Sex: F
Vaccine: VARZOS
Symptoms: Anterior chamber cell, Cytomegalovirus test negative, Disseminated varicella zoster virus infection, Fundoscopy abnormal, Gene sequencing
Clinical narrative: Acute retinal necrosis; disseminated varicella zoster; viral pneumonia; hypoxic respiratory failure; systemic vesicular rash; vitreous haze; peripheral multifocal areas of retinal whitening; viral retinitis; peripheral atrophy; Floaters; progressive blurry vision; left afferent pupillary defect; artery sheathing; This case was reported in a literature article and described the occurrence of retinal necrosis in a 65-year-old female patient who received Herpes zoster (Shingrix) for prophylaxis.   The patient's past medical history included autologous hematopoietic stem cell transplant. Concurrent medical conditions included multiple myeloma. Concomitant products included daratumumab and pomalidomide.   On an unknown date, the patient received the 1st dose of Shingrix. On an unknown date, unknown after receiving Shingrix and an unknown time after starting Valacyclovir, the patient experienced retinal necrosis (serious criteria hospitalization and GSK medically significant), varicella zoster (serious criteria hospitalization), viral pneumonia (serious criteria hospitalization and GSK medically significant), hypoxic respiratory failure (serious criteria hospitalization and GSK medically significant), vesicular rash (serious criteria hospitalization), vitreous haze (serious criteria GSK medically significant), retinal exudates (serious criteria GSK medically significant), viral retinitis (serious criteria GSK medically significant), retinal atrophy (serious criteria GSK medically significant), floaters, blurred vision, marcus gunn pupil and retinal perivascular sheathing. The patient was treated with acyclovir, valaciclovir hydrochloride (Valacyclovir) and foscarnet. On an unknown date, the outcome of the retinal necrosis, vitreous haze, retinal exudates, viral retinitis, retinal atrophy, floaters, blurred vision, marcus gunn pupil and retinal perivascular sheathing were recovered/resolved and the outcome of the varicella zoster, viral pneumonia, hypoxic respiratory failure and vesicular rash were unknown.   The reporter considered the retinal necrosis, varicella zoster, viral pneumonia, hypoxic respiratory failure, vesicular rash, vitreous haze, retinal exudates, viral retinitis, retinal atrophy, floaters, blurred vision, marcus gunn pupil and retinal perivascular sheathing to be possibly related to Shingrix.  Additional details were provided as follows: This case was reported in a literature article and described the occurrence of acute retinal necrosis (ARN), disseminated varicella zoster, viral pneumonia, hypoxic respiratory failure in a 65-years-old female patient, who was vaccinated with Shingrix (GlaxoSmithKline) for prophylaxis. The patient had a past medical history of multiple myeloma treated with a previous autologous hematopoietic stem cell transplant and now with daratumumab and pomalidomide. No information on patient's family history, concurrent condition or concomitant medication was provided. On an unspecified date, 2 months prior to presentation, the patient received 1st (first) dose of Shingrix (recombinant zoster subunit vaccine) (administration route and site unspecified; batch number not provided). The age of vaccination was not provided. On an unspecified date, 6 (six) weeks after the vaccination, the patient was hospitalized after developing a systemic vesicular rash and hypoxic respiratory failure, during which the patient was treated for disseminated varicella zoster and viral pneumonia. The patient was treated with intravenous acyclovir 10 mg/kg every 8 hours and discharged on oral acyclovir 400 mg twice daily. Two weeks after discharge from the hospital, the patient developed floaters, followed by progressive blurry vision (OS). The patient presented with 2-week history of worsening floaters and blurred vision in her left eye (OS) for 5 days. On exam, her best corrected visual acuity was 20/25 in the unaffected right eye (OD) and 20/70-1 in the left eye. The patient had a left afferent pupillary defect and intraocular pressures of 14 and 21 mmHg in her right and left eyes, respectively. Full ocular examination of the right eye was unremarkable. Slit lamp examination of the left eye revealed 2+ anterior chamber and 2+ anterior vitreous cells. Funduscopic exam OS demonstrated 2+ vitreous haze and peripheral multifocal areas of retinal whitening with associated artery sheathing. An anterior chamber paracentesis was performed on the left eye due to the high suspicion of viral retinitis based on her presentation. Her aqueous was sent for polymerase chain reaction (PCR) detection of varicella-zoster virus (VZV), herpes simplex virus (HSV), cytomegalovirus (CMV), and toxoplasmosis. The patient was given an intravitreal injection of foscarnet (2.4 mg/0.1 ml) and started on valacyclovir 2 g three times per day. The patient was asked to stop her immunotherapy. Five days after presentation, PCR testing for HSV, CMV, and toxoplasmosis DNA resulted as undetectable. VZV DNA was detected. Genotyping performed by the Centers for Disease Control (CDC) identified the virus as wild-type and not associated with the Oka strain used to manufacture the live attenuated vaccine. The patient was continued on therapeutic dose valacyclovir and treated with biweekly intravitreal injections of foscarnet for a total of 11 weeks. At week 8, there was consistent regression of retinitis, and the patient was asked to restart her immunotherapy for multiple myeloma. At her most recent follow-up, 19 weeks after presentation, her examination remains free of active retinitis. [Fundus photograph of the patient's left eye 19 weeks after initial presentation showed resolution of retinitis with large areas of peripheral atrophy]. Her visual acuity had improved to 20/50+ with resolution of her afferent pupillary defect. This case has been considered as serious due to hospitalization. The author commented, "Ocular adverse events following any VZV vaccination are rare. Our patient developed a systemic vesicular rash and viral pneumonia 6 weeks after Shingrix, followed by ARN secondary to VZV. As Shingrix is a subunit vaccine and not an attenuated live virus, iatrogenic infection is theoretically impossible. In our patient's case, the VZV isolate was genotypically confirmed to be wild-type, without evidence of recombination or mutation. The temporal relationship of this patient's disseminated zoster and ARN shortly following receipt of the recombinant subunit vaccine raises the possibility of an immunomodulatory phenomenon contributing to dormant VZV reactivation. It is also possible that the disseminated zoster and ARN are not related to the Shingrix vaccine. Our patient is the first reported case of disseminated zoster and ARN occurring shortly after Shingrix administration amongst 11 million patients who received at least one dose." The author concluded, "In conclusion, our case of disseminated zoster and acute retinal necrosis following vaccination with the recombinant subunit has important clinical implications. The Practices has recommended the use of the recombinant glycoprotein E (gE) vaccine over the live-attenuated Zostavax vaccine for secondary prevention of herpes zoster due to its wider range of efficacy. Additionally, there is significant interest in the recombinant vaccine's potential to benefit immunosuppressed patients in whom Zostavax is contraindicated, and the off-label use of Shingrix in these populations has been supported up to this point by studies demonstrating its relative safety in hematopoietic stem cell or solid organ transplant recipients. Though post-vaccination VZV infection or reactivation appears to be rare, clinicians should be aware of this potential complication to the recombinant subunit vaccine."