A 44-year-old gentleman with a history of acute myeloid leukaemia presented 24 days following cyclophosphamide/total body irradiation (TBI) conditioned T-cell deplete sibling allogeneic peripheral blood stem cell transplantation with a 48 h history of a painful, weeping and red left eye. Medications included immunosuppression with mycophenolate mofetil 1 g three times daily and antimicrobial prophylaxis with itraconazole, aciclovir and trimethoprim-sulfamethoxazole. The patient had no other significant past medical history and no previous similar episodes. Following cursory examination a diagnosis of bacterial conjunctivitis was made and the patient was given treatment with chloramphenicol ointment, which was applied as directed. After 1 week, the symptoms had progressed and were bilateral with additional visual blurring and photophobia (Figure 1). At this time opthalmological examination revealed marked eyelid swelling with conjunctival injection and chemosis, and evidence of a mucoid discharge. Subconjunctival haemorrhages were present bilaterally. Visual acuity was preserved and fundal appearances were unremarkable. Bacterial cultures from eye swabs taken at the time of presentation remained negative. Subsequent swabs sent for virological analysis revealed the presence of adenovirus DNA by PCR testing, and adenovirus particles were isolated by viral culture. A diagnosis of bilateral haemorrhagic adenovirus keratoconjunctivitis was made. Genotypic studies confirmed the virus to be subgroup D. Urine, blood and stool samples tested for the presence of adenovirus by PCR remained negative. Potential viral exposures included close contact with a patient, also posthaematopoietic stem cell transplantation, in whom adenovirus DNA was subsequently identified in blood. Genotyping revealed the virus in this patient to be subgroup C, thus excluding the possibility of transmission to the index case. No other potential exposures were identified.
The patient was initially treated symptomatically with artificial tears and lubricants but failed to improve with this conservative approach. Reduction of immunosuppression was not feasible due to risks of graft versus host disease. Treatment with intravenous cidofovir 1 mg/kg was eventually instituted 11 days after the initial presentation. Cidofovir was given three times a week for a period of 4 weeks (total of 12 doses). This resulted in rapid clinical improvement and the patient was successfully discharged.
Adenoviruses are non-enveloped, lytic DNA viruses. There are 51 known subtypes capable of infecting humans.1, 2 Keratoconjunctivitis is a rare but recognized complication of adenoviral infection and cases are specifically associated with subgroup D viruses. Reported rates of adenoviral infection posthaematopoietic stem cell transplantation vary from 5 to 32% depending on methods of viral detection used.1 Risk factors for infection in this group include age (with children more likely to be affected than adults), adenovirus antibody positivity in the donor, unrelated or HLA mismatched allografts, total body irradiation and T-cell depletion.2 Antiviral treatments for adenoviral infections and the evidence for their efficacy in vivo is limited. Cidovovir has been shown to have in vitro activity against all adenoviral serotypes3 and data suggests an antiviral effect in certain treated individuals.4 In contrast, Ribavirin appears to have in vitro activity primarily against subgroup C viruses3 and this factor may contribute to the limited data supporting the antiviral efficacy of Ribavirin in vivo.5 In addition to existing antiviral strategies, adoptive immunotherapy using cytotoxic adenovirus-specific T-cells may be a promising future therapeutic alternative.1, 2, 6
Leen A, Bollard C, Myers G, Rooney C . Adenoviral infections in haematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006; 12: 243–251.
Leen A, Rooney C . Adenovirus as an emerging pathogen in immunocompromised patients. Br J Haematol 2005; 128: 135–144.
Morfin F, Dupuis-Girod S, Mundweiler S, Falcon D, Carrington D, Sedlack P et al. In vitro susceptibility of adenovirus to antiiral drugs is species-dependent. Antiviral Ther 2005; 10: 225–229.
Leruez-Ville M, Minard V, Lacaille F, Buzyn A, Abachin E, Blanche S et al. Real-time blood plasma polymerase chain reaction for management of disseminated adenovirus infection. Clin Infect Diseases 2004; 38: 45–52.
Lankester AC, Heemskerk B, Claas EC, Schilham MW, Beersma MF, Bredius RG et al. Effect of ribavirin on the plasma viral DNA load in patients with disseminating adenovirus infection. Clin Infect Diseases 2004; 38: 1521–1525.
Lenaerts L, Naesens L . Antiviral therapy for adenoviral infections. Antiviral Res 2006; 71: 172–180.
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Castleton, A., Kottaridis, P. A case of ‘red eye’ post allogeneic stem cell transplantation. Bone Marrow Transplant 39, 241–242 (2007). https://doi.org/10.1038/sj.bmt.1705568
Non-Graft-versus-Host Disease Ocular Complications after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation
Biology of Blood and Marrow Transplantation (2019)
Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT
Bone Marrow Transplantation (2019)
Current Ophthalmology Reports (2014)