I. Introduction

The exact cause of HS is not yet known, but we do know a number of different factors that are more common in people with HS. This chapter discusses the role of genetics, epigenetics, and inflammation in HS.

II. Genetics

Genes are instructions in every cell of the body that give it instructions on how to behave, how to grow and how and when to die. Everyone inherits genes from both their mother and their father.

People with HS are more likely to carry variations of certain genes that are not found in people without HS. Some of these genes control the machinery inside the cell, which carry signals on how to behave. A number of these genes affiliated with HS code for a group of proteins called the “Gamma Secretase Complex.” Not all people with HS carry these different genes, and they may be much more common in certain parts of the world than others. For example, HS patients from China are more likely to carry copies of these genes than HS patients from Europe. Scientists believe that up to 70% of the reason you get HS may be found in your genes. People with HS have certain genes that are also found in people with gut conditions such as Crohn’s disease as well as in people with other rare conditions that trigger periodic spontaneous fevers.

You cannot test for an “HS gene” currently, but scientists are sure that there are many other genes specific to people with HS that have yet to be discovered. Further research needs to be done to identify what genes signal HS, so that genetic screening tests can be developed in the future.

III. Epigenetics

Some factors in the environment (such as food, infections, and stress) can sometimes alter the activity of genes. This change in activity is called “epigenetics.” Some epigenetic differences have been identified between people with HS and people without HS. However, they are also seen in many other diseases where there is a lot of inflammation. Scientists are currently trying to determine if these epigenetic changes are actually a part of HS or whether they are just present in the background. There is currently no safe effective treatment for changing these epigenetic signals.

IV. Inflammation

There are many different types of ways that inflammation can occur in the body. Some inflammation fights off viruses, some inflammation fights off cancer, and some inflammation fights off fungal infections. The immune system, which controls inflammation, is incredibly complex, and even the best scientists do not yet completely understand how it all works.

What we do know is that inflammation is everywhere in people with HS, not just in the skin. This inflammation is “dysregulated,” which means the inflammation is not working the way it should. When someone has HS, inflammation in the skin is triggered by something small, but the normal signals that tell the body to stop the inflammation are not working properly. The uncontrolled inflammation and follicular occlusion, or blocking of the hair follicles, cause HS. The result is painful swollen cysts, boils, and in some cases, permanent scar formation and odorous, pus-draining tunnels.

Testing the blood of people with HS shows inflammation throughout the body. The type of inflammation associated with HS is a mixture of different types. Numerous kinds of blood cells gather in the skin and produce chemicals that, in turn, produce the inflammation. This inflammation helps explain why people with HS tend to have other conditions such as arthritis, gut problems, and non-healing wounds.

Controlling excess inflammation helps stop the pain, swelling, lesions, and disease activity of HS.

This is how many medications for HS work: by reducing inflammation. There are specific inflammatory molecules that have been found to be elevated in people with HS. These include tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-17, IL-23, and IL-36. There are medications that specifically target these molecules to reduce inflammation and treat HS. Some people have HS that is well-controlled with these types of medication; however, people with severe HS have higher levels of these inflammatory molecules so the disease can be more difficult to treat. The fact that people with HS have varying levels of inflammation – and therefore varying degrees of disease severity – helps explain why the same treatment does not work for everyone. For more information on factors that contribute to HS inflammation, see Chapter 4.