Cytomegalovirus papilitis in a child with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common neoplasm in children.¹ 15–20% of patients suffer relapses that worsen the prognosis.² In addition, due to immunodeficiency derived from chemotherapy or leukemia, opportunistic infections may develop.

Cytomegalovirus (CMV) is a cause of morbidity and mortality in immunocompromised individuals and can affect several organs; eye infection in children is rare³ and usually appears as retinitis. CMV accesses the eye haematogenously. Histologically, it is characterised by a full-thickness necrotising retinitis. It can spread to the optic nerve, causing papillitis, inflammation of the optic nerve head with focal haemorrhages, with isolated papillitis being rare.⁴

Our objective is to show an atypical manifestation of CMV and the usefulness of aqueous humour analysis for differential diagnosis.

We present the case of a 9-year-old girl diagnosed with ALL who, after finishing maintenance treatment for leukemia, went to the emergency department owing to decreased visual acuity in her left eye.

On examination, she presented a visual acuity of 0.1 in the left eye with afferent pupillary defect. At the bottom of the left eye, papillitis was evident without vitritis or foci of chorioretinitis.

The analysis showed high values of acute phase reactants and in the microbiological study she presented a positive CMV IgM (1.55), with CMV IgG of 143 UA/ml. The CMV PCR in blood was 152,000 copies, but it was negative in the cerebrospinal fluid. It was decided to perform an anterior chamber puncture and repeat the lumbar puncture under general anaesthesia since a leukaemic infiltration could not be ruled out.

The CMV PCR of aqueous humour and cerebrospinal fluid were positive; she was diagnosed with CMV papillitis. She was treated with an injection of intravitreal ganciclovir, a descending corticosteroid regimen and antiviral treatment combined with ganciclovir 5 mg/kg/12 h for 18 days and foscarnet 60 mg/kg/8 h for 7 days. Subsequently, valganciclovir 450 mg/12 h orally was indicated for 8 months.

At one week, visual acuity had improved to 0.8 and improvement in papillitis was observed, which has been maintained until now (12 months).

Patients with ALL and ocular manifestations are a diagnostic challenge, since it is important to differentiate whether it is a recurrence or an opportunistic infection.

In this case, the patient had just finished the maintenance treatment, showed no signs of recurrence and the analysis showed elevated IgM antibodies for CMV. However, the absence of retinitis and the first negative lumbar puncture PCR caused doubt on the diagnosis of CMV papillitis, so it was decided to analyse the aqueous humour and repeat the lumbar puncture.

The first lumbar puncture PCR was possibly negative due to the small sample; in the second one, a greater amount could be collected.

Given the positive CMV PCR, CMV papillitis was diagnosed. In a study⁵ that evaluated PCR for the diagnosis of infectious uveitis in the posterior segment, it is concluded that when there is involvement of the optic nerve, the result is more likely to be positive. However, 71% of the patients had inflammation of the anterior chamber and none presented an isolated papillitis.

Analysis by aqueous humour PCR has also been studied in patients with CMV retinitis, confirming the high sensitivity and specificity of this test in different studies, although in many it is not necessary if there is inflammation of the anterior chamber.^6–8 This is the first case to date of isolated papillitis in which the aqueous humour analysis determined the cause of the infection.

CMV retinal involvement is a cause of blindness in patients with acquired immunodeficiency syndrome; however, there are few cases described in children with ALL.^3,9 Our patient had no retinitis, but an isolated papillitis; no papillitis has been described in any child with ALL.

Given the low incidence of CMV papillitis in the paediatric population, we believe it is important to publicise this manifestation for it to be taken into account in the differential diagnosis of leukaemic infiltration. Aqueous humour analysis is a useful technique to establish this diagnosis and carry out an appropriate treatment.