Guía Argentina de urticaria y angioedema

Se actualiza el diagnóstico de la urticaria crónica (UC) y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas), y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE) o inducible (UCI). El diagnóstico es sencillo, pero incluye un minucioso estudio para descartar diagnósticos diferenciales; para UCI son útiles las pruebas de provocación en la caracterización y manejo. Los estudios complementarios se deben limitar y orientar según sospecha clínica. El tratamiento se divide en tres enfoques: evitación, eliminación o tratamiento del estímulo desencadenante o de la causa, y tratamiento farmacológico. Recientemente éste se modificó, con empleo de antihistamínicos de segunda generación como primera línea y aumento de dosis de antihistamínicos H1 no sedantes, hasta 4 veces, como segunda línea. Los antihistamínicos son fundamentales para tratar la UC; sin embargo, un 40% de los pacientes no logra un buen control pese al aumento de dosis y requiere otro medicamento adicional. La evidencia más reciente considera que un grupo de fármacos puede utilizarse como tercera línea en estos casos, para mejorar la calidad de vida y limitar la toxicidad por el uso frecuente o crónico de esteroides sistémicos. Se recomiendan para esta tercera línea solo 3 fármacos: omalizumab, ciclosporina A o antileucotrienos.

This interdisciplinary paper summarizes the news in the diagnosis and treatment of chronic urticaria (CU), and provides concepts, definitions and evidence-based suggestions for its management. Urticaria occurs in at least 20% of the population at some point in their lives. Acute urticaria (less than 6 weeks' duration), differs from CU in its etiology, but the onset of this disease is always acute. CU may occur as spontaneous (SCU) or induced (ICU). The diagnosis is simple, although a careful evaluation is necessary for differential diagnosis. ICU´s diagnosis is mainly clinical, even if provocation tests can be useful. Supplementary studies should be limited and based on the clinical suspicion. Treatment may be divided into three approaches: avoidance, elimination or treatment of the cause, and pharmacological treatment. Recently treatment has been modified with the use of second-generation antihistamines as first-line and increased doses of nonsedating H1 antihistamines, up to 4 times, as second line. Antihistamines are essential to treat CU; however, 40% of patients do not achieve good control despite increased doses and require additional treatment. The most recent evidence indicates a group of drugs to be used as third line in these cases, to improve quality of life and to limit toxicity from frequent or chronic use of systemic steroids. Only 3 drugs are recommended as third line: omalizumab, cyclosporin A or anti-leukotrienes.

Eosinophilic Esophagitis: Update 2012 / 대한소화기학회지

Eosinophilic esophagitis (EoE) with adults, as a new disease emerging during the last decade, is a clinicopathologic disorder of the esophagus characterized by a dense esophageal eosinophilic infiltration and typical esophageal symptoms. As numerous studies about EoE had been reported during last several years, updated consensus of EoE was reported in July 2011. The conceptual definition of EoE is coming. EoE is defined as a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominat inflammation. Other important addition is genotyping feature that implicates thymic stromal lymphopoietin genes or filagrrin as EoE susceptibility genes. The majority of patients has the concurrent allergic disease, especially food or aeroallergen sensitization. Main therapeutic options include topical steroids and dietary modification. Recent issues of EoE include a new concept for proton pump inhibitor-responsive esophageal eosinophilia that it should be excluded to diagnose EoE.

A Case of Occupational Rhinitis Caused by Porcine Pancreatic Extract Developing into Occupational Asthma

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

Present study on the forensic medicine diagnosis of the sudden erethistic death / 法医学杂志

The death caused of anaphylactic shock is common in clinical medicine and medicolegal expertise, but it is a nodus to diagnose sudden death from allergy. In recent years, to provide objective and precise morphological evidence and index of diagnosis for sudden death from allergy, scholars of internal and overseas studied the content of IgE, HT, mast cell tryptase and SP in the serum of the death died of anaphylactic shock, and their immune express in lung and stomach intestine. In this text we reviewed the present study and existing problems of the forensic medicine diagnosis of the sudden erethistic death.

IgE expression on the surface of B1 and B2 lymphocytes in experimental murine schistosomiasis

In a previous study we monitored the distribution and phenotype expression of B1 cells during the evolution of experimental murine schistosomiasis mansoni and we proposed that the B1 cells were heterogeneous: a fraction which originated in the spleen and followed the migratory pathway to mesenteric ganglia, while the other was the resident peritoneal B1-cell pool. In the present study, we have addressed the question of whether these two B1-lymphocyte populations are involved in the production of the late Ig isotype IgE, which is present in high levels in schistosomal infection. Lymphocyte expression of surface markers and immunoglobulins were monitored by immunofluorescence flow cytometry. Both in the spleen and mesenteric ganglia, the B1 and B2 cells were induced to switch from IgM to IgE in the early Th2-dominated phase of the disease, with an increase of IgE in its later phases. Conversely, peritoneal B1-IgM+ switched to the remaining IgE+ present in high numbers in the peritoneal cavity throughout the disease. We correlated the efficient induction of the expression of late Ig isotypes by B1 cells with high levels of inflammatory cytokines due to the intense host response to the presence of worms and their eggs in the abdominal cavity. In conclusion, B1 cells have a different switch behavior from IgM to IgE indicating that these cell sub-populations depend on the microenvironment.

Modulation of tryptase and histamine release from human lung mast cells by protease inhibitors.

Inhibition of IgE dependent histamine release from human mast cells by protease inhibitors has been observed in skin, tonsil and synovial tissues. However, little is known about the actions of protease inhibitors on tryptase release from human lung mast cells. We therefore examined the ability of protease inhibitors to modulate tryptase and histamine release from human lung mast cells. IgE dependent tryptase release from dispersed lung mast cells was inhibited to a maximum of approximately 53.8% and 44.5% by N-a-tosyl-L-lysine chloromethyl ketone (TLCK) and N-p-Tosyl-L-phenylalanine chloromethyl ketone (TPCK), respectively. A similar degree of inhibition of calcium ionophore A23187 (CI) induced tryptase release was also observed with these two inhibitors. Preincubation of TLCK or TPCK with the mast cells at 37 degrees C for 20 minutes before addition of anti-IgE or CI did not improve their ability to inhibit anti-IgE and CI induced tryptase release. At a concentration of 10 microg/ml, protamine inhibited anti-IgE or CI induced tryptase release; but at 100 microg/ml, it increased anti-IgE and CI induced release of tryptase from lung mast cells. A concentration dependent inhibition of anti-IgE and CI induced release of histamine from lung mast cells was also observed with TLCK, TPCK and protamine. The maximum inhibition of anti-IgE induced histamine release was approximately 40.7%, 40.2% and 33.4% with TLCK, TPCK and protamine, respectively. At the concentrations tested, TLCK and TPCK by themselves did not stimulate tryptase and histamine release from lung mast cells. A specific inhibitor of aminopeptidase, amastatin, had no effect on anti-IgE induced tryptase and histamine release and was used as control. In conclusion, it was demonstrated that protease inhibitors are able to inhibit IgE dependent tryptase and histamine release from human lung mast cells, which suggested that they could be developed to a novel class of anti-inflammatory drugs to treat allergic conditions in man.

Ovalbumin fused with diphtheria toxin protects mice from ovalbumin induced anaphylactic shock

For those with allergy, vaccination with a specific allergen has often been used as a major therapeutic measure. However, the universal application of this technique in clinics have been restricted due to its low success rates and the risk of active systemic anaphylactic shock (ASAS). In this regard, we constructed a fusion protein (OVA-DT), ovalbumin (OVA) fused with diphtheria toxin protein (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE. Its therapeutic effect was evaluated in mice (BALB/c) sensitized with OVA (Os-mice). OVA challenges to the OVA-sensitized mice (Os-mice) caused ASAS to death within 30 min, but OVA-DT treatment afforded mice complete protection. When OVA-DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged 48 h after the treatment. OVA-DT itself was not found to be toxic or allergenic in normal mice. The effect of OVA-DT on the biological functions of mast cells was also studied. Binding of OVA-DT to OVA-specific IgE bearing mast cells and the inhibition of histamine release from these cells were observed. In addition, OVA-DT treatment inhibited the proliferation of OVA-specific B cells in mice. In Os-mice treated with OVA-DT, levels of anti-OVA IgG2a in serum and the production of IFN-gamma by splenic lymphocytes were found to increase, but the production of IL-4 by these cells decreased. Re-direction of cytokine profiles from OVA-specific Th2 to OVA-specific Thl is suggested. These results indicate that OVA-DT can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA-specific IgE-expressing cells, including mast cells and B cells.

Detection of specific IgE antibodies in parasite diseases

Activation of Th1 or Th2 cells is associated with production of specific immunoglobulin isotypes, offering the opportunity to use antibody measurement for evaluation of T cell function. Schistosomiasis and visceral leishmaniasis are diseases associated with Th2 activation. However, an IgE response is not always detected in these patients. In the present study we evaluated specific IgE antibodies to S. mansoni and L. chagasi antigens by ELISA after depletion of serum IgG with protein G immobilized on Sepharose beads or RF-absorbent (purified sheep IgG antibodies anti-human IgG). In schistosomiasis patients, specific IgE to SWAP antigen was demonstrable in only 10 of 21 patients (48 percent) (mean absorbance + or - SD = 0.102 + or - 0.195) when unabsorbed serum was used. Depletion of IgG with protein G increased the number of specific IgE-positive tests to 13 (62 percent) and the use of RF-absorbent increased the number of positive results to 20 (95 percent) (mean absorbances + or - SD = 0.303 + or - 0.455 and 0.374 + or - 0.477, respectively). Specific IgE anti-L. chagasi antibodies were not detected in unabsorbed serum from visceral leishmaniasis patients. When IgG was depleted with protein G, IgE antibodies were detected in only 3 (11 percent) of 27 patients, and the use of RF-absorbent permitted the detection of this isotype in all 27 visceral leishmaniasis sera tested (mean absorbance + or - SD = 0.104 + or - 0.03). These data show that the presence of IgG antibodies may prevent the detection of a specific IgE response in these parasite diseases. RF-absorbent, a reagent that blocks IgG-binding sites and also removes rheumatoid factor, was more efficient than protein G for the demonstration of specific IgE antibodies

IgE binding patterns to German cockroach whole body extract in Korean atopic asthmatic children

It is widely known that the cockroach is an inhalant allergen in atopic asthma and allergic rhinitis. Even though Bla g I and Bla g II are considered as the major allergens, several relatively high-molecular weight (MW) cockroach allergens have also been recently identified by IgE-immunoblot in western countries. However, the environmental control and diagnostic tests mainly focussed on Bla g I and Bla g II. Furthermore there is no data about major IgE-binding cockroach antigens in Korea. We performed this study to identify the major German cockroach allergens in Korean atopic children. By the results of allergy skin tests, 14 children with atopic asthma (9 were cockroach-sensitive and 5 were cockroach-nonsensitive atopics) were enrolled in this study. We conducted IgE immunoblot and autoradiographic analysis using Yonsei-extract of German cockroach antigen produced in our laboratory, individual sera from 9 cockroach- sensitive children, and the pooled sera of 5 house-dust-mites-only-sensitive children. We performed an allergic skin test to cockroach mix, and a radioallergosorbent test (RAST) using German cockroach crude extract on all subjects. German cockroach-specific IgE was detected in 6 out of 9 subjects by RAST. We identified at least 15 IgE-binding protein bands, and among them, the components of MWs of 76, 64, 50, 38, and <14 kilodaltons (kDa) were the major German cockroach allergens in study subjects. Therefore, Bla g I (25-30 kDa) and Bla g II (36 kDa) could not be the absolute indicators of German cockroach sensitization and parameters of environmental control.

Effects of autologous sera on immediate and late skin reaction to the house dust mite in atopic individuals

To evaluate the in vivo effect of autologous serum including antibodies to house dust mite in atopic individuals, we observed the immediate (15 mins) and late (6 hours) skin reactions (ISR, LSR) on intradermal (ID) test of serially diluted Dermatophagoides farinae antigens (DFa, Allergopharma, Germany) mixed with autologous sera (DFa-S) and diluent alone (DFa-D). We tested 34 DFa-skin reactive atopic individuals including 12 asthmatics (BA), 8 asthmatics on immunotherapy with DFa (IT), and 14 healthy atopic controls (AC). We observed complete inhibition of ISR in the lowest allergen dose of DFa-S in 7 (58.3%) of 12 BA, 3 (37.5%) of 8 IT, and 2 (14.3%) of 14 AC. In BA, the inhibition of ISR was more frequent than AC (p or = 1.5 X size; accentuation of LSR). Accentuation of LSR were shown more frequently by DFa mixed with larger amount of serum (25% in 1:1 mix; 80% in 1:3 mix, p< 0.05). But there were no differences of DFa-specific IgE and IgG subclass antibodies regardless of the inhibition of ISR or the accentuation of LSR. In conclusion, some autologous sera from DFa-sensitive individuals showed the inhibition of ISR and the accentuation of LSR on DFa-ID test.

Immunoelectron-microscopic localization of IgE binding site of mugwort pollen

To elucidate the IgE binding site of mugwort (Artemisia vulgaris r.) pollen, pollen grains were frozen and fixed using a cryocut. They were incubated with antibodies according to the following sequence: Sera pool of individuals who showed mugwort-RAST class 3 or 4, biotin-labeled goat anti-human IgE antibody, streptavidin-peroxidase and diaminobenzidine. Then, they were observed under electron microscopy. The control section was incubated with the sera pool from individuals who showed a negative result on a skin prick test to mugwort pollen. Antigenic activity (electrondense line) was noted on the surface of the exine. There was no activity in cytoplasm or the intine layer. The control section was completely free of activity. It was suggested that the IgE binding site of mugwort pollen was present on the surface of the exine.

Identification of major allergens from the house dust mites, Dermatophagoides farinae and Dermatophagoides pteronyssinus, by electroblotting

The allergens were separated from the extracts of house dust mites by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and identified by autoradiography. Over 30 protein bands of the whole body extract of Dermatophagoides farinae were apparent on 10-20% gradient SDS-PAGE, and 13 bands with MW between 93KD and 12KD bound with specific IgE antibodies in patients' sera sensitive to house dust mites. The major allergenic component of the whole body extract of D. farinae was the protein of MW 14-15KD, which was detected in 95.7% of 47 patients' sera sensitive to house dust mites. The extract of Dermatophagoides pteronyssinus supplied by Bencard Company, England was thought to contain feces enriched material as noted in a few broad protein bands on SDS-PAGE. Seven allergenic components were shown by autoradiography. The protein band of MW 14-15KD was one of the most frequently revealed allergens on autoradiography, which has appeared in 32.5% of 40 patients' sera sensitive to house dust mites. The electrobotting technique used in the present study was fast, convenient and highly useful for both the identification of allergen components and the screening of specific IgE antibody. The individual variations of IgE immune responses to the allergenic components of the two house dust mites were discussed.

The significance of specific IgE and IgG to dermatophagoides farinae according to the types of asthmatic reaction in house dust asthmatics

To investigate the role of specific IgE and IgG in the various types of asthmatic reaction, we measured specific IgE and IgG levels to Dermatophagoides farinae (D.farinae) using the D. farinae-radioallergosorbent test (RAST) and Phadebas IgG-RAST in 39 house dust asthmatics (11 early responders, 21 dual responders and 7 isolated late responders) and 12 negative responders on house dust bronchoprovocation. There were significant differences in the D. farinae-specific IgE level and skin reactivity to D. farinae and house dust among the 4 groups (p less than 0.05) and the specific IgE level of dual asthmatic responders was the highest and was significantly higher than that of early responders (p less than 0.05). The specific IgG level showed no differences among the 4 groups. These results suggested that the types of asthmatic reaction in house dust asthmatics were closely related to specific IgE level to D. farinae and the specific IgG level seemed not to be related to an isolated late response.

Effect of praziquantel treatment on antibody levels and lymphoproliferative responses in patients with opisthorchiasis.

The purpose of this study was to explore alternative method(s) to monitor the efficacy of anthelmintic treatment of patients with opisthorchiasis. Therefore, in our initial attempt, we studied the changes in antibody levels and lymphoproliferative responses in O. viverrini infected patients before and 2 months after successful praziquantel treatment. The results showed that although a substantial reduction of the antibody levels occurred after such a treatment, it did not occur in all patients. In those showing reduction, the final level were still above 2 standard deviations of the normal mean value. The reduction was more profound for IgG antibody. With regard to the IgA antibody isotype, the reduction was not as marked. In contrast, IgE antibody levels in most patients not only failed to decline, but instead, showed a tendency to be elevated after praziquantel treatment. Unlike the antibody levels, there was no alteration in the lymphoproliferative response to PHA stimulation and therefore this parameter is not useful for our intended objective. It was suggested that studies of a more specific O. viverrini component may be more reliable than the current method of parasitological examination of eggs in the feces of suspected individuals.

Immunological defects in allergic asthmatic children and working mechanisms of hyposensitization--a review.

Patients with allergic diseases are characterized by the presence of elevated serum IgE and specific IgE antibodies against a variety of environmental allergens, especially house dust, mites and molds in Taiwan. A series of studies on allergic asthmatic children have been conducted to explore the non-immunological and immunological causes for their augmented production of IgE antibody and to explore the working mechanisms of hyposensitization. The results showed that the patients had multiple defects in their defects in their defense mechanisms, including hyper-permeability of mucosae, hyperreactivity of target organs, defective phagocyte functions, and deficient helper and suppressor T-cell functions. Hyposensitization was able to partially correct the immunological aberrations. More over, a newly found lymphokine termed "T-cell growth factor" or "interleukin 2" may be used not only as an indicator for the initiation and termination of hyposensitization, but may also provide a promising tool for the treatment of allergic diseases in the future because of its capability of enhancing and expanding allergen-specific suppressor T cells.