IL-8/IL-17 gene variations and the susceptibility to severe viral bronchiolitis.

Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to severe respiratory failure. The response to respiratory viral infections is possibly influenced by genetic polymorphisms linked to the regulation of the inflammatory response. In the present study, we investigated whether interleukin-8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the severity of AB. A group of Brazilian infants hospitalized with AB and a control group (infants with no or mild AB, without hospitalization) were genotyped for four IL-8/IL-17 variations. For replication, we studied an Argentinean population sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL-17 (rs2275913) variants showed significant associations with the severity of AB. The effect of the IL-8 variation could be replicated in the Argentinean sample. This finding suggests that IL-8 variations may influence the severity of AB in young infants. Further genetic association studies in low- or middle-income populations are necessary with the aim of expanding knowledge in this area.

Diagnosis and management of immunodeficiencies in adults by allergologists.

Primary immunodeficiencies (PIDs) are genetic diseases that cause alterations in the immune response and occur with an increased rate of infection, allergy, autoimmune disorders, and cancer. They affect adults and children, and the diagnostic delay, morbidity, effect on quality of life, and socioeconomic impact are important. Therapy (gamma-globulin substitution in most cases) is highly effective. We examine adult PIDs and their clinical presentation and provide a sequential and directed framework for their diagnosis. Finally, we present a brief review of the most important adult PIDs, common variable immunodeficiency, including diagnosis, pathogenesis, clinical signs, and disease management.

In vitro diagnosis of immediate allergic reactions to drugs: an update.

Evaluation of allergic reactions to drugs is difficult because of the poor sensitivity of in vivo tests, which makes controlled administration of the drug necessary to confirm the diagnosis. In vitro tests are important in order to avoid the risks of in vivo testing. In the present review, we describe the different methods for detecting immunoglobulin (Ig) E antibodies that are specific to drugs involved in the development of type I (immediate) reactions. The 2 main in vitro methods are immunoassays and the basophil activation test, both of which have sufficient sensitivity and specificity for the detection of specific IgE antibodies, although with a limited number of drugs, and they have proven complementary to in vivo methods. We show the importance of the allergological workup of the patient within less than 1 year from the occurrence of the allergic reaction in order to obtain positive results in both in vivo and in vitro tests.

Guidelines on the clinical usefulness of determination of specific immunoglobulin E to foods.

The diagnostic gold standard for food allergy is challenge with the culprit food, particularly in double-blind placebo-controlled challenge. This approach involves risks and consumes both time and resources. A more efficient system would be desirable. The detection of serum specific immunoglobulin E (sIgE) against the culprit food enables us to establish sensitization, although this is not always accompanied by clinical reactivity. Age, symptoms (immediate/late reaction, local/systemic reaction), concomitant condition (eg, atopic dermatitis, pollinosis) and selection sample criteria (eg, presence of symptoms related to ingestion, positive skin prick test result) can influence the detection and concentration of IgE against foods. We analyze the clinical usefulness of sIgE determination in light of studies in which oral food challenge is used as the diagnostic method. We review clinical usefulness at diagnosis and in the decision to reintroduce the food, as well as the prognostic value of the determination of IgE to foods.

Endoscopic, bioptic, and manometric findings in eosinophilic esophagitis before and after steroid therapy: a case series.

BACKGROUND AND AIM: Eosinophilic esophagitis can be associated with a wide range of endoscopic patterns. The aim of the present case series report is to describe and classify endoscopic appearances before and after corticoid therapy in relation to histopathology and manometry. PATIENTS AND METHODS: In 30 patients (m : f, 27 : 3; mean age 36.2 years) with eosinophilic esophagitis, endoscopic findings were prospectively classified according to luminal diameter and mucosal pattern. Manometric and bioptic histopathologic findings were also recorded. Endoscopy was repeated following a 3-month course of steroid therapy. RESULTS: In total, 20 % of patients showed a concentric esophageal stricture, and in 57 % simultaneous contraction rings were visible. Mucosal alterations consisted of granular mucosa (20 %), longitudinal furrows (33 %) and transversal undulations (3 %). Lower esophageal sphincter dysfunction and distal esophageal dysfunctional manometry were seen in 73 % and 57 % of cases, respectively. Following steroids, the esophagus showed a normal caliber in 97 % of patients, and 63 % of patients had normal mucosa. CONCLUSIONS: The most frequent findings were narrowing of the esophageal lumen, which returned to normal following steroid treatment to a larger extent than mucosal alterations.

Associations among pollen sensitizations from different botanical species in patients living in the northern area of Madrid.

OBJECTIVE: To determinate the existence of associations among sensitizations to antigens produced by pollen grains of different botanical species as assessed by skin prick tests in patients with respiratory disorders. METHODS: Six hundred twenty nine consecutive patients living in the northern area of Madrid who underwent clinical evaluation because of rhinoconjunctivitis, and/or asthma were studied. All patients were tested with a skin prick test using a battery of inhalants including pollens, dust mites, molds and danders. The exploratory multivariate technique of Multiple Correspondence Analysis was used to compare the homogeneity of sensitizations between groups. Of the 629 patients, 459 (73.0%) had positive skin prick tests to pollen and were selected as the study group. RESULTS: The most prevalent pollen sensitization was to Gramineae pollen (83.7%) followed by Oleaceae sensitisation (75.8%). Multiple Correspondence Analysis revealed the existence of an association among pollen sensitizations, showing that they clustered two groups: sensitizations to Gramineae, Oleaceae, Cupressaceae, Chenopodiaceae, Plantaginaceae (group I), and sensitizations to Betulaceae, Platanaceae, Compositae (group II). Sensitization to Parietaria was not included in any of the sensitization groups and showed an independent behaviour. CONCLUSION: Pollen sensitizations in our area cluster into two association groups which have not previously been reported.

Mastocitosis sistémica y anafilaxia secundaria a picadura de los himenópteros / Systemic mastocytosis and severe hymenoptera sting anaphylaxis

Introducción: La mastocitosis sistémica comprende varias enfermedades caracterizadas por una proliferación anormal de los mastocitos en diversos tejidos del organismo y una producción excesiva de sus mediadores. La mastocitosis sistémica asociada a la anafilaxia recurrente, con o sin una causa precisa, es una forma relativamente frecuente de la enfermedad y está infradiagnosticada en pacientes con anafilaxia secundaria a la picadura de los himenópteros. La eficacia del tratamiento con inmunoterapia específica hiposensibilizante frente al veneno de himenópteros, y su conveniencia o no en pacientes con mastocitosis sistémica, es un tema discutido que genera controversias. Objetivos: 1) Llamar la atención sobre lo importante que es descartar una mastocitosis sistémica indolente en todo paciente que presenta anafilaxia secundaria a la picadura de los himenópteros. 2) Evaluar la posible repercusión de la mastocitosis sistémica en la eficacia y tolerancia de la inmunoterapia específica con veneno de himenópteros en aquellos pacientes con IgE específica frente al veneno. 3) Revisar los trabajos publicados sobre la mastocitosis sistémica y la anafilaxia tras la picadura de los himenópteros. Material y métodos: Pacientes que acudieron a las consultas externas de alergia para el estudio de una reacción anafiláctica tras una picadura de los himenópteros y en los cuales se sospechó la existencia de una mastocitosis sistémica indolente. Se les realizó una anamnesis y una exploración física detalladas y pruebas cutáneas en intradermorreacción (ID) con extractos comerciales disponibles de veneno de avispa (polistes y véspula) y de abeja además de determinaciones de IgE sérica total, IgE específica frente a veneno de la avispa véspula, la avispa polistes y la abeja, determinación de IgG específica y determinación de triptasa sérica basal. Resultados: Presentamos los casos clínicos de 4 pacientes que acudieron a nuestras consultas tras sufrir cuadro de anafilaxia secundaria a la picadura de los himenópteros. Uno de los pacientes presentó resultados negativos en las pruebas cutáneas con el veneno de los himenópteros y las determinaciones de IgE específica y una cifra baja de IgE sérica total. Las pruebas cutáneas de los otros tres pacientes fueron positivas (de un tamaño moderado) con la máxima concentración, con cifras de IgE total y específica bajas y poco significativas. Dos de los pacientes seguían tratamiento con inmunoterapia específica hiposensibilizante bien tolerada. La elevación de las cifras de triptasa sérica basal nos hizo sospechar la existencia de una mastocitosis sistémica indolente. El diagnóstico se ha confirmado en 2 de los 4 pacientes tras una biopsia medular; los otros dos están en estudio. Conclusiones: En casos de shock anafiláctico secundario a la picadura de los himenóptero, especialmente cuando las pruebas cutáneas sean dudosas o incluso negativas y la IgE específica baja o negativa (o en casos de intolerancia a la inmunoterapia hiposensibilizante) siempre hay que considerar el diagnóstico de mastocitosis sistémica. La determinación basal (fuera del episodio agudo) de triptasa sérica debería realizarse en todos los casos de anafilaxia sea cual sea su causa, y sobre todo en la anafilaxia secundaria a la picadura de los himenópteros

Introduction: Systemic mastocytosis comprises several diseases characterized by an abnormal increased number of mast cells in several tissues and overproduction of mast cells mediators. Systemic mastocytosis associated to recurrent anaphylaxis with or without an specific etiology represents a relatively frequent group of the illness and is overrepresented in patients with Hymenoptera sting anaphylaxis. Efficacy of venom specific immunotherapy, and their therapeutics convenience in patients with systemic mastocitosis, is under discussion and generates controversies. Aims: 1) To draw attention about the importance to rule out an indolent systemic mastocytosis in every patient with anaphylaxis after Hymenotera sting. 2) To assess the possible repercussion of systemic mastocytosis in the venom specific immunotherapy efficacy and tolerance in those patients with positive venom specific IgE 3) To review the reported literature about systemic mastocytosis and Hymenoptera sting anaphylaxis. Material and Methods: Patients who underwent evaluation at our outpatient Allergy consult for study of severe Hymenoptera sting anaphylaxis and in whom an indolent systemic mastocytosis was suspected. A detailed allergic history and physical exploration was recorded. Skin tests (intradermal) were performed with available commercial extracts of wasp (Vespula spp. and Polistes spp.) and bee venom. Measurements of serum total IgE, venom specific IgE and IgG were carried out, and at least, one baseline serum tryptase determination. Results: We report the clinical cases of 4 patients who were studied at our consult after severe Hymenoptera sting anaphylaxis. One of them had negative skin tests to Hymenoptera venoms, with negative venom specific IgE and low serum total IgE. The other three patients had positive skin tests (moderate size) with the maximum venom concentration and low serum total and specific IgE. Two of them were under venom specific immunotherapy with good tolerance. An elevated baseline tryptase level in serum made us to suspect the existence of indolent systemic mastocytosis. Diagnosis was confirmed in two of the patients, after a positive bone marrow biopsy; the other two ones continue under study. Conclusions: In case of anaphylactic shock to Hymenoptera sting, specially when skin tests are doubtful or even negative and specific serum IgE is low or negative (or in cases of intolerance to hyposensitization) the diagnosis of systemic mastocytosis should be always considered. Baseline serum tryptase level determination should be performed routinely in all cases of anaphylaxis whichever the etiology and mainly after anaphylaxis to Hymenoptera sting

Epidemiology of urticaria in Spain.

BACKGROUND: In spite of the frequency of chronic urticaria there are very few epidemiological studies of its prevalence and distribution. OBJECTIVE: We wanted to approach the real prevalence of chronic urticaria in a population-based study and to depict demographic distribution and personal perception of the disease. We also wanted to describe the frequency of acute urticaria episodes in the population studied. METHODS: We conducted a population-based study among adults in Spain. We questioned 5003 individuals after calculating a sample size for a maximum variability (conservative approach p=q=0.5). RESULTS: We found a 0.6% (95% CI: 0.4-0.8) prevalence of chronic urticaria. The prevalence is significantly higher in women than in men with a OR=3.82 (95%CI 1.56-9.37). Chronic urticaria is a self-limited disease, yet in 8.7% of cases chronic urticaria lasts from one to 5 years and in 11.3%, for more than 5 years. The average age of onset is 40 years. CONCLUSIONS: We offer large epidemiology study data on the prevalence of chronic urticaria. The prevalence of chronic urticaria has not yet been defined in an adult population-based study. With this work we offer such data to describe the prevalence and features of this disease.

[Latex allergy]. / Alergia al látex.

Latex allergy has become an increasing cause of morbility in the last few years and is now recognized as an international health problem. The prevalence of latex sensitization among the general population is less than 1 %. The groups at highest risk include healthcare workers, rubber industry workers, patients with a history of multiple surgical procedures, particularly children with spina bifida and urogenital abnormalities, atopic individuals, and patients with certain fruit allergies (especially kiwi, avocado, chestnut and banana). The molecular and immunological characteristics of several natural latex allergens have been identified. Symptoms range from contact urticaria to anaphylaxis. Diagnosis is based on clinical history and is confirmed by skin prick tests. Measurement of serum specific IgE to latex can also be useful. The best treatment is latex avoidance and substitution by other materials. However, because latex products are ubiquitous in medical and nonmedical devices of daily use, a latex-free environment is not easy to achieve. In some patients, immunotherapy could be an alternative.

Optical sectioning by two-pinhole confocal fluorescence microscopy.

A two-pinhole axially superresolving confocal fluorescence imaging system is presented. Based on the concept of subtractive incoherent imaging, the system described here is equipped with a zero-focus complex-transmittance pupil filter in one of the collector paths. The optical sectioning capacity of the system is 25% superior to that of a free-pupil one-pinhole instrument.

Sidelobe decline in single-photon 4Pi microscopy by Toraldo rings.

We demonstrate theoretically the feasibility of single-photon 4Pi-confocal microscopy. By inserting a pair of properly designed multi-ring phase-only pupil filters in the illumination path of a 4Pi microscope the height of the sidelobes of the point spread function substantially reduced, so that there is no ambiguity in the 3D image. Then, an axial resolution up to four times higher than that of single-photon confocal microscope can be effectively achieved.

Focal-shift formula in apodized nontelecentric focusing systems.

A single analytical formulation for evaluating the focal shift in any apodized nontelecentric focusing setup is reported. The formulation is also useful in the case of imaged paraxial beams. We show explicitly that the magnitude of the focal shift is determined by only one parameter that depends on the effective width of the pupil filter and its axial position. To illustrate our approach we examine different focusing setups.

Importance of albumin in cross-reactivity among cat, dog and horse allergens.

Different allergenic proteins have been involved in cross-reactivity among animals. Albumins seem to be cross-sensitizing allergenic components. The aim of this study was to assess the importance of albumin as a cross-reactive allergen in patients sensitized to cat, dog and horse. One hundred and seventeen patients sensitized to cat were tested for IgE reactivity using skin prick tests and RAST assays with cat, dog and horse hair/dander extracts and their purified albumin extracts. RAST-inhibition studies were carried out to assess cross-reactivity among cat, dog and horse and among their purified albumins. It was found that 22% of patients exhibited specific IgE to cat albumin; 41% of patients sensitized to cat were also sensitized to dog and horse. Out of these patients, 21% had IgE to three albumins and 17% to two. Reciprocal inhibitions were observed among cat, dog and horse albumins and also among cat, dog and horse hair/dander extracts, using in the latter experiment sera from patients not sensitized to albumins. IgE binding to horse extract was inhibited 30% by its homologous albumin and IgE binding to cat and dog extracts in almost 15% by their respective albumins. It was concluded that albumins from these three animals share some epitopes that account for the cross-reactivity observed in around one-third of patients sensitized to cat, dog and horse. Nevertheless, more than 50% of specific IgE that cross-reacts among these three animals is directed to allergens other than albumin.

Gastroallergic anisakiasis: findings in 22 patients.

BACKGROUND AND AIMS: Ingestion of Anisakidae larvae in raw seafood may cause anisakiasis. However, despite the high level of consumption of seafood in Spain, only a few cases of anisakiasis have been reported until now. Anisakis simplex can cause allergic reactions in sensitized patients as a result of its parasitism in the gastrointestinal tract. The purpose of this study was to analyse the clinical findings in 22 patients with gastroallergic anisakiasis. METHODS: Patients with allergic and/or gastric symptoms after seafood ingestion were evaluated in the emergency room of the La Paz General University Hospital. Skin testing for Anisakis simplex and tests on the implicated seafood were performed and amounts of serum-specific immunoglobulin E were assessed. A gastroscopy was performed in those patients with severe allergic or/and persistent gastric symptoms after ingestion of raw or undercooked seafood. RESULTS: Twenty-two patients were diagnosed with gastroallergic anisakiasis in 1 year. Most patients presented to the emergency room of our hospital with allergic symptoms. Gastric symptoms were usually moderate. Gastroscopy revealed local mucosal oedema and gastric erosion at the point of fixation. Two or more worms were detected in three patients. The mean time of latency of allergic symptoms was 5 h, while the mean time for gastric symptoms was 3 h. CONCLUSION: Anisakis simplex parasitism was the causative agent of allergic and gastric symptoms. Gastroallergic anisakiasis appears to be a relatively common disease, that may have been underdiagnosed.

[Systemic inflammatory response syndrome: is it comparable with severe sepsis?]. / Síndrome de respuesta inflamatoria sistémica severa: es comparable a la sepsis severa?

BACKGROUND: In 1992, a consensus conference defined the terms systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock. Since then, numerous reports have validated the prognostic usefulness of these operative definitions. AIM: To evaluate if sepsis severity criteria, as defined by the Consensus Conference, can be applied to noninfectious SIRS. PATIENTS AND METHODS: Five hundred eighteen patients admitted to 5 intensive care units (ICU) from 4 hospitals were prospectively evaluated during a 3 months period. Patients that met at least one severity criteria were included. SIRS etiology, organ dysfunction and evolution were recorded in each patient. RESULTS: One hundred two patients were included: 79 with sepsis (group I) and 23 with noninfectious SIRS (group II). ICU and hospital mortality were comparable (43 and 48% in sepsis compared to 43 and 51% in non infectious SIRS). The most common sources of sepsis were pneumonia and peritonitis. Group II patients had a wide variety of diseases. ICU stay, APACHE score and number of organs with dysfunction were not different among groups. Only the incidence of renal dysfunction was higher in the septic group. CONCLUSIONS: The Consensus sepsis severity criteria can be applied to noninfectious SIRS, defining a population subset with similar high mortality and organ dysfunction incidence, although with greatly heterogeneous etiologies.

Delayed hypersensitivity to enoxaparin.

A 65-year-old woman experienced immediate itchy erythematous patches at the subcutaneous injection sites of sodium enoxaparin. An erythematous and infiltrated 40 x 20 mm lesion on the abdominal wall could be observed at the site of enoxaparin injection when she was referred to our clinic 48 h after injection. Lesions subsided spontaneously within 1 week. She had been on this treatment 1 and 3 years before without any adverse reaction. To clarify the nature of the reaction, epicutaneous tests with sodium enoxaparin, calcium nadroparin and calcium heparin were performed, all with negative results. Skin prick test with sodium enoxaparin was also negative. Biopsy of the cutaneous lesion showed spongiotic dermatitis, strongly suggesting a delayed hypersensitivity mechanism. We report here on a new case of delayed hypersensitivity to enoxaparin. Being female, overweight and having prolonged application of the drug were suggested risk factors present in our patient. Biopsy was essential for diagnosis. Although type IV hypersensitivity reactions to enoxaparin are rare, we should start to suspect this condition in order not to underdiagnose it.

Allergic reactions to anisakis simplex parasitizing seafood.

BACKGROUND: The ingestion of Anisakidae ssp larvae parasitized fish can cause anisakiasis. Allergic reactions after ingestion of safely cooked but parasitized fish have been reported. METHODS: Twenty-three patients who suffered allergic reactions after seafood ingestion, with negative skin tests were studied. Anisakis simplex sensitization was assessed by skin prick test and/or specific serum Immunoglobulin E (IgE). Total serum IgE and specific IgE against the implicated seafood and Ascaris lumbricoides were also determined. RESULTS: Manifestations of Anisakis simplex allergy were urticaria/angioedema (18/23) patients and anaphylaxis (5/23). Gastric symptoms were also observed (3/23). Sea fish and shellfish were implicated. Raw and cooked seafood ingestion caused reactions. Total serum IgE ranged from 13 to 7200 KU/L. Specific IgE to Anisakis simplex was positive (> 0.35 KU/L) in all patients, and skin tests were positive in 20. Serum-specific IgE and skin tests to the involved seafoods were negative in every patient. Serum-specific IgE to Ascaris lumbricoides was negative in 13 patients. No association between total IgE and the eosinophil count (r < 0.1) was observed, but there was some association between total IgE and specific IgE to Anisakis simplex (r = 0.58). CONCLUSION: Anisakis simplex sensitization is the cause of allergic reactions after seafood ingestion. It is important to pay attention to this new "food allergy" to diagnose correctly the etiology of adverse food reactions.

Booster responses in the study of allergic reactions to beta-lactam antibiotics.

The observation of negative skin and challenge tests to beta-lactams in some patients with prior histories of reactions to these antibiotics led us to develop a protocol ("booster study") which systematically included the performance of skin and challenge tests to beta-lactams ten to thirty days after the study to confirm the negative results. From a total of 430 patients who came to our outpatient clinic because of a reaction to a beta-lactam or unknown antibiotic, 249 completed the study. Out of the patients who completed the second phase, or "booster study," the results were positive in the first phase, or conventional study in 42 patients, and negative in 207. The booster study was negative in 197 patients (95 percent) and positive in ten patients (5 percent). Skin tests were positive in 5 of them (penicilloyl-polylysine: 5; benzylpenicillin: 3; amoxicillin: 2; minor determinant mixture: 1), and 5 patients developed an allergic reaction after rechallenge (benzylpenicillin: 4; amoxicillin: 1). One patient with both negative skin tests and amoxicillin oral challenge in the booster study developed an immediate generalized urticaria with the oral intake of amoxicillin one month later at home; skin tests became positive at that moment. The negative results in the first phase of the study and the development of positive results in the second phase could be due to the existence of an immunological amnestic reaction or to sensitization after reexposure to beta-lactams in the diagnostic procedures.

[Private habits and public interest. Breast-feeding in popular medical literature, Barcelona 1880-1890]. / Costumbres privadas e interés público. La lactancia materna en la literatura médica de divulgación. Barcelona, 1880-1890.

From the latter decades of the 19th century onward, the style of life of the lower classes was threatened by increasing standardization that bourgeois culture introduced in industrial societies. One way in which the patterns of private and public behavior were influenced was by the transmission of new values through different communication channels availabale at that time. Feeding and hygiene became fundamental subjects in a pattern od cultural change that was favored by politicians and supported by influential institutions and social groups, which moreover played the role of mediator in class conflicts. Breast-feeding was one of the main subjects of popular hygiene and health literature at the end of the century, and represented an attempt not only to palliate infant mortality, but to mold women's behavior and consolidate a certain type of family within a context that required stability, thrift, and work to cope with the dangers of poverty and the rootlessness that were faced by the masses of workers arriving in the industrialized city.