Pediatricians Should Be Aware of C1-INH-HAE, Hereditary Angioedema, Study Says

Although the symptoms of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) present in childhood, most patients are diagnosed in adulthood, highlighting a need for increased awareness of C1-INH-HAE among pediatricians, according to a new study.

The research, “Pediatricians diagnosed few patients with childhood-presented hereditary angioedema: Icatibant Outcome Survey findings,” was published in the Journal of Allergy and Clinical Immunology.

C1-INH-HAE is challenging to diagnose; its signs and symptoms are similar to other, more common diseases. Misdiagnosis and long delays to diagnosis are common, sometimes leading to the administration of ineffective or harmful therapies.

However, there is little data on the causes of diagnostic delays in this patient population.

Researchers used data from the Icatibant Outcome Survey (IOS) database to determine the specialties of physicians involved in diagnosing C1-INH-HAE, and whether the type of diagnosing physician affects the delay in diagnosis.

IOS (NCT01034969) is a currently ongoing international clinical trial designed to monitor the safety and effectiveness of Firazyr (icatibant) – a treatment developed by Shire for acute attacks of C1-INH-HAE.

Among 685 patients included in IOS with confirmed C1-INH-HAE, data on physician specialization was available for 271. Overall, patients waited a median of six years and three months before receiving a diagnosis.

The majority of patients received a diagnosis from a specialist (83.9%) — including allergists (35.2%), clinical immunologists (21.8%), and dermatologists (19.2%). Pediatricians and pediatrician-immunologists diagnosed only 5.5% of patients.

Of the non-specialist physicians, non-emergency hospital physicians were responsible for 16.1% of diagnoses, general practitioners for 3.8% , non-hospital physicians for 1.7%, and emergency physicians for 0.8%.

When looking at the impact of the diagnosing physician, patients diagnosed by a specialist were diagnosed at a median age of 21.6 years, with a median delay in diagnosis of 8.2 years. Findings were similar for emergency and non-emergency hospital physicians.

Shorter delays in diagnosis were reported for patients diagnosed by non-hospital-based physicians, pediatricians, and general practitioners.

“These findings indicate that, despite the onset of first symptoms of C1-INH-HAE in childhood or adolescence, most patients are diagnosed as adults,” investigators wrote.

Researchers found that pediatricians were responsible for the shortest delay in diagnosis (0.5 years), but made few diagnoses, suggesting that patients are generally referred to specialists.

HAE specialists made approximately 4% of C1-INH-HAE diagnoses with a median delay in diagnosis of 7.6 years. This is likely because the patients are being referred after diagnosis,   ensuring they receive specialist management and care.

As expected, researchers found that patients with a family history of C1-INH-HAE had a shorter delay in diagnosis than those without a family history.

“Our results demonstrate that although symptoms of C1-INH-HAE present in childhood or adolescence, pediatricians currently diagnose few patients,” researchers concluded.

“Increasing the awareness of C1-INH-HAE symptoms among pediatricians could shorten the delay in diagnosis experienced by patients through prompt referral to disease specialists or increases in the frequency of pediatrician-led diagnoses,” they added.