Bilateral Cytomegalovirus Retinitis in a 4-year-old Boy with Primary Immune Deficiency

Case Report

A 4-year-old boy who had B and T cell combined immunodeficiency was admitted with complaints of squint and bilateral visual loss for three days. He had a history of severe atopic dermatitis, multiple food allergies (milk, egg, wheat), hyperkeratosis, recurrent pneumonia, nail dystrophy, and dilated cardiomyopathy since 2 months of age. He was on trimethoprim/sulfamethoxazole and fluconazole prophylaxis, cutaneous steroid ointment, and in addition to 4-weekly immunoglobulin and omalizumab treatments. He was diagnosed with cytomegalovirus (CMV) pneumonia at the age of 3 years and received intravenous (iv) ganciclovir and then oral valganciclovir therapy by monitoring the CMV DNA blood titer. Antiviral treatment was stopped at the 12th month after obtaining two consecutive negative blood CMV DNA results. Ophthalmological evaluations were performed intermittently during the antiviral therapy for possible CMV retinitis. The last eye examination was performed one month after the cessation of antiviral treatment and the fundus examination was unremarkable at that time. Existing visual complaints started 2 months after antiviral treatment was discontinued. On ophthalmological examination, there was only light perception in the right eye and the left eye could barely follow objects. On slit-lamp examination, the anterior segment was unremarkable bilaterally. Yellow-white cloudy retinal lesions implying the presence of retinal necrosis, retinal hemorrhages, peripapillary and macular cotton wool spots, inferior retinal detachment, and perivascular sheathing were detected in the right eye ([Fig. 1a]). Extensive retinal opacification and satellite lesions commencing from the optic disc towards the retinal periphery were present in the left eye ([Fig. 1b]). The retina appeared necrotic and there were some hyperreflective dots on optical coherence tomography ([Fig. 1c]) of the left eye. Laboratory results demonstrated a white blood cell count of 7100/uL (neutrophil 2800/uL, lymphocyte 4200/uL), platelets 179000/uL, hemoglobin 11.5 g/dL, C-reactive protein 1.2 mg/L. CMV DNA was 370,265 (log10: 5.5) copies in the blood (analytical sensitivity of the test 43 copies/ml). Syphilis and Toxoplasma gondii serology and Quantiferon test all turned out to be negative. The HIV Ag/Ab test of the patient was negative. In immunological tests, he had high immunoglobulin E, low immunoglobulin G, and M. CD20: 14%, CD19: 7%, Central memory T: 31.9%, Temra: 2.1%, CD3: 84%, CD 16+56: 3%, CD4: 44.8% were evaluated in the lymphocyte panel. An adequate response was not obtained in the T cell proliferation test. In vitro T cell response after stimulation with Phytohemagglutinin (PHA) was found to be lower than the healthy control. Switch memory B, marginal zone B, and plasmablast cells were low. Vaccine titer responses of the patient were checked and the anti-HBs and anti-tetanus IgG titers were 2 IU/ml and <0.1 IU/ml, respectively. ADA-deficiency as well as Hyper IGE syndrome (STAT3, DOCK8, PGEM3) could be ruled out by genetic testing as no pathogenic variants could be identified. No pathogenic variants were detected in the whole exon scanning previously performed on the patient. T-cell dysfunction and B-cell deficiency were considered in the patient with this clinical history and laboratory test results.

Fig. 1 Grayscale fundus pictures of the right (a) and left (b) eyes at the initial presentation. Retinal necrosis, yellow-white cloudy retinal lesions, hemorrhages and cotton wool spots around the optic disc and over the posterior pole, retinal detachment in the inferior retina and perivascular sheathing in the superior retina were observed in the right eye, while there were extensive retinal opacification and satellite lesions starting from the optic disc towards the retinal periphery in the left eye. The necrotizing retina appeared necrotic (arrowhead) and there was hyperreflective dots (arrows) on optical coherence tomography (c). Retina was reattached with silicone oil endotamponade in the right eye two weeks after the surgery (d) and 12 weeks (f) postoperatively. The improved appearance of left fundus after two (e) and six (g) ganciclovir injections was demonstrated.

Intravenous ganciclovir (10 mg/kg/day, every 12 hours) and foscarnet (60 mg/kg, every 8 hours) treatments were initiated for the patient. Pars plana vitrectomy with silicone endotamponade surgery (TÖ) was performed in the right eye and ganciclovir (30 µg/ml) was put into the infusion solution (Singh R et al., J Pediatr Hematol Oncol 2013; 35: e118–119). The left eye had nine intravitreal ganciclovir (4 mg/0.1 mL) injections in a period of 18 weeks by the same surgeon (TÖ). The retina remained attached in the right eye ([Fig. 1d and f]) postoperatively. Appearance of the left fundus was significantly improved after two ([Fig. 1e]) and six ([Fig. 1g]) ganciclovir injections and the left fundus looked almost free of active disease.

He received 21 days of iv foscarnet and 28 days of iv ganciclovir treatments and subsequently was put on oral valganciclovir. The patient had allogeneic stem cell transplantation at another institution but unfortunately passed away two months after the last injection. We obtained written consent from his family to publish this report.

Publication History

Article published online:
16 November 2023