Histamines, Autoimmune Conditions, and Axial Spondyloarthritis

Histamine is a chemical that plays a key role in allergies. It is also involved in inflammation and autoimmune conditions. When it is released from immune cells, histamine triggers events that worsen inflammation.^1-3

Histamine intolerance refers to having high histamine levels. There is a complex link between histamine intolerance and autoimmune conditions like axial spondyloarthritis (axSpA). Some autoimmune conditions increase the risk of histamine intolerance. High histamine levels may then trigger pathways that increase inflammation.^4-7

Talk to your doctor about managing histamine levels. They may suggest a diet that reduces certain trigger foods. They may also suggest that you take antihistamines or other medicines.

What is histamine?

Histamine is a chemical in your body that sends messages between cells. Your body gets histamine from certain foods. Your body also makes histamine itself. Histamine is stored mostly in immune cells called mast cells.^1,2

Histamine is well-known for its role in allergies. If you are allergic to something, your immune system thinks it is harmful. When you are exposed to the allergen, your mast cells release histamine.^2,3

The effect of histamine depends on which protein it binds to. Histamine can bind to and activate 4 different proteins. These are called histamine receptors (HRs). They are involved in different processes:^1,2

• H1 receptor – Causes allergy symptoms
• H2 receptor – Leads to stomach acid secretion
• H3 receptor – Regulates release of neurotransmitters
• H4 receptor – Plays a role in inflammation and autoimmune conditions

After mast cells release histamine, it must be quickly stored or inactivated. Your body breaks down histamine using enzymes. An important enzyme in this process is diamine oxidase (DAO). DAO helps prevent excess histamine. Problems with DAO lead to histamine intolerance.³

What is histamine intolerance?

Histamine intolerance happens when you have high levels of histamine in your body. It can happen from eating a lot of histamine-rich foods. It can also happen when you have problems with DAO.^1,3,4

Histamine intolerance can cause a range of symptoms, including:^1,4

• Diarrhea
• Bloating
• Nausea or vomiting
• Headache
• Runny or stuffy nose
• Itching, rash, or hives
• Painful or irregular periods

What is the link between histamine intolerance and autoimmune conditions?

The link between histamine intolerance and autoimmunity is complex. Certain autoimmune conditions increase the activity of mast cells, which can increase the risk of histamine intolerance. For example, mast cell activation syndrome (MCAS) causes overactive mast cells. People with axSpA have high levels of mast cells.^5,8

In addition, some medicines can cause histamine intolerance. Some cause mast cells to release more histamine. Others affect enzymes that break down histamine. For example, anti-inflammatory drugs can cause increase histamine levels.⁴

Histamine intolerance also can worsen autoimmune conditions. Histamine can bind the H4 receptor on immune cells called T helper 17 (Th17) cells. Activated Th17 cells release a pro-inflammatory chemical called interleukin 17 (IL-17). IL-17 plays a key role in many autoimmune conditions. Several axSpA treatments work by blocking IL-17 activity.^2,9,10

How is histamine involved in axial spondyloarthritis?

A few studies have found direct links between histamine and axSpA. These studies focus on the H4 receptor. They suggest that histamine levels and inflammation reinforce each other.^6,11

One study looked at several variations of the gene for the H4 receptor. They found that 1 variant may be more common in people with axSpA. But the relationship between the H4 receptor variant and axSpA is unclear.¹¹

In another study using mice, blocking the H4 receptor reduced inflammation. Treatment with an H4 receptor blocker reduced mast cells, Th17 cells, and IL-17 levels. Th17 cells are also linked to HLA-B27, a protein that is the major genetic risk factor for axSpA.^6,7,10

From these studies, a complicated picture emerges. People with axSpA may have a higher risk of histamine intolerance. In turn, high histamine levels may worsen inflammation. This cycle may involve some combination of:^2,5,6,9-11

• High mast cell levels
• Problems with DAO
• Changes in the H4 receptor gene
• High Th17 cell levels
• High IL-17 levels
• Presence of HLA-B27
• Use of anti-inflammatory or other medicines

How is histamine intolerance treated?

The main treatment for histamine intolerance involves avoiding trigger foods. Talk to your doctor about foods that increase histamine levels. They can suggest ways to avoid triggers while getting the nutrients you need. Common foods that can increase histamine levels include:⁴

• Alcohol, especially wine, beer, and champagne
• Processed meat
• Certain cheeses
• Sauerkraut
• Certain vegetables and tropical fruit
• Certain fish and shellfish
• Nuts and peanuts
• Licorice
• Chocolate

Your doctor may suggest that you take antihistamines. These drugs are often used to treat allergies or digestive symptoms. Along with dietary changes, they may improve symptoms of histamine intolerance.^1,4

Treating underlying conditions also can help. Antihistamines that block the H4 receptor may help treat autoimmune conditions. But the US Food and Drug Administration (FDA) has not approved any H4 receptor blockers. More research is needed to understand their benefits.^6,12