Children in Egypt see delayed HAE diagnosis, small study finds
Wait is three years on average, even for those with family history of disease
Children in Egypt with hereditary angioedema (HAE) wait an average of three years to be diagnosed, according to a small study. Delayed diagnosis was common despite more than half the children in the study having a family history of the disease.
About half of the 18 patients in the study were misdiagnosed with an allergic reaction. In most, swelling attacks affected the face and/or abdomen.
The study, “Clinical and laboratory spectrum of hereditary angioedema in a group of Egyptian children: a cross sectional study,” was published in the Egyptian Pediatric Association Gazette.
“The recognition and management of HAE can be improved by screening individuals with recurring bouts of intense unexplainable gastrointestinal pain, those with repeated [swelling attacks], as well as relatives of HAE patients,” the researchers wrote.
HAE is a rare disorder characterized by sudden and recurrent swelling attacks in the deeper layers of the skin and/or the mucus membranes in the upper airways and gastrointestinal tract.
Delayed diagnosis could be linked to HAE rarity, overlapping features
The most common forms of HAE, types 1 and 2, are caused by mutations in the SERPING1 gene that disrupt either the production or the activity of a protein called C1 esterase inhibitor (C1-INH). This protein blocks the activity of other proteins that promote the production of the signaling molecule bradykinin, excess levels of which can trigger swelling attacks by causing fluid to leak from blood vessels and pool into nearby tissues.
HAE due to absent or faulty C1-INH is also marked by low levels of C4, a protein of the complement cascade, which is part of the immune system.
A less common form of HAE, type 3, is caused by mutations in genes other than SERPING1 and marked by normal levels or activity of C1-INH.
Due to its rarity, the prevalence of HAE, as well as its clinical presentation in children in Egypt, remains unknown. The researchers analyzed data from children with HAE who were followed at the Zagazig University Children’s Hospital between January 2022 and January 2023.
A total of 18 children (14 girls and four boys), with a median age of 12 (range 6-18), were identified and included in the study. The majority of patients (83.3%) had HAE type 1, while the remaining 16.7% had HAE type 2.
Symptom onset occurred between the ages of 2 and 10, and diagnosis was confirmed at ages ranging from 4 to 13 — meaning the children waited an average of 3.2 years for a correct diagnosis.
This delayed diagnosis occurred despite the fact that 11 children (61.1%) had a family history of hereditary angioedema.
Allergic reactions were the most common misdiagnosis (50%), followed by familial Mediterranean fever (27.8%), an inherited autoimmune condition that causes frequent fevers and painful inflammation.
“The considerable risk of incorrect diagnosis can be due to the scarcity of HAE, the variety of individual features, and the clinical presentations that coincide with those of common diseases,” the researchers wrote.
Comprehensive history, tests recommended
Attack frequency ranged from four to 48 attacks a year, with a median annual frequency of 17 attacks. Attacks lasted from two to seven days, with a mean duration of 2.9 days.
Swelling attacks lasted between two and seven days, and most frequently affected the face (77.8%) and abdomen (77.8%). Fewer than half of the children (44.4%) experienced attacks affecting the larynx, or voice box, and 22.2% had attacks in the eyes, lips, feet, and hands.
For most patients (83.3%), trauma was the main trigger of HAE attacks, but spontaneous angioedema was also reported in 77.8% of the children.
More than half of the children (61.1%) experienced severe attacks, 22.2% had moderate attacks, and 16.7% saw mild attacks. The most common treatment during an HAE attack was antihistamines (given to 94.4% of patients), followed by steroids (83.3%).
Danazol was used as a long-term preventive treatment in 38.9% of the cases.
Statistical analysis showed no significant associations between attack severity and several variables. These included patient’s age, diagnostic delay, number and duration of attacks, and blood levels of C4, C1-INH, or total immunoglobulin E, a type of antibody involved in allergic responses. However, the severity of the attacks was directly linked with C1-INH activity levels.
In Egypt, “failures in recognition persist as physicians did not consider HAE as a possible cause of gastrointestinal pain or limb and facial [swelling],” the researchers wrote. “As a result, individuals frequently remain untreated or receive inaccurate diagnoses for many years until receiving an HAE evaluation,” they wrote.
A physician could distinguish HAE from “diseases with overlapping presentations” with “a comprehensive medical history, thorough physical examination, and laboratory tests including C1-esterase inhibitor level and activity in a child with recurrent attacks of [swelling] involving various body parts,” the researchers wrote.
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