angioedema

angioedema
Name	Angioedema
Synonyms	Angioneurotic oedema, Quincke's edema
Caption	Swelling of the lower lip in a case of angioedema
Field	Allergy and immunology, Dermatology
Symptoms	Rapid swelling of the skin, mucous membranes, and submucosal tissues
Complications	Airway obstruction, Anaphylaxis
Onset	Minutes to hours
Duration	Hours to days
Types	Allergic, drug-induced, hereditary, acquired
Causes	Mast cell degranulation, Bradykinin-mediated pathways, ACE inhibitors
Risks	Hereditary angioedema, Chronic spontaneous urticaria, Lupus
Diagnosis	Based on clinical presentation, C1 esterase inhibitor testing, Skin prick test
Differential	Cellulitis, Contact dermatitis, Anaphylaxis
Prevention	Avoidance of known triggers
Treatment	Antihistamines, Corticosteroids, Epinephrine, Icatibant, C1-INH concentrate
Prognosis	Generally good with treatment
Frequency	~15% lifetime prevalence for acute episodes

angioedema is a condition characterized by the rapid swelling of the deeper layers of the skin and submucosal tissue, often affecting areas like the face, lips, tongue, and larynx. It is frequently associated with urticaria (hives) but can occur independently, posing a significant risk when it involves the upper airway. The underlying mechanisms are broadly divided into mast cell-mediated (often allergic) and bradykinin-mediated pathways, with causes ranging from common allergens to genetic deficiencies like hereditary angioedema.

Signs and symptoms

The hallmark sign is the sudden onset of asymmetric, non-pitting swelling in areas with loose connective tissue, such as the eyelids, lips, and genitalia. Involvement of the gastrointestinal tract can mimic an acute surgical abdomen, causing severe abdominal pain, nausea, and vomiting. Life-threatening complications arise from laryngeal edema, which can lead to stridor, hoarseness, and acute airway obstruction, a medical emergency often requiring intervention in an emergency department. Unlike urticaria, angioedema typically does not itch but may cause a burning or tingling sensation, and swelling can persist for up to 72 hours.

Causes and pathophysiology

Pathophysiologically, angioedema is classified as either mast cell-mediated or bradykinin-mediated. Mast cell-mediated angioedema, often linked to IgE and allergic reactions, involves the release of histamine and other mediators from cells like basophils in response to triggers such as foods (e.g., shellfish, nuts), medications (e.g., penicillin, NSAIDs), or insect stings. Bradykinin-mediated angioedema is central to forms like hereditary angioedema (caused by mutations in the SERPING1 gene affecting C1 esterase inhibitor) and acquired angioedema, as well as a well-known side effect of ACE inhibitor drugs like lisinopril. This pathway involves the uncontrolled generation of bradykinin, a potent vasodilator, leading to increased vascular permeability.

Diagnosis

Diagnosis is primarily clinical, based on history and physical examination. A detailed patient history focusing on medication use, such as ACE inhibitors or ARBs, and family history is crucial. For suspected hereditary angioedema, laboratory confirmation involves measuring serum levels of C4 complement and functional C1 esterase inhibitor activity. Allergy testing, including skin prick tests or specific IgE blood tests, may identify triggers for mast cell-mediated cases. Differential diagnosis must rule out conditions like cellulitis, contact dermatitis, and superior vena cava syndrome, while abdominal imaging may be needed to assess gastrointestinal involvement.

Treatment

Acute management depends on the suspected etiology and severity. For mast cell-mediated or idiopathic angioedema, first-line treatments include second-generation antihistamines like cetirizine, corticosteroids such as prednisone, and for severe reactions with airway threat, intramuscular epinephrine. Bradykinin-mediated angioedema does not respond to these agents; acute attacks of hereditary angioedema are treated with C1 esterase inhibitor concentrate (e.g., Berinert), the bradykinin B2 receptor antagonist icatibant (Firazyr), or the kallikrein inhibitor ecallantide (Kalbitor). Long-term prophylaxis for frequent hereditary angioedema attacks may involve tranexamic acid, danazol, or newer agents like lanadelumab.

Epidemiology

Acute angioedema is relatively common, with a lifetime prevalence estimated around 15% in the general population, often co-occurring with chronic spontaneous urticaria. Drug-induced angioedema, particularly from ACE inhibitors, accounts for a significant proportion of cases, affecting an estimated 0.1-0.7% of users, with higher incidence noted in African American populations. Hereditary angioedema is a rare autosomal dominant disorder with a prevalence of approximately 1 in 50,000 individuals worldwide, though it is often underdiagnosed. Acquired forms are associated with lymphoproliferative disorders like chronic lymphocytic leukemia or autoimmune diseases such as systemic lupus erythematosus.

History

The condition was first described in detail by the German physician Heinrich Quincke in 1882, who characterized the non-inflammatory swelling, leading to the eponym Quincke's edema. The hereditary form was later delineated by William Osler in 1888, who reported cases in a Canadian family. The pivotal link to a deficiency in C1 esterase inhibitor was established in the 1960s through research by Virginia Donaldson and Fred Rosen. The development of specific therapies, such as plasma-derived C1-INH concentrate, marked a major advance in the late 20th century, followed by the approval of targeted agents like icatibant by the European Medicines Agency and the U.S. Food and Drug Administration in the 2000s.

Category:Allergology Category:Dermatology Category:Medical emergencies