# Hereditary Angioedema With Normal C1 Esterase Inhibitor: A Case of a Late Diagnosis in a 48-Year-Old Male

## TL;DR

A 48-year-old man with a rare form of hereditary angioedema was diagnosed late after ineffective treatments and recurring symptoms.

## Contribution

The case highlights diagnostic challenges and treatment needs for HAE-nC1-INH, a subtype lacking standard biomarkers.

## Key findings

- The patient's symptoms were unresponsive to antihistamines or corticosteroids.
- Icatibant and berotralstat were prescribed for acute and prophylactic treatment.
- Delayed diagnosis of HAE-nC1-INH can lead to severe outcomes.

## Abstract

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent, non-pitting edema affecting the mucosal, submucosal, or subcutaneous tissues. A rarer subtype, HAE with normal C1 esterase inhibitor (HAE-nC1-INH), lacks universally accepted biomarkers.

We present a 48-year-old male with a history of Epstein-Barr virus (EBV) and hyperlipidemia, who experienced recurrent episodes of angioedema involving the lips, face, throat, hands, feet, and genitalia. Prior treatments, including corticosteroid injections and oral prednisone, were ineffective. The patient denied any relevant family history and reported symptom exacerbations, potentially triggered by stress. Laboratory evaluation included antinuclear antibody (ANA), C1-INH functional and protein levels, C1Q, total complement, rheumatoid factors, Smith (SM) antibodies, and anti-double-stranded DNA (anti-dsDNA) antibodies. The patient was prescribed icatibant for acute flares and berotralstat for prophylaxis.

This case highlights the diagnostic challenges of HAE-nC1-INH, a subtype not responsive to standard treatment with antihistamines or corticosteroids. Although this patient did not experience life-threatening airway compromise, delayed diagnosis of this condition can lead to severe outcomes. Increased awareness of HAE-nC1-INH among clinicians is essential to improve timely diagnosis and appropriate treatment. This case underscores the importance of differentiating HAE-nC1-INH from other forms of angioedema to prevent misdiagnosis.