Hereditary angioedema and aortitis

Summary A 28-year-old male with hereditary angioedema died of an extensive stroke. Autopsy revealed cicatricial aortitis with narrowing of the coronary ostia, myocardial infarctions, and a left ventricular mural thrombus. There was neither acute inflammation of the aorta nor systemic vasculitis. A possible association of the aortitis with the hereditary angioedema is discussed.Abbreviations ANA Antinuclear antibodies - C1-INA C1-inactivator - CH 50 Total hemolytic complement - HBS-AG Hepatitis surface antigen - TPHA Treponema pallidum hemagglutination - VDRL Agglutination reaction for syphilis     

Chronic urticaria and angioedema

Of 231 patients evaluated for chronic urticaria and angioedema (CUA), 192 were diagnosed as having an idiopathic condition. The roles of serum IgE, complement (CH₅₀), and immune complexes (IC) were investigated in 112 patients with idiopathic CUA. Immediate skin tests were not helpful, but total IgE was elevated in 13%, equally divided between dermographic (D) and non-dermographic (ND) patients. Depressed haemolytic complement (CH₅₀) was noted in 10% of CUA, all of whom were D. Serum IC were elevated in 38%, equally divided between D and ND patients. There was no relationship between depressed CH₅₀ and elevated IC. Skin biopsies, evaluated by both light and immunofluorescent techniques, were negative for all specimens tested. The pathophysiology of idiopathic CUA is multifactorial, with a variety of immunological mechanisms involving serum IgE, CH₅₀, and IC. The relationship between depressed CH₅₀ and dermographism was noted but unexplained by serum or tissue studies.     

Idiopathic recurrent angioedema

The treatment of idiopathic, chronic, recurrent angioedema with or without urticaria is difficult, both for patients and their physicians, because treatment often is only partially effective and is labor-intensive, expensive, and lengthy. New medications for urticaria and angioedema that currently are being tested clinically may prove effective.     

Allergic urticaria and hereditary angioedema

A patient presented with both allergic urticaria and hereditary angioedema. The two conditions occurred independently, the urticaria being associated with allergy to food (which could be managed by control of the diet), whereas the angioedema was associated with C₁ esterase inhibitor deficiency.     

Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide

Summary In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.Dedicated to Professor Dr. Werner Kaufmann on the occasion of his 65th birthdayThe paper contains major parts of the thesis of A. Gentges and A. Masselink. Smaller parts of the results were presented at the international symposium on Vasodepressor Hormones in Hypertension, Nürnberg, 1986     

C1-inhibitor deficiency and angioedema

C1-inhibitor deficiency can be inherited or acquired; both conditions lead to recurrent angioedema that can be life threatening when the larynx is involved (hereditary angioedema, HAE; acquired angioedema, AAE). The genetic defect is due to the heterozygous deficiency of C1-Inh that is transmitted as an autosomal dominant trait. Mutations causing HAE have been found distributed over all exons and splice sites of C1-Inh structural gene: only a few of them have been found more than once. Depending on DNA defect, C1-Inh is not transcribed, or not translated or not secreted. Finally, in 15% of HAE patients, an antigenically normal, but non-functional C1-Inh is present in serum (HAE type II). C1-Inh deficiency can be acquired, due to an accelerated consumption. Such an accelerated consumption can depend on circulating autoantibodies that bind C1-Inh causing its inactivation and catabolism; or to associated diseases, usually lymphoproliferative diseases, that consume C1-Inh with different mechanisms. Effective therapies can prevent or revert angioedema symptoms in C1-Inh deficiency, the main problem of this condition remaining misdiagnosis. The common knowledge that angioedema is an allergic symptom frequently prevents a correct diagnostic approach: C1-Inh deficiency goes unrecognized and the disease can still be lethal. Correct prophylactic treatment is based on attenuated androgens in HAE and on antifibrinolytic agents in AAE. Life threatening laryngeal attacks and severe abdominal attacks are effectively reverted, in both conditions, with C1-Inh plasma concentrate. A special remark to this treatment should be made for autoantibody-mediated AAE where very high doses can be needed depending on the rate of C1-Inh consumption.     

Masqueraders of angioedema and urticaria.

OBJECTIVES: Reading this article will remind the reader that some patients presenting with complaints of urticaria and angioedema may not have urticaria or angioedema at all, but may have other causes, often unusual, sometimes treatable. It will also increase the reader's ability to recognize masqueraders of angioedema, urticaria, and facial swelling thought to be angioedema. DATA SOURCES: Data for this article come mainly from the authors' personal experiences and selected references to illustrate points made in the article. STUDY SELECTION: The criteria used are patients and articles from the authors' experiences that illustrate the point of this article that patients presenting with urticaria and angioedema may have other diseases and some of these are treatable. RESULTS: The objectives will be met by patient presentations plus pertinent literature review. CONCLUSIONS: Some patients presenting as angioedema and urticaria have swelling and skin lesions attributable to other causes. Although they are uncommon, they are sometimes treatable. Not all patients referred to an allergist for angioedema have angioedema.