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Systemic lupus erythematosus (SLE) is a potentially lethal, chronic autoimmune disease that can involve the eye. It is characterized by the production of numerous autoantibodies, some of which are pathogenic. Retinal vasculitis is the most serious of ocular manifestations; it is potentially blinding and associated with a decreased survival rate.1,2Immunosuppressive therapy is the mainstay of treatment3but plasmapheresis can be helpful acutely by rapidly removing circulating immune complexes and immune reactants while the patient is receiving immunomodulators. We present 2 cases of severe retinal vasculitis due to SLE that were treated successfully with a combination of plasmapheresis and immunosuppression.
Case 1. A 54-year old white woman was admitted because of renal failure and changes in mental status. A month earlier the patient had complained of decreased vision in both eyes and was diagnosed as having “retinal lesions” by her ophthalmologist. On admission, findings from the medical examination revealed pericardial effusion, rash, arthritis, and pancytopenia. The visual acuity was 20/50 OD and 20/70 OS and indirect ophthalmoscopy disclosed bilateral occlusive retinopathy (Figure 1).
Case 1. Fundus photograph of the right (A) and the left eyes (B) at examination show multiple cotton-wool spots and dot/blot hemorrhages in the posterior pole, bilaterally.
Systemic lupus erythematosus, polyarteritis nodosa, Wegener granulomatosis, and sepsis were included in the differential cell count. Sepsis was excluded following multiple blood cultures negative for organisms, and intravenous methylprednisolone acetate (1000 mg/d) was administered for 3 days. The patient responded with slight overall improvement, but her condition deteriorated after discontinuation of the steroid therapy. Immunosuppressive treatment was deferred because of pancytopenia with agranulocytosis seen on bone marrow biopsy specimens. Therefore, therapy with intravenous methylprednisolone acetate (80 mg/d) was reinstituted in combination with intravenous immunoglobulin (200 mg/kg per day) for 5 days. The patient's mental status deteriorated further and brain vasculitis was disclosed on magnetic resonance imaging. The visual acuity dropped to 20/65 OD and 20/100 OS and dyspnea developed; pulmonary hemorrhage was discovered. However, the pancytopenia improved and a single intravenous infusion of cyclophosphamide (750 mg) was added to the regimen. No improvement was noted. The results of blood tests revealed high levels of antinuclear antibodies, soluble interleukin 2 receptors, circulating immune complexes, and decreased C3 complement levels. The diagnosis of SLE was proposed based on the clinical symptoms and these laboratory findings. Plasmapheresis was administered for 5 days followed by a single intravenous infusion of cyclophosphamide (750 mg). The patient's overall medical status improved dramatically. She became capable of fluent communication, her creatinine levels decreased rapidly, and the visual acuity improved to 20/30 OD and 20/40 OS. One month after admission, the patient was discharged with the recommendation for monthly treatment with intravenous cyclophosphamide that was never implemented. The patient died of cardiac tamponade in a local hospital 3 months later.
Case 2. A 30-year-old Asian woman was referred owing to bilateral retinopathy that was progressive despite the use of high-dose intravenous and oral steroid therapy. Three months prior to her hospital admission, the patient was diagnosed as having SLE, which had manifested as arthritis, malar rash, and anemia. She was initially treated with hydroxychloroquine sulfate (200 mg/d). Two months later the patient developed profound bilateral loss of vision and retinal vasculitis was diagnosed. Treatment with intravenous methylprednisolone acetate (1000 mg/d) for 3 days followed by oral prednisone (60 mg/d) was administered, but the vision deteriorated further. When we examined her, her visual acuity was 20/400 OD and 20/200 OS (Figure 2).
Case 2. Fundus photographs of the right (A) and left eyes (B) at examination. Note the bilateral disc pallor (+1) and multiple retinal infarcts with cotton-wool spots and intraretinal hemorrhages in the posterior pole, more prominent in the peripapillary area.
The patient was admitted and treatment with oral methotrexate (15 mg weekly) was initiated in combination with plasmapheresis daily for 3 days and then once weekly for another 5 weeks. At the end of the third week of treatment visual acuity had improved to 20/80 OD and 20/40 OS. The dose of methotrexate was increased to 25 mg/wk; the prednisone therapy was reduced to 50 mg/d. Slow prednisone tapering continued and the patient did well for another 3 weeks, but then her visual acuity decreased to 20/400 OD and 20/200 OS. A fluorescein angiogram disclosed active, bilateral retinal vasculitis (Figure 3). The dose of methotrexate increased to 30 mg/wk and prednisone tapering continued.
Case 2. Late frames of the fluorescein angiography of the right (A) and left eyes (B) show excessive leakage of both arteries and veins throughout the macula and extensive areas of drop-out in the choriocapillaris.
On the patient's most recent follow-up examination, 10 months after her initial visit with us, the patient was no longer receiving treatment with prednisone but was taking methotrexate (25 mg/wk) and hydroxychloroquine (200 mg/d). Her visual acuity had stabilized to 20/125 OD and 20/30 OS (Figure 4).
Case 2. Fundus photographs of the right (A) and left eyes (B) 10 months after examination. Note the sheathing of the arteries and the optic disc pallor in the right eye. Some residual intraretinal hemorrhages and cotton-wool spots in the left eye indicate low-grade ongoing vasculitis.
Retinal vasculitis has the worst systemic and visual prognosis of all ocular manifestations of SLE. Approximately 88% of patients with retinal vasculitis have active systemic disease4and 50% end up with a visual acuity less than 20/200.2The survival rate of these patients is significantly decreased compared with patients with SLE who do not have retinal involvement.1,2
Close follow-up and preemptive treatment of SLE patients with retinal vasculitis is imperative even if the findings on first examination suggest that the underlying disease is “in remission.” Serologic markers of vasculitis should be monitored since they may indicate impending clinically important systemic disease. Effective control of the disease activity is associated with a decrease in retinal lesions and usually requires a combination of agents.
Acute exacerbation of SLE, as it was the case with our patients, is usually treated with a combination of high-dose steroids and an immunosuppressive agent. Therapy with intravenous cyclophosphamide is the agent best studied for SLE. Intravenous immunoglobulin has also proven to be beneficial in selected patients. The role of methotrexate in the treatment of SLE remains unproven, but its safety record makes it an attractive alternative, especially for the control of some steroid-refractory manifestations of SLE.3
Plasmapheresis could, by rapidly removing circulating immune complexes, provide acute relief in the severely ill patient in whom cyclophosphamide is not effective (case 1) or is undesirable (case 2). However, it could not have a lasting therapeutic effect unless it is combined with an immunosuppressive agent to retard the re-accumulation of immune complexes.
Although randomized controlled clinical trials failed to document a generalized benefit of plasmapheresis when added to standard immunosuppressive therapy, patients with SLE who are in crisis seem to benefit from the concomitant use of plasmapheresis with systemic prednisone and sequential intravenous cyclophosphamide.5
To the best of our knowledge, this is the first report of patients with SLE retinal vasculitis who were successfully treated with a combination of plasmapheresis and immunosuppressive chemotherapy.
Correspondence: Dr Foster, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research & Surgery Institute, Eighth Floor, 5 Cambridge Center, Cambridge, MA 02142 (email@example.com).
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by a grant from the Embeirikeion Foundation (Drs Papadaki and Zacharopoulos) and the Manasaki Scholarship of the University of Crete, Greece (Dr Papadaki).
Papadaki TG, Zacharopoulos IP, Papaliodis G, Iaccheri B, Fiore T, Foster CS. Plasmapheresis for Lupus Retinal Vasculitis. Arch Ophthalmol. 2006;124(11):1654–1656. doi:10.1001/archopht.124.11.1654