Intestinal Angioedema - Types, Causes, and Treatment

Introduction

Angioedema is a localized temporary swelling that affects the skin's layers. It can also affect the hollow internal organs like the bronchi, oropharynx, and bowels. Intestinal angioedema is a rare condition that causes swelling of the intestinal walls. It can affect both the small intestine and the large intestine. As the condition is rare and the symptoms are similar to other gastrointestinal conditions, it is often misdiagnosed. Patients complain of vague symptoms like nausea, vomiting, and abdominal pain. Intestinal angioedema can be caused due to various factors like food allergy, medications, or heredity. Treatment aims at identifying the cause and treating it.

What Is Angioedema?

Angioedema is the body's reaction to a trigger that causes swelling in the skin’s deeper layers, like the dermis and submucosa. It occurs due to the leakage of fluids from the blood vessels into the surrounding tissues. It starts unexpectedly and lasts only for a day or two, commonly involving the eyes and lips. It is not fatal but can be alarming when it affects internal organs like the airways. In such cases, angioedema requires immediate medical attention.

Angioedema is classified into several types:

1. Acute allergic angioedema.

2. Non-allergic drug-induced angioedema.

3. Hereditary angioedema.

4. Idiopathic angioedema.

5. Acquired C1 deficiency angioedema.

6. Vibratory angioedema.

7. Intestinal angioedema.

What Are the Causes of Intestinal Angioedema?

Angioedema usually affects the deeper layers of the skin (called the lower dermis), the subcutaneous tissue (part beneath the skin), and the submucosal layers. The mucosal and submucosal layers cover the intestines. In intestinal angioedema, the blood vessels of the submucosal layer become ‘leaky’. This results in seepage of fluid from the vessels into the submucosal layer leading to swelling in the intestinal walls.

The most common cause of intestinal angioedema is drug-induced angioedema. ACE (angiotensin-converting enzyme) is an enzyme in the body that causes the contraction of the muscles in the blood vessels. Prolonged contraction can result in hypertension. ACE inhibitors are medicines that act against ACE by blocking muscle contractions. This leads to the relaxation of the vessel muscles, thereby controlling blood pressure. ACE inhibitors also increase bradykinin levels which further aids in vasodilation. Relaxation of blood vessels, along with vasodilation, helps in reducing blood pressure. However, bradykinin also increases vascular permeability, which enables substances to ‘leak out’ of the blood vessels. This fluid enters the submucosa's interstitial spaces, causing edema or swelling. Severe swelling can also lead to the narrowing of the lumen of the small intestine. Discontinuation of the drug helps in resolving the swelling in a short span of time.

Patients with acquired or hereditary angioedema are at an increased risk of developing intestinal angioedema. Complement is a type of immune chemical. In patients with acquired or hereditary angioedema, an enzyme called C1-INH (C1-inhibitor) is deficient. This enzyme is responsible for inhibiting the activity of complement. Deficiency of the enzyme thereby increases the activity of complement C1. This, in turn, activates kinins which cause ‘leaky vessels’, leading to swelling of the submucosa. Intestinal angioedema can also occur due to allergies or unknown reasons.

What Are the Signs and Symptoms of Intestinal Angioedema?

The commonly reported signs and symptoms of intestinal angioedema include:

• Nausea and vomiting.

• Abdominal pain that aggravates soon after eating.

• Intestinal cramps.

• Abdominal distension, in severe cases, can be mistaken for bloating.

• Shortness of breath.

Abdominal pain can lead to loss of appetite and weight loss over a period of time. Also, digestion and absorption of nutrients can be severely affected if angioedema involves the large intestine. This can further cause malabsorption syndromes and nutritional deficiencies. Intestinal angioedema is often associated with the involvement of other organs like the skin and air passages. It can present as hives or urticaria. Impaired air intake causes shortness of breath.

How Is Intestinal Angioedema Diagnosed?

The following tests can diagnose intestinal angioedema:

• CT (Computed Tomography) Scan: A CT scan helps detect the narrowing of the lumen.

• Colonoscopy: It is a procedure in which a long, flexible tube with a camera at the end is passed through the rectum to view the structures of the large intestine. This procedure mainly detects polyps or cancers of the large intestine. It also aids in detecting intestinal narrowing due to intestinal angioedema.

• Laparoscopy: A laparoscopy or a keyhole surgery is a procedure that aids the surgeon in viewing the internal parts of the abdomen to detect reasons for pain and other complications. Laparoscopy is of little help in diagnosing intestinal angioedema.

• Barium Swallow Test: A barium swallow test is a special test that uses X-rays and barium to create images of the small intestine. This test helps detect small intestine angioedema.

• MRI: MRI or magnetic resonance imaging provides precise details of the soft tissues using radio waves and magnetic fields. MRI scan helps detect intestinal angioedema.

• Blood Tests: Blood tests that help determine C1-INH levels help to diagnose acquired and hereditary angioedema that may contribute to intestinal angioedema.

How Is Intestinal Angioedema Treated?

Management of intestinal angioedema depends on the cause. If the reason is a drug, it is advised to discontinue it. Post discontinuation, there is relief from symptoms within 24 hours. However, when intestinal angioedema is associated with acquired or hereditary angioedema, then the treatment may include the following:

• Serine Proteinase Inhibitors (Serpins): Serpins are a class of proteins involved in regulating serines and other proteases. In simpler terms, serines regulate the function of proteases that are involved in the body's response to an injury.

• Kallikrein Inhibitors: Kallikrein inhibitors are a class of drugs that help treat or prevent episodes of hereditary angioedema in patients above twelve years of age.

• Anabolic Steroids: Anabolic steroids are androgen steroids. One of their many uses is the treatment of hereditary angioedema.

Intestinal angioedemas must be diagnosed and treated by a healthcare provider. They must not be mistaken for some ‘allergy’ and are self-treated with drugs like antihistamines.

Conclusion

Intestinal angioedema is a relatively rare condition. It occurs due to swelling of the intestines due to fluid leakage from the blood vessels. The use of certain drugs is the common cause. As the symptoms coincide with other gastrointestinal conditions, they must not be ignored, and prompt medical attention must be sought to prevent complications.