Herpes Zoster Ophthalmicus: A Review

Herpes zoster is caused by reactivation of varicella zoster virus. When primary infection by varicella during childhood (chickenpox) is resolved, the virus particles remain as a dormant in the dorsal root or other sensory ganglion for many decades. The virus then reactivates as a result of aging, excessive stress, immunosuppressive illness, or other medical treatment that suppress the immunity. This reactivation of latent varicella zoster causes herpes zoster.

Herpes zoster ophthalmicus (HZO) involves the ophthalmic branch, which is the first division of the trigeminal nerve. According to several studies ophthalmic division of the trigeminal nerve are involved in about 10-25% of reported cases of herpes zoster cases. Zoster ophthalmicus is estimated to occur approximately in 10% of zoster patients under the age of 10 years and about 30% of patients aged 80-year-old and older. Thus patients older than 50 years of age are frequently at increased risk of that HZO [1]. The rash of ophthalmic zoster may extend from the level of the eye to the vertex of the skull and does not cross the midline of the forehead.

Signs and Symptoms of Herpes zoster ophthalmicus

Influenza-like illness with malaise and low-grade fever are common at the start of HZO that lasts up to 5 days before the appearance of rash on the forehead, eyelids and periorbital region. Subsequently, erythematous macules appear along the involved dermatome, rapidly progressing to papules and vesicles containing clear serous fluid and pustules over several days. Then finally these lesions rupture and get crusted. The eye very rarely gets involved when the maxillary branch of nerve is involved. Involvement of the nasociliary branch of the ophthalmic nerve which is evidenced by a zosteric rash on the tip and side of the nose (Hutchinson’s sign) is seen in about one-third of patients HZO and is usually accompanied by ocular symptoms. Thus, when ophthalmic zoster affects the side and the tip of the nose, careful attention must be given to the condition of the eye and immediate ophthalmologic consultation is necessary in order to prevent complications of the eye and central nerve system Zoster Infection.

Herpes Zoster Ophthalmicus

Herpes Zoster Ophthalmicus

The reactivated VZV travels down the ophthalmic nerve ganglion resulting in HZO. It takes about 3-4 days for the virus to reach the nerve ending. Nasociliary branch innervates both the tip and the homolateral side of the nose as well as the cornea so most serious ocular involvement will develop if this branch is affected. Hutchinson’s sign is classical sign representing the involvement of ocular structures. VZV-DNA was detected in conjunctival swabs of some cases of acute ophthalmic zoster disease [2]. All the patients who develop herpes zoster adjacent to eye do not develop ocular involvement, but in those that do, there can be a wide variety of manifestations.

Acute Stage of Ocular Involvement

Besides pain and rash in the affected ophthalmic dermatome other acute stage ocular involvement includes swelling and reddening of eye, ptosis with some even developing blepharitis and vesicular lesions which mostly resolves with scarring. Conjunctivitis is also common finding usually presents with the appearance of rash and resolves within 1 week. Episcleritis and scleritis are also not uncommon and involvement of cornea occurs if the condition lasts more than 1 week. Keratitis is another common presentation which occurs in various forms e.g. nummular keratitis and disciform keratitis and is detected about 10–21 days after onset of rash. There is also a stromal haze surrounding the lesions. Anterior uveitis which is also quite frequently seen develops 2 weeks after the onset of rash, can result in iris atrophy due to sever inflammation of rash. Also endothelial dysfunction of the cornea may occur leading to edema with central vision loss [3].

Chronic Stage of Ocular Involvement

Chronic involvement of sclera and cornea is much more common than the acute clinical findings. Stromal keratitis which may develops after 3-4 months of initial onset of disease is characterized by infiltrates of differing degree and is usually localized in the center of cornea. Keratitis may finally result in neurotrophic keratopathy. Corneal thinning with bullous keratopathy and corneal perforation may also lead to vision loss.

Acute retinal necrosis syndrome (ARN) and progressive outer retinal necrosis syndrome (PORN) are almost very rare findings in young patients. ARN and PORN are characterized by pain and blurred vision in one or both eyes (30% bilateral involvement). Clinically the fundus of ARN shows whitening and peripheral patches with occlusive vasculitis and vitreous inflammation. In case of PORN, vitreous cells are absent as immunocompromised individuals are not able to produce an inflammatory response. In such cases even early course of antiviral therapy may not work and may lead retinal detachment in about 70% of the cases.

Recent study has reported several ocular manifestations of HZO. Pain was the most presenting symptoms in all individuals. Eyelid and ocular adnexal involvement is most commonly seen in patients with herpes zoster ophthalmicus followed by conjunctivitis, corneal complication, uveitis and PHN. As HZO may cause visual loss, regular ophthalmic examination is very important.

Treatment of Herpes Zoster Ophthalmicus

Beside, commonly used antivirals agents for herpes zoster like acyclovir, Famciclovir, valacyclovir, and brivudin, immediate use of a single intravitreal injection of foscarnet is usually recommended to further stop viral replication and progression to retinitis especially in case of ARN or PORN [4]. Systemic steroids are generally recommended for immunocompetent patients and those over 60 years of age but are strictly contraindicated in immunocompromised individuals at any age. Oral antiviral agents when given early have better prognosis and in management to PHN. Study shows that, Brivudin [5] had an 11% lower PHN rate than acyclovir and was as seen as effective as famciclovir to reduce zoster associated pain. In case of resistance to common antivirals agents, intravenous foscarnet, 40 mg/ kg body weight 3 times a day or 50 mg/ kg body weight twice a day is recommended. Treatment with cidofovir is recommended in case of resistance with intravenous foscarnet. These two antiviral agents should only be given in special cases when required as they have severe side effects like nephrotoxicity, ocular hypotony etc.

References:
[1] Hardening SP, Lipton JR, Wells JCD: Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br J Ophthalmol 1987:353–358.
[2] Zaal MJW, Völker-Dieben HJ, Wienesen M, DÀmaro J, Kijlstra A: Longitudinal analysis of aricella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus. Am J Ophthalmol 2001:25–29.
[3] Zaal MJW, Völker-Dieben HJ, DÁmaro J: Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus. Acta Ophthalmol Scand 2003:216–220.
[4] Gümbel H, Ohrloff C: Opportunistic infections of the eye in immunocompromised patients. Ophthalmologica 1997:53–61.
[5] Vij O, Bornfeld N, Roggendorf M, Fiedler M, Schilling H: Brivudin as an alternative systemic therapy to acyclovir and ganciclovir in acute retinal necrosis syndrome due to varicella zoster virus. Klin Monatsbl Augenheilkd 200:710–715.

Herpes Zoster Oticus

Herpes zoster oticus usually accounts for 1% of all the zoster infection and manifests as cutaneous vesicular eruption of the internal or external canal and pinna and is characterized by severe ear pain, a rash around the ear and usually associated with facial paralysis so called Ramsay Hunt Syndrome which was coined after the neurologist James Ramsay Hunt who had described the disease in 1907. He suggested that the disease resulted from a geniculate ganglionitis after reactivation of surviving viruses (VZV), a theory that recently proved true for many cases examined. Ramsay Hunt syndrome is considered as a rare complication of the varicella zoster virus and is characterized by peripheral facial palsy resulting from facial and auditory nerves injury during VZV infection. In addition, Ramsay Hunt syndrome may be also be associated with cranial nerves V, VI, IX, X and XII [1]

Facial palsy as a most important clinical symptom may be related to a necrotizing inflammation of the ganglion. However, sometimes it may occur without the involvement of ganglion or may be due to neuritis or perineuritis of nerve itself. Histological studies in temporal bones of decedents within the course of the disease revealed various perineural, perivascular or intraneural infiltration with different degrees of tissue destruction. Secondary effects like swelling by edema and/or hemorrhage may cause compression of the nerve within its bony canal. In those areas blood circulation may severely be impaired, leading to additional damage. Hearing loss, vertigo and tinnitus which are often seen is caused by inflammation of the inner ear structures.

Generally, herpes zoster oticus is considered as a disease of elderly and immunocompromised individuals. However, it may also be seen in young adults during stressful condition.[2] Even in children with acute peripheral facial paralysis, varicella zoster virus reactivation is considered an important factor [3]. Surgical manipulation is sometimes considered as a cause of outbreak of the disease. The disease is often unilateral and bilateral involvement is very rare but may be seen in immunocompromised individuals.

Although clinical course may vary from individual to individuals, general a prodromal period with fatigue and other sickness-like symptoms (approximately 7–14 days) is followed by a phase of erupting herpetiform lesions. Erythematous maculopapular lesions around or on the auricle (most often in the concha or the superficial part of the outer ear canal) soon vesiculate and sometimes turn to ulcers. Vesicles in the buccal mucosa of the corresponding sides or oropharynx can also be seen in rare cases. There may be slightly increase in body temperature and moderate to severe pain in the ear and surrounding which may persist even after the resolution of the lesions. Lesions usually turn dry and crust out after 1 week. Regional lymphadenopathy may be common findings. In about 8% to 10% of the patients zoster oticus may occur without the classical zoster rash also known as zoster sine herpete. [4]

Herpes zoster oticus accounts for about 10% all the facial palsy. Facial nerve involvement is seen in about 70% of the zoster oticus patients. Facial palsy is usually seen after the eruption of rash, proceeding from mild facial weakness to complete unilateral paralysis. If untreated the prognosis is very poor and chances of recovery is 70% in partial paralysis and only 10% in complete paralysis.[5]

References:
1. Sun WL, Yan JL, Chen LL: Ramsay Hunt syndrome with unilateral polyneuropathy involving cranial nerves V, VII, VIII, and XII in a diabetic patient. Quintessence Int. 2011 Nov-Dec;42(10):873-7.
2. Meister W, Neiss A, Gross D, Doerr HW, Höbel W, Malin JP, von Essen J, Reimann BY, Witke C, Wutzler P: Demography, symptomatology and course of disease in ambulatory zoster patients. Intervirology 1998;41:272–277.
3. Furuta Y, Ohtani F, Aizawa H, Kukuda S, Kawabata H, Bergstrom T: Varicella-zoster virus reactivation is an important cause of acute peripheral facial paralysis in children. Pediatr Inf Dis J 2005;24:97–101.
4. Rudra T: Zoster sine herpete. Br J Clin Pract 1990;44:284
5. 21 Devriese PP, Moesker WH: The natural history of facial paralysis in herpes zoster. Clin Otolaryngol 1988;13:289–298.

Is shingles Contagious

Many of you might be wondering if herpes zoster or shingles is contagious. We would like to further explain it here. Before we talk about shingles, let me tell you shingles is caused by Varicella Zoster Virus, the same virus that causes chickenpox.

Chicken pox is primary infection cause by varicella zoster virus that is highly contagious and spread rapidly. After the primary attack the virus stays in latent state in ganglion cells of dorsal nerve or cranial nerve roots for several years and is noninfectious. Later when there is decrease cell-mediate immunity, that may be due to old age, trauma, stress, sunburn or any other disease, the virus reactivates to cause secondary infection called as shingles or zoster.

Although less contagious then primary varicella (chickenpox), shingles can still be highly contagious between the periods of rash eruption and crusting and dryness. During this infectious period shingles lesion contains high concentration of VZV that can transmit via airborne route[1,2] and cause chickenpox in susceptible individual (those individuals who have not had chickenpox before, especially child and immuno-compromised patients).

For those who have already had chickenpox during their childhood or at any time, shingles cannot be acquired by contact with other person with chickenpox or shingles. However one may have risk of developing shingles later in their life. The risk of developing shingles is determined by factors that influence the host-virus relationship.

Person with localized zoster are thought to be less contagious if the lesion are covered. After all the blisters are crusted and dried, the virus is no longer contagious and can no longer spread.

References:

1.Josephson A, Gombert ME. Airborne transmission of nosocomial varicella from localized zoster. J Infect Dis 1988;158:238–41
2.Sawyer MH. Chamberlin CJ. Wu YN. Aintablian N. Wallace MR. Detection of varicella-zoster virus DNA in air samples from hospital rooms. J Infect Dis 1994;169:91–4.