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)

The IgE and IgG subclass antibody response to foods in babies during the first year of life and their relationship to feeding regimen and the development of food allergy.

This follow-up study of 191 babies investigated the development of food allergy in an unselected population and its relationship to total and antigen-specific IgE and IgG subclass levels. Sensitization to egg, as indicated by a positive skin test or RAST, was found in 5% of 1-year-old babies, but none of the babies in this series fulfilled the clinical criteria for immediate-type milk allergy. For both bovine casein (CAS) and egg albumin, the IgG response was largely restricted to IgG1 in contrast to the predominant IgG4 response to these antigens that is found in adults. The level of IgG4, but not IgG1, antibody to CAS and ovalbumin (OV) was lower in some of the babies compared with that of their mothers (N = 166; p less than 0.05, Student's paired t test). However, there was no difference in the total serum IgG subclass levels between mothers and babies. These results demonstrate that, in the population of babies studied, (1) type I hypersensitivity to egg occurred in 5% of 1-year-old babies, (2) the predominant IgG subclass of antibodies to CAS and OV in babies is IgG1, and (3) in the 22% of babies, there was substantially (greater than 1000-fold) less IgG4 antibody to CAS and OV than in their mothers, suggesting specific exclusion of some IgG4 antibodies.

Plasma histamine and clinical tolerance to infused histamine in normal, atopic and urticarial subjects.

Five subjects with a recent history of urticaria (U), five atopic (A) subjects and a non-atopic (NA) control group were given intravenous infusions of histamine starting at 0.05 micrograms/kg/min, increasing by 0.05 micrograms/kg/min every 30 minutes to a maximum of 0.35 micrograms/kg/min. Plasma histamine levels were monitored every 15 minutes. The infusion was stopped when an objective clinical endpoint was reached, involving either evidence of peripheral vasodilatation (rise of skin temperature by at least 1 degree C) or a 20% fall of peak expiratory flow rate. There were no significant differences in resting plasma histamine in the three groups. Those with urticaria reached the clinical endpoint at a lower infusion rate than non-atopic subjects (U 0.22 +/- 0.02 micrograms/kg/min; A 0.26 +/- 0.02 micrograms/kg/min; NA 0.32 +/- 0.2 micrograms/kg/min. p less than 0.008) they also received a lower total histamine dose (U 1.12 +/- 0.33 mg; A 1.42 +/- 0.38 mg, NA 2.2 +/- 0.51 mg, p less than 0.008). Atopic subjects with a history of asthma, eczema or rhinitis also tolerated histamine poorly, some subjects reaching a clinical endpoint while the plasma histamine level was still relatively low (U 1.52 +/- 0.4 ng/ml, A 0.85 +/- 0.19 ng/ml, NA 1.4 +/- 0.44 ng/ml, p = 0.05). After the histamine infusion was stopped, the fall in the blood level of histamine was slower in urticarial subjects than in the other two groups, with a half-life of 6.2 +/- 1.3 min (A 3.0 +/- 1.2 min, NA 4.0 +/- 0.7 min, p less than 0.02). There were thus differences in the metabolism of histamine in our non-atopic urticarial subjects and increased histamine sensitivity in atopic subjects which require further study.

Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects.

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.

Recurrent urticaria and reduced diamine oxidase activity.

An abnormal metabolism of histamine has been suspected in urticaria and the role of diamine oxidase (DAO: histaminase) is therefore of interest. We have studied DAO activity in plasma and jejunal biopsy material and have measured the post-heparin DAO release in 11 control subjects and nine with recurrent urticaria, three of whom had had concurrent episodes of abdominal pain. Two of the nine urticaria subjects had only a minimal rise in plasma DAO activity after heparin, three had a response which was at the lower end of the normal range, and four were normal. In four out of five cases in which jejunal biopsy activity was obtained, there was concordance between mucosal DAO activity and the post-heparin plasma DAO response. Those with abdominal symptoms had abnormally low mucosal DAO activity and the subject who was most severely affected had proven episodes of small bowel oedema.

IgG subclass antibody production in human serum sickness.

The role of IgG-subclass antibodies in the spectrum of immunologic disorders has not yet been fully defined. In an attempt to understand its role in an immune complex-mediated disease, we studied patients who developed serum sickness (SSX) after treatment with an equine-derived immunoglobulin, antithymocyte globulin (ATG), for bone marrow failure. The predominant IgG subclass produced was IgG1, representing nearly 80% of all IgG anti-ATG activity present. The appearance of IgG anti-ATG antibodies and C1q-containing immune complexes was closely correlated with symptoms of SSX. Although other antibody isotypes were present and may have contributed to the patients' symptoms, it is evident that IgG1 is the predominant IgG subclass produced in human SSX caused by a heterologous protein.

The relationship between anti-IgE auto-antibodies and the IgE response to wasp venom during immunotherapy.

During immunotherapy with wasp venom, levels of venom-specific IgE antibodies increase and then fall, whereas the concentration of IgG antibodies rises and then remains at a high level. Successful treatment is therefore associated with both increased concentrations of serum IgG and decreased serum IgE antibodies to venom. In this study we have investigated the possible role of auto-antibodies in inducing the decrease in serum IgE antibody. Levels of auto-anti-IgE were measured by a radioimmunoassay. Anti-IgE auto-antibodies were not generated during immunotherapy and there was no significant difference in the levels of anti-IgE auto-antibodies between patients whose venom-specific IgE antibody levels fell more than fivefold after immunotherapy and those patients in whom IgE antibody levels did not change significantly. We conclude that anti-IgE auto-antibodies do not play a part in IgE suppression induced by immunotherapy.

Comparison of a new type of skin test (Phazet) with existing skin test methods and the radioallergosorbent test (RAST).

A new skin test method (Phazet) for diagnosis of immediate-type allergic disease was tested in 232 patients attending the Guy's Hospital Allergy Clinic, and compared with conventional skin test methods, using Bencard and Pharmalgen allergen solutions, and with serum IgE antibody tests (RAST). Six allergens (cat, dust mite, Cladosporium, grass pollen birch pollen and plantain pollen) were used, as well as histamine and a negative control. Phazet proved easy to use and was popular with inexperienced operators (medical and dental students). For the majority of allergens there was reasonably good agreement with the different tests, but overall Phazet and RAST produced fewer positive results than the other skin tests methods. In particular, the frequency of positive histamine tests was lower with Phazet (82%) than with Bencard or Pharmalgen (99%), but this discrepancy was lower in the second part of the study when the minimum time for the insertion of the needle (1 sec) was more scrupulously observed. Phazet offers a convenient and practical alternative to conventional 'wet' skin test methods.

The subclass of IgG antibody in allergic disease: II. The IgG subclass of antibodies produced following natural exposure to dust mite and grass pollen in atopic and non-atopic individuals.

In an attempt to understand the role of the different IgG subclasses in allergic disease, we have studied the subclass of IgG antibody to dust mite (HDM) and grass pollen (GP) produced as a result of natural exposure. Studies were carried out on 40 atopic children and 100 atopic adults who had never received immunotherapy. Thirty-two non-atopic adult controls were also studied. The specificity of the assay for IgG antibodies to dust mite was confirmed by inhibition with the homologous extract but not mite culture medium or fetal calf serum. IgG1 antibodies to HDM could be detected in most atopics (94%) and non-atopics (97%), and similar results were obtained for GP (81% and 100%, respectively). IgG4 antibodies to HDM were detected in more atopics (66%) than non-atopics (53%) and the difference was more marked for GP (72% vs. 19%). While the levels of IgG1 antibodies were not significantly different in the two groups, the levels of IgG4 antibodies were much lower in the non-atopics (P less than 0.001, Mann-Whitney U-test). These data show that all subjects were capable of recognizing and mounting an IgG1 antibody response to these inhaled antigens. Atopic individuals differed from normal subjects in the frequency with which they made IgG4 antibodies in response to natural exposure to both dust mites and pollen.