Monday, Jun. 22, 1992

Allergies Nothing to Sneeze At

By LEON JAROFF

Spring was suddenly in the air, a little later than usual, and trees were tardily emerging from their long winter dormancy, budding and flowering with vigor. Arboreal petals opened, exposing pollen-covered anthers to the breezes, which wafted pollen grains into the air, carrying some of them for many miles. By June, while the late-blooming trees were still in blossom, flowering grasses began contributing to the airborne assault, and many regions in the East began reporting record pollen counts.

As nature intended, the sheer number of pollen grains -- the botanical bearers of sperm -- ensured that at least some would reach and adhere to their natural goal: the stigma, a moist and sticky receptor of the female organ of the flower. That would start a fertilization process eventually resulting in seed and the propagation of the species. As a result of one of nature's oversights, however, many of the pollen grains reached another moist and sticky target first: a human eye or the mucous membranes of a nose or bronchial tube, where they set off a chain of events with a decidedly different outcome.

-- "It's been hell," says Mari Cox, 37, a medical assistant in Kansas City, Kans. A wet spring and wind in the region have whipped up pollen counts, so debilitating Cox that she hasn't been gardening -- her hobby -- or even playing with her five kids. Instead she is lying low, taking antihistamines and decongestants. "I'm miserable," she says.

-- On a Fire Island beach near New York City, weekenders are peacefully sunbathing when the wind suddenly rises, blanketing them with swirling clouds of pollen. Coughing, wheezing, their eyes tearing, some of the bathers beat a hasty retreat from the beach. "It was just like yellow smoke," says an awestruck city dweller.

-- "The new grass, the trees, especially those goofy cottonwood things that fly around here," laments Dorothy Jiganti, 48, an oncology nurse at Chicago's Grant Hospital. "It absolutely kills me." If you forget to take your pills, she says, "you just feel like you've got a cold all the time. It's a constant feeling of blah."

The malady afflicting these people is allergic rhinitis, more commonly called hay fever. It has nothing to do with hay and rarely produces a fever, but the Medical Gazette used that term in 1829, and the name stuck. The years since have produced no vaccine, no guaranteed cure and ever rising numbers of sufferers. In the U.S. alone, the sneezing, wheezing, teary-eyed multitudes are now estimated at 22 million.

What has improved is scientific understanding of the mysterious chain reaction that causes tiny pollen grains to make a human being miserable. Fresh insights into the process, combined with the new techniques of molecular biology and genetic engineering, offer hope that this plague will someday be brought under control.

That is little comfort, however, in this excruciating season of sniffles, which will not fade until ragweed -- the antagonist that may claim more victims than any other plant -- stops flowering in the fall. There is no precise way to measure how bad an allergy season is, since pollen counts are notoriously unreliable and as variable as local weather. But in the East, where spring was unusually concentrated this year, some readings have gone off the charts. At this time in 1991, Robert Hamilton, a researcher at Johns Hopkins University in Maryland, generally measured 1,000 to 2,000 pollen grains per cu m of air. This year there have been several days when the reading topped 8,000.

Personal anecdotal testimony is more emphatic. "This year has been the worst," pronounces Marina Gomes, 36, of Monroe, N.Y. Her head is constantly stuffed, her eyes water and itch, and she can't sleep. "It's horrible," she says. Dr. William Davis, director for pediatric allergies at Columbia Presbyterian Medical Center in New York City, calls 1992 the worst year in a decade. He says he is seeing patients who have not suffered such nasty symptoms for years, and his first-time visits are up 20%.

Those allergic to pollen are only the most numerous group in a much broader class of people who react badly to invisible tormentors usually in the air. In a sense, hay fever sufferers are among the lucky ones, since they have at least some idea of what is bothering them, how to minimize the problem and when it will stop. Millions of others are vulnerable all year round and unexpectedly come down with a dismaying variety of symptoms. They swell up, - break out in hives and blisters, develop eczema or upset stomachs, and have breathing difficulties. After the initial reaction comes the frustrating detective work to find the culprit among such widely disparate menaces as dust, cat dander, mold spores, foods, medications and insect bites.

At their worst, these allergens produce sudden death -- a result of what is called anaphylactic shock -- in 2,000 Americans a year. Another occasionally deadly complication is asthma, a chronic breathing disorder that kills 4,000 Americans a year (see following story). Altogether, allergies and asthma affect as many as 50 million people in the U.S., costing them up to $5 billion annually and accounting for 1 of every 9 visits to the doctor, including 1 of every 5 trips to a pediatrician. Despite the mass discomfort, the allergy branch of the National Institutes of Health spent only $29 million on studies of allergic disease in fiscal 1991 and another $15 million on asthma-related research.

Yet scientists report that they are making progress. In both academic and private labs, molecular biologists are unraveling the complex process that produces allergies, and geneticists are homing in on the genes that direct it. "What has changed dramatically over the past decade is an appreciation of how the inflammatory response is orchestrated," says Dr. Stephen Wasserman, chairman of the medicine department at the University of California, San Diego. "We are beginning to understand the fundamental regulators of the entire process."

Allergies, like autoimmune diseases such as arthritis and lupus, result from aberrant functioning of the human immune system, the body's remarkable defense against dangerous invaders, including viruses, bacteria and parasites. In the case of hay fever, the immune system perceives the fuzzy grain of pollen as a threat. The cause of the confusion, explains botanist Walter Lewis of Washington University in St. Louis, is a chemical message encoded by proteins in the pollen grain's cell wall.

When this message is delivered and read by a stigma in a flower of the same species, the fertilization process begins. But when the grain lodges in the mucous membrane of a person susceptible to allergies, its protein message is heeded by the human immune system, which confuses it with a menacing invader. Alarmed, the system immediately begins churning out legions of IgE (for immunoglobulin E) antibodies, stationing them on "mast cells," which patrol the body's tissues.

The next time similar pollen grains are detected, the antibodies signal the mast cells, which release a flood of chemicals, including histamine, against the harmless intruder. It is histamine that causes swelling, itching and other irritations all too familiar to hay fever sufferers. At the same time, additional IgE antibodies are produced and placed in position on mast cells, so that the next exposure to the pollen may produce a more severe response.

Another type of immune cell that swings into action at the first hint of pollen produces a substance that is toxic to parasitic worms. "Probably the IgE response is there primarily to protect people against parasites," says Dr. Harold Nelson of the National Jewish Center for Immunology and Respiratory Medicine in Denver. Its response to pollen, he says, is simply a mistake.

What causes the error? "The improper choice of parents," says Wasserman. "Probably there is a genetic predisposition to respond with IgE, and if you're unlucky enough to have both the exposure and the predilection, then you're more likely to have allergies."

David Marsh, a specialist in the genetics of allergy at Johns Hopkins, believes his laboratory has found evidence of a recessive gene that is at least partly responsible for susceptibility to allergies. And allergies indeed tend to run in families. If one parent has allergies, the odds are that close to 1 in 4 of the children will also be allergic. If both mother and father are allergic, probably most of their offspring will be too.

While pollen is the No. 1 troublemaker for allergy sufferers, hundreds of other substances can provoke the immune system into an irrational IgE response. Among the more formidable and difficult to avoid are the droppings of the dust mite, a microscopic insect that thrives by the millions wherever dust collects in a house. Living on sloughed-off flecks of human skin (dander) and other unappetizing protein, it leaves droppings that are about the size of pollen grains -- and just as easy to inhale. Mite dung, unfortunately, is an allergen that produces the familiar sneezing, coughing, itching symptoms in half of all people who have allergies.

Other pervasive allergens are the spores made by molds, both the outdoor kind that grow on crops, grass and dead leaves and the household variety found on foods, leather, furniture and in air conditioners. All these fungi spores can produce vigorous allergic reactions. "Molds are boggling," says Washington University's Lewis. "There can be hundreds of thousands of mold spores per cubic meter of air." And, he points out, a person inhales about 10 or 12 cu m of air each day.

Members of some 2 million U.S. families are allergic to cats. Feline saliva contains the offending substance, a protein called Fel d1 (for Felis domesticus 1) that is left on the fur and skin during preening, a full-time preoccupation of most cats. As a result, houses full of cat hair and dander cause uncomfortable reactions in 25% of allergy sufferers. "Some 70% of cat owners allow their cats to sleep with them in their beds," says Dr. Joseph Wedner, chief of allergy and clinical immunology at Washington University. "There's no better way to make someone allergic to a cat or to make a cat allergy worse than lying there with a cat pressed up against your face." Even the innocent suffer. One example is Dr. Arthur Torre, a Fairfield, N.J., allergist who occasionally treats cat owners. "I'll go in the room with them," he says, "and I'll start wheezing just from the cat dander they have on their person."

At home or away, threats lurk in the form of foods that produce allergic reactions ranging from nausea to death. Shellfish and nuts, especially peanuts, are among the most dangerous to the vulnerable, with the potential of causing anaphylactic shock, which is marked by sudden bronchial spasms, vomiting, plummeting blood pressure and heart arrhythmias. "Peanut allergy is a life-threatening disease," says Dr. John Oppenheimer of Denver's National Jewish Center. "The greatest nightmare for someone with a peanut allergy is dropping dead on a restaurant floor or at a potluck supper or a friend's dinner party."

While shellfish can be avoided, peanuts and peanut products, including some forms of peanut oil, are ubiquitous in foods, showing up unrecognized in such items as chili, stews and meat patties. Canadian businessman Paul Motz has learned to be wary -- and prepared. With seven severe reactions already in his medical dossier, he always carries a vial of the hormone epinephrine (for relaxing bronchial muscles and jump-starting the heart). He also has a supply of cards to hand out to waiters, each bearing the warning "I have an acute allergy to peanuts. Any contact could kill me immediately. Please double-check your recipes." An appropriate tip, to be sure.

Equally lethal to some are insect bites, which cause a fatal allergic reaction in some 40 Americans each year. As many as 20% of people in the U.S. have a severe local response to bites from yellow jackets, hornets, honeybees, wasps and fire ants. An arm swollen to twice its normal size is not unusual. Of the 2 million annually whose reactions to stings spread throughout the body, a few hundred thousand will break out in hives and suffer shortness of breath. Yet, according to the estimate of Dr. Martin Valentine, an allergist at Johns Hopkins, half of those people who would have such dangerous reactions are unaware that they are at risk.

Being aware offers little protection to those who fall prey to the kissing bug in Southwestern states. The dark brown insect, featuring a protruding proboscis and a splash of orange at the edge of its wings, strikes at night, quietly feasting on the blood of the slumbering victim. Most involuntary donors awaken the next morning itching from what seems to be a mosquito bite. But some immediately develop alarming and occasionally fatal allergic symptoms. Dr. Jacob Pinnas of the University of Arizona suggests that kissing- bug deaths may be underestimated. Some people who die in their sleep and have their death attributed to other causes, he says, may be victims of the not-so-amorous insect.

Other allergies abound, including one surprisingly associated with the aids epidemic: sensitivity to latex gloves, which are being worn in increasing numbers by health workers to guard against infection by the deadly virus. Latex, it seems, contains an allergen that can produce reactions as drastic as anaphylactic shock in allergy-prone people.

Despite energetic research into the nature and mechanics of the allergic immune response, and some improvement in treatment, no easy, surefire cure is in sight. Without question, says Washington University's Wedner, "the very best way of curing an allergy is to take away the allergen. No one is allergic to something that isn't there." In a few cases, that prescription is simple. Sufferers can get rid of the cat, for example, or avoid obviously allergenic foods and switch to nonlatex (but more expensive) gloves.

Avoiding pollen, especially ragweed pollen, is another matter. North America is host to 17 species of ragweed, a coarse, hairy plant with a slightly noxious odor and small yellow flowers. In most regions it blooms from August until October, each plant producing a billion pollen grains during an average season. These grains, carried by winds, can travel up to 400 miles -- even out to sea, where they can bedevil sufferers seeking relief aboard a cruise ship. Other places once considered havens because of less airborne pollen -- Tucson and Phoenix, for example -- are no longer ideal. Immigrants from other regions have brought their lawns, bushes and mulberry trees with them, making both the desert and pollen counts bloom.

Still, one sure way to cut down exposure to pollen is to take refuge in sealed, air-conditioned office buildings and houses, where filters cleanse most of the offending grains from incoming air. But even here, sufferers cannot win. Indoor allergens -- particularly spores from molds that grow on irregularly cleaned evaporative coolers and humidifiers -- can be circulated throughout the structure, bringing on the familiar allergic symptoms often attributed to "sick-building syndrome." In houses, keeping air-treatment units free of molds will not suffice; sealed-in, circulating cat dander and dust-mite dung often more than compensate for the absence of spores.

Dander and dung can apparently be brought under control -- although in each case the victory may not be worth the trouble. In the midst of experiments with cat dander, allergist Wedner made a serendipitous discovery. "If you wash cats once a month," he says, "then over a period of three to eight months they will stop making Fel d1. In essence, you've created a nonallergenic cat." To nail down his findings, Wedner now has his cat-owning patients experimenting with the technique on their pets.

For those allergy sufferers unconcerned with domestic decor, the National Institutes of Health recommends the following steps to achieve a dust-free, and therefore dust-mite-free, bedroom: Get rid of carpeting, upholstered furniture, heavy curtains, venetian blinds, fuzzy wool blankets and comforters stuffed with wool or feathers. Empty the room, scrub it and everything that is to be returned to it, and thereafter thoroughly clean the room every week. If replacing curtains, hang some that are lightweight and can be laundered weekly. Replace the comfortable chairs with wooden or metal ones that can be scrubbed, keep clothing in plastic zippered bags and shoes in closed boxes off the floor. Talk about suffering!

Most people use the term allergic freely, but often confuse allergies with other conditions that produce similar symptoms. Surveys have shown that as many as 70% of Americans believe they are allergic to at least one particular food. "That's absolute nonsense," says Columbia Presbyterian's Davis. "The actual number is less than 10%."

To determine if a reaction is allergic, Davis and other reputable doctors use a rather crude but effective technique. They combine a careful study of a patient's medical history with tests that involve injecting bits of suspected allergens, each in a different place under the skin, or applying them to scratches on the arm or the back. If a particular area swells, reddens and itches, the patient more often than not is allergic to the substance placed there. Ordinary citizens wondering whether their clogged nasal passages and sneezes are signaling an allergic attack or simply a cold can perform their own quick diagnosis. If there is no fever, if the mucous secretions are clear and if sneezes occur in rapid, multiple sequence, an allergy is almost certainly involved.

For temporary relief of mild allergies, doctors usually prescribe antihistamines, drugs that block the action of histamine, which is responsible for allergic symptoms. The antihistamine drugs in use for decades reduced swelling and other symptoms but led to drowsiness, an inconvenience in the office and a clear danger behind the wheel. But a newer antihistamine, terfenadine (trade name: Seldane), does not induce the need to nod. Other drugs helpful to allergy sufferers are cromolyn sodium, which in nasal-spray and eye-drop forms suppresses the release of histamine, and beclomethasone, triamcinolone and flunisolide, cortisone-based preparations that some doctors find to be even better inflammation fighters.

Permanent cures are more elusive. But for more severe allergies, doctors have had some success with a course of treatment that resembles the folk- medicine cure for hangover: patients are immunized with a little hair from the dog that bit them. In this seemingly primitive therapy, allergy shots consisting of allergens taken from such exotic sources as cat saliva, dust- mite droppings and pollen and mold spores are often administered over a few years. Early on, the shots are given as little as six days apart, but as the treatment progresses, the frequency of shots is decreased until it levels off to a monthly pace. Over the same span, the doses are gradually increased until they reach a maintenance level.

In some cases, the treatment pays off. "For pollen," says Dr. Jacquelynne Corey, an allergist at the University of Chicago, "the success rate is great, | around 90%." For dust mites, mold and animal dander, the results are more variable. But why the shots do -- and sometimes don't -- work remains a mystery. Medical researchers know, for instance, that administering the allergens directly into the bloodstream results in the production of immunoglobulin G, rather than IgE, antibodies. Does the presence of IgG block the IgE response? Or does the hair-of-the-dog procedure eventually desensitize key cells in the immune system to the offending allergen? No one knows.

Most doctors are convinced that a faster, more successful cure for allergies is bound to come. Using molecular-biology techniques, researchers have already identified IgE receptors on the mast cell, basically little berths in which the antibody docks. If they can find or synthesize another substance that blocks those receptors, they can prevent IgE from docking and unleashing the mast cell's stream of debilitating chemicals. And as scientists isolate and analyze more and more human genes, they may find the ones that, when defective, cause allergic reactions. Such discoveries could quickly lead to precise tests for allergies and eventually to permanent cures.

Until that time, millions of Americans will continue to sneeze and suffer, victimized by errant genes, pollen grains, mold spores, dust-mite dung and the family cat.

With reporting by J. Madeleine Nash/Chicago, Andrew Purvis/New York and Dick Thompson/Washington