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Retinopathy in systemic lupus erythematosus. A case report and review of the literature

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Retinopathy in Systemic Lupus Erythematosus
A Case Report and Review of the Literature
Frederic Bishko
Retinal lesions occur frequently in systemic lupus erythematosus, however, they
rarely cause visual impairment. A patient btinded by severe lupus retinopathy is
described, and the pertinent literature is reviewed.
Systemic lupus erythematosus not infrequently causes retinopathy (1-4). Subsequent visual impairment, however, is not
common and blindness due to lupus retinopathy is rare (2). Clinically observed retinal lesions include cotton wool exudates
in 9 4 4 % of cases (2, 3, 5) and superficial
flame-shaped, or preretinal hemorrhages in
about 10% (6). Less common are retinal
arteritis and phlebitis, which when severe
may lead to perivascular sheathing and
fibrosis (7). Papilledema with optic atrophy and retinal detachment are seen only
rarely and most often terminally (6,7).
Severe retinopathy was more commonly
seen in the presteroid era and, at present,
occurs most frequently in patients whose
generalized lupus activity has not been well
controlled. It is of interest then to report a
case of probable lupus erythematosus in
which the eyes were involved early in the
course and were the organs most severely
affected by the disease process.
From the Rheumatic Diseases Study Group, Department of Medicine, New York University Medical Center, 550 First Avenue, New York, NY 10016.
Supported by US Public Health Service Training
Grant AM05064.
Reprint requests should be addressed to: Dr.
Frederic Bishko, Hawthorn Medical Associates, Inc,
570 Hawthorn St, North Dartmouth, Mass 02747.
Submitted for publication Mar 12, 1971; accepted
May 25, 1971.
T h e patient was a 23-year-old black woman, well
until one month prior to admission when she
developed a malar eruption, anorexia, weight loss,
malaise, myalgias, low grade fever and fatigue. She
denied a history of arthritis, chest pain, headaches,
abdominal pain or change in bowel habits. She had
used oral contraceptives for three years prior to the
onset of her illness.
Initial examination revealed a thin black woman
in minimal physical distress, with a blood pressure
of 110/60 mmHg, regular pulse of 84, and oral
temperature of 101°F. Other pertinent findings
included a discoidal skin eruption i n a malar
distribution; medullated nerve fibers in the left eye;
bilateral, tender, easily movable 3 X 3 cm axillary
lymph nodes, and several small petechiae on the
right foot.
Laboratory findings included a persistent pancytopenia with WBC of 2,800-3,500/cu mm, hematocrit
of 33-38%, and platelet counts between 75,000 and
160,OOO/cu mm. ESR on multiple occasions was between 55-110 mm/hr. Urinalyses showed 3-25
WBC/hpf, 3+ proteinuria, occasional RBCs and no
casts. A 24-hour urine contained 600 mg of protein.
Total serum protein was 8.2 8% with an albumin
of 3.4 g%. Serum protein electrophoresis showed a
nonspecific y globulin elevation. Antinuclear antibody (using mouse liver as the substrate), was 4+
with a speckled pattern, LE preparations were
negative X 5, serum complements were 173 and 186
hemolytic units (normal greater than 150 hemolytic
units) : latex fixation test was negative. Serum
electrolytes, CO,, fasting blood sugar, creatinine
clearance, SGOT, SGPT, Ca and P were normal.
Serology was nonreactive and the EKG was within
normal limits. T h e chest X-ray demonstrated mini-
Arthritis and Rheumatism, Vol. 15, No. 1 (January-February 1972)
ma1 to moderate linear streaking in the right lower
lung field.
Bone marrow examination revealed a normocellular marrow with adequate megakaryocytes, and
normal maturation of the RBC and WBC series.
Myeloid/erythroid ratio was 4/1. On a simultaneous
peripheral smear the RBC were normochromic with
minimal anisocytosis. White blood cell morphology
and a differential count were normal. Platelets were
reduced with many large forms. Antiplatelet antibodies were not present. Coombs test, both direct
and indirect was negative and blood viscosity was
normal. Microcirculatory studies performed by Dr.
Walter Redisch demonstrated “meandering of the
capillary loops with dilatation, RBC aggregation
and extravisation, compatible with SLE.” A diagnosis of SLE was made on December 26, 1969 and the
patient was started on 30 mg of prednisone daily in
hopes of suppressing disease activity manifested by:
skin eruption, fever, myalgias and pancytopenia.
T h e patient was seen by the Ophthalmology Service
on December 30, 1969 for symptoms of blurring of
vision in the right eye and frontal headaches. At
that time, she had 20/20 vision OU. Funduscopic
examination showed only the medullated nerve
fibers previously mentioned. However, repeat funduscopic examination on January 9, 1970 revealed
the following: OD-the foveal reflex was absent, the
disc was normal, there were occasional superficial
exudates, extensive deep edema of the posterior
pole, and scattered superficial hemorrhages. Arteriolar spasm and venous stasis were als6 noted.
OS-there were scattered superficial perivenous hemorrhages. Vision OD was 20/80 and OS 20/100.
Fluorescein photography of the right retina on
January 16, demonstrated poor perfusion of the
capillary bed with large areas of non-perfusion
around the optic disc, compatible with small arteriole (precapillary arteriole) occlusion. T h e veins
showed marked stasis with segmentation of the
fluorecein column in the venous lumen and some.
late extravasation of dye. These studies and simultaneous retinal photographs (Fig 1) presumably
indicate involvement of the entire retinal circulatory system with arteritis, arteriolar occlusion and
secondary venous stasis.
T h e patient’s prednisone was increased to 80 mg
daily for two days and then decreased to 30 mg
daily because there was no improvement and the
feeling by some that steroids could be, in part,
responsible for the severe retinal lesions. Low
molecular weight dextran, 500 ml daily, given
intravenously over three to four hours, was added
to the treatment regimen for 10 days without effect.
T h e patient remained stable except for progression of her retinopathy (Fig 2) until February 1,
1970 when she had a grand ma1 seizure. Lumbar
puncture revealed normal opening and closing
pressures and normal cerebiospinal fluid protein
and glucose. All cultures including those for fungi
were negative. T h e patient’s prednisone was increased to 120 mg daily for fourteen days and then
tapered to 65 mg daily over one month. Her vision
continued to deteriorate and by February 21, 1970
she was capable only of light perception. Funduscopic examination a t that time revealed bilaterally
pale discs, posterior pole edema, sheathing of the
veins and perivenous flame-shaped hemorrhages in
peripapillary areas (Fig 3). On March 5 , 1970 the
patient was transferred to Johns Hopkins Medical
Center to be closer to her family. At the time of
transfer, funduscopic examination showed further
evolution and healing of the patient’s retinal lesions
(Fig 4 ) . All other evidence of lupus activity had
regressed. Her blood pressure had remained normal
throughout her hospital stay.
T h e patient described presented with
fever, myalgias, weight loss, malar eruption
and petechiae. While hospitalized she developed retinal vasculitis and had a grand
ma1 seizure. Her pertinent laboratory results included: pancytopenia, hyperglobulinemia,
studies, and a strongly positive, though
nonspecific ANA. She did not have a positive LE preparation nor depressed serum
complement levels. While a definitive diagnosis of systemic lupus erythematosus cannot be made, it is felt that clinically, the
patient’s findings are consistent with that
diagnosis. Although work from this and
other institutions have shown that most
patients with SLE have a positive LE
preparation and peripheral pattern ANA
during periods of clinical activity (8-1 l),
this serologic data is not a prerequisite for
diagnosis. Kay and Tuffanelli, using immunofluorescent staining of skin biopsies have
demonstrated changes consistent with systemic lupus erythematosus in patients with
the clinical syndrome but without a posi-
Arthritis and Rheumatism, Vol. 15, No. 1 (January-Februav 1972)
Fig 1. January 16, 19704D-The disk is normal, there is inflammatory perivenous sheathing and
blotchy flame-shaped superficial hemorrhages along the course of the veins in the posterior pole. The
arterioles are narrowed in an irregular manner. There is deep retinal edema of the posterior pole.
tive ANA or LE prep (12). And we are
currently following five patients ,in our
Lupus Clinic with the diagnosis of systemic lupus who have never had a positive LE
preparation or peripheral pattern ANA.
Other causes for retinal vasculitis in this
patient were ruled out. She was not hypertensive at any time during her hospitalization, her lipid profile was normal, and her
fasting blood glucose was consistently below 100 mg%. Central retinal artery and
central retinal vein occlusion were not seriously considered because of the widespread
involvement of the retinal circulatory system.
It is interesting that the patient had been
taking oral contraceptives for three years
prior to the onset of her illness. A number
of neuro-ophthalmologic side effects have
been associated with oral contraceptives.
These include vascular headaches, cerebrovascular accidents, pseudotumor cerebri,
central retinal artery occlusion, central retinal vein occlusion, neuritis, and cranial
nerve palsies (13). Symptoms have a p
peared in some women within the first
week of treatment and in others only after
years of therapy. Walsh reviewed postmortem material from young women who had
taken oral contraceptives and died from
cerebrovascular accidents. He found the
major lesion to be arterial thrombosis (14).
Arthritis and Rheumatism, Vol. 15, No. 1 (January-February 1972)
Fig 2. January 26, 1970-OD-There
peripheral temporal area.
is a marked increase in periarteriolitis and periphlebitis in the
I n one case there was inflammation in the
media of the involved arterial wall but no
evidence of necrotizing vasculitis or
perivasculitis (15). I n experimental work
in owl monkeys given Norethynodrel, Kulvin demonstrated retinal vein dilatation
which was often dose dependent. He was
not able to demonstrate hemorrhages or
papilledema (16). T o date there have been
no reported cases of retiha1 vasculitii associated with oral contraceptives similar to
the type experienced by our patient.
Inflammatory lesions of small arteries
and veins are among the most common
pathologic findings in systemic lupus erythematosus ( 2 4 ) and account for many
clinical manifestations of the disease. It is
difficult to discern the incidence of retinal
vasculitis in the present day lupus population since many of the patients have complicating hypertension and/or renal insufficiency which can produce a similar
retinopathy. These conditions were absent
in our patient.
Vascular lesions in the eye are similar to
those found in other parts of the body.
Intimal and medial thickening of the retinal vessels as well as deposition of
fibrinoid material cause varying degrees of
obliteration in both the superficial (17)
and deep nerve fiber layers (17, 18). With
severe vascular involvement there is both
Arthritis and Rheumatism, Vol. 15, No. 1 (January-February 1972)
Fig 3. February 21, 1970-OLLThe disk is now pale. The arteries are reduced to fibrotic threads and
there is now a more regular sheathing of the veins. Deep retinal edema is still present and new retinal
hemorrhages are seen.
focal and widespread necrosis associated
with a cellular infiltrate made u p mostly of
lymphocytes and plasma cells. Degenerative changes in the ganglion cell and
internuclear layer are not uncommon ( I ,
Recently, retinal lesions in three patients
with lupus erythematosus were studied
with the aid of fluorescein photography
(18). Obstructive changes in the posterior
retinal arterioles with secondary delay in
venous filling, retinal edema, cotton wool
exudates, and hemorrhages were found.
Retinal fluorescein photography carried
out on our patient on January 16, 1970,
demonstrated similar lesions. I n the inter-
val between January 16th and January 26,
when followup retinal photographs were
taken, the patient’s lesions had progressed
so markedly that it was impossible to make
any definitive statements as to their evolution. In a period of two weeks the patient’s
vision had gone from normal to OD 20/80,
0s 20/100 and within a few more days, the
patient was blind. Her vision is unimproved at the present time (20).
Systemic lupus erythematosus is a systemic disease and by virtue of its pathophysiology may affect a variety of organ systems.
T h e patient reported here had widespread
vasculitis. Lupus vasculitis, especially
when involving the central nervous system
Arthritis and Rheumatism, Vol. 15, No. 1 (January-February 1972)
Fig 4. March 13, 197O-OD-There is minimal resolution of the edema and an increase of arterial and
venous fibrosis.
can be rapidly fatal and i t is imperative
that appropriate therapy be initiated
quickly. Doses of corticosteroids or other
immunosuppressive agents sufficient to s u p
press disease activity may have altered the
prognosis of o u r patient.
Trans Amer Ophthal Soc 44:166-186, 1946
2. Dubois EL: Effect of the LE cell test on
the clinical picture of the systemic lupus
The author is indebted to Dr. Paul Rutkowsky of
the Retinal Clinic, Department of Ophthalmology,
New York University Medical Center who did the
retinal and fluorescein photography on our patient,
and Drs. Munro Levitsky, Ronald Carr and Edward
C. Franklin, who graciously reviewed this paper.
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acute disseminated lupus erythematosus.
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Harvey AM, Shulman LE, Tumulty P, et
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lupus, report, retinopathy, literatury, systemic, erythematosus, case, review
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