Carmen Gómez-Traseira

Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project

BackgroundThere is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase.Methods/DesignSemi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains.DiscussionTo the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.

Usefulness of abdominal ultrasonography in the follow-up of patients with hereditary C1-inhibitor deficiency

BACKGROUND Hereditary angioedema (HAE) is caused by the deficiency of functional C1 inhibitor. Symptoms of this disease include cutaneous angioedema, abdominal pain, and even laryngeal edema. OBJECTIVE To evaluate the usefulness of abdominal ultrasonography in patients with hereditary C1-inhibitor deficiency in diagnosing acute abdominal edema attacks and possible adverse effects of long-term prophylaxis with attenuated androgens. METHODS Fifty-nine adult patients with HAE regularly observed in our department were included whether they were symptomatic or not and whether they received long-term androgen prophylaxis or not. We evaluated the ultrasonographic findings in the assessments performed routinely or in the moment of an acute abdominal attack. RESULTS Of the 59 patients, 55 ever had any symptom due to HAE (abdominal location, 78% of the symptomatic patients); 4 patients were asymptomatic. In 11 cases, ultrasonography was performed during acute attacks. Ascites and intestinal wall swelling were found in 7 of these 11 cases and, thus, diagnosis was confirmed. Of the 59 patients, 33 were or had been receiving androgen prophylaxis. Abdominal ultrasonographic assessments were performed routinely in 31 of these patients. Four cases of angiomas, 4 of steatosis, and 1 each of portal hypertension, hepatic cysts, and hepatomegaly were found. Assessments were also performed in 17 patients who did not receive androgen prophylaxis; there were no findings in any of these patients. CONCLUSION Abdominal ultrasonography has been proved useful as an early tool for diagnosing the adverse effects of therapy and for confirming diagnosis in the case of an acute abdominal attack.

Management of angioedema without urticaria in the emergency department

Abstract Angioedema refers to a localized, transient swelling of the deep skin layers or the upper respiratory or gastrointestinal mucosa. It develops as a result of mainly two different vasoactive peptides, histamine or bradykinin. Pathophysiology, as well as treatment, is different in each case; nevertheless, the resulting signs and symptoms may be similar and difficult to distinguish. Angioedema may occur at any location. When the affected area involves the upper respiratory tract, both forms of angioedema can lead to an imminent upper airway obstruction and a life-threatening emergency. Emergency physicians must have a basic understanding of the pathophysiology underlying this process. Angioedema evaluation in the emergency department (ED) should aim to distinguish between histamine- and bradykinin-induced angioedema, in order to provide appropriate treatment to patients. However, diagnostic methods are not available at the ED setting, neither to confirm one mechanism or the other, nor to identify a cause. For this reason, the management of angioedema should rely on clinical data depending on the particular features of the episode and the patient in each case. The history-taking should be addressed to identify a possible etiology or triggering agent, recording complete information for an ulterior diagnostic study in the outpatient clinic. It is mandatory quickly to recognize and treat a potential life-threatening upper airway obstruction or anaphylaxis. This review focuses on the underlying mechanisms and management of histamine- and bradykinin-induced angioedema at the emergency department and provides an update on the currently available treatments.

Trimethoprim–sulfamethoxazole (cotrimoxazole) desensitization in an HIV-infected 5-yr-old girl

To the Editor, Opportunistic infections are a major cause of morbidity and mortality in HIV-infected patients. Trimethoprim–sulfamethoxazole (TMP-SMX) (cotrimoxazole) has been shown to dramatically reduce the risk of opportunistic infections, particularly Pneumocystis carinii pneumonia, and has been used extensively in their treatment and prevention (1). Since 2006, WHO has recommended cotrimoxazole preventive therapy for all HIV-exposed infants and children born to mothers living with HIV, and continuing until cessation of risk of HIV transmission (cessation of breastfeeding) and infection can be exclude (2). In HIV-infected patients, cotrimoxazole use causes a higher rate of adverse drug reactions than in the general population (20–100% compared with 5–8% of healthy individuals) (3, 4). Hypersensitivity to cotrimoxazole is the most frequent drug reaction among HIV-infected patients, typically manifesting as a maculopapular rash, with or without fever, and usually occurring 1–2 wk after commencing treatment (5). IgE-mediated hypersensitivity is rare. The pathogenesis of TMP-SMX reactions is complex, multifactorial, and not completely understood. One or more metabolic, toxic, immunologic, or viral factors are likely to contribute, and the typical explanation is based on the variability in metabolic parameters for N-acetylation and N-oxidation (HIV-infected patients are more likely to have a slow acetylator phenotype, which results in greater oxidation and the formation of toxic intermediate SMX-derived metabolites thereby stimulating an immune response) (3, 5, 6). There are three options for the clinical management of hypersensitivity to cotrimoxazole in these patients: treating through the reaction (continuing therapy despite adverse reaction), rechallenge, or desensitization (4). Although a variety of cotrimoxazole desensitization protocols have emerged for HIV-infected patients, there is a lack of desensitization protocols for use in pediatric patients (4). A 5-yr-old Nigerian girl, with no known allergies, who was infected with HIV at birth (MTCT) was referred to the allergy department because a pruritic erythematous maculopapular rash had appeared on her face, chest, and limbs after 2 wk of treatment with cotrimoxazole, 7 ml/day, 3 times/wk (Septrim Pediatric oral suspension : 8 mg trimethoprim/40 mg sulfamethoxazole/1 ml). The reaction had occurred 15 days before she was first seen in the allergy department. She did not present fever or systemic symptoms. Hematological analysis showed a leukocyte count of 6.02 9 10/ll with 44.5% (2.68 9 10/ll) neutrophils and 43.9% (2.64 9 10/ll) lymphocytes. The CD4 T lymphocyte (CD4) count was 6% (158.4 9 10/ll). As CD4 cell count was <200 cells/mm (<200 cells/ll), prophylaxis with cotrimoxazole for at least 6 months was mandatory. After informed consent was obtained, the patient underwent a routine allergy work-up (skin tests) following the protocol of the Drug Allergy Interest Group of European Academy of Allergy and Clinical Immunology (7). Afterward, an oral desensitization protocol was carried out. The procedure was performed at the hospital, with a physician and nurse in attendance and emergency medications readily available. The results of skin prick test (SPT) with trimethoprim (10 mg/ml; Almofarma SL, Barcelona, Spain), and SPT (10 mg/ml), and intradermal test (IDT) with sulfamethoxazole (10 mg/ml; Almofarma SL) were negative. As the reaction related to cotrimoxazole use was very likely a hypersensitivity drug reaction, an oral challenge test was not performed. Instead, an oral desensitization protocol was carried out (Table 1). On the first day, gradually increasing doses of cotrimoxazole (Septrim Pediatric oral suspension ) at 15-min intervals (1 and 5 ml of dilution 1/200 and 1 and 2 ml of dilution 1/20) were tolerated. On the second day, the patient received 3 and 4 ml of 1/20 dilution at 15-min intervals with good tolerance, and on the third day, 2 undiluted doses of 0.5 and 1 ml at 45-min intervals were tolerated. On the fourth day, 30 min after the undiluted dose of 4 ml was administered (cumulative dose 6 ml), she developed a generalized pruritic erythematous maculopapular rash. The reaction immediately subsided after oral administration of dexchlorpheniramine and

Classification of angioedema without wheals

We read with interest the article by Azofra et al regarding off-label treatment of some patients with idiopathic nonhistaminergic acquired angioedema (InH-AAE) with omalizumab. 1 Besides describing the response to omalizumab of some patients with InHAAE, this article opens the discussion on the need to improve the classification of patients with angioedema without wheals. 2 Concerning InH-AAE, Cicardi et al in their consensus report claim that the term bradykinin mediated should be substituted for nonhistaminergic because, although bradykinin is assumed to mediate this type of angioedema, experimental evidence supporting this mechanism is limited. On the other hand, idiopathic acquired angioedema is classified into histaminergic and nonhistaminergic based on the prevention of angioedema by antihistamines. This way, InH-AAE comprises a heterogeneous group of patients with angioedema mediated by bradykinin but also by other mediators, such as cysteinyl leukotrienes, prostaglandins, or platelet-activating factor, and therefore with very different treatment approaches. This classification could lead to misunderstanding because the term nonhistaminergic is not synonymous of an assumed bradykinin-mediated angioedema. When reading the article by Azofra et al, physicians not very familiar with angioedema consensus and guidelines could interpret that bradykininmediated angioedema could be treated with omalizumab. InH-AAE has therefore been described as a heterogeneous group and should not be assumed to be bradykinin mediated. 1,2 The response to omalizumab of some patients with InH-AAE 1 supports that this type of angioedema is not synonymous with idiopathic bradykinergic angioedema. Moreover, it should be clarified which patients with InH-AAE should be treated with immunosuppressors or omalizumab and which ones with bradykinin-targeting drugs. In this regard, clinical characteristics of angioedema and response to corticosteroids or epinephrine in acute episodes should be considered. The patients described by

Hypersensitivity to nabumetone: cross reactivity with naproxen

have further investigations been performed showing the drug itself to be the allergen.3e5 In both of these cases, tetracycline hydrochloride was the culprit. The tetracyclines, which also include doxycycline and minocycline, share a common core structure but have different side chains,6 and therefore anti-immunoglobulin Eemediated reactions may be class or drug specific. Desensitization was preserved across the different routes of administration in our case. The excipients and other ingredients in intravenous doxycycline are mannitol and ascorbic acid, whereas those in the tablet preparation are ethylcellulose, hypromellose, magnesium stearate, microcrystalline cellulose, propylene glycol, sodium lauryl