Vesicular rash on an erythematous base. A case is here reported of Herpes zoster involving the contralateral eye, associated with a midline skin rash, following cataract extraction under local anaesthesia. Early intervention with high-dose oral acyclovir has been effective in preventing many of these complications, while reducing the duration of the acute infection. Postherpetic neuralgia remains a difficult therapeutic problem, and options are offered. One fifth of the population, mainly elderly people, will present with this neurocutaneous infection during their lifetime. Most immunocompetent patients will experience spontaneous and complete recovery within a few weeks. Some, however, will develop complications such as postherpetic neuralgia and, in cases of ophthalmic herpes zoster, sight threatening eye problems.
We outline the main points that general practitioners should keep in mind when faced with a case of ophthalmic herpes zoster. In February 2005, we searched the Cochrane Controlled Trial Register (keyword: “herpes zoster”), Embase, and Medline (MESH terms: “herpes zoster” and “therapy”) for clinical trials, randomised controlled trials, meta-analyses, practice guidelines, and reviews. We selected only articles written in English and disregarded any studies of immunocompromised patients. Herpes zoster is a commonly seen disorder; one fifth of the population will present with the disease during their lifetime. The reported incidence varies from 2.2 per 1000 to 3.4/1000 people per year. Herpes zoster develops mainly in elderly people: its incidence in people aged over 80 is about 10 in 1000/year.1 2 It is caused by reactivation of the varicella zoster virus (human herpes virus type 3). In temperate climates, primary infection with this virus usually occurs before the age of 10 and manifests itself clinically as chickenpox (varicella).
The virus then becomes latent, nestling in the sensory ganglia. Later it may become active again, spread to the corresponding dermatome by means of a spinal or cerebral nerve (usually the trigeminal nerve), and generate the characteristic unilateral vesicular exanthema. The accompanying inflammation of the sensory nerve and skin damage are supposedly responsible for the acute pain.3 Reactivation of the virus is linked to a diminished virus specific and cell mediated immunity, which is related to age. Immunocompromised patients also run an increased risk of developing herpes zoster (especially patients with haematological malignancies or those receiving immunosuppressive drugs). In contrast to other herpes infections, recurrence of herpes zoster is relatively rare (6-14%).1 Since it has not yet been proved that herpes zoster is provoked by any serious underlying pathological condition (for example, a malignancy),4 a search for possible risk factors is not warranted in otherwise healthy patients in whom herpes zoster develops. My complaints started as tender skin when I ran my hand through my hair―a stinging feeling as if my scalp were covered with glass splinters. Initially, I thought it was because I had driven with my car window open.
In addition, I did not feel that well. I had a slight fever and a headache. After a few days, I noticed some red spots on the left side of my forehead. For this reason I consulted the general practitioner in attendance. Because my forehead hurt, he thought I had sinusitis. I have had that a few times in the past. The doctor diagnosed the red spots as eczema.
I was prescribed nose spray and painkillers. The pain was worse the next day. I felt really sick and stayed in bed. I also noticed several blisters on my forehead and my left upper eyelid was swollen. My own doctor came to my house and diagnosed me as having shingles. He prescribed antiviral drugs. A day later, the eyelids of my left eye were so swollen that I could no longer see out of that eye.
As a result, my doctor referred me to an ophthalmologist. Fortunately, only my eyelid was affected―there was no eye infection. Now, three weeks after my complaints started, I am feeling better. I still have some scabs on my forehead, but I can see again with my left eye. The skin over my forehead, however, is still tender to the touch. Ophthalmic herpes zoster represents 10-20% of all zoster cases.5 In other words, one out of every 100 individuals will develop ophthalmic zoster during his or her lifetime. The disease is potentially serious and may result in severe and lasting pain, particularly in elderly patients.
Moreover, without antiviral treatment, about half of all patients will develop various eye disorders. Conjunctivitis, for example, is seen in nearly all of ophthalmic zoster patients with ocular involvement. More severe disorders include keratitis, uveitis, and optic neuritis of the affected eye. If these latter disorders are not diagnosed and treated adequately the patient’s sight may become permanently affected. The cornea may lose optical quality because of clouding and surface irregularities. Moreover, a decreased corneal sensitivity combined with inadequate blinking may lead to severe problems with dry eyes with subsequent corneal complications (neurotrophic ulceration and exposure keratopathy, secondary bacterial infection). The risk of corneal ulceration is particularly enhanced in patients with a substantial loss of corneal sensitivity.
The risk of ophthalmic complications is not related to age or severity of the skin rash. In box 1, a patient shares her experiences with the condition, and in box 2, a close family member, a son, reports how he was affected by his father’s illness. The skin of the forehead and upper eyelid is commonly affected and may give rise to substantial periorbital oedema in the early phase of the disease. In patients with severe dermal inflammation, late phase contraction scars may lead to incomplete eyelid closure and corneal exposure. Conjunctivitis is a common finding in ophthalmic zoster with involvement of the eye. The conjunctiva appears oedematous and injected, sometimes with petechial haemorrhages. These signs usually resolve within a week.
Episcleritis and scleritis may be diagnosed when a localised redness with dilatation of the deeper vessels appears. The presence of pain, however, is not helpful in differentiating between these complications, as ocular sensitivity is invariably affected. After the inflammation has resolved completely, patchy scleral atrophy may become apparent. Small corneal epithelial defects may be visible during the acute phase, but those microdendritic lesions will disappear within days. In patients with a red eye, corneal sensitivity is often substantially and irreversibly reduced. Although corneal hyposensitivity is the norm, hypersensitivity can sometimes occur.10 In prolonged keratitis, regular eye examinations by an ophthalmologist are necessary to evaluate and treat surface problems and deep corneal inflammation and to prevent subsequent neovascularisation. In a minority of patients, topical steroids are indicated on the advice of an ophthalmologist to control inflammation and to maintain corneal transparency.
Inflammatory cells may be observed in the anterior chamber when a biomicroscope is used. In most patients, the inflammatory signs will gradually disappear within weeks to months without topical steroid treatment. The release of viral antigens in the iris and ciliary body initiates a mild uveitis often accompanied by temporary elevation of the intraocular pressure. Chronic uveitis, possibly related to an insufficient immune response and prolonged viral activity, is a rare finding in patients who have not been treated with steroids. In the acute phase, profound swelling of the eyelids may hinder examination of the eye. Although often difficult to detect (even with the aid of a slit lamp), small corneal epithelial lesions may be visible when the ocular surface is stained with fluoresceine. Corneal sensation of the inflamed eye is often affected, and corneal sensitivity of both eyes should be tested with a cotton wool fibre to assess the risk of future ocular complications.
A painful response to light combined with blurred vision may be a symptom of uveitis. These are two photographs of my late father, one taken during the acute phase of shingles and the other several months later. I can still vividly remember the horrible skin rash and the agony of his pain when his shingles started. He was 70 years old at that time and already had pulmonary emphysema. I do not know to what extent the pain or itching sensations influenced his daily life or night’s sleep, because my father didn’t complain about his health problems. The disease, however, affected his appearance permanently, and he sometimes couldn’t stop rubbing the eye because of severe itching. His inability to sleep―he slept only a few hours a night―may also be related to his shingles.
Since the onset of shingles, my father had regular check ups for dry eye disease. Until his death at age 84, his right eye was treated with a lubricating eye gel during the day (three times daily) and an ophthalmic ointment before sleep. An ophthalmologist had prescribed this treatment because eyelid closure remained insufficient despite corrective surgery. During the last years of his life, my father’s vision gradually deteriorated because of macular degeneration. His inability to read, even with the aid of a low vision device, was dramatic for him personally. Fortunately, he could still recognise his close relatives with his poorly functioning, herpes zoster affected right eye. Hutchinson’s sign in the early phase of ophthalmic zoster, visual complaints, or an unexplained red eye are indications for referral to an ophthalmologist.
Immediate consultation, however, is usually not required, since vision threatening ophthalmic complications that require specific treatment usually do not develop during the first week after onset of skin rash. Importantly, the patient should start taking antiviral medication as soon as possible, independent of the ophthalmic condition. Once an eye has been affected by herpes zoster it will always remain vulnerable. Complications can develop even months or years after the acute phase. The cornea, for example, may be damaged because epithelial regeneration is delayed, particularly in eyes with corneal anaesthesia. Doctors should, therefore, remain alert when the natural defensive mechanisms of the eyes of patients with “cured” ophthalmic zoster are affected, as in the state of decreased consciousness and after ophthalmic surgery. Accordingly, we recommend that a past infection with ophthalmic zoster should be registered in the patient’s medical file.
Van der Lelij A, Ooijman FM, Kijlstra A, Rothova A. Anterior uveitis with sectoral iris atrophy in the absence of keratitis: a distinct clinical entity among herpetic eye diseases. Ophthalmology 2000;107: 1164-70. Hilt DC, Buchholz D, Krumholz A, Weiss H, Wolinsky JS. Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused by cerebral angiitis: diagnosis and management approaches. Ann Neurol 1983;14: 543-53. Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T.
Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology 2000;107: 1507-11. Tyring S, Engst R, Corriveau C, Robillard N, Trottier S, Van Slycken S, et al. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study. Br J Ophthalmol 2001;85: 576-81. Zaal MJ, Volker-Dieben HJ, Wienesen M, D’Amaro J, Kijlstra A. Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.
Am J Ophthalmol 2001;131: 25-9. Neoh C, Harding SP, Saunders D, Wallis S, Tullo AB, Nylander A, et al. Comparison of topical and oral acyclovir in early herpes zoster ophthalmicus. Eye 1994;8 (Pt 6): 688-91.