June 12, 2017
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Young woman who went blind in one eye presents years later with symptoms in fellow eye

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A 21-year-old Hispanic woman presented to the University of New Mexico with a 1-month history of worsening flashes of light and scotomas in her left superior field of vision.

Regarding her medical and ocular history, the patient had previously been diagnosed with a “generalized vasculitis.” When she was 14 years old, she developed joint pain in her wrists, ankles and knees. Within a week of the onset of the arthralgias, she also lost vision in the right eye and has since only seen bare light perception in that eye. She was followed by an outside ophthalmologist who told her he had seen “inflammation and a vitreous hemorrhage” in her right eye. She subsequently had a vitrectomy with no improvement in her vision. According to the patient, she had a complete systemic workup at that time that was unremarkable. Medical records provided by the patient indicated that her working diagnosis was “lupus retinal vasculitis.” However, the patient refuted this diagnosis, reporting that she had tested negative. She was followed closely by a rheumatologist who had prescribed her a high dose of methotrexate, which she was able to be weaned off within 2 years at age 16 given that she had not experienced any subsequent flares. Since that time, she had moved to Albuquerque, New Mexico, but had not re-established immediate care with a new rheumatologist.

Two months before her initial presentation, she developed recurrent joint pain but was unable to see a rheumatologist. A month later, she began to see intermittent flashes of light as well as dark areas in the superior visual field of her left eye, but the patient reported that these quickly resolved. A week later, she developed a new rash on her lower extremities, at which time her primary care physician started her on 2.5 mg of methotrexate as she was unable to establish immediate care with a rheumatologist. She became frustrated when she had no improvement so she went to an outside emergency room where she was prescribed 60 mg of prednisone 4 days before presentation. The patient again began experiencing visual disturbances in her left eye, with the flashes of light and scotomas becoming constant. At this point, she feared that she could become blind in her remaining good eye, so she presented to the University of New Mexico Emergency Department, where she was admitted for further management and workup.

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On review of systems, she endorsed mild sacroiliac joint pain and two elective abortions but denied any history of spontaneous abortion. She also reported having rashes resembling targetoid lesions on her lower extremities that had resolved before presentation. She otherwise denied oral or genital ulcers, sinusitis, hemoptysis, insect bites, nosebleeds and easy bruising.

Examination

On exam, the patient’s best corrected visual acuity was light perception in the right eye and 20/20 in the left eye. She had a relative afferent pupillary defect in the right eye; both pupils were 3 mm and the left pupil briskly reacted to light. IOP was within normal limits. She had a right exotropia on primary gaze but demonstrated full extraocular movements. Anterior segment exam was remarkable only for a dense right posterior subcapsular cataract. Otherwise, the eyes were white and quiet with no anterior chamber cells in either eye. The fundus exam in the right eye revealed extensive proliferative vitreoretinopathy and a pallid optic nerve. The fundus exam in the left eye showed extensive retinal whitening and edema along the inferior arcade with dense interspersed intraretinal hemorrhages (Figure 1). The retinal whitening extended up to the macula but appeared to spare the fovea. There was some sheathing of the inferior retinal veins as well as congestion and tortuosity of the distal retinal veins. There were no vitreous cells.

OCT of the left macula demonstrated hyperreflective band-like lesions of the middle retina indicating ischemia of the deep retinal capillary plexus. There was no intraretinal fluid or macular thickening (Figure 2). OCT cuts through the retinal whitening along the inferior arcade, demonstrating an elevated area of hyperreflectivity of the inner retina (Figure 3).

Figure 1. Fundus photo of the left eye depicting intraretinal whitening and edema along the inferior arcade with dense intraretinal hemorrhages and tortuosity of the distal inferotemporal retinal veins.

Images: Moon J, Tosi J

Figure 2. OCT of the left macula demonstrating hyperreflective band-like lesions of the middle retina but no retinal thickening or intraretinal fluid.
Figure 3. OCT cuts through the inferior retinal whitening of the left eye showing an elevated area of hyperreflectivity of the inner retina and underlying outer retinal edema partially obscured by reverse shadowing.
Figure 4. Fluorescein angiography of the left eye at 9 minutes 43 seconds with late staining of the inferotemporal veins but no obvious sites of leakage.

Fluorescein angiography of the left eye showed blockage in the area of the intraretinal whitening and hemorrhage and some delay in filling of the more distal veins but otherwise normal arterial and venous fill. At 9 minutes 43 seconds, there was late staining of the inferotemporal veins but no obvious sites of leakage (Figure 4).

Examination of the patient’s lower extremities revealed bilateral, nonpalpable, nonpainful and non-blanching petechial lesions along her ankles.

What is your diagnosis?

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Unilateral retinal vasculitis

The differential for a unilateral retinal vasculitis in a young woman in the setting of joint pain and a new rash can be categorized into infectious, inflammatory and neoplastic etiologies.

Given her medical history and current systemic symptoms, an inflammatory etiology was highest on the differential. Lupus vasculitis has been known to cause joint pain and rash, so it was high on the differential despite the fact that her previous lupus workup was reportedly negative. An ANCA vasculitis such as Wegener’s, polyarteritis nodosa and microscopic polyangiitis must also be considered. Other considerations included Behçet’s, sarcoidosis and rheumatoid arthritis.

An infectious etiology was lower on the differential but still a consideration. Given that tuberculosis, syphilis and Lyme can masquerade as the aforementioned inflammatory conditions, they must be considered. Other infectious etiologies on the differential, though with low suspicion, include toxoplasmosis and HIV.

Possible neoplastic considerations include paraneoplastic syndrome, leukemia and lymphoma. However, these were low on the differential. Given an unremarkable complete blood count with differentiation, it was decided that these would only be explored if the infectious and inflammatory workup was negative.

Diagnosis and management

After the initial ophthalmology exam, a rheumatology consult was placed immediately. A panel of labs was sent for infectious and inflammatory etiologies. Additionally, a chest X-ray was done and was unremarkable.

The ANA result was 1:160 in a speckled pattern, but this was not considered positive (positive ANA > 1:320). p-ANCA was positive, and the anti-MPO antibody was greater than 8.0 (normal < 0.09). Based on the patient’s constellation findings including recurrent joint pain, petechial rash, retinal vasculitis of the left eye, and positive p-ANCA and anti-MPO antibodies, she was diagnosed with microscopic polyangiitis.

Upon admission, she was continued on 60 mg of prednisone, and methotrexate was held. Once she was diagnosed with microscopic polyangiitis, she was started on cyclophosphamide. Before her first dose, a reproductive medicine consult was placed to discuss her options for ovarian preservation due to the well-known side effects of infertility. Cyclophosphamide can cause permanent infertility in 50% of women started on cyclophosphamide in their 20s who receive a cumulative dose of 20 g or more. She expressed interested in having children in the future and opted to have further outpatient discussions with the gynecologist.

The patient received her first dose of 850 mg of cyclophosphamide; she tolerated the medication with no side effects. She was discharged with close ophthalmology and rheumatology follow-up and plans for monthly cyclophosphamide.

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Discussion

Microscopic polyangiitis (MPA) is a rare condition. Due to overlapping features, MPA has been confused with many other diseases throughout the years. In 1994, the Chapel Hill Consensus Conference clearly delineated microscopic polyangiitis as a separate disease. The revised 2012 Chapel Hill Consensus Criteria defines MPA as a necrotizing vasculitis with few or no immune deposits and without necrotizing granulomas. This differentiates the disease from the ANCA vasculitis known as granulomatosis with polyangiitis (formerly known as Wegener’s disease), which is defined by the presence of necrotizing granulomas. MPA affects the small vessels such as capillaries, venules and arterioles.

MPA can affect any ethnic group or age. Common clinical manifestations include kidney inflammation, specifically a necrotizing glomerulonephritis, constitutional symptoms such as weight loss or fever, skin lesions, muscle and joint pains, and lung involvement. The skin lesions tend to occur in dependent areas such as the lower extremities.

Ocular involvement occurs less commonly in MPA than in granulomatosis with polyangiitis. Known ophthalmic manifestations include conjunctivitis, scleritis, episcleritis, peripheral ulcerative keratitis and retinal vasculitis. There have been a few case reports of retinal vasculitis in the setting of microscopic polyangiitis. One report described a 63-year-old man with MPA who developed bilateral scleritis and retinal vasculitis; he did well with cyclophosphamide treatment. Another report described a 57-year-old woman with MPA who developed retinal vasculitis that was refractory to cyclophosphamide but went into regression after switching to tacrolimus.

To diagnose microscopic polyangiitis, blood should be sent for all ANCA levels. The presence of both p-ANCA and anti-MPO antibodies has a sensitivity of 67% and specificity of 99%. Urinalysis should be performed frequently to monitor for the development of kidney disease. Sometimes a tissue biopsy may be necessary, but the biopsy must be taken from an involved organ.

The treatment of MPA involves starting prednisone in combination with an immunomodulatory agent such as cyclophosphamide or rituximab. This treatment is usually continued for 6 months to induce remission. The patient will then be continued on maintenance therapy.