By David N. Leff

Termites, powder-post beetles and wasps all nest inside houses, at great cost in extermination services.

But there's another, nearly subvisible, house-infesting creature that wages biowarfare against the homes' human occupants, who can't possibly get rid of them, at any cost. These are the house-dust mites (Dermatophagoides pteronyssimus and D. farinae), which proliferate astronomically in dwellings the world over. The minute arthropods — typically 300 microns long — live largely on sloughed human skin cells, and fill the air with their own desiccated feces, encapsulated in an enzymic protein coat.

When inhaled, this highly allergenic dust provokes strong immune reactions in an estimated 10 percent of the world's human population. Symptoms range from runny or obstructed noses, itching, sneezing, and swollen eyelids of rhinoconjunctivitis (better known as hay fever), to the wheezing strangulation of asthma. In the U.S. alone, asthma costs the economy some $2 billion dollars a year for medical care and time off from work.

Defensive countermeasures against house-dust-mite symptoms take the form of desensitization — aimed at accustoming the immune system to tolerate first small, then increasing, doses of exposure to the allergenic protein, administered as injections under the skin. To be maximally effective, the shots are continued the year round, often several times a week.

Because the allergen enters the body mainly via the nasal mucosa, many allergists, particularly in Europe, have tried liquid solutions of the mite protein delivered by mouth or nostrils as a noninvasive alternative to the subcutaneous desensitization injections.

Some European pharmaceutical companies have produced tablets that dissolve under the tongue. An article in the current issue of The Lancet, dated Feb. 28, 1998, reports the first clinical study of such sublingual desensitization. The paper bears the title: "Randomized controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis."

Its lead author is Giovanni Passalacqua, at the University of Genoa's Allergy and Clinical Immunology Service.

"We have a very extensive clinical experience with this kind of sublingual treatment," he told BioWorld Today. "And we needed only to formally demonstrate in a double-blind, scientific manner that the therapy is effective."

How Under-Tongue Treatment Works

The under-the-tongue tablets, produced by an Italian manufacturer, consist of protein from the two mite strains, chemically modified to facilitate dosing. "It's not a new kind of treatment," Passalacqua pointed out. "In Europe there are many kinds of oral immunotherapies commercialized.

"The mode of action," he continued, "is probably very similar to a lot of subcutaneous immunotherapies, by reaching the TH1 and TH2 lymphocytes. Obviously, when we give the allergen sublingually, the kinetic approach is different. Part of it is swallowed, absorbed and degraded. Part remains absorbed to the sublingual mucosa, so we hypothesized that a local immunity is activated."

Passalacqua chose 20 long-suffering men and women from his outpatient rhinoconjunctivitis clinic, and divided them into two groups. One cohort received under-the-tongue tablets in seven escalating doses, from 25 to 1,000 allergy units. After this build-up, they went on to 2,000-unit doses twice weekly for two years.

The placebo panel got dummy tablets of identical flavor and appearance.

During the 24-month trial period, participants kept a daily diary of their symptoms, graded from "absent" to mild, to moderate to severe.

Besides this subjective testimony, they were periodically tested for production of intercellular adhesion molecule-1 (ICAM-1), which is expressed on epithelial cells during an allergic reaction. "So ICAM-1 is a hallmark of allergic information," Passalacqua observed.

His study revealed "a seasonal trend in treatment scores. Allergen exposure was greater, and symptoms more severe, in both groups during the winter months." He attributed this effect to the simple phenomenon that during the winter months, people spend more time indoors. The houses are warmed and the mites proliferate, so the symptoms are more pronounced.

"Symptom redirection," his paper concluded, "remains the main measurement of immunotherapy effectiveness, and our scores confirmed the clinical efficacy of this kind of immunotherapy, with constant and significant clinical improvement."

US Expert Cites Innovations In Italian Study

Pioneer research allergist Philip Norman for years headed the Allergy and Immunology Division at the Johns Hopkins University School of Medicine in Baltimore. "The Italian paper," he told BioWorld Today, "added two things to sublingual therapy. One, it's in tablet form; the other, that it's an allergoid — the allergen modified by chemical treatment. This makes the molecules less capable of eliciting an allergic response," he explained, "but preserves their ability to make the immune system give a protective response. At least that's the theory."

Norman continued: "There's a considerable history in the U.S. of allergists taking the extracts that we commonly inject for treatment, but instead putting it in drops that are held under the tongue for a time, then either spit out or swallowed. There never was to my knowledge," he said, "a scientific study of that. And most of us who do regular allergy therapy by injection don't see how that could work. So it's never been an accepted technique among the majority of allergists."

He recalled having done "some experiments where we administered ragweed extract, a common allergen in the U.S., by mouth. Patients took it home in the form of liquid drops. We found that it worked if you give about 100 times more by mouth than by injection."

No one has yet determined what makes the mite's protein allergenic to 10 percent of the population. "The difference between allergic and nonallergic people," Norman went on, "is clearly inheritable in some way, but we have not identified a gene at this point." An active search for said gene is under way at Hopkins and several other centers, he added. *