Systemic Lupus Erythematosus (SLE)

• Definition
• Incidence
• Etiology
• Symptoms
• Diagnosis
• Treatment
• Recent Advances
• Conclusion

TREATMENT OF SLE

CONSERVATIVE MANAGEMENT

Arthritis, Arthralgia, and Myalgia
 
Arthritis, arthralgia, and myalgia are the most common manifestations of SLE. Severity ranges from mild to disabling. For patients with mild symptoms, administration of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), or salicylates may provide adequate relief, although none of these is as effective as glucocorticoids.

In many SLE patients, musculoskeletal symptoms are not well controlled by salicylate or NSAID therapy. A trial of antimalarial drugs may be useful in such individuals.

Hydroxychloroquine is the preferred antimalarial agent in the United States (chloroquine may be more effective but has a higher incidence of retinal toxicity: quinacrine is often effective but rarely can cause aplastic anemia). The usual dose of hydroxychloroquine for SLE patients with arthritis is 400 mg daily. If response does not occur within 6 months, the patient can be considered a nonresponder and the drug stopped. If hydroxychloroquine is used for more than 6 months or chloroquine is used for more than 3 months, regular examination by an ophthalmologist for retinal damage is mandatory. If antimalarials are effective, the maintenance dose should be reduced periodically if possible, or the drug should be withdrawn when a patient is doing well, because the retinal toxicity is cumulative.

Some patients with arthritis or arthralgia do not benefit from NSAIDs or salicylates with or without antimalarials. Administration of dihydroandrosterone (DHEA), 100 to 200 mg daily, lowers activity of SLE in some patients, including arthritis/arthralgias.

Methotrexate in weekly oral or parenteral doses of 10 to 20 mg may also be considered, because there are reports of its efficacy in some cases.

However, none of these interventions is as reliable as glucocorticoid therapy in suppressing lupus arthritis and arthralgia. If quality of life is seriously impaired by pain (or by the deformities that develop in about 10 percent of individuals with lupus arthritis), the physician should consider institution of low-dose glucocorticoids, not to exceed 15 mg each morning.
 
Rare patients require high-dose glucocorticoids or even cytotoxic drugs. Such interventions should be avoided if possible. In fact, if arthritis is the major manifestation of disease that compels the physician to choose high-dose immunosuppressive treatments, it may be preferable to use around-the-clock non-narcotic or narcotic analgesics to control pain, rather than to risk life-threatening side effects of aggressive immunosuppression.

Cutaneous Lupus

As many as 70 percent of patients with SLE are photosensitive..Patients should begin with preparations that block UVA and UVB. Sunscreens can be locally irritating (especially those that contain PABA); patients may need to try several preparations to find one that is not irritating.

Local glucocorticoids, including topical creams and ointments and injections into severe skin lesions, are also helpful in lupus dermatitis. [ Patients with disfiguring (discoid) or extensive lesions should be seen by a dermatologist, because management of severe lupus dermatitis can be difficult.

Antimalarial agents are useful in some patients with lupus dermatitis, whether the lesions are those of SLE, subacute cutaneous lupus, or discoid lupus. Antimalarials have multiple sunblocking, anti-inflammatory, and immunosuppressive effects. They also bind melanin and serve as sunscreens, and they have antiplatelet and cholesterol-lowering effects. All these properties may be beneficial to patients with SLE.

Responses to chloroquine and quinacrine are usually demonstrable within 1 to 3 months; responses to hydroxychloroquine may require 3 to 6 months.

Antimalarials may be steroid sparing. Recommended initial doses of antimalarials are hydroxychloroquine, 400 mg daily, chloroquine phosphate, 500 mg daily, and quinacrine, 100 mg daily. Higher doses can be given for brief periods (2 to 4 weeks). After disease is well controlled, the drugs can be slowly tapered. Daily doses can be reduced, or the drug can be given less frequently (e.g., a few days each week). The combination of hydroxychloroquine (or chloroquine) and quinacrine is probably synergistic and can be used in patients refractory to single-drug therapy.

Toxicities of these agents are important but infrequent in comparison with other agents used to treat SLE. Retinal damage is the most important; it can occur in up to 10 percent of patients receiving chronic chloroquine therapy but is much less frequent in those receiving hydroxychloroquine. Regular ophthalmologic examinations with appropriate special testing identify retinal changes early. If changes occur, antimalarial therapy should be stopped or the daily dose decreased. This strategy substantially lowers the incidence of clinically important retinal toxicity. Retinopathy is rare in patients treated with quinacrine.

For individuals with lupus rash resistant to antimalarials and other conservative strategies, etretinate has been beneficial. The retinates are teratogenic, cause cheilitis in most patients, and elevate cholesterol and triglyceride levels in some. Patients resistant to antimalarials and retinates may require systemic glucocorticoids, which improve lupus skin lesions of any type. Additional treatments, which should be considered experimental for dermatologic lupus, include dapsone, thalidomide, and cytotoxic drugs.

Dapsone has been used in discoid lupus, urticarial vasculitis, and bullous LE lesions with some success. It has significant hematologic toxicities (including methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia) and can occasionally worsen the rashes of LE. Some steroid-resistant cases have improved when treated with cytotoxic drugs such as azathioprine or methotrexate.

Successful treatment of refractory lupus rashes with thalidomide has been reported. Development of peripheral neuropathy associated with thalidomide is not uncommon. This highly teratogenic drug is available on special request from the manufacturer, with appropriate assurances that the patient cannot become pregnant.

Fatigue and Systemic Complaints

Fatigue is common in patients with SLE and may be the major disabling complaint. It reflects multiple problems, including depression, sleep deprivation, and fibromyalgia. Fever and weight loss, if mild, can be managed with the conservative approaches outlined in the preceding paragraphs. When severe, systemic glucocorticoid therapy is necessary.

Serositis

Episodes of chest and abdominal pain may be secondary to lupus serositis. In some patients, complaints respond to salicylates, NSAIDs (indomethacin may be best), or antimalarial therapies, or to low doses of systemic glucocorticoids, such as 15 mg/day In others, systemic glucocorticoids must be given in high doses to achieve disease remission.