HAE-AS: A Specific Disease Activity Scale for Hereditary Angioedema With C1-Inhibitor Deficiency.

BACKGROUND AND OBJECTIVE: The activity of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) varies between patients and within individual patients. Objective: This study aims to develop a disease activity scale for C1-INH-HAE (HAE-AS) with sound measurement properties. METHODS: Eleven countries participated in a prospective multicenter cohort study. A clinical questionnaire was self-completed by 290 adult patients with C1-INH-HAE. Patients also completed 2 quality of life scales, the SF-36v2 and the HAE-QoL. Rasch analysis and classic psychometric methods were used to preselect a series of clinical items: number of attacks by location and number of treated attacks, emergency room visits, psychological/psychiatric treatment, missed school/workdays in the previous 6 months; general health; and impairment in everyday work/activities due to pain. RESULTS: The mean (SD) age was 41.5 (14.7; range, 18-84) years, and 69% were females. The final 12-item Rasch model showed that the HAE-AS had satisfactory reliability (person separation index, 0.748), local item independence, unidimensionality, and no item bias by age or sex. The HAE-AS provided scores in a linear measure, with a mean of 10.66 (3.92; range, 0-30). Further analysis with classic psychometric methods indicated that the HAE-AS linear measure presented moderate-to-high convergent validity with quality of life scales (SF-36v2: physical component, r=-0.33; mental component, 0.555; HAE-QoL, -0.61), and good discriminative validity by age, sex, and disease severity (P<.05). CONCLUSIONS: The HAE-AS is a short, valid, reliable, and psychometrically sound measure of the activity of C1-INH-HAE that could prove useful for research studies.

Consensus document on dog and cat allergy.

The prevalence of sensitization to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitized to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitized patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.

Piperacillin-induced DRESS: distinguishing features observed in a clinical and allergy study of 8 patients.

BACKGROUND: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is characterized by fever, rash, eosinophilia, and multiorgan failure. Previous reports have described differences in clinical and laboratory findings of DRESS syndrome depending on the inducing drug. Piperacillin has been reported as the drug responsible for this syndrome in 3 patients. OBJECTIVE: To analyze and describe the clinical, laboratory, and allergy study findings of piperacillin-induced DRESS. PATIENTS AND METHODS: Retrospective case series of patients diagnosed with DRESS associated with piperacillin-tazobactam (Pip/Taz) according to the Kardaun diagnostic score criteria. Assessment of causality was established using the Spanish Pharmacovigilance System and the lymphocyte transformation test (LTT). The allergy study included skin and epicutaneous tests. RESULTS: Eight patients were diagnosed with DRESS due to Pip/Taz (3 probable and 5 definite cases). Skin rash was observed in all cases and facial edema in 50%; the mean latency period was 18 days. Fever was present in 7 patients. Liver and kidney injuries were detected in 6 and 3 patients, respectively. All patients had eosinophilia and a full recovery. The LTT to Pip/Taz was strongly positive in all patients, with a stimulation index of over 6. Three of 3 patients had a positive intradermal test to Pip/Taz, and 1 of 4 had a positive patch test. All patients had a negative LTT to carbapenems. CONCLUSIONS: We have reported on the first case series of piperacillin-induced DRESS. A latency period of 18 days, skin rash, eosinophilia, fever, liver injury, and good prognosis were the most common features. The allergy study, and the LTT in particular, was highly useful for identifying Pip/Taz as the culprit drug and piperacillin as the responsible active ingredient.

SLIT: indications, follow-up, and management.

Specific sublingual immunotherapy (SLIT) has been proved to be a safe and effective approach in respiratory allergy. However, further research is required on aspects such as patient selection, use of optimal dosing, effects on asthma, long-term effects, and management of adverse reactions. In addition, the widely heterogeneous nature of studies on SLIT performed to date and the application of the criteria for subcutaneous immunotherapy make it difficult for the prescribing clinician to draw accurate and useful conclusions. Therefore, the QUASAR Group (QUality in the Administration of SLIT in Allergic Rhinitis), which comprises allergologists with broad clinical experience in SLIT, investigated the latest research findings and available data on this approach. Working parties were formed in 3 different categories: selection of candidates for SLIT, treatment efficacy, and adverse reactions. We performed a PubMed search for articles that were representative of each category and found 850. From these, we finally selected 266 articles, which were reviewed to retrieve data on SLIT. Evidence for each clinical question was graded according to the Oxford classification. The resulting text was evaluated on 3 occasions by all the members of the group until the final version was agreed upon. In this version, we review available evidence on SLIT, particularly with pollens, which is the subject of most articles. In areas where evidence is insufficient, an alternative agreed upon by the members of the QUASAR group is presented. Finally, we propose algorithms for selecting candidates for SLIT and for management of adverse events.

Proton pump inhibitors are associated with hypersensitivity reactions to drugs in hospitalized patients: a nested case-control in a retrospective cohort study.

BACKGROUND: Previous research has shown that gastric acid suppression by antacid drugs can promote allergic reactions to acid-labile food proteins. No data are available about whether antacid drugs can promote drug hypersensitivity reactions. The most potent and longer lasting inhibition of gastric secretion is provided by proton pump inhibitors (PPIs). We hypothesized that gastric acid suppression by proton pump inhibitors could be causative of drug hypersensitivity reactions during hospitalization. OBJECTIVE: To estimate the risk of developing drug hypersensitivity reactions during the hospitalization of patients treated with proton pump inhibitors, and other associated factors. METHODS: A nested case-control in a retrospective cohort study of hospitalized patients from September 2008 to December 2010 (70 771 admissions) was conducted using the registry of cases of interconsultations to the Allergy Department (161 confirmed cases of drug hypersensitivity reactions). A total of 318 controls were matched by first drug suspected in the hypersensitivity reaction, time of admission, age, gender and hospitalization wards. RESULTS: The relative risk of drug hypersensitivity reaction occurrence during hospitalization of patients treated with PPIs compared with those not treated in the period of study was significant (RR: 3.97; 95% CI: 1.97-8.29). After controlling for confounders in the nested case-control cohort, the use of PPIs persists as a predisposing factor (OR: 4.35; 95% CI: 2-9.45). Personal history of drug allergy and a long hospitalization time were other predisposing factors of drug hypersensitivity reactions (DHRs). The hazard that a DHR has occurred during PPI treatment was 3.7% per day. The hazard for immediate or accelerated reactions was 1.706 (P = 0.003) times that of delayed reactions. CONCLUSION AND CLINICAL RELEVANCE: In hospitalized patients, the use of proton pump inhibitors was associated with a significant increase risk of drug hypersensitivity reactions along with a personal history of drug allergies and long hospitalization time.

Management of dental-oral procedures in patients with hereditary angioedema due to C1 inhibitor deficiency.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) has considerable implications for dental health care providers, since dental procedures may trigger severe and even life-threatening episodes. The aim of the present study was to analyze the efficacy and safety of premedication with attenuated androgens (AAs), plasma-derived human C1 esterase inhibitor concentrate (pdhC1INH), or both to prevent the development of upper airway angioedema after dental-oral procedures in patients with HAE-C1-INH. MATERIAL AND METHODS: All dental-oral procedures performed on patients with HAE-C1-INH who were followed up at La Paz University Hospital, Madrid, Spain were reviewed. Demographic data, maintenance treatment, preprocedure prophylaxis, disease severity, and occurrence of upper airway angioedema were recorded. RESULTS: Twenty-four patients (14 male/10 female; mean age, 42.6 years) underwent 66 procedures. Most procedures were performed on patients with severe HAE-C1-INH (20 procedures) or moderate HAE-C1-INH (26 procedures). Only 9 procedures were performed without short-term prophylaxis. Mild upper airway angioedema developed after 3 procedures performed without short-term prophylaxis in patients with minimal or asymptomatic HAE-C1-INH. A statistically significant association was found between development of mild postprocedure upper airway angioedema and lack of maintenance treatment with AA, lack of increased dose of preprocedure AA, and failure to administer preprocedure pdhC1INH (P = .002, Fisher exact test). CONCLUSIONS: Increased doses of prophylactic AA, administration of pdhC1INH, or both were good options for ambulatory management of dental-oral procedures in patients with HAE-C1-INH. Prophylaxis with pdC1INH or increased doses of AA is advisable before dental-oral procedures, even in patients with low disease severity.

Expression of α-defensin 1-3 in T cells from severe cutaneous drug-induced hypersensitivity reactions.

BACKGROUND: Cytotoxic T cells seem to be the main effector cells in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). However, recent data support a role of the innate immune system in the etiopathology of drug-induced cutaneous reactions. In this study, we analyzed the expression of α-defensins 1-3 in mononuclear cells from patients with SJS/TEN, drug-induced maculopapular exanthema (MPE), and healthy donors. METHODS: DEFA1A3 gene expression was analyzed by quantitative and end-point RT-PCR. Intracellular flow cytometry, immunofluorescence and immunohistochemistry were carried out to verify α-defensin 1-3 protein expression in mononuclear cells from peripheral blood and skin infiltrates. α-Defensin 1-3 concentration was evaluated in plasma and blister fluid samples by ELISA. RESULTS: We herein describe DEFA1A3 gene expression in peripheral blood mononuclear cells (PBMCs) from patients with drug-induced cutaneous diseases. Gene expression analysis unveiled transcription in CD4 and CD8 peripheral blood T cells. Protein expression was confirmed by intracellular flow cytometry in mononuclear cells from the patients, including monocytes, NK cells, and T cells from peripheral blood and blister fluid. Further analysis of protein content by flow cytometry revealed higher protein levels in CD56(+) CD3(+) lymphocytes from patients with SJS/TEN when compared to MPE and healthy donors. Immunohistological analysis was used to confirm expression in dermal infiltrates. α-Defensin levels were estimated by ELISA to be 3- to 175-fold higher in blister fluid when compared to simultaneously drawn plasma samples. CONCLUSION: Upregulation of innate immune molecules such as α-defensins 1-3 in T cells from patients with SJS/TEN may be involved in the etiopathology of these life-threatening diseases induced by medications.

Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part I. Classification, epidemiology, pathophysiology, genetics, clinical symptoms, and diagnosis.

BACKGROUND: There are no Spanish guidelines or consensus statement on bradykinin-induced angioedema. AIM: To review the pathophysiology, genetics, and clinical symptoms of the different types of bradykinin-induced angioedema and to draft a consensus statement in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals. METHODS: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema (SGBA), a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings of the SGBA were held in Madrid to reach the consensus. RESULTS: The pathophysiology, genetics, and clinical symptoms of the different types of angioedema are reviewed. Diagnostic approaches are discussed and the consensus reached is described. CONCLUSIONS: A review of bradykinin-induced angioedema and a consensus on diagnosis are presented.

Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part II. Treatment, follow-up, and special situations.

BACKGROUND: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. AIM: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals. METHODS: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus. RESULTS: Treatment approaches are discussed, and the consensus reached is described. Specific situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation. CONCLUSIONS: A review of and consensus on treatment of bradykinin-induced angioedema is presented.

Use of the lymphocyte transformation test in the diagnosis of DRESS syndrome induced by ceftriaxone and piperacillin-tazobactam: two case reports.

Drug-related rash with eosinophilia and systemic symptoms (DRESS) syndrome, or drug-induced hypersensitivity syndrome (DIHS), is a life-threatening multiorgan systemic reaction characterized by rash, fever, lymphadenopathy, hepatitis, and leukocytosis with eosinophilia. Aromatic anticonvulsant drugs and allopurinol have been reported to be the most frequent eliciting agents. Our search of the literature revealed only 2 cases induced by piperacillin and 1 case by ceftriaxone.We present 2 cases of DRESS syndrome induced by the beta-lactam drugs ceftriaxone and piperacillin-tazobactam. An allergological workup including skin prick test, intradermal tests, patch tests, and lymphocyte transformation test (LTT) was performed. LTT was shown to be a useful technique in both cases to help to identify the drugs involved.

Diagnosis of aspirin-induced asthma combining the bronchial and the oral challenge tests: a pilot study.

BACKGROUND: We investigated the usefulness of the bronchial challenge (BC) with lysine-acetylsalicylate (L-ASA) in the diagnosis of aspirin-exacerbated respiratory disease (AERD) using a protocol that combined both the oral challenge (OC) and the BC tests. METHODS: Adult asthmatic patients with suspected AERD who underwent BC with L-ASA were included in the study. If the BC result with L-ASA was negative, an OC was carried out to establish the diagnosis. AERD was ruled out if both the BC and the OC results were negative (nonresponders). Both responders and nonresponders were compared for age, gender, a personal or family history of atopy, underlying disease, current asthma treatment, and presence of nasal polyps. Six patients with asthma but no suggestive history of AERD were included as controls. RESULTS: Twenty-two patients completed the study. Ten patients tested positive to the BC and/or OC (responders), whereas 12 did not (nonresponders). Seven out of the 10 responders had a positive BC result and 3 a positive OC result. After BC, 4 patients had an early asthmatic response, 1 had a dual response, and 2 had isolated late responses. No significant differences were observed in the aforementioned variables between responders and nonresponders. The results of both challenges were negative in the 6 controls. CONCLUSIONS: The BC had a high positive predictive value, was safe, and when negative, the subsequent OC did not result in any severe adverse reactions. The BC elicited an isolated late asthmatic response that has not been previously described in the literature.

Rapid Effects of an Aggressive Interaction on Dehydroepiandrosterone, Testosterone and Oestradiol Levels in the Male Song Sparrow Brain: a Seasonal Comparison.

Across vertebrates, aggression is robustly expressed during the breeding season when circulating testosterone is elevated, and testosterone activates aggression either directly or after aromatisation into 17ß-oestradiol (E2 ) in the brain. In some species, such as the song sparrow, aggressive behaviour is also expressed at high levels during the nonbreeding season, when circulating testosterone is non-detectable. At this time, the androgen precursor dehydroepiandrosterone (DHEA) is metabolised within the brain into testosterone and/or E2 to promote aggression. In the present study, we used captive male song sparrows to test the hypothesis that an acute agonistic interaction during the nonbreeding season, but not during the breeding season, would alter steroid levels in the brain. Nonbreeding and breeding subjects were exposed to either a laboratory simulated territorial intrusion (L-STI) or an empty cage for only 5 min. Immediately afterwards, the brain was rapidly collected and flash frozen. The Palkovits punch technique was used to microdissect specific brain regions implicated in aggressive behaviour. Solid phase extraction followed by radioimmunoassay was used to quantify DHEA, testosterone and E2 in punches. Overall, levels of DHEA, testosterone and E2 were higher in brain tissue than in plasma. Local testosterone and E2 levels in the preoptic area, anterior hypothalamus and nucleus taeniae of the amygdala were significantly higher in the breeding season than the nonbreeding season and were not affected by the L-STI. Unexpectedly, subjects that were dominant in the L-STI had lower levels of DHEA in the anterior hypothalamus and medial striatum in both seasons and lower levels of DHEA in the nucleus taeniae of the amygdala in the breeding season only. Taken together, these data suggest that local levels of DHEA in the brain are very rapidly modulated by social interactions in a context and region-specific pattern.

HAE-AS: A Specific Disease Activity Scale for Hereditary Angioedema With C1-Inhibitor Deficiency

Background: The activity of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) varies between patients and within individual patients. Objective: This study aims to develop a disease activity scale for C1-INH-HAE (HAE-AS) with sound measurement properties. Methods: Eleven countries participated in a prospective multicenter cohort study. A clinical questionnaire was self-completed by 290 adult patients with C1-INH-HAE. Patients also completed 2 quality of life scales, the SF-36v2 and the HAE-QoL. Rasch analysis and classic psychometric methods were used to preselect a series of clinical items: number of attacks by location and number of treated attacks, emergency room visits, psychological/psychiatric treatment, missed school/workdays in the previous 6 months; general health; and impairment in everyday work/activities due to pain. Results: The mean (SD) age was 41.5 (14.7; range, 18-84) years, and 69% were females. The final 12-item Rasch model showed that the HAE-AS had satisfactory reliability (person separation index, 0.748), local item independence, unidimensionality, and no item bias by age or sex. The HAE-AS provided scores in a linear measure, with a mean of 10.66 (3.92; range, 0-30). Further analysis with classic psychometric methods indicated that the HAE-AS linear measure presented moderate-to-high convergent validity with quality of life scales (SF-36v2: physical component, r=–0.33; mental component, 0.555; HAE-QoL, –0.61), and good discriminative validity by age, sex, and disease severity (P<.05). Conclusions: The HAE-AS is a short, valid, reliable, and psychometrically sound measure of the activity of C1-INH-HAE that could prove useful for research studies (AU)

Piperacillin-induced DRESS: distinguishing features observed in a clinical and allergy study of 8 patients

Background: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is characterized by fever, rash, eosinophilia, and multiorgan failure. Previous reports have described differences in clinical and laboratory findings of DRESS syndrome depending on the inducing drug. Piperacillin has been reported as the drug responsible for this syndrome in 3 patients. Objective: To analyze and describe the clinical, laboratory, and allergy study findings of piperacillin-induced DRESS. Patients and Methods: Retrospective case series of patients diagnosed with DRESS associated with piperacillin-tazobactam (Pip/Taz) according to the Kardaun diagnostic score criteria. Assessment of causality was established using the Spanish Pharmacovigilance System and the lymphocyte transformation test (LTT). The allergy study included skin and epicutaneous tests. Results: Eight patients were diagnosed with DRESS due to Pip/Taz (3 probable and 5 definite cases). Skin rash was observed in all cases and facial edema in 50%; the mean latency period was 18 days. Fever was present in 7 patients. Liver and kidney injuries were detected in 6 and 3 patients, respectively. All patients had eosinophilia and a full recovery. The LTT to Pip/Taz was strongly positive in all patients, with a stimulation index of over 6. Three of 3 patients had a positive intradermal test to Pip/Taz, and 1 of 4 had a positive patch test. All patients had a negative LTT to carbapenems. Conclusions: We have reported on the first case series of piperacillin-induced DRESS. A latency period of 18 days, skin rash, eosinophilia, fever, liver injury, and good prognosis were the most common features. The allergy study, and the LTT in particular, was highly useful for identifying Pip/Taz as the culprit drug and piperacillin as the responsible active ingredient (AU)

Antecedentes: El síndrome DRESS se caracteriza por fiebre, erupción cutánea, eosinofilia y afectación multiorgánica. Publicaciones previas han descrito diferencias en la presentación clínica y analítica de este síndrome dependiendo del fármaco inductor. Se han publicado 3 casos de DRESS inducidos por Piperacilina. Objetivo: Analizar y describir las características clínicas, analíticas y el estudio alergológico del DRESS inducido por Piperacilina. Pacientes y métodos: Estudio retrospectivo de una serie de pacientes diagnosticados de DRESS (de acuerdo a escala diagnóstica de Kardaun) por Piperacilina-Tazobactam (Pip/Taz). El establecimiento de causalidad se estableció según el algoritmo del Sistema Español de Farmacovigilancia y el Test de Transformación Linfocitaria (TTL). El estudio alergológico incluyó también pruebas cutáneas y epicutáneas. Resultados: Ocho pacientes diagnosticados de DRESS por Pip/Taz (3 diagnóstico probable y 5 definitivo). Todos los casos presentaron erupción cutánea y el 50% edema facial, tiempo medio de latencia de 18 días. 7 presentaron fiebre y se detectó afectación hepática y renal en 6 y 3 pacientes, respectivamente. Todos los pacientes presentaron eosinofilia y una recuperación completa. El TTL a Pip/Taz fue muy positivo en todos los pacientes con un Índice de Estimulación > 6. 3/3 pacientes presentaron prueba intradérmica positiva a Pip/Taz y 1/4 parche positivo. Todos los pacientes tuvieron TTL negativo a carbapenémicos. Conclusiones: Presentamos la primera serie de casos de DRESS inducido por Piperacilina. Un tiempo de latencia de 18 días, erupción cutánea, eosinofilia, fiebre y afectación hepática junto a un buen pronóstico fueron las características más comunes. El estudio alergológico, principalmente el TTL, fue muy útil para identificar a la Piperacilina/Tazobactam como el fármaco responsable y concretamente a la Piperacilin (AU)

The comorbidity of anxiety and depression.

OBJECTIVE: This study explored the effect of comorbid anxiety disorders in patients admitted to an inpatient specialist Mood Disorders Unit for the treatment of a primary major depressive episode. METHOD: Subjects were assessed on admission and discharge. DSM-III-R diagnoses for major depression and anxiety disorders were established using CIDI-Auto; comorbid anxiety disorders were coexistent in time with the major depression, with both conditions meeting diagnostic criteria at the time of assessment. Severity of illness was assessed using the Hamilton Depression/Melancholia Scale, the revised Hamilton Anxiety Scale and the revised Beck Depression Inventory. RESULTS: For the analysis, the study cohort was divided into three groups: depression alone (n = 33), one comorbid anxiety disorder (n = 15), and two or more comorbid anxiety disorders (n = 24). No particular anxiety disorder predominated. Interestingly, the presence or absence of comorbid anxiety with severe major depression made no significant difference to treatment choice or outcome results. Specifically, there was no significant difference between the three groups in the utilisation of electroconvulsive therapy and pharmacotherapy (including antidepressants, benzodiazepines and neuroleptics); all subjects improved significantly on both depression and anxiety ratings, and length of inpatient stay did not vary significantly between the three groups. CONCLUSIONS: The existence of comorbid anxiety disorders in those patients who presented for treatment of a primary major depressive episode did not significantly effect choice of treatment or treatment outcome, suggesting that there is a close interrelationship between the two conditions.

SLIT: indications, follow-up, and management

La inmunoterapia específica sublingual (SLIT) ha demostrado ser un tratamiento seguro y eficaz para la alergia respiratoria. Sin embargo, aspectos como la selección del paciente, el empleo de dosis óptimas, sus efectos en el asma y a largo plazo, o el manejo de las reacciones adversas necesitan una mayor investigación. Además, la gran heterogeneidad de estudios realizados con SLIT y la aplicación de los mismos criterios que los que se aplican a la inmunoterapia subcutánea dificultan la obtención de conclusiones precisas y útiles al clínico que prescribe este tratamiento. Por ello, el grupo Quasar (QUality in the Administration of SLIT in Allergic Rhinitis), grupo de alergólogos con amplia experiencia clínica con SLIT, se propuso recoger el estado de la investigación actual y los datos reales disponibles con SLIT. Para ello, se establecieron grupos de trabajo en tres categorías distintas: selección del paciente candidato a recibir SLIT, eficacia del tratamiento y reacciones adversas. Se realizó una búsqueda de artículos representativos para cada tema, localizándose inicialmente en PubMed 850, de los que se seleccionaron y analizaron 314 para extraer la evidencia disponible con SLIT, incorporando finalmente 266 al documento. Se realizó la gradación de la evidencia para cada pregunta clínica según la clasificación de Oxford. El texto resultante fue evaluado hasta en tres ocasiones por todos los miembros del grupo hasta consensuar el documento final que revisa el cuerpo de la evidencia existente hasta el momento sobre SLIT, particularmente con pólenes, sobre los que existe un mayor número de artículos, y, para aquellos aspectos en los que se ha demostrado evidencia insuficiente, propone una alternativa consensuada entre los miembros del grupo Quasar. Finalmente, se proponen algoritmos de selección del paciente candidato para SLIT y de manejo de reacciones adversas (AU)

Specific sublingual immunotherapy (SLIT) has been proved to be a safe and effective approach in respiratory allergy. However, further research is required on aspects such as patient selection, use of optimal dosing, effects on asthma, long-term effects, and management of adverse reactions. In addition, the widely heterogeneous nature of studies on SLIT performed to date and the application of the criteria for subcutaneous immunotherapy make it difficult for the prescribing clinician to draw accurate and useful conclusions. Therefore, the QUASAR Group (QUality in the Administration of SLIT in Allergic Rhinitis), which comprises allergologists with broad clinical experience in SLIT, investigated the latest research findings and available data on this approach. Working parties were formed in 3 different categories: selection of candidates for SLIT, treatment efficacy, and adverse reactions. We performed a PubMed search for articles that were representative of each category and found 850. From these, we finally selected 266 articles, which were reviewed to retrieve data on SLIT. Evidence for each clinical question was graded according to the Oxford classification. The resulting text was evaluated on 3 occasions by all the members of the group until the final version was agreed upon. In this version, we review available evidence on SLIT, particularly with pollens, which is the subject of most articles. In areas where evidence is insufficient, an alternative agreed upon by the members of the QUASAR group is presented. Finally, we propose algorithms for selecting candidates for SLIT and for management of adverse events (AU)

Management of Dental-Oral Procedures in Patients With Hereditary Angioedema due to C1 Inhibitor Deficiency

Antecedentes: El angioedema hereditario por déficit de C1 Inhibidor (AEH-C1-INH) tiene unas importantes implicaciones para los profesionales de la salud bucodental ya que una cirugía dental puede desencadenar episodios de angioedema potencialmente mortales. El objetivo del estudio fue analizar la eficacia y seguridad de los andrógenos atenuados (AAs) y/o del concentrado plasmático de C1 Inhibidor derivado de humanos (pdhC1INH) para prevenir el desarrollo de angioedema de vías respiratorias superiores tras procedimientos odontoestomatológicos en pacientes con AEH-C1-INH. Material y métodos: Se revisaron los procedimientos odontoestomatológicos realizados en el Hospital Universitario La Paz. Se consideraron datos demográfi cos, tratamiento de mantenimiento, profi laxis pre-procedimiento, grado de severidad de la enfermedad y aparición de angioedema faringolaríngeo. Resultados: Veinticuatro pacientes (14H/10M) (edad media: 42,6 años) se sometieron a 66 procedimientos. La mayor parte se realizaron en pacientes con estadio grave (20 procedimientos) o moderado (26 procedimientos) de la enfermedad. Sólo nueve procedimientos se realizaron sin profilaxis de corto plazo (PCP). En tres procedimientos realizados sin PCP se desarrolló angioedema faríngeo leve ocurriendo en pacientes en estadio asintomático o mínimo de la enfermedad. Se encontró una asociación estadísticamente significativa entre desarrollo mínimo de angioedema de vías respiratorias superiores y ausencia de tratamiento de mantenimiento con AA, ausencia de incremento de dosis y no-administración de pdhC1INH preprocedimiento (Test exacto de Fisher: P=.002). Conclusiones: El aumento de dosis preprocedimiento de AA y/o la administración de pdhC1INH son buenas opciones para el manejo ambulatorio de los procedimientos odontoestomatológicos en pacientes con AEH-C1-INH. El tratamiento profiláctico con pdC1INH o el incremento de dosis de AA es recomendable antes de la manipulación dental, incluso en pacientes con estadio bajo en la escala de gravedad de la enfermedad (AU)

Background: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) has considerable implications for dental health care providers, since dental procedures may trigger severe and even life-threatening episodes. The aim of the present study was to analyze the efficacy and safety of premedication with attenuated androgens (AAs), plasma-derived human C1 esterase inhibitor concentrate (pdhC1INH), or both to prevent the development of upper airway angioedema after dental-oral procedures in patients with HAE-C1-INH. Material and Methods: All dental-oral procedures performed on patients with HAE-C1-INH who were followed up at La Paz University Hospital, Madrid, Spain were reviewed. Demographic data, maintenance treatment, preprocedure prophylaxis, disease severity, and occurrence of upper airway angioedema were recorded. Results: Twenty-four patients (14 male/10 female; mean age, 42.6 years) underwent 66 procedures. Most procedures were performed on patients with severe HAE-C1-INH (20 procedures) or moderate HAE-C1-INH (26 procedures). Only 9 procedures were performed without short-term prophylaxis. Mild upper airway angioedema developed after 3 procedures performed without short-term prophylaxis in patients with minimal or asymptomatic HAE-C1-INH. A statistically significant association was found between development of mild postprocedure upper airway angioedema and lack of maintenance treatment with AA, lack of increased dose of preprocedure AA, and failure to administer preprocedure pdhC1INH (P=.002, Fisher exact test). Conclusions: Increased doses of prophylactic AA, administration of pdhC1INH, or both were good options for ambulatory management of dental-oral procedures in patients with HAE-C1-INH. Prophylaxis with pdC1INH or increased doses of AA is advisable before dental-oral procedures, even in patients with low disease severity (AU)