Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency

Department of Dermatology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 07/2012; 130(3):692-7. DOI: 10.1016/j.jaci.2012.05.055
Source: PubMed


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.

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    • "[1-4]. Acute upper airway obstruction caused by edema may lead to suffocation [5]. The management of the disease consists of the prevention and therapy of edematous attacks. "
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    ABSTRACT: Hereditary angioedema (HAE) resulting from C1-inhibitor deficiency is characterized by attacks of subcutaneous and submucosal edema. Many factors have been presumed to induce edema. Our study analyzed these factors in a fairly large patient population. In the first stage of our study, we analyzed the data recorded by 92 subjects in their patient diaries over seven years. The second phase included 27 HAE patients, who had been completing the diary entry 'Trigger factors' every day for seven months whether or not they had experienced an attack. During the initial stage, 91% of the subjects described some factor possibly related to the onset of an attack. They could identify a trigger factor - most commonly (21%) mental stress - in 30% of the 3176 attacks. We found a significant (p < 0.001) difference in the distribution of the trigger factors of the edematous attacks of different locations. The 27 participants of the second phase identified 882 potential trigger factors and recorded 365 attacks. Of these, 246 (67%) occurred on days when the patients identified a potential trigger factor. The likelihood of edema-formation associated with the latter was as follows: menstruation - 63%, infection - 38%, mental stress - 26%, physical exertion - 25%, meteorological changes - 21%, fatigue - 17%. This analysis of the trigger factors explored, for the first time, their potential role in inducing HAE attacks. Our findings might open new perspectives in extending the indications for edema-prophylaxis, and could contribute to a better understanding of the pathomechanism of HAE attacks.
    Orphanet Journal of Rare Diseases 03/2014; 9(1):44. DOI:10.1186/1750-1172-9-44 · 3.36 Impact Factor
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    • "The prevalence has been estimated to be around 1 in 50,000 [6,7]. Attacks vary unpredictably with respect to severity, frequency, and body site, and can be life-threatening due to risk of asphyxiation [4,8,9]. Symptoms often begin in early childhood and persist throughout patients’ lives, and an accurate diagnosis may be delayed for 10 years or more [2,5,6]. "
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    ABSTRACT: Background Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the patient perspective in Europe. Methods The study was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE via a cross-sectional survey of HAE patients, including direct and indirect resource utilization during and between attacks for patients and their caregivers over the past 6 months. A regression model examined predictors of medical resource utilization. Results Overall, 164 patients had an attack in the past 6 months and were included in the analysis. The most significant predictor of medical resource utilization was the severity of the last attack (OR 2.6; p < 0.001). Among patients who sought medical care during the last attack (23%), more than half utilized the emergency department. The last attack prevented patients from their normal activities an average of 4–12 hours. Patient and caregiver absenteeism increased with attack severity and frequency. Among patients who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. Conclusion HAE poses a considerable burden on patients and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks.
    Allergy and Asthma Proceedings 11/2013; 9(1). DOI:10.2500/aap.2013.34.3685 · 3.06 Impact Factor
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    • "Without an accurate diagnosis, HAE patients may not receive treatment that can effectively treat their attacks. Inappropriate treatment could result in higher morbidity and mortality, adverse events, and unnecessary surgical interventions [8,9]. "
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    ABSTRACT: Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening disease characterized by recurrent edema attacks. Important advances in HAE treatment have been made, including the development of new therapies for treating or preventing attacks. Nevertheless, the disease is still frequently misdiagnosed and inappropriately treated, potentially exposing patients with laryngeal attacks to the risk of asphyxiation. The Icatibant Outcome Survey (IOS) is an international, observational study that documents the clinical outcome of HAE patients eligible for treatment with icatibant. Patient ages at first symptoms and at diagnosis were recorded at enrolment, and the delay between first symptoms and diagnosis was calculated. The median [range] diagnostic delay in HAE type I and II patients across eight countries was 8.5 years [0--62.0]. The median delay in diagnosis was longer for HAE type II versus type I (21 versus 8 years, respectively), although this did not quite reach statistical significance. Although it can be difficult to differentiate HAE symptoms from those of more common angioedema sub-types (e.g. idiopathic or acquired angioedema), our results show that HAE type I and II patients have an unacceptable delay in diagnosis, even those with a family history of the disease. Raising physician awareness of this disabling and potentially fatal disease may lead to a more accurate diagnosis and timely treatment.
    Allergy Asthma and Clinical Immunology 08/2013; 9(1):29. DOI:10.1186/1710-1492-9-29 · 2.03 Impact Factor
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