Treatment of Systemic Lupus Erythematosus: Introduction
Systemic lupus erythematosus (SLE) is a heterogeneous, multisystem disease. SLE manifests in a unique way in each patient, and treatment should be tailored to the type and severity of organ system involvement (Table 22–1). Unfortunately, this is more easily said than done, because there are few large studies to guide decision-making. The lack of large scale, randomized controlled trials has resulted in therapeutic strategies that are largely empiric. Despite these limitations, well-accepted community standards exist and are helpful in guiding treatment. In the end, the patient and his or her physician must weigh the potential risks and benefits of a particular therapy and agree upon a course of action.
| Agent | Typical Dose | Potential Toxicities | Follow-up | Comments |
|---|---|---|---|---|
| Glucocorticoids |
| Hypertension, dyslipidemia, atherosclerosis, hyperglycemia, osteoporosis, avascular necrosis, infection, weight gain, adrenal insufficiency | Lipid profile yearly, urinalysis for glucose, bone densitometry, blood pressure | Regimen for organ- or life-threatening disease: prednisone, 1 mg/kg/d, or pulse intravenous methylprednisone, 1 g/d for 3 days |
| Hydroxychloroquine |
| Ocular effects including inability to focus, corneal deposits, and retinopathy; rash, hyperpigmentation, myopathy, headache, nausea | Ophthalmologic examination with fundoscopy and visual field testing yearly |
|
| Methotrexate | 7.5–15 mg/d | Myelosuppression, lymphoproliferative disorders, cirrhosis, pulmonary inflammation and fibrosis | CBC, platelets, liver function tests, albumin, creatinine every 8 weeks or more frequently during dose changes |
|
| Azathioprine |
| Myelosuppression, hepatotoxicity, malignancy, nausea and vomiting, infection | CBC and platelets every 2 weeks with dosage change, and every 8 weeks thereafter | Consider testing for the thiopurine methyltransferase gene prior to drug initiation; reduce dose in renal insufficiency |
| Mycophenolate mofetil | Target dose of 2–3 g/d | Myelosuppression, nausea, diarrhea | CBC and platelets every 2 weeks with dosage change, and every 8 weeks thereafter | Reduce dose in renal insufficiency |
| Cyclophosphamide |
| Myelosuppression, malignancy, hemorrhagic cystitis, bladder cancer, gonadal failure, infection |
| Reduce dose in renal insufficiency, obesity, and advanced age; use PCP prophylaxis; ensure adequate hydration during treatment; use antiemetics and mesna with intravenous dosing; consider use of leuprolide in women receiving intravenous therapy |
As a foundation for any lupus treatment regimen, lifestyle modification including regular exercise, sufficient rest, a healthy diet, smoking cessation, and sun protection is critical. Lupus patients are at increased risk for accelerated atherosclerosis and, thus, aggressive risk factor modification is also required. In particular, hypertension and hyperlipidemia should be appropriately treated. Each patient should receive an inactivated influenza vaccine yearly and be up-to-date on their pneumococcal vaccine. Attention to bone health and prevention of glucocorticoid-induced osteoporosis with calcium, vitamin D, and bisphosphonates is necessary. Because of this adverse effect of glucocorticoid therapy, as well as many others, it is important to minimize the use of long-term glucocorticoids if at all possible. Studies suggest that there may be an increased risk of malignancy in patients with SLE and that these patients are less likely than the general population to undergo routine cancer screening. Thus, age appropriate cancer screening should be reinforced. Unlike the general population, women with SLE should undergo screening for cervical cancer on a yearly basis.
Constitutional Symptoms
Fatigue is prevalent in SLE patients and can be a disabling symptom. Treatment depends on the underlying etiology of the fatigue, with reversible factors such as hypothyroidism, anemia, and diabetes needing to be being addressed first. Pain and depression are positive predictors of fatigue in SLE patients, while social support mitigates fatigue. Thus, a multidisciplinary approach with attention to these issues can be helpful. Regular aerobic exercise followed by periods of rest should also be encouraged. Not infrequently, successful treatment of other manifestations of SLE (eg, with antimalarials) has a beneficial impact on fatigue as well.
Cutaneous Manifestations
Photosensitivity occurs in approximately 75% of SLE patients. Although sensitivity to UVB light as found in sunlight and fluorescent lights occurs most commonly, some individuals are also sensitive to UVA light or visible light. Photosensitive lesions include the malar rash, discoid lupus erythematosus (DLE), and subacute cutaneous lupus erythematosus. Prompt treatment of cutaneous lupus is necessary to prevent the development of scarring, dyspigmentation, and alopecia.
Sun protection forms the cornerstone of the management of cutaneous lupus. Patients should be educated about the use of sunscreens and the avoidance of intense sun exposure during peak daylight hours. Daily use of sunscreen with an SPF value of 30 is recommended. Patients are urged to apply the sunscreen 30–60 minutes prior to exposure and to reapply the sunscreen every 4–6 hours. Sun-protective clothing is also very important. Smoking cessation is an important goal because smokers tend to have worse skin disease than nonsmokers.
Cutaneous lupus is often treated initially with topical glucocorticoids. The selection of a topical glucocorticoid is based on the location of the lesion as well as the type of lesion. In general, a low potency glucocorticoid such as hydrocortisone is used first, with escalation to more potent, fluorinated preparations as needed. When treating facial lesions, the use of fluorinated glucocorticoids is limited to 2 weeks because of concern about side effects, such as skin atrophy, striae, depigmentation, and telangiectasias. Medium potency preparations such as triamcinolone acetonide or betamethasone valerate are often used for trunk and limb lesions, while high-potency preparations such as clobetasol are reserved for severe, hypertrophic lesions. It is thought that ointments are generally more effective than creams and that lotions are most useful for hairy areas such as the scalp. Intralesional injections of triamcinolone acetonide are often used to treat refractory lesions, such as DLE occurring on the scalp. The injection is performed with a 30-gauge needle and is directed into the active, erythematous regions of the lesions. It is important to remember that adrenal suppression can occur as a consequence of the use of high-potency topical glucocorticoids.
Topical tacrolimus and pimecrolimus, which are approved for the treatment of atopic dermatitis, are sometimes used as second-line agents for the treatment of acute lupus lesions, subacute cutaneous lupus erythematosus, and DLE. They are often used in an attempt to minimize exposure to prolonged use of topical glucocorticoids. Enthusiasm for their use has been tempered in recent years by an FDA advisory warning clinicians about the risk of lymphoma and non-melanoma skin cancer with topical tacrolimus. This warning was based primarily on information from animal studies and case reports from small numbers of patients. Another class of topical therapies, retinoids, might be effective in patients with DLE.
