Herpes zoster ophthalmicus: declining age at presentation

Herpes Zoster Ophthalmicus Clinical Presentation and Risk Factors for Loss of Vision

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4–20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO.

To determine the prognostic value of nasociliary skin lesions (Hutchinson's sign) for ocular inflammation and corneal sensory denervation in acute herpes zoster ophthalmicus. A longitudinal observational study with a 2-month follow-up was performed involving 83 non-immunocompromised adults with acute herpes zoster ophthalmicus, with a skin rash duration of less than 7 days, referred by their general practitioner. All skin lesions at the tip, the side and the root of the nose, representing the dermatomes of the external nasal and infratrochlear branches of the nasociliary nerve, were documented by taking photographs and marking anatomical drawings. Ocular inflammatory signs were observed by slit-lamp biomicroscopy, and corneal sensitivity was measured with the Cochet-Bonnet esthesiometer at 2-month follow-up. Hutchinson's sign was a powerful predictor of ocular inflammation and corneal denervation in herpes zoster ophthalmicus [relative risks: 3.35 (CI 95%: 1.82-6.15) and 4.02 (CI 95%:1.55-10.42), respectively]. The manifestation of herpes zoster skin lesions at the dermatomes of both nasociliary branches was invariably associated with the development of ocular inflammation. Clinicians should be alert for early skin lesions within the complete nasociliary dermatome, because they are a reliable prognostic sign of sight-threatening ocular complications in acute herpes zoster ophthalmicus.

Herpes zoster is identified as a reactivation of latent varicella zoster virus (VZV) within a single dorsal root or cranial sensory ganglion (Oxman 2009). When the latent VZV reactivates in the ophthalmic branch of the trigeminal nerve, herpes zoster ophthalmicus (HZO) occurs (Vrcek et al. 2017). Of those patients with HZO, about 70% may develop ocular complications (Weinberg 2007). This cohort study aimed to explore the relationship between HZO and the subsequent risk of neovascular AMD using a population-based data set in Taiwan. Medical records for this cohort study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005) (TMU-JIRB N201705073). For the study cohort, we initially identified 1668 patients who had received a first-time principal diagnosis of HZO (ICD-9-CM codes 053.2) during an ambulatory care visit between 2001 and 2010. The date a patient received their first HZO diagnosis was identified as the index date. We then excluded 499 patients who were aged less than 40 years. In addition, we excluded 21 patients who had a medical history of dry AMD (ICD-9-CM code 362.51) or neovascular AMD (ICD-9-CM codes 362.52) prior to the index date. Finally, 1148 patients with HZO were recruited in the study cohort. The matched comparison cohort (n = 5740) (five comparison subjects per HZO patient) was selected from the remaining beneficiaries of the LHID2005. The comparison cohort was identified by matching HZO patients in terms of propensity score. The matching variables included patients’ sex, age, monthly income, urbanization level, geographical region, hypertension, coronary heart disease, hyperlipidaemia, tobacco use disorder and diabetes. The date of a comparison patient's first use of ambulatory care during that matched year was defined as the index date. Additionally, we ensured that none of the selected comparison subjects had been diagnosed with neovascular AMD before the index date. Each patient was individually tracked for a 3-year period starting from their index date to define those who were subsequently diagnosed with neovascular AMD. Table 1 shows that among all sampled patients, the incidence rate of neovascular AMD per 1000 person-years within the 3-year follow-up period was 2.31 (95% CI: 1.69–3.08). In addition, the findings indicated that incidence rates of neovascular AMD per 1000 person-years within the 3-year follow-up period were 6.82 (95% CI: 4.27–10.32) for HZO patients and 1.44 (95% CI: 0.92–2.13) for comparison subjects. The stratified Cox proportional analysis (stratified by propensity score) revealed that the hazard ratio of neovascular AMD during the 3-year follow-up period was 4.62 (95% CI: 2.59–8.24) for HZO patients compared to comparison subjects. This population-based cohort study found that HZO patients were 4.62 times more likely to suffer from neovascular AMD compared to those patients without HZO. Even though the actual pathogenesis of the association between HZO and neovascular AMD is uncertain, abnormal inflammation in HZO patients may be one of the possible mechanisms to explain this connection. The previous literature indicated that HZO patients usually also had ocular inflammation (Liesegang 2008; Sanjay et al. 2011). Some studies also reported that VZV infection via ophthalmic division of the trigeminal nerve may trigger a local inflammatory response that can further affect the retina, optic nerve, cornea, conjunctiva, iris (Bandeira et al. 2016; Vrcek et al. 2017), etc. Furthermore, the vasculopathy due to VZV infection might be another potential pathway to elucidate the relationship between HZO and subsequent neovascular AMD. This study revealed that HZO patients had a higher risk of subsequent neovascular AMD than matched comparison cohort. We suggest that further large epidemiological studies are warranted to ascertain the relationship between HZO and neovascular AMD in different populations.

Herpes zoster ophthalmicus (HZO) has already been reported in young healthy children, most of them with a history of chickenpox or varicella zoster virus (VZV) vaccination [1–10].We present a case of HZO in a previously healthy 2.5-year-old boy. To our knowledge, our case report is the first publication in which both serological analyses showed VZV seroconversion and polymerase chain reaction (PCR)-confirmed VZV DNA in the fluid from the patient’s vesicular rash. History and Clinical Examination A 2.5-year-old boy presented with acute onset of a vesicular rash involving the left forehead with swelling and erythema of the left upper eyelid since day 1. The patient had previously always been healthy, and, more specifically, he had never had any clinical manifestations of varicella or herpes simplex virus (HSV) infections and had never received a vaccine against varicella. The mother had developed chickenpox during childhood and was known to experience recurrent herpes labialis. An older brother had developed varicella at the time of birth of the patient after a normal pregnancy and full-term normal delivery. Our patient did not develop any rash or fever at that time. Further family history was unremarkable. The clinical examination revealed a subfebrile temperature (peak 38.3°C), but other vital signs were normal. The rash was vesicular, covered with golden yellow crusts, and distributed according to the ophthalmic division of the left trigeminal nerve (forehead and periocular). Inspection of the left eye showed marked erythema and swelling of the upper eyelid. Hutchinson’s sign, a predictor of ocular inflammation and corneal sensory denervation, was absent. Eye movements and visual acuity were normal. Macroscopic inspection of the anterior segment of the eye did not show any fluorescein staining of the corneal epithelium. There were no signs of ocular complications. Further clinical examination was unremarkable. Because of a clinical suspicion of HZO with bacterial superinfection (impetigo), the patient empirically received intravenous and topical acyclovir and intravenous flucloxacillin. Laboratory Investigations At admission, hematological investigation revealed a white blood cell count of 4.9 × 10 3 cells/μL (reference range, 5.5–15.5 × 10 3 cells/μL). Basic biochemical (sodium, potassium, chloride, bicarbonate, anion gap, bilirubin, serum glutamic pyruvic transaminase, and serum glutamic oxaloacetic transaminase) and basic immunological tests (immunoglobulin [Ig]G, IgG subclasses, IgM, IgA, complement C3 and C4 levels) showed no abnormalities. The C-reactive protein level was normal. Serological analyses for VZV and HSV were performed. Both VZV, anti-VZV IgM and anti-VZV IgG (Liaison VZV IgM and IgG kit; DiaSorin, Saluggia, Italy), and HSV, anti-HSV IgM and anti-HSV IgG (Enzygnost assay on BEP 2000 Advance System; Siemens, Erlangen, Germany), antibodies were negative. Fluid from the vesicular rash was collected, and real-time PCR (DNA extraction with NucliSENS easyMAG nucleic acid extractor [bioMerieux SA, Marcy l’Etoile, France] and real-time PCR with Affigene VZV tracer kit [Cepheid, Bouwel, Belgium] on the Rotor-gene 6000 [Qiagen, Venlo, Netherlands]) for the detection of VZV DNA was positive. Culture from an ESwab (Becton, Dickinson and Company, Erembodegem, Belgium) (forehead and upper eyelid) confirmed secondary bacterial infection with Staphylococcus aureus. Six days after initial serologic analyses, anti-VZV IgM and anti-VZV

IntroductionAlthough varicella zoster virus (VZV)-induced vasculopathy and stroke after herpes zoster (HZ) attacks have been previously reported, data regarding stroke frequency after zoster attacks are lacking. This study investigates the...

Herpes zoster ophthalmicus (HZO) is a clinical manifestation of the reactivation of latent varicella zoster virus (VZV) infection in the trigeminal ganglia that affects the nerve's ophthalmic division.1 Timely diagnosis and treatment are critical in reducing visual morbidity. HZO can result in a variety of long-term and recurrent complications, which can be sight-threatening.1 Herein, we report a very rare case of ulcerated keloid on HZO scar that developed in an immunocompetent young woman. A 26-year-old white female presented with a blurred vision. She had a history of herpes zoster ophtalmicus involving the right side of the forehead 4 months earlier. The infection was insufficiently treated with oral valacyclovir as the patient only received the drug for 3 days. Clinical examination revealed a keloid scar in the forehead with a sharp vertical demarcation line, associated with a palpebral retraction and eyelid necrosis (Figure 1). Dermatological examination was otherwise normal, with no further keloid scars. The extraocular motility was full. Her visual acuity was limited to hand motion on the right eye and 20/20 in the left eye. Anterior segment examination found an ulcerative stromal keratitis and corneal hypoesthesia. The posterior segment was unremarkable. She had a negative HIV test. She underwent superior eyelid reconstruction with intralesional injections of corticosteroids for her keloid scar with a favorable outcome. Keloid is a benign connective tissue tumor that develops as a result of a complex aberrant wound-healing response.2 It can result in disfiguration, restriction of movement, infection, and ulceration as seen in our patient.2 The mechanisms underlying the development of keloids are not well known. Both hereditary and environmental factors play a role in keloid formation. Given the absence of family history and the unique anatomical site of the keloid in our case, the familial predisposition may not apply. Indeed, old scars in other parts of her body showed no signs of keloid even in high-risk areas like the chest. The term Wolf's isotopic phenomenon refers to the development of new skin disease at the site of a previously cured one.3 In most cases, the preceding disease is HZ.4 The most frequent isotopic responses that develop on the site of HZ are granulomatous and lichenoid reactions and infiltrations of hematologic diseases.5 Keloid formation is an extremely rare but well-documented isotopic response of HZ. It was initially reported by Requena et al.5 who investigated cutaneous reactions at sites of HZ scars in 16 patients. Among them, only one patient developed keloid. In another study, among 246 HIV-positive patients, 23 patients had keloid development as a complication of HZ.6 Only one case of keloid formation in HZ ophthalmicus has been described, it occurred in an African woman following the use of traditional herbs to the herpetic rash.7 A wide range of latency durations between infection and cutaneous reaction, spanning from days to years, was described.3 The pathogenesis of these skin reactions is not totally understood. Viral and immunological etiologies were proposed. Viral infection may alter local skin immunity which would favor hyperreactivity, leading to inflammatory processes, or local immunosuppression, leading to tumor infiltrations or infections.3 We report here the first case of ulcerated keloid after HZO in an immunocompetent woman. We hypothesize that keloid formation, in our patient, can be explained by Wolf isotopic phenomenon. Herpes zoster (HZ) lesions were also deep and poorly treated, which could have played a role. Rym Maamouri and Anissa Zaouak wrote the manuscript with support from Refka Frioui. Amri Ali analyzed the data. Monia Cheour supervised the project. All authors have read and approved the final manuscript. None declared. The authors certify that they have obtained all appropriate patient consent forms, in which the patients gave their consent for imagesand other clinical information to be included in the journal.

Approximately 1 million new cases of herpes zoster (HZ) occur in the United States annually, including 10%-20% with herpes zoster ophthalmicus (HZO). Postherpetic neuralgia, a debilitating pain syndrome occurs in 30% HZ, whereas 50% HZO develop ophthalmic complications. Diplopia from cranial nerve palsy occurs in less than 30% HZO, whereas optic neuropathy is seen in less than 1% HZO. We reviewed recent developments in the diagnosis, treatment, and prevention of HZ as well as neurological and ophthalmological complications of relevance to the neuro-ophthalmologist. We searched the English language literature on Pubmed and Google scholar for articles relevant to the various sections of this review. Antiviral treatment should be initiated within 48-72 hours of onset of HZ and HZO to decrease pain and reduce complications. We recommend neuroimaging in all patients with neuro-ophthalmic manifestations such as diplopia and acute vision loss. Diagnostic confirmation using polymerase chain reaction and serology on paired serum and cerebrospinal fluid samples should be obtained in those with neurological signs and symptoms or abnormal imaging. Patients with neurological and/or retinal varicella zoster virus (VZV) infection should be treated promptly with intravenous acyclovir. Patients with isolated optic neuropathy or cranial nerve palsy can be managed with oral antivirals. The prognosis for visual recovery is good for patients with isolated optic neuropathy and excellent for patients with isolated ocular motor cranial nerve palsy. HZ produces a spectrum of potentially blinding and life-threatening complications that adversely affect quality of life and increase health care costs. Individuals at risk for HZ, such as the elderly and immunocompromised, should be encouraged to receive the highly effective VZV vaccine to prevent HZ and its complications.

Varicella zoster virus (VZV) infection, early in life, has been shown to have a protective role against the development of asthma and atopy in children. It is unknown whether VZV infection in late childhood and adolescence also has an asthma protective effect. We studied whether VZV infection in late childhood and adolescence, or administration of the live attenuated varicella vaccine, provides a similar protective effect. In the present study, we use a retrospective chart review of a pediatric practice (N = 62) to analyze the effect of wild-type (WT) VZV infection or recombinant varicella vaccine in children (age 3–21 years) diagnosed with asthma. We found (1) asthma onset occurred 9.4 ± 4.4 years after WT VZV infection (4.4 ± 2.2) by age 13.9 ± 6.5 years, but only 3.0 ± 1.7 years after recombinant vaccine (3.2 ± 3.0 years) at age 5.0 ± 3.6 years (P = 0.05); (2) asthma classifications were 61.5% intermittent, 15.4% mild persistent, and 23.1% moderate persistent after WT VZV infection, but were 30.0% inte...

Herpes zoster (HZ) is associated with complications such as postherpetic neuralgia (PHN) and HZ ophthalmicus (HZO). However, few studies have focused on identifying patients having a high risk of PHN and HZO according to the initial presentation sites. The current study investigated these factors in a nationwide population-based cohort derived from Taiwan’s Longitudinal Health Insurance Database. The results indicate that the initial presentation sites can predict the complication site of HZ. In this study, elderly patients were found to be more susceptible to HZ and were the first to present with neurological signs (HZN). Furthermore, compared with patients with HZO and other signs (HZT), those with HZN had a higher comorbidity risk. Patients with HZN showed a significantly higher visceral complication risk than did those with HZO (adjusted hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 1.27–1.71). In addition, patients with HZT showed lower risks of ocular and neurological complications than did those with HZN after stratification by age and sex (adjusted HR = 0.46, 95% CI = 0.31–0.68 and HR = 0.73, 95% CI = 0.59–0.91, respectively).

Varicella-zoster virus-induced orbital apex syndrome with superior ophthalmic vein occlusion and malignant intraocular pressure rise

Varicella vaccination in children with nephrotic syndrome: A report of the Southwest Pediatric Nephrology Study Group

Herpes zoster is a common diagnosis in the emergency department which is caused by reactivation of varicella zoster virus (VZV). Reactivation in ophthalmic division of trigeminal nerve causes Herpes zoster ophthalmicus. It is associated with a rash in the distribution of the trigeminal nerve dermatomes especially in ophthalmic and maxillary divisions. The most often complications of HZO are episcleritis, keratitis, glaucoma, and cataracts. HZO with cranial neuropathy is a very rare condition. So herewith we report a case 51 years old female with swelling, redness in right eye and drooping of eyelids on the right side. She had tearing and double vision. She was diagnosed with herpes zoster ophthalmicus with neuropathy of 3rd, 4th and 6th cranial nerves. The patient was treated and discharged in a healthy condition. Timely diagnosis and treatment can decrease morbidity and prevent the complication.

Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited. To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO). Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217,061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period. Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship-trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases. One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO. AND RELEVANCE The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

To report an unusual case of a late-stage reactivation of immune stromal keratitis associated with herpes zoster ophthalmicus (HZO), occurring without any apparent predisposing factors, more than 4 years after an acute zoster dermatomal rash. Significant corneal hypoesthesia and a central band keratopathy developed within 6 months of the late-stage reactivation. The clinical case management, issues associated with management, and management options are discussed, including the use of standardized, regulatory approved, antibacterial medical honey. An 83-year-old woman presented for routine review with a reactivation of right anterior stromal keratitis and mild anterior uveitis, occurring more than 4 years after an acute HZO dermatomal rash and an associated initial episode of anterior stromal keratitis. Corneal sensation became markedly impaired, and over the subsequent 6 months, a right central band keratopathy developed despite oral antiviral and topical steroid therapy. Visual acuity with pinhole was reduced to 20/100 in the affected eye and moderate irritation and epiphora were experienced. The patient declined the surgical intervention options of chelation, lamellar keratectomy, and phototherapeutic keratectomy to treat the band keratopathy. Longer-term management has involved preservative-free artificial tears, eyelid hygiene, standardized antibacterial medical honey, topical nonpreserved steroid, and UV-protective wraparound sunglasses. The clinical condition has improved over 14 months with this ocular surface management regimen, and visual acuity of 20/30 is currently achieved in a comfortable eye. The chronic and recurrent nature of HZO can be associated with significant corneal morbidity, even many years after the initial zoster episode. Long-term review and management of patients with a history of herpes zoster stromal keratitis are indicated following the initial corneal involvement. Standardized antibacterial medical honey can be considered in the management of the chronic ocular surface disease associated with HZO and warrants further evaluation in clinical trials.