Sunday, June 7, 2020

What is happening in skin that leads to chronic hives?

A useful pathway gone awry

It all begins right at the interface of blood vessel and the tissue.  Blood vessels are present in all tissues. These pipes (vessels) lined by a special layer  of cells called ‘endothelial cells’ carry components of blood. Endothelial cells fit into each other like ‘paver stone’. Under normal situations, cells fit tight to keep the ‘pipe’ from leaking. Blood flows through and very little fluid (plasma) leaks out into the tissue. The hives occur due to leakage of fluid into tissue more than normal. This leads to expansion of tissue spaces with fluid. Under the skin this looks like a hive (wheal) and in deeper tissue can present as angioedema. Thus, angioedema is the same process but in a different location.

A simple version of events is in the diagram that follows,

A process diagram showing why hives cause swelling and itch

A bit more detailed explanation is in the remainder of the article if you still are interested.

If this tissue swelling process is a problem, why do we even have it in the first place? Under specific situations, this process is useful and serves a purpose.  For example, when we are bit by a mosquito, or stub a toe, there is tissue damage.  Injury causes local inflammation and the blood vessels to be leaky, to begin repair. Therefore, mosquito bites wheal and a stubbed toe swells. This leaked fluid, rich in plasma proteins and healing factors starts tissue repair.

The main chemical that is known to cause this is histamine, released by the immune cells in the tissue. So in the discussion of triggers of acute hives, Histamine released from immune cells in allergic reaction or infection triggers hives. Thus, hives can either be local response to injury, or generalized immune activation.

The problem becomes chronic when tissue immune cells release histamine without provocation. This happens over and over again, without an obvious trigger, or specific purpose.
Thus chronic hives are due to,
  • Inappropriate release of histamine from skin immune cells (such as the mast cell)
  • Histamine causes endothelial lining to leak. This in turn causes fluid to move into the tissue from circulation.
  • This leaked fluid with expanded tissue spaces, manifests as hive (under skin). Swelling in deep tissue becomes angioedema.
  • Histamine will also stimulate the itch nerve fibers stimulating a profound itch. Angioedema (deep tissue swelling) does not itch but the area can feel numb. Pain and pressure fibers send signals to brain so a swollen lip feels as if a dentist anesthetized it.
In chronic secondary urticaria, another disease, triggers immune cells to release histamine. Appearance of chronic hives is then a symptom of that underlying condition

A simplified flow diagram showing the cascade of events leading to hives (click for higher resolution image)

Histamine is not the only chemical released by the skin/tissue immune cells. It is but, the most famous and primary culprit. The immune cells produce other inflammatory chemicals leukotrienes (LTs) , prostaglandins (PGs), chemokines, cytokines.  These are all potent molecules like histamine. There are also other immune factors we may not even have discovered, all involved in the process outlined above.

Histamine  (acting through its receptor(s) is the primary chemical playing a role in hives, though some other can also participate. (Click for higher resolution)

It is easy to recognize the complexity of the pathways in perpetuation of chronic hives. To jump directly to other sections in this topic
  1. Why do I get hives all the time with seemingly no cause?
  2. What if my hives bruise, blister, scar or heal with marks on skin?
  3. How to effectively manage hives and why do antihistamines work in most cases?
  4. What are lifestyle recommendations in management of chronic hives?

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