Identification of Human Herpesvirus 6 in a Patient With Severe Unilateral Panuveitis FREE

Human herpesvirus 6 (HHV-6) is a member of the HHV family¹ and has been associated with immunodeficiency disorders and neurologic diseases.² This widespread virus can be classified into 2 groups: variant A (HHV-6A) and variant B (HHV-6B).² Although HHV-6B is the known causative agent in exanthema subitum,³ the association of HHV-6A with clinical entities is still unknown. We describe a patient with severe right-sided panuveitis and multiple subretinal lesions. The HHV-6A genome was detected in the ocular fluid of this patient.

A 75-year-old man developed a sudden decrease in vision in the right eye in 2005. Slitlamp examination of the right eye disclosed ciliary hyperemia, moderate mutton-fat keratic precipitates, and severely inflamed anterior chamber cells with hypopyon. Funduscopic examination of the right eye revealed dense vitreous opacities, optic disc swelling, yellowish-white massive retinal lesions measuring approximately 1.5 optic disc diameters, and whitish retinal exudates (Figure 1). The left eye was normal. Results of all systemic examinations, including serologic testing for human immunodeficiency virus, were negative, and results of serologic testing for HHVs (herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and HHV-6) were positive except for varicella zoster virus. On the basis of the ocular manifestations, a viral infection was suspected. After informed consent was obtained, an aliquot of aqueous humor and an aliquot of peripheral blood were collected and examined for further investigations. Immunoglobulin G for Toxocara larval excretory-secretory antigen in the aqueous humor and serum was detected using an anti-Toxocara antibody detection kit.⁴ A multiplex polymerase chain reaction demonstrated HHV-6 genomic DNA in both samples but not other HHVs (herpes simplex virus type 1 or 2, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, HHV-7, or HHV-8). To acquire quantitative data, a real-time polymerase chain reaction was performed at different stages of the clinical course. In the acute phase with active inflammation, a high copy number for the HHV-6 DNA was detected in the samples (aqueous humor: 2.4 × 10⁶ copies/mL; serum: 5.4 × 10⁶ copies/mL). Because the patient indicated that there was progression of intraocular inflammation, right eye diagnostic pars plana vitrectomy was performed. A high copy number for the HHV-6 genome was detected in the vitreous fluid, retinal membrane, and peripheral blood mononuclear cells. In addition, IgG for Toxocara larval excretory-secretory antigen in the vitreous was also detected. These data led us to make the diagnosis of panuveitis related to a Toxocara canis larva or an HHV-6 infection. Next we examined whether the HHV-6 infection was indicative of variant A or variant B. A high number of copies of HHV-6A was detected in the samples, and the HHV-6A genome decreased after antiviral valganciclovir hydrochloride treatment associated with systemic corticosteroids, whereas the HHV-6B genome was not detected (Figure 2). After treatment, funduscopic examination of the right eye revealed resolution of the vitreous opacities, optic disc swelling, and retinal exudates.

It is difficult to be certain whether HHV-6 was the causative agent in intraocular inflammation in this patient. Anti-Toxocara antibodies were also detected in serum and aqueous humor and vitreous samples, the significance of which is difficult to interpret. Another hypothesis could be that HHV-6 favored Toxocara-generated inflammation. However, the viral DNA and intraocular inflammation decreased in response to antiviral agents, suggesting that HHV-6A has some role in the pathogenesis of the ocular inflammation. To our knowledge, this is the first report of a case of HHV-6A associated with intraocular inflammation. These observations suggest that HHV-6A infection may have a role as a causative agent in severe intraocular inflammation.

Correspondence: Dr Sugita, Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan (sunaoph@tmd.ac.jp).

Financial Disclosure: None reported.

Funding/Support: This work was supported by Grant-in-Aid for Young Scientists (B) 18791263 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Additional Contributions: Ken Watanabe, PhD, and Miki Mizukami, PhD, provided technical assistance, and Yoshiharu Sugamoto, MD, PhD, obtained the samples.