As the winter weathers entrench themselves I thought cold induced urticarial would be a fitting topic for my winter blog entry. Also I had a suggestion from my small but very appreciated twitter followers! Thank you.
Urticaria is essentially the medical word for “hives”. We define acute versus chronic somewhat arbitrarily based on whether or not the hives occur for less than 6 weeks of more than this amount of time for the later.
Now there is a subset of chronic urticaria that really presents as acute intermittent urticarial. What I mean by this, if a person is exposed to a particular trigger, it becomes chronic based on definition alone (i.e. the hives are occurring on more days than not for more than 6 weeks). When the triggers to the hives are physical triggers this is termed physical urticaria.
Physical urticaria encompasses many different stimuli including, but not limited to: pressure, heat, sweating (cholinergic), vibration, light, and you guessed it cold.
Now the critical concept not discussed in most medical texts and journal articles is why we even have the ability to form urticarial lesions in the first place. For this we have to go back to the fundamental understandings of the immune system.
As humans, like most animals on this planet, need a robust way of dealing with all manner of critters that are out to either live off us, harm us, or even worse kill us. As such we needed a way to counter this so that we don’t succumb to these attacks. The “hive” that you are getting is actually your body “naturally” committing chemical warfare on whatever parasite, bacteria, or virus is coming in!
There are a lot of junk science articles out there that explain hives as a being the end result of an underactive immune system. This is simply wrong! Incidentally, stating that it’s the end result of an over active immune system is also kind of wrong! It’s technically best described as an incorrect regulation of the immune system.
In most developed countries we are no longer subjected to a barrage of attacks from little critters and as such forget why we even need this type of immune response. If a parasite is burrowing it’s way into you, your body may sense some vibration, pressure, or temperature change at that site. Naturally your body needs a way of letting you know something is happening there and hence substances such as histamine get released to cause you to itch (i.e. alert you that something is trying to breach your borders!).
Other chemicals also get released in a hive reaction such as major basic protein (that fights micro-organisms) and heparin (helps open the blood vessels up so that other white blood cells can get in on the action later). It also increases the propensity, first locally then systemically (throughout your body) to alert other first, second, and third line defenders of the immune system to be on “red alert” (no pun intended!) through the release of cytokines and chemokines (the chemical signals that your immune system uses to communicate) and activating factors such as “stem cell factor” which temporarily increases the longevity and aggressiveness of some lines of your immune system.
So now in terms of cold urticaria there are really 2 broad types of cold induced urticaria.
1) systemic (requires a fall in body temperature)
2) local (requires only a part of your body to become cold)
Some people will also split up the categorizations by whether of not one responds to the “ice cube challenge” test done in the clinic. There are now all sorts of fancy devices that can tell a physician exactly what temperature is required to induce an urticarial reaction but in a public health care system don’t expect this to be available any time soon!
In any event, systemic cold induced urticaria is far more rare. This occurs when there is a fall in the core body temperature of someone. So this would be someone who gets urticaria after going outside on a cold day. The hives will occur not only on areas of exposed skin but throughout the body (systemic).
Local cold induced urticaria is more common than systemic. This occurs in skin that is exposed to cold. Various temperature thresholds are required and it varies from patient to patient.
Occasionally cold induced urticaria is associated with an underlying medical problem. Some things your physician should rule out if this has become chronic is cryoglobulins, cryofibrinogens, presence of low complement levels, some hematologic malignancies, hepatitis (whether it be autoimmune or viral), renal disease, and other auto immune conditions.
There are a known few familial forms of this including the recently described one herein http://www.ncbi.nlm.nih.gov/pubmed/22236196 or as part of CAPs syndromes. However, routine testing is very difficult to do. Even in cases of CAPs, not all gene mutations have been identified so the genetic testing is not always necessary or useful in whether or not we decide to test for the mutations.
Treatment includes avoidance like anything in allergy. Two particular situations patients need to be careful about is swimming and ice cold beverages or things such as ice cream. Swimming can induce urticaria throughout the body resulting in hypotension (low blood pressure). In some cases the diffuse urticaria will cause in drowning due to loss of consciousness. Occasionally some patients with this condition will experience angioedema with the ingestion of cold beverages and as such eating something cold can potentially cause throat constriction.
Management includes carrying of epinephrine in some cases as well if there has been any prior anaphylaxis. I typically advise patients to avoid swimming. A medic alert bracelet identifying that the patient carries epinephrine autoinjectors (EPI pen ® or Allerject ® / Auvi-Q®) with anaphylaxis labeled is highly advised as well.
There are two exciting developments though that I’d also like to share. If a patient has been diagnosed as having a CAPs syndrome, two new drugs in the class of anti-IL-1 monoclonal antibodies are a game changer. In particular they are called anikinra® and elaris®. However I want to emphasize that these conditions are extremely rare and that it is best if you speak to your specialist clinical immunologist and allergist about this. If you’ve seen me, don’t worry I’ve already thought about it and ruled it out in most cases.
The other really exciting development, as is the case in all causes of chronic urticaria is the use of another monoclonal antibody called Xolair ®. This is currently approved to treat moderate-severe asthma where it works great! However, most dermatologists and clinical immunologists and allergists who remembered a little bit about basic science immunology suspected it would likely work even better on chronic urticaria. I have my own theories on the exact mechanism of action on this and I am told there are already ongoing studies globally and in Montreal exploring the postulated mechanisms.
The very first study on chronic “spontaneous” urticaria patients published in the New England Journal specifically excluded patients with cold induced urticaria strangely enough for reasons that are unclear. However subsequent studies show that it is very effective in cold induced urticaria as well. It is unclear if this is permanent.
So the $1 000 000 question is what causes people to be “allergic” to the cold? Well it depends. Most of the time we do not know! The theory is that there is something that agitates the cells that cause most of the hives (mast cells). I do want to emphasize that it can be a self limited and self resolving condition in most benign cases.
Of the known causes it is important to treat the underlying condition.
With that I wish everyone the best in 2014!
Dr. Jason K Lee, MD, FRCPC