Bilateral Choroidal Occlusion in Antiphospholipid Syndrome Associated with Systemic Lupus Erythematosus

Yang Zhang, Shunhua Zhang, Ailing Bian, Youxin Chen＊

Department of Ophthalmology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China

Bilateral Choroidal Occlusion in Antiphospholipid Syndrome Associated with Systemic Lupus Erythematosus

Yang Zhang, Shunhua Zhang, Ailing Bian, Youxin Chen＊

Department of Ophthalmology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100730, China

anticardiolipin antibodies; antiphospholipid antibodies; choroidal vessels;systemic lupus erythematosus

This article reports a rare case of bilateral choroidal occlusion that occurred in a 24-year-old woman with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE). This young lady concurred with aorta ventralis thrombosis and bilateral iliac artery occlusion when presented, and experienced a rapid deterioration of vision. She also has a history of recurrent miscarriage. Corticosteroid,immunosuppression and anticoagulation therapy were administered. Patients with APS associated with SLE are at risk for thrombotic phenomena, which may affect the ocular vessels of all sizes, including choroidal vessel.Our case alerts ophthalmologists and rheumatologists that bilateral choroidal occlusion may indeed be developed in patients with APS associated with SLE, and is a potential cause of visual morbidity.

A NTIPHOSPHOLIPID syndrome (APS) is an autoimmune disease with moderate to high levels of antiphospholipid antibodies (aPL) in the blood.It’s main clinical characteristics include arterial and venous thrombosis and recurrently spontaneous abortion.1APS may occur primarily in the absence of systemic disease, or accompany with a known systemic autoimmune disease, such as systemic lupus erythematosus (SLE).2,3In the current paper, we report a rarecase of bilateral choroidal occlusion as a complication of APS associated with SLE in a woman.

CASE DESCRIPTION

A 24-year-old female was referred to our clinic,complaining of bilateral progressively reduced visual acuity in the past 2 months. The patient had been suffering from general fatigue, inappetence and intermittent fever for 3 months, and went to see rheumatologists prior to the presence at our clinic. She had no history of malar or discoid rash, no history of photosensitivity, arthralgias, or Raynaud’s phenomenon. She had an experience of four miscarriages for unknown reason.

Clinical work-up was conducted for diagnosis. Laboratory investigation (Table 1) revealed prolonged prothrombin time (PT) and activated partial thromboplastin time(APTT). Antinuclear antibodies (ANA) was 1:80, Coombs test was positive. Levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anticardiolipin antibody (aCL),and the antibody titer to β-2-glycoprotein 1 (β2GP1) were elevated. Complement levels of C3 and C4 were reduced.Thrombocytopenia was present with an extremely low count of platelet (11×109/L). Analyses for anti-doublestranded DNA (anti-dsDNA) antibodies, anti-neutrophil cytoplasmic antibodies with cytoplasmic staining pattern(c-ANCA) and with peripheral staining pattern (p-ANCA),rheumatoid factor, anti-Ro (SSA) and anti-ribonucleoprotein were all negative.

Contrast enhanced abdominal CT revealed thrombosis in aorta ventralis and bilateral iliac arteries. There was no evidence of deep vein thrombosis or pulmonary embolism.No abnormity was found in chest CT, brain MRI, carotid Doppler sonography and colonoscopy.

The best-corrected visual acuity was 40/200 OD and counting fingers OS. Binocular Goldmann applanation intraocular pressures were 10 mmHg OD and 8 mmHg OS.Examinations of cornea, anterior chamber and lens were unremarkable. Clear vitreous was present. Bilateral pupils were equal in diameter with good direct and indirect reactions. Fundus examination revealed slightly pale optic discs. Multifocal choroidal infarction was bilaterally widespread, and choroidal atrophy was seen in all quadrants of both eyes. There were a few retina folds at the posterior pole of the left eye, with macular involvement. Retinal pigment epithelium atrophy in the areas of infarcted choroid was shown. No vasculitis or periphlebitis was found (Fig. 1).

Fluorescein angiography showed normal perfusion of retinal vessels in the early stage, and hypofluoresence in the areas of choroidal infarction; in the late stage,hyperfluoresence was present in the areas around the choroidal infarction and the left foveolar avascular zone(Fig. 2). The indocyanine green angiography (ICGA) of both eyes revealed large wedge-shaped and lobular areas of hypofluorescence corresponding to the location of choroidal non-perfusion lesion (Fig. 3). Optical coherence tomography (OCT) revealed that the thicknesses of bilateral choroid，especially in areas of choroidal infarction,reduced distinctly (Fig. 4).

Table 1. Results of laboratory examination of a 24-year-old patient with APS associated SLE

Figure 1. Fundus photography of both eyes.

Figure 2. Fluorescein angiography (FA) of both eyes.

Figure 3. Indocyanine green angiography (ICG) of both eyes.

Figure 4. Optical coherence tomography (OCT) of the non-perfused choroid.

According to the results of above examinations, the diagnosis of APS associated with SLE was established.The patient had not been on anticoagulation therapy or any other offending medications prior to the consultation.Anticoagulant treatment, corticosteroid and immunosuppression were then given. Antico-agulation therapy began with intravenous heparin 0.4 ml once a day for 10 days, followed by oral warfarin 5 mg once a day, for the purpose of preventing from further vaso-occlusion.Intravenous pulsed methyl-prednisolone was followed by oral corticosteroids and cyclophosphamide therapy.

After 4 weeks of therapy, the best-corrected visual acuity recovered slightly to 60/200 OD and 20/200 OS.However, the fundus appearance did not improve signifi-cantly. The six-month follow-up showed no further visual acuity improvement.

DISCUSSION

The diagnosis of this patient, APS associated with SLE,was established according to American College of Rheumatology classification criteria and the strict diagnostic criteria established in 1998 at the International Symposium on antiphospholipid antibodies in Sapporo, Japan.4

APS is an autoimmune disorder characterized by arterial or venous thrombosis, which can affect any organs,and develop systemic and cerebral thromboembolism, with the results of deep vein thromboses, pulmonary emboli,myocardial infarction, cerebral stroke and increase of miscarriage rate.5-7

APS could be a primary pathogenesis, or secondary to some systemic autoimmune diseases, such as SLE. The clinical features of SLE vary, with musculoskeletal and cutaneous disorders being the most common. Both APS and SLE have a high frequency of ocular involvement,which even may be the initial manifestation of the disease.8,9Generally, the anterior segment is not likely to be involved. The most common ocular findings are optic neuropathy and retinopathy that are due to ocular vessel disorder, such as anterior ischemic optic neuropathy,vessel obstruction and capillary non-perfusion, and are always correlate with the activity of SLE disease.

Retinal vascular occlusive diseases have been documented in patients with APS or SLE. Although vascular occlusion can occur in any part of retinal vessels, choroidal vessel occlusion is rare. Very few reports have described choroidopathy in primary antiphospholipid syndrome and SLE.10,11Retinopathy in SLE always manifests as a benign form, which has been attributed to immune complexmediated vasculitis, and the prognosis of vision deterioration in most cases is favorable. However, the most common ocular feature of APS is vaso-occlusive retinopathy, where the histology of the lesion is thrombosis. We proposed that the ocular symptoms of our patient were caused by vascular thrombosis secondary to APS rather than vasculitis from SLE.

Meanwhile, the clinical features of ocular involvement seem to be different between primary and secondary APS.Ocular vasculopathy is the typical manifestation of primary APS, whereas thrombophilia is more common in APS secondary to SLE.12The latter is consistent with the characteristics of the current case.

Antibodies associated with APS include aCL, lupus anticoagulant, and antibodies directed against β2GP1.These molecules all play roles in inhibiting the coagulation cascade, promoting thrombosis, causing a hypercoa-gulable state. The characteristic feature of APS is retinal vessel occlusion, which is more common in individuals with high titer of aCL.13Several studies suggested that a moderate-tohigh titer of aCL was associated with an increased risk of thrombosis.14Our presented case had a high titer of aCL,which implied her high risk of thrombosis.

Although the exact role of antiphospholipid antibodies in the development of thrombosis is unclear, anticoagulation therapy consisting of intravenous heparin followed by oral warfarin was recommended as the initial therapy, which should be implemented as early as possible, and last for at least 6 months; otherwise, recurrent thrombosis may occur, and even develop thrombotic complications while still staying on the treatment.2

In our case, immunosuppression therapy was given for controlling SLE; meanwhile, anticoagulation therapy was performed for APS to prevent further thrombophilia and complications caused by neovascularization. However,after 4 weeks of therapy, visual acuity showed slight improvement and no change in the fundus defects. We believe that the unsatisfactory therapeutic effects may be due to that the patient did not have regular treatment during the two months of her visual loss before the diagnosis.Therefore, early diagnosis and timely treatment are important for a better prognosis in this situation.

Our case raises an alert to ophthalmologists and rheumatologists that in APS associated with SLE, bilateral vascular occlusion occurs not only in retina, but also in choroid, and both could constitute the potential causes of visual morbidity. Fundus phyfluoresce angiography is necessary to evaluate the vessels of patients with ocular symptoms. Furthermore, full thrombophilic panel work-up is strongly recommended for young patients who present occlusive ocular and/or vascular disorders, but have no conventional risk factors for thrombosis, especially when they have concomitant syndromes that are suspicious for SLE and/or APS.

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10.24920/J1001-9294.2017.049

November 18, 2016.

＊Corresponding author Tel: 86-10-69151660, E-mail: chenyouxinpumch@163.com