Introduction
Ernest Goodpasture first identified Goodpastureʼs syndrome (GS) in 1919. It is a rare
disease with an estimated incidence of about 0.5 – 1 case per million per year. GS
most frequently occurs
in two age ranges, 20 – 30 years and 60 – 70 years, and typically includes the following
triad: acute renal failure, pulmonary hemorrhage, and presence of anti-glomerular
basement membrane
(anti-GBM) antibodies. Although the overall incidence is relatively low, GS is the
cause of approximately one-fifth of all cases of acute renal failure with rapidly
progressive
glomerulonephritis. If accompanied by pulmonary hemorrhage or secondary malignant
hypertension, the disease may be life-threatening [1].
A deeper understanding of GS was gained after the discovery of the anti-GBM antibodies
binding reactive epitopes in the basement membranes of the kidneys and lungs, causing
activation of the
complement cascade, lastly resulting in tissue damage. These antigens are found in
other specialized basement membranes, including Bruchʼs membrane, but clinically only
the glomerular and
alveolar basement membranes are usually affected. The reason for this seems to be
the greater expression and accessibility of epitopes of the NC1 domain of the alpha
3 chain of type IV
collagen units in these tissues [2], [3].
The exact cause of GS is still unknown. Genetics with an increased prevalence of HLA-DR15
and HLA-DRB1 and also certain behavioral and environmental factors (e.g., exposure
to metallic dust,
tobacco smoke, as well as lymphocyte depletion therapy, e.g., alemtuzumab) are thought
to increase the risk [4].
GS symptoms can develop gradually, or rapidly in as little as a few days. Sixty to
eighty percent of patients have clinical manifestation of both pulmonary and renal
disease, 20 – 40% have
renal disease alone, and less than 10% develop only lung disease. Some cases have
been reported to develop autoimmune inner ear disease (AIED), presenting with sudden
hearing loss [5], [6].
A kidney biopsy delivers a definitive diagnosis. Serologic assays for anti-GBM antibodies
are important for initial diagnosis and monitoring of the disease treatment. The therapy
involves
rapid removal of circulating antibodies, primarily by plasmapheresis, as well as immunosuppression
(e.g., corticosteroids and cyclophosphamide) to reduce the new production of antibodies.
Currently, a 5-year survival of 80% can be reached with this treatment [4].
While systematic clinical data is missing about GS, numerous case reports and small
case series have been published. However, only a few address or include potential
ophthalmic manifestations
of the syndrome [7], [8], [9], [10], [11], [12], [13], [14], [15].
Overall, there are two potential pathophysiological pathways by which GS can lead
to ocular symptoms. On the one hand, GS involves anti-basement membrane auto-antibodies,
which could lead to
primary changes to eye structures due to immunoglobulin deposition in the basement
membranes. On the other hand, GS can cause secondary complications, such as severe
arterial hypertension,
which may lead to vascular and structural changes in the ocular tissue [10].
In the following description, ocular findings in a young patient with GS are carefully
described.
Case Description
After complaining about bilateral blurred vision and an unusual headache since the
previous day, a 17-year-old male patient under immunosuppression was referred to our
clinic for suspected
acute infectious retinitis. Three months before, Goodpastureʼs syndrome with glomerulonephritis
and pulmonary involvement had been diagnosed. Plasmapheresis and immunosuppressive
therapy with
cyclophosphamide and corticosteroids had been initiated. Due to rapidly progressive
glomerulonephritis and consecutive renal failure, the patient required regular dialysis.
On initial examination, best-corrected visual acuity (BCVA) was 0.64 in both eyes,
intraocular pressure was within normal range, and the anterior segment slit lamp findings
were unremarkable.
Fundus examination revealed bilateral optic disc edema, splinter bleedings along the
retinal nerve fibers, multiple cotton wool spots, as well as hard exudates in the
macula, suggesting
cystoid macular edema (CME; [Fig. 1]). Optical coherence tomography (OCT) confirmed the presence of CME in both eyes
([Fig. 2 a]).
Fundus changes were consistent with hypertensive retinopathy grade IV, and the patientʼs
arterial blood pressure was 190/112 mmHg.
Fig. 1 Optos fundus photography at first clinical presentation.
Fig. 2 Optical coherence tomography (OCT) at first clinical presentation (a), at 3 months (b), and at the 12-month (c) follow-up.
A sudden rise in blood pressure values above 180/120 mmHg by definition is an urgent
hypertensive crisis, and in conjunction with severe organ damage, as suggested by
the fundus findings, is
considered an emergency hypertensive crisis [16]. Immediate emergency department admission for antihypertensive treatment was organized.
Under tight blood pressure control, follow-up visits at 1 week and 1, 3, and 6 months
revealed a significant improvement of BCVA and reduction of CME. At the 3-month visit,
BCVA was restored
to 1.25 in both eyes. Biomicroscopy of the fundus revealed almost complete resolution
of hemorrhages and cotton wool spots. While central retinal thickness was again normal
in the OCT
examination, intraretinal hyperreflective foci and irregularities of the external
limiting membrane (ELM) and ellipsoid zone (EZ) were still detectable ([Fig. 2 b]).
Final examination was conducted 1 year after the onset of the ocular symptoms: BCVA
was 1.6 in the RE and 1.25 in the LE. Fundoscopic examination revealed normal optical
discs and
physiological macular reflexes. A discrete retinal vessel tortuosity was still observable.
The OCT showed a slight remaining irregularity of the outer plexiform and nuclear
layers in both eyes
([Fig. 2 c]).
One month after the final ophthalmological examination, the patient received a renal
transplantation. At the time of obtaining the patientʼs consent for this case report,
the patient stated
that he had returned to work full time as a gardener and had no ocular complaints.
Discussion
Ocular involvement in the presented case is likely due to secondary complication of
GS and may indicate an emergency.
The few reported cases of GS with ocular fundus changes involve patients between 19
and 44 years of age [7] – [12], [14], [15]. At 17 years, the presented patient is the youngest GS case with ocular manifestation
with full clinical and morphological workup
over a time span of 12 months.
In a literature review from 1964 by Benoit et al., in only 2 cases (4%) of 52 patients
described with GS were ocular fundus changes (asymptomatic hemorrhages and exudates)
described [15]. A later review reported fundus abnormalities in 6 out of 56 patients with GS (11%)
[14]. In 1988, Köhler published a case report of a
19-year-old patient with GS and unilateral macular edema. Similar to our case, there
was also an association with severe hypertension [9]. Thirty years later,
Lommatzsch et al. described hypertensive retinopathy with cotton wool spots, hard
exudates, and hemorrhages related to GS in a 22-year-old man [7]. Other ocular
findings, such as serous retinal detachment and choroidal neovascular membranes, are
also described in the literature [10], [12], [13]. In 1975, Jampol et al. described two cases of central retinal detachment in association
with malignant hypertension due to GS.
In these cases, the eye is an observation window that can provide information about
potentially fatal end-organ damage. Especially in an adolescent patient, as presented
here, acute
hypertension, with blood pressure values well above the threshold, often presents
only with mild systemic symptoms [17]. Furthermore, the ocular examination can aid
in the detection of circumstances, where the definition of severe hypertension with
respect to the numeric blood pressure values is not met but still end-organ damage
is likely. In the
presented case, the sum of the ocular findings and the elevated blood pressure indicated
a hypertensive emergency requiring blood pressure control within 24 hours [18] – [21].
At the time of the onset of ocular symptoms, immunosuppressive therapy was still in
place to control GS. Therefore, the deposition of anti-GBM antibodies, causing an
occlusive vasculitis in
the deep capillary plexus and leading to the presented ocular findings, seems less
likely. Also, to date, no specific anti-GMB antibodies in human ocular tissue have
been demonstrated [10], [12]. Rather, the observed ocular findings were most likely due to the GS-related renal
insufficiency with secondary development of
acute arterial hypertension and subsequent retinal perfusion disturbances, clinically
presenting as hypertensive retinopathy grade IV. Furthermore, once blood pressure
control was achieved,
the retinal findings showed improvement.
Nevertheless, even 1 year after acute hypertensive retinopathy, subtle OCT findings
can be detectable. As this case shows, residual changes with irregularities and blurriness
of the outer
plexiform and outer nuclear retinal layers could still be observed. Hypertensive foci
and changes to the EZ nearly completely resolved after 1 year.
In conclusion, if signs of hypertensive retinopathy are present, blood pressure should
be measured routinely. As this rare case displays, signs of hypertensive retinopathy
in a young patient
may indicate a rare life-threatening state.
