How can we improve our use of allergen immunotherapy as a treatment option for asthma and severe asthma?

INTRODUCTION: In patients suffering from allergic asthma, especially in the pediatric age-group, allergen immunotherapy (AIT) could be of benefit and has the potential of long-term disease modification. AREAS COVERED: We reviewed the evidence for a beneficial effect of AIT in allergic asthma. A correct selection of the possible candidates for AIT is crucial. We define the comprehensive allergic asthma diagnosis: confirming asthma, confirming allergic sensitization and having symptoms on exposure to the relevant allergens.We analyze why the first trials on AIT for asthma were contradictory; we consider the results of systematic reviews and discuss the high degree of heterogeneity often found in meta-analysis. We assess recent, double-blind, placebo-controlled trials in sublingual AIT that provide robust evidence for a reduction in acute asthma exacerbations and a decrease in the use of inhaled corticosteroids. Further, we demonstrate how real-world trials and large pharmacy data-based analyses confirm these findings for SLIT and SCIT. Finally, we explore the option of AIT in severe asthma patients, once well-controlled on biologic therapy. EXPERT OPINION: Clear indications for AIT in asthma guidelines would benefit allergic asthmatics. AIT is a therapeutic option in appropriately selected asthmatics. Three years treatment has the potential for long-term tolerance, with persisting benefits years after discontinuation.

Aeroallergen immunotherapy associated with reduced risk of severe COVID-19 in 1095 allergic patients.

Introduction: Allergen immunotherapy (AIT) brings along changes in the immune system, restoring dendritic cell function, reducing T2 inflammation and augmenting the regulatory cell activation. Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, interferes with the immune system causing immune suppression during the first phase and over-activation in more advanced disease. We decided to explore the interaction of both in a real-world observational trial. Methods: We registered COVID-19 outcomes in patients with allergic disorders in Latin America, treated with and without AIT. The registry was conducted during the first 1.3 years of the pandemic, with most of the data collected before COVID-19 vaccination was concluded in most countries. Data collection was anonymous via a web-based instrument. Ten countries participated. Results: 630/1095 (57.6%) of the included patients received AIT. Compared to patients without AIT, those treated with AIT had a reduced risk ratio (RR) for COVID-19 lower respiratory symptoms (RR 0.78, 95% CI: 0.6703-0.9024; p = 0.001662) and need for oxygen therapy (RR 0.65, 95% CI: 0.4217-0.9992; p = 0.048). In adherent patients on maintenance sublingual immunotherapy/subcutaneous immunotherapy (SLIT/SCIT) the RR reduction was larger [RR = 0.6136 (95% CI 0.4623-0.8143; p < 0.001) and RR: 0.3495 (95% CI 0.1822-0.6701; p < 0.005), respectively]. SLIT was slightly more effective (NS). We excluded age, comorbidities, level of health care attendance, and type of allergic disorder as confounders, although asthma was related to a higher frequency of severe disease. When analyzing patients with allergic asthma (n = 503) the RR reduction favoring AIT was more pronounced with 30% for lower respiratory symptoms or worse (RR 0.6914, 95% CI 0.5264 to 0.9081, p = 0.0087) and 51% for need of oxygen therapy or worse (RR 0.4868, 95% CI 0.2829-0.8376, p = 0.0082). Among severe allergic patients treated with biologics (n = 24) only 2/24 needed oxygen therapy. There were no critical cases among them. Conclusion: In our registry AIT was associated with reduced COVID-19 severity.

[Risk factors for food allergy]. / Factores de riesgo para padecer alergia alimentaria.

Allergy is the result of genetic and environmental interactions, including time, route, and dose of food exposure in susceptible patients. Risk factors can be: 1) genetic and 2) environmental, and these, in turn, are divided into prenatal, perinatal and postnatal. Food allergy appears frequently and depends on multiple risk factors (genetic and environmental), which in turn are divided into: prenatal, natal and postnatal factors; They participate in the expression of the disease and clinical intervention is not possible in all cases.

La alergia es el resultado de interacciones genéticas y ambientales, incluso de tiempo, ruta y dosis de exposición a alimentos en pacientes susceptibles. Los factores de riesgo pueden ser: 1) genéticos y 2) ambientales, y estos, a su vez, se dividen en prenatales, perinatales y posnatales. La alergia alimentaria aparece frecuentemente y depende de múltiples factores de riesgo (genéticos y ambientales), que a su vez se dividen en: factores prenatales, natales y posnatales; participan en la expresión de la enfermedad y no en todos los casos es posible la intervención clínica.

[Hematemesis in a newborn baby with Heiner syndrome. A case report]. / Hematemesis en un neonato con síndrome de Heiner. Reporte de caso.

INTRODUCTION: Heiner syndrome is a very rare but reversible lung disease caused by non-IgE-mediated hypersensitivity to cow's milk proteins resulting in an atypical pulmonary disease in babies and infants. Very few cases have been reported. Due to its heterogeneous manifestations, the diagnosis can be delayed since it can occur with chronic or recurrent infections of the upper or lower respiratory tract, fever, growth failure, or gastrointestinal symptoms. Pulmonary infiltrates can be mistaken for pneumonia, but Heiner's syndrome is refractory to antibiotic treatment. CASE REPORT: We describe the case of a 1-month-old newborn baby whose main symptom was hematemesis, which is a rare symptom. The diagnosis was confirmed with the complete disappearance of the symptoms when milk and dairy products were strictly avoided. CONCLUSIONS: The prognosis is favorable if a milk-free diet is begun early. Most children will tolerate cow´s milk within a few years.

Introducción: El síndrome de Heiner es una enfermedad pulmonar muy rara, pero reversible, debida a una hipersensibilidad no mediada por IgE a las proteínas de la leche de vaca resultando en una enfermedad pulmonar atípica en bebés y lactantes. Se han reportado muy pocos casos. Debido a sus manifestaciones heterogéneas, el diagnóstico puede retrasarse, ya que puede cursar con infecciones respiratorias crónicas o recurrentes de vía aérea alta o baja, fiebre, falla en el crecimiento o síntomas gastrointestinales. Los infiltrados pulmonares pueden ser confundidos con neumonía, pero el síndrome de Heiner es refractario al tratamiento con antibióticos. Reporte de caso: Describimos el caso de un neonato de un mes cuyo síntoma principal fue hematemesis, que es un síntoma muy raro. El diagnóstico se confirmó con la remisión total de los síntomas al suprimir de forma estricta la leche y sus derivados. Conclusiones: El pronóstico es favorable si se instaura una dieta libre de lácteos tempranamente. La mayoría de los niños tolerarán la leche en pocos años.

"Chronic urticaria and obstructive sleep apnea: Is there a significant association?"

BACKGROUND: Few studies have explored the association between obstructive sleep apnea (OSA) and chronic urticaria (CU). Our study aims to fill this gap by determining the frequency of the risk categories for OSA and how they might correlate with the specific CU patient reported outcome measures urticaria activity score (UAS7), urticaria control test (UCT) and CU quality of life questionnaire (CU-Q2oL). METHODS: We conducted a cross-sectional study involving a cohort of 171 Latin American CU patients. Descriptive statistics were used to determine frequency and proportions for demographic and clinical variables, while a chi-squared test for association between STOP-Bang OSA questionnaire categories and both UAS7 and UCT categories was performed to analyze how such variables interact. To further assess the strength of the correlation a Cramer's V coefficient was reported. Finally, a Kendall-Tau b correlation coefficient was performed to measure the correlation between the STOP-Bang score and other independent continuous variables. RESULTS: The average STOP-Bang score was 2.5, with 24% and 21% of patients falling into the intermediate and high-risk category for moderate-to-severe OSA, respectively. There was a strong statistically significant association (Cramer's V = 0.263; p = .000) between UAS-7 categories and STOP-Bang risk categories. A similar pattern of strong significant association (Cramer's V = .269; p = .002) was observed between UCT categories and STOP-Bang risk categories. A weak positive correlation between the STOP-Bang score and the CU-Q2oL average score (τb = 0.188, p = .001) was identified. Overall, 72.5% patients reported limitations with respect to sleep in a varied degree according to the CU-Q2oL. CONCLUSIONS: Our results suggest that a considerable proportion of patients with CU are at intermediate to high risk for OSA. Higher disease activity, poor CU control, and worse quality of life were all found to be associated with an increased risk. Additional studies are needed to determine the exact link between these conditions, and to determine whether screening and treatment for OSA might benefit patients with CU.

[Anaphylaxis caused by dermal exposure with cow's milk in an adult with food allergy. A case report]. / Anafilaxia por contacto con leche en un adulto con alergia alimentaria. Reporte de caso.

BACKGROUND: Allergy to cow's milk proteins is the most frequent food allergy and its prevalence has increased in the last decade. Although most patients have symptoms after the intake of dairy milk, other routes of sensitization through skin and mucous membranes have been described. CASE REPORT: A 31-year-old male patient who is a professional chef and started with oropharyngeal symptoms after the intake of milk. Since he tolerated other dairy products, he did not suppress them from his diet. However, the clinical picture progressed and cutaneous symptoms were added; finally, anaphylaxis occurred by contact with bread dough that contained butter and milk. The patient was treated in the emergency department, where an increase in serum tryptase was verified. Skin prick tests and serological tests were positive for milk and its fractions. CONCLUSION: Reports of anaphylaxis caused by dermal contact with cow's milk are very scarce and they have been reported only in children. We believe that repeated food handling could favor cutaneous sensitization in adults with a personal history of atopy.

Antecedentes: La alergia a proteínas de leche de vaca es la alergia alimentaria más frecuente y su prevalencia se ha incrementado en la última década. Aunque la mayoría de los pacientes presenta síntomas por ingestión, se ha descrito sensibilización cutánea y de mucosas. Caso clínico: Hombre de 31 años, chef de profesión, en quien se iniciaron síntomas orofaríngeos después de la ingesta de leche. No suprimió de su dieta otros productos lácteos que toleraba en ese momento, sin embargo, los cuadros alérgicos fueron progresando y se añadieron manifestaciones cutáneas; finalmente presentó anafilaxia por contacto con masa de pan que contenía mantequilla y leche. El paciente fue atendido en urgencias, donde se comprobó la elevación de la triptasa sérica. Las pruebas cutáneas y serológicas resultaron positivas para leche y sus derivados. Conclusión: La anafilaxia por contacto con leche es infrecuente y solo se ha informado en niños. Consideramos que la manipulación repetida de alimentos pudiera favorecer la sensibilización cutánea en adultos con historia personal de atopia.

[The prevalence of allergic diseases in children with short bowel syndrome]. / Prevalencia de enfermedades alérgicas en niños con síndrome de intestino corto.

BACKGROUND: Short bowel syndrome is the result of an extensive surgical resection that leaves the length of the small intestine at a critical value for the proper nutritional absorption. An increased risk of food allergy has been described in patients who suffer from this condition. OBJECTIVE: To describe the prevalence of allergic diseases in a group of patients with short bowel syndrome. METHODS: A descriptive, cross-sectional, and ambispective study was carried out; it included patients with short bowel syndrome who had attended the nephrology service of the National Institute of Pediatrics in a period of 18 months. Information about medical records, surgery history, diet history, and food tolerance was collected with prior authorization of parents or legal guardians. Likewise, there was questioning about history of atopy, and validated questionnaires for allergic diseases were applied in Spanish. The following tests were carried out: skin tests with allergen extracts, determination of four foods specific immunoglobulin E, patch test, and open oral food challenge. The protocol was authorized by the research ethics committee. RESULTS: Fifteen patients with a median age of 44 months (range of 8-128 months) and with a male/female ratio of 2:1 were included. The most common causes of SBS were necrotizing enterocolitis and intestinal atresia. 27% of the patients had a family history of atopy and 40 % of the patients had a personal history that suggested an allergy to cow's milk in infancy. Allergic diseases were found in 40 %. CONCLUSIONS: Allergic diseases seem to have high prevalence in patients with SBS. More studies in large populations are required in order to confirm this discovery.

Antecedentes: El síndrome de intestino corto es el resultado de una resección quirúrgica extensa que deja la longitud del intestino delgado en un valor crítico para una adecuada absorción nutricional. Se han descrito un incremento en el riesgo de alergia alimentaria en pacientes que sufren esta condición. Objetivo: Describir la prevalencia de enfermedades alérgicas en un grupo de pacientes con síndrome de intestino corto. Métodos: Se llevó a cabo un estudio descriptivo transversal y ambispectivo, en el cual se incluyeron pacientes con síndrome de intestino corto que acudieron al servicio de nefrología del Instituto Nacional de Pediatría en un período de 18 meses. Con previa autorización del padre o tutor se recabaron los expedientes médicos, los antecedentes de la cirugía, historial de alimentación y tolerancia a alimentos. De igual manera, se interrogaron antecedentes de atopia y se aplicaron cuestionarios validados en español para enfermedades alérgicas. Se realizaron pruebas cutáneas con extractos alergénicos, determinación de inmunoglobulina E específica para cuatro alimentos, prueba del parche y reto oral abierto con alimentos. El protocolo fue autorizado por el comité de ética e investigación. Resultados: Se incluyeron 15 pacientes con una mediana de 44 meses (rango 8-128 meses) y la relación hombre/mujer fue de 2:1. Las causas más frecuentes de síndrome de intestino corto fueron enterocolitis necrozante y atresia intestinal. El 27 % tenía historia familiar de atopia y 40 % antecedentes personales sugestivos de alergia a las proteínas de la leche de vaca en la infancia. Se encontraron enfermedades alérgicas en 40 %. Conclusiones: Las enfermedades alérgicas parecen tener una alta prevalencia en pacientes con síndrome de intestino corto. Se requieren más estudios en poblaciones extensas para confirmar este hallazgo.

Learnings from real-life experience of using omalizumab for chronic urticaria in Latin America.

BACKGROUND: Updated urticaria guidelines recommend that patients should be assessed for disease activity, severity, control, and quality of life at baseline and follow up. Regarding treatment, guidelines consider second generation antihistamines as the cornerstone in therapy for chronic urticaria (CU), while other drugs, such as omalizumab, are conceived as second-line alternatives. In regards to omalizumab, despite advances in the management of CU, there are still open questions about timing, dosing, and objective measures for clinical response. This study was designed to portray the use of patient-reported outcomes (PROs) in chronic urticaria management, as well as the effectiveness and treatment patterns of omalizumab in CU, as seen in a real-life setting in Latin America. METHODS: This is a retrospective observational study, involving 72 Latin American patients with chronic urticaria treated with omalizumab. Patient reported outcomes and treatment patterns, response, quality of life improvement and discontinuation were analyzed. RESULTS: From the 72 patients, 91.7% (n = 66) were assessed through PROs, where urticaria control test (UCT) was the most used (79.2%; n = 57). Overall, 80.0% (n = 44) responded to omalizumab at some point of the treatment. Omalizumab 300 mg was associated with earlier response compared to lower doses. Regardless of dosage, most patients assessed with CU-Q2oL improved quality of life (80.8%; n = 21). With respect to omalizumab discontinuation, 20.8% (n = 15) patients interrupted omalizumab before the 3rd month of treatment (p = .000). CONCLUSIONS: The present study highlights how the use of PROs and omalizumab in Latin America differ from guidelines' recommendations and clinical trials. Even though most patients were initiated under omalizumab 300 mg, most of them finished with lower doses. Regardless of dosage, most patients responded to omalizumab and improved quality of life at some point during treatment. However, such features were seen earlier with omalizumab 300 mg. Regarding treatment discontinuation, one-fifth of patients interrupted omalizumab before the third month.

[Reactivation of patch-stage mycosis fungoides caused by oral administration of dialyzable leukocyte extract. Case report]. / Reactivación de micosis fungoide en estadio de placa por administración de extracto dializado de leucocitos vía oral. Reporte de caso.

BACKGROUND: Mycosis fungoides is a cutaneous T-cell lymphoma. The patch stage is limited to the skin and may spontaneously involute or progress, spreading to peripheral blood, lymph nodes and viscera. CASE REPORT: 64 year-old female with a 6-year history of dermatosis with scaly, poorly delimited and pruritic plaques on the chest and extremities. She had received oral steroids and antihistamines, with transient partial remissions been experienced. Skin biopsy revealed Pautrier's microabscesses, which are pathognomonic of mycosis fungoides. Positron-emission tomography and peripheral blood smear ruled out dissemination and confirmed patch-stage mycosis fungoides. She received nitrogen mustard topical derivatives, psoralen plus UVA therapy, steroids and tacrolimus. She achieved complete remission at 6 months. Two years later, she was treated with dialyzable leukocyte extract, which reactivated the patch lesions with severe itching; the extract was discontinued. The lesions resolved two weeks after topical clobetasol was applied. CONCLUSIONS: Th2 predominates in mycosis fungoides. Given that dialyzable leukocyte extract reinforces the Th1 profile, it was unlikely for it to reactivate the disease, but the diversity of lymphocyte immunophenotypes in mycosis fungoides and the complex activation networks caused a paradoxical reactivation.

Antecedentes: La micosis fungoide es un linfoma cutáneo de células T. El estadio de placa se encuentra limitado a piel y puede involucionar o progresar, diseminándose a sangre periférica, ganglios y vísceras. Reporte de caso: Mujer de 64 años de edad con dermatosis de seis años de evolución con placas descamativas, mal delimitadas y pruriginosas en tórax y extremidades. Había recibido esteroides orales y antihistamínicos, con los que presentaba remisiones parciales transitorias. Mediante biopsia cutánea se encontraron microabscesos de Pautrier, patognomónicos de micosis fungoide. La tomografía por emisión de positrones y el frotis de sangre periférica descartaron diseminación y confirmaron micosis fungoide en estadio de placa. La paciente recibió derivados tópicos de mostaza nitrogenada, psoralenos con radiaciones ultravioleta A, esteroides y tacrolimus. Presentó remisión total a los seis meses. Dos años después recibió extracto dializado de leucocitos, con el que se reactivaron las lesiones con prurito intenso; suspendió el extracto. Las lesiones involucionaron dos semanas después de iniciar el clobetasol tópico. Conclusiones: En la micosis fungoide predomina Th2. Dado que el extracto dializado de leucocitos refuerza el perfil Th1 no se esperaba que reactivara la enfermedad, pero los diversos inmunofenotipos de los linfocitos en la micosis fungoide y las complejas redes de activación ocasionaron reactivación paradójica.

[Prevalence of allergic diseases in children with secondary renal tubular acidosis attending a tertiary care pediatric center]. / Prevalencia de enfermedades alérgicas en niños con acidosis tubular renal secundaria que acudieron a un hospital pediátrico de tercer nivel.

BACKGROUND: It has been suggested a high prevalence of allergic disease in children with RTA. OBJECTIVE: To describe the prevalence of allergic diseases in children with secondary RTA (renal tubular acidosis) in the nephrology department of the National Institute of Pediatrics (NIP), México. METHODS: An observational, prospective, cross-sectional, descriptive study. Children with secondary RTA < 18 years who attended the outpatient nephrology service in the NIP for 24 months, were included. ISAAC questionnaire and the EAACI guidelines were applied. To prove a suspected allergy, skin tests, total and specific IgE, patch testing and food challenge were performed. Using SPSS 19, frequency of allergic diseases was described. RESULTS: 113 patients were included. Age 8 to 168 months. Male: 53.9 %. RTA types: Distal (64.6 %), proximal (26.5 %), mixed (1.8 %) and undetermined (7 %). Age of onset between 1 and 96 months. Serum bicarbonate 10.1 to 20 mEq/L. Allergic diseases were found in 24.8 %: allergic rhinitis (18.4 %), food allergy (9.7 %), atopic dermatitis (8 %), asthma (8 %) and allergic conjunctivitis (6.1 %). Total IgE was increased in 9 patients. Positive skin tests in 14.2 %. Positive chemiluminescence in 18 children; positive open food challenge in 11 children and patch tests in 4. CONCLUSION: Secondary RTA is common in children attending tertiary care hospitals. The prevalence of allergic disease in children with secondary ATR, is similar to that described in the general population.

Antecedentes: Se ha sugerido elevada prevalencia de enfermedades alérgicas en niños con acidosis tubular renal. Objetivos: Describir la prevalencia de enfermedades alérgicas en niños con acidosis tubular renal secundaria atendidos en el Servicio de Nefrología del Instituto Nacional de Pediatría, México. Métodos: Estudio observacional, prospectivo, transversal, descriptivo. Se incluyeron niños atendidos durante 24 meses. Se aplicó el cuestionario ISAAC y los criterios de la guía EAACI. Ante sospecha de alergia se realizaron pruebas cutáneas, IgE total y específica, pruebas del parche y reto alimentario. Resultados: Se incluyeron 113 pacientes con edades entre 8 y 168 meses; 53.9 % del sexo masculino. Tipos de acidosis tubular renal: distal (64.6 %), proximal (26.5 %), mixta (1.8 %) y no determinada (7 %). La edad de inicio osciló entre 1 y 96 meses. Se registró 10.1 a 20 mEq/L de bicarbonato sérico; 24.8 % mostró enfermedades alérgicas: 18.4 % rinitis alérgica, 9.7 % alergia alimentaria, 8 % dermatitis atópica, 8 % asma y 6.1 % conjuntivitis alérgica. Se observó IgE total elevada en 9 pacientes. En 14.2 % las pruebas cutáneas fueron positivas y la quimioluminiscencia en 18 niños; el reto abierto con alimentos fue positivo en 11 y las pruebas del parche en 4. Conclusiones: La prevalencia de enfermedades alérgicas en niños con acidosis tubular renal secundaria fue similar a la de la población general.

[Immunological evaluation during treatment of a case of borderline lepromatous leprosy]. / Evaluación inmunológica durante el tratamiento de un caso de lepra dimorfa lepromatosa.

BACKGROUND: Leprosy is a chronic granulomatous infection that affects skin and peripheral nerves. Its prevalence has declined, but is still observed mainly in poor rural areas. CASE REPORT: A male city dweller with photophobia and chronic dermatosis in the face: nodular and erythematous lesions, pustules, keratitis and entropion, partial eyebrows loss, and edema on eyelids, chin, and nose bridge. The rest of the body had no lesion or lymphadenopathy. Biopsy revealed Langhans giant cell proliferation in the superficial dermis without epidermal atrophy. BAAR staining for detection were positive, no Virschow cells were observed, and Fite-Franco staining (leprosy-specific) was negative. Cutaneous tuberculosis was diagnosed. Rifampicin/isoniazid/pyrazinamide and dialysate leukocyte extract were prescribed. A month later, the swelling had decreased significantly. Polymerase chain reaction (PCR) test was positive for Mycobacterium leprae. Flow cytometry showed CD4 count normalization. Long-term treatment with rifampicin, clofazimine, and dapsone was established. CONCLUSIONS: The host's immune response determines the clinical features of the disease: if response is bad there will be vacuolated macrophages filled with bacilli (lepromatous leprosy). Clinical and histopathological findings help typing.

Antecedentes: La lepra es una infección granulomatosa crónica que afecta piel y nervios periféricos. Aunque su prevalencia ha disminuido, se sigue observando principalmente en el medio rural pobre. Caso clínico: Hombre residente de una ciudad, con fotofobia y dermatosis crónica en la cara: lesiones nodulares y eritematosas, pústulas, queratitis y entropión, pérdida parcial de las cejas y edema de párpados, barbilla y puente nasal. El resto del cuerpo sin lesiones ni adenomegalias. La biopsia reveló proliferación de células gigantes de Langhans en la dermis superficial, sin atrofia epidérmica. Las tinciones para búsqueda de BAAR fueron positivas. No se observaron células de Virschow y la tinción de Fite-Franco (específica de lepra) fue negativa. Se diagnosticó tuberculosis cutánea. Se prescribió rifampicina-isoniazida-pirazinamida y extracto dializado de leucocitos. Un mes después, la inflamación había disminuido de forma importante. La reacción en cadena de la polimerasa fue positiva para Mycobacterium leprae. Con la citometría de flujo de seguimiento se observó normalización de la cuenta de CD4. Se estableció tratamiento a largo plazo con rifampicina, clofazimina y dapsona. Conclusiones: La respuesta inmune del huésped determina las características clínicas de la enfermedad: si la respuesta es mala habrá macrófagos vacuolados llenos de bacilos (lepromatosa). Los hallazgos clínicos e histopatológicos ayudan a la tipificación.

Drug-Induced Anaphylaxis in Latin American Countries.

BACKGROUND: Information regarding the clinical features and management of drug-induced anaphylaxis (DIA) in Latin America is lacking. OBJECTIVE: The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. METHOD: A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. RESULTS: There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P < .01). Severe DIA was less frequent with underlying asthma (N = 22 vs 35 [38.6% vs 61.4%], P < .05) or atopy (N = 62 vs 71 [43% vs 59% ], P < .01). Nonsteroidal anti-inflammatory drugs (NSAIDs) (N = 178 [57.8%]), beta-lactam antibiotics (N = 44 [14.3%]), and other antibiotics (N = 16 [5.2%]) were the most frequently implicated drug classes. Anaphylaxis was rated as severe in N = 133 (50.4%) and anaphylactic shock (AS) was present in N = 90 (34.1%). Epinephrine was only used in N = 73 (27.6%) overall, but in N = 70 (77.8%) of patients with AS. CONCLUSION: In Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve management of DIA.

Multinational experience with hypersensitivity drug reactions in Latin America.

BACKGROUND: Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. OBJECTIVE: To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. METHODS: An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. RESULTS: Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), ß-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. CONCLUSION: Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged.

[Cow's milk protein allergy in disability children]. / Alergia a las proteínas de leche de vaca en niños con discapacidad.

BACKGROUND: Cow's milk protein allergy (CMPA) is the most common food allergy in children. However, the prevalence of CMPA in disability children is unknown. OBJECTIVE: To know the frequency of CMPA in disability children and to assess the clinical improvement after a suppression diet. MATERIAL AND METHODS: We conducted a cohort study at the Children's Rehabilitation Center Telethon of Puebla, in which children aged 6 months to 5 years with clinical symptoms of CMPA were included, between January and September 2012. An exploratory questionnaire about clinical symptoms of CMPA was applied before and after the cow's milk proteins suppression diet. RESULTS: We identified 26 cases among 145 assessed children (18%). The mean age was 2 years and 7 months. All children had a history of multiple clinical symptoms. Respiratory symptoms were the most common, follows for gastrointestinal symptoms, including regurgitation, which suggests the association with gastroesophageal reflux. CONCLUSIONS: CMPA is frequent in disability children. Respiratory and gastrointestinal symptoms were the most common. Cow's milk proteins suppression diet was a useful diagnostic and therapy tool for these children.

ANTECEDENTES: la alergia a las proteínas de la leche de vaca es la alergia alimentaria más frecuente en niños. Sin embargo, se desconoce la prevalencia de ésta en niños con discapacidad. OBJETIVO: conocer la frecuencia de alergia a las proteínas de la leche de vaca en niños con discapacidad y evaluar la mejoría clínica posterior a una dieta de supresión. MATERIAL Y MÉTODO: estudio de cohorte efectuado en pacientes con datos clínicos de alergia a las proteínas de la leche de vaca, de seis meses a cinco años de edad, atendidos en el Centro de Rehabilitación Infantil Teletón de Puebla, de enero a septiembre de 2012. Se aplicó un cuestionario de manifestaciones clínicas de alergia a las proteínas de la leche de vaca antes y después de una dieta de supresión de proteínas de leche de vaca. RESULTADOS: se identificaron 26 casos entre 145 niños evaluados (18%). La media de edad fue de 2 años y 7 meses. Todos los niños tenían antecedentes de múltiples manifestaciones clínicas; las más frecuentes fueron las respiratorias, seguidas por las digestivas, que incluyeron regurgitaciones, lo que sugiere asociación con reflujo gastroesofágico. Todos los pacientes mostraron mejoría clínica después de la dieta de supresión. CONCLUSIONES: la alergia a las proteínas de la leche de vaca es frecuente en niños con discapacidad. Las manifestaciones respiratorias y digestivas fueron las más comunes. La dieta de supresión de proteínas de leche de vaca resultó en un procedimiento diagnóstico y de tratamiento de gran valor en este grupo de niños.

[Anaphylaxis Due to Ingestion of Ivy Syrup (Hedera hÈlix). Report of two Cases]. / Anafilaxia por ingesta de jarabe de hiedra (Hedera helix). Reporte de dos casos.

Common ivy is an ornamental plant, that is ubiquitous in Mexico. Its allergens can cause contact dermatitis, asthma and allergic rhinitis. We describe two cases of anaphylaxis related to common ivy syrup ingestion. We performed skin prick test with Hedera helix syrup, and using a dialized and ultrafiltered of common ivy syrup commercial presentation (dry common ivy extract: 7mg/ml), as well as using Hedera helix pollen extract. We describe two cases of anaphylaxis related to ingestion of Hedera helix syrup. Skin prick test with the commercial presentation and with the pollen extract were positive in both patients. In this study we confirmed the causal relationship of anaphylaxis due to the ingestion of ivy syrup in two patients through skin prick tests with ivy syrup and ivy pollen extract. Common ivy can cause contact dermatitis, asthma and allergic rhinitis, but we do not know the allergens that could be related to systemic and respiratory reactions, then, more studies in this topic are requiered.

[Transfer factor effectiveness patients with persistent genital human papillomavirus infection]. / Beneficios del factor de transferencia en pacientes con virus del papiloma humano genital persistente.

BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. METHODS: One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. RESULTS: We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. CONCLUSIONS: The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.

Prevalence of sensitization to inhaled and food allergens in a group of children with primary renal tubular acidosis.

OBJECTIVE: Some reports associate certain illnesses of the urinary system with allergies. Thus, we decided to examine the prevalence of sensitization to allergens in a group of children with primary renal tubular acidosis (RTA). METHODS: Children with primary RTA who attended the nephrology department at a third level pediatric hospital during a four-month period, were included. With informed parental consent, a questionnaire and skin prick test, total IgE, specific IgE and milk precipitins were performed. RESULTS: Forty-three children were included, aged 5 months to 9 years (mean, 3.4 ± 1.8 years), and a male/female ratio of 1.7:1. The age of onset of ATR ranged from 2 to 18 months. The most common symptoms at the beginning of disease were: failure to thrive and lack of appetite. Twenty-one parents (48.8%) noticed an association between the introduction of cow´s milk and the beginning of symptoms. Skin tests were positive in 27.9%. Total IgE levels were elevated in 34.9%, ranged from 5.9 to 324 IU/mL. Allergen-specific IgE was positive in 25.6%, mainly for milk, wheat and egg white. The milk precipitins test was positive in 9 patients (21%). CONCLUSIONS: Although this study demonstrated the existence of allergen sensitization in a group of children with RTA, it is necessary to look for this association in studies with larger sample size and to use tests with higher specificity and sensitivity.

[Angioedema and paradoxical bronchoconstriction secondary to ipratropium bromide/salbutamol administered by metered dose inhaler in patients with soy allergy]. / Angioedema y broncoconstricción paradójica secundarios a bromuro de ipratropio/salbutamol administrados por inhalador de dosis medida en pacientes alérgicos a la soya.

BACKGROUND: There are some reports on the association between the use of ipratropium bromide/salbutamol and paradoxical bronchoconstriction and urticaria in patients with soy allergy. METHODS: We describe four patients who displayed angioedema and paradoxical bronchoconstriction secondary to ipratropium bromide/salbutamol administered by metereddose-inhaler (MDI). In all of them soy allergy was demonstrated. RESULTS: Four patients, two children and two adults, exhibited paradoxical bronchoconstriction and angioedema secondary to ipratropium bromide/salbutamol administered by MDI. In all of them, soy allergy was substantiated by skin prick test and IgG/IgE RAST. The symptoms quickly disappeared with antihistaminics and nebulized salbutamol. CONCLUSIONS: In the cases where paradoxical bronchoconstriction and angioedema associated with the use of ipratropium bromide/salbutamol in MDI an immediate hypersentivity reaction to soy was confirmed, which is used as an additive in the MDI, through allergen-specific IgE determination and skin tests.

[Risk factors related to allergic diseases at Mexico City]. / Factores de riesgo relacionados con enfermedades alérgicas en la Ciudad de México.

BACKGROUND: Several studies suggest that the prevalence of allergic diseases has been increasing worldwide in recent years; then it is very important to identify some risk factors that could be related. OBJECTIVE: To know some hereditary and environmental risk factors that could be related to the development of allergic diseases in open population from Mexico City. PATIENTS AND METHOD: It was an open-population, cross-sectional trial, in two phases with a random sample size of 4272 individuals in 214 public health centers. A questionnaire was applied by health workers. Statistical analysis was made with Excel 97-2004 using the Mann-Whitney U test for continuous variables and chi-square-test for discrete variables. p < 0.001 was considered statistically significant. RESULTS: The prevalence of allergic diseases in Mexico City was 42.6%, allergic rhinitis was the most frequent. The most important risk factors for allergic diseases were: family history of atopy in first and second degree; early consumption of cow's milk; early weaning with cereal, egg, beef, fish and pulses; living with some animals, indoor plants, active and passive smoking, to keep stuffed toys in the rooms, as well as living in dwellings with dust, cold temperatures, wall saltpeter and with dampness (mold growth). CONCLUSION: Because genetic factors can not be modified, it is important to identify environmental factors related to the development of allergic diseases in order to promote preventive measures.

[Theophylline, a new look to an old drug]. / Teofilina, una nueva mirada a un medicamento antiguo.

OBJECTIVES: To emphasize the safety and efficacy of theophylline in chronic inflammatory respiratory diseases. To mention its immunomodulatory effects. DATA SOURCES: PubMed search using the keywords: theophylline, histone deacetylase, antiinflammatory, asthma, chronic obstructive pulmonary disease (COPD), corticoresistance. RESULTS: Theophylline is a methylxantine, that inhibits phosphodiesterase (PDE), induces histone deacetylase and antagonizes adenosine. Its main effect is to relax airway smooth muscle. The immunomodulatory effects of theophylline are obtained at low plasma concentrations (less than 10 mg/L). The combination of inhaled corticoesteroids and theophylline exerts a synergistic antiinflammatory effect that improves asthma control and reduces COPD exacerbations. Histones are a group of transcriptional cofactors involved in chromatin remodeling. Histone deacetylases (HDACs) suppress inflammatory gene expression. In patients with COPD and severe asthma there is a reduction in HDAC-2 secondary to the increased oxidative and nitrative stress. HDAC-2 is required by corticosteroids to switch off activated inflammatory genes, then its reduction favors corticosteroid resistance. Theophylline via HDAC-2 induction and PDE inhibition, suppresses inflammatory gene expression, and inhibits free oxygen radicals production. CONCLUSIONS: Theophylline at low plasma concentrations exerts antiinflammatory effects, restoring corticosteroid sensitivity in COPD and severe asthma.