INTRODUCTION	Section 2 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems that is defined clinically and associated with antibodies directed against cell nuclei. Its multisystem manifestations and attendant complications from use of immunosuppressive agents make the diagnosis and management of this entity challenging.

Pathophysiology: Autoantibodies, circulating immune complexes, and T lymphocytes all contribute to the expression of disease. Organ systems affected include dermatologic, renal, central nervous system (CNS), hematologic, musculoskeletal, cardiovascular, pulmonary, the vascular endothelium, and gastrointestinal. The revised criteria for SLE must include 4 of the following at any time during a patient's history (specificity 95% and sensitivity 75%):

• Malar rash

• Discoid rash

• Photosensitivity

• Oral ulcers

• Arthritis

• Serositis

• Renal disorder

• Neurologic disorder

• Hematologic disorder

• Immunologic disorder

• Antinuclear antibody

Frequency:

• In the US: Because of variable reporting, the overall prevalence ranges from 14.6-50.8 cases per 100,000. Incidence varies from 1.8-7.6 cases per 100,000 per year.

• Internationally: Incidence varies worldwide. In Northern Europe, it has been reported to be 40 cases per 100,000.

Mortality/Morbidity: Recent studies in Europe and Canada have shown a reduction in mortality in patients with lupus with 20-year survival rates close to 70% and 10-year survival rates ranging from 75-85%, with more than 90% of patients surviving more than 5 years.

• Early deaths usually are caused by active disease. Atherosclerosis is a leading cause in late deaths. Infection and nephritis are major causes of mortality in all stages of SLE.

• After dialysis or transplantation, a reduction in disease activity and flares has been reported.

• Thrombosis, often secondary to antiphospholipid syndrome, carditis, pneumonitis, pulmonary hypertension, stroke, myocardial infarction, and cerebritis cause severe morbidity and mortality.

Race: SLE is more common in blacks (1:250) than in whites (1:1000). However, all ethnic groups are susceptible.

Sex: Ninety percent of cases are in women. Also, women who are exposed to estrogen-containing oral contraceptives or hormone replacement have an increased risk of developing SLE. The sex distribution is more equal in those who develop SLE during childhood or when older than 50 years.

Age: Most (80%) cases have been reported to occur in women in their childbearing years.

	CLINICAL	Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History: Manifestations are protean, and the mean length of time between onset of symptoms and diagnosis is 5 years. The disease is characterized by exacerbations and remissions. Many women relate flares of their lupus to the postovulatory phase of the menstrual cycle, with resolution of symptoms at the time of menses.

• Systemic symptoms include a low-grade fever, fatigue, malaise, anorexia, nausea, and weight loss. Initial presentation may involve one or more organ systems.

• Arthralgias (53-95%) are the initial complaint in many patients. Often, the pain is out of proportion to physical findings.

• Malar, butterfly rash over the cheeks and bridge of the nose (55-90%) with photosensitivity to ultraviolet (UV) light has been reported (mostly in whites). It also often involves the chin and ears.

• Painful or painless ulcers in the nose and mouth are frequent complaints.

• CNS symptoms may range from mild cognitive dysfunction to a history of seizures (12-59%). Any region of the brain, meninges, spinal cord, and cranial and peripheral nerves can be involved. CNS events often occur when SLE is active in other organ systems. Intractable headaches and difficulties with memory and reasoning are the most common features of neurologic disease in patients with lupus.

• Psychiatric symptoms (high-dose steroids also can cause psychosis [5-37%]) - If the psychosis gets worse after stopping the steroid, it is most likely related to the disease process.

• Pleuritic pain (31-57%), dyspnea, cough, fever, and chest pain are important cardiopulmonary complaints.

• Patients may present with abdominal pain, diarrhea, and vomiting. Intestinal perforation and vasculitis are important diagnoses to exclude.

• A number of other symptoms can be elicited by history which can help identify other pathology, including the following:

• Stroke

• Pulmonary embolus

• Deep venous thrombosis (DVT)

• Acute ischemia

• Retinal vasculitis

Physical:

• Fever is a challenging problem in SLE. It can be a manifestation of active lupus or a representation of infection, malignancy, or a drug reaction. Temperature higher than 102°F should prompt a search for infection and may be a lower-grade temperature in patients on immunosuppressive agents.

• Malar rash is a fixed erythema sparing the nasolabial folds. It is a butterfly rash that can be flat or raised over the cheeks and bridge of the nose. It also often involves the chin and ears.

• Discoid rash occurs in 20% of patients with SLE and can be disfiguring secondary to scarring. It presents as erythematous patches with keratotic scaling over sun-exposed areas of the skin and may occur in the absence of any systemic manifestations.

• All patients experience painless or painful oral or vaginal ulcers at some time in their illness, which are helpful in making the diagnosis.

• Gastrointestinal findings include vague abdominal discomfort, nausea, and diarrhea. Acute crampy abdominal pain, vomiting, and diarrhea may signify vasculitis of the intestine.

• Joint findings

• Tenderness, edema, and effusions accompany polyarthritis that is symmetric, nonerosive, and usually nondeforming. It frequently involves the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands, as well as the wrists and knees.

• Consider avascular necrosis, which is common in patients receiving glucocorticoids.

• Also consider septic arthritis when one joint is inflamed out of proportion to all other joints.

• Central nervous system findings

• All types of seizures have been reported, with grand mal being the most common. Sensory or sensorimotor neuropathies are also common.

• Incidence of stroke is high in the first 5 years of disease. Patients with antiphospholipid antibodies are at higher risk for such events.

• Funduscopic examination is important in patients with visual complaints. Retinal vasculitis can lead to blindness and are demonstrated by sheathed narrow retinal arterioles with white exudates adjacent to the vessels.

• Renal system - Specific signs and symptoms of renal disease may not be apparent until advanced nephrotic syndrome or renal failure is present; therefore, obtaining a urine analysis and serum BUN and creatinine levels on a regular basis is important.

• Cardiovascular system findings

• Atherosclerosis occurs prematurely in patients with SLE and is an independent risk factor for cardiovascular disease.

• Pulmonary hypertension, vasculitis with digital infarcts, and splinter hemorrhages may be observed.

• Systolic murmurs are reported in up to 70% of cases. They may be secondary to fever, hypoxia, anemia, or Libman-Sacks endocarditis (associated with antiphospholipid antibodies).

• Pericarditis has an incidence of 20-30% and is the most common presentation of heart involvement. It is usually associated with small effusions, but it may involve larger effusions when uremia is concomitant. Myocarditis can cause heart failure, arrhythmias, and sudden death.

• Pulmonary findings

• Tachypnea, cough, and fever are common manifestations of lupus pneumonitis.

• Hemoptysis may signify pulmonary hemorrhage. However, infection is the most common cause of infiltrates seen on radiographs.

Causes:

• Many of the clinical manifestations of SLE are caused by the effects of circulating immune complexes on various tissues or to the direct effects of antibodies to cell surface components.

• Whether polyclonal B-cell activation or a response to specific antigens exists is unclear.

• A lack of immune tolerance is observed in animal models.

• A genetic predisposition to the development of SLE exists. The concordance rate in monozygotic twins is approximately 25-70%. Each patient manifests his or her disease differently.

• If a mother has SLE, her daughter's risk of developing the disease is 1:40, and her son's risk is 1:250.

	DIFFERENTIALS	Section 4 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Other Problems to be Considered: