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Human papilloma virus (HPV) is the most common sexually transmitted infection in the USA with 6.2 million new cases diagnosed annually.1 The majority of infections are asymptomatic, but high-risk HPV types act as a carcinogen in the development of cervical and anogenital cancers.2 In June 2006, the Food and Drug Administration licensed a quadrivalent HPV vaccine (GARDASIL, Merck, Whitehouse Station, New Jersey) for females aged 9 to 26 years. To our knowledge there are no reports of HPV-related intraocular inflammation and no reports of quadrivalent HPV vaccine-related ocular inflammation. We report a case of ampiginous choroiditis following the administration of the quadrivalent HPV vaccine.
A 17-year-old female was referred for new-onset vision loss in both eyes 3 weeks after being vaccinated with the quadrivalent HPV vaccine. A standard dose of 0.5 ml was injected intramuscularly into the left deltoid without any resulting skin reaction. Her medical history was significant for depression treated with quetiapine. Three weeks following vaccination, she developed painless vision loss in the left eye followed 2 days later with painless vision loss of the right eye. The patient denied any viral prodrome. On examination, visual acuity measured 20/60 in the right eye and 20/100 in the left eye. Intraocular pressure measured 14 mm Hg in both eyes, and there was no conjunctival injection, no anterior chamber cells and no anterior vitreous inflammation. On dilated fundus exam she was found to have multiple creamy chorioretinal infiltrates in the macula extending into the mid-periphery, left eye greater than right (fig 1). On fluorescein angiography, the lesions demonstrated early hypofluorescence and late hyperfluorescence (fig 1). Systemic evaluation was within normal limits and included a complete blood count with differential, tuberculin skin test, chest radiograph, lyme titres, rapid plasma reagin and fluorescent treponemal antibody. There was no family history of autoimmune disease. The patient was diagnosed as having acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and observed. After 5 days, the patient’s vision deteriorated to 20/400 in the right eye and count fingers at six feet in the left eye, and fundus exam demonstrated chorioretinal scarring in the macula with persistent activity of the lesion margins. At this time, because of the scarring, the diagnosis shifted to ampiginous choroiditis, and oral prednisone 1 mg/kg/day was initiated. The prednisone was successfully tapered off within 3 months without recurrence of the choroiditis, but extensive macular scarring remained (fig 2). The final visual acuity was 20/50 in the right eye and 20/60 in the left eye.
Ampiginous choroiditis, a variant of serpiginous choroiditis, is a bilateral aggressive posterior uveitis that appears multifocal and placoid in its initial phases but coalesces and shows progression of lesions in its evolution.3 The visual prognosis is poor in ampiginous as compared with APMPPE, and it is our standard practice to employ high-dose oral prednisone if there is any sign of persistent activity or progression of lesions consistent with an ampiginous choroiditis diagnosis. APMPPE has been reported following administration of various vaccinations, including swine flu vaccine, hepatitis B vaccine, meningococcal C conjugate vaccine and varicella vaccination, but to our knowledge there have been no reports linking the HPV vaccine to intraocular inflammation.4 In addition, we are not aware of reports of ampiginous or serpiginous choroiditis associated with any vaccination, although contradictory reports exist regarding the involvement of herpes virus in serpiginous choroiditis.5 6
Quadrivalent HPV- vaccine is designed as a prophylactic immunisation against HPV types 6, 11, 16 and 18, and is given in three injections over a 3-month period. The Advisory Committee on Immunization Practices currently recommends this vaccine at the age of 11 or 12 years.1 2 Molecular mimicry has been reported in a comparative computer analysis between HPV type 16 oncoprotein and human self-proteins and showed high and widespread similarity in a number of critical regulatory processes.7 Possible mechanisms linking the quadrivalent HPV vaccine and this case of ampiginous choroiditis include a widespread, non-specific immune response or a molecular mimicry aetiology, but with a lack of a viral prodrome it is unlikely to involve a non-specific immune response.
This case does not prove causation, but the temporal relationship between quadrivalent HPV vaccination and onset of an aggressive ampiginous choroiditis is intriguing and may shed light on the immunological triggers involved in posterior non-infectious uveitis. Ophthalmologists as well as primary care physicians should be cognisant that the HPV vaccine may be a trigger for uveitis.
Funding The Department of Ophthalmology at UCSF is supported by a core grant from the National Eye Institute, EY02162. Dr Acharya is supported by a National Eye Institute K23EY017897 grant and a Research to Prevent Blindness Career Development Award.
Competing interests None.
Patient consent Obtained.
Provenance and Peer review Not commissioned; externally peer reviewed.