Skin diseases - Causes of angioedema

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Angioedema is the sudden swelling under the skin. The dermis, subcutaneous tissue, mucosa and submucosal tissues are involved in these inflammatory reactions.

Angioedema is often caused by the immune responses to the pathogens, allergins or other triggering factors. These deeper skin reactions are either hereditary or acquired. The acquired angioedema may be due to the reactions to allergens, drugs or unknown (idiopathic) causes. The skin edema may or may not be accompanied by hives. If there are severe swellings of the tongue or throat, they need to be taken seriously as they can cause difficulty in breathing.

Known triggering factors of acquired angioedema

Allergens such as certain types of food, medicines, insect stings, insect bites and harsh chemicals may trigger the angioedema associated swelling. Certain drugs may also induce the reactions. Many swelling reactions do not have known cause and are idiopathic in nature.

Allergic angioedema

• Food items such as peanuts, fish, shellfish, canned vegetables, alcohol, caffeine, legumes, berries, chocolate, milk and eggs may cause the condition.
• Medicines and antibiotics such as penicillin, sulfa drugs, anti-inflammatory drugs, vaccines and aspirin can be the triggering factors.
• Stings of spiders, centipedes, wasps and bees may cause the condition.
• Chemicals such as detergents, dyes and latex may trigger the condition.
• Cosmetics, moisturizers and skin whiteners containing harsh chemicals can also cause angioedema.
• Animal dander and pollen are known to trigger the condition.   

Non-allergic, drug-induced angioedema

In the treatment of high blood pressure, ACE (angiotensin converting enzyme) inhibitors and Beta-blockers are usually prescribed. In some patients these drugs may cause swelling of the face, throat and tongue. In patients who are already prone to hives, the drug reaction may be severe. The swellings are usually not itchy or painful, and the skin colour may be normal. Bupropion, selective serotonin reuptake inhibitors (antidepressant), COX-II inhibitors (painkillers), proton pump inhibitors (to treat stomach ulcers) and statins are also known to induce the swellings.

Idiopathic angioedema

If the exact cause is not known the swellings are considered idiopathic. Stress, infections, alcohol, spices, hot bath, tight clothes have been found to trigger this condition.

Hereditary angioedema

This is a rare condition in which C 1 esterase inhibitor enzyme (aka: C1-inhibitor or C1INH) levels are low. The low levels of C1INH result in bradykinin release leading to increased vascular permeability. The end result is the leakage of fluid and its rapid accumulation in the interstitium. The hereditary form is similar to ACE-induced form in that the swellings are not itchy or painful, and the skin colour is normal.

The hereditary type does not respond to antihistamines or steroids. The episodes may be recurrent and affect the stomach. The patients experience abdominal pain, intense vomiting, diarrhea and general weakness.

There are three types of hereditary angioedema. In type I, there is decrease in the levels of C1INH. In type II, though C1INH levels are normal, there is decreased function of C1INH. In type I and II are caused by mutation of C1NH (SERPING1) gene on chromosome 11, which encodes C1 inhibitor protein. In type III there is mutation in F12 gene on chromosome 12, which encodes coagulation factor XII. In type III the reactions are severe in women.

There are some conditions which can result in swellings of lips, eyes and face. These non-angioedema swellings may be caused by contact dermatitis, connective tissue disease, dermatomyositis, endocrine disease, myxedema, parasitic disease or SVC syndrome. These swellings are slow in progression. Angioedema is usually characterized by sudden swellings. A complete differential diagnosis may be required to exclude these above conditions.

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References:
1.Dreskin SC. Urticaria and angioedema. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier;2011:chap 260.
2.Wasserman SI. Approach to the person with allergic or immunologic disease. In: Goldman L, Schafer AI, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier;2011:chap 257.
3.Zuraw BL. Novel therapies for hereditary angioedema. Immunol Allergy Clin North Am. 2006 Nov;26(4):691-708.
4.Chinen J, Shearer WT. Advances in basic and clinical immunology. J Allergy Clin Immunol. 2007 Aug;120(2):263-70.

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Angioedema - Causes.