the next incremental dosage available orally, 500 mg/day, puts dosing into the toxic range for patients weighing less than 125 kg. [61]

General Management

The three major classes of drugs used in treating SLE are nonsteroidal anti-inflammatory agents, corticosteroids, and nonsteroidal immunosuppressive agents [62]. Nonsteroidal antiinflammatory agents (including aspirin) and antimalarials (usually hydroxychloroquine, Plaquenil 200–800 mg/day) are useful for nonspecific manifestations of disease such as fever, arthralgias, arthritis, and serositis. Systemic corticosteroids are used orally (prednisone 1–2 mg/kg/day) and intravenously (methylprednisolone 1–2 g/day for 3–6 days) for major organ involvement and for hematological complications such as hemolytic anemia and thrombocytopenia. Immunosuppressive drugs, especially azathioprine, are used when life-threatening complications of lupus are unresponsive to corticosteroids. Cyclophosphamide, chlorambucil, nitrogen mustard, methotrexate, and cyclosporine A have also been employed in the treatment of SLE.

The development of new drugs for systemic SLE such as mycophenolate mofetil, abatacept, rituximab, abetimus, and belimumab, among others, has also been tested, and there seem to be new therapeutic approaches that appear rational and likely to target important mechanisms of autoimmunity and inflammation. Plasmapheresis can reduce levels of circulating immune complexes and antibodies [62]. Hemodialysis and renal transplantation are used in lupus patients who have renal failure. Thrombotic events associated with antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) are often treated with oral anticoagulants, though no treatment exists that is consistently effective for this major lupus-associated complication. Anticoagulation may prevent recurrent thrombosis, and there is a recognized tendency for rebound thrombosis if anticoagulation therapy is stopped. Cutaneous lesions may respond to topical or intralesional steroids, antimalarials, systemic steroids, immunosuppressives, topical or systemic

steroids, topical or systemic retinoids, or oral gold. Sunscreens are useful in preventing photosensivity skin eruptions.

Appropriate therapy for specific complications of SLE is also important and may include antihypertensive agents for lupus-induced hypertension and antibiotics for infections in these immune-compromised patients. Varying combinations of drugs and other modes of therapeutic intervention have dramatically improved the prognosis for SLE patients.

Since the ocular complications of SLE are generally associated with active disease elsewhere in the body, control of the systemic disease may lead to resolution of ocular manifestations. Systemic steroids with or without immunosuppressive agents have been used in the treatment of lupus optic neuropathy, choroidopathy, orbital inflammation, and pseudotumor cerebri [30, 42]. Simultaneous control of any associated systemic hypertension is also important. Treatment of the sequelae of retinal vascular occlusive disease has generally been limited to local ocular measures. Retinal neovascularization responds to scatter laser photocoagulation in a manner similar to that observed in diabetic retinopathy, retinal vein occlusion, and other retinal neovascular disorders [63–65]. Anterior segment ischemia has been observed as a complication following laser treatment in a patient with SLE [65]. Vitrectomy and scleral buckling may be required for cases involving vitreous hemorrhage or retinal detachment.

Controversies and Perspectives

Systemic lupus erythematosus is a chronic, immunological disorder that may affect multiple organ systems. The etiology of this disease continues to be unclear. In recent years, new therapeutic modalities have led to some improvement in morbidity and mortality.

Ocular manifestations are not included among the 11 diagnostic criteria of lupus, and the inclusion of ocular lesions among these criteria would lead to earlier diagnosis and therapeutic intervention in those instances. Their presence should alert the clinician to the likely presence of extraocular disease activity [17, 30, 63–65].

Severe retinal arterial occlusive disease [63–65] and lupus optic neuropathy [42, 66] have been particularly associated with CNS lupus. Lupus choroidopathy [30] (or other ocular complications) may coexist with widespread systemic vascular disease. All patients with ocular lupus should be carefully evaluated by a rheumatologist for potentially treatable and preventable complications of the disease.

Focal Points

General diagnosis of SLE (see Table 18.1), using the analogy of the American Rheumatism Association (ARA) criteria for the diagnosis of rheumatoid arthritis, suggests that patients be classified as follows:

1.Classical SLE—many criteria

2.Definite SLE—4 or more criteria

3.Probable SLE—3 criteria

4.Possible SLE—2 criteria (of the patients with probable or possible SLE, some experience resolution of symptoms, some evolve into another illness, and a few develop SLE)

•When you get a positive ANA, order an ANA profile, which should include anti- double-stranded DNA, anti-Smith, antiSSA and anti-SSB, and anti-RNP.

•Anti-dsDNAand anti-Sm are virtually 100% (96–100%) specific for SLE (they are ONLY positive in patients with SLE). However, their sensitivity is not as good—52% for Crithidia anti-dsDNAand 73% for Farr antidsDNA, and 18–31% for anti-Smith.

•IfANAisnegativeandclinicalsignsstrongly suggest SLE, check for anti-SSA(Ro) antibodies. If this is positive, the patient probably has “ANA-negative” SLE (rare). As many as 62% of patients with “ANAnegative” SLE have anti-SSA antibodies.

•Complement levels can also be helpful diagnostically—total serum hemolytic complement (CH50) and individual complement components (C3 and C4) may be low in patients with active SLE due to the presence of immune complexes: low sensitivity (40%) but high specificity (90%).

Acknowledgments The authors have no proprietary or financial interest in any products or techniques described in this chapter.

Supported in part by theArévalo-Coutinho Foundation for Research in Ophthalmology, Caracas, Venezuela.

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