Atopic dermatitis and skin disease
Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency

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Background

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.

Objective

This study determined the mortality of patients with and without the diagnosis of HAE-C1-INH and analyzed fatal laryngeal attacks.

Methods

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.

Results

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).

Conclusions

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.

Section snippets

Methods

Our partly retrospective and partly prospective study analyzed death cases among patients with HAE-C1-INH. To determine mortality, a series of 182 unrelated families with HAE-C1-INH registered at our Angioedema Outpatients Service (AOS) of the University of Mainz was studied. These 182 families included 728 patients with HAE-C1-INH, identified from their family history and corresponding family pedigrees.

On diagnosis of HAE-C1-INH, the family pedigree was constructed on the basis of the

Estimation of mortality based on total number of deaths

A total of 182 families with HAE-C1-INH were analyzed (Table I). According to the pedigrees and the criteria mentioned earlier, 728 patients with HAE-C1-INH could be identified. At the time of evaluation (October 2011), 514 of these patients were alive and 214 patients had died. Seventy of these 214 patients (32.7%) had died of asphyxiation due to an LA (Fig 1). In 63 patients (36 men and 27 women) who died of asphyxiation (29.4%; 95% CI, 23%-36%), the death occurred before HAE-C1-INH had been

Discussion

The results of our study showed that in all patients whose death could be attributable to HAE-C1-INH, the death occurred because of asphyxiation. With some caution, it could be concluded that asphyxiation is the exclusive cause of death when specifically attributable to HAE-C1-INH.

References (12)

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Disclosure of potential conflict of interest: K. Bork has received consultancy fees from CSL Behring, Shire, and Viropharma. J. Hardt has received research support from Stiftung Innovation. G. Witzke declares that he has no relevant conflicts of interest.

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