Once triggered, SLE's autoimmune reaction affects many sites through multiple mechanisms such as deposition of immune complexes, effects of cytokines and other chemical neuromodulators, direct attack by autoantibodies or activated leukocytes, and others.
Non-neurologic sites of damage include the renal glomeruli, joints, pleural or pericardial serosa, integument, cardiac or vascular endothelium, cardiac valves, and the oral and conjunctival mucosa. Multiple sites may be involved within the nervous system.
Medical Care
Treatment of 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.
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.
Various steroid-sparing strategies have evolved for chronic 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.
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.
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 patient presents with acute polyradiculopathy resembling Guillain-BarrΓ© 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 Coumadin (warfarin) possibly in conjunction with immunosuppressant therapy to suppress production of the antibody, other authorities support antiplatelet therapy initially, with stronger measures reserved for repeated stroke, progressive myelopathy, or other clear-cut, clinical treatment failure.
DRUG THERAPY : The goal of therapy is to suppress the autoimmune activity.
1. 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
- PREDNISONE
- CYCLOPHOSPHAMIDE
- AZATHIOPRINE
- METHOTREXATE
2. ANTIMALARIAL : USED AS ALTERNATIVE TO STEROIDS OR AS SUPPLIMENTS TO ACCELERATE STEROID TAPER.
- HYDROXYCHLOROQUINE ( HCQS )