Subject(s)
Hereditary Angioedema Type III/diagnosis , Laryngeal Edema/diagnostic imaging , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antifibrinolytic Agents/therapeutic use , Bradykinin/analogs & derivatives , Bradykinin/therapeutic use , Child , Female , Hereditary Angioedema Type III/complications , Hereditary Angioedema Type III/drug therapy , Hereditary Angioedema Type III/prevention & control , Humans , Laryngeal Edema/etiology , Peptides/therapeutic use , Tomography, X-Ray Computed , Tranexamic Acid/therapeutic useABSTRACT
Hereditary angioedema (HAE) is a relatively rare clinical entity that can potentially cause life-threatening airway or intestinal oedema, patients with the latter usually presents with symptoms of gastroenteritis like vomiting, diarrhoea and abdominal pain. Here, we present a unique case of a less recognised type of HAE that is type III in a patient who presented with signs and symptoms consistent with infectious colitis. She previously had similar episodes and was managed multiple times with antibiotics, with no satisfactory response. There, she underwent extensive diagnostic evaluation. On the basis of findings of further investigations on the current visit, she was eventually diagnosed with intestinal angioedema. To the best of our knowledge, the present paper represents the third reported case of type III HAE-induced intestinal angioedema. Additionally, we undertake a literature review of HAE.
Subject(s)
Colitis/diagnosis , Hereditary Angioedema Type III/diagnosis , Intestinal Diseases/diagnosis , Intraabdominal Infections/diagnosis , Diagnosis, Differential , Female , Hereditary Angioedema Type III/complications , Humans , Intestinal Diseases/etiology , Middle AgedABSTRACT
Hereditary angio-oedema (HAE) is a rare, potentially fatal disease characterized by recurrent swelling of skin and mucosa. Besides HAE with quantitative (type I) or qualitative (type II) deficiency of complement C1-inhibitor (C1-INH), a new subtype of HAE is now described with normal levels of C1-INH. This subtype is possibly underdiagnosed, and a treatment regimen and general knowledge about the condition is still in its infancy. The purpose of this article is to inform Danish doctors about the disease to identify more Danish patients.
Subject(s)
Hereditary Angioedema Type III , Complement C1 Inactivator Proteins/genetics , Complement C1 Inactivator Proteins/metabolism , Diagnosis, Differential , Hereditary Angioedema Type III/diagnosis , Hereditary Angioedema Type III/drug therapy , Hereditary Angioedema Type III/pathology , Hereditary Angioedema Type III/physiopathology , Humans , PedigreeSubject(s)
Capillary Leak Syndrome/diagnosis , Diagnostic Errors , Hereditary Angioedema Type III/diagnosis , Immunoglobulins, Intravenous/therapeutic use , Abdominal Pain/etiology , Acute Kidney Injury/etiology , Capillary Leak Syndrome/therapy , Complement C1 Inhibitor Protein/analysis , Delayed Diagnosis , Dyspnea/etiology , Humans , Hypotension/etiology , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Pericardial Effusion/etiology , RecurrenceABSTRACT
Hereditary angioedema with normal C1 esterase inhibitor and mutations in the F12 gene (HAE-FXII) is associated with skin swellings, abdominal pain attacks, and the risk of asphyxiation due to upper airway obstruction. It occurs nearly exclusively in women. We report our experience treating HAE-FXII with discontinuation of potential trigger factors and drug therapies. The study included 72 patients with HAE-FXII. Potential triggers included estrogen-containing oral contraceptives (eOC), hormonal replacement therapy, or angiotensin-converting enzyme inhibitors. Drug treatment comprised plasma-derived C1 inhibitor (pdC1-INH) for acute swelling attacks and progestins, tranexamic acid, and danazol for the prevention of attacks. Discontinuation of eOC was effective in 25 (89.3%) of 28 women and led to a reduction in the number of attacks (about 90%). After ending hormonal replacement therapy, three of eight women became symptom-free. Three women with exacerbation of HAE-FXII during intake of quinapril or enalapril had no further HAE-FXII attacks after discontinuation of those drugs. Eleven women were treated with pdC1-INH for 143 facial attacks. The duration of the treated facial attacks (mean: 26.6 h; SD: 10.1 h) was significantly shorter than that of the previous 88 untreated facial attacks in the same women (mean: 64.1 h; SD: 28.0 h; P < 0.01). The mean reduction in attack frequency was 99.8% under progestins after discontinuing eOC (16 women), 93.8% under tranexamic acid (four women), and 100% under danazol (three women). For patients with HAE-FXII, various treatment options are available which completely or at least partially reduce the number or duration of attacks.
Subject(s)
Complement C1 Inhibitor Protein/therapeutic use , Hereditary Angioedema Type III/drug therapy , Adolescent , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Biomarkers , Chemoprevention , Child , Disease Progression , Estrogens/adverse effects , Factor XII/genetics , Female , Hereditary Angioedema Type III/blood , Hereditary Angioedema Type III/diagnosis , Hereditary Angioedema Type III/genetics , Humans , Male , Middle Aged , Mutation , Risk Factors , Treatment Outcome , Young AdultSubject(s)
DNA Mutational Analysis , Factor XII/genetics , Genetic Testing/methods , Hereditary Angioedema Type III/genetics , Mutation , Adult , Female , Genetic Markers , Genetic Predisposition to Disease , Hereditary Angioedema Type III/blood , Hereditary Angioedema Type III/diagnosis , Hereditary Angioedema Type III/immunology , Hereditary Angioedema Type III/therapy , Humans , Phenotype , Predictive Value of Tests , Risk Factors , Tomography, X-Ray ComputedABSTRACT
In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented.
Subject(s)
Hereditary Angioedema Type III/genetics , Adult , Complement C1 Inhibitor Protein/metabolism , Estrogens/metabolism , Female , Hereditary Angioedema Type III/diagnosis , Hereditary Angioedema Type III/therapy , Humans , Lip , Mutation , Treatment OutcomeABSTRACT
In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented.
Neste artigo são relatados três casos de angioedema hereditário do tipo III (estrógeno-dependente ou com inibidor de C1 normal), que foi inicialmente descrito em mulheres da mesma família, em associação com condições de alto nível estrogênico, como uso de anticoncepcionais orais e gravidez. Não há alteração do inibidor de C1, como acontece nos outros tipos de angioedema hereditário, e são observadas mutações no gene codificador do fator XII da coagulação em várias pacientes. O diagnóstico atualmente é eminentemente clínico e o tratamento consiste na suspensão dos fatores desencadeantes e controle dos sintomas agudos. Também é apresentada breve revisão da fisiopatogenia, quadro clínico, alterações genéticas e tratamento.
Subject(s)
Adult , Female , Humans , Hereditary Angioedema Type III/genetics , Complement C1 Inhibitor Protein/metabolism , Estrogens/metabolism , Hereditary Angioedema Type III/diagnosis , Hereditary Angioedema Type III/therapy , Lip , Mutation , Treatment OutcomeABSTRACT
Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE type III, is a familial condition only clinically recognized within the past three decades. Similar to HAE from C1-INH deficiency (HAE types I and II), affected individuals experience unpredictable angioedema episodes of the skin, gastrointestinal tract, and airway. Unique clinical features of HAE with normal C1-INH include the predominance of affected women, frequent exacerbation by estrogen, and a prominence of angioedema that involves the face and oropharynx. The underlying pathophysiology of HAE with normal C1-INH is poorly understood, but indirect evidence points to contact pathway dysregulation with bradykinin-mediated angioedema. Currently, evaluation is complicated by a lack of confirmatory laboratory testing such that clinical criteria must often be used to make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been identified in only a minority of persons affected by HAE with normal C1-INH, limiting the utility of such analysis. To date, no controlled clinical studies have examined the efficacy of therapeutic agents for HAE with normal C1-INH, although published evidence supports frequent clinical benefit with medications shown effective in HAE due to C1-INH deficiency.
Subject(s)
Hereditary Angioedema Type III , Complement C1 Inactivator Proteins/genetics , Complement C1 Inhibitor Protein , Hereditary Angioedema Type III/diagnosis , Hereditary Angioedema Type III/epidemiology , Hereditary Angioedema Type III/etiology , Hereditary Angioedema Type III/metabolism , HumansSubject(s)
Abdominal Pain/diagnosis , Hereditary Angioedema Type III/diagnosis , Abdominal Pain/diagnostic imaging , Abdominal Pain/etiology , Adult , Contraceptives, Oral, Hormonal/adverse effects , Female , Fibrin Fibrinogen Degradation Products/analysis , Hereditary Angioedema Type III/complications , Hereditary Angioedema Type III/diagnostic imaging , Humans , Irritable Bowel Syndrome/diagnosis , Tomography, X-Ray ComputedABSTRACT
Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema.