Identificar la satisfacción de los turistas en los hoteles de categoría cuatro

R. J. MARSH

D epartm ent o f C linical O phthalm ology, Institute o f O phthalm ology, M oorfields E ye H ospital, London

Ophthalmic herpes zoster is a disease ranging from trivial to devastating. Poor management can lead to disastrous skin scarring, neuralgia, and loss of the eye. Methodical and regular care can prevent many of the severe complications. In about 50 per cent of cases ocular complications develop (Edgerton, 1945), and these fall into three broad categories: those associated with inflammatory changes; those resulting from nerve damage; and those secondary to tissue scarring.

The inflammatory changes may be expressed directly in the form of nummular, disciform, and mucus- plaque keratitis, or indirectly as a vasculitis in cases of episcleritis/scleritis, iritis, papillitis, and proptosis with total 3rd nerve palsy. The complications associa­ ted with nerve damage are neuroparalytic keratitis, ocular muscle palsies, and neuralgia. Chronic tissue scarring, especially of the skin, lids, and conjunctiva, leads to neuralgia, exposure keratitis, trichiasis, lid margin deformities, and tear film problems.

These ocular complications may be considered in three phases: acute, chronic, and relapsing. The acute changes usually occur 2 or 3 days after the onset of the rash, but may rarely precede it. The acute lesions include those associated with inflammatory changes, external ocular muscle palsies, and some cases of neuroparalytic keratitis. The vasculitis tends to become chronic, leading to ischaemic atrophy, and the inflam­ matory changes in the cornea lead to dense cellular infiltrates and lipid keratopathy. Energetic treatment in the actute stage can prevent many of the later and chronic complications, especially those related to scarring. Ophthalmologists are fortunate in that cases present in the early stages of the disease, most patients being referred to the eye casualty department by the general practitioner at the first sign of the rash. One of the most, important aspects of the ocular complications is their tendency to relapse—even years after the rash. The stimulus to the relapse is often unknown, although the precipitate withdrawal of topical steroids is a potent cause. It should be remem­ bered that some relapses may occur when the original

Address for reprints: R . J. Marsh, F.R .C .S ., Departm ent o f Clinical Ophthalmology, Moorfields Eye Hospital, C ity Road, London E C lV 2 F D

attack of herpes zoster has either been forgotten or was so mild as to pass unnoticed.

A small proportion of patients with ophthalmic zoster go on to develop a systemic varicella-like rash 1 to 2 weeks after the onset of the disease. A large number of these cases turn out to have reticuloses, other malignant tumours, or defective immunity, or to be receiving immunosuppressive therapy (Stevens and Merigan, 1972). Thus all patients who develop a systemic rash should be carefully examined, preferably by an oncologist. I now screen all new patients by haemoglobin, white blood count, differential count, erythrocyte sedimentation rate, blood film, liver function tests, plasma protein electrophoretic strip, blood sugar and cholesterol, and radiography of the chest. It is also important for ophthalmologists to be aware that in rare cases encephalitis (Appelbaum, Kreps, and Sunshine, 1962) may occur in the acute stage, and that a delayed mild contra-lateral hemi­ plegia may occur after 7 weeks (Laws, 1960; Acers, 1964).

Management

This may be considered under eight headings.

Admission

Patients with acute ophthalmic herpes zoster are often very ill, aged, and infirm. It is very difficult for them to take their treatment, feed themselves, and rest at home, and by far the best and kindest course is to admit them for one week to hospital. This offers the patient rest in bed, nursing care, proper diet, and correct administration of treatment. The patient should be barrier nursed in a side ward until all the vesicles have dried (usually within 5 days). It is preferable that all nurses in contact with the patient at this stage have had chickenpox, since this can be acquired from patients with herpes zoster by pre­ viously uninfected individuals. The converse, however, is not true (Hope-Simpson, 1965).

Analgesia

Pain in this condition is notoriously difficult to treat. It is nearly always severe in the first 2 weeks, but

Ophthalmic herpes zoster 335

usually eases at the end of this time. During this acute phase patients should be given sufficient drugs to suppress their pain. There is an old, distinct, and widely held clinical impression that, if pain is ade­ quately treated at the start of the disease, troublesome post-herpetic neuralgia is less common. The correct analgesic has to be found by trial and error—I usually start with Distalgesic, then move to Fortral, DF118, and finally to pethidine (the anti-inflammatory content of these drugs is also useful).

Post-herpetic neuralgia is a poorly understood phenomenon. It can be expressed by varying degrees of paraesthesia, may closely resemble tic douloureux

(although on the whole it responds very poorly to Tegretol), or can take the form of a constant ache. I find the incidence of severe neuralgia to be about 7 per cent and this can be so bad as to lead to suicide. The mechanism of pain is speculative—sometimes it is associated with severe skin scarring, suggesting fibrotic constriction o f nerves (as after bums and amputa­ tions), but in other cases there may be minimal scar­ ring. Pain and paraesthesia generally tend to be worse at night and aggravated by heat and wind. It is obviously best to suggest extra analgesia at these times. Unfortunately, the older inhabitants of the United Kingdom, being rather stoical, seem to loathe taking analgesics and much encouragement may be necessary.

Antidepressants

Depression frequently occurs in the acute phase of herpes zoster, especially after the first week, and is also an important component in some cases of post­ herpetic neuralgia. It is important to treat this in addition to other complications. I have found ami­ triptyline particularly useful.

Antibiotics

These are indicated where secondary infection of the skin or eye is threatened. I have found that topical application is usually sufficient for this purpose. At Moorfields Eye Hospital I routinely use an antibiotic/ steroid combination ointment such as Neocortef for the skin and lids. This seems to prevent adequately the development of undesirable large crusts and severe secondary infection. It should be emphasized that the acute oedema which occurs shortly after the onset of the rash is not due to bacterial cellulitis and will settle without antibiotics within a few days.

Similarly, in the eye, I use an antibiotic/steroid combination drop (Predsol-N) in the acute stage of the disease when lid vesicles are discharging and forming crusts, and when there is a mucopurulent con­ junctivitis.

In the case of later comphcating comeal ulceration, usually of neuroparalytic origin, it is vital to use a topical antibiotic to prevent infection until the epithelium has healed.

Lastly, antibiotic ointment (chloramphenicol) should be applied morning and evening to the chronically scarred and inflamed lid margins which occasionally complicate herpes zoster. Left untreated, lid margin scarring becomes a focus for staphylococcal secondary infection and chronic conjunctivitis.

Anti-inflammatory agents

The main drugs in current use in this group are sys­ temic or topical steroids and systemic oxyphenbu- tazone.

In my opinion steroids are the bulwark of therapy in many of the ocular comphcations o f herpes zoster. Treatment of the skin and lids with a steroid antibiotic combination ointment or cream has already been mentioned. This is applied three times a day and continued until all the crusts have separated (usually within 3 weeks of the onset of the rash). It has proved a safe form of therapy with no evidence of severe topical or systemic toxic effects in over 600 cases.

The main use of steroids is, however, in the eye. It may be used for all inflammatory lesions, and is essential for lesions linked with vasculitis: i.e.

episcleritis/scleritis, sclerokeratitis, and iritis. At the first evidence of these I usually start dexamethasone alcohol 0 1 per cent drops 4-hrly, with Betnesol ointment at night. My principle is to strike hard and swiftly at the start of vasculitis to cut down the ischaemic and fibrotic scarring which usually develops. Once control is achieved the potency and frequency of administration can be reduced. The iritis of herpes zoster is frequently hypertensive and it is interesting that high intraocular pressures can occur with small amounts of flare, cells, and keratic precipitates. Fortunately, it is very responsive to steroid therapy, control usually being achieved with this drug alone within a few days. This comphcation usually occurs at the onset of the disease, but it may constitute a late relapsing phenomenon years after the acute attack. I have now seen several cases of unilateral chronic open angle glaucoma that have been referred from the Glaucoma Clinic after the typical iris, scleral, and skin scarring of herpes zoster have been noticed on the appropriate side (Marsh, Easty, and Jones, 1974).

The inflammatory keratitis of herpes zoster responds well to steroid therapy, but does not require such high doses as the above. Disciform keratitis, in particular, responds well and is unlike the keratitis of herpes simplex in that epithelial ulceration does not occur. The nummular keratitis fades on low doses of Predsol drops, but as in adenovirus keratitis the opacities recur if the drug is suddenly withdrawn. Mucus-plaque keratitis is a strange comphcation of herpes zoster, occurring in 5 per cent of cases at any time from 1 week to 3 years after the rash (Marsh, 1973). Super­ ficially it resembles herpes simplex dendritic ulcers with a stromal keratitis. On closer inspection it proves to consist of dendritiform mucus plaques deposited

336 Transactions o f the Ophthalmological Society o f the United Kingdom

on swollen epithelium with underlying mild diffuse stromal keratitis and iritis. The last two are distinctly benefited by topical steroids without adverse effect on the mucus plaques or the formation o f ulcers. In contrast, treatment with antivirals and no steroids causes marked deterioration in the keratitis. Therefore it is important to be aware of the differential diagnosis here, and to remember that herpes simplex superin­ fection of the affected cornea is very unusual (Marsh, Fraunfelder, and McGill, in press).

All these complications have a great propensity to relapse, especially on too rapid withdrawal of steroid therapy. Indeed, some of the worst ocular complica­ tions I have seen in cases of herpes zoster have been due to this phenomenon. In this respect the condition resembles many other systemic and ocular diseases requiring steroids, such as rheumatoid arthritis, ulcera­ tive colitis, collagen disease, etc., vernal catarrh, and herpes simplex stromal keratitis. I like to titrate the dose of topical steroids against the degree of disease activity in the eye. This, of necessity, is a slow, cautious process and may extend over a period of years. As well as reducing the frequency of administration of the drug, serial logarithmic dilutions can be made, or a change to another weaker steroid may be made,

e.g. from dexamethasone drops to Betnesol drops to Predsol drops. It is interesting that many of the more intelligent patients can titrate their own dose, which may be reduced to as little as Predsol drops 0 • 03 g/100 ml strength once a day to maintain control. The important essentials of steroid management are careful follow-up and examination to detect toxic side-effects. In particular, the danger of steroid- induced glaucoma must be remembered and regular measurements of intraocular pressure made. Steroids should be used sparingly in patients with diseased corneal epithelium and not at all when neuroparalytic ulcers are present. The long-term dangers are fungal superinfection and the development of lens opacities (although it is often difficult to know whether to attribute the lens opacities to chronic iritis or to the steroids). Regular slit-lamp examination of the cornea and lens is therefore essential.

Systemic steroids are routinely used in some depart­ ments for all cases of ophthalmic herpes zoster (Elliott, 1964; Scheie, 1970), but there has been much contro­ versy over this, especially with the risk of systemic spread of the disease (Rado, Tako, Geder, and Jeney, 1965 ; Haggerty and Eley, 1956). I use them only in cases of progressive proptosis with total 3rd nerve palsy and at the onset of optic neuritis. These condi­ tions are most probably due to occlusive vasculitis threatening sight and are therefore a logical indication for this means of therapy. I start with 60 mg per day and rapidly reduce to a maintenance dose.

Systemic oxyphenbutazone (Tanderil) is useful in cases of severe scleritis and sclero-keratitis that have not fully responded to the strongest doses of topical

steroids. The dosage is that recommended by Watson, Lobascher, Sabiston, Lewis-Faning, Fowler, and Jones (1966).

Artificial tears and mucolytic agents

A fairly common ocular complication in herpes zoster is loss of comeal sensitivity and damage to the mechanisms producing a stable pre-corneal tear film. This results in toxic changes o f the corneal epithelium, rapid formation of dry spots on the cornea, and de­ posits of abnormal mucus aggregations in the tear film. A combination of artificial tears and mucolytics will help to stabilize the tear film and improve the health of the corneal epithelium. The particular agents to use are largely determined by trial and error—I usually start with hypromellose, and then try BJg, PVP at differing concentrations. Adapt and Adapette, and varying concentrations of acetylcysteine.

I have not found the high water content soft contact lens of very much use in this complication, although it has proved useful in two cases of chronic neuro­ paralytic ulceration not totally controlled by a lateral tarsorrhaphy.

Surgery

The older methods of treatment are often the best, and this certainly applies to the tarsorrhapy in cases of the neuroparalytic ulcers of herpes zoster. After several years of trying the more progressive treatments I have found an immediate lateral half tarsorrhaphy invaluable at the start of neuroparalytic ulceration. It can be difficult to persuade patients to accept it, but it gives such rapid healing and security, reducing out-patient visits dramatically, that they can usually be won round.

Lid surgery may have to be considered for lid margin deformities such as ectropion and trichiasis.

Grafting

Neglected disciform keratitis and sclero-keratitis frequently give rise to dense scarring and lipid deposits in the central cornea. Rarely a strange, progressive fatty lipid keratopathy may spread across the cornea causing severe visual embarrassment. All of these cases, providing the cornea is not too vas­ cularized, tend to do well with perforating corneal grafts ; this may be because of the overall preservation of comeal sensation.

Emergency grafting may have to be done in cases of neuroparalytic ulceration with perforation. The prognosis is not as good in these cases as considerable difficulty may be encountered in establishing a stable corneal epithehum over the graft.

Antivirals

Over the last decade a new group of compounds has appeared for the treatment of viral disease. They

Ophthalmic herpes zoster 337

include cytosine arabinoside, adenine arabinoside, trifluorothymidine, and idoxuridine.

Several trials have been carried out using intra­ venous cytosine arabinoside (Hall, Wilfert, and Jaffe, 1969; Mann, 1971; Juel-Jensen, 1971 ; IPierce and Jenkins, 1973), but a recent double-blind trial (Stevens, Jordan, Waddell, and Merigan, 1973) showed that patients taking the placebo seemed to do better. A recent blind trial of systemic adenine arabinoside, using intravenous doses of 10 mg/kg daily for 7 days, showed equivocal results (Marsh and others, un­ published).

I have used Dr. Juel-Jensen’s technique of treatment with 40 per cent idoxuridine in dimethyl sulphoxide topically for the last 2 years at the Western Ophthal­ mic Hospital (Juel-Jensen and MacCallum, 1972). While there is undoubted improvement in comfort and the rash in the acute phase, my impression is that, in the late stages, the incidence of post-herpetic neuralgia is not significantly altered. Results of topical treatment of the rash with adenine arabinoside and trifluorothymidine have not been published. In my experience, idoxuridine applied topically to the eye does not significantly affect the course of the lesions. In fact, it seems to have an adverse effect on an already compromised corneal epithelium. However, as ophthalmic herpes zoster and its complications are initiated by a virus, it would seem logical to continue

to seek an effective antiviral agent. For maximum effect this must be given at the onset of the disease when virus replication is occurring, it must reach the site of replication in adequate concentrations, and it must be non-toxic. Lastly, but practically, it must be easy and economical to produce.

Conclusions

Ophthalmic herpes zoster presents many problems o f management in both the short and the long term. It is vital to follow the ocular complications regularly and to withdrawn topical steroids slowly and cautiously. It should be remembered that the complications have a tendency to relapse and that when they do so after a long interval may account for apparently new cases of ocular inflammation. Lastly, the pathogenesis of the disease is still very poorly understood. In particular,, the way in which the virus infection is linked to many of the ocular lesions is totally unknown. Therefore, treatment in many cases is palliative rather than direct­ ed at the cause of the disease. It is to be hoped that further advances in immunology and virology will eventually provide an effective treatment.

I am grateful for the encouragement received from Profes­ sor Barrie Jones in this w ork, and to M rs. Jane Field fo r secretarial assistance.

References

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E d g e r t o n , A . E . (1945) Arch. Ophthal., 34, 40

E l l i o t t , F . A . (1964) Lancet, 2, 610

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