It happens to some people when they open the refrigerator, and to others when sweat evaporates from their skin and cools it down. In either case, these people break out in itchy hives as soon as their skin temperature decreases, and they look as if they had just touched a bunch of nettles. Bizarre, swollen spots can also appear on the face. People who react in such a way to a cold stimulus within five to ten minutes probably have a specific type of urticaria, known as cold urticaria.
Not only is the trigger a characteristic of this disease, but also the fact that “the symptoms appear only on the parts of the body that have experienced the cold sensation”, says allergologist Markus Magerl. “This means that if the patient has gone into the water up to his knees, the hives will be visible from the knees down, and everything above the knees in normal.”
However, the term ‘cold’ is misleading. The temperature of the stimulus is not a factor in the disease. What matters is the skin temperature, and it doesn’t even have to become extremely cold in order for symptoms to develop. Some people even have reactions at a skin temperature of 30 degrees Celsius. “For example, symptoms can be triggered when the forearm touches a table or the thighs touch a toilet seat,” explains Magerl. “The higher the threshold value, the more severe the symptoms.” Even so, the hives disappear half an hour after the skin has ‘warmed up’ again (or after several hours in some cases).
Jumping into water can be dangerous
Cold urticaria can become dangerous in rare cases, such as when hives appear all over the body after jumping into cold water. Magerl says that hives covering such a large area can be hard on the circulation. “Significant amounts of fluids can seep from the blood into the skin. This can lead to a drop in blood pressure and eventually shock and loss of consciousness. Patients should be made aware of this possibility.” Urticaria can also cause difficulties for people whose mucous membranes react to the cold. “Whenever these patients eat ice cream or drink cold water, swelling can occur in the throat, making it difficult to breathe.”
Hives develop when the body’s immune cells, known as mast cells, are activated and then release messenger substances. Since the mast cells play an important role in allergies, the disease is often referred to as a ‘cold allergy’. But this is not entirely accurate, says Magerl. The body cannot form antibodies against the cold as a physical stimulus and therefore cannot develop an allergy. It is more likely that substances released by the nerve endings to constrict the blood vessels when it gets cold also have an effect on the mast cells. “Another possibility is that certain proteins undergo a structural change when it gets cold and can then have an allergenic effect. But we still don’t know what happens in the phase between the effect of the cold and the activation of the mast cells.”
Doctors generally use a provocation test to confirm a diagnosis of cold urticaria. This is done by placing a plastic bag filled with ice cubes against the skin and testing the reaction to the cold stimulus. At Charité, the non-standardised ‘ice cube test’ has been replaced by an electronic measuring system. The testing device, developed at Allergie-Centrum, can measure the exact threshold temperature at which the hives are triggered. This information can be very useful for patients. “If the patient knows that his threshold temperature is 20 degrees Celsius, he knows that he needs to take precautions when swimming, for example”, explains Magerl. The allergologist also points out that it is useful to pinpoint the threshold value in order to determine whether a certain type of treatment is working.
Various medications are available for the treatment of cold urticaria. The hives can be prevented by avoiding cold stimuli – by wearing warm clothing or using face cream, for example. But this is not always practical, so antihistamines are the next best option. Although they cannot cure the disease, they can reduce the symptoms. If they are not effective, the doctor can increase the dosage by four. According to studies, some patients also respond to the IgE antibody omalizumab. However, it is not approved for use in treating cold urticaria and until now has only been used off-label for it. When medications are used off-label, the effects and side effects have not always been sufficiently tested. Furthermore, health insurers only cover the cost of the medication in exceptional cases.
According to Magerl, nearly one third of patients respond to a two to three-week course of the antibiotics doxycycline or penicillin. It is still unclear why these medications help and why the urticaria sometimes even disappears for good. The remarkable thing, says Magerl, is that they are effective even when no infection has been detected. It may have something to do with the anti-inflammatory properties of the medications.
For severe cases, the search for the right therapy requires patience and persistence. But the good news is that cold urticaria goes away by itself after some time, although it does take on average four to five years.