Systemic Lupus Erythematosus in Emergency Medicine
- Author: Mark J Leber, MD, MPH, FACEP; Chief Editor: Rick Kulkarni, MD more...
Background
Systemic lupus erythematosus (SLE) is a multiorgan system autoimmune disease with numerous immunological and clinical manifestations. It is characterized by an autoantibody response to nuclear and cytoplasmic antigens. The disease mainly involves the skin, joints, kidneys, blood cells, and nervous system. Diagnosing and managing SLE in the emergency department can be very challenging if it is not considered in one's differential diagnosis. Also, the laboratory testing of SLE may be unavailable on an emergent basis.
Pathophysiology
Systemic lupus erythematosus (SLE) is a multifactorial disease involving genetic, environmental, and hormonal factors. Its precise pathogenesis is unclear. There is growing evidence in favor of a clearance deficiency of apoptotic cells as the core mechanism in the pathogenesis of SLE.[1] Defective clearance of apoptotic cells causes secondary necrosis with release of intracellular content and inflammatory mediators. Macrophages respond and present self-antigens to T and B cells.[1]
Pathogenic autoantibodies are the primary cause of tissue damage in patients with lupus. The production of these antibodies arises by means of complex mechanisms involving every key facet of the immune system.[2] The abnormal cellular and humoral response to the formation of these autoantibodies is modulated by genetic, environmental, and hormonal factors:
- Genetic factors
- Genes of the MHC HLA-A1, B8, and DR3 have been linked to lupus.
- Genetic deficiency of complement factors C1q, C2, or C4
- Environmental factors[3]
- Occupational exposure - Silica, pesticides, mercury
- Drugs - Many drugs have been implicated in drug-induced lupus.
- Sunlight
- Epstein-Barr virus (EBV) has also been identified as a possible factor in the development of lupus.[3]
Epidemiology
Frequency
United States
In the United States, the annual incidence of systemic lupus erythematosus (SLE) averages 5.1 per 100,000 per year. The incidence of SLE in black women is approximately 4 times higher than in white women. SLE is more frequent in Asian women than in white women.[4]
The reported prevalence of SLE in the population is 52 cases per 100,000.[5]
The frequency of SLE could be increasing due to mild forms of the disease that are being recognized.
International
The highest prevalences of systemic lupus erythematosus (SLE) were reported in Italy, Spain, Martinique, and the UK Afro-Caribbean population.[5] SLE is more common in women with West African ancestry who have emigrated from their home area, suggesting that there may be an environmental trigger as well as a genetic basis for their disease.
Mortality/Morbidity
The life expectancy of such patients has improved from an approximate 4-year survival rate of 50% in the 1950s to a 15-year survival rate of 80% today.[6] A patient in whom SLE is diagnosed by age 20 years still has a 1 in 6 chance of dying within 15 years, most often from lupus or infection.[7] After 35, the patient is more likely to die from myocardial infarction or stroke.[7]
Infectious diseases have emerged as one of the leading causes of morbidity and mortality, accounting for 29% of all deaths in these patients.[8]
Women with SLE between 35 and 44 years of age had a 52-fold higher risk of having a myocardial infarction than matched women from the Framingham cohort.[9]
Ten-year survival rates in other countries in Asia and Africa are significantly lower, ranging from 60-70%.[10, 11, 12]
Race
Black women have a higher rate of SLE than any other race, followed by Asians, then white women.[5]
In the United States, black women are 4 times more likely to have SLE than white women.[5]
Sex
For all ages, the female-to-male ratio is 7:1 and 11:1 during the childbearing years.[13]
Age
Onset of systemic lupus erythematosus (SLE) is usually after puberty, typically in the 20s and 30s.
Twenty percent of all cases of lupus are diagnosed during the first 2 decades of life.[14]
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| Criterion | Definition |
| 1. Malar rash | Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds |
| 2. Discoid rash | Erythematous raised patches with adherent keratotic scaling and follicular plugging (Atrophic scarring may occur in older lesions) |
| 3. Photosensitivity | Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation |
| 4. Oral ulcers | Oral or nasopharyngeal ulceration, usually painless, observed by a physician |
| 5. Arthritis | Nonerosive arthritis involving ≥2 peripheral joints, characterized by tenderness, swelling, or effusion |
| 6. Serositis | (A) Pleuritis: Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion or |
| (B) Pericarditis: Documented by ECG or rub or evidence of pericardial effusion | |
| 7. Renal disorder | (A) Persistent proteinuria >0.5 g/d or >3+ if quantitation not performed or |
| (B) Cellular casts: May be red blood cell, hemoglobin, granular, tubular, or mixed | |
| 8. Neurologic disorder | (A) Seizures: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance) or |
| (B) Psychosis: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance) | |
| 9. Hematologic disorder | (A) Hemolytic anemia: With reticulocytosis or |
| (B) Leukopenia: < 4000/mm3 total on ≥2 occasions or | |
| (C) Lymphopenia: < 1500/mm3 on ≥2 occasions or | |
| (D) Thrombocytopenia: < 100,000/mm3 in the absence of offending drugs | |
| 10. Immunologic disorder | (A) Anti-DNA: Antibody to native DNA in abnormal titer or |
| (B) Anti-Sm: Presence of antibody to Sm nuclear antigen or | |
| (C) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption tests | |
| 11. Antinuclear antibody | An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome |
| A person can be diagnosed with SLE if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation. |
| Definite Association | |
| Chlorpromazine | Methyldopa |
| Hydralazine | Procainamide |
| Isoniazid | Quinidine |
| Possible Association | |
| Beta-blockers | Methimazole |
| Captopril | Nitrofurantoin |
| Carbamazepine | Penicillamine |
| Cimetidine | Phenytoin |
| Ethosuximide | Propylthiouracil |
| Hydrazines | Sulfasalazine |
| Levodopa | Sulfonamides |
| Lithium | Trimethadione |
| Unlikely Association | |
| Allopurinol | Penicillin |
| Chlorthalidone | Phenylbutazone |
| Gold salts | Reserpine |
| Griseofulvin | Streptomycin |
| Methysergide | Tetracyclines |
| Oral contraceptives | |
| *Data from Tierney et al.[23] | |

