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A faulty production line

Effective control of hay fever

is increasingly common in the UK. We have good evidence the number of British children with hay fever tripled between 1964 and 1989; now nearly 20 per cent of children aged 10 to 18 are affected. Compare this with the 19th century when Dr Charles Blackley took several years to find seven cases, including himself, for his thesis. There are few accurate prevalence estimates before 1960.

Hay fever, eczema and asthma are all linked to allergy: many patients start with atopic eczema in infancy, progress to rhinitis in childhood and become asthmatic in adolescence. Sometimes called the 'allergic march', this phenomenon raises interesting questions about whether having eczema increases the chance of becoming sensitised to pollen, and whether treating allergic rhinitis aggressively might reduce the risk of developing asthma.

In infancy and early childhood, allergies are mainly directed to food allergens. IgE antibodies to grass pollen appear in mid-childhood, and hay fever symptoms follow soon afterwards, peaking in teenagers. The immune system is most active between 18 and 25 years, and declines in activity thereafter. This reduces resistance to infections, but also causes declining production of sensitising antibodies. Losing your hay fever is one of the few compensations of age.

Although allergies run in families and clearly have a genetic component, the rise in hay fever cannot be blamed on a sudden change in the gene pool. Rather it reflects the action of environmental factors on a genetically susceptible subpopulation.

Suggestions that air pollution may be responsible have largely been rejected, as areas with heavy pollution, such as pre-1989 Eastern Europe, had much lower allergy prevalence than cleaner Western Europe.

While car exhaust pollution is greater in the West, the differences are small. With improved air quality post-1989, hay fever in eastern Germany is catching up quickly with rates in the West. These East:West comparisons suggest factors associated with our prosperous Western lifestyle are probably responsible. Among the two front-runners are differences in exposure to infections and differences in diet. Both relate to the so-called hygiene hypothesis.

The rape seed myth

Many patients believe they are allergic to rape seed or that it worsens their hay fever. Bright yellow fields of flowering rape are a very visible feature of the British landscape each spring, and they give off a characteristic cabbage-like smell. In general, highly-visible flowers are less likely to cause allergies than small, insignificant flowers.

Plants with gaudy flowers use insects to achieve pollination, and have heavy, sticky pollen grains that adhere to insects but do not travel far on the wind. Conversely, wind-pollinated plants have insignificant flowers because they do not need to attract insects.

If you walk through a field of flowering rape, you get covered in pollen, but rape pollen can only stay airborne for short distances. Agricultural workers can become sensitised to rape, but rape allergy is rare among non-farmers. However, rhinitis and asthma patients are affected by the smell of rape, which causes non-specific irritation, like paint, perfume and petrol.

Do the new antihistamines really work better

or is it all marketing hype?

Early antihistamines were pharmacologically dirty, with sedative and cardiac side-effects. Introduction of the non-sedating antihistamines, terfenadine and astemizole, in the 1980s was a great advance. Astemizole was very long-acting and often caused weight gain, but terfenadine was a great success and became the most widely used drug worldwide. However, when taken in overdose, terfenadine caused an unusual cardiac rhythm disturbance called torsade de pointes. Terfenadine is a pro-drug that is metabolised by cytochrome p450 to become active. Initially it was unclear whether the dysrhythmias were due to terfenadine or its metabolites. It turns out the parent drug blocks calcium-dependent potassium channels which affect the stability of heart muscle fibres. Unfortunately, cytochrome p450 is inhibited by several other drugs, most notably erythromycin and ketoconazole. Several episodes of torsade de pointes occurred in patients on normal doses of terfenadine who had taken antibiotics or antifungals. Terfenadine finally lost its place when it emerged grapefruit juice inhibited cytochrome p450 and can cause accidental overdose of terfenadine.

Loratadine and cetirizine were launched in the 1990s. Cetirizine is a stable metabolite of the older antihistamine hydroxyzine. Cetirizine rarely causes sedation at its recommended dose, but can be sedative at higher doses. Loratadine is metabolised by cytochrome p450, but has no cardiac side-effects, even in overdose.

Terfenadine and loratadine have now been replaced by their metabolites fexofenadine and desloratadine. These are not handled by p450 and are at least as effective as their parents.

It is claimed certain antihistamines have anti-allergic effects, over and above their antihistamine activity. Most of these effects are only seen in vitro, at concentrations not achieved in normal clinical use. While these observations are interesting for researchers, they have no bearing on choice of antihistamines for clinical use.

Are depot steroid injections really dangerous?

Depot steroids certainly work, and can make you feel you are giving a single injection to cover the season, but their biological impact is equivalent to using any other medium-term systemic steroid. Side-effects may be immediate (insulin resistance and hypertension) or longer-term, including osteoporosis and even avascular necrosis of bone. If topical steroids and antihistamines do not control symptoms, consider immunotherapy. Oral steroids can be used for short-term rescue at the height of the pollen season, and sometimes for special occasions like weddings and exams.

Prednisolone in a dose of 5-10mg per day will bring hay fever rapidly under control. Once symptoms are under control, the patient should revert immediately to topical steroids and antihistamines.

Are desensitising injections still available?

Why were they once widely used and could they make a comeback?

Specific injection immunotherapy (SIT) consists of a course of injections of pollen extracts, starting at a very low dose and escalating gradually over several weeks, followed by maintenance injections every six weeks for two to three years. SIT is effective in patients with hay fever, even in those who are poorly responsive to standard drug therapy, but side-effects can be serious and careful assessment of risks and benefits is needed.

Before 1986, many GPs gave SIT injections, but after a series of deaths in the 1970s and 1980s, SIT was restricted to specialist centres and is now generally reserved for patients who cannot be controlled by antihistamines and nasal steroids. But if treating rhinitis reduces the risk of developing asthma, this would bolster the case for much wider use of SIT.

How can GPs manage hay fever patients better?

Our survey of 64,000 patients on GP registers in Wessex found only 46 per cent of hay fever patients reported good control with current medication, while 15 per cent had poor control of their symptoms. Only one in four patients were using their medications as advised, so there is scope to optimise use of existing therapy. Most treatments work best when taken regularly, and nasal steroids should be started before the pollen season rather than when symptoms appear.

Generally, antihistamines are more effective against itch, rhinorrhoea and systemic symptoms than nasal congestion. Nasal congestion is due to a combination of vascular dilatation, mucosal inflammation and tissue oedema driven in part by histamine. But several other cells and mediators are involved that are insensitive to antihistamines. Montelukast can be helpful in some cases.

Rather than use systemic steroids, consider referral for SIT, while specialist allergy or ENT opinions are appropriate if hay fever symptoms become perennial.

Alternative and complementary therapies remain popular, despite limited evidence of efficacy. A recent BMJ report of benefit with butterbur has rekindled interest in herbal remedies. Unfortunately this trial did not study efficacy directly, but argued the case for butterbur on the grounds that it had fewer side-effects; further evidence in this area would be welcome.

What is the hygiene hypothesis? Could the recent rise in allergies be due to the loss of a protective effect from exposure to infections and environmental bacteria?

Perhaps we live in an environment that is too clean for our own good. Gut bacteria play a major role in the developing immune system, and the gut flora of Westerners has changed in the past 40 years, possibly due to technology and supermarket shopping. Early evidence suggests restoring a pre-1960 gut flora may protect against allergy.

First-born children are more likely to be allergic than younger siblings, and it seems the immune systems of younger siblings may be directed away from becoming allergic by fighting off viral infections caught from older siblings.

Children who grow up on farms in Austria are protected from becoming allergic, especially if they spend time with their mothers in the cow byre in the first year of life.

These strands of evidence support the idea that microbial influences may be important, but it is wrong to extrapolate that we should abandon vaccination or normal standards of personal hygiene.

With GP waiting rooms once again full of seasonal sufferers, Professor Anthony Frew and Professor Helen Smith share the latest thinking on hay fever management

 · Pollen counts are highest on sunny days when there is a stable high-pressure system

 · Follow weather forecasts and plan outdoor activities on dull days

 · Some of the highest pollen counts occur just before thunderstorms

 · Pollen grains are released in the mid-morning as the dew evaporates, and then ascend into the upper atmosphere, where they remain until the air cools

 · In the countryside pollen levels peak in the early evening (around 6pm) but in towns where the air remains warmer for longer, levels may be high after dark


 · Plan activity for very early morning, midday or early afternoon

 · Take an antihistamine before going out walking, playing golf, etc

 · Wrap-around sunglasses will reduce the number of pollen grains reaching the eyes

 · Many modern cars are fitted with

pollen filters

 · Always drive with the windows closed (easier to do if you have air conditioning)

Oral steroids are useful for short-term control but the patient should revert immediately to their usual therapies~

Only one in four patients use their medications

as advised~

Effective control of hay fever

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