Introduction		Treatment of the acute infection
Incidence		Treatment of established PHN
Pathology		Conclusions
Clinical considerations

Introduction

Following the initial infection the chicken pox virus may lie in the dorsal horn of the spinal cord for decades before its unwelcome presence becomes evident when it is activated to cause an acute attack of shingles. Typically, this presents as a burning, tingling pain with occasional stabbing components that may precede the onset of small cutaneous vesicles in the distribution of a cutaneous nerve or nerves by as much as two or three days. In turn, this may lead to the unpleasant persistence of pain in the form of post-herpetic neuralgia (PHN). PHN is defined as pain arising or persisting in areas affected by herpes zoster at least three months after the healing of the skin lesions. The early recognition and treatment of herpes zoster prevents viral replication, relieves the acute pain and may reduce the complications of the disease of which PHN is the most feared. However, while it is important to emphasise that treatment may help PHN, there remains a core of patients who are incredibly difficult to treat successfully even in the most optimum circumstances. 

Incidence

The incidence of PHN is between 9 and 14% one month after the herpes zoster eruption. There is a definite tendency for PHN to improve with time and as few as 3% of patients may be left with severe PHN after one year. There is no way of predicting who will recover and some series report that as many as 40% of patients with PHN will continue to have long-term problems because of incomplete or no pain relief from our best treatments.

There is no difference between the incidence in males and females, but the incidence is directly related to age; with PHN becoming much more common and more incapacitating as the patient gets older. There is no seasonal incidence and the areas affected tend to be on the chest and abdomen and the ophthalmic division of the trigeminal nerve. One study has shown that black patients have a significantly lower risk of developing herpes zoster than whites. There is an increase in the incidence of herpes zoster with lymphoproliferative disorders (leukaemia / lymphoma) and severe disease and aggressive treatment seem to increase the likelihood of severe PHN. Herpes zoster seems to be more common in any condition with a change in immune status and is not uncommon in patients with HIV. 

Pathology

It is thought that the varicella virus passes to the dorsal root ganglion via the skin during the initial infection (chicken pox) and lies dormant. The latent virus becomes reactivated when immune mechanisms are impaired and the revived activity of the virus is manifest by the rash and the pain. Some cases of pain in PHN may be due to persistent inflammation in the dorsal root ganglion and this may be the reason that anti-inflammatory or antiviral agents can be useful in some individuals. Evidence exists that the small pain fibre activity begins to predominate as the disease advances and that there is increased sensitivity to mechanical stimuli, alpha-adrenergic agonists and to sympathetic efferent activity. These mechanisms suggest that the success of antidepressants in treating PHN may be related to their serotonergic and nor-adrenergic effects. 

Clinical considerations

Herpes zoster usually starts with pain, paresthesiae (numbness / tingling) and dysaesthesiae (unpleasant sensations) in the affected dermatomes, followed a few days later by the rash. The pain is usually severe and particularly so in the elderly. The characteristic vesicles usually scab within a week and heal in a month. Generalised zoster is rare but may occur in immunocompromised patients. Infection in the sacral segments can occasionally give rise to urinary retention and there are rare cases of motor nerve involvement, usually in the facial nerve. No evidence exists to support the view that PHN occurs more frequently in the presence of an occult malignancy.

About 5% of patients develop a systemic response to herpes zoster, with fever, stiff neck, headache and nausea. This does not lead to a higher incidence of PHN. Ophthalmic shingles may jeopardise vision and early and aggressive management is advised. Recurrent attacks of herpes zoster are uncommon but may be associated with immunosuppression or malignant disease.

The scarred areas are at least less sensitive, and often anaesthetic. Paradoxically the skin may exhibit marked superficial pain with light touch (allodynia) or an increased sensitivity to noxious stimulation (hyperesthesia). There may be two types of pain: one a steady burning or aching, the other a paroxysmal, lancinating (stabbing) pain. Both may occur spontaneously and may be aggravated by even the lightest contact with the involved skin. Curiously, firm pressure may lead to pain relief whereas light brushing may be unbearable. Severe pain also may be provoked by physical activity, temperature change, emotional upsets or, in rare cases, by stimuli as trivial as noise from the street or light breezes.

Examination of the affected, scarred skin may reveal that there is a loss of sensation to pinprick, pain and temperature over a far wider area than the scars and in addition, that the area of sensitive or painful skin is even wider still. This phenomenon is thought to be due to the damaged central neurons becoming sensitive to stimuli from a wider area. 

Treatment of the acute infection

The acute pain can be treated topically and systemically. Covering the lesions with calamine lotion, petroleum jelly, local anaesthetic creams or an occlusive bandage may give some symptomatic relief. Non-steroidal anti-inflammatory drugs and paracetamol (acetaminophen) with or without codeine or other opioids, may be indicated because of the severity of the pain. There is every justification for using stronger opioids in cases with severe pain that is not relieved by other methods. It makes sense to treat the acute infection as well as possible as this may prevent alterations in the central nervous system that may be responsible for the development of PHN.

It has been suggested that the use of antiviral agents within the first 72 hours may prevent viral replication and thus reduce the severity of the acute eruption and prevent PHN. There is now some evidence to support the use of these agents in this fashion. The use of low dose (10- 50 mg) of amitriptyline at night may reduce the onset of PHN in anyone developing shingles. Use of corticosteroids has been suggested but results of clinical trials have been confusing and their use cannot be recommended as a method of preventing PHN. The initial infection seems to clear up earlier but there was no effect upon the incidence of PHN. Regional anaesthesia has been the subject of several uncontrolled trials, but no clear answer has been achieved. Suffice it to say that the pain of acute shingles can be relieved by appropriate somatic or sympathetic blockade, or both, and that sometimes this is the only way of getting symptomatic relief in difficult cases. 

(Continued ...)

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