Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency
ABSTRACT Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is characterized by relapsing skin swellings, abdominal pain attacks, and, less frequently, potentially life-threatening laryngeal attacks.
This study determined the mortality of patients with and without the diagnosis of HAE-C1-INH and analyzed fatal laryngeal attacks.
A cohort of 728 patients from 182 families with HAE-C1-INH was evaluated for death cases by analyzing pedigrees. Detailed information on fatal laryngeal attacks in 36 patients was obtained by questioning relatives and treating physicians.
Of the 214 patients who had died, 70 asphyxiated during a laryngeal attack. Mortality by asphyxiation was higher in patients with undiagnosed HAE-C1-INH (63 cases) than in patients with diagnosed HAE-C1-INH (7 cases). The lifespan of asphyxiated patients with undiagnosed HAE-C1-INH was on average ∼31 years shorter than patients with undiagnosed HAE-C1-INH who died of other causes. Three phases were distinguished in the fatal laryngeal attacks. Phase 1, the predyspnea phase, lasted on average for 3.7 ± 3.2 hours (range, 0-11 hours). Phase 2, the dyspnea phase, lasted on average for 41 ± 49 minutes (range, 2 minutes to 4 hours). Phase 3, the loss of consciousness phase, lasted on average for 8.9 ± 5.1 minutes (range, 2-20 minutes).
The high mortality in patients with undiagnosed HAE-C1-INH underscores the need to identify these patients and diagnose their condition. The analysis of fatal laryngeal attacks gives further insight into their course, thus helping to avoid fatalities in the future.
SourceAvailable from: Suranjith L Seneviratne[Show abstract] [Hide abstract]
ABSTRACT: C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organisation. This article is protected by copyright. All rights reserved.Clinical & Experimental Immunology 01/2015; DOI:10.1111/cei.12584 · 3.28 Impact Factor
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ABSTRACT: Hereditary angioedema (HAE) is a rare disease that causes recurrent mucosal and cutaneous swelling. Skin swelling, abdominal pain, and airway swelling cause significant morbidity and potential mortality. Symptoms often appear early in life and accelerate around puberty. Despite this, there is a paucity of both data and treatment options for HAE in children in the United States. Our objective was to summarize the published data and perform a retrospective chart review on children with HAE to improve care of the child with the disease. A retrospective chart review study was performed after Institutional Review Board approval. A search of electronic medical records from 2001 to 2011 was performed for children aged 1 to 18 years with a confirmed diagnosis of HAE. Demographic patient information was obtained and analyzed. Twenty-five pediatric patients were identified with the diagnosis of HAE: 13 female and 12 male. The median age at diagnosis was seven years. The most common initial presenting symptom was swelling of the upper extremity, followed by abdominal pain, swelling of the face and/or lower extremity, and scrotal swelling. Three patients reported no previous symptoms and were diagnosed due to family history of HAE and positive laboratory testing. The majority of patients (84%) reported a family history of HAE. Accurate and timely diagnosis of HAE is imperative for children to prevent further morbidity and mortality associated with the disease.Allergy and Asthma Proceedings 02/2015; 36(1):70-3. DOI:10.2500/aap.2015.36.3806 · 3.35 Impact Factor
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ABSTRACT: Cutaneous involvement characterized by urticarial lesions with or without angioedema and itch is commonly observed in routine medical practice. The clinical approach may still remain complex in real life, because several diseases may display similar cutaneous manifestations. Urticaria is a common disease, characterized by the sudden appearance of wheals, with/without angioedema. The term Chronic Urticaria (CU) encompasses a group of conditions with different underlying causes and different mechanisms, but sharing the clinical picture of recurring wheals and/or angioedema for at least 6 weeks. Hereditary Angioedema (HAE) is a rare disorder characterized by recurrent episodes of non-pruritic, non-pitting, subcutaneous or submucosal edema affecting the extremities, face, throat, trunk, genitalia, or bowel, that are referred as “attacks”. HAE is an autosomal dominant disease caused by a deficiency of functional C1 inhibitor, due to a mutation in C1-INH gene (serping 1 gene) characterized by the clonal proliferation of mast cells, leading to their accumulation, and possibly mediator release, in one or more organs. In childhood there are two main forms of mastocytosis, the Systemic and the Cutaneous. The clinical features of skin lesions in urticaria, angioedema and mastocytosis may differ depending on the aetiologic factors, and the underlying pathophysiological mechanisms. The diagnostic process, as stepwise approach in routine clinical practice, is here reviewed for CU, HAE and mastocytosis, resulting in an integrated method for improved management of these cutaneous diseases. Taking into account that usually these conditions have also a relevant impact on the quality of life of children, affecting social activities and behavior, the availability of care pathways could be helpful in disentangle the diagnostic issue achieving the most cost-effective ratio.World Allergy Organization Journal 02/2015; 8(1). DOI:10.1186/s40413-014-0052-x