as the face, scalp, and ears. Untreated, lesions extend and develop central atrophy and scarring. There may be widespread scarring alopecia. Mucous membrane involvement may be prominent, especially in the mouth. Sometimes lesions are hypertrophic and may mimic lichen planus (called hypertrophic or verrucous lupus).
Patients presenting with typical discoid lesions should be evaluated for systemic lupus erythematosus (SLE) Diagnosis Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more . Antibodies against dsDNA are almost invariably absent in DLE. Although it does not differentiate DLE from SLE, biopsy can rule out other disorders (eg, lymphoma or sarcoidosis). Biopsy should be done from the active margin of a skin lesion.
Early treatment of DLE can prevent permanent atrophy. Exposure to sunlight or ultraviolet light should be minimized (eg, using potent sunscreens when outdoors).
Topical corticosteroid ointments (particularly for dry skin) or creams (less greasy than ointments) 3 to 4 times a day (eg, triamcinolone acetonide 0.1 or 0.5%, fluocinolone 0.025 or 0.2%, flurandrenolide 0.05%, betamethasone valerate 0.1%, and, particularly betamethasone dipropionate 0.05%) usually cause involution of small lesions; they should not be used excessively or on the face (where they cause skin atrophy). Resistant lesions can be covered with plastic tape coated with flurandrenolide.
Alternatively, intradermal injection with triamcinolone acetonide 0.1% suspension (< 0.1 mL per site) may resolve lesions, but secondary atrophy frequently follows. Antimalarials (eg, oral hydroxychloroquine 5 mg/kg once a day or 2.5 mg/kg 2 times a day) are also considered first-line therapy, including for facial lesions.
If first-line therapy fails, combination therapy with hydroxychloroquine 200 mg/day plus oral quinacrine 50 to 100 mg once a day or hydroxychloroquine plus methotrexate, mycophenolate mofetil, or azathioprine is used.
Subacute cutaneous lupus erythematosus (SCLE)
Patients with SCLE develop extensive recurring rashes. Annular or papulosquamous lesions (psoriasiform lesions) may develop on the face, arms, and trunk. Lesions are usually photosensitive and can develop hypopigmentation but rarely scar. SCLE can be drug-induced, for example, triggered by antihypertensives (eg, diuretics, calcium channel blockers, beta blockers), proton pump inhibitors (eg, omeprazole, pantoprazole), anti-tumor necrosis factor (TNF) biologics (eg, adalimumab), and antifungal drugs (eg, terbinafine).
About 30 to 62% of patients with SCLE fulfill the American College of Rheumatology's classification criteria for SLE. Arthritis and fatigue are common in SCLE, but neurologic and renal manifestations are not. Patients may be antinuclear antibody (ANA)-positive or ANA-negative. Patients usually have antibodies to Ro (SSA). Infants whose mother has Ro antibodies may have congenital SCLE or congenital heart block. SCLE is treated similarly to SLE Treatment Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more .
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|No brand name available|
|Procanbid, Pronestyl, Pronestyl-SR|
|ASTAGRAF XL, ENVARSUS, HECORIA, Prograf, Protopic|
|Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep|
|Benlysta, Benlysta SC|
|A-Methapred, Depmedalone-40, Depmedalone-80 , Depo-Medrol, Medrol, Medrol Dosepak, Solu-Medrol|
|Cyclophosphamide, Cytoxan, Neosar|
|RIABNI, Rituxan, RUXIENCE, truxima|
|Deltasone, Predone, RAYOS, Sterapred, Sterapred DS|
|Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin|
|Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3|
|Anacin Adult Low Strength, Aspergum, Aspir-Low, Aspirtab , Aspir-Trin , Bayer Advanced Aspirin, Bayer Aspirin, Bayer Aspirin Extra Strength, Bayer Aspirin Plus, Bayer Aspirin Regimen, Bayer Children's Aspirin, Bayer Extra Strength, Bayer Extra Strength Plus, Bayer Genuine Aspirin, Bayer Low Dose Aspirin Regimen, Bayer Womens Aspirin , BeneHealth Aspirin, Bufferin, Bufferin Extra Strength, Bufferin Low Dose, DURLAZA, Easprin , Ecotrin, Ecotrin Low Strength, Genacote, Halfprin, MiniPrin, St. Joseph Adult Low Strength, St. Joseph Aspirin, VAZALORE, Zero Order Release Aspirin, ZORprin|
|Aristocort, Aristocort A, Aristocort Forte, Aristocort HP, Aristo-Pak, Aristospan, Azmacort, Children's Nasacort Allergy 24HR Nasal Spray, Cinalog, Cinolar, Flutex, Hexatrione, Kenalog, Kenalog in Orabase, Kenalog-10, Kenalog-40, Kenalog-80, Nasacort, Nasacort AQ, Oralone, SP Rx 228 , Tac-3 , Triacet , Triamonide , Trianex , Triderm , Triesence, XIPERE, Zilretta|
|Cordran, Cordran SP, Cordran Tape, Nolix|
|Adbeon, Alphatrex, Beta 1 Kit, Beta Derm , Betanate , Betatrex, Beta-Val, BSP 0820, Celestone, Del-Beta , Diprolene, Diprolene AF, Diprosone, Luxiq Foam, Maxivate, ReadySharp Betamethasone, Sernivo, Valisone|
|Prilosec, Prilosec OTC|
|Desenex Max, Lamisil, Lamisil AT, Lamisil AT Athletes Foot, Lamisil AT Jock Itch, Terbinex|