Basics
Description
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with multi-organ involvement.
- Characterized by excessive autoantibody production, immune complex formation, and tissue injury
Epidemiology
- Peak incidence occurs in women between the ages of 15 and 45, but can occur at any age.
- Female to male ratio:
- Ratio 10:1 between the age of 15 and 45
- Ratio 2:1 during childhood or postmenopause
- More common in African Americans, Afro-Caribbeans, and Hispanic Americans
Incidence
In the US, 2 " 8 cases per 100,000 person years
Prevalence
- Approximately 40 " 50 cases per 100,000 in the general population
- One of the most common autoimmune diseases in women during childbearing years
Risk Factors
There are no known risk factors in SLE, but there are triggers to the immune system that may initiate the cellular response in SLE:
- Ultraviolet light
- Drugs
- Viruses (EBV)
Genetics
- Does not follow typical inheritance pattern, but there is about a 10% chance that any given patient with SLE will have another family member with SLE
- Concordance rate of identical twins is 24% compared to 2 " 3% for fraternal twins.
- Associated with HLA-DR2 and DR3
Pathophysiology
- Complex autoimmune disease involving the interaction of both T cells and B cells primarily producing pathogenic autoantibodies
- Autoantibody production is driven by polyclonal B-cell activation and autoantigen-driven immune stimulation.
- Autoantibodies mediate tissue injury by immune complex deposition.
Etiology
- Unknown etiology
- Genetic susceptibility and environmental factors both contribute to its pathogenesis.
Associated Conditions
SLE may occur with other autoimmune diseases such as:
- Hemolytic anemia
- Thyroiditis
- Idiopathic thrombocytopenia purpura
- Fibromyalgia can occur in 1/3 of the patients with SLE.
Diagnosis
Classification of SLE includes the presence of at least 4 out of the 11 criteria:
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Arthritis (nonerosive)
- Serositis
- Renal involvement
- Persistent proteinuria >0.5 g/day or 3+
- Presence of cellular casts
- CNS involvement
- Hematologic abnormalities
- Hemolytic anemia
- Leukopenia
- Thrombocytopenia
- Immunologic markers
- Antibodies to native DNA, Smith antigen
- Anticardiolipin IgG, IgM, lupus anticoagulant
- False-positive serologic test for syphilis
- Antinuclear antibody (ANA)
History
- Constitutional complaints are common presenting features of SLE:
- Malaise, fatigue, fever, and weight loss
- Diverse clinical presentations depending on organ system involved:
- Rash, joint pain, myalgias, Raynaud 's, seizure, headache, pleuritic chest pain, oral ulcers, photosensitivity, or alopecia
Physical Exam
- Can have a variety of physical findings depending on organ system involved, such as:
- Arthritis: Usually symmetric involving small joints in hands, wrists, and knees
- Rash
- Oral ulcers
- Alopecia
Tests
Lab
- Hematologic abnormalities:
- Leukopenia
- Anemia
- Thrombocytopenia
- Renal abnormalities:
- Elevated creatinine
- Proteinuria
- Active urinary sediment
- Hypocomplementemia (C3,C4)
- Autoantibodies:
- ANA: Positive in virtually all patients with SLE (98%), but lack specificity
- Antibodies to double-stranded DNA
- Present in 60 " 90% of patients with SLE
- Specificity of 95%
- Presence of these antibodies may be associated with development of nephritis
- Anti-Smith antibodies
- Present in 10 " 30% of patients with SLE
- Specificity of 75 " 100%
- Antiphospholipid antibodies
- Present in 30 " 50% of patients with SLE and are associated with increased thrombo-occlusive events
Imaging
Imaging is not needed for diagnosis but may be helpful depending on the clinical situation:
- Plain radiograph of involved joints
- Chest radiograph
- Echocardiography
- MRI
Surgery
Biopsy of an involved organ (kidney or skin) may be necessary for diagnostic purposes and to help guide treatment decisions.
Pathological Findings
- Inflammation, blood vessel abnormalities (vasculopathy or vasculitis), and immune-complex deposition
- Renal involvement occurs in 60% of patients with SLE.
- WHO Classification of Lupus Nephritis:
- Class I: Normal glomeruli
- Class II: Mesangial nephritis
- Class III: Focal proliferative glomerulonephritis
- Class IV: Diffuse proliferative glomerulonephritis
- Class V: Membranous glomerulonephritis
- Class VI: Chronic sclerosing glomerulonephritis
Differential Diagnosis
Extremely broad differential diagnosis for SLE since it has a wide variety of clinical presentations. Some categories to consider include:
- Infection
- Malignancy
- Endocrinopathy
- Rheumatic disease
- Systemic vasculitis
- Rheumatoid arthritis
- Polymyositis
- Still 's disease
- Fibromyalgia
- Medication side effects
- Carbamazepine, hydralazine, isoniazid, methyldopa, minocycline, phenytoin, procainamide, sulfasalazine, quinidine, ethosuximide, chlorpromazine, and penicillamine
- There have been several case reports that the newer biologic agents (TNF-alpha antagonists) can cause drug-induced lupus.
Treatment
Patients with SLE generally require medications to control their symptoms as well as lifestyle modifications to prevent flares (1)[A].
Medication
- NSAIDs: (1)[A]
- Used to treat arthritis, soft tissue complaints, and mild serositis
- Caution in patients with renal insufficiency
- Corticosteroids:
- Typically prescribed orally in low, medium (0.5 mg/kg), or high doses (1 mg/kg) depending on the manifestation
- Pulse steroids (IV methylprednisolone 1 g for 3 consecutive days) used to treat severe organ-threatening features of disease
- Antimalarials:
- Used to treat constitutional symptoms, musculoskeletal complaints, skin rashes, and pleuritic chest pain
- Hydroxychloroquine 400 mg/day
- Most commonly prescribed antimalarial
- Generally well tolerated
- Annual ophthalmologic exam is recommended as can cause ocular toxicity.
- Immunosuppressive medications:
- Azathioprine: 1.5 " 2.5 mg/kg/day
- Used as steroid-sparing agent and as maintenance therapy for nephritis
- Can cause bone marrow suppression and hepatotoxicity
- Methotrexate: 7.5 " 15 mg/week
- Used to treat arthritis, serositis and as a steroid-sparing agent
- Cyclophosphamide
- Used to treat nephritis and in some cases of CNS lupus
- Associated with several adverse side effects including bladder toxicity, ovarian failure, bone marrow suppression, and increased risk of infection
- Mycophenolate mofetil: 1 " 3 g/day
- New evidence supports use as induction and maintenance therapy for nephritis (2)[A]
- Generally well tolerated; few adverse effects including leukopenia, nausea, and diarrhea
- There is a new biologic medication that is a monoclonal antibody that inhibits B cells and is currently in trials and pending FDA approval in the near future (3)[C].
- SLE is not associated with infertility unless patient treated with cyclophosphamide which can lead to premature ovarian failure.(1)[A]
- Pregnancy should be planned for a time when disease (especially renal) is relatively well controlled.
- Maternal morbidity includes flares (especially renal), preeclampsia, preterm labor, and thrombosis (primarily in those with antiphospholipid antibodies).
- Fetal morbidity includes fetal loss, preterm birth, intrauterine growth retardation, and neonatal lupus.
- Medications should be adjusted during pregnancy to avoid risk to the fetus:
- Must consider the risks and benefits of medications in pregnant patients with SLE
Additional Treatment
Issues for Referral
- A rheumatologist should follow patients with SLE closely.
- Consider referral to nephrologist, dermatologist, neurologist, pulmonologist depending on individual symptoms
Additional Therapies
All patients with SLE should be counseled on proper use of sunscreens and avoidance of ultraviolet light since this is known to trigger flares.
Surgery
Renal transplantation is an alternative for lupus patients who develop renal failure.
Ongoing Care
Follow-Up Recommendations
Patient Monitoring
- Patients with SLE should be carefully followed to monitor disease activity.
- Routine laboratory tests include:
- CBC
- ESR
- Urinalysis and serum creatinine
- DsDNA levels
- Complement levels (C3, C4)
- Clinical indices used to assess disease activity in research studies include:
- Systemic lupus erythematosus disease activity index (SLEDAI)
- Systemic lupus activity measure (SLAM)
- British Isles lupus assessment group (BILAG)
Prognosis
- There is a 3- to 5-fold increased mortality compared with the general population. (1)[A]
- Early deaths are generally due to active disease, especially renal or CNS; later deaths result from complications of SLE or treatment.
- Most crucial predictor of mortality is renal disease; the second is CNS disease.
- Patients of African or Hispanic descent appear to have greater mortality rates.
Complications
Complications and mortality result directly from disease activity or treatment toxicity and include:
- Cardiovascular (CV) disease
- Premature atherosclerosis is now recognized as a serious concern in patients with SLE.
- There is a 10- to 50-fold increase in CV disease compared to age-matched controls.
- Infection accounts for 20 " 40% of deaths in SLE.
- Renal failure occurs in 20% of patients.
- Cerebrovascular events
- Osteonecrosis from chronic steroid use
- Certain malignancies occur more frequently in SLE.
References
1Bertsias G, Ioannidis JPA, Boletis J. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis. 2008;67:195 " 205. [View Abstract]2Lee Y, Lee H-S, Choi SJ. Induction and maintenance therapy for lupus nephritis: A systemic review and meta-analysis. Lupus. 2010;19:703 " 710. [View Abstract]3Bertasias G, Salmon J, Boumpas D. Therapeutic opportunities in systemic lupus erythematosus: State of the art and prospects for the new decade. Ann Rheum Dis. 2010;69:1603 " 1611.
Codes
ICD9
710.0 Systemic lupus erythematosus
ICD10
- M32.9 Systemic lupus erythematosus, unspecified
- M32.10 Systemic lupus erythematosus, organ or system involv unsp
SNOMED
55464009 systemic lupus erythematosus (disorder)
Clinical Pearls
- Systemic lupus erythematosus is an autoimmune disease commonly affecting women of childbearing years.
- Variable clinical symptoms from mild (rash and arthritis) to severe organ-threatening disease
- Treatment ranges from using NSAIDs to potent immunosuppressive medications guided by degree of severity of symptoms and organ system involvement.