[Risks of hyposensitization].
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Desensitization, Immunologic↗
Biomedical subjects
H J Malling
Publications and source records attributed to H J Malling.
Diagnosis and immunotherapy of mould allergy. III. Diagnosis of Cladosporium allergy by means of symptom score, bronchial provocation test, skin prick test, RAST, CRIE and histamine release.
Thirty-three adult asthmatic patients suspected of mould allergy were investigated by in vivo and in vitro tests in order to establish a specific diagnosis of asthma caused by the mould species Cladosporium. The patients were evaluated by daily symptom scores in the peak Cladosporium season, bronchial provocation test (BPT), skin prick test (SPT), RAST, histamine release from basophil granulocytes (HIST), and crossed radioimmunoelectrophoresis (CRIE), and the results were scored as negative (score 0), equivocal (score 1) or positive (score 2). Based on daily symptom scores and the result of BPT the patients were classified as being manifest allergic (asthma) to Cladosporium (positive allergy), inconclusive or negative. Positive allergy was defined as asthma symptoms oscillating with the spore concentration and a BPT score 2 (positive at allergen concentration less than 10,000 BU). Negative allergy was defined as no asthma symptoms and a negative BPT (score 0) and inconclusive in the case of symptoms and BPT sum of score 1-3. According to the classification a final diagnosis (positive or negative) could be established in 85% of the patients. "False positive" tests were found: for BPT in 27%, SPT 18%, RAST 0%, HIST 18%, and CRIE 0%. The corresponding figures for "false negative" were: BPT 0%, SPT 0%, RAST 27%, HIST 18%, and CRIE 23%. The relative risk of being allergic in spite of a negative test result was 0% for BPT and SPT, and 25-30% with RAST, HIST, and CRIE. In the case of positive test the risk was 90-100%. Excluding BPT, SPT was found to be the optimal single test to predict/rule out clinical allergy. A stepwise combination of positive SPT and positive RAST was found exclusively in patients clinically evaluated as positive, and does not call for an additional BPT. Using a potent allergenic extract a negative SPT excluded clinically important allergy. The primary conclusion of the study, however, is that the final diagnosis of Cladosporium asthma could not be based on a positive BPT alone (due to "false positive"), but only on a combination of clinical symptoms during the spore season and a positive BPT.
Adult↗
A preliminary study of immunotherapy with a monomethoxy polyethylene glycol modified honey bee venom preparation.
Monomethoxy polyethylene glycol (mPEG) modified honey bee venom (HBV) immunotherapy (IT) has been studied in 14 patients allergic to honey bee venom. Doses could be increased more rapidly and higher doses were reached compared to regular venom immunotherapy. No general side effects were seen, although large local swellings were found somewhat more often than with regular HBV. Most patients could easily be switched from the modified to the unmodified venom. Eight patients experienced and tolerated field stings. Skin testing showed a decreased allergenicity of the mPEG-HBV. The mean HBV-specific IgE level was below pre-treatment level already after only 6 weeks of IT. The HBV-specific IgG response was very good.
Adult↗
IgG and IgE antibody patterns after immunotherapy with monomethoxy polyethyleneglycol modified honey bee venom.
Antibody responses to honey bee venom (HBV) were studied in 13 patients during a 4-month course of immunotherapy with monomethoxy polyethyleneglycol (mPEG) modified venom. There was a rise of HBV-specific IgG antibodies as measured by IgG-RAST in all patients and a slight decrease of IgE antibody in most of them. The IgG-antibody responses during mPEG-HBV treatment as examined by crossed radioimmunoelectrophoresis were directed to phospholipase A, hyaluronidase, acid phosphatase and to another allergen, antigen 1. Thus, despite a high degree of mPEG-modification of HBV, the immunogenicity of the most important HBV allergens was retained.
Adult↗
Immunotherapy with yellow jacket venom. A comparative study including three different extracts, one adsorbed to aluminium hydroxide and two unmodified.
Thirty-two patients with previous systemic allergic reaction to yellow jacket stings were randomly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom: 1) extract adsorbed to aluminium hydroxide (Alutard-SQ), 2) Pharmalgen extract or 3) non-adsorbed extract from Allergologisk Laboratorium (ALK aq.). Regular examinations showed a decrease in skin prick test size in nearly all patients. Specific IgE-antibody (RAST and CRIE scores) showed a similar, but not significant tendency to decrease in all three groups. Specific IgG-antibody increased considerably in the Alutard group only; after 2 years, however, no difference could be detected between the three groups. During dose increase, patients treated with ALK aq. generally had smaller local reactions to injections than those treated with Pharmalgen. Few systemic reactions occurred in all three groups. Nineteen patients treated for 2 1/2-3 1/2 years were challenged in-hospital with stings from yellow jackets. No systemic and only minor local reactions occurred. Consequently, with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated.
Adult↗
Diagnosis and immunotherapy of mould allergy. IV. Relation between asthma symptoms, spore counts and diagnostic tests.
Twenty-four adult asthmatics with autumnal asthma and positive bronchial provocation test to the mould species Cladosporium were evaluated by daily symptoms scores during 11 weeks in the peak mould spore season. A significant association with fluctuation in Cladosporium spore count was found regarding the relative weekly symptom score (mean of subjective asthma and peak flow scores), relative use of antiasthmatic medication and the combined (total) score (mean of symptom and medication scores). The median weekly symptom, medication, and total scores were positively correlated to Cladosporium spore count, but only significantly so in the medication score. Eighteen patients were allergic to both Cladosporium and Alternaria, but asthma symptoms were not associated to Alternaria spore counts; on the contrary, a negative correlation indicated that Alternaria only played a minor role in eliciting asthma. Neither mugwort nor house dust mites seemed to be of importance. The results of diagnostic tests (bronchial provocation test, quantitative skin prick test, RAST and histamine release) were correlated to the mean absolute symptom score of the spore season. The highest correlation to asthma score, peak flow score, medication score, and the combined score was found with the bronchial provocation test. The data indicate that autumnal asthma, to a high degree, is elicited by Cladosporium spores, and further, that the specific allergic diagnosis can only be established by a combination of positive diagnostic tests and careful recording of symptoms elicited by the causative allergen.
Adolescent↗
Diagnosis and immunotherapy of mould allergy. V. Clinical efficacy and side effects of immunotherapy with Cladosporium herbarum.
A placebo-controlled, double-blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics. The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season. An aqueous preparation of a potent, biologically standardized and purified extract was used in a clustered dose-increase regimen. The clinical efficacy was evaluated by a combination of symptoms (asthma score + peak flow) and consumption of antiasthmatic medication. The mean changes in symptoms and medication consumption over a 10-week registration period (peak Cladosporium season) in 1982 after 5-7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10-week period. A significant (P = 0.03) difference in terms of "improved", "unchanged" and "deteriorated" patients in favour of Cladosporium treatment was found. Approximately 80% in the Cladosporium group showed improved/unchanged symptoms contrary to 30% of the placebo treated. Side effects were observed frequently but only in the Cladosporium-treated. About 70% experienced a large local reaction and 100% had episodes of asthma during dose-increase phase. Only a few severe systemic reactions occurred. Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics.
Adolescent↗
The IgE and IgG subclass antibody response in patients allergic to yellow jacket venom undergoing different regimens of venom immunotherapy.
We developed a three-layer immunoradiometric assay for quantitation of IgG antibodies of all four subclasses to YJV. We studied the IgE and IgG subclass antibody response to YJV in 31 patients allergic to YJV who were undergoing three different kinds of venom immunotherapy. Group A received weekly single injections with alum-adsorbed venom, group B received weekly clustered injections with aqueous venom, and group C received fortnightly clustered injections with aqueous venom during the increasing dose phase of our study. All patients received alum-adsorbed venom during maintenance therapy. Results from the first 6 months of observation are reported. After 6 months of therapy the IgE antibody level rose significantly in group A, was unchanged in group B, and tended to fall in group C. The fall in IgE antibody level in group C correlated significantly to the pretreatment IgE antibody level. The IgG subclass antibody assays measured IgG antibodies of different subclasses in comparable units. No IgG2 or IgG3 antibodies to YJV were found. Before the start of immunotherapy, 23 patients had significant concentrations of IgG1 antibodies to YJV, and 14 had significant concentrations of IgG4 antibodies. In group A the IgG1 antibody level rose significantly after 6 months, and the IgG4 antibody level rose significantly after 3 months. In group B the IgG1 antibody level rose after 2 weeks and the IgG4 antibody level rose after 3 weeks. In group C the IgG1 antibody level rose after 2 weeks and the IgG4 antibody concentration rose after 8 weeks. When the maintenance dose was reached, the IgG1 antibody level in group C was significantly higher than that in group A. The possibility that IgG1 antibodies formed during venom immunotherapy take part in a feedback inhibition of the IgE antibody production is discussed.
Adult↗
Clinical and immunological aspects of a case of monoclonal hyper-IgE. Isolation of IgE-protein, estimation of basophil cell bound IgE and histamine release.
A case of monoclonal IgE type lambda with IgE levels about 1 mg/ml has been followed for 6 years. Except for a slight asthma no signs of malignancies, parasitic infestations or other known diseases compatible with hyper-IgE have been found. By the combination of fractional ammonium sulphate precipitation, gel filtration, chromatofocusing, and subtraction affinity chromatography the IgE protein was isolated in an immunochemically pure and homogeneous form. Immunofluorescence of bone marrow cells showed about 1% IgE plasma cells. The amount of basophil bound IgE was 42 ng/10(6) cells, and histamine release from basophils challenged with anti-IgE was not different from that in atopic control persons, indicating a within-allergic-patients normal amount of IgE receptors. The protein-A reactivity was 0.4% equivalent to well-known IgE myeloma proteins. No antigen specificity of the IgE protein was found. Only a few cases of asymptomatic hyper-IgE are known, and it cannot be ruled out that this represents a premyeloma condition, since a similar case terminated in a malignant lymphoma.
Aged↗
Reproducibility of histamine skin prick test. Inter- and intravariation using histamine dihydrochloride 1, 5, and 10 mg/ml.
The reproducibility of skin prick test using histamine dihydrochloride 1, 5, and 10 mg/ml was tested by three nurses in five non-atopics in a double-blind trial. The variations day-to-day, within-day, between and for the same tester were calculated. Seventy-five percent of wheal reactions obtained by histamine 1 mg/ml were less than 15 mm2. With histamine 5 mg/ml there were only a few wheals less than 15 mm2 and none at all with histamine 10 mg/ml. The mean coefficient of variation of wheals greater than 15 mm2 was between 20-30%, in contrast to figures between 30-60% with wheals less than 15 mm2. No significant day-to-day or within-day variation was shown concerning histamine wheal areas. It is suggested that histamine dihydrochloride 10 mg/ml should replace histamine dihydrochloride 1 mg/ml as the positive reference in routine skin prick tests and biological standardization.
Adult↗
Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test.
To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Clustered immunotherapy with Yellow Jacket venom. Evaluation of the influence of time interval on in vivo and in vitro parameters.
To evaluate difference in clinical efficacy, side effects, in vivo and in vitro parameters, 25 patients allergic to Yellow Jacket were treated with clustered immunotherapy using either 7 or 14 days interval between clusters. Twenty-one patients completed the 6 months' treatment period and four were withdrawn due to adverse reactions (2 cases of anaphylactic shock). Sixteen patients were challenged by in-hospital sting and the clinical efficacy was complete. Local side effects were observed in the majority of patients, but only rarely limited the course of immunotherapy. Skin sensitivity estimated as the venom concentration eliciting a wheal equal to histamine HCl 0.1 mg/ml using intradermal test was significantly reduced after 6 months of treatment. Specific IgE showed an initial increase, thereafter declining to pretreatment levels. IgG subclasses were determined by a triple antibody assay. Only subclasses 1 and 4 showed response. Subclass 4 showed a steady increase contrary to subclass 1 which decreased after reaching maintenance dose. No unambiguous relation between either the absolute value or the change of IgG1 and IgG4 at the time of challenge was observed in the patients who tolerated a sting. Furthermore, the IgG response was not correlated to the cumulative dose of venom administered. No simple regulatory function of IgG subclasses in the skin and IgE response was found, and the occurrence of local side effects did not seem to be determined by IgG antibodies. We conclude that clustered immunotherapy with Yellow Jacket venom is highly effective and that the frequency of side effects is acceptable.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Serum aluminium in hyposensitized allergics.
The concentration of serum aluminium was examined in hyposensitized subjects receiving subcutaneous injections of solutions of allergens precipitated with or adsorbed to aluminiumhydroxide and in non-hyposensitized allergics. No correspondence between the serum values and the quantity of aluminium mediated with the injections was found. It was concluded that the investigation did not incriminate this type of treatment in causing rising serum concentrations of aluminium.
Adolescent↗
HEP versus PNU standardization of allergen extracts in skin prick testing. A comparative randomized in vivo study.
During 1 year, all patients referred to an allergy outpatient clinic for adults were skin prick tested with a panel of standard allergen extracts from two manufacturers using different methods of standardization. One company referred to the histamine equivalent prick (HEP) and the other used the more traditional protein nitrogen units (PNU). Standard extracts and five-fold dilution were tested. The results indicate that the ratio of concentration between two extracts of the same allergen should be measured by the absolute difference of the wheal diameters. We found significant differences between corresponding extracts from the two manufacturers.
Adult↗
Diagnosis and immunotherapy of mould allergy. I. Screening for mould allergy.
In order to screen for mould allergy, extracts of five common atmospheric moulds (Cladosporium, Alternaria, Penicillium, Aspergillus and Mucor) from various manufacturers were investigated in 130 patients (5-60 years old) with clinical symptoms indicating possible mould allergy. The patients were screened by skin prick test (SPT) and radioallergosorbent test (RAST). SPT seemed to be more sensitive than RAST as a diagnostic screening procedure (80% positive reactions to one or more species compared to 50%). With a partially purified, standardized preparation of Cladosporium herbarum more positive reactions were obtained than with crude extracts without evidence of any unspecific reactions. The difference between commercial and standardized extracts is most probably a result of a variation of both the biological potency of allergenic determinants and the allergenic composition. A considerable number of negative RAST reactions with standard discs were found in patients with positive skin reactions to partially purified Cladosporium, but RAST seemed to be more sensitive than SPT with the other commercial mould extracts. Based on the screening, a very convincing tendency to IgE-reactivity to other moulds was found in patients reacting to Cladosporium, the most common cause of mould allergy. The results confirm the inadequacy of most mould extracts used in diagnostic procedures and strengthen the value of using standardized extracts.
Adolescent↗
Reproducibility of skin sensitivity using a quantitative skin prick test.
The reproducibility of repeated quantitative skin prick test titrations was evaluated in seven asthmatic patients tested 2-4 times within 6 weeks. The skin sensitivity was estimated as endpoint titration and histamine equivalent reaction using both 1 and 10 mg/ml histamine dihydrochloride. The histamine equivalent reaction had a significantly higher reproducibility compared to endpoint titration, with a coefficient of variation less than 10% for histamine 10 mg/ml. Further, using this histamine concentration, the deviation in repeated testing was for practical purposes less than 0.5 log step. The same constancy in skin sensitivity was found in one patient tested 3 times and then retested another 3 times 6 months later by a different tester. The results indicate that the quantitative skin prick test and histamine-estimated skin sensitivity have a clinical application in the assessment of pharmacologically or immunotherapy-induced changes in the releasability of skin mast cells.
Adult↗
Skin prick testing and the use of histamine references.
The skin prick test is a fundamental test in biological allergen standardization and in evaluation of changes in skin sensitivity due to treatment. The allergen concentration eliciting a wheal equal to that produced by histamine 1 mg/ml is generally accepted as the skin sensitivity. Using a standardized quantitative skin prick test, 25 mould allergic patients were tested with quadruplicate determinations of five 10-fold allergen concentrations of highly purified and standardized extracts. Histamine 1 and 10 mg/ml were used as positive references. The 10-fold increase of histamine resulted in a doubling of the histamine reaction and increased the mean wheal diameter from 4 to 7 mm. The correlation between skin sensitivity estimated by histamine 1 and 10 mg/ml is significant, but with a dissociation between the two ways of estimating the sensitivity of 0.25 log step in the low sensitivity range and 1.8 log step in the high sensitivity range (the difference at median sensitivity is 1 log step). No correlation was found between histamine- and allergen-induced wheal area increase, and the discrepancy might be caused by a difference in the endogenous histamine release and/or difference in the number of histamine receptors at different degrees of sensitivity. With the use of median values it is possible to perform biological standardization with histamine 10 mg/ml and interpolate to histamine 1 mg/ml. However, the response in individual patients varies, and because of the small wheal area and the low reproducibility with histamine 1 mg/ml we recommend the exchange of histamine 1 mg/ml to histamine 10 mg/ml as an international positive reference.
Adolescent↗
Basophil histamine release and humoral changes during immunotherapy. Dissociation between basophil-bound specific IgE, serum value, and cell sensitivity.
An in vitro pilot study was performed to determine whether basophil cell-bound specific IgE was correlated to serum-specific IgE and to basophil cell sensitivity during immunotherapy with a well-documented treatment. The findings showed a clear dissociation between these three parameters, which is in contrast to the situation before hyposensitization and to our previous study in a comparable group of non-hyposensitized patients, where highly significant correlations were observed. Further investigations are in progress to clarify whether the dissociation is involved in the clinical improvement.
Allergens↗