New-variant hereditary angioedema in three brothers with normal C1 esterase inhibitor level and function.

Abstract

Hereditary angioedema (HAE) is secondary to deficiency of C1 esterase inhibitor (C1 INH) (1) or a nonfunctioning protein (2) while acquired angioedema (AAE) is caused by an underlying disease (Table 1) (3). Recently, two types of inherited variant angioedema have been described where the affected patients were women, have a presentation similar to HAE, but have normal qualitative and quantitative C1 INH levels. In 2000, Bork et al. (4) identified 10 females with normal C1 INH levels and function and 26 of their female relatives. Binkley and Davis (5) in 2001 identified a family with Italian heritage where angioedema was dependent on high estrogen levels. This case study was conducted at the Los Angeles Veterans Affairs allergy clinic from December 2001 to March 2002. Consultation with the each brother included history, physical examination and laboratory data. All three brothers had normal C1 INH level and function. The brothers were African American with ages ranging from 71 to 74 years. Past medical history is significant for hypertension, reflux, hypothyroidism, hypercholesterolemia, dilated cardiomyopathy, and nonmetastatic prostate cancer status, post-prostatectomy in two brothers. Angioedema is limited to the face, extremity, or genitalia with no respiratory or gastrointestinal involvement. Angioedema lasted 24 h in each patient and occurred several times every year for the last 15–20 years. Each brother utilized a unique regimen of antihistamines to abort or suppress the attacks. All three brothers denied any triggers, urticaria, or occupational associations. They were the offspring of identical unaffected parents and siblings to one unaffected brother and sister. Offspring from two brothers were also unaffected. A physical examination was performed on each brother, which was unremarkable. Laboratory data to evaluate the common underlying causes of angioedema were obtained, but were unremarkable except for an elevated prostate-specific antigen level in one brother, but his prostate biopsy was negative for malignancy. In all brothers C4, C1q, and C1 INH levels were normal. In two brothers C1 INH function was normal. Hereditary angioedema occurs in a variety of forms: HAE, AAE, variant HAE, and these cases were classified as new-variant HAE. The clinical presentation of new-variant HAE is similar to HAE. In our patients, angioedema was limited to cutaneous involvement and without any identifiable triggers. Treatment of angioedema varies between HAE and the other forms. HAE can be treated with attenuated steroids or C1 INH concentrate and is typically unresponsive to antihistamines. In our patients, their AL LERGY 2 0 0 4 : 5 9 : 5 5 7 – 5 5 9 • COPYR IGHT a 2004 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REVIEW, BUT WILL BE REV IEWED BY THE ASSOCIATE EDITORS •