Basics
Description
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by production of antibodies to various components of the cell nucleus, in conjunction with a variety of clinical manifestations. ‚
Epidemiology
- Age
- 20% of lupus begins in childhood, but it is very rare younger than 5 years old.
- Female-to-male ratio:
- Between 3 " “5:1 (prepubertal) and 9 " “10:1 (postpubertal)
- SLE occurs about 3 times more often in African Americans than Caucasians. It is also more common in Hispanic, Asian, and Native Americans.
Incidence
- Peak incidence: between ages 15 and 40 years
- Incidence in children is from 10 " “20 cases/100,000 children per year.
Prevalence
- U.S. estimate: 5,000 " “10,000 children
Risk Factors
Genetics
- Increased frequency in 1st-degree family members of patients with SLE
- 10% of patients have ≥1 affected relative.
- Concordance rate of 25 " “50% in monozygotic twins and 5% in dizygotic twins
- Some major histocompatibility complex antigens are associated with increased incidence of lupus, such as HLA-DR2 and DR3 in whites and DR2 and DR7 in blacks.
Etiology
Although exact etiology is unknown, lupus is an autoimmune disease, with genetic, environmental, and hormonal factors playing a role. ‚
Diagnosis
Classification criteria: 4 of the following 11 criteria, developed by the American College of Rheumatology, must be met to classify a patient as having SLE: ‚
- Malar (butterfly) rash
- Discoid rash
- Photosensitivity
- Oral or nasal ulcers
- Arthritis
- Cytopenia
- Anemia, leukopenia (<4,000/mm3), lymphopenia (<1,500/mm3), or thrombocytopenia (<100,000/mm3)
- Neurologic disease: seizures or psychosis
- Nephritis: >0.5 g/day proteinuria or cellular casts
- Serositis: Pleuritis or pericarditis
- Positive immunoserology (revised 1997): antibodies to double-stranded DNA or Smith nuclear antigen, false-positive serologic test for syphilis, lupus anticoagulant, or antiphospholipid antibodies
- Positive ANA
- Meeting 4 of 11 classification criteria is highly sensitive and specific for diagnosis of SLE.
History
- History of photosensitivity or malar rash common but not necessary
- Many patients have systemic complaints, such as fever, fatigue, and malaise.
- Many patients complain of joint pain, Raynaud phenomenon, or alopecia.
- Chest pain from pericarditis or pleural effusions may be present.
- Signs and symptoms:
- Immune complex " “mediated vasculitis, which can occur in almost any organ system
- Cutaneous lesions: very variable; include
- Erythematous malar or "butterfly " ¯ rash
- Maculopapular rashes (can occur anywhere on body)
- Periungual erythema
- Mucosal membrane vasculitis
- Arthritis: can affect large and small joints; usually symmetric and nonerosive
- Hematologic pathology includes the following:
- Hemolytic anemia
- Anemia of chronic disease
- Leukopenia
- Lymphopenia
- Thrombocytopenia
- Neurologic symptoms include the following:
- Headaches
- Psychosis
- Depression
- Seizures
- Organic brain syndromes
- Peripheral neuropathies
- Renal pathology (present in up to 75% children with SLE)
- Includes mesangial changes and glomerulonephritis (focal, diffuse proliferative, or membranous)
- First signs of renal disease in lupus patient are often proteinuria and active urinary sediment.
- Hypertension, nephrotic syndrome, and renal failure can also occur.
- Serositis: usually seen as pericarditis or pleuritis but peritonitis can also occur
- Constitutional symptoms are very common: fatigue, weight loss, fever.
Physical Exam
- Rash: may be malar, discoid, or vasculitic. Periungual erythema may also be seen.
- Oral or nasal ulcers (usually on hard or soft palate) that are painless and often go unnoticed by patients
- Arthritis of large and small joints
- Pericardial friction rub if patient has pericarditis
- Edema may be present secondary to renal disease.
- CNS changes such as personality changes, psychosis, or seizures
Diagnostic Tests & Interpretation
Lab
- ANA
- Found in >95% of patients with SLE, but a positive ANA can occur in many diseases and in up to 20% of normal population
- Anti " “double-stranded DNA and anti " “Smith nuclear antigen
- Very specific to lupus, but not all patients with lupus have these autoantibodies. In many patients, anti-DNA levels vary with activity of disease.
- CBC
- Anemia, leukopenia, lymphopenia, and/or thrombocytopenia may be seen.
- Urinalysis
- May show proteinuria or active urinary sediment if there is renal dysfunction
- Complement levels
- Can fall very low during a lupus flare (C3 and C4)
- PTT
- Patients may also have prolonged PTT, as result of antiphospholipid (APL) antibodies, often seen in SLE.
- Patients with APL antibodies are at increased risk for thrombotic events, such as deep venous thrombosis, stroke, and fetal loss during pregnancies.
Differential Diagnosis
- Systemic-onset juvenile idiopathic arthritis
- Oncologic disease (leukemia, lymphoma)
- Viral or other infectious illness
- Other vasculitic disorders
- Dermatomyositis
- Fibromyalgia
- Drug-induced lupus
- Pitfalls:
- Avoid overdiagnosis; positive ANA in the absence of clinical signs or symptoms of SLE is not lupus.
Treatment
Medication
- NSAIDs
- May be used for musculoskeletal and mild systemic complaints, although ibuprofen has been noted to cause aseptic meningitis in a small number of patients with SLE.
- NSAIDs can also exacerbate renal disease in lupus.
- Hydroxychloroquine often used to help control cutaneous manifestations and to help minimize the chance of lupus flares
- Steroids often necessary to control systemic and renal manifestations
- Patients with renal disease often need immunosuppressive agents such as cyclophosphamide (usually given as monthly IV boluses). Mycophenolate mofetil, cyclosporine, or azathioprine may also be used.
- Patients with mainly arthritic symptoms may be treated with weekly methotrexate, PO or SC.
- Patients with antiphospholipid antibodies can be treated with a baby aspirin daily. If they have already had a significant clotting event, they need stronger anticoagulation.
- Angiotensin-converting enzyme (ACE) inhibitors are often used to help prevent renal damage from proteinuria.
- Patients with abnormal lipid profiles that do not respond to diet may need statins.
- Rituximab (anti-CD20 antibody) causes B-cell depletion and is used in SLE, especially for thrombocytopenia.
- Belimumab, a BLyS (B-lymphocyte stimulator) inhibitor, has been approved in adults but not yet in children.
- Antibodies to CD40 and C5 are also being studied
- Plasmapheresis and IVIG have been used as well.
Additional Treatments
General Measures
Avoid excessive sun exposure and use sunscreen liberally. ‚
Additional Therapies
For very severe lupus, bone marrow immunoablation or transplantation are options. ‚
Ongoing Care
Prognosis
- Extremely variable. Renal disease and CNS involvement are poor prognostic signs, whereas systemic complaints and joint findings are not.
- 10-year survival in children presenting with SLE is >90%.
Complications
- End-stage renal disease
- Infections secondary to treatments used to control disease
- Atherosclerosis and myocardial infarctions at a young age
- Libman-Sacks endocarditis, which increases risk of subacute bacterial endocarditis
- Neonatal lupus
- Neonatal lupus erythematosus (NLE) is due to maternal autoantibodies (usually SS-A or SS-B antibodies) that cross the placenta and can cause rashes, congenital heart block, cytopenias, and/or hepatitis in the newborn.
- Most symptoms of NLE resolve by 6 months of age, but heart block, if it occurs, is permanent.
- Many mothers of babies with NLE are asymptomatic and unaware that they have these autoantibodies.
- The rash, erythema annulare, can begin a few days after delivery or within the first few weeks of life.
- Topical steroids can minimize skin lesions.
- Congenital heart block is due to damage of the conducting system of the developing fetal heart.
- Bradycardia may be noted by 22 weeks ' gestation, and CHF with nonimmune hydrops fetalis may ensue.
Additional Reading
- Brunner ‚ HI, Huggins ‚ J, Klein-Gitelman ‚ MS. Pediatric SLE " ”towards a comprehensive management plan. Nat Rev Rheumatol. 2011;7(4):225 " “233. ‚ [View Abstract]
- Gottlieb ‚ BS, Ilowite ‚ NT. Systemic lupus erythematosus in children and adolescents. Pediatr Rev. 2006;27(9):323 " “330. ‚ [View Abstract]
- Macdermott ‚ EJ, Adams ‚ A, Lehman ‚ TJ. Systemic lupus erythematosus in children: current and emerging therapies. Lupus. 2007;16(8):677 " “683. ‚ [View Abstract]
- Silverman ‚ E, Eddy ‚ A. Systemic lupus erythematosus. In: Cassidy ‚ JT, Petty ‚ RE, Laxer ‚ RM, et al, eds. Textbook of Pediatric Rheumatology. Philadelphia, PA: Elsevier; 2011:315 " “343.
- Yildirim-Toruner ‚ C, Diamond ‚ B. Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol. 2011;127(2):303 " “312. ‚ [View Abstract]
Codes
ICD09
- 695.4 Lupus erythematosus
- 710.0 Systemic lupus erythematosus
ICD10
- L93.0 Discoid lupus erythematosus
- M32.9 Systemic lupus erythematosus, unspecified
- L93.2 Other local lupus erythematosus
- M32.10 Systemic lupus erythematosus, organ or system involv unsp
- M32.19 Oth organ or system involv in systemic lupus erythematosus
SNOMED
- 200936003 lupus erythematosus (disorder)
- 55464009 Systemic lupus erythematosus (disorder)
- 95332009 rash of systemic lupus erythematosus (disorder)
- 239887007 systemic lupus erythematosus with organ/system involvement (disorder)
- 80258006 Drug-induced lupus erythematosus (disorder)
FAQ
- Q: If a patient has a positive ANA but no clinical signs of SLE, how often should the ANA be followed?
- A: A positive ANA will usually remain positive indefinitely, but it has no real significance in the absence of clinical or other laboratory disturbances. Up to 20% of the normal population may have a positive ANA, so there is no need to repeat the test.
- Q: Can SLE patients with end-stage renal disease obtain renal transplants?
- A: Yes, and SLE usually does not recur in the new kidney.