DIAGNOSING HAE

Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent attacks of subcutaneous or submucosal edema that can affect the face, respiratory tract, extremities, gastrointestinal tract, genitalia or other parts of the body.¹

Although a general lack of awareness and misunderstanding of symptoms can contribute to delays in diagnosis, once HAE is suspected, diagnostic methods have been established.^2,3

Camila

Jorge

Camila

Jorge

Differential diagnosis checklist

HAE should be suspected when a patient history includes³:

Recurrent angioedema without urticaria and/or pruritus
HAE-positive family history (present in 75% of patient population)
Onset of symptoms in childhood/adolescence
Recurrent abdominal pain attacks
Occurrence of laryngeal edema
Failure to respond to treatment with antihistamines, glucocorticoids, and/or epinephrine
Prodromal signs or symptoms before swellings

How hereditary angioedema is diagnosed

Certain genetic mutations can result in reduced or abnormal levels of C1-inhibitor (C1-INH), a protein responsible for controlling inflammation. As a result, bradykinin increases, and the patient may start to experience the symptoms associated with HAE.^4,5

HAE due to C1 deficiency is classified into two types^3-5:

HAE Type I – Reduced levels of C1-INH with normal C1-INH function

HAE Type II – Normal levels of C1-INH with abnormal C1-INH function

A diagnosis of either HAE Type I or II should be confirmed with laboratory testing. Consider the following blood evaluations^4,6*:

Serum C4

Low results (<50% normal) suggest HAE^†

C1-INH Function

Low (<50% normal)

C1-INH antigen

Low results (<50% normal) suggest HAE Type I
Normal or high results suggest HAE Type II

C1q

C1q levels are normal in HAE

For reference, the ICD-10 code associated with a diagnosis of HAE is D.84.1.

*Laboratory tests should be repeated 1–3 months later to confirm results; blood samples should be handled with care to avoid decay of functional C1-INH, which may produce equivocal results.

^†~90% of HAE patients have perpetually low C4.

Delays in diagnosis

Historically, delays in diagnosis ranged from 10 to 22 years.⁴ Today, delays are still common. In a 2015 survey of 106 people with HAE Type I or II, 25% were diagnosed within one year of experiencing symptoms. However, the same survey showed there was a delay of 10 years or more in 47% of patients.⁷ In 2017, a survey of 445 people with HAE showed the average delay in diagnoses was 8.4 years.⁸

Consequences of misdiagnosis

Misdiagnosis can contribute to delays in diagnosis and put patients at risk of ineffective management or unnecessary procedures.^1,2
Symptoms of HAE mimic those of other, more common conditions. For example, an episode of subcutaneous edema may be mistaken for an allergic reaction. Abdominal attacks have been misdiagnosed with appendicitis or irritable bowel syndrome.¹
Undiagnosed HAE patients are at a higher risk of mortality by asphyxiation following a laryngeal attack.^2,9 Laryngeal attacks are rare. However, at least 50% of patients with HAE experience at least 1 laryngeal attack in their lifetime. Historically, mortality of 14% to 33% due to untreated and unrecognized laryngeal attacks has been reported.⁹
By recognizing and accurately diagnosing patients with HAE, you can help mitigate these risks.

DIAGNOSING HAE

Differential diagnosis checklist

How hereditary angioedema is diagnosed

HAE due to C1 deficiency is classified into two types3-5:

A diagnosis of either HAE Type I or II should be confirmed with laboratory testing. Consider the following blood evaluations4,6*:

Delays in diagnosis

Consequences of misdiagnosis

Once HAE is diagnosed, treatment can be individualized to meet each patient's needs.3

HAE due to C1 deficiency is classified into two types^3-5:

A diagnosis of either HAE Type I or II should be confirmed with laboratory testing. Consider the following blood evaluations^4,6*:

Once HAE is diagnosed, treatment can be individualized to meet each patient's needs.³