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Allergy. Conventional and alternative concepts. A report of the Royal College of Physicians Committee on Clinical Immunology and Allergy.

Allergy is an exaggerated response of the immune system to external substances. It plays a role in a wide range of diseases. In some, such as summer hayfever, the symptoms are due entirely to allergy. In other conditions, particularly asthma, eczema and urticaria, allergy plays a part in some patients but not all. In these situations, allergy may have either a major role or provide just one of many triggers. In an individual patient's illness, the importance of allergy may change with time. The most common allergens (substances causing allergy) are grass and tree pollens, the house dust mite, products from pets and other animals, agents encountered in industry, wasp and bee venom, drugs, and certain foods. Food allergy presents a particularly difficult problem. Some individuals who react to food suffer from food allergy in its strict sense but in others there is no evidence of an alteration in the immune system. Here the term 'food intolerance' is preferable. Conventional doctors treat allergy by allergen avoidance--where this is possible--and drugs that relieve symptoms. In a few selected cases, in which other methods have failed, immunotherapy (desensitisation or hyposensitisation) is recommended. Although patients who consult practitioners of alternative allergy may do so by preference, it is often also because they are dissatisfied with the conventional approach to diagnosis and treatment, or because they have conditions which conventional doctors do not accept as having an allergic basis. There is a very wide range of alternative approaches to allergy, including the methods used by clinical ecologists and other treatments such as acupuncture and homoeopathy. Hypnosis may have a small role to play in helping the asthmatic and similar effects have been suggested for acupuncture. Furthermore, it is likely that there are still many active ingredients in medicinal plants used by herbalists but these need to be clearly identified and purified before their usefulness can be evaluated properly. Apart from these situations, we have yet to be convinced by substantial evidence that any of the other alternative methods of diagnosing or treating allergic disease are of proven value. There have, however, been many false and misleading claims and serious harm may be caused by misdiagnosis or delays in appropriate treatment. The public should be warned against costly methods of diagnosis and treatment which have not been validated.(ABSTRACT TRUNCATED AT 400 WORDS)

Allergens

Allergy: conventional and alternative concepts. Summary of a report of the Royal College of Physicians Committee on Clinical Immunology and Allergy.

Allergy is an exaggerated response of the immune system to external substances. It plays a role in a wide range of diseases. In some, such as summer hayfever, the symptoms are entirely due to allergy. In other conditions, particularly asthma, eczema and urticaria, allergy plays a part in some patients but not all. In these situations, allergy may either have a major role or provide just one of many triggers. In an individual patient's illness, the importance of allergy may change with time. The most common allergens (substances causing allergy) are grass and tree pollens, the house dust mite, products from pets and other animals, agents encountered in industry, wasp and bee venom, drugs, and certain foods. Food allergy presents a particularly difficult problem. Some individuals who react to food suffer from true food allergy but in others there is no evidence of an alteration in the immune system. Here the term 'food intolerance' is preferable. Conventional doctors treat allergy by allergen avoidance--where this is possible--and drugs that relieve symptoms. In a few selected cases, in which other methods have failed, immunotherapy (desensitisation or hyposensitisation) is recommended. Patients who consult practitioners of alternative allergy often do so because they are dissatisfied with the conventional approach to diagnosis and treatment, and sometimes because they have conditions which conventional doctors do not accept as having an allergic basis. There is a very wide range of alternative approaches to allergy, including the methods used by clinical ecologists, acupuncturists and homoeopathists. Hypnosis may have a small role to play in asthma, and similar claims for acupuncture need to be evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma

Local immune response in patients with cow milk allergy: follow-up of patients retaining allergy or becoming tolerant.

To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.

Animals

Clinical and immunological aspects of food allergy in childhood. I. Estimation of IgG, IgA and IgE antibodies to food antigens in children with food allergy and atopic dermatitis.

Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.

Adolescent

Investigations on group allergy reactions to cefazedone in patients with penicillin allergy of the anaphylactic type (type I) and of the delayed type (type IV).

Allergological investigations (scratch test, intracutaneous test, RAST test, patch test) on 19 patients displaying allergies of type I or IV, respectively, against penicillin G according to Coombs and Gell, in the skin test with (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) revealed in two cases group allergy against cefazedone. The studies demonstrate that group allergic reactions against cefazedone are quite possible in patients with primary allergy to penicillin derivatives or other beta-lactam antibiotics.

Anaphylaxis

Immediate-type hypersensitivity to a bean lectin source with commentary on occupational allergy in allergy-immunology laboratory and research workers.

A case of acute, severe allergic conjunctivitis is reported in a biochemist who had been grinding Bandeiraea simplicifolia, the source of an anti-B lectin. A crude extract of these beans produced immediate-type skin test reactivity, and reaginic antibodies were demonstrated in her serum. Several other examples of occupationally induced allergy in laboratory and research workers in the field of allergy-immunology are briefly cited. Exposure to potential allergens in a dry, powdered form seems particularly hazardous.

Adult

Serological investigations in hymenoptera sting allergy: IgE and haemagglutinating antibodies against bee venom in patients with bee sting allergy, bee keepers and non-allergic blood donors.

Specific IgE-antibodies and haemagglutinins to bee venom were determined in fifty-five bee sting allergic patients, fifty-seven bee keepers and fifty-two blood donors without evident allergy to hymenoptera stings. IgE-antibodies were detected by RAST in 70% of allergic patients, 40% of bee keepers and 12% of blood donors. Most bee keepers with detectable IgE-antibodies to bee venom recorded severe local or even general reactions to bee stings. Most blood donors with detectable specific IgE had been stung by hymenoptera in the past. High titres of haemagglutinating antibodies against phospholipase A were found in most bee keepers, occasionally in bee sting allergic patients but only rarely in blood donors. The determination of specific IgE-antibodies to insect venoms by RAST seems to be a valuable method for the diagnosis of hymenoptera sting allergy.

Agglutinins

Whither allergy or wither allergy.

The specialty of allergy appears to be at a scientific and economic crossroad. With a significant number of scientific papers questioning the value of immunotherapy, the movement of the country towards prepaid care and the necessity for demonstrating cost/benefit ratio for all therapeutic procedures, the specialty of allergy can present an enigma.

Delivery of Health Care

[Antigenicity of serum albumin in allergy against cat or dog epithelium (significance of the radioallergosorbens test in the diagnosis of allergies)].

Intracutaneous, nasal provocation (NPT) and radioallergosorbens (Phadebas RAST) tests were performed on 49 subjects hypersensitive to cats and (or)dogs using serum albumin and epithelium extracts from cats and dogs. Serum albumin elicited intracutaneous reactions in most of the subjects, but gave positive NPT und RAST results in only a few and was, therfore, of limited clinical importance. The intracutaneous tests with epithelium extracts were positive in some subjects in whom other tests had been negative. It is possible that these false-positive skin tests were caused by serum albumin present in the extracts, while in others non-specific skin reactions were apparently caused by epithelial components. On the other hand, the results suggest that the few patients allergic to dogs were incorrectly diagnosed with the RAST. But the described in-vitro method increases the chances of diagnosing allergies against animal epithelia. It is furthermore useful in the interpretation of equivocal skin tests.

Adolescent

Respiratory allergies (bronchial asthma and rhinitis) due to sensitization of type I allergy to red spider mite (Panonychus ulmi KOCH).

The inhabitants of a fruit growing area often report spontaneously of sensitization to the red spider mite (RSM) (Panonychus ulmi KOCH). These are for the most part sensitizations with low clinical symptoms (rhinitis, conjunctivitis and erythema). Severe clinical developments with bronchial asthma have been observed. We investigated six patients working in a fruit growing area sensitized by RSM. The sensitizations corresponded to a Type I allergy. Skin tests and provocation tests (nasal as well as bronchial) with RSM showed immediate reactions and RAST positive results were obtained using RSM allergen disks. RAST measurements of sera from nine house-dust mite Dermatophagoides pteronyssinus allergic patients using RSM allergen disks showed RAST-class > 1 for eight patients. RAST inhibition and immunoprint suggest a possible cross-reaction between RSM and D. pteronyssinus.

Adult

Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy.

Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine whey) were measured in 39 infants with cow milk protein allergy (CMPA) at birth (cord blood), at time of diagnosis and before and after milk challenge at the age of 12 months. Immunological measurements were also undertaken in 33 control infants without CMPA at birth, at 6 months and at 18 months. At no time, were differences found between the levels of IgG and IgG subclass AB to OA and BLG in control versus infants with CMPA. In the 39 infants with CMPA no correlation was found between the levels of IgE, IgG and IgG subclass AB in cord blood and subsequent levels of these values, irrespective of the type of CMPA (IgE-mediated (CMA) or non-IgE-mediated (CMI)), and irrespective of whether remission had occurred. In cord blood 25/33 (76%) of the infants with CMPA had specific IgE-AB to one or more of the bovine milk proteins indicating a prenatal intrauterine sensitization to cow milk protein. At 6 months the frequency of specific IgE-AB to bovine milk proteins was significantly (p less than 0.05) higher in infants with CMA versus CMI, and at 12 months total serum-IgE and the increase of these specific IGE-AB and RAST to CMP were significantly higher (p less than 0.05) in infants with persistent CMA. From 6 to 12 months withholding milk resulted in a significant fall in specific IgE-AB to CMP, and IgG, IgG1 and IgG4 anti-BLG followed by an increase after milk challenge. Decreasing levels of IgG anti-OA from birth to 6 months reflect passive maternal transfer of IgG through the placenta, and increasing levels of IgG anti-BLG, already from birth to 6 months, may represent an early exposure to CMP in all infants. Significantly higher levels (p less than 0.05) of IgG anti-OA AB, IgG1 and IgG4 anti-BLG AB were found in infants with persistent CMA, indicating a close relation between the synthesis of IgE and IgG and between IgE and IgG subclasses (IgG1 and IgG4) in symptomatic cow milk-allergic individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Child, Preschool

[Quality control in the allergy laboratory--4 years "Allergy Ring Trial" in Austria].

In 1988 the Austrian Society for Allergology and Immunology initiated an external quality control program for the in vitro allergy diagnosis. In 12 mailings, 62 sera from allergic patients were sent to selected laboratories in order to determine total and antigen specific IgE according to the laboratory-specific methods. The values for total IgE varied considerably (73.9% were within +/- 1 SD, 94.3% within +/- 2 SD and 99.1% within +/- 2 SD, but only 0.9% beyond that). Sources of error were mainly attributable to inappropriate equipment and low quality reagents, but also bad test performance, with respect to personnel and the routines. In contrast, antigen specific IgE against pollen, mites, moulds, insect venoms, animal danders, drugs, parasites, environmental and food antigens revealed quite homogeneous results. Out of 1492 data, only 46 (3.1%) had to be declared as "wrong", and the variability of the RAST-classes was low. Whereas the quality of the reagents from all the different suppliers was not absolutely reliable at the beginning of the study, it improved considerably with time, as consequence of our complaints. The comparability of the methods for detecting total-IgE were non-satisfactory, whereas those for antigen specific IgE were generally good. The variety of methods employed (radio- and enzyme immunologic, fluoro- and nephelometric methods, etc.) should entail appropriate consequences, especially critical comparisons within one and the same laboratory; in addition, international standardization of the "normal" values should replace company-standards, and quality control programs for each test system before it is marketed should be mandatory. Our results confirm, that external control should be obligatory for any laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens

Investigation of the response to some haptenic determinants in penicillin allergy by skin and in vitro allergy tests.

The role of three penicillin metabolites in human allergic reaction to penicillin has been assessed using sensitive in vitro tests in addition to skin testing. Conjugates of the benzylpenicilloyl (BPO), benzylpenicillenate (BPE) and penicillamine (PA) groups with human serum albumin (HSA) and bovine gamma globulin (BGG) have been made. In the passive haemagglutination test antibodies specific for all three determinants were found but there was no difference between allergic and non-allergic groups. However, the ratio IgG/IgM, specific for each determinant, was higher in normals than in allergics. In skin tests, histamine release from leucocytes and the lymphocyte transformation test, the BPO group was confirmed as the major determinant, but in some individuals the BPE or PA groups are more important.

Drug Hypersensitivity

A case of fallow deer allergy. Cross-reactivity between fallow deer and horse allergy.

We report the case of a 25-year-old housewife, a native of Mexico City, with rhinitis and asthma induced by exposure to fallow deer in an animal park close to her home. In the literature, we could find only one previous case. The patient presented a polyvalent IgE sensitization in prick skin tests and RAST to several animals' dander and epithelia, but RAST inhibition experiments showed a cross-reactivity only between fallow deer and horse allergen extracts.

Adult