OPTOMETRY. Herpes zoster ophthalmicus

Transcription

1 C L I N I C A L A N D E X P E R I M E N T A L OPTOMETRY REVIEW and CASE REPORT Herpes zoster ophthalmicus David M Cockburn DSc hc Ian S Douglas BSc Optom Department of Optometry and Vision Sciences, The University of Melbourne Accepted for publication: 12 May 2000 Introduction: Herpes zoster is a common disease which may cause serious ocular sequelae when it affects the trigeminal nerve. Although involvement of the nasociliary branch of the first division of the trigeminal nerve is well recognised to be associated with serious and direct ocular morbidity, the need for careful long-term follow-up of cases of frontal branch involvement is perhaps less well known. Methods: The pathogenesis, epidemiology, risk factors, clinical course and treatment of herpes zoster are discussed with emphasis on trigeminal nerve involvement. A case report is presented which illustrates the importance of continuing management when the frontal branch of the trigeminal nerve is affected. Discussion: Clinical guidelines are suggested for optometric management of these cases in cooperation with medical practitioners. (Clin Exp Optom 2000; 83: 2: 59-64) Key words: complications, herpes zoster ophthalmicus, management guidelines The term herpes zoster comes from the Greek meaning a creeping girdle and its synonym shingles from the Latin, which also means a belt or girdle. These terms are apt because the disease most commonly presents with skin eruptions extending around half of the trunk. The intense pain and burning sensation accompanying the skin eruptions has led to descriptions in antiquity of it being the girdle of roses from hell. EPIDEMIOLOGY The incidence of herpes zoster in people having competent immune systems is approximately 1.5 per 1,000 per year, but rises to 15 to 20 per 1,000 in the elderly, where cell mediated immunity to the virus has declined. In patients with acquired immune deficiency syndrome, the condition has a prevalence of approximately 25 to 30 per cent and may be the first detected manifestation of this disease. Although herpes zoster affects otherwise healthy young adults, its appearance in people younger than 45 years is grounds for eliminating the possibility of concomitant human immune deficiency virus infection (HIV).5.4 Children and young adults already having had chickenpox occasionally develop herpes zoster in which the signs and symptoms are usually relatively mild.5 In all, approximately 90 per cent of people acquire the varicella virus in childhood and 20 per cent of people will have reactivation of the virus in their lifetime. About four per cent will have herpes zoster more than once.6 Table 1 summarises the risk of acquiring herpes zoster. lmmunocompetent subjects: incidence per 1,OOO per year General population Elderly lmmunocompromised subjects: incidence per 1,OOO per year Bone marrow transplant 500 Hodgkins lymphoma 250 (with half within 6 months) Rheumatoid arthritis on prednisolone or methotrexate treatment 14.5 Acquired immune deficiency syndrome prevalence 300 Patients receiving radiotherapy not recorded Table 1. Incidence of herpes zoster in high risk populations. (After Liesegang TJ. Eye and Skin Disease. Mannis MJ, Macsai MS, Hun+ AC, eds. Philadelphia: Lippincott-Raven, ) 59

2 Herpes zoster ophthalmicus Cockbum and Douglas CAUSE OF HERPES ZOSTER Herpes zoster is caused by the varicella virus, a member of the family Hn-pewiridne, for which humans are the sole natural host. The first exposure of an individual to this virus very commonly occurs in childhood, before about eight years of age, when the result is development of chickenpox. After the initial infection and recovery, the virus remains latent in the sensory dorsal ganglia where it reactivates and replicates, often many decades later in patients having competent immune systems, but more commonly when the immune system is compromised. The reactivated virus spreads distally, causing skin eruptions (vesicles) to appear within discrete areas of erythema over the distribution of the affected dermatomes. The morbidity of herpes zoster is caused partly by direct viral attack and partly by an inflammatory response in neural and vascular tissue^.^ CLINICAL MANIFESTATIONS The earliest manifestations of herpes zoster are typically malaise, headache and mild fever for two or three days before the other signs emerge. The next stage is an exquisite tenderness of the skin and localked, indurated swellings over one or more affected dermatomes. Within about 36 hours, vesicles form over these dermatomes. Occasionally there is some overlap of vesicles to adjacent dermatomes, but rarely to the opposite side of the body.' The vesicles become pustular and bleed by about the third day, then finally crust over to heal, often leaving pitted scars. This course may become complicated by secondary bacterial infection of the vesicles. The patient is moderately contagious for approximately 10 days when the virus may cause chickenpox in other people, usually children, who have not previously contracted the virus. The area around the trunk is the most common location of herpes zoster lesions, but the cranial nerves are the next most commonly involved, with the ophthalmic division of the trigeminal nerve the most frequently affected and accounting for 10 per cent to 15 per cent of all cases." HERPES ZOSTER OPHTHALMICUS The ophthalmic division of the trigeminal nerve divides into the frontal, nasociliary and lacrimal branches. Herpes zoster may affect any or all of these branches, with lesions located according to their dermatomes. When any of these branches is involved, the condition is referred to as herpes zoster ophthalmicus. With trigeminal involvement the signs may include ocular motor dysfunction with ptosis and mydriasis. Occasionally there may also be paresis of the fourth and sixth nerves, indicating that the infection may affect not only sensory nerves but also the brainstem and other motor nerve rootsx Indeed, a case of total ocular motor palsy has been described in which this event was the first sign of herpes zoster." The symptoms of herpes zoster affecting the trigeminal nerve commence as described earlier and proceed to include a severe ache and lancinating pain or burning, itching and tingling with pain referred to deep tissues. These symptoms may alternate one with the other and with diminished sensation or itching, typically over three to four weeks when they usually subside. However, particularly in the elderly and when the lesions are numerous and severe, a post herpetic neuralgia is common and may persist for months, years, or indefinitely. These patients experience pain and headache, particularly at night, which may lead to sleep disturbances, a general malaise, mood changes and depression. These complications occur in between 12 and 20 per cent of patients, with greater frequency and less resolution in the aged.' Nasociliary branch Involvement of the nasociliary branch of the trigemimal nerve poses the greatest risk for the eye because this branch is responsible for its entire sensory innervation together with that of the nose. This gives rise to an important clinical marker, in that lesions appearing on the tip of the nose (Hutchinson's sign) indicate that this division is affected and serious ocular involvement is likely. When the nasociliary branch of the first division of the trigeminal nerve is affected, keratitis is very common and may precede the formation of the skin lesions and development of post herpes zoster neuralgia. This corneal involvement commences with an epithelial and sub-epithelial keratitis which may later affect the stoma. The cornea may ulcerate, Descemet's membrane may develop folds and finally resolution occurs, with scaring and new vessel invasion of the cornea after a variable period of time. At the time keratitis begins it is very commonly accompanied by uveitis and raised intraocular pressure, with glaucoma a common sequela. On the other hand, the intraocular pressure may become low and hypotony ensue due to atrophy of the ciliary processes. Scleritis and episcleritis are potential later complications. In some cases, eruptions similar to those on the skin appear on the iris and are accompanied by hyphaenia or hypopyon with later evidence of a stromal ischaemia and iris stromal atrophy.'" These complications are sight-threatening and extremely painful. Frontal branch Involvement of the frontal branch of the trigeminal nerve causes lesions from the eyebrow, over the frontal area and extending to the occiput on the affected side, with occasional lesions on the conjunctiva of the upper lid or the globe. Although the eye is not directly affected by viral invasion in frontal branch involvement, there are secondary conditions of allergic or toxic origin for which the patient should be monitored. Maxillary branch This branch of the trigeminal nerve is the least frequently affected and only rarely is the eye affected as a result of involvement with this branch alone."' However, complications similar to those of the frontal branch should be sought. ADDITIONAL. OCULAR COMPLICATIONS In 40 to 60 per cent of patients with herpes zoster ophthalmicus of any branch, an iridocyclitis appears one to two weeks 60

3 Herpes zoster ophthalmicus Cockburn and Douglas after the onset of the skin vesicles. Approximately 10 per cent of these patients have elevated IOP in association with the iridocyclitis. A persistent unilateral glaucoma develops in two per cent of affected eyes as a result of trabecular dysfunction." A further complication of herpes zoster, Ramsay-Hunt syndrome, is due to involvement of the geniculate ganglion which may lead to severe ear pain, redness of the external meatus, seventh cranial nerve paresis, loss of taste in the anterior portion of the tongue and hemi-facial palsy. The diagnosis of established herpes zoster is generally straightforward because of the location of vesicles over dermatomes and the pain associated with the later stages. When the trunk is affected, abdominal pain may wrongly be ascribed to gastrointestinal disease or pleurisy," myocardial infarction, gallstones, renal calculi or appendicitis." The diagnosis of herpes zoster ophthalmicus is usually readily established and is not usually discussed in medical texts. However, the severe headache and pain may also present a diagnostic problem in the early stage prior to vesicle formation as occurred in the case described here. Figure 1 shows a female who has herpes zoster affecting all three branches of the trigeminal nerve. Herpes simplex infection and dermatological conditions need to be excluded. If necessary, immunofluorescence and serologic tests are available for herpes zoster. Table 2 details the dermatologic and ophthalmologic findings in herpes zoster oph thalmicus. TREATMENT OF PRIMARY LESIONS The treatment of herpes zoster is first directed to an attempt to stop replication of the virus and limit the skin and nerve lesions. It is also important to attempt to limit the risk of post-herpetic neuralgia and secondary eye disease and to control pain. These requirements are not yet fully attainable and many, particularly the elderly and immunosuppressed patients, experience severe pain and are left with significant ocular disabilities after trigeminal nerve involvement. Oral acyclovir or its derivatives should be given early in the disease and within 72 hours of the appearance of the rash.'' This treatment is typically oral valaciclovir, aciclovir, or famci~lovir.~~ The benefit of this treatment is unclear and, although studies have shown a reduction in the number and severity of skin lesions, the ocular protective effect has not been impre~sive.'~'"'~ There appears to be little or no reduction in the prevalence or severity of post herpetic neuralgia as a result of the antiviral treatments although this question is not yet settled."'." Marsh and Cooper' conclude that there is no single best treatment fcr herpes zoster ophthalmicus. Mild inflammation may not require treatment but more severe problems do. The uveitis accompanying nasociliary herpes zoster may be due to the presence of the virus in the eye, or to toxic or allergic reaction to the products of inflammation elsewhere, particularly from keratitis. It is treated by the addition of mydriatics and steroids to the other medications, while attention is given to the likely onset of raised intraocular pressure. Pain relief in both the initial stage and in post-herpetic neuralgia is provided by use of simple analgesics, transcutaneous electric nerve stimulation, tricyclic antidepressants (amitriptyline or doxepin), the anti-convulsant, carbamazepine (Tegretol) and local treatment of lesions with capsaicin cream after the vesicles have healed. Acupuncture is sometimes used for pain relief with partial success in some cases. MANAGEMENT OF HERPES ZOSTER OPHTHALMICUS Optometrists may be consulted in the early stage of the disease when conjunctivitis is present as one of the early symptoms and later if other ocular signs appear. If the nasociliary branch is involved, as evidenced by lesions on the nose and midfrontal brow, the patient should be referred to an ophthalmologist as a matter of some urgency, because the eye will almost certainly become involved. The mainstay of treatment of the resulting keratitis and intraocular inflammation is the use of topical corticosteroids and topical ophthalmic aciclovir, but doubt exists about the value and safety of the available therapies."-'4 If uveitis is present, mydriasis should be maintained to prevent synechial development. Nonsteroidal antiinflammatory drugs may be useful to help control this inflammation and pain. Artificial tears are used to provide comfort and prevent further drying of the cornea, but in some cases tarsorrhaphy may be necessary to control exposure keratitis. Although the ocular signs are less dramatic when the frontal branch of the trigeminal nerve is affected, there is still risk of serious sequelae. These patients should be inspected for anterior chamber flare and cells, keratic precipitates, corneal endothelial disruption, stromal infiltrates, epithelial damage or raised intraocular pressure (IOP). The patient should be reviewed on a weekly basis for at least four weeks and longer if the condition does not resolve. The emergence of any of these signs merits early referral for ophthalmological management. Intraocular pressure should be assessed in ophthalmic herpes zoster patients and any difference between the two eyes noted. The pressure in the affected eye may be raised due to reduced outflow facility caused by trabeculitis or lowered due to ciliary body dysfunction. If either of these arises, the patient should be referred to an ophthalmologist. Raised IOP is usually controlled by the use of topical steroids (fluorometholone qqh) which reduce the inflammatory reaction causing malfunction of the trabeculae, but more potent steroids may be required when the uveitis is severe. Ocular anti-hypertensive medication may also be necessary. I I More potent steroids may be required when the uveitis is severe. Topical beta blocking drugs are the treatment of choice if IOP is not adequately reduced by steroid control of the inflammation. There may be a difficulty in some cases where there is the possibility of a steroid response contributing to the IOP rise above the reduction attributable to its antiinflammatory effect. Topical carbonic anhydrase inhibition (Trusopt) may be 61

4 Herpes zoster ophthalmicus Cockburn and Douglas Dermatological findings Dermal contracture Macules Papules Pigmentation Pitting Vesicles Fig 1. Severe herpes zoster involving the ophthalmic and maxillary divisions of the trigeminal nerve in a female. All three branches of the ophthalmic division are affected. Note the lesion on the tip of the nose (Hutchinson s sign). added. Surgery may be required in some refractory cases. Latanoprost (Zalatan) is contraindicated because it has been shown to reactivate uveitis in eyes with a history of this conditi~n. ~.~~ Miotics are also contraindicated because of the risk of formation of posterior synechiae. A foreign-body sensation suggests the presence of conjunctival lesions which are relieved by artificial tears during the day and lubricating ointment at night. Photophobia may be a problem for which darkly tinted lenses provide relief. Table 3 summarises the management of herpes zoster ophthalmicus. PREVENTION A vaccine for herpes zoster virus has been developed and trialed,* but there are problems in introducing a vaccination program because its success would require vaccinating all children. If immunisation was not provided to all children, those who were not vaccinated but escaped contact with the virus as children could become exposed to varicella in adult life. Varicella in chickenpox form has far more serious morbidity and mortality when contracted by adults than when it occurs in children. REPORT OF A CASE A 74year-old male developed tender, painful nodular areas in the left frontal region. A general practitioner made the alternative diagnoses of temporal arteritis or herpes zoster and arranged an immediate erythrocyte sedimentation rate (ESR) study to exclude cranial arteritis. The ESR was within the normal range so arteritis was unlikely to be the cause of the symptoms. The patient was advised to return immediately if vesicles formed. Vesicles Ophthalmological findings Acute retinal necrosis Anterior segment ischaemia Conjunctivitis Corneal endotheliitis Horner s syndrome Iris ischaemic atrophy with sectoral loss of pigment Keratitis: neurotrophic, discoid and stromal, exposure keratitis, corneal scarring Lid retraction, ptosis, ectropionlentropion, abnormal tear film Multiple neurological complications Ocular hypertension and glaucoma or hypotony Ocular motor dysfunction Optic neuritis, atrophy Photophobia Post-herpetic neuralgia Retinal and optic nerve vasculitis Scleritis, episcleritis Uveitis Table 2. Dermatologic and ophthalmologic findings in herpes zoster ophthalmicus appeared two days later over the left frontal branch of the ophthalmic division of the trigeminal nerve from the eyebrow to the occiput. The anti-viral drug valaciclovir one gram to be taken orally three times daily was prescribed for seven days. At this stage the patient was experiencing extreme pain in the affected region and unremitting headache which was only partly resolved by Panadeine Forte (Sanofi Winthrop). Capsaicin cream was 62

5 Herpes zoster ophthalmicus Cockburn and Douglas Nasoclllary branch Immediate referral to an ophthalmologist Frontal branch Examination Visual acuity and comparison with previous examination if available Conjunctival inspection for zoster lesions Assess loss of corneal sensitivity, particularly a difference between eyes Slitlamp examination of the cornea for epithelial defects, stroma infiltration, endothelial disruption or keratic precipitates Inspection of the aqueous for flare or free cells Assessment for raised intraocular pressure or significant difference between eyes Management If not already under medical care refer to a general practitioner. Review weekly for at least four weeks amd report to GI? Arrange ophthalmological referral if any of the above signs appear. Record findings and patient instructions. Maxillary branch Examine and manage as for frontal branch for four weeks, then as arranged with GP or on occurrence of symptoms. It is unlikely that ocular involvement will occur. Table 3. The optometrist s examination and management of patients having herpes zoster ophthalmicus applied to the skin to ease the pain of the eruptions. Several days after the diagnosis of herpes zoster ophthalmicus was confirmed, the patient consulted his optometrist with the complaint of a foreign body sensation and photophobia in the left eye. On examination there was diffuse left corneal punctate keratitis which stained with fluorescein. The tear film was of poor quality and was judged to be responsible Figure 2. Fine keratic precipitates on the left eye of the patient reported here. These appeared shortly after the herpes zoster skin vesicles appeared and were accompanied by an acute intraocular pressure rise from 14 to 33 mm Hg. Only the frontal branch of the nerve was affected in this case, which illustrates that structures not directly affected by the virus may become involved. for the symptoms and the slightly reduced visual acuity of 6/6 (previously 6/4.8). No evidence of a corneal foreign body was found and no anterior chamber aqueous flare, cells or keratic precipitates were present. The IOP was 14 mm Hg in the left eye. The patient was given artificial tears to take when necessary and a review appointment was arranged for two days later. Before this appointment was due, the eye became significantly more uncomfortable and the patient self-referred to an ophthalmologist. At this visit, the ophthalmologist detected 12 keratic precipitates grouped around the central region of the cornea, hut no cells or flare. The IOP was 33 mm Hg in the left eye and 14 mm Hg in the right. Figure 2 shows keratic percipitates in the patient described here. Betoptic S (Alcon Laboratories Aus- tralia), 0.5 per cent twice daily was prescribed for the raised IOP, and fluromethylone 1.5 per cent three times daily for the low grade anterior uveitis. The patient was returned to the optometrist for monitoring of the IOP and the uveitis. Three days after commencing treatment the IOP of the left eye was recorded as 17 mm Hg and the keratic precipitates remained as initially described. The ophthalmologist suggested that this treatment would probably be necessary for 12 months after which it could be tapered during careful monitoring of signs. After discussion with the ophthalmologist the patient was scheduled for review by the optometrist at monthly intervals. Over the following months the keratic precipitates migrated more peripherally over a mildly oedematous endothelium while the IOP remained in the high teens. 63

6 Herpes zoster ophthalmicus CockOurn and Douglas The corneal epithelium regained its normal appearance and the foreign body se 11s a ti o n and p h o top h o bi a resolved. Vision in the left eye was variable between 6/9.5 and 6/6 and the eye remained comfortable at all times. However, the patient continued to have pain over the left frontal region as an expression of postherpetic neuralgia. SUMMARY Optometrists and general practitioners are generally well aware of the almost inevitable and serious nature of the eye complications of herpes zoster ophthalmicus when it affects the nasociliary branch of the ophthalmic division of the fifth cranial nerve. The need for urgent ophthalmological management in these cases is clear. The more subtle but still serious ocular complications occurring with frontal branch involvement as described in this case are probably less well recognised. Optometrists are trained and equipped to detect uveitis, raised IOP and the other signs of eye involvement. They are ideally situated to provide a readily accessible and economical monitoring service for these signs in co-operation with a general practitioner and an ophthalmologist if complications arise. This case illustrates the optometrist s role in a patient in whom the initial ocular symptoms were subtle but had a potentially serious outcome. ACKNOWLEDGEMENT The authors would like to thank the librarian of the Royal Victorian Eye and Ear Slide Library for supplying and allowing publication of Figure 1. REFERENCES Raggozzino MW, Melton LJ, Kurland LT et al. Population based studies of herpes zoster and its sequelae. Medicine 1982; 61: Balfour HH. Varicella zoster virus infections in inimunocompromised hosts: a review of the natural history and management. Am J Med 1988; 85: Liesegang TJ. Diagnosis and therapy of herpes zoster oph thalmicus. Ophthalmology 1991; 98: , Friedman-Klien AE, Lafleur FL, Glendler E. Herpes Zoster: A possible early sign for the development of acquired immunodefi- ciency syndrome in high-risk individuals. JAm Acad Dtrmatoll986: 14: Mescon H, Bachta M. Dermatology in general practice in Medicine In: Wilkins RW, Levinsky NG, eds. Essentials of Clinical Practice. Boston: Little Brown, 1978: Hope-Simpson RE. The nature of herpes zoster: a long term study and a new hypothesis. Prof R Sac Med 1965; 58: Marsh RJ, Cooper M. Ophthalmic herpes zoster. Eye 1993; 7: Beeson PB, McDermott W. Textbook of Medicine, 14th ed. Philadelphia: WB Saunders, 1975: 66. 9, Awan KJ. Total ocular motor palsy as a presentation of herpes zoster ophthalmicus. Pak J Ophthalmol 1989; 66: KanskiJ. Clinical Ophthalmology. L.ondon: Butterworths, 1984: Higginbotham E, Lee DA. Management of Difficult Glaucoma. Boston: Blackwell, 1994: Snider GL. Diseases of the pleura. In: Wilkins RW, Levinsky NG. Medicine: Essentials of Clinical Practice, 2nd ed. Boston: Little Brown, 1978: Nagington J, Rubenstein D. Viruses. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford Text Book of Medicine. Oxford: Oxford University Press, 1983; 5: Murtagh J. General Practice Sydney: McGraw-Hill, 1996: Merk Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station Merk & C:o Section 8 Ch 9.-www. merek.com/ pubs/mmanual (23 March 2000). 16. Cobo LM, Foulks GN, Liesegang T, Lass J et al. Oral acyclovir in the treatment of acute herpes zoster ophthalmicus. Ophthalinology 1986; 93: Hoang-Xuan T, Buchi ER, Herbort CP, Denis J et al. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology 1992; 99: Herbort CP. Acylovir in herpes zoster ophthalmicus. BrJOphthalmol1992; 76: Marsh JR. Reply: Acyclovir in herpes zoster ophthalmicus. BrJOphthalmoll992; 76: Liesegang TJ. Herpes Zoster. In: Mannis MJ, Macsai MS, Huntly AC, eds. Eye and Skin Disease. Philadephia: Lippincroft-Raven, 1996 : Lloyd AR. Varicella and herpes zoster. In: Mims Disease Index. Crows Nest: IMS Publishing, 1992: McGill J. Topical acyclovir in herpes zoster ocular involvement. Br J Ophthalmol 1981; 65: Marsh RJ, Cooper M. Acyclovir and steroids. In: Herpes Zoster Keratouveitis. Br J Ophthalmol1984; 68: Marsh RJ, Cooper M. Double masked trial of topical acyclovir and steroids in the treatment of herpes zoster ocular inflammation. Br J Ophthalmol 1991 ; 75; Warwar RE, Bullock JD, Ballal D. Cystoid macular oedema and anterior uveitis associated with latanoprost use. Ophthalmology 1998; 105: Fetchner RD, Khouri AS, Zimmerman TJ, Bullock J et al. Anterior uveitis associated with latanoprost. Am JOphthnlmol1998; 126: Weibel RE, Neff BJ, Kuter BJ et al. Live attenuated varicella virus vaccine efficiency trial in children. N Eng J Med. 1984; 310: Author s address: Associate Professor David M Cockburn Department of Optometry and Vision Sciences The University of Melbourne Parkville VIC 3052 AUSTRALIA 64