Angioedème bradykinique d'évolution fatale suite à une prise d'énalapril. A propos d'un cas

L'angiœdème bradykinique est une maladie rare et grave qui constitue une complication exceptionnelle du traitement aux Inhibiteurs de l'Enzyme de Conversion (IEC). Elle engage le pronostic vital des patients dans 75% des cas et représente une urgence médicale majeure. L'évolution de cette affection est totalement imprévisible avec un risque de décès par asphyxie. Les auteurs rapportent l'observation d'une patiente de 70 ans hypertendue qui a présenté un angiœdème bradykinique d'évolution fatale deux jours après l'initiation de son traitement antihypertenseur par les IEC. Au travers cette observation, les auteurs voudraient mettre en lumière cette affection mortelle, de diagnostic difficile souvent méconnue

Diagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency.

BACKGROUND: Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare disease with no prevalence data or approved therapies. OBJECTIVE: To report data on patients with C1-INH-AAE followed at Angioedema Center, Milan (from 1976 to 2015). METHODS: Diagnostic criteria included history of recurrent angioedema without wheals; decreased C1-INH antigen levels and/or functional activity of C1-INH and C4 antigen less than 50% of normal; late symptom onset (>40 years); no family history of angioedema and C1-INH deficiency. RESULTS: In total, 77 patients (58% females; median age, 70 years) were diagnosed with C1-INH-AAE and 675 patients with hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) (1 patient with C1-INH-AAE/8.8 patients with C1-INH-HAE). Median age at diagnosis was 64 years. Median time between symptom onset and diagnosis was 2 years. Sixteen patients (21%) died since diagnosis, including 1 because of laryngeal edema. Angioedema of the face was most common (N = 63 [82%]), followed by abdomen (N = 51 [66%]), peripheries (N = 50 [65%]), and oral mucosa and/or glottis (N = 42 [55%]). Forty-eight of 71 patients (68%) had autoantibodies to C1-INH. In total, 56 patients (70%) used on-demand treatment for angioedema including intravenous pdC1-INH 2000 U (Berinert, CSL Behring, Marburg, Germany) (N = 49) and/or subcutaneous icatibant 30 mg (Firazyr, Shire; Milano, Italy) (N = 27). Eventually, 8 of 49 patients receiving pdC1-INH became nonresponsive; all had autoantibodies. Thirty-four patients received long-term prophylaxis with tranexamic acid (effective in 29) and 20 with androgens (effective in 8). CONCLUSIONS: The incidence of C1-INH-AAE was 1 for every 8.8 patients with C1-INH-HAE. Thirty percent of the deaths were related to the disease. Treatments approved for C1-INH-HAE are effective in C1-INH-AAE, although with minimal differences.

Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

BACKGROUND: Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. OBJECTIVE: This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. METHODS: A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. RESULTS: A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). CONCLUSIONS: RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

Angiotensin-converting Enzyme Inhibitor Angioedema Requiring Admission to an Intensive Care Unit.

OBJECTIVE: The purpose of this study was to review consecutive cases of angiotensin-converting enzyme (ACE) inhibitor angioedema admitted to an intensive care unit. METHODS: Fifty subjects with ACE-inhibitor angioedema admitted from 1998-2011 were reviewed. RESULTS: All 50 subjects were men, 62.8 ± 8.4 years of age, 76% African Americans. Fifteen (30%) required ventilatory support and 2 (4%) required tracheostomy. Over half (56%) had taken ACE inhibitors for over a year. Logistic regression identified dyspnea and tongue involvement with the need for ventilatory support (P < .01). Hypercapnia (PaCO2 = 45.2 ± 6.7; P = 0.046) also identified patients needing ventilatory support. CONCLUSIONS: Ventilatory support was provided for about one-third of those with ACE inhibitor-associated angioedema. Angioedema can occur even after extended use. Dyspnea and tongue involvement identified patients requiring ventilatory support.

Angioedema deaths in the United States, 1979-2010.

BACKGROUND: Hospital admission data indicate that the angioedema incidence has increased during the past several decades. Little is known about mortality trends. OBJECTIVES: To count the number of deaths associated with angioedema in the United States, investigate correlations with age, sex, race, and other contributory causes, and analyze trends from 1979 to 2010. METHODS: All US death certificates in which angioedema was listed as an underlying or contributing cause of death during 1979 to 2010 were analyzed. Age-adjusted mortality rates were analyzed by age, sex, and race. Other conditions designated as the underlying cause of death were investigated. RESULTS: From 1979 to 2010, there were 5,758 deaths in which angioedema was listed as a contributing cause. The age-adjusted death rate for hereditary angioedema decreased from 0.28 (95% confidence interval [CI] 0.25-0.32) to 0.06 (95% CI 0.05-0.08) per million persons per year. Conversely, mortality for angioedema increased from 0.24 (95% CI 0.21-0.27) to 0.34 (95% CI 0.31-0.37) per million. Blacks constituted 55% of angioedema deaths that were associated with use of angiotensin-converting enzyme inhibitors. On death certificates that listed hereditary angioedema as the underlying cause of death, cancer (frequently lymphoma or leukemia) was the second most commonly listed cause. CONCLUSION: Angioedema-associated deaths were very rare from 1979 to 2010. Hereditary angioedema deaths became even more so, whereas nonhereditary angioedema deaths increased. Risks associated with angiotensin-converting enzyme inhibitors were higher in blacks. Lack of specific coding for acquired angioedema most likely explains the observed association between cancer and hereditary angioedema. In the future, more granular coding systems may help distinguish hereditary from acquired angioedema.

Life-threatening angioedema induced by angiotensin-converting enzyme inhibitors: characteristics and risk factors.

BACKGROUND: Angioedema induced by angiotensin-converting enzyme inhibitors (ACEIs) is a well-known phenomenon and roughly accounts for one-third of angioedema cases presenting to the emergency departments. This study aimed to characterize the patients with severe reactions that required hospitalization and tried to identify the risk factors for these life-threatening events. METHODS: The records of all patients hospitalized with the diagnosis of "angioedema" over a 10-year period were retrospectively analyzed. Patients' characteristics as well as the characteristics of the angioedema-induced hospitalizations were studied. RESULTS: In 46 of 165 patients (28%) the angioedema was ACEI induced. The severity of the event was mild in 12 patients (26%), moderate in 25 patients (54%), and severe in 9 patients (19%). Twelve patients (26%) were admitted to the intensive care unit and six patients (13%) underwent intubation. Epinephrine was administered to 13 patients (29%), steroids were administered to 40 patients (87%), and anti-histamines were administered to 36 patients (78%). One patient died as a consequence of the event (2%). Twenty patients (45%), including the deceased patient, had recurrent events of angioedema before admission. Obese patients had significantly more recurrent events compared with nonobese patients (p = 0.03). There was also a tendency for more severe events in the obese patients (p = 0.079). Diabetes was significantly associated with moderate-to-severe events (p = 0.009) whereas treatment with beta-blockers or diuretics was significantly associated with milder events (p = 0.007 and p = 0.044, respectively). CONCLUSION: The high recurrence rate of ACEI-induced angioedema preceding subsequent life-threatening events suggests underdiagnosis of this potentially fatal adverse reaction. Diabetes and probably obesity are risk factors for more severe events. Physicians following patients receiving ACEI should be more aware of possible shortcomings associated with these medications.

Epidemiology of non-hereditary angioedema.

The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C(1) esterase inhibitor protein (functional C(1) INH). The general population sample (44% response rate) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C(1) INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain, were more frequent than previously reported.

Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993-1994 to 2004-2005.

BACKGROUND: Recent investigations in developed countries have found marked increases in the prevalence of allergic conditions. OBJECTIVE: We sought to examine recent time trends in the prevalence of anaphylaxis, angioedema, and urticaria by describing trends and age and sex differentials in hospitalizations for these conditions in Australia. METHODS: Data on hospital admissions and deaths for anaphylaxis, angioedema, and urticaria were extracted for the periods 1993-1994 to 2004-2005 and 1997-2004, respectively. For hospital admissions, age-standardized rates were calculated. Time trends and sex differences were quantified by using negative binomial models. RESULTS: During the study period, there was a continuous increase in the rate of hospital admissions for angioedema (3.0% per year), urticaria (5.7% per year), and, most notably, anaphylaxis (8.8% per year). There was a particularly steep increase in the incidence of hospitalization for food-related anaphylaxis among children aged less than 5 years. Admissions for non-food-related anaphylaxis occurred predominantly in adults, particularly those more than 35 years of age. Among children, admission rates were higher in boys, but the sex difference was reversed among adults. Over an 8-year period, there were 106 deaths associated with anaphylaxis or angioedema. CONCLUSION: Hospitalization rates for allergic conditions are on the increase, but the nature and causative factors differ between adults and children. The relation of these changes to those in the prevalence of specific allergen sensitization in the community requires further investigation in population studies. CLINICAL IMPLICATIONS: Among older persons, angioedema is becoming an increasing problem. Among children, hospitalization because of food-induced anaphylaxis is a growing concern.

Tongue swelling in the recovery room: a case report and discussion of postoperative angioedema.

We present a case of potentially life-threatening postoperative swelling of the tongue and oropharynx that developed in the postanesthesia care unit in a patient taking lisinopril. The principal treatment of angioedema is the discontinuation of the precipitating agent and airway management. Patients with swelling limited to the face and oral cavity may only require monitoring. However, those with swelling in the floor of the mouth, tongue, and supraglottic or glottic areas should have their airway secured by tracheal intubation immediately. Early intubation in patients displaying these characteristics may decrease the incidence of emergent surgical airways. Angioedema is self-limiting, and the swelling usually resolves spontaneously in two to 3 days. Proper identification of angiotensin-converting enzyme inhibitor-associated angioedema requiring a timely airway intervention may reduce mortality, and recognition of its self-limiting course can prevent unnecessary tracheostomy.

Life-threatening severe allergic reactions: urticaria, angioedema, and anaphylaxis.

Urticaria, angioedema and anaphylaxis are life threatening skin diseases. Allergological emergencies are common; drugs, food, food ingredients/additives, insects, and many other factors have been reported to elicit anaphylactic reactions. The severity of symptoms ranges from pruritus to generalized skin eruptions, gastrointestinal, bronchial problems to systemic anaphylaxis and cardiovascular emergencies. The pathomechanisms and treatment of urticarias, angioedema and anaphylaxis are described. In some situations emergency kit: antihistamines, steroids, betamimetics and adrenaline is needed. Familiarity with the early diagnosis and correct management should be acknowledegable for dermatologists to recognize these allergic reactions and must be prepared to administer emergency kit.

Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine.

AIMS: To explore drug exposure, frequency of adverse drug reactions (ADRs), types of ADRs, predisposing risk factors and ADR-related excess hospital stay in medical inpatients. METHODS: Structured data regarding patient characteristics, 'events' (symptoms, laboratory results), diagnoses (ICD10) and drug therapy were collected using a computer-supported data entry system and an interface for data retrieval from electronic patient records. ADR data were collected by 'event monitoring' to minimize possible bias by the drug monitor. The causality of each event was assessed in relation to disease(s) and drug therapy. RESULTS: The analysis included 4331 (100%) hospitalizations. The median observation period was 8 days. The median number of different drugs administered per patient and day was 6 and varied between 4 (Q1 ) and 9 (Q3 ) different drugs in 50% of all hospital days. In 41% of all hospitalizations at least one disease-unrelated event could be possibly attributed to drug therapy. Clinically relevant ADRs occurred in 11% of all hospitalizations. In 3.3% of all hospitalizations ADRs were the cause of hospital admission. The incidence of possibly ADR-related deaths was 1.4. Factors predisposing for clinically relevant ADRs were female gender and polypharmacy. ADR-related excess hospital stay accounted for 8. 6% of hospital days. CONCLUSIONS: These data demonstrate the feasibility of the developed 'event monitoring' system for quantitative analysis of ADRs in medical inpatients. With increasing numbers of recorded patients the pharmacoepidemiological database provides a valuable tool to study specific questions regarding drug efficacy and safety in hospitalized patients.

Type I hereditary angio-oedema. Variability of clinical presentation and course within two large kindreds.

OBJECTIVES: Hereditary angio-oedema (C1-inhibitor deficiency) is a disease with protean manifestations which is often misdiagnosed initially. The purpose of this study was to delineate the clinical spectrum and course of this potentially life-threatening disease. SETTING: Ten members of two unrelated affected kindreds were repeatedly hospitalized in our service with attacks of angio-oedema. Among the 271 members of the two kindreds 69 were identified who reported typical attacks. DESIGN AND SUBJECTS: Detailed information on the clinical course and laboratory data (C1-inhibitor concentration and activity, C4 concentration) were obtained from 59 of the 69 affected subjects. RESULTS: C1-inhibitor concentration and activity were low in all affected patients. The disease had become manifest by age 30 years in 98%. Most patients suffered from attacks of subcutaneous swellings and abdominal pain, and half of the patients have had attacks affecting the airways. The frequency of attacks ranged from less than one to over 26 per year. Forty-two per cent had to be hospitalized at least once. Four have died of acute airway obstruction. Thirty-eight attacks in 10 patients hospitalized in our service were all treated successfully with fresh frozen plasma or with C1-inhibitor concentrate. Trauma, stress, insect stings and foodstuff were triggering factors, but the majority of attacks occurred without an identifiable trigger. Oral contraceptives and pregnancy led to worsening of symptoms. Nonetheless, all 36 pregnancies reported were carried to term. Twenty-five patients were on continuous treatment with attenuated androgens or tranexamic acid, but only seven were free of attacks in the year preceding the survey. CONCLUSION: Hereditary angio-oedema is an autosomal dominant disease with great variability of clinical expression and severity, even within a single kindred. It often goes unrecognized over years, and it may lead to death if, in case of impending airway obstruction, specific therapy is not instituted.

Hereditary angioneurotic oedema in Finland. Clinical, immunological and genealogical studies.

A total of 7 families with hereditary angioneurotic oedema (HANE) have been found in Finland. Six HANE patients have died from laryngeal oedema, 27 patients with diagnosed HANE are alive and 21 members have a haematological abnormality typical of HANE, i.e. a deficiency of the inhibitor of the activated first component of complement (C1-INH), but no manifest symptoms. The largest family has 363 living members, 303 of whom were investigated for C1-INH, C4 and C3. Fourteen patients had HANE, 18 relatives were symptomless but had C1-INH deficiency, and 3 members of the family had died from laryngeal oedema. In two families only one case of HANE was diagnosed, the parents in both cases being symptomless with normal C1-INH levels. All patients who had died from laryngeal oedema and 10 of the 27 HANE patients still alive had a typical triad of paroxysmal abdominal pain, peripheral oedema and laryngeal oedema. Six patients have had abdominal attacks alone, three peripheral oedema alone and two only laryngeal oedema. The age at onset of symptoms was 1-51 years. Three patients, who have received continuous methyltestosterone therapy, had hardly any symptoms during the treatment. Thirteen patients have received tranexamic acid, either during an attack or continuously, with positive effects in all except two. Cinnarizine treatment was beneficial in three out of four cases, both when given continuously or during an attack.