Hereditary Angioedema: Dermatological Features

G.Y. Wu et al. (eds.), Atlas of Dermatological Manifestations of Gastrointestinal Disease, DOI 10.1007/978-1-4614-6191-3_54, © Springer Science+Business Media New York 2013 Clinical signs and features include: Affects 1:10,000–1:50,000 persons; begins in childhood • and worsens after puberty, although severity lessens after the sixth decade of life [ 1 ] Characterized by recurrent swelling attacks of the face, • abdomen, extremities, genitalia, oropharynx, and/or larynx without urticaria and typically unilateral, nonpruritic, nonpitting, uncomfortable but painless (see Fig. 54.1 ) Fifty percent of patients have an episode of laryngeal edema • at some point with a mortality rate as high as 30% [ 1 ] When affecting the gastrointestinal (GI) tract, attacks • present with severe abdominal pain, nausea, vomiting, and diarrhea Without treatment, patients experience swelling episodes • every 7–14 days [ 1 ] . Swelling episodes generally worsen for 12–36 h, peak, and then improve in 2–3 days [ 1 ] Aura/prodromal symptoms such as tingling, headache, mood • changes, and anxiety are common and may be followed by erythema marginatum. This nonpruritic rash is characterized by serpiginous, slightly raised borders and affects the trunk and inner surfaces of the extremities. Attacks of angioedema may have triggers (trauma, especially dental procedures, surgery, menstruation, oral contraceptives, hormone replacement therapy, angiotensin-converting enzyme [ACE] inhibitors, infection, stress) but they often occur without an inciting event. Associated with autoimmune diseases, particularly glom• erulonephritis, systemic lupus erythematosus, Sjogren syndrome, thyroiditis [ 2 ] Pathogenesis of this disease involves: Autosomal dominant: 75% with a family history, 25% • spontaneous mutations; mutation on chromosome 11; signi fi cant variability in penetrance [ 3 ] Functional de fi ciency of C1 esterase inhibitor (C1-Inh) • results in increased bradykinin formation Histopathological features include: Edema of deep dermis and underlying subcutaneous fat, • fascia, muscles Separation of collagen bundles due to the edema ( see • Fig. 54.2 ) Vascular dilation with wide endothelial cell gaps and • extravasation of vascular contents Scant mononuclear cells perivascularly but a paucity of • immune cells compared with an allergic reaction Erythema marginatum: perivascular and interstitial neu• trophils with lymphocytes but without vasculitis; dense deposits of bradykinin in stromal and endothelial tissue seen via immuno fl uorescence [ 4 ] The diagnosis is made using a combination of: Clinical signs: attacks aggravated by estrogen and unre• sponsive to corticosteroids, antihistamines, and epinephrine Measurement of complement levels [ • 5 ] : Type 1 (85% of cases): C1-Inh de fi ciency; decreased – C1-Inh antigen; C4 decreased between and during attacks Type 2 (15% of case): C1-Inh functional abnormality; – C1-Inh antigen normal to increased; C4 decreased between and during attacks Type 3 occurs primarily in women and is often estro – gen dependent; C1-Inh levels and function are normal; C4 and other complement levels are normal; factor XII mutation may be present Hereditary Angioedema: Dermatological Features