A 17-year-old boy is brought to the emergency department due to facial swelling. This morning, he developed mild swelling of the lips, which then progressed to severe diffuse facial swelling by the afternoon. The patient has had no fever, recent infections, abdominal pain, vomiting, or other swelling. He is a junior in high school and has been very stressed this week due to midterm examinations. His mother says that he had a similar episode when he had a tooth extracted a year ago. The patient has no chronic medical conditions and takes no medications. His father and paternal grandmother both have hypertension. Temperature is 36.9 C (98.4 F), blood pressure is 120/80 mm Hg, pulse is 82/min, and respirations are 18/min. Examination shows severe edema of the entire face; the patient is unable to open his eyes. The lungs are clear to auscultation, and neither stridor nor muffled voice is present. No rashes are detected. Mild edema of the hands is also seen. Which of the following best explains the pathophysiology of this patient's condition?
Hereditary angioedema | |
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This patient likely has hereditary angioedema, a condition characterized by recurrent edema without associated pruritus or urticaria. Deficiency or dysfunction of C1 inhibitor (previously referred to as C1 esterase inhibitor) leads to elevated bradykinin, which causes edema due to vasodilation and increased vascular permeability. Although autosomal dominant inheritance is most common, up to 25% of patients have de novo mutations with no family history of the disorder.
Hereditary angioedema typically presents in late childhood or adolescence with an acute onset of cutaneous swelling, often after emotional stress or trauma (eg, dental procedure). The face, limbs, and genitalia are most commonly affected, and pruritis and urticaria are absent. Bowel wall edema can also occur and presents as colicky abdominal pain, vomiting, and diarrhea. Less commonly, progressive laryngeal edema can lead to life-threatening airway obstruction.
Most episodes of angioedema self-resolve in 2-5 days. However, acute treatment (eg, C1 inhibitor concentrate) is typically recommended to prevent airway involvement.
(Choice A) Antibody-mediated type II hypersensitivity is seen with autoimmune hemolytic anemia, in which IgG or IgM antibodies react with cell-bound antigens, leading to complement activation and cell destruction. Swelling is not associated with type II reactions.
(Choice C) The most common examples of cell-mediated type IV hypersensitivity are the tuberculin skin test and allergic contact dermatitis. Direct contact of the allergen with the skin causes dermal inflammation and a localized rash after a latent period of 1-2 days.
(Choice D) ACE inhibitors can cause elevated bradykinin, resulting in angioedema. Although accidental or intentional ingestion of an ACE inhibitor could explain an isolated episode of swelling, this patient has had recurrent episodes a year apart, both following periods of stress (eg, dental procedure, examinations), making hereditary angioedema more likely.
(Choice E) IgE-mediated type I hypersensitivity, as seen with anaphylaxis, is caused by mast cell and basophil degranulation. Acute onset of swelling may occur, but pruritus and urticaria are also expected.
(Choice F) Immune complex–mediated type III hypersensitivity can be seen in serum sickness. Antibody complexes activate the complement cascade wherever the immune complexes deposit. Joint swelling, fever, and rash are typical findings; isolated facial swelling would not be expected.
Educational objective:
Hereditary angioedema is characterized by deficiency or dysfunction of C1 inhibitor causing recurrent episodes of edema (eg, face, limbs, genitalia, bowel, larynx) without associated pruritus or urticaria.