Pediatric Angioedema Clinical Presentation

Hereditary angioedema is characterized by episodic attacks that generally last 1-4 days. Attacks typically involve the extremities, the abdomen, or the throat.

The extremities are the most common site of attacks. Swelling is usually brawny and is not associated with urticaria, pruritus, or pain.

Abdominal attacks are due to edema in the submucosa and serosa of the bowel wall and are often associated with nausea, vomiting, and severe pain, but not with diarrhea. Abdominal pain may resemble that of acute abdomen.

Episodes involving the throat are the most dangerous manifestation of angioedema. Edema of the upper airway may progress rapidly and result in asphyxiation.

Angioedema episodes may occur spontaneously or may be triggered by trauma, particularly the injection of an anesthetic (eg, in dental procedures, during tooth extraction), or even emotional stress. Approximately one half of patients with hereditary angioedema have attacks precipitated by trauma; interestingly, the other half do not.

In hereditary angioedema, initial manifestations occur in children at a median age of 4.8 years (range, 3-9.7 y). Angioedema attacks occur by age 13 in most hereditary angioedema cases and may increase in severity after puberty. Attacks occur more often with sex hormone fluctuation, with more severe symptoms associated with menses.

Only 25% of patients provide a positive family history. However, patients may have a family history of abdominal pain and unexplained diarrhea or of sudden death from asphyxia. In the past, the mortality rate for attacks involving the upper airways exceeded 25%. Patients live with the constant threat of life-threatening laryngeal obstruction.

The acquired form of angioedema (AAE1 or AAE2) may present like classic hereditary angioedema, except for the age of onset. Usually, this type of angioedema occurs in the fourth decade of life or later. Because it is an acquired defect, a family history is negative for angioedema.

The idiopathic form of angioedema may cause swelling anywhere in or on the body and may be accompanied by urticaria (hives).

Swelling due to nonhistaminergic angioedema (INAE) may occur anywhere, including the face, arms, legs, genitalia, throat, and abdomen, although abdominal symptoms are far less common than in those with hereditary angioedema. Furthermore, symptoms do not change with menstrual period or pregnancy.

Allergic angioedema may cause swelling, most often in the face and throat. Urticaria (hives) is often present. If the condition persists longer than 6 weeks, it is considered chronic idiopathic urticaria and is not a classic allergic reaction.

In patients with ACE-inhibitor–induced angioedema, swelling may occur just about anywhere, including the throat, face, lips, tongue, hands, feet, genitalia, and intestines. Urticaria (hives) is very rare in this form of angioedema.

If a patient has urticaria-related angioedema, lesions appear as large swellings with indistinct borders around the eyelids and lips. They may also appear on the face, trunk, genitalia, and extremities. The face, hands, and feet are involved in 85% of patients; other areas are involved in 15%. As many as 50% of children with urticaria exhibit angioedema with swelling of the hands and feet.

Patients with hereditary angioedema have associated repeated attacks of swelling of extremities, face, and throat accompanied by abdominal pain. Edematous swelling of the skin is not accompanied with itching but causes an unpleasant sensation of distension within the involved lesion.^[10]

A generalized, nonpruritic skin rash (erythema marginatum) may be observed in 8% of children prior to the onset of an angioedema attack.

Angioedema manifests as a diffuse brawny swelling of the extremities in 75% of patients, abdominal pain in 52%, and swelling of the face and throat in 30%. Patients do not have typical urticarial wheals but exhibit targetlike lesions. Abdominal pain eventually becomes a major symptom in 93% of patients. Severe airway edema accounts for the almost 30% mortality rate in untreated patients.

Angioedema associated with ACE inhibitors affects fewer than 5% of patients taking these drugs. Affected patients experience episodic swelling of the lip or face, or tissue swelling on any part of the body; it is not usually accompanied by pruritus or pain.

Evidence of impaired sense of smell in hereditary angioedema has been reported. Using 3-stages Sniffin'-Sticks kit, Perricone et al observed a significant decrease in olfactory function observed in patients with hereditary angioedema compared with controls, as measured by threshold, discrimination, and identification (TDI) scores. Anosmia was present only in hereditary angioedema patients (3.3%). In addition, reduction of olfactory function in these cases seems to correlate with complement C4 and CH50 levels. This suggests that immune and genetic mechanisms might play a role in this defect.^[11]