How can I stop sneezing at night?

University of Cologne

Doctors are researching new therapeutic methods against allergies


Constantly runny nose, shortness of breath, excruciating itching - allergies can really spoil your day. Doctors at Cologne University Hospital are trying to curb the excessive immune reactions, for example with an oral vaccination against house dust mite allergies. In the case of chronic hives, a drug that not only suppresses the symptoms is now on the horizon for the first time.


The immune system actually planned everything perfectly: if foreign pathogens, so-called antigens, penetrate the body, antibodies immediately pull the potentially dangerous troublemakers out of circulation. Each type of antibody has its own special task: Immunoglobulin E specializes in the defense against worms and other parasites. But for many people this system has gotten out of control: They suddenly form immunoglobulin E against substances that are harmless in themselves, such as grass pollen or cat hair; on contact, the antibodies stimulate a violent defense and inflammatory reaction.

The triggers of an allergy are called allergens - the misdirected immune response is directed against them. "People allergic to grass suffer from around April to August, but patients who are allergic to house dust mites are affected all year round," says Nicolas Hunzelmann, allergist at the Clinic and Polyclinic for Dermatology and Venereology at Cologne University Hospital. In the allergy competence center he diagnoses and treats allergies of all kinds. "Dust mites are also found all over the world."

The tiny arachnids that live in beds, sofas or on dust-covered books, among other things, are not themselves the trigger for the immune reaction - it is their feces that house dust allergy sufferers react to, or more precisely: individual substances in them. So far, researchers have identified seven allergens in mite faeces, including protein D.he p1, presumably an excreted digestive enzyme. Patients respond with constant cold, sneezing fits, or itchy eyes. “In some, the lower respiratory tract is also affected,” says Hunzelmann, “they suffer from severe asthma. The airways narrow and the patients can no longer breathe. "


Under the tongue instead of the skin


In the case of slight allergies to house dust mites, it is often sufficient if the animals feel less at home in the apartment - in other words, the allergy sufferer regularly hot washes his bed linen, avoids thick velvet curtains and, especially in winter, often airs his bedroom. If the allergy is more severe, however, an additional desensitization is recommended: the doctor regularly administers the allergy trigger to the patient until the body tolerates the foreign substance and the allergy symptoms subside. Among other things, the immune system forms during therapy allergen-specific immunoglobulin G; these antibodies can change the extent of the allergic reaction inhibit on contact with the trigger. In principle, a desensitization works similar to one Vaccination.


In practical use, this has previously meant: The patient has to come to the doctor's office regularly for three years and there receives injections with the purified allergen. For several years now, doctors have been researching a new form of administration, reports Nicolas Hunzelmann: "With sublingual immunotherapy, the allergy sufferer gets a tablet with the allergen under the tongue, where it dissolves and from there comes into contact with the immune system via the oral mucous membrane", so the medic.

One tablet a day at home instead of an injection every few weeks in the doctor's office - the advantages are obvious. "In addition, the possible side effects of sublingual immunotherapy are lower," says Hunzelmann. If the allergen is administered by syringe, severe, even life-threatening allergic shocks can occur in very rare cases. This is hardly possible with the tablet. The only side effects that often occur are swelling of the oral mucosa. The solutions for the classic, subcutaneous administration of immunotherapy contain much lower amounts of allergen than the sublingual administration.

“The initial fear was that when administered in tablet form, the patient would take in too little allergen for it to work,” says Hunzelmann. “But these concerns did not prevail.” Several large studies have shown that sublingual immunotherapy is effective against hay fever, for example due to an allergy to grass pollen.

However, it is not yet known whether it will also help patients who are allergic to house dust mites and who suffer from asthma. Nicolas Hunzelmann and his colleagues are now investigating this in a clinical study. “We want to find out whether sublingual immunotherapy can not only influence cold symptoms, but also asthma.” So far, the current guideline of the German Society for Allergology and Clinical Immunology advises against using the method in patients with allergic asthma. There is simply too little data available.


Itching - worse than pain


Doctors do not know the cause of the violent immune response in all allergy sufferers; in some cases, even after careful medical history and all available examinations, they do not know what the trigger is - as in urticaria, the chronic hives. "The patients wake up at night, they are covered with red wheals and suffer from terrible itching," says Nicolas Hunzelmann, describing the disease. This lasts for a few hours, then the wheals disappear again, only to reappear in another place a short time later.

In less than five percent of patients, an external cause for the condition can be found, for example an allergy to certain dyes and preservatives in the food. Physical stimuli such as cold or warmth also rarely cause hives. And often there is no external trigger at all, says Hunzelmann: “Up to a quarter of patients react by forming wheals at the injection site, if you inject their own blood serum into their skin. In other words, it is not an allergy in the true sense of the word, but possibly an autoimmune reaction. ”The exact mechanism is still a mystery to the medical community.

There is currently no causal therapy for chronic hives. "You can only fight the symptoms, that is, block the receptors of the messenger substance histamine with antihistamines," says Hunzelmann. Histamine mediates the defense and inflammatory reactions in the body. "But many Urticaria patients are not symptom-free even with four times the dose of antihistamines. ”In very bad cases, cortisone can also bring relief to the patient for a limited period of time. Otherwise no therapy options are available. "Many patients are desperate," says the allergist.


An anti-antibody being tested


To treat chronic hives, Nicolas Hunzelmann tested a new drug with medical colleagues all over Germany. The active ingredient called omalizumab has already been approved - but for the treatment of severe allergic asthma. The substance acts as an anti-antibody: It binds and neutralizes immunoglobulin E. "It was by chance that this active ingredient could also help with chronic hives," says Hunzelmann. A patient who suffered from asthma and urticaria at the same time received the drug - and lo and behold, the wheals also went away. “That's why we took a closer look at this in a clinical study.” The study was initiated by the doctor Marcus Maurer from the Allergy Center at the Charité in Berlin. A total of 16 clinical centers in Germany took part.

42 patients with chronic hives between the ages of 18 and 70 participated in the study. Half of the test subjects received the drug regularly injected under their skin for almost six months, the other half received a placebo. After just one week, the patients' condition improved with omalizumab. After six months, almost three quarters of these test subjects were completely free from the annoying wheals, and over half stated that they no longer had any symptoms at all. Overall, all patients had to swallow much fewer antihistamines than normal. The observed side effects were minor and the drug was well tolerated. The study was a complete success.


Finally a drug for chronic hives?


"The treatment increased the patient's quality of life enormously," says Hunzelmann. For the first time, there is a prospect of a drug that tackles the root cause of urticaria. “This is a big step forward,” says the doctor, “you can say: a quantum leap in the treatment of urticaria.” A second clinical study is currently underway to approve the drug for the treatment of chronic urticaria. If it is successful, doctors can soon be given something effective to treat their urticaria patients.

It is not yet clear how the drug works exactly. Several working groups are now trying to decipher the mechanism on a biochemical level.