eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Systemic Lupus Erythematosus: Treatment & Medication

Author: Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Coauthor(s): James Santiago Grisolia, MD, Active Staff, Scripps Mercy Hospital
Contributor Information and Disclosures

Updated: Oct 30, 2008

Treatment

Medical Care

Treatment of systemic lupus erythematosus (SLE) should be provided in cooperation with a consulting rheumatologist. Therapeutic intensity correlates with the severity of an acute attack. NSAIDs and other symptomatic agents are used for less threatening symptoms. Corticosteroids are used in low-dose oral, high-dose oral, or high-dose IV regimens according to the severity of potential organ damage.

Clinical studies supporting this approach were generally performed in lupus nephritis because of its frequency, severity, and quantifiable improvement or deterioration, but the same treatment approaches are generally applied to other organ systems, including the central and peripheral nervous systems and muscular disease. This overall treatment approach should be familiar to neurologists who are accustomed to the evaluation and treatment of other autoimmune conditions such as multiple sclerosis, myasthenia gravis, or polymyositis.

With little evidence base to the therapeutic modalities, a logical approach to the treatment of cerebral lupus is to build a treatment strategy around the various possible pathogeneses: (1) ischemia due to thromboses secondary to the antiphospholipid syndrome, (2) small-vessel noninflammatory proliferative vasculopathy due to cell-mediated immune mechanisms, and (3) antibody-mediated damage to spinal cord and optic nerve—akin to Devic disease.¹⁵

The standard treatment for the non-thrombotic syndromes associated with SLE is immunosuppression, first with corticosteroids and with early recourse to cyclophosphamide. A Cochrane Database Systematic Review found no randomized controlled trials comparing these two treatments and concluded there was no evidence of a treatment advantage of cyclophosphamide.¹⁶

• High-dose IV corticosteroid regimens consist of methylprednisolone 1-2 g daily for 3-6 doses, followed by oral prednisone 60 mg daily, then tapering according to clinical recovery. Less threatening flare-ups may be treated with as much as 100 mg or as little as 10 mg prednisone PO qd (or other agents in equivalent dosage), again tapering gradually according to clinical symptoms, with an increase of 10-20% during the taper if clinical disease flares again. Tapering to an every other day steroid regimen reduces adverse effects substantially but probably will not be successful until clinical disease is quite stable. In acute high dosage, steroids may provoke status epilepticus, psychosis, hypokalemia, hyperglycemia, or hypertension and clinical evidence of any intercurrent infection may be reduced.
  • With chronic use, steroids cause familiar adverse effects including weight gain, diabetes mellitus, cataracts, immunocompromise, and osteoporosis. Calcium supplementation (1 g daily for men or premenopausal women, 1.5 g daily for postmenopausal women) should be initiated early and continued even when steroids are tapered successfully to qod.
  • Thrush and herpetic outbreaks may be treated symptomatically or prophylactically.
• The discovery that Toll-like receptor signaling and interferon-alpha abundance are central elements of the disease process has led to a new appreciation for hydroxychloroquine as an essential baseline medication. Modulation of the immune system via B-cell depletion is entering clinical practice. Mycophenolate mofetil is an effective and safer alternative to cyclophosphamide for patients with lupus nephritis. Other therapeutic approaches under development include anticytokine therapies, co-stimulatory blockade, antigen-specific immune modulation, and hematopoietic stem cell transplantation.¹⁷
• Various steroid-sparing strategies have evolved for long-term use, including cyclophosphamide 0.5-2 mg/kg/d, azathioprine 1-2 mg/kg/d, and methotrexate 10-15 mg given once weekly with folate rescue, permitting gradual reduction or elimination of chronic steroid therapy. Higher dose ranges or dosing based on body surface area may be used for these medications based on the experience of individual clinicians.
• All chronic cytotoxic regimens present substantial risks and should be followed only by physicians familiar with these agents. In acute, life-threatening illness, one option is to initiate cyclophosphamide PO or a single dose of 8-20 mg/kg IV, along with IV methylprednisolone.
• Jonsdottir et al (2008) reported that the majority of patients improved following rituximab plus cyclophosphamide.¹⁸ The differential downregulation of anti-DNA of the IgG and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19⁺ cells at baseline predict a less impressive clinical and serological response suggests that more flexible dosing could be advantageous.
• Antimalarials, especially hydroxychloroquine in dosage of 100-400 mg daily, are used as alternatives to steroids or as supplements to accelerate steroid taper. They have not been studied in central or peripheral nervous system disease. Antimalarials generally require months to become effective, and, therefore, they are not used in the acute treatment of organ-threatening disease.
• The treatment of Devic syndrome in isolated myelopathy or optic neuropathy associated with the antiphospholipid syndrome or lupus needs further study. In view of their lack of pathological similarity to classical multiple sclerosis, treatments such as interferon-beta cannot be justified. Also, there is no hard evidence to support the use of anticoagulation, in the absence of evidence for progressive ischemia of isolated anatomical sites. Therefore, therapy is generally aimed at circulating pathogenic antibodies, with steroids and cyclophosphamide. Plasma exchange has proven effective in nonlupus Devic disease. Because of the analogy with nonlupus Devic disease, plasma exchange is also an attractive alternative in SLE-Devic disease.¹⁹
• Generally, mild myopathy or polyneuropathy may be treated with NSAIDs and other symptomatic medications (eg, anticonvulsants, tricyclics, other medications used for neurogenic or musculoskeletal pain). Symptoms may be caused by medications (eg, steroids, antimalarials) or other etiologies in addition to SLE. If alternative explanations are unlikely and symptoms are more bothersome, low-to-medium dose prednisone may be tried, possibly with a longer-term transfer to antimalarial therapy.
• If a patient with SLE presents with acute polyradiculopathy resembling Guillain-Barré syndrome or chronic relapsing polyradiculopathy resembling chronic inflammatory demyelinating polyneuropathy, treatment with IV immunoglobulin (IVG) in conventional doses should be considered. When IVG is unavailable or poorly tolerated, plasma exchange should be considered as an alternative. Unfortunately, few therapeutic studies exist on these rare presentations of SLE.
• Seizures are common sequelae of SLE and may result from acute or chronic disease. Acute electrolyte disturbance, response to high-dose steroids, or other acute disturbance may only require temporary anticonvulsant treatment, while more chronic epileptogenic foci may require lifetime prophylaxis. Anticonvulsants may be used in a conventional fashion, emphasizing medications most effective for focal onset or secondarily generalized seizures. Phenytoin and other agents associated with drug-induced lupus are unlikely to actually increase disease activity in SLE, but with chronic use may cause diagnostic confusion for physicians.
• Treatment of the antiphospholipid syndrome remains controversial, with therapy based predominantly on anecdotal experience. Although many authorities recommend full anticoagulation with warfarin (Coumadin) (although there is no randomized clinical trial to prove this), other authorities support antiplatelet therapy initially, with stronger measures reserved for repeated stroke, progressive myelopathy, or other clear-cut, clinical treatment failure. It is clear that aiming for an INR of 2.0–3.0 is as good as at reducing the risk of further events than more intensive anticoagulation.²⁰  This could be done possibly in conjunction with immunosuppressant therapy to suppress production of the antibody.   

Cerebral lupus, like the neurological vasculitides, is best managed jointly by neurologists, clinical immunologists, renal physicians, rheumatologists and the primary physicians.

For a CME activity, see Systemic Lupus Erythematosus: From the Clinic to New Treatments.

Consultations

• Generally, new-onset SLE diagnosed based on neurologic symptoms should be managed in conjunction with a rheumatologist or internist.
• If neurologic signs or symptoms present in a patient with SLE that is well established, the need for additional consultations beyond the treating internist or rheumatologist is determined by the presence and severity of concomitant organ disease. For example, in patients with severe lupus nephritis, renal consultation may be needed for initiation of hemodialysis.

Diet

A special diet may be required for renal, cardiac, or SLE complications but is generally not required for the neurologic aspects of SLE.

Activity

• The usual activity restrictions (eg, driving, operating machinery, swimming) that apply to patients with seizures apply to patients with SLE who have seizures.
  • Regulations for driving vary by state in the United States.
  • Recommendations may be tailored to the individual based on frequency, seizure type, duration of aura (if any), and concomitant morbidity (including dementia or psychosis).
• Activity restrictions also may apply to patients with organic brain impairment in the absence of seizures or to patients with myelopathy, visual disturbance, or neuromuscular syndromes.

Medication

The goal of therapy is to suppress the autoimmune activity.

Immunosuppressants

Used for disease modification and reduction of organ-threatening or life-threatening damage. Often needed on acute and chronic bases, these drugs should be used by physicians who are familiar with their use and potential complications (eg, opportunistic infections and common adverse effects).

Methylprednisolone (Solu-Medrol)

For the most acute or severe manifestations of CNS or PNS disease.

Prednisone (Deltasone, Sterapred)

Used for acute CNS or PNS disease that is not deemed sufficiently dangerous to warrant acute IV methylprednisolone. Also used to follow IV therapy for a gradual outpatient taper.

Cyclophosphamide (Cytoxan, Neosar)

This antineoplastic agent is used acutely for life-threatening symptoms, generally in combination with IV corticosteroids.
Various PO and IV protocols exist for long-term management of active disease.
Physicians who are comfortable in follow-up of this agent should manage patients.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Methotrexate (Folex, Rheumatrex)

Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Satisfactory response seen in 3-6 wk following administration.

Antimalarial

Used as alternative to steroids or as supplements to accelerate steroid taper.

Hydroxychloroquine (Plaquenil)

Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

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