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Dr. Maria Michailidou


                                             SYSTEMIC LUPUS ERYTHEMATOSOUS

Essentials of Diagnosis

General Considerations

SLE is an inflammatory autoimmune disorder characterized by autoantibodies to nuclear antigens. It can affect multiple organ systems. Many of its clinical manifestations are secondary to the trapping of antigen-antibody complexes in capillaries of visceral structures or to autoantibody-mediated destruction of host cells (eg, thrombocytopenia). The clinical course is marked by spontaneous remission and relapses. The severity may vary from a mild episodic disorder to a rapidly fulminant, life-threatening illness.

The prevalence of SLE is influenced by many factors, including gender, race, and genetic inheritance. About 85% of patients are women. Sex hormones appear to play some role; most cases develop after menarche and before menopause. Among older individuals, the gender distribution is more equal. Race is also a factor, as SLE occurs in 1:1000 white women but in 1:250 black women. Familial occurrence of SLE has been repeatedly documented, and the disorder is concordant in 25–70% of identical twins. If a mother has SLE, her daughters' risks of developing the disease are 1:40 and her sons' risks are 1:250. Aggregation of serologic abnormalities (positive antinuclear antibody) is seen in asymptomatic family members, and the prevalence of other rheumatic diseases is increased among close relatives of patients. The importance of specific genes in SLE is emphasized by the high frequency of certain HLA haplotypes, especially DR2 and DR3, and null complement alleles. Genes that regulate programmed cell death (apoptosis) also appear to be important in the pathogenesis of SLE.

Before making a diagnosis of SLE, it is imperative to ascertain that the condition has not been induced by a drug (Table 20–8). Procainamide, hydralazine, and isoniazid are the best-studied drugs. While antinuclear antibody tests and other serologic findings become positive in many persons receiving these agents, clinical manifestations occur in only a few.

Four features of drug-induced lupus separate it from SLE: (1) the sex ratio is nearly equal; (2) nephritis and central nervous system features are not ordinarily present; (3) hypocomplementemia and antibodies to native DNA are absent; and (4) the clinical features and most laboratory abnormalities usually revert toward normal when the offending drug is withdrawn.

The diagnosis of SLE should be suspected in patients having a multisystem disease with serologic positivity (eg, antinuclear antibody, false-positive serologic test for syphilis). Differential diagnosis includes rheumatoid arthritis, systemic vasculitis, scleroderma, inflammatory myopathies, viral hepatitis, sarcoidosis, acute drug reactions, and drug-induced lupus.

Table . Criteria for the classification of SLE. (A patient is classified as having SLE if any 4 or more of 11 criteria are met.)

1. Malar rash

2. Discoid rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

6. Serositis

7. Renal disease  

a. > 0.5 g/d proteinuria, or—

b. 3+ dipstick proteinuria, or—

c. Cellular casts

8. Neurologic disease  

a. Seizures, or—

b. Psychosis (without other cause)

9. Hematologic disorders  

a. Hemolytic anemia, or—

b. Leukopenia (< 4000/mcL), or—

c. Lymphopenia (< 1500/mcL), or—

d. Thrombocytopenia (< 100,000/mcL)

10. Immunologic abnormalities  

a. Positive LE cell preparation, or—

b. Antibody to native DNA, or—

c. Antibody to Sm, or—

d. False-positive serologic test for syphilis

11. Positive ANA

Clinical Findings

Symptoms and Signs in systemic lupus erythematosous

The systemic features include fever, anorexia, malaise, and weight loss. Most patients have skin lesions at some time; the characteristic "butterfly" (malar) rash affects less than half of patients. Other cutaneous manifestations are discoid lupus, typical fingertip lesions, periungual erythema, nail fold infarcts, and splinter hemorrhages. Alopecia is common. Mucous membrane lesions tend to occur during periods of exacerbation. Raynaud's phenomenon, present in about 20% of patients, often antedates other features of the disease.

Joint symptoms, with or without active synovitis, occur in over 90% of patients and are often the earliest manifestation. The arthritis is seldom deforming; erosive changes are almost never noted on radiographs. Subcutaneous nodules are rare.

Ocular manifestations include conjunctivitis, photophobia, transient or permanent monocular blindness, and blurring of vision. Cotton-wool spots on the retina (cytoid bodies) represent degeneration of nerve fibers due to occlusion of retinal blood vessels.

Pleurisy, pleural effusion, bronchopneumonia, and pneumonitis are frequent. Restrictive lung disease can develop. Alveolar hemorrhage is rare, but potentially life-threatening.

The pericardium is affected in the majority of patients. Cardiac failure may result from myocarditis and hypertension. Cardiac arrhythmias are common. Atypical verrucous endocarditis of Libman-Sacks is usually clinically silent but occasionally can produce acute or chronic valvular incompetence—most commonly mitral regurgitation—and can serve as a source of emboli.

Mesenteric vasculitis occasionally occurs in SLE and may closely resemble polyarteritis nodosa, including the presence of aneurysms in medium-sized blood vessels. Abdominal pain (particularly postprandial), ileus, peritonitis, and perforation may result.

Neurologic complications of SLE include psychosis, cognitive impairment, seizures, peripheral and cranial neuropathies, transverse myelitis, and strokes. Severe depression and psychosis are sometimes exacerbated by the administration of large doses of corticosteroids. Several forms of glomerulonephritis may occur, including mesangial, focal proliferative, diffuse proliferative, and membranous (see Nephrology). Some patients may also have interstitial nephritis. With appropriate therapy, the survival rate even for patients with serious renal disease (proliferative glomerulonephritis) is favorable, albeit a substantial portion of patients with severe lupus nephritis still eventually require renal replacement therapy.

Laboratory Findings

(Tables 20–10, 20–11, and 19–2.) SLE is characterized by the production of many different autoantibodies, some of which produce specific laboratory abnormalities (eg, hemolytic anemia). Antinuclear antibody tests are sensitive but not specific for SLE—ie, they are positive in virtually all patients with lupus but are positive also in many patients with nonlupus conditions such as rheumatoid arthritis, various forms of hepatitis, and interstitial lung disease. Antibodies to double-stranded DNA and to Sm are specific for SLE but not sensitive, since they are present in only 60% and 30% of patients, respectively. Depressed serum complement—a finding suggestive of disease activity—often returns toward normal in remission. Anti-double-stranded DNA antibody levels also correlate with disease activity in some patients; anti-Sm levels do not.

Treatment in systemic lupus erythematosous

Patient education and emotional support, as described for rheumatoid arthritis, are especially important for patients with lupus. Since the various manifestations of SLE affect prognosis differently and since SLE activity often waxes and wanes, drug therapy—both the choice of agents and the intensity of their use—must be tailored to match disease severity. Patients with photosensitivity should be cautioned against sun exposure and should apply a protective lotion to the skin while out of doors. Skin lesions often respond to the local administration of corticosteroids. Minor joint symptoms can usually be alleviated by rest and NSAIDs.

Antimalarials (hydroxychloroquine) may be helpful in treating lupus rashes or joint symptoms that do not respond to NSAIDs. When these are used, the dose should not exceed 400 mg/d ( 6.5 mg/kg/d), and annual monitoring for retinal changes is recommended. Drug-induced neuropathy and myopathy may be erroneously ascribed to the underlying disease. The androgenic corticosteroid danazol may be effective therapy for thrombocytopenia not responsive to corticosteroids. Dehydroepiandrosterone (DHEA) has a therapeutic role comparable to that of the antimalarial agents in the treatment of SLE, but its side effects (particularly acne) are troubling to some patients.

Corticosteroids are required for the control of certain complications. (Systemic corticosteroids are not usually given for minor arthritis, skin rash, leukopenia, or the anemia associated with chronic disease.) Glomerulonephritis, hemolytic anemia, pericarditis or myocarditis, alveolar hemorrhage, central nervous system involvement, and thrombotic thrombocytopenic purpura all require corticosteroid treatment and often other interventions as well. Forty to 60 mg of oral prednisone is often needed initially; however, the lowest dose of corticosteroid that controls the condition should be used. Central nervous system lupus may require higher doses of corticosteroids than are usually given; however, corticosteroid psychosis may mimic lupus cerebritis, in which case reduced doses are appropriate. Immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil, and azathioprine are used in cases resistant to corticosteroids. Treatment of severe lupus nephritis includes an induction phase and a maintenance phase. Cyclophosphamide, which improves renal survival but not patient survival, was for many years the standard treatment for both phases of lupus nephritis. More recently, mycophenolate mofetil, which may be more effective and is less toxic than cyclophosphamide, is emerging as the treatment of choice for many patients with lupus nephritis. Very close follow-up is needed to watch for potential side effects when immunosuppressants are given; these agents should be administered by clinicians experienced in their use. When cyclophosphamide is required, gonadotropin-releasing hormone analogs can be given to protect a woman against the risk of premature ovarian failure. For patients with the antiphospholipid syndrome—the presence of antiphospholipid antibodies and compatible clinical events—anticoagulation is the treatment of choice (see Antiphospholipid Antibody Syndrome, below). Moderate intensive anticoagulation with warfarin to achieve an INR of 2.0–3.0 is as effective as more intensive regimens. Pregnant patients with recurrent fetal loss associated with antiphospholipid antibodies should be treated with low-molecular-weight heparin plus aspirin.

systemic lupus erythematosous rash oral ulcer systemic lupus erythematosous clinical signs