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A study of the relationship between childhood nephrotic syndrome and allergic diseases.

The incidence of atopic diseases in 206 children with nephrotic syndrome (NS) was studied. Boys with NS had three times higher incidence of bronchial asthma than the general population. There was no difference in the girls. Both boys and girls with NS had about three times more allergic rhinitis and ten times more atopic dermatitis than the general population. In NS patients with associated allergic disease, skin test and allergen-specific IgE antibodies by radioallergosorbent test (RAST) were performed. Most of the patients with dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), egg white, or cow's milk protein-specific antibodies had positive skin tests. One hundred of the 206 children with NS received renal biopsies and serum IgE levels were measured. During the acute nephrotic phase the geometric mean serum IgE levels in minimal change nephrotic syndrome (MCNS), IgM mesangial nephropathy (IgMN), hepatitis B virus-associated membranous nephropathy, and treatment-responsive focal segmental glomerular sclerosis patients were all significantly elevated, in descending order of significance. These high serum IgE levels decreased in remission of NS and elevated again during relapse. The relationship between high serum IgE levels in NS patients and the incidence of allergic diseases showed that one third to one fourth of either IgMN or MCNS patients developed allergic diseases. These results suggest that NS patients had a higher allergic disease incidence. Serum IgE level may serve as one of the prognostic factors. However, an increase in the IgE level may be a reflection of body immunoregulatory imbalance that plays a direct pathogenic role in the occurrence of NS and proteinuria.

Child↗

Biological miracles and misadventures: identification of sensitization and asthma in enzyme detergent workers.

The discovery that the enzymes used in biological washing powders were asthma-causing sensitizers derived initially from the concern of an industrial physician as to the possibility of pulmonary damage due to the proteolytic nature of the material. This caused a search for possible cases of enzyme-related illness. Careful history-taking led to a hypothesis concerning sensitization and allergic illness which was supported experimentally by skin prick tests and inhalation challenge tests, and later by radioallergosorbent tests (RAST). It seems that the consequences of handling this potentially allergenic material as a fine powder had not been anticipated; and failure to analyze cases of sickness, to identify asthma, and to consider its workplace source had prevented its recognition elsewhere. Contributing to this failure was the pattern of development and manifestations of allergic illness, which seldom occurred in the workplace and was not confined to enzyme workers or atopics. In some cases the incidence of illness had been suppressed, or investigation prevented.

Asthma↗

Sensitization following Hymenoptera whole body extract therapy.

Treatment of an insect-sensitive patient with Hymenoptera whole body extracts (WBE) led, on five occasions, to a serum sickness--like syndrome which did not recur after therapy was stopped. The patient was found to be sensitive by skin test, histamine release, and radioallergosorbent test (RAST) to both venom and WBE as well as to venomless bee body preparations. Subsequent therapy with honeybee and yellow jacket venoms was without sequelae, and after treatment the patient did not react to a sting. In order to assess the frequency of sensitivity to irrelevant body proteins in patients treated with WBE we carried out WBE RASTs on sera from 15 such patients and compared them with those from 15 nontreated insect-allergic patients who had similar venom-specific IgE antibody levels. None of the patients allergic to insects who had not been treated with WBE had detectable IgE anti-WBE antibodies, while about 50% of those treated with WBE had developed IgE antibodies against these proteins. It appears that sensitization to nonvenom WBE proteins in terms of the development of IgE antibody is a common result of this therapy, and, rarely, repeated challenge with this complex antigenic mixture can also lead to clinical illness.

Adolescent↗

Structure and activity of ragweed antigen E. II. Allergenic crossreactivity of the subunits.

Recently we have reported the isolation of the two subunits (alpha and beta) of ragweed antigen E (AgE) in their active form. In the present work we have compared the allergenic activity of the two subunits with native AgE by the radioallergosorbent test (RAST) and by inhibition of the RAST. Also, the amounts of IgE antibodies in 30 ragweed-sensitive sera bound to alpha and beta subunits as well as native AgE were measured by RAST. In all individuals the percentage of RAST binding was greatest to native AgE; however, varying patterns of reactivity to alpha and beta subunits were noted. In RAST inhibition experiments, free beta subunit was equally effective in inhibiting the binding of IgE antibody (from a pooled ragweed-sensitive sera) to immoblized alpha or beta subunit. Similarly, fluid-phase alpha subunit inhibited in a comparable manner the binding of IgE antibody to solid-phase alpha or beta subunits. In further RAST inhibition experiments 7 x 10(-13) moles of fluid-phase native AgE was required for 50% inhibition of the binding of IgE antibody to solid-phase native AgE. Larger molar amounts of fluid phase beta (3.5 x 10(-11) and alpha (3 x 10(-10) were needed for 50% inhibition of the binding of IgE antibody to solid-phase native AgE. AgE allergenicity as measured by RAST could not be totally reconstituted by recombination of equimolar quantities of alpha and beta subunits. Less than 1 x 10(-12) moles of fluid-phase native AgE inhibited the binding of IgE antibody to solid-phase alpha or beta, greater than 50%. Finally, the isolated chains are bioligcally active as demonstrated by their ability to provoke wheal-and-flare skin reactions in subjects allergic to ragweed pollen, and the activities of the chains were approximately equivalent on a weight basis to native AgE.

Allergens↗

Eyelid dermatitis: experience in 203 cases.

Allergic contact dermatitis has been considered the most common of the many dermatologic conditions found with eyelid dermatitis. This is a retrospective study of 203 patients who presented with persistent or recurrent eyelid dermatitis with or without dermatitis elsewhere. Almost all underwent patch testing and, when indicated, radioallergosorbent test, skin prick and intradermal tests, and in many cases, usage tests as part of the workup. Relevant allergic contact dermatitis was found in 151 of 203 patients (74.%): 46 (23.%) had protein contact dermatitis, but only 7% had protein contact dermatitis without concurrent allergic contact dermatitis. Less than 1% had irritant dermatitis alone. Twenty-three patients had atopic eczema, of whom 16 also had allergic contact dermatitis, protein contact dermatitis, or both. Other conditions included seborrheic dermatitis (n = 11), psoriasis (n = 7), dry eyes (n = 9), and dermatomyositis or overlapping connective tissue disease (n = 7). Important sources of contact sensitivity include cosmetics, metals, topical medications including corticosteroids, eye medications, dust mites, animal dander, and artificial nails; only 5 cases were caused by nail lacquer. Eyelid dermatitis is a multifaceted clinical problem, but in this group of patients, allergic contact dermatitis was a common cause, even among those with atopic eczema.

Cosmetics↗

Stinging insect allergy. Avoidance, identification, and treatment.

The incidence of anaphylaxis from insect stings is about 0.4%, most commonly caused by Hymenoptera species. Diagnosis is aided if the patient can reliably identify the insect, and more specific diagnosis depends on venom skin testing for individual sensitivity. Radioallergosorbent testing is also used but fails to identify about 15% to 20% of sensitivities. Avoidance of high-risk situations is the best approach for patients with known sensitivity. Treatment includes relief of local symptomatic reactions, pharmacologic arrest of anaphylaxis, and venom immunotherapy.

Anaphylaxis↗

Discontinuing venom immunotherapy.

The decision to discontinue venom immunotherapy requires a great deal of clinical judgement because of the potential for a life-threatening reaction to a sting. The risk of recurrence is a combination of the frequency of reaction and the severity of reaction. Early studies reported a relapse rate of 8-14% in radioallergosorbent test-negative patients when therapy was stopped after 3 years. Unfortunately, the venom skin test or radioallergosorbent test becomes negative in only 25% of patients after 5 years of treatment. An alternative criterion for stopping treatment after 5 years regardless of the skin test has been equally successful, with most post-treatment reactions being much milder than pre-treatment reactions. There was no evidence of a rebound of venom sensitivity when therapy was stopped, even when patients were stung. The level of venom-specific IgE antibodies is better suppressed by 5 than by 3 years of treatment. The risk of relapse is higher in honeybee-allergic patients and in patients who had a systemic reaction (to a sting or an injection) during therapy. The frequency of reaction may be low, but patients who had very severe pre-treatment reactions have a greater chance of the reaction being severe again, and should remain on therapy for life. Long-term observations show that the incidence of systemic reaction to a sting remains 10% for each sting that occurs, even 10-15 years after stopping treatment. Because patients may not react to one sting and then subsequently react to another sting, the cumulative frequency of sting reactions is approximately 17% after 10 years off treatment. Moreover, negative venom skin tests are not a guarantee of safety because there is almost the same 10% frequency of reaction in patients who appear to lose sensitivity. It is not yet clear whether some low-risk patients (children, mild reactors) could discontinue treatment after just 3 years.

Adult↗

Physico-chemical properties and specific activity of a purified allergen (codfish).

The major allergen (Allergen M) from codfish is an acidic protein, mol. wt. 15000 with 114 amino acid residues and only one sugar (glucose) residue. It is highly active in skin testing on codfish-allergic individuals, in passive transfer (PK) testing and in the radioallergosorbent test (RAST). The activity resists denaturation and incomplete tryptic hydrolysis. Two fragments (TM 1, mol. wt. 8500, and TM 2, mol. wt. 6500) are obtained from allergen M. The fragments are equally active and allergenically identical in biological tests, but somewhat less active than Allergen M itself. Smaller peptides obtained from TM 2 are inactive. The amino acid sequence of TM 2 is given as the first reported example of a full structural analysis of an active allergen. The information obtained in studies of this model allergen is compared with information published from other studies of allergens. Similarities and differences are pointed out.

Allergens↗

[The basophilic histamine liberation test as a diagnostic method in Hymenoptera venom allergy].

In 181 patients with systemic reactions to hymenoptera stings as a result of immediate-type allergy to bee or wasp venom confirmed by history, skin testing and demonstration of hymenoptera venom-specific IgE antibodies on radioallergosorbent testing (RAST), in vitro histamine release from peripheral basophilic granulocytes following stimulation with bee or wasp venom was evaluated. Suspensions of washed peripheral leukocytes at a density of 2 x 10(6)/ml were incubated with four different concentrations of hymenoptera venoms. Histamine was measured by spectrofluorometry, and histamine release was calculated as a percentage of the total histamine content. Tests performed with peripheral leukocytes obtained from 18 non-allergic individuals served as controls. In both bee venom allergy and wasp venom allergy the corresponding allergen induced concentration-dependent histamine release. Upper normal limits of histamine release were defined for the venom concentrations used. When these were used as reference values the basophil histamine release test exhibited a specificity of 94% and a sensitivity of 82% in the diagnosis of bee venom allergy, and a specificity of 83% and a sensitivity of 68% in the diagnosis of wasp venom allergy. Since there was no relevant significant correlation between the results of the basophil histamine release test on one hand and the severity of sting reactions and the prick test and RAST results on the other, it seems that the histamine release test determined additional parameters of sensitization. Thus, the method is a valuable adjunct to the in vitro methods available for the diagnosis of hymenoptera venom allergy.

Adolescent↗

Development of a reverse enzymoallergosorbent test (REAST) to detect timothy-specific IgE antibodies. Comparison with RAST.

Radioallergosorbent test (RAST) for the measurement of IgE antibodies has been introduced more than 15 years ago and a number of technical modifications have since improved its sensitivity and reproducibility. The test has been applied to the diagnosis of allergy and to determine changes in the levels of IgE antibodies following immunotherapy. However, specific IgG antibodies are raised during such a therapy and can interfere with the RAST. We have developed a reverse enzymoallergosorbent test (REAST) where microtiter plates are first coated with a purified polyclonal anti-IgE antibody, then with the serum to test and finally with peroxidase-labeled antigen. This assay is antigen specific as shown by the significant inhibition of binding of the labeled antigen in presence of unlabeled specific antigen (greater than 95%) and the absence of inhibition in presence of irrelevant antigens. The values found in atopic patients (85 subjects) were significantly higher than in the non-atopic donors (35 subjects) (1.14 U +/- 1.20 vs. 0.01 U +/- 0.02, P less than 0.0005) and there was a good correlation with the Pharmacia RAST (P less than 0.0005). The levels of specific IgE by both REAST and RAST correlated well with the clinical symptomatology.

Allergens↗

Detection of specific IgE antibodies in sera from patients with hydatidosis.

A simple and sensitive immunoenzymatic assay for detection of specific IgE in hydatid disease is presented. Sera from 43 patients with hydatidosis, eight with schistosomiasis, two with taeniasis, two with cancer and 16 healthy blood donors were tested by both the immunoenzymatic technique and the classical radioallergosorbent test. Data were analysed in terms of different sensitivity and specificity of the two methods. The results indicate that the enzymatic method performed in microplates is as sensitive as the radioimmunological one (77% of positivity for both the tests), but the latter suffers from an higher rate of false positive reactions with sera from patients with other helminthic diseases (80% vs 20%). When the specific IgE evaluation is compared with other classical serological techniques, such as indirect haemagglutination and double diffusion in terms of different sensitivity in revealing an anti-Echinococcus immunological reactivity, the results suggest that specific IgE evaluation represents a useful addition to the classical serodiagnostic tests.

Echinococcosis↗

[Immediate hypersensitivity to quinine].

Systemic anaphylactic reaction with shock was observed after ingestion of an antipyretic combination product containing quinine. That quinine was responsible for the reaction was proven by immediate skin tests and by oral challenge tests. The demonstration of specific IgE's by a radioallergosorbent test (RAST) provided evidence for an immediate hypersensitivity mechanism.

Adult↗

RAST atopy screen.

A single in vitro screening test for atopic allergy is described. It uses the radioallergosorbent test (RAST) principle, and has been applied to screening sera from U.K. patients with possible atopic symptoms. When compared with the Phadebas RAST, the test sensitivity was 97% and the specificity 100%, and these results suggest that it is useful in any preliminary allergy investigation.

Animals↗

[The oral Prausnitz-Küstner reaction in food allergies].

The oral Prausnitz-Küstner (P-K) reaction was examined in 41 children suspected of IgE-mediated food allergy. The recipients were served by their mothers in this study. A positive reaction was observed in 9 children when used hen's egg, cow's milk, chicken, buckwheat, red-bean, salmon or common-dolphin. Among them, seven have had an anaphylactic skin reaction (systemic urticaria and/or angioedema) to the foods. The other two were babies who were fed only by the breast milk. Therefore, the oral P-K test may be useful for the diagnosis and the prediction of food-anaphylaxis. The sera that had the radioallergosorbent test (RAST) scores of 3 or greater were negative in the oral P-K reaction in 26 out of 36 tests, and the sera that showed the positive oral P-K reaction to buckwheat or chicken were zero in the RAST scores. These results suggest that a soluble substance (e.g., histamine-releasing factor) in addition to the IgE antibody might be involved in the oral P-K reaction, and that the RAST technique does not always detect the IgE antibody that recognizes the food antigens degenerated during the absorption in vivo.

Child↗

In vitro testing methodologies. Evolution and current status.

Almost 25 years after the development of the radioallergosorbent test, in vitro technology has become firmly established as an outstanding diagnostic tool for physicians treating the allergic patient. The American Academy of Otolaryngic Allergy (AAO), in its most current position statement, endorses the modified RAST as reproducible, sensitive, and specific. A new organization called the American In Vitro Allergy and Immunology Society (AIVAIS) has been formed to promote and monitor the use of these tests. Both societies suggest that in vitro tests should be part of a complete clinical evaluation by a well informed physician knowledgeable about the contraindications and limitations of in vitro technology. Such physicians should be capable of incorporating this information into responsible, judicious, and effective management of allergic patients. Only after the correct diagnosis has been made can appropriate treatment be started. Whichever route you choose, you and your patients can benefit from the use of in vitro allergy testing.

Allergens↗

Cold air challenge and platinum skin reactivity in platinum refinery workers. Bronchial reactivity precedes skin prick response.

An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.

Adult↗

Respiratory allergy to urine proteins of rats and mice.

Five atopic laboratory workers with asthma and other manifestations of allergy to rats and mice were sensitive to low-molecular-weight urine proteins--an alpha2-globulin in the rat and a prealbumin in the mouse. Positive skin prick and inhalation test reactions to the urine proteins were obtained; and radioallergosorbent tests (R.A.S.T.) for specific IgE antibody were also positive. These findings show that proper control of the collection and disposal of the animals' urine is necessary to minimise the likelihood of sensitisation.

Aerosols↗

Histamine release from peripheral blood leukocytes with purified bee venom allergens: effect of hyperimmune beekeeper plasma.

The response of 15 strongly bee-venom-allergic patients to highly purified venom allergens was compared using skin prick test titration, peripheral blood leukocyte (PBL) histamine release and radioallergosorbent test with three highly purified bee venom allergens: phospholipase (PLA2), hyaluronidase (HYAL) and acid phosphatase (ACID P). Sensitivity to the three allergens ranked in the same order for all three tests and in each case PLA2 was found to the most potent allergen. In the presence of hyperimmune beekeeper plasma, maximum histamine release was reduced significantly for all three allergens (p less than 0.001). Furthermore, hyperimmune beekeeper plasma increased the amount of allergen required for a comparable release of histamine (mean shift in dilution curve PLA2 917-fold; HYAL, 492-fold; ACID P, 61-fold). The release of histamine from whole blood was also compared with PBL + 10% normal human serum (NHS). For all three allergens maximum release was much lower from whole blood compared with washed cells + 10% NHS (p less than 0.001). These data confirm PLA2 as the major bee venom allergen by all three tests. Hyperimmune beekeeper plasma reduces maximum histamine release and increases its threshold. Histamine release in response to ACID P appears harder to block with hyperimmune beekeeper plasma than that provoked by PLA2 or HYAL (p less than 0.01). Whole blood releases less histamine and requires more allergen than washed cells, indicating that sensitivity of PBL in vivo is unlikely to be as great as washed PBL in vitro.

Adult↗