Angioedema without Urticaria

The differential diagnosis for angioedema without urticaria (“hives”) is fairly narrow, and requires a unique workup and management strategy.

Clinical presentation

• Patients present with sudden, profound, non-erythematous, non-pruritic localized edema of distensible tissues such as lips, eyelids, tongue and external genitalia. The key here is that they are negative for hives, itching, or bronchospasms.
• Two things that one aught to be particularly concerned about are laryngeal edema (stridor), which can lead to acute respiratory failure, and bowel wall edema, which can lead to gastrointestinal colic and small bowel obstruction.

Etiology

• Angiotensin-Converting Enzyme inhibitors (Acute ACE inhibitor-induced angioedema): think about this diagnosis in any patient on ACE inhibitors for any length of time who presents with otherwise-unexplained recurrent abdominal pain.
• Angiotensin II receptor blockers (ARBs)
• Hereditary angioedema: look for a younger patient with a family history of angioedema or of sudden death at an early age from unexplained “suffocation.”
• Acquired angioedema: older patient, not on an ACE inhibitor and with a negative family history.

Management

• Discontinue potential offenders.
• Monitor and protect the airway. Intubation may be very difficult because of upper airway edema so make sure to have an experienced airway specialist involved and available early.
• Treatment of hereditary angioedema is with intravenous purified human C1 inhibitor. That’s the correct choice both in real life and on multiple choice questions. Epinephrine, glucocorticoids and antihistamines are ineffective. Fresh frozen plasma can be used if human C1 inhibitor fails or is not available.
• The diagnosis of hereditary angioedema can be confirmed with a complement workup (↓ C4) and with C1 inhibitor assay. Patients should be advised to wear a medical alert bracelet. A referral to an allergist for long term management should be considered.
• For acquired angioedema, consider potential causes. These include lymphoproliferative and autoimmune diseases. Work up for these as appropriate, or refer.

References