At first glance, Sjögren’s disease and hereditary angioedema (HAE) may seem like very different conditions. Sjögren’s is an autoimmune disease meaning the immune system mistakenly attacks the body’s own healthy tissues. HAE is a rare genetic disorder that can cause repeated episodes of swelling, called angioedema attacks.

Even so, researchers have explored whether these two conditions may be more closely connected than they appear.

The relationship between Sjögren’s disease and HAE isn’t fully understood, but research has pointed to a link between the two conditions.

In this article, we’ll explain what Sjögren’s disease is, what current research says about its possible link to HAE, and what to know about diagnosis and treatment.

How Sjögren’s and HAE May Be Connected

Researchers are studying whether there may be a connection between Sjögren’s disease and HAE. So far, findings suggest that the link may involve how the immune system works.

The most common forms of HAE are caused by low levels or dysfunction of a protein called C1 inhibitor (C1INH). Health experts believe that HAE related to C1INH deficiency may be linked to autoimmune diseases because C1INH helps regulate parts of the immune system.

The theory is that when C1INH levels are low or the protein doesn’t work properly, the body may be less effective at clearing out damaged cells and other triggers of inflammation. Over time, this could contribute to immune system changes that increase the risk of autoimmune disease.

What the Research Says

Scientists are investigating whether people with HAE may be more likely to develop autoimmune diseases like Sjögren’s. As of now, only a small number of studies have looked at this possible link.

One Italian study looked at 855 people with HAE due to C1INH deficiency, which includes type 1 and type 2 HAE. The researchers checked for rare connective tissue diseases (RCTD), including Sjögren’s. They found that 18 people, or 2.1 percent, had one RCTD. Systemic lupus erythematosus (SLE) — the most common form of lupus — was reported most often, followed by Sjögren’s.

A Swedish study compared people with type 1 or type 2 HAE with people who didn’t have HAE. The researchers found that people with these types of HAE had a higher risk of developing autoimmune disorders.

The Swedish study noted that the risk of developing more than one autoimmune condition was also higher in people with HAE. Among autoimmune conditions, SLE was reported most often in people with HAE.

Results from another study suggest that autoimmune diseases occur more often in people with C1 inhibitor deficiency HAE than in the general population. Those with HAE had significantly higher rates of autoimmune diseases — with 11.6 percent versus 3.2 percent having one or more. Again, the most common was lupus. Sjögren’s occurred in 1.7 percent of those with HAE and 0.2 percent of those without.

It’s also important to note that these studies have limitations. Both studies that compared rates of autoimmune disease in people with HAE to those without were retrospective (analyzed data previously gathered).

Because these studies looked at past events, they weren’t able to control for other factors that may have influenced outcomes. This means they can point out potential links, but they can’t say that one thing definitely causes the other.

Autoimmune vs. HAE Swelling

Both autoimmune diseases and HAE can cause swelling. However, the root causes of swelling are different.

In many autoimmune diseases, swelling is driven by inflammation caused by the immune system attacking healthy tissues. In allergic swelling, mast cells release histamine and other inflammatory chemicals that cause blood vessels to widen and become leaky.

Leaky blood vessels allow fluid and immune cells to seep into nearby tissues, which leads to swelling. Histamine is also to blame for the swelling that occurs due to allergic reactions.

In contrast, HAE swelling is often caused by excess levels of bradykinin. This inflammatory peptide builds up when the C1INH protein isn’t present in large enough amounts or isn’t working correctly.

Like histamine, bradykinin can cause blood vessels to leak fluid into nearby tissues. This leakage can result in swelling of the skin, airways, or gastrointestinal (GI) tract.

When To Suspect Sjögren’s and HAE

HAE is known to cause episodes of swelling that recur without explanation. Attacks usually last between three and five days.

HAE swelling may be visible on the skin of the face, tongue, hands, or feet, but it may also occur internally. If swelling affects the airways or GI tract, it can lead to symptoms like diarrhea or vomiting, belly pain, or difficulty swallowing or breathing.

If you have HAE, your doctor may evaluate you for Sjögren’s if you’re having symptoms outside of those explained by HAE. People with Sjögren’s can develop swelling of the salivary glands and joints. Other symptoms that may occur with Sjögren’s include:

• Eye and mouth dryness
• Joint pain
• Muscle pain
• Fatigue

Ruling Out Other Causes

Diagnosing Sjögren’s and HAE can be difficult. Both conditions can cause symptoms that can overlap with other conditions. Other potential causes of symptoms often need to be ruled out before these conditions can be diagnosed.

For example, HAE-related GI swelling isn’t the only reason someone may experience belly pain or diarrhea. Several conditions, including irritable bowel syndrome (IBS), will have to be ruled out as the cause of symptoms. Meanwhile, Sjögren’s symptoms like fatigue, pain, and swelling can be due to many health conditions.

Hives, which are raised, itchy welts, can help doctors find the cause of some swelling. Hives often occur with allergic swelling, but don’t typically appear with HAE.

Testing for Sjögren’s and HAE

Certain testing can help identify Sjögren’s and HAE. Blood tests to assess C1INH levels and function, as well as genetic tests, can help diagnose HAE. Tests used to diagnose Sjögren’s disease may include:

• Blood tests for autoantibodies SS-A (Ro) and SS-B (La)
• Eye tests to measure tear production and eye dryness
• Oral tests to assess the salivary glands

It’s possible to have both Sjögren’s and HAE. If you’ve already been diagnosed with HAE, your provider may test you for Sjögren’s if you’re experiencing symptoms that aren’t explained by HAE.

Treating Sjögren’s and HAE

Because Sjögren’s and HAE have different root causes, they require different treatment approaches.

Sjögren’s treatment often focuses on relieving symptoms related to dryness and an overactive immune system. Treatment options may include:

• Artificial tear eye drops
• Saliva substitutes
• Medications to calm the immune system, such as corticosteroids or immunosuppressants

Meanwhile, HAE treatment focuses on treating and preventing swelling attacks. Depending on the type of HAE you have, your treatment plan may include medications to stop and prevent attacks. It may also include avoiding triggers that can cause swelling.

Most HAE swelling isn’t caused by histamine. This means allergy treatments, such as antihistamines, corticosteroids, and epinephrine, don’t usually work. That’s why it’s important to find the cause of swelling so it can be treated the right way.

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