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Ocular Involvement in Patients With Posttransplant Lymphoproliferative Disorder
Andrew S. Cho, MD;
Gary N. Holland, MD;
Ben J. Glasgow, MD;
Sherwin J. Isenberg, MD;
Barbara L. George, MD;
Sue V. McDiarmid, MD
Arch Ophthalmol. 2001;119:183-189.
ABSTRACT
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Objectives To describe ocular disease in 3 patients with posttransplant lymphoproliferative
disorder (PTLD) and to identify the frequency of such ocular involvement.
Methods Medical record reviews. Using Kaplan-Meier analysis, we calculated the
frequency of ocular involvement among pediatric patients with systemic PTLD
after liver transplantation.
Results Each patient had bilateral anterior chamber cells. Biopsy of an iris
nodule from a patient who had undergone cardiac transplantation confirmed
the diagnosis of PTLD, but no signs of systemic PTLD were found. The other
2 patients had systemic PTLD after liver transplantation; 1 presented with
iris nodules in both eyes and a subretinal mass in the left eye, while the
other had bilateral anterior chamber cells only. Ocular signs improved slowly
after reduction of immunosuppressive drug therapy. Ophthalmological examinations
were performed on 22 of 25 pediatric patients with PTLD after liver transplantation;
2 had ocular disease. Kaplan-Meier analysis indicated a 20% risk of ocular
involvement at 3 years after development of PTLD (95% confidence intervals,
0%-50%).
Conclusions Posttransplant lymphoproliferative disorder should be considered in
the differential diagnosis of uveitis after organ transplantation. Anterior
chamber cells and iris nodules are the most common ocular signs, but the posterior
segment can be involved. Ocular involvement can occur without evidence of
systemic disease and can be asymptomatic. Reduction of immunosuppressive drug
therapy is an appropriate treatment.
INTRODUCTION
POSTTRANSPLANT lymphoproliferative disorder (PTLD) results from an abnormal
proliferation of lymphocytes that occurs in the setting of immunosuppression
after surgery. It is characterized by a spectrum of disease findings that
ranges from benign polyclonal polymorphic B lymphocyte hyperplasia to monoclonal
B lymphocyte lymphoma.1-2 Experimental
and clinical evidence supports the notion that Epstein-Barr virus, which can
be oncogenic in immunodeficient hosts, is responsible for PTLD.1-2
Posttransplant lymphoproliferative disorder can appear months to years
after transplantation.3-5
The overall prevalence of PTLD seems to be less than 5%, but rates vary with
the type of organ transplanted and the nature of the immunosuppression.5 The manifestations of PTLD are protean, and they include
constitutional symptoms, lymphadenopathy, upper airway obstructive symptoms,
alterations in mental status, neck stiffness, focal neurologic findings, gastrointestinal
perforation or obstruction, graft dysfunction, or localized solid tumor masses.
Widely disseminated disease can occur.
Ocular involvement with PTLD has been described infrequently as isolated
case reports.6-9
We report 3 additional patients with ocular manifestations of PTLD who had
signs and symptoms of uveitis. We also calculated the frequency of ocular
disease among all pediatric patients who were being observed at our institution
for systemic PTLD after liver transplantation.
PATIENTS AND METHODS
PATIENTS
The following information was obtained from the records of 3 patients
with PTLD and ocular involvement who had been referred to the Jules Stein
Eye Institute: age, sex, type of organ transplanted, reason for organ transplantation,
immunosuppressive drugs used, nature of systemic PTLD, treatment for PTLD,
ocular and visual symptoms, initial visual acuity, slitlamp biomicroscopic
examination findings, intraocular pressure, dilated fundus examination findings,
and the course of disease, including response to treatment.
An iris nodule was excised surgically from 1 patient for diagnostic
purposes and was examined by light microscopy after staining with hematoxylin
and eosin. Immunohistochemical studies were performed to determine the clonality
of the lesion, and in situ RNA hybridization studies were performed to detect
the presence of Epstein-Barr virus.
We routinely perform complete ophthalmological examinations on all patients
at the University of California, Los Angeles (UCLA), Medical Center who have
undergone liver transplantation and have a history of systemic PTLD. All patients
are followed up in the practice of 1 author (S.V.M.). We reviewed the ophthalmic
examinations of these patients to determine the rate of ocular involvement
in this population.
We identified previously reported cases of ocular involvement in patients
with PTLD through computerized literature searches for the years 1966 through
2000 using MEDLINE. This study conformed to regulations of the UCLA Office
for the Protection of Human Subjects.
REPORT OF CASES
Case 1
A 14-year-old boy underwent cardiac transplantation for a congenital
cardiac anomaly and was subsequently immunosuppressed with oral cyclosporine
(5.7 mg/kg per day) and oral azathioprine (0.46 mg/kg per day), with a mean
cyclosporine level of 161 ng/mL during the fourth posttransplant year. We
examined him 5 years after transplantation because of a "lump on the iris,"
which had been detected on routine eye examination. He had no visual disturbance
or ocular symptoms. Uncorrected visual acuity was 20/20 OU. Pupils were round
and reactive to light without an afferent pupillary defect. Slitlamp biomicroscopic
examination revealed normal eyelids, noninflamed ocular surfaces without focal
lesions, and clear corneas. There were rare to occasional cells in the right
anterior chamber and 3+ cells in the left anterior chamber. There was minimal
flare in both eyes. The right iris appeared normal. The left iris had numerous
nonpigmented nodular elevations consistent with mass lesions arising from
the iris stroma (Figure 1). On dilated
examination, both vitreous bodies were clear, and there were no fundus lesions
in either eye. Laboratory studies included a normal complete blood cell count
with differential, nonreactive purified protein derivative skin test, normal
chest x-ray films, and nonreactive fluorescent treponemal antibody absorption
test. There was no serologic evidence of toxoplasmic, cryptococcal, or coccidioidal
infections. Results of a bone marrow biopsy were negative for abnormality.
Computed tomographic scan of the chest and abdomen did not show any mass lesions.
Serologic tests for Epstein-Barr virus infection were performed yearly on
a routine basis and had been positive for the previous 4 years; the most recent
test results had been consistent with active infection (viral capsid antigen
immunoglobulin G[IgG], >1:2560; viral capsid antigen immunoglobulin M, <1:20;
early antigen, >1:2560; Epstein-Barr nuclear antigen, >1:20), but the patient
has no history of PTLD.
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Figure 1. Case 1, left eye. View of the
iris at initial visit. There are multiple peripheral tan-white iris nodules
involving the iris stoma (arrow).
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Therapy was initiated using topical prednisolone acetate 1% every hour
with no change in size of the iris nodules or in severity of the anterior
chamber cellular reactions. An incisional biopsy of an iris nodule in the
left eye was performed through a superonasal limbal incision 3 months after
initial visit. Light microscopic examination showed a dense collection of
plasma cells and slightly atypical lymphocytes (Figure 2). Immunoperoxidase staining showed an equal mixture of 
and  light chains. In situ hybridization studies for Epstein-Barr virus
were positive (Figure 3). A diagnosis
of PTLD was made on the basis of these results. Azathioprine administration
was discontinued, and the dose of cyclosporine was decreased to 2.3 mg/kg
per day. Prednisone (0.11 mg/kg per day) and acyclovir sodium (53.3 mg/kg
per day) were added 4 months after the presentation. The iris nodules were
noted to decrease in size after 3 months, and the anterior chamber cellular
reaction continued to decrease during the subsequent 6 months.
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Figure 2. Case 1, left eye. Iris nodule
biopsy demonstrating dense collection of plasma cells and slightly atypical
lymphocytes. There are occasional histiocytes and rare eosinophils (hematoxylin-eosin,
original magnification x40)
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Figure 3. Case 1, left eye. In situ RNA
hybridization studies demonstrating the presence of Epstein-Barr virus RNA.
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Case 2
A 5-year-old girl underwent liver transplantation for end-stage liver
disease resulting from biliary atresia and was subsequently maintained on
cyclosporine (14.0 mg/kg per day), azathioprine (1.6 mg/kg per day), and prednisone
(0.25 mg/kg per day), with a mean cyclosporine level during the third posttransplant
year of 130 ng/mL. She developed fever of unknown origin, tonsillar enlargement,
and cervical and axillary lymphadenopathy approximately 3 years after transplantation
and was diagnosed with PTLD by tonsillar biopsy. At that time, her anti–Epstein-Barr
virus IgG titer was noted to be highly elevated (1:2560). Azathioprine was
stopped, cyclosporine was decreased to 13.0 mg/kg per day, and acyclovir (35
mg/kg per day) was added to her treatment regimen.
We examined her 4 years after transplantation when she complained of
mild photosensitivity in both eyes. Visual acuity was 20/30 OD and 4/200 OS.
The right pupil was briskly reactive to light, while the left pupil was sluggishly
reactive to light. There was a trace afferent pupillary defect in the left
eye. On slitlamp biomicroscopic examination, there were numerous nonpigmented
nodules in the iris stroma of both eyes. Examination of the anterior chamber
revealed 2+ cells in the right eye and 3+ cells in the left eye. Flare was
prominent in both eyes. There were mutton fat keratic precipitates in both
eyes. The left eye had nearly 360° of posterior synechiae. In the left
eye, there was optic disc edema with elevation of much of the posterior pole
because of a subretinal mass (Figure 4).
A presumed diagnosis of PTLD was made, given the history of systemic PTLD
and similarity of the iris nodules to those previously noted in case 1. Initial
therapy consisted of topical prednisone acetate 1% every 2 hours and cyclopentolate
1% at bedtime. The cyclosporine dosage was reduced to 10.4 mg/kg per day 2
months after our initial examination. During the next 1 month, the iris nodules
of both eyes disappeared, and the subretinal mass in the left eye flattened
with the return of visual acuity to 20/50 OS. The cyclosporine dosage was
further decreased to 5.2 mg/kg per day 6 months later, followed by an episode
of decreased vision, with increased anterior chamber cells and increased peripapillary
infiltration in the left eye. Intravenous ganciclovir was added to the treatment
regimen and cyclosporine was stopped. During the next 2 months, inflammation
and the peripapillary infiltrate decreased, and visual acuity returned to
20/40 OS. Blood tests for Epstein-Barr virus remain markedly positive at 847
viral DNA copies or µg DNA by polymerase chain reaction (PCR) technique.
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Figure 4. Case 2, left eye. Fundus view
demonstrating retinal elevation associated with a subretinal mass lesion and
optic disc edema.
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Case 3
A 10-year-old girl underwent liver transplantation because of biliary
atresia. Because of hepatic artery thrombosis in the first allograft, a second
liver transplant was performed 1 month later. She was immunosuppressed with
tacrolimus for chronic rejection, but the drug was discontinued 3 years later
after she developed generalized lymphadenopathy and was diagnosed with PTLD,
based on results of mediastinal lymph node and liver biopsies. Immunosuppression
therapy was temporarily stopped, and a regimen of acyclovir (34.8 mg/kg per
day) was started. Administration of cyclosporine (7.0 mg/kg per day) and prednisone
(0.1 mg/kg per day) was eventually resumed. She subsequently had 1 episode
of acute allograft rejection approximately 3 years after the initial transplantation.
The mean cyclosporine level during the fifth year after transplantation was
210 ng/mL.
We examined her 6 years after initial transplantation, following identification
of asymptomatic bilateral anterior uveitis on routine examination, and initiation
of therapy using topical 1% prednisolone acetate every 4 hours in the left
eye and homatropine 5% twice daily in the left eye. Visual acuity was 20/20
OD and 20/25 OS. Both pupils were reactive to light without afferent pupillary
defects. She had palpable cervical adenopathy. Corneas were clear. Examination
of the anterior chambers revealed occasional cells in the right eye and 2+
cells in the left eye. Flare was minimal in both eyes. There were remnants
of old keratic precipitates in the left eye. No iris nodules were seen and
there were no posterior synechiae. Lenses were clear. Intraocular pressure
was 14 mm Hg OD and 16 mm Hg OS. There were cells in the anterior vitreous
humor of the left eye. Optic discs appeared normal. No posterior segment inflammatory
lesions were seen in either eye. A presumed diagnosis of PTLD with ocular
involvement was made on the basis of history and lack of other identified
causes. Cyclosporine doses were reduced only moderately (5.5 mg/kg per day)
because of ongoing liver rejection. The frequency of topical prednisolone
acetate 1% was raised to 7 times daily in both eyes. Administration of homatropine
5% was stopped. There was a transient episode of elevated intraocular pressure
(38 mm Hg) of uncertain cause in the right eye. Topical prednisolone was discontinued
temporarily in the left eye, but there was no appreciable change in the level
of cells, and it was reinstituted without an increase in intraocular pressure.
During the following several months, vision remained stable with little change
in the level of anterior chamber cells, despite changes in the frequency of
topical medications. Blood tests for Epstein-Barr virus remain elevated at
492 viral DNA copies or µg DNA by PCR technique.
RESULTS
Characteristics of the 3 patients with PTLD and ocular involvement are
summarized in Table 1. Common
features included anterior chamber cells (all cases) and iris nodules (cases
1 and 2). The disease was bilateral, albeit asymmetrical, in all cases. One
patient (case 2) had posterior segment involvement consisting of a subretinal
mass with optic disc swelling. Only 1 patient (case 2) had posterior synechiae;
neither of the cases without posterior synechiae had prominent anterior chamber
flare. Ocular disease was diagnosed 53 to 68 months after initial transplantation,
and at 10 and 38 months after the diagnosis of systemic PTLD in the 2 cases
with preexisting disease.
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Patients With Posttransplant Lymphoproliferative Disorder and Ocular
Involvement
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We performed complete ophthalmological examinations on 22 of 25 patients
with systemic PTLD after liver transplantation who were observed at the UCLA
Medical Center. All 22 patients underwent liver transplantation between 1984
and 1997. Posttransplant lymphoproliferative disorder was confirmed in all
cases by biopsy results. The median interval from liver transplantation to
diagnosis of systemic PTLD was 22 months (range, 3-88 months). The median
duration of PTLD until ophthalmologic examination was 26 months (range, 10-116
months). The mean age at the time of ophthalmologic examination for this population
was 8 years, with a median age of 7 years.
Only the 2 girls in our case series had ocular disease. On the basis
of our experience, Kaplan-Meier analysis (Figure 5) indicates that the risk for development of ocular involvement
is 20% at 3 years after diagnosis of systemic PTLD (95% confidence intervals,
0%-50%). Confidence intervals have been included to show that a large degree
of uncertainty exists because of the small sample sizes. The intervals may
be inaccurate, however, because the calculation of these intervals in a Kaplan-Meier
analysis is based on the assumption of large sample results.
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Figure 5. Kaplan-Meier analysis showing
risk of ocular involvement with posttransplant lymphoproliferative disease
in 22 pediatric patients after liver transplantation. Solid line indicates
the observed prevalence of disease; dotted lines, 95% confidence intervals;
and PTLD, posttransplant lymphoproliferative disorder.
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Of the 22 patients, 19 were immunosuppressed with tacrolimus and 3 patients
were immunosuppressed with cyclosporine. None of the patients receiving tacrolimus
had ocular involvement, whereas 2 of the 3 patients receiving cyclosporine
had ocular involvement (P = .013 [Fisher exact 2-tailed
test]). The boy who had undergone cardiac transplantation and developed PTLD
with ocular involvement, and was not included in the series of 22 patients,
was also receiving cyclosporine.
COMMENT
Posttransplant lymphoproliferative disorder is defined as an abnormal
proliferation of lymphoid cells in a patient receiving immunosuppressive therapy
following organ transplantation. The disorder is thought to occur as the result
of failure of the host immune system to defend against Epstein-Barr virus
infection by limiting the T-lymphocyte responses that normally control the
proliferation of the B lymphocytes infected with the virus. In general, the
use of immunosuppressive therapies in the setting of solid organ transplantation
is associated with a 20-fold to 50-fold increased risk of lymphoproliferative
disease.2
In the early 1980s, Hanto et al10-13
defined the clinical features of PTLD and suggested a role for Epstein-Barr
virus in its pathogenesis. In a report of 6 transplantation patients with
lymphoproliferative lesions, all had evidence of oropharyngeal Epstein-Barr
virus shedding, and 5 had multiple copies of the Epstein-Barr virus genome
in the tumor tissue.10-13
Epstein-Barr virus infection also results in lymphoproliferative diseases
in several animal models. Mice with severe combined immunodeficiency develop
lymphoproliferative disease after intraperitoneal injection of Epstein-Barr
virus–seropositive blood.14-15
The cotton-top tamarin, an Old-World primate, develops fatal lymphoproliferative
disease after inoculation with Epstein-Barr virus.16
Posttransplant lymphoproliferative disorder may appear clinically in
several ways. Some patients develop an infectious mononucleosis-like illness
with pharyngitis, fever, tonsillitis, lymphadenopathy, and hepatospenomegaly.
Others have a localized disease that is more likely to be extranodal than
nodal. One of the most common initial sites of PTLD is the central nervous
system, which is involved in 28% of cases in the transplantation population.17 Among patients treated with cyclosporine and tacrolimus,
the gastrointestinal tract is the most common site of presentation.2 Patients may present with abdominal pain, gastrointestinal
bleeding, symptoms of obstruction, or bowel perforation. Lymph node, bone
marrow, kidney, liver, and lung involvement is also common.18
The disorder can also appear in the allograft with organ dysfunction and failure.19
Factors associated with the development of PTLD include young age, primary
Epstein-Barr virus infection, type of organ transplanted, and type and intensity
of immunosuppression.2 Epstein-Barr virus–associated
PTLD is more common in pediatric than in adult transplant recipients because
many pediatric patients, particularly liver recipients, fulfill the other
high-risk criteria.20 In addition, there is
increasing use of partial liver grafts from adults, who are frequently Epstein
Barr virus–positive, in noninfected pediatric recipients. It has been
estimated in several studies that the rate of primary, asymptomatic Epstein-Barr
virus infection in seronegative pediatric recipients is between 60% and 80%,
and that approximately 50% of children are seronegative before transplantation.21 Symptomatic Epstein-Barr virus disease develops in
a subset of infected children, and PTLD more commonly occurs with primary
infection.21 Data from many small North American
series suggest a lifetime risk for the development of PTLD for renal allograft
recipients of less than 1%, while it is 2% to 4% for adult liver allograft
recipients, slightly higher for heart recipients, and as high as 10% for heart-lung
recipients.22
Ocular involvement in patients with PTLD is thought to be unusual. We
identified only 4 cases of intraocular involvement in the medical literature.
Brodsky et al6 reported the case of a 7-year-old
girl who was immunosuppressed with cyclosporine after liver transplantation.
She developed bilateral iris tumors associated with anterior chamber cells
and flare, and mutton-fat keratic precipitates, but no posterior segment abnormalities.
Robinson et al7 reported the case of a young
girl who was receiving cyclosporine after liver transplantation and developed
multiple large pigmented iris nodules associated with 1+ to 2+ anterior chamber
cellular reactions in both eyes and fine-sized and medium-sized keratic precipitates,
but no posterior segment involvement. In these 2 cases, the patients did not
have a known diagnosis of systemic PTLD, although 1 patient had splenomegaly.6-7 In the case reported by Brodsky et
al,6 the large iris tumors responded to irradiation,
while nodules in the case reported by Robinson et al7
resolved with the reduction of cyclosporine dose. Clark et al8
reported a case of intraocular PTLD in a 2-year-old boy who developed unilateral
anterior chamber inflammation (1+ cells) and an iris tumor. This patient was
immunosuppressed with cyclosporine and prednisone after undergoing liver transplantation
at age 4 months, but had no evidence of systemic PTLD. Wedge resection of
the iris lesion was performed with no recurrence at 6 months' follow-up. Ocular
involvement has also been reported in an adult with PTLD. Demols et al9 reported the case of a 59-year-old man with PTLD after
lung transplantation, who developed an anterior chamber cellular reaction
and a subretinal, plaque-like lesion with overlying retinal vascular occlusion
in one eye. The posterior lesion resolved with acyclovir and a reduction of
cyclosporine dosage. Posttransplant lymphoproliferative disorder has also
been reported to involve the orbit.23
Our study suggests that the risk of ocular involvement in pediatric
liver transplantation patients with PTLD to be 20% at 3 years, although the
risk cannot be stated with certainty because of the small sample sizes. The
prevalence of ocular involvement associated with transplantation of other
organs is not known.
There is evidence that the rate of PTLD after first orthotopic liver
transplantation in children who are immunosuppressed with tacrolimus can be
decreased if high-risk recipients (Epstein-Barr virus–positive donor,
Epstein Barr virus–negative recipient) are treated preemptively with
a course of intravenous ganciclovir. Levels of Epstein-Barr virus in peripheral
blood are also monitored by PCR technique in these patients; if Epstein-Barr
virus levels rise, tacrolimus levels are dropped. Using this protocol, the
rate of PTLD in one study fell from 10% to 5%.24
No information is available regarding the potential effect of such protocols
on ocular involvement in those patients who do develop PTLD.
Our 3 cases and the 4 cases reported previously in the medical literature
have many common features, although the signs and severity of ocular involvement
varied between cases. All cases had anterior chamber cells. Iris nodules were
a common, although not universal, finding. Each of our cases and 2 of the
4 previously reported cases were bilateral, although findings were asymmetrical.
Bilaterality is consistent with the fact that PTLD is a multifocal condition.
Our case 2, with severe panuevitis and a subretinal mass, shows that children
with PTLD may develop posterior segment lesions as described by Demols et
al9 in an adult. There was no distinct difference
in the ocular manifestations between the cardiac transplantation patient and
liver transplantation patients in our series.
The clinical course of the ocular disease seems to be chronic and fluctuating.
In case 2, inflammation was unchanged for 4 months, followed by dramatic improvement
for 4 months, followed again by recurrent inflammation. Ocular lesions showed
minimal response to topical corticosteroids, but there was a slow response
to lowering of immunosuppressive drugs. Response of ocular lesions to decreased
immunosuppressive drugs was not observed for 2 to 4 months.
The role of antiviral medication for treatment of PTLD is undetermined.
Davis et al25 reported a lower rate of PTLD
in patients receiving intravenous ganciclovir followed by high-dose oral acyclovir.
Two of our 3 patients (cases 2 and 3), both of whom had a history of PTLD,
were already receiving acyclovir when they were diagnosed with ocular involvement.
In contrast, oral acyclovir may have contributed to improvement seen in the
other patient (case 1). This observation might suggest viral resistance to
acyclovir with chronic therapy or that virus replication might not play as
important a role in pathogenesis during the later stages of PTLD as it does
at disease onset.
There is increasing evidence that the use of a more potent, multiagent
approach to immunosuppression, which has resulted in improved graft survival
in many types of organ transplantation, has accelerated the development of
PTLD. The OKT-3 cell, a monoclonal antibody that specifically targets cells
bearing the CD3 determinant, results in a decrease in the number and function
of circulating T lymphocytes and is associated with an increased risk of PTLD.17, 19, 26-28
Newell et al29 reported that use of OKT-3 for
corticosteroid-resistant rejection increased the risk of developing PTLD.
Morgan and Superina30 reported 7 cases of PTLD
in 66 pediatric liver transplantation patients. All 7 of the 43 patients who
received OKT-3 had PTLD, compared with none of the 23 patients who did not
receive OKT-3. Swinnen et al28 also reported
the rate of PTLD to increase from 1.3% to 11.4% in a group of cardiac allograft
recipients receiving OKT-3.
Cyclosporine may also increase the rate of PTLD.31
Tanner et al32 demonstrated that Epstein-Barr
virus–infected human peripheral blood mononuclear cells cultured in
the presence of cyclosporine showed increased proliferation of Epstein-Barr
virus–infected B lymphocytes and increased expression of interleukin
6 in T lymphocytes, when compared with those cultured without cyclosporine,
thereby promoting B lymphocyte proliferation and immortalization. Although
tacrolimus immunosuppression has also been associated with an increased risk
of PTLD in children,33 there was a significant
association between the use of cyclosporine as an immunosuppressive agent
and ocular involvement in our series. A causal relationship cannot be determined;
other unrecognized factors such as disease severity may have influenced both
the choice of drug and the development of ocular lesions.
Our series provides additional evidence that PTLD can involve the eye,
and, to our knowledge, gives a more detailed description of its ocular manifestations
than has been provided in previously reported cases. It provides an estimate
of the risk for ocular involvement not previously available from isolated
case reports. It also provides additional evidence that the spectrum of ocular
manifestations includes posterior segment lesions, and that a localized form
of PTLD can occur in the eye without systemic disease.
Posttransplant lymphoproliferative disorder can present as a masquerade
syndrome and should be considered in the differential diagnosis of uveitis
in immunosuppressed patients. Although we are unable to establish the rate
of disease precisely, screening of all children with PTLD seems to be appropriate;
2 of our 3 cases were identified on routine examinations. The prognosis for
systemic PTLD is variable depending on the severity, extent, location, and
malignancy of the infiltrating cells and their response to treatment. The
same is probably true for ocular lesions.
Subsequent to submission of this manuscript, another case of ocular
involvement in a child with PTLD was published.34
A 4-year-old girl who had undergone cardiac transplantation developed iris
lesions and an anterior chamber cellular reaction as seen in our case 1. Studies
revealed the iris lesion to be a monoclonal neoplasm of B cell origin. It
regressed with local radiation therapy. This additional case emphasizes that
the spectrum of possible ophthalmic manifestations of PTLD can include lymphoma.
AUTHOR INFORMATION
Accepted for publication August 16, 2000.
Supported in part by Research to Prevent Blindness Inc, New York, NY
(Drs Holland and Glasgow); the David May II Endowed Professorship (Dr Holland);
and the Skirball Foundation, Los Angeles, Calif (Dr Holland).
Dr Holland is the recipient of a Research to Prevent Blindness Inc,
Lew R. Wassermann Merit Award. Fei Yu, PhD, of the Department of Ophthalmology
and the Jules Stein Eye Institute Center for Eye Epidemiology, UCLA School
of Medicine, and William G. Cumberland, PhD, of the Department of Biostatistics,
UCLA School of Public Health, provided assistance with the statistical analysis
of data.
Corresponding author and reprints: Gary N. Holland, MD, Jules Stein
Eye Institute, University of California, Los Angeles, 100 Stein Plaza, UCLA,
Los Angeles, CA 90095-7003.
From the University of California, Los Angeles, Ocular Inflammatory
Disease Center, the Jules Stein Eye Institute, and the Department of Ophthalmology
(Drs Cho, Holland, Glasgow, and Isenberg); and the Departments of Pathology
(Dr Glasgow) and Pediatrics (Drs George and McDiarmid), University of California,
Los Angeles, School of Medicine.
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