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[Allergic contact dermatitis: how to re-induce tolerance?].

Allergic contact dermatitis (ACD) is a skin inflammatory disease mediated by activation of CD8+ cytotoxic T cells specific for haptens in contact with the skin. CD4+ T cells behave as both regulatory and tolerogenic cells since they down-regulate the skin inflammation in patients with ACD (regulation) and prevent the development of eczema (tolerance) in normal individuals. Thus, ACD corresponds to a breakdown of immune tolerance to haptens in contact with the skin. Several regulatory CD4+ T cell subsets (Treg), especially CD4+CD25+ natural Treg cells, are involved in immunological tolerance and regulation to haptens through the production of the immunosuppressive cytokines IL-10 and TGF-beta. Ongoing strategies to re-induce immune tolerance to haptens in patients with eczema include improvement of existing methods of tolerance induction (oral tolerance, low dose tolerance, allergen-specific immunotherapy, UV-induced tolerance) as well as development of new drugs able to activate IL-10 producing Treg cells in vivo. Ongoing and future progress in this area will open up new avenues for treatment of eczema and more generally autoimmune and allergic diseases resulting from a breakdown of tolerance to autoantigens and allergens, respectively.

Allergens↗

Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. III. Effect on mite-specific immunological parameters and correlation to changes in mite-sensitivity and symptoms.

Forty-six adult asthmatics allergic to D. pteronyssinus (Dp) participated in a 2-year study. Thirty-one underwent hyposensitization (HS-group). Fifteen were treated with Dp-extract (Dp-group), and 16 with a similar extract modified by monomethoxypolyethylene glycol with reduced allergenicity (mPEG-Dp-group). Fifteen patients served as controls. Dp-specific antibodies and histamine release from blood basophils were determined and compared with Dp-sensitivity in lungs and skin. In addition, IgG and IgE against the major allergen Der p I were followed in a subgroup. Dp-specific IgG, IgG1, and IgG4 increased significantly in both HS-treated groups after 1 and 2 years (median: 2.5- to 11.6-fold). IgG4 was not induced if maintenance dose during the first year was less than 20,000 BU. Median skin sensitivity decreased 4.4- to 8.2-fold after 1 year and 7.4- to 21.4-fold after 2 years. Der p I specific IgG response was unrelated to the occurrence or change in IgE with the same specificity. The mPEG-Dp-extract tended to have less effect on skin sensitivity and immunological parameters, differences reaching statistical significance for skin sensitivity only. In the HS-group, the decrease in bronchial sensitivity was significantly correlated to a decrease in IgE (r = 0.36), IgG1/IgG4 (r = 0.49), Dp-specific histamine release (r = 0.58), and to an increase in Dp-specific IgG4 (r = -0.36) and IgG4/IgE (r = -0.48). In patients improving clinically, Dp-specific IgG4/IgE increased, and median Dp-specific IgE was reduced to 80% compared with an increase to 150-160% seen in the unchanged or deteriorated group (P less than 0.05). Findings indicate an improvement of effect, if the allergen dose is sufficient to reduce specific IgE and/or induce an IgG and especially IgG4 response.

Adult↗

The cross-reactivity and immunology of beta-lactam antibiotics.

Allergic reactions to beta-lactam antibiotics are well described; however, only the immunochemistry of penicillin has been characterised. Although the major determinant of benzylpenicillin (penicillin G) is commercially licensed for diagnostic applications, minor determinants are only available at some centres to be used for identification of hypersensitive individuals. Cephalosporins share a common bicyclic nuclear structure with penicillin and most cross-reactivity is generated to the beta-lactam ring. It is not possible to determine the actual incidence of cross-reactivity between penicillins and cephalosporins, but evidence suggests the true rate is lower than usually appreciated. In vitro testing demonstrates extensive cross-reactivity between penicillin and the carbapenems. Although the rate of clinical cross-reactivity is not known, imipenem should not be given to patients with proven penicillin hypersensitivity. In contrast, aztreonam and the monobactams can be safely given to penicillin-allergic patients.

Anti-Bacterial Agents↗

Immunological changes associated with a successful outcome of pollen immunotherapy.

Changes in immunological measurements thought to be important in the mechanism of immunotherapy for hay fever were related to objective measurements of treatment outcome. Antigen-specific IgE and IgG, and T suppressor cell status, using monoclonal antibodies and a specific functional assay, were measured before and after immunotherapy. Treatment outcome was assessed using nasal and conjunctival challenge tests. Seventeen subjects received immunotherapy for 6 months. Nine showed a decrease in nasal and/or conjunctival sensitivity, compared with 2 of 13 control subjects (P less than 0.05). Subjects responding to immunotherapy had a significantly higher post treatment IgE level and a higher pre- and post-treatment IgG level than non-responders and controls. Immunotherapy had no effect on suppressor cell status.

Adolescent↗

Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper.

The World Health Organization and various allergy, asthma, and immunology societies throughout the world met on January 27 through 29, 1997, in Geneva, Switzerland to write guidelines for allergen immunotherapy. Over the ensuing year, the editors and panel members reached a consensus about the information to include in the WHO position paper "Allergen immunotherapy: Therapeutic vaccines for allergic diseases." The historical term allergen extract was changed to allergen vaccine to reflect the fact that allergen vaccines are used in medicine as immune modifiers. The document summarizes the scientific literature and rationale for the appropriate use of such therapy to treat allergic rhinoconjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. It also includes recommendations to improve safety, discusses new techniques being developed that may result in better efficacy and less risk, and offers recommendations for areas of additional and necessary research.

Allergens↗

[Failure of allergen-based immunotherapy in adults with allergic asthma].

BACKGROUND: The allergic asthma is the reversible chronic inflammatory process at the airways, secondary to exaggerate reply to the allergens exposition, its treatment includes: avoiding the exposure to allergens, pharmacology therapy and the specific immunotherapy with allergens (ITA), which is based on the growing dosages of the extract allergenic; the objectives are to modify the immune response and to improve the allergic disease. The ITA can fail due to causes attributable to the patient, vaccine-inherent causes and/or factors related to the allergic disease. OBJECTIVE: To determine the main causes of specific immunotherapy with allergens' failure in our hospital. MATERIAL AND METHODS: In the present study 126 records of patients with allergic asthma treated in the extern consultation service of the clinical immunology and allergy department of the CMN 20 de Noviembre, ISSSTE, were reviewed from January 1996 to December 2001. RESULTS: It was found that specific immunotherapy with allergens, failed in 32 (23%) patients. Main causes of failure were: 1) withdrawal in the vaccine application in 19 (59%) patients; 2) high serum levels of IgE. The co-morbidities that contribute to poor responses to the treatment were: obesity, gastroesofageal reflux and chronic rhynosinusitis. CONCLUSIONS: Specific immunotherapy with allergens is an alternative method of allergic asthma's treatment which has been approved by national and international medical consensus. Main causes of failure in our hospital are the abandon of treatment and high serum levels of IgE, as well as the existence of other conditions.

Adult↗

Immunotherapy with partially purified and standardized tree pollen extracts. II. Results of skin prick tests and nasal provocation tests from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Patients allergic to tree pollen entered a 3-year course of immunotherapy (1980-83) with either birch pollen extracts alone (n = 26) or patient-tailored extracts of birch, alder and hazel pollen (n = 27). The clinical and immunological results of this study are published elsewhere. This paper contains an evaluation of skin prick test and nasal provocation test results. There were no significant differences between the two treatment groups concerning these two parameters. In both groups the allergen-specific sensitivity in the skin showed seasonal variations but a significant decrease. During the years of treatment there was also a significant decrease in the specific sensitivity of the nasal mucosa. With the present demands for purification and standardization of allergen extracts it is of practical and economic interest to know that tree pollen-allergic patients showing positive reactions to birch, alder and hazel extracts can be effectively treated using birch pollen extract alone.

Asthma↗

Immunological mechanisms of specific immunotherapy with pollen vaccines: implications for diagnostics and the development of improved vaccination strategies.

This review deals with specific immunotherapy performed with pollen vaccines. Pollen allergens, the immunological mechanism of allergic inflammation and the mechanisms behind successful specific immunotherapy treatment of seasonal pollen allergy shall be discussed. The different approaches to develop improved regimes for specific immunotherapy based on new diagnostic tools, improved pollen vaccines and alternative routes for administration of the vaccines will be highlighted. Diagnostic tools to select patients for specific immunotherapy and for monitoring the treatment are quantitative measurements of allergen-specific immunoglobulin E, G and G4 antibodies and component-resolved diagnostics based on immunoglobulin E binding to individual allergenic components. Future pollen vaccines may consist of hypoallergenic recombinant allergens and T-helper cell type 1-inducing immunostimulatory adjuvants. Both sublingual and nasal administration of pollen vaccines for specific immunotherapy may be used more in future.

Administration, Intranasal↗

[Allergens].

The clinical signs linked with immediate hypersensitivity, correspond with an abnormal reactivity of the immune system, which appears following contact with external substances, the allergens. Over the last few years there has been considerable progress in research on these substances in the domain of structural characterisation, biochemistry and immunological properties. Besides the definition of the word allergen linked to its immunological characteristics, our usual language maintains a certain ambiguity in its use which may characterise different states, including successive steps of the manufacture of an allergen extract. In effect the word allergen may designate the agent that is responsible for the allergic disease, for example cat, but also the raw material used for the manufacture of the corresponding extract, whether it be hair or squames; it may also apply to the final allergenic extract, the extract of cat hair or squames, as well as a precise molecule such as the major allergen of cat Fel d1 in the same example. After having reviewed several definitions as well as the nomenclature we will study the general characteristics of pneumoallergens and trophallergens, those of recombinant allergens, then the parameters of manufacture of allergen extracts.

Allergens↗

Advances in upper airway diseases and allergen immunotherapy.

Evidence of an increased prevalence of rhinitis in patients with asthma, and asthma in patients with rhinitis, supports the 1 airway concept. However, there are basic differences between the upper and lower airways, such as the virtual absence of remodeling in the nose compared with the bronchi, despite the presence of similar inflammation. Etiologic factors in chronic rhinosinusitis (CRS) attract increasing interest. Peripheral blood monocytes from patients with CRS release IL-4, IL-13, and IFN-gamma on stimulation with fungal antigens, especially those from Alternaria. This is not seen with cells from normal controls. However, a double-blind trial of intranasal amphotericin in CRS was negative. Evidence continues to accumulate of the pivotal role of regulatory T-lymphocytes secretion of IL-10 in the response to allergen immunotherapy. In patients with asthma and house dust mite allergy who are receiving appropriate pharmacotherapy and have instituted environmental controls, house dust mite immunotherapy provides marginal additional benefits in asthma control. Immunotherapy with cat dander extract at a maintenance dose containing 15 microg Fel d 1 produces a more consistent immunologic response than with maintenance doses containing 3.0 microg, whereas doses containing only 0.6 microg are no more effective than placebo. Sublingual immunotherapy for seasonal grass allergy can be safely administered by general practitioners, but symptom relief begins only in the second season of therapy. Sublingual immunotherapy for seasonal grass allergy in children reduced symptoms and onset of new asthma symptoms but, again, beginning only in the second year of treatment. A course of 6 weekly injections of ragweed Amb a 1 bound to cytosine phosphorothionate guanosine containing DNA produced a shift from T H 2 to T H 1 cytokine release both in peripheral blood cells and in the nose after allergen challenge. No symptom improvement was seen the first year, but symptoms were reduced the second year without further treatment.

Allergens↗

Sublingual specific immunotherapy reduces PBMC proliferations.

BACKGROUND: Subcutaneous specific immunotherapy has been demonstrated capable of inducing T regulatory response. There is few evidence concerning immunological changes induced by sublingual immunotherapy. OBJECTIVE: The aim of this study was to evaluate T cell proliferation in subjects successfully treated with SLIT for HDM. METHODS: PBMCs were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic and healthy control subjects. After 3 and 6 days of in vitro stimulation with PHA, Candida albicans, Dermatophagoides farinae, grasses, Parietaria judaica, and cat, proliferation. RESULTS: Subjects treated with SLIT showed significant reduction of proliferation induced by Candida albicans, Parietaria, and grasses in comparison with untreated atopics (p=0.0002, 0.0033, and 0.009 respectively). CONCLUSION: This pilot study confirms reduced T cell proliferation in allergic subjects treated with SLIT.

Administration, Sublingual↗

Immunotherapy with alginate-conjugated two grass pollen extract in patients with allergic rhinoconjunctivitis.

The aim of the present study was to evaluate the clinical and immunological effects of specific immunotherapy with alginate-conjugated two grass pollen extract in patients with rhinoconjunctivitis. A total of 52 patients were admitted to the study. Before and after 3 years of immunotherapy quantitative skin test (QST) to Dactylis glomerata (Dg) and to Phleum pratense (Php), variation of grass specific IgE and IgG4 and nasal challenge with the aqueous extract of the two grasses were compared. Each patient kept a daily record of symptoms and medication required during pollen season. In all patients a significant decrease in QST and a significant increase in grass specific IgG4 was observed. In 47 patients a significant decrease in nasal symptom scores and drug consumption was observed. In 5 patients no significant decrease in nasal symptom scores was observed.

Alginates↗

Main mechanisms of therapeutic action in atopic asthma in children.

Immunological disorders are clearly demonstrated in children suffering from the atopic form of bronchial asthma, namely increase in the levels of total and specific IgE and a decrease in the number of T cells. Specific hyposensitization produces, in addition to a good clinical effect, an immunomodulating action which is not restricted to the formation of blocking antibodies but is displayed also by T cell stimulation. Our studies revealed a reduction in the level of prostaglandins E and increase in the content of prostaglandins F-2 as well as a decrease in the cAMP levels in blood serum and urine in the period free of attacks; the demonstrated effect of Euphylline, Intal and Zaditen on these values confirms the expediency of introducing these agents into the therapeutic complex.

Aminophylline↗

Injection immunotherapy. British Society for Allergy and Clinical Immunology Working Party.

A working party of the British Society for Allergy and Clinical Immunology has reviewed the role of specific allergen immunotherapy in the treatment of allergic disease and produced a position statement summarising the available evidence for efficacy and safety. The working party recommends specific allergen immunotherapy for treating summer hay fever uncontrolled by conventional medication and for wasp and bee venom hypersensitivity. It is not recommended for asthma or for allergic rhinitis due to other allergens. For the recommended indications the risk:benefit ratio is acceptable provided patients are carefully selected; in particular, patients with asthma should be excluded as they are especially vulnerable to adverse reactions. Injections should be given only by doctors experiences in this form of treatment in a clinic where full resuscitative facilities are immediately available. Provided patients remain symptom free a 60 minute observation period after injection is sufficient to detect all serious adverse reactions.

Asthma↗

Immunotherapy with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ): immunologic and clinical results of a prospective study over 3 years.

This prospective study over 3 years investigated the safety, immunogenicity, and effectiveness of immunotherapy (IT) with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ, ALK Laboratories) in patients with previous, severe, systemic, IgE-mediated, anaphylactic reactions to Hymenoptera stings. Seventeen patients were treated with honeybee venom (BV), 13 with yellow-jacket venom (YJV), and 5 with both. No severe reactions to IT were noted. Only 3 BV-allergic patients experienced mild systemic reactions of grades I or II (1 per 139 injections) during the increase phase. As for the immunologic data, there was a significant decrease in specific IgE antibodies after 1 year, and a significant increase in specific IgG and IgG4 antibodies on reaching the maintenance dose, with a further rise after 1, 2, and 3 years. Moreover, a significant decrease in anti-IgE autoantibodies was observed in the BV group. Out of the 11 patients that were occasionally restung by the relevant insect (totaling 19 stings in all), only one patient developed mild systemic allergic symptoms after a third sting. In view of these results, we consider IT with aluminum hydroxide adsorbed insect venom extracts to be safe, immunogenic, and effective. The low rate of side-effects may be due to the slow release of the venom in the aluminum hydroxide adsorbed form.

Adolescent↗

[Efficacy of specific immunotherapy in children with seasonal allergic rhinitis and conjunctivitis, sensitized to grass pollen].

The aim of this study was the evaluation of efficacy of the specific immunotherapy using Pollinex for 3 years before the period of pollen dust in children with seasonal allergic rhinitis and conjunctivitis induced by grass pollen. The study was carried out in a group of 40 children aged 5-18 years, from the Outpatient Department of Immunology at the National Research Institute of Mother and Child. The children demonstrated clinical symptoms of seasonal allergic rhinitis with conjunctivitis and had a medical history typical for this disease. Diagnostic procedures including skin prick tests and estimation of specific IgE to grass pollen by Pharmacia - CAP system, gave positive results. The efficacy of therapy was monitored by a clinical score with 4-0 points, recording symptoms relating to intensity of rhinoedema, rhinorrhea, sneezing, itching, oedema, conjunctival congestion, pain and lacrimation. In the study group, 39 children (97%) with seasonal rhinitis and conjunctivitis treated by specific immunotherapy (Pollinex) improved. This was confirmed by a statistically significant difference. The results indicate that the specific immunotherapy is an effective treatment of seasonal allergic rhinitis with conjunctivitis in children sensitized to grass pollen.

Adolescent↗

Nasal immunotherapy to Parietaria: evidence of reduction of local allergic inflammation.

Studies over 10 yr have demonstrated local nasal immunotherapy (LNIT) to be an effective treatment for rhinitis due to pollens and mites. The aim of our work was to investigate the effects of LNIT on the local inflammatory phenomena, employing the model of nasal allergenic challenge, since no evidence has been yet provided about LNIT effects on the events due to allergic reactions. We evaluated, in addition, the possible effects of LNIT on some systemic immunologic parameters and its clinical efficacy. The study involved a double-blind, placebo-controlled trial of preseasonal immunotherapy with Parietaria in 20 adults. A significant reduction of symptoms, inflammatory infiltration, and intercellular adhesion molecule-1 (ICAM-1) expression on epithelial cells after nasal challenge was evidence as long-lasting effect. No changes in serum allergen-specific IgE, IgG, and soluble eosinophil cationic protein were detected, whereas an unexpected increase of soluble ICAM-1 was found in the placebo group only. The treatment was well tolerated and a significant clinical improvement under natural allergenic exposure was observed in the active group. The present study provides, for the first time, evidence that LNIT is able to modulate the nasal allergic inflammation.

Administration, Intranasal↗

[Efficacy of specific immunotherapy in children with bronchial asthma, sensitised to dermatophagoides pteronyssinus].

The aim of study was the evaluation of efficacy of specific immunotherapy using Alavac S HDM for 2-4 years in children with atopic bronchial asthma induced by Deramtophagoides pteronyssinus. The study was carried out in a group of 33 children aged 5-18 years, from the Outpatient Department of Immunology at the National Research Institute of Mother and Child. The children demonstrated clinical symptoms of asthma and had a medical history typical for this disease. Diagnostic procedures including skin prick tests and estimation of specific IgE to Dermatophagoides pteronyssinus by Pharmacia-CAP system gave positive results. The efficacy of therapy was monitored by a clinical score of symptoms with 0-10-20-30 points, recording symptoms relating to intensity of dyspneaa, wheezing, cough, value of PEF and concomitant medications for example corticoids and beta-antagonists. In the study group, 31 children (94%) with asthma treated by specific immunotherapy (AlavacS HDM) improved. This was confirmed by a statistically significant difference. The results indicate that specific immunotherapy is effective in the treatment of asthma in children sesitized to Dermatophagoides pteronyssinus.

Adolescent↗