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Sensitivity to nonsteroidal anti-inflammatory drugs.
BACKGROUND: Aspirin can provoke reactions ranging from respiratory to cutaneous in susceptible individuals. There has been particular attention looking at the role of cyclo-oxygenase enzymes 1 and 2 and their role in aspirin-exacerbated respiratory disease. OBJECTIVE: Patients who present with a spectrum of allergic and pseudoallergic reactions to aspirin pose a special challenge for the physician. This article discusses proposed classification system, clinical manifestations, pathogenesis of disease, and current treatment options of aspirin-related disease. DATA SOURCES: Relevant articles in the medical literature were derived from searching the MEDLINE database with key terms aspirin-sensitive asthma, cyclo-oxygenase enzymes 1 and 2. Sources also include review articles, randomized control trials, and standard textbooks of allergy and immunology. RESULTS: Aspirin-exacerbated respiratory disease remains a complex, heterogenous disease with varied clinical presentations. There have been many advances in trying to elucidate the pathogenesis of this disease. The classification system presented will provide greater ease when reading the literature and communicating with one another. Oral aspirin challenge remains the diagnostic test of choice for both respiratory and cutaneous reactions. Aspirin desensitization is an option for those with refractory respiratory disease or who require aspirin for other medical conditions. CONCLUSIONS: This review discusses the challenges in classification, diagnosis, and treatment of those patients with a sensitivity to aspirin. Special attention is made to the possible mechanisms mediating disease progression and how specific therapies, such as leukotriene modifiers, may be helpful.
Enzyme potentiated hyposensitization: IV. effect of protamine on the immunological behavior of beta glucuronidase in mice and patients with hay fever.
The ability of beta glucuronidase and a small dose of antigen to modify the anaphylactic reaction of previously sensitized mice has been further investigated. Protamine has an important effect on the immunological behavior of the enzyme. A trial on hay fever patients shows that the results in mice are relevant and that the method can produce significant clinical hyposensitization.
[A bronchial allergy to vine pollen and 2 precipitin lung diseases. Various approaches to etiological diagnosis].
Three observations are adduced to illustrate the relative importance of clinical and immunologic data and the patient's history in the diagnosis of allergic lung disorders. A case of sensitization to vineyard pollen has been identified by intradermal test and the effect of specific hyposensitization.
[Systemic therapy of atopic dermatitis].
The optimal treatment of atopic dermatitis requires regular medical supervision. The course of this chronic skin disease is influenced by multiple triggers which are relevant for the treatment. The mainstays of topical therapy include regular use of emollients coupled with antimicrobial substances, corticosteroids and immune modulators as required. Ultraviolet radiation and immunosuppressive regimens represent further options for the treatment of severe exacerbations and may lead to long term improvement. Data from experimental studies provide insight into possible future treatment methods.
PULMONARY EMPHYSEMA.
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[The immunological background of the allergen vaccines application].
The review and critical estimation of the studies concerning the mechanism of action of SIT was performed. The presented data give the reasons to view the allergen vaccines as the immunomodulators motivating simultaneously the applicability of these agents as the causative treatment of the allergic diseases.
Sublingual immunotherapy for allergic rhinoconjunctivitis--the seeming and the real.
BACKGROUND: Subcutaneous specific immunotherapy (SIT) has been shown to be a causal treatment with long-term efficacy for allergic rhinoconjunctivitis and asthma, and a preventive measure against the development of asthma and new sensitizations. As it is associated with several inconveniences and serious side effects, sublingual immunotherapy (SLIT) has been developed to evade these problems. METHODS: The present review of previously published studies on allergic rhinoconjunctivitis aimed to determine the efficacy of SLIT in comparison with subcutaneous treatment and to summarize long-term results of immunotherapy and its effects on the prevention and treatment of asthma and the prevention of new sensitizations. RESULTS: The effect of SLIT on allergic rhinoconjunctivitis is low to moderate, depends on the allergen used and is more pronounced in adults than in children, in whom a consistent effect has not been demonstrated. Direct comparison with SIT shows conflicting and inconsistent results. Detailed studies on the prevention of asthma and new sensitizations are not available. Consistent effects of asthma treatment on both symptom and medication scores and lung function have not been reported. A quantitative evaluation is not possible due to indistinct inclusion criteria and different outcome criteria. In summary, currently SLIT plays no significant role in the treatment of asthma, apart from children monosensitized to house dust mites in whom it may have low-moderate effects. Only one study deals with the long-term efficacy of SLIT, which demonstrated a persistent positive effect on asthma, whereas data on rhinoconjunctivitis are completely lacking. CONCLUSIONS: Primary and secondary targets of specific immunotherapy have not been answered satisfactorily for the sublingual route. To date, SLIT cannot be recommended as an adequate alternative to the subcutaneous form. Questions regarding the cumulative dose, duration of therapy and immunological mechanisms have also not been answered. The indication should thus be limited to adult patients with pollen-induced rhinoconjunctivitis being unable to perform SIT, e.g. due to significant side effects.
Cellular immunity and immunostimulation in paracoccidioidomycosis.
We have evaluated clinical and laboratorial effects of immunostimulation scarification with antigen of Paracoccidioides brasiliensis in patients with paracoccidioidomycosis, who often show depressed immunity. We have studied 62 Brazilian patients with paracoccidioidomycosis, 46 with active disease and 16 cured, in a 10-year period between 1982 and 1992. Among the 46 patients with active disease: 10 had acute form, 12 chronic unifocal form and 24 the chronic multifocal form of the disease; 16 showed positive paracoccidioidin intradermal reaction and 30 negative reaction. Amongst 16 cured patients, 5 showed negative paracoccidioidin intradermal reaction and 11 positive reaction. We immunostimulated 20 patients by scarification with polysaccharide antigen of Paracoccidioides brasiliensis. All 20 immunostimulated patients had negative paracoccidioidin intradermal reaction, and 18 patients had active disease and 2 were cured. Out of 18 immunostimulated patients with active disease, 3 had active form, 10 chronic multifocal form and 5 chronic unifocal form of the disease. Before and after immunostimulation, each patients was inmunologically evaluated by in vivo and in vitro methods; in vivo methods consisted of intradermal reactions and DNCB sensitization tests; and in vitro methods consisted of total sub-set lymphocyte counting, leukocytes migration inhibition test, chemotaxix of total leukocytes and monuclear leukocyte phagocytosis. Remaining 42 patients served as a non-immunostimulated control group who has followed only clinically. We have observed significant clinical and immunological improvement in immunostimulated patients. We conclude that the immunostimulation by scarification with antigen of P. brasiliensis can be a helpful adjuvant therapy for paracoccidioidomycosis.
Sensitization and elicitation of inflammation in contact dermatitis.
The problem of contact allergic dermatitis in humans and contact hypersensitivity in animals begins with the observation that certain reactive compounds when placed on skin lead to the development of a reproducible and characteristic inflammatory reaction. The immunologic processes which conspire to produce this damaging tissue reaction are derived from the normal immunologic balance between a protection of self and a destruction of nonself. Experimental work in the last decade has focused on the role of antigen-presenting cells, and specifically Langerhans cells, in the initiation of contact hypersensitivity as well as on the competing roles of subsets of T lymphocytes in its regulation. For humans, an important goal has been the development of techniques by which tolerization and desensitization may be achieved, and for those who work with laboratory animals CH has provided methods to examine immune regulation in general. In the coming decade, we anticipate that new techniques from molecular biology, molecular genetics, tissue culture, and, above all, shrewd clinical observation will provide a new array of ideas and possibilities.
INCIDENCE OF REACTIONS FOLLOWING ADMINISTRATION OF ANTIRABIES SERUM; STUDY OF 526 CASES.
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[Allergen specific-IgG4 in circulating immune complexes in patients with inhalant allergy undergoing specific immunotherapy].
The mechanism of action of specific immunotherapy (SIT) is still not definitely clear. The problem of the presence of allergen specific-IgG4 in circulating immune complexes (CIC) of patients with inhalant allergy is being discussed. The aim of the study was to determine the allergen specific-IgG4 serum levels and concentration in CIC in patients with inhalant allergy who underwent specific immunotherapy with relevance to its clinical benefits. The trial was carried out on 57 patients with seasonal allergic rhinitis (SAR) and 55 with perennial allergic rhinitis (PAR). Each of them underwent 3-year specific immunotherapy with Allergovit (Nexter-Allergopharma) or Novo Helisen Depot (Nexter-Allergopharma). 56 patients with pharmacologically treated allergic rhinitis served as a control group. Serum levels of allergen specific-IgG4 (as-IgG4), IgE, as-IgE and as-IgG4 concentration in CIC were measured in each patient and correlated with the clinical score of the disease activity. Nonparametric tests (the U Mann-Whitney test, Kruskall-Wallis test and Spearman's correlation rang test) were used. Serum levels of as-IgG4 and bound in CIC were statistically higher in the SIT group than in the control group and differed significantly between SAR and PAR groups. Immunotherapy caused significantly higher concentrations of as-IgG4 in CIC in PAR group than in SAR patients. No significant associations were found between studied immunological indices and clinical effects of SIT. Specific immunotherapy of allergic rhinitis is connected with the increase of as-IgG4 serum level and its concentration in circulating immune complexes.
The role of catecholamines in specific hyposensitization.
With the use of modern techniques for the evaluation of catecholamines, this work studies the behavior of catecholamines in the urine of a group of 33 allergic patients before and after injection of allergens as part of immunotherapy. In 24 of these patients the amount of adrenalin and norepinephrine had increased 24 hours after the injection of the allergens (p less than 0.001). This confirms the noradrenergic role of the allergen, apart from the release of histamine as a result of the immunologic mechanism. Histamine is released as a result of the increase of the norepinephrine and is evidence of a homeostatic mechanism, as had been established in a previous investigation by the authors.
Diagnosis and immunotherapy of mould allergy. VII. IgG subclass response and relation to the clinical efficacy of immunotherapy with Cladosporium.
The IgG subclass response was evaluated by a sensitive allergen- and subclass-specific solid phase immunoradiometric assay during a 1-year placebo-controlled, double-blind study of immunotherapy with Cladosporium herbarum in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG2 and IgG3 responders. An intense and early IgG1 response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom-medication score was significantly correlated to the preseasonal IgG1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG1 and IgG4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome. Little or no increase of IgG1 and IgG4 was associated with improvement, i.e. decrease in symptom-medication score. The magnitude of the IgG1 response during the dose-increase phase was directly correlated to the number of systemic side effects. No relation of IgG1, IgG4 or IgG4/IgG1 ratio to changes in the IgE-mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects.
Specific IgE, IgG and IgG4 antibodies against house dust mite in patients with bronchial asthma.
Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001) and adults (r = 0.629, p less than 0.01). However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.
[Current aspects of hyposensitization].
Hyposensitation (HS) or immunotherapy has long been used to block the allergic response to inhaled allergens. Double-blind studies with a placebo arm have established the effectiveness of HS, especially in allergic rhinitis. The aim of HS is to achieve a better tolerance after exposure to inhaled allergens by subcutaneous injections of the relevant allergen extract in repeated doses of increasing concentrations. Although the clinical efficacy is obvious, the pathogenesis of HS is not yet fully understood. The HS must be used strictly in accordance with the guidelines of the European Academy of Allergology and Clinical Immunology (EAACI) with respect to therapeutic effect, side-effects, and cost for doctor and patient. The indications, relative and absolute contraindications, guidelines for the HS and the therapeutic monitoring of the patients during HS are outlined. In addition to the correct therapeutic regimen, a critical criterion is the quality and standardization of the allergen extracts. The recommendations of the International Union of Immunological Societies (IUIS) should be respected. Semi-depot extracts are preferred nowadays. The side-effects consist of local reactions, general reactions with urticaria, asthma, and even anaphylactic shock. The immediate therapy, precautions and drugs necessary to treat this life-threatening event are described.
Characterization of the early phase of the tuberculin reaction in rabbits.
The dermal response to purified protein derivative (PPD) in rabbits sensitized with Mycobacterium bovis strain Bacille Calmette Guèrin (BCG) is composed of at least two distinct phases. The early phase occurs within 24 h after injection of tuberculin and is characterized by accumulation of polymorphonuclear leukocytes. The second phase is delayed in onset, depending on mononuclear cell accumulation, and constitutes the classic delayed hypersensitivity reaction. The early component of the reaction of PPD is not immunologically specific, in that it can be elicited in either BCG-sensitized or nonsensitized rabbits and appears to be induced by pyrogenic components present in tuberculin preparations. Rabbit fever index assays indicated the presence of sufficient pyrogen in tuberculin PPD to account for the observed reactions; however, Limulus amebocyte pyrogen assays were negative. These findings suggest that tuberculin contains pyrogenic components other than endotoxin. Radiometric assays for mononuclear cell accumulation as well as desensitization experiments indicated that the early phase was independent of the delayed mononuclear phase.
One year observation of immunotherapy for Artemisia hay fever in China: a clinical and immunological study.
A controlled trial of one year immunotherapy was conducted in 50 Artemisia-sensitive hay fever patients (treatment group). From October 1985 to July 1986, all of the treatment group patients received one year regular injection of Artemisia pollen allergen extract totalling 30,000 protein nitrogen units (PNU). For these patients, symptom score indices of the posttreatment 1986 pollination season were compared with those from the pretreatment 1985 season and also with the scores of a similar group of 30 Artemisia-sensitive patients treated only with symptomatic medications during the 1986 season (control group). The 1986 symptom scores to the treatment group were significantly improved and the effective rate was 78%. Immunological study with the Human Basophil Degranulation Test (HBDT) showed a significant decrease in degranulation reactions after immunotherapy. Moreover, The decline of the HBDT positive rate in the treatment group was significantly greater in patients with improved symptoms than patients with unchanged symptoms. No difference was observed in basophil degranulation in those patients tested with a pollen-free plant extract, which was not applied in immunotherapy. The results suggested that immunotherapy could induce desensitization of basophils and that the induction might be allergen specific. Basophil desensitization may play an important role in the mechanism of immunotherapy.