- Clinical science
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that predominantly affects women of childbearing age. The exact cause is still unknown, but hormonal and immunological influences as well as genetic predisposition are considered likely etiological factors. The presentation of the disease is variable and may range from mild localized symptoms to life-threatening systemic disease. Typical findings include fever and fatigue, a malar rash (facial butterfly rash), myalgia, and arthritis. SLE may affect any organ, but damage to the kidneys (lupus nephritis) or the nervous system (neuropsychiatric systemic lupus erythematosus, NSLE)is associated with an especially poor prognosis. The diagnosis of SLE is based on clinical findings and is further supported by antibody tests, particularly for ANA and anti-dsDNA. Management consists of supportive measures, such as avoiding sun exposure, and medication adapted to disease severity. Long-term pharmacotherapy typically involves hydroxychloroquine, which has been shown to reduce flares and decrease mortality. For acute flares, glucocorticoids are given as induction therapy, with dose and treatment duration being adapted to the severity of the flares. In severe cases, additional immunosuppressants (e.g., mycophenolate, azathioprine) may be given.
- Sex: ♀ >> ♂ (10:1)
- Peak incidence: women aged 20–40 years; no particular age of manifestation in men
- US prevalence: highest in African-American, Hispanic, and Asian populations
Epidemiological data refers to the US, unless otherwise specified.
The exact etiology is unknown, but several predisposing factors have been identified:
- Genetic predisposition:
- Hormonal factors: : studies suggest that hyperestrogenic states (e.g., due to oral contraceptive use, postmenopausal hormonal therapy, endometriosis) are associated with an increased risk of SLE. 
- Environmental factors: UV light; , stimulation of immune cells through infection with bacteria and viruses (in particular EBV; , which causes disease flares following infection), medications (e.g., procainamide, hydralazine) 
Hormonal and environmental factors as well as genetic predisposition (see “Etiology” above) → loss of self-tolerance → production of antibodies against perceived nuclear and cellular antigens → damage to tissue via reaction; and, to a lesser extent, reaction
Possible mechanisms for the development of autoantibodies 
- Deficiency of classical complement proteins (C1q, C4, C2) → failure of to phagocytose immune complexes and apoptotic cell material; (i.e., plasma and nuclear antigens) → dysregulated, intolerant lymphocytes begin targeting normally protected intracellular antigens → autoantibody production (e.g., ANA, anti-ds DNA)
- Mechanism of tissue damage
The severity of SLE varies. While some individuals only experience mild symptoms, others suffer from severe symptoms and rapid disease progression. SLE is typically characterized by phases or remission and relapse. It can affect any organ.
Most common symptoms (see alsofor SLE diagnosis below)
- Skin (> 70% of cases)
- Arthritis and arthralgia (> 90% of cases)
- Mostly nonerosive polyarthritis (normal x-ray)
- Fever; (> 50% of cases), fatigue (> 80% of cases), weight loss
Other signs and symptoms
- Musculoskeletal: myalgia and lymphadenopathy
- Serositis: pleuritis and pericarditis; effusions and chest pain may occur
- Kidneys: nephritis with proteinuria (see )
- Heart: involvement of the myocardium, pericardium, valves, and coronary arteries; (LSE)
- Lungs: pneumonitis, interstitial lung disease, pulmonary hypertension
- Gastrointestinal: esophagitis, hepatitis, pancreatitis
- Vascular: , vasculitis, thromboembolism (see )
- Neurologic: : e.g., seizures, psychosis, personality changes, aseptic meningitis, polyneuropathy, myasthenia gravis
- Hematologic: hemolytic anemia, thrombocytopenia, leukopenia; for other features, see “Diagnosis” below.
SLE can cause LSE (Libman-Sacks endocarditis).
Damage to the kidneys or nervous system is associated with a poor prognosis!References:
Cutaneous lupus erythematosus
- Accounts for 50–85% of cases of cutaneous lupus erythematosus
- Clinical features
Rare form: chilblain lupus
- Violaceous plaques on acral areas from exposure to cold
- Prognosis: Patients with DLE have a 10–15% risk of developing SLE.
- Accounts for approx. 10% of cases of SLE
- Clinical features
- Usually affects the neck, shoulders, and forearms, but spares the face
- Small erythematous lesions that develop into either annular or psoriasiform lesions
- Description: lupus-like symptoms triggered by medication that resolve within days to months after discontinuation of the drug
- Sulfa drugs
- Certain non-sulfa drugs: hydralazine, methyldopa, isoniazid, procainamide, phenytoin, TNF-α inhibitors (e.g., etanercept)
- Risk factor: decreased acetyltransferase activity causing slow acetylation of the above-mentioned drugs
- ♂ = ♀
- More common in older individuals (50–70 years)
- Prognosis: remission after discontinuation of offending drugs
Drug-induced lupus erythematosus may manifest with a variety of the features also seen in idiopathic SLE, e.g., fever, arthritis, malar rash, and serositis. However, unlike idiopathic SLE, DILE typically does not affect the oral mucosa, CNS, or kidneys!
- Suspect SLE; in patients with symptoms in more than two of the organ systems listed in the .
- Screening test: ANA titer (SLE is unlikely if the test is negative)
↑ ANA titer → confirm diagnosis with tests that are highly specific for SLE
Anti-dsDNA antibody testing: autoantibody against double-stranded DNA (dsDNA)
- Positive in 70% of patients and highly specific
- Levels correlate with disease activity
- Associated with lupus nephritis
- Anti-Sm antibody testing
- Anti-dsDNA antibody testing: autoantibody against double-stranded DNA (dsDNA)
- Tests listed in “Other laboratory tests” below may support the diagnosis.
Diagnostic criteria (according to the American College of Rheumatology, ACR) 
Requirements: at least 4 of the 11 criteria must be met (specificity: 95%, sensitivity: 85%)
|ACR criteria for SLE|
|Internal organs|| |
|Laboratory tests|| |
“SOAP BRAIN MD” is the acronym for the ACR diagnostic criteria for SLE:
S = Serositis
O = Oral ulcers
A = Arthritis
P = Photosensitivity
B = Blood disorders
R = Renal involvement
A = Antinuclear antibodies
I = Immunologic phenomena
N = Neurologic disorder
M = Malar rash
D = Discoid rash
Other laboratory tests
- Complete blood count and differential: thrombocytopenia, leukopenia, lymphopenia,
- ESR is frequently elevated, while CRP is often normal.
- Electrophoresis: elevated γ-globulin
- ↓ C3 and C4 complement levels
- Urinalysis and urine microscopy: proteinuria and/or casts
- Additional antibody tests
- Lupus band test (LBT): direct immunofluorescence staining of immunoglobulin and complement component deposits (IgG, IgM, IgA und C3); found along the dermoepidermal junction in affected as well as unaffected skin
- Kidney biopsy: if lupus nephritis is suspected(proteinuria, red blood cell casts, or acanthocytes in urinary sediment)
- Imaging studies: assessment of organ or joint involvement (e.g., x-ray for joint symptoms, ultrasound to evaluate renal complications)
- Avoid exposure to UV light (sunlight)
- Smoking cessation
- Immunize patients before initiating immunosuppressants
|Mild symptoms, no vital organs affected||Severe symptoms, no vital organs affected||Organ damage|
|Induction therapy|| || || |
Lupus nephritis (LN)
- Most crucial prognostic factor in SLE
- Can be nephritic or nephrotic (see also )
- Epidemiology: common (∼ 50% of individuals with SLE)
- Pathology: classically, immune complex-mediated glomerulonephritis; is the most common type.
- Classification: classified according to different grades of severity (WHO classes I–VI)
- Treatment: Depending on the severity of the disease, corticosteroids, cytostatic drugs (mycophenolate, cyclophosphamide), and general measures to protect the kidneys (e.g., blood pressure control) may be necessary.
- Description: neurological and psychiatric syndromes found in individuals with SLE that cannot be attributed to any other disorder 
- Epidemiology: found in ∼ 50% of individuals with SLE 
Classification: American College of Rheumatology (ACR) distinguishes 19 NSLE syndromes 
Central nervous system
- Cerebrovascular disease
- Acute confusional state
- Cognitive impairment
- Mood disorder
Peripheral nervous system
- Acute inflammatory demyelinating polyradiculoneuropathy ( )
- Autonomic disorder
- Single mononeuropathy or
- Cranial neuropathy
- Central nervous system
- Specific tests depend on syndrome (see the corresponding learning cards)
- To assess mental symptoms, a battery of neuropsychological tests proposed by ACR is used 
- Treatment 
- Accelerated atherosclerosis and cardiovascular complications (e.g., myocardial infarction)
- Pulmonary hypertension
- ↑ Risk of thrombosis (particularly in individuals with antiphospholipid syndrome) → avoid treatment with estrogens
We list the most important complications. The selection is not exhaustive.
- 10-year survival rate > 90%
- Mortality is highest in individuals > 45 years of age (65% of deaths)
- Causes of death
Cardiovascular disease is the most common cause of death in SLE.
SLE and pregnancy
- Risk assessment 
- Pregnancy planning and counseling
- Prednisolone , azathioprine; cyclosporin, tacrolimus , and hydroxychloroquine are considered safer drug options during preconception, pregnancy, and breastfeeding.
- Some immunosuppressive medications used to treat SLE (e.g. mycophenolate and cyclophosphamide) have severe teratogenic and other adverse fetal effects.
- Low-dose aspirin is recommended in all pregnant women from 12 weeks gestation
- Neonatal lupus syndrome