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Cytomegalovirus Retinitis in Patients With Good Syndrome
Arch Ophthalmol. 2002;120:510-512.
Hypogammaglobulinemia and secondary systemic opportunistic infections
are recognized associations in patients with thymoma,1
and the simultaneous occurrence of thymoma and hypogammaglobulinemia is referred
to as Good syndrome.2
We report herein the presentation, clinical course, and outcome of 2
consecutive patients with vitreous biopsy–proved cytomegalovirus (CMV)
retinitis associated with thymoma and immunodeficiency but with no evidence
of other systemic CMV infection.
Report of Cases
Case 1
A 45-year-old woman was referred to Moorfields Eye Hospital, London,
England, in November 1998 with a 2-month history of bilateral posterior uveitis
that was not responding to topical treatment. The patient had no history of
ocular disease, and her medical history included a thymoma treated by excision
and postoperative radiotherapy in 1996, myasthenia gravis (positive acetylcholine
receptor antibody), vasculitis (p–anti-neutrophil cytoplasmic antibody
positive) with mild renal impairment, and recurrent chest infections. She
also had had a recent episode of chicken pox before the onset of ocular symptoms.
The patient was being treated with prednisolone, 10 mg/d, and azathioprine,
100 mg/d.
On examination, her visual acuities were 20/20 OD and 20/40 OS. Bilateral
mild anterior uveitis was present, with normal intraocular pressures. Funduscopic
examination showed a bilateral mild vitritis associated with bilateral superotemporal
active retinitis (Figure 1). There
was also an associated superotemporal macula-on rhegmatogenous detachment
of the retina in the right eye. A clinical diagnosis of bilateral acute retinal
necrosis was made, and the patient was treated with intravenous valacyclovir
hydrochloride (10 mg/kg 3 times daily), oral prednisolone (45 mg/d), and topical
1% prednisolone acetate and 1% cyclopentolate hydrochloride. The patient subsequently
underwent a right vitrectomy with injection of silicone oil for treatment
of her detached retina and bilateral argon laser to demarcate the areas of
active retinitis. Polymerase chain reaction examination of a vitreous sample
taken during vitrectomy was positive for CMV DNA and negative for herpes simplex
virus 1 and herpes zoster virus DNA. Analysis of blood samples disclosed a
marked selective CD4 T-cell lymphocytopenia, with a reduced CD4/CD8 ratio
of 0.25 (reference range, 0.66-3.52) but a normal B cell count. The patient
had no serum antibodies for human immunodeficiency viruses 1 and 2 and had
markedly low IgA levels (44 mg/dL), with mildly elevated IgM (199 mg/dL) and
IgG (2020 mg/dL) levels. Polymerase chain reaction examination of peripheral
blood was negative for CMV DNA. The patient's CD4 cell count did not return
to normal, and her immune status remained unchanged despite cessation of azathioprine
therapy. A chest x-ray film was clear, with no evidence of opportunistic infection.
Because her retinitis was improving after a week of systemic treatment, the
patient was discharged from the hospital on a regimen of oral acyclovir (because
the patient preferred not to receive ganciclovir) and a tapering course of
oral prednisolone. Six weeks later, the retinitis relapsed in the left eye
and treatment was changed to intravenous ganciclovir followed by insertion
of a slow-release intravitreal implant. The retinitis in her left eye resolved
after 1 week, and the ganciclovir implant has been subsequently exchanged
on a regular basis to control the patient's disease because her CD4 cell count
has remained low.
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Figure 1. Funduscopic photograph of the
left eye of patient 1 showing mild vitritis with peripheral cytomegalovirus
retinitis.
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Case 2
A 65-year-old woman was referred to Moorfields Eye Hospital in April
2000 with a 1-week history of floaters and progressive reduction in visual
acuity of the right eye after a flulike illness that lasted a few days. The
patient had no history of ocular disease, but her medical history was remarkable
for a malignant thymoma that had been excised in 1998 and recurrent chest
infections associated with bronchiectasis. On examination, her visual acuities
were hand movements and 20/20 OS, with a right-sided relative afferent pupillary
defect. Slitlamp examination showed a mild right anterior uveitis with normal
intraocular pressures. Funduscopic examination showed a moderate vitritis
and a swollen, hyperemic optic disc associated with retinitis along the right
inferotemporal vascular arcade and affecting the macula (Figure 2). Polymerase chain reaction examination of a vitreous tap
confirmed the presence of CMV DNA and was negative for herpes simplex viruses
1 and 2, herpes zoster virus, and Epstein-Barr virus DNA.The patient was treated
with topical corticosteroids and repeated intravitreal injections of foscarnet
sodium (2.4 mg each) and oral gancyclovir (1 g 3 times daily). Despite control
of the retinitis, the patient's vision failed to improve because of optic
atrophy. Polymerase chain reaction examination of peripheral blood was negative
for CMV DNA. A chest x-ray film was not suggestive of any acute opportunistic
infections, and analysis of blood samples showed a raised CD8 cell count of
976 cells/µL (reference range, 200-900 cells/µL), with a reduced
CD4/CD8 ratio of 0.6 (reference range, 0.66-3.52) and a low B lymphocyte count
of 1 (reference range, 100-500). The patient had no serum antibodies for human
immunodeficiency viruses 1 and 2, low IgA (56 mg/dL) and IgM (43 mg/dL) levels,
and a normal IgG level (640 mg/dL).
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Figure 2. Funduscopic photograph of the
right eye of patient 2 showing cytomegalovirus retinitis along the inferotemporal
vascular arcade with involvement of the macula and optic nerve head.
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Comment
About a third of thymomas are associated with more than 20 different
paraneoplastic syndromes, the 3 most commmon being myasthenia gravis, pure
red cell aplasia, and hypogammaglobulinemia (6% of cases).1
The simultaneous occurrence of thymoma and hypogammaglobulinemia was first
described in 19542 and was referred to as Good syndrome. Other systemic associations reported with
thymomas include myasthenia gravis, IgG gammopathy, disorders of cell-mediated
immunity, polyarthropathy, lichen planus, and hemolytic anemia.3
To the best of our knowledge, the 2 patients described herein are the first
reported cases of CMV retinitis associated with the syndrome of thymoma and
immunodeficiency.
Recurrent bronchopulmonary disease often leading to bronchiectasis is
the most common clinical presentation of Good syndrome, and both our patients
had had recurrent chest infections. Conversely, CMV is the opportunistic pathogen
most frequently reported in the literature and has caused bronchopneumonia,
watery diarrhea, disseminated infection, and fatal encephalitis.4-5
No retinal lesions have been previously reported in patients with Good
syndrome and systemic CMV infections. The ocular manifestations of this syndrome
described in the literature are limited to 2 cases of toxoplasma retinitis6-7 and 1 case of bilateral, nonsimultaneous
recurrent herpetic keratitis.8
Although CMV disease occurs most often in patients with depressed cell-mediated
immunity, there is evidence that humoral immunity plays a protective role
against the virus.9 Before the acquired
immunodeficiency syndrome epidemic, fewer than 50 cases of CMV retinitis in
patients with noncongenital CMV disease were reported in the literature. These
cases developed in severely immunocompromised patients with organ transplants
or a variety of malignancies associated with the use of immunosuppressive
chemotherapy.9
Therefore, our cases illustrate a widening clinical spectrum of CMV
disease in patients with immunodeficiency associated with thymoma. Clinicians
should be aware of this association, as early recognition and treatment can
improve prognosis.
AUTHOR INFORMATION
Alexandre C. Assi, BSc, MBBS, FRCOphth;
Susan Lightman, PhD, FRCP, FRCOphth, FMedSci
London, England
Corresponding author and reprints: Susan Lightman, PhD, FRCP, FRCOphth,
FMedSci, Moorfields Eye Hospital, City Road, London EC1V 2PD, England (e-mail: s.lightman{at}ucl.ac.uk).
REFERENCES
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1. Rosenow III EC, Hurley BT. Disorders of the thymus: a review. Arch Intern Med. 1984;144:763-770.
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2. Good RA. Agammaglobulinaemia: a provocative experiment of nature. Bull Univ Minn Hosp. 1954;26:1-19.
3. Benson MK. Mediastinal tumours and cysts. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford Textbook of Medicine. Vol 2, section 17. 3rd ed. Oxford, England:
Oxford University Press; 1996:2898-2899.
4. Gupta S, Saverymuttu SH, Gibbs JSR, Evans DJ, Hodgson HJ. Watery diarrhea in a patient with myasthenia gravis, thymoma, and immunodeficiency. Am J Gastroenterol. 1985;80:877-881.
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deficiency. Am J Med. 1979;67:724-728.
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6. Shaikh S, Schwab IR, Morse LS. Association of ocular toxoplasmosis and thymoma. Retina. 1997;17:354-356.
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7. Figuier P, Saragoussi JJ, Cavaille-Coll M, Le Hoang P, Offret H. Toxoplasmose oculaire acquise et immunodépression d'origine
thymique tumorale. J Fr Ophtalmol. 1984;7:813-817.
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8. Eiferman RA, Hoffman RS, Pence HL. Good syndrome and herpetic keratitis [letter]. Arch Ophthalmol. 1993;111:736.
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9. Holland GN, Tufail A, Jordan MC. Cytomegalovirus diseases. In: Pepose JS, Holland GN, Wilhelmus KR, eds. Ocular Infection and Immunity. St Louis, Mo: Mosby–Year Book
Inc; 1996:1088-1128.
SECTION EDITOR: W. RICHARD GREEN, MD
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ABSTRACT
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