Hereditary angioedema: classification, pathogenesis, and diagnosis.

Allergy Asthma Proc. 2011 Nov-Dec;32(6):403-7

Authors: Banerji A

Abstract
Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder associated with a deficiency in C1 inhibitor. More than 200 mutations in this gene, located on chromosome 11, have been identified. Although HAE is often inherited, 20-25% of cases are from new spontaneous mutations and they have no family history of swelling. Decreased C1 inhibitor activity leads to inappropriate activation of multiple pathways, including the complement and contact systems and the fibrinolysis and coagulation systems. Reduced C1 inhibitor activity results in increased activation of plasma kallikrein-kinin system proteases and increased bradykinin levels. Bradykinin is felt to be the main mediator of symptoms in HAE. Patients with HAE have recurrent episodes of swelling of the extremities, abdomen, face, and upper airway. Angioedema involving the gastrointestinal tract can lead to intestinal wall edema, which results in abdominal pain, nausea, vomiting, and diarrhea. Laryngeal swelling is life-threatening and may lead to asphyxia. Common triggers of an attack include trauma, stress, infection, menstruation, oral contraceptives, hormone replacement therapy, and angiotensin-converting enzyme inhibitors. Laboratory testing including C4, C1 inhibitor level, and function is needed to confirm or rule out the diagnosis of HAE. The treatment of HAE has improved significantly in recent years with the availability of several safe and effective therapies. Several consensus guidelines have been created to further assist in the management of HAE patients. This review will provide an update on the classification, pathophysiology, clinical presentation, and diagnosis of HAE.

PMID: 22221432 [PubMed - indexed for MEDLINE]

Update on laboratory tests for the diagnosis and differentiation of hereditary angioedema and acquired angioedema.

Allergy Asthma Proc. 2011 Sep-Oct;32 Suppl 1:S17-21

Authors: Frazer-Abel A, Giclas PC

Abstract
The importance of laboratory testing in the diagnosis of hereditary angioedema (HAE) has increased with the advent of new treatment options in recent years. It has been 50 years since HAE was linked to a decrease of C1INH (the inhibitor of complement enzyme, C1 esterase), a link that provided for the first laboratory test available for this disorder. HAE is subdivided into types that can be differentiated only by laboratory testing. The Type I form is characterized by low levels and function of C1INH in the circulation. The Type II form is characterized by normal levels of C1INH, but low function. Sample collection and handling is critical for the functional assays. The serum samples for the functional analysis must be collected, separated, and frozen at less than -60°C within 2 hours of the blood draw. Additionally some suspected Type II patients may benefit from looking closely at what method is used for the functional testing. The acquired forms of angioedema (AAE) can benefit from the same clinical testing, because most are ultimately due to decreased C1INH. Measurement of C1q levels and testing for anti-C1INH autoantibodies can help differentiate AAE from HAE. Diagnostic testing for the third hereditary form, alternately called estrogen-dependent HAE, HAE with Normal C1INH or HAE Type III, still presents challenges, and definitive testing may have to wait until there is a more complete understanding of this mixed group of patients. The next steps will include genetic analysis of C1INH and other proteins involved in HAE.

PMID: 22195757 [PubMed - indexed for MEDLINE]

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Pharmacotherapy of asthma: what do the 2007 NAEPP guidelines say?

Allergy Asthma Proc. 2007 Nov-Dec;28(6):628-33

Authors: Schatz M

The purpose of this article is to review the recommendations for pharmacotherapy in the new National Asthma Education and Prevention Program (NAEPP) guidelines. There are four main changes regarding pharmacotherapy in the updated guidelines. First, the recommendations for three age groups (0-4 years, 5-11 years, and > or =12 years) are presented separately. Second, the steps of therapy have been expanded from 4 steps to 6 steps to simplify the action within each step. Third, medium dose inhaled corticosteroids (ICS) or low-dose ICS plus add-on therapy are recommended for patients 5 years of age and older who are not controlled on low dose ICS. Finally, consideration of omalizumab is recommended for allergic patients 12 years of age and older who are not controlled on medium dose ICS plus long-acting beta agonists. For all age groups, the first step of therapy is inhaled short-acting beta agonists as needed and the second step is low dose ICS. Oral corticosteroids are part of step 6 therapy for all age groups. In patients not already on long-term control medications, the step of initiation of therapy is based on the assessment of severity. In patients on long-term control medications, therapy is adjusted based on the level of asthma control. If the patient is not well controlled, therapy is usually advanced one step. If the patient is very poorly controlled, consider stepping up two steps, a course of oral corticosteroids, or both. It is hoped that the updated NAEPP guidelines will lead to improved quality of life for patients with asthma.

PMID: 18201425 [PubMed - indexed for MEDLINE]