DEVELOPMENT OF CLINICAL IMMUNOLOGY AND ALLERGY IN THE UK—COMMON PROBLEMS AND SOLUTIONS

721

approach will lead to unnecessary rigidity in developing health education programmes, previous guidelines for dietary change seem vague and have not led to health-workers having a clear set of goals. The use of figures is also justified by the epidemiological approach which underlies the present attempt to develop preventive measures on a public health basis. The use of quantitative guidelines is not new and the figures in this document are derived whenever possible from the Government and expert committee reports listed earlier. REFERENCES 1 National Academy of Sciences. Toward healthful diets. Washington, DC, 1980. 2 DHSS. Report on health and social subjects, no 15. Recommended daily amounts of

food, energy and nutrients for groups of people in the United Kingdom. HM Stationery Office, London: 1979. 3. Rose G. Strategy of prevention: lessons from cardiovascular disease. Br Med J 1981; 282: 1847-51. 4. Keys A, Anderson JT, Grande F. Serum cholesterol in man: diet fat and intrinsic responsiveness. Circulation 1959; 19: 201. 5. Cummings JH, Branch W, Jenkins DJA, Southgate DAT, Houston H, James WPT. Colonic response to dietary fibre from carrot, cabbage, apple, bran and guar gum. Lancer 1978; i: 5-9. 6. James WPT, Trayhurn P. Thermogenesis and obesity. Br Med Bull 1981; 37: 43.

Occasional

advances in

immunological

science there is comparatively little expertise in clinical immunology in British medical schools and the health service. There is no logical reason why clinical immunology and allergy should be considered separately and a joint approach toward the correction of these deficiencies is required. The most immediate service needs are for the appointment of more laboratory-based consultant immunologists to develop and coordinate clinical services in each centre in conjunction with organ-based specialists who should receive specific training in immunology. Key developments in the science and technology of immunology point toward novel ways of diagnosing, treating, and preventing immunological disorders. Academic units have an important role in exploiting these basic advances as speedily and effectively as possible and teaching contemporary immunology at undergraduate and postgraduate levels. A reduction in the morbidity of any of the common immunologically-mediated diseases would produce considerable savings for the health service.

Immunologically-mediated disorders are found in all the traditional specialties.5-7 Each example in the accompanying table has a well-established immunological basis, unlike some disorders, for example, nasal polyposis and pre-eclamptic toxaemia, where such a basis is likely but not confirmed. Many of the immunologically-mediated disorders are chronic and disabling-for example, asthma, diabetes, glomerulonephritis, multiple sclerosis, and rheumatoid arthritis-and generate enormous costs for the health service. clinical The table the breadth of illustrates and who diagnose and immunology/allergy, practitioners these need disorders manage adequate knowledge of and immunological principles processes.

THE application of immunology to clinical medicine is substantial and so many major advances have taken place in immunobiology,immunochemistry,2 and immunogenetics3 in recent years4 that the possibility of diagnosing, treating, and even preventing many kinds of disease by immunological means now seems very likely. Unfortunately, many doctors Immunology Working Party

on

Clinical

Disease

Specialty

Cardiology

Rheumatic

carditis, cardiomyopathy, post-

cardiotomy/post-infarction syndromes. Extrinsic and intrinsic alveolitis, extrinsic asthma. Bullous skin disorders, dermatitis.

angio-oedema, contact

Endocrinology

Addison’s disease, type I diabetes,

ENT

Allergic rhinitis, secretory otitis media.

Gut and liver

Coeliac disease, ulcerative colitis, chronic

Haematology .

Infectious and

tropical diseases Obstetrics and

gynaecology Ophthalmology

Nephrology

Neurology

Paediatrics

thyroiditis. acute

and

hepatitis.

Autoimmune

haemolytic anaemia, neutropenia thrombocytopenia, pernicious anaemia. Tuberculosis (granuloma), Chagas’ disease (myocarditis), malaria (anaemia, nephrotic syndrome). Rhesus disease, infertility. and

Allergic/vernal conjunctivitis, uveitis, kerato-conjunctivitis sicca.

Glomerulonephritis eg, post-streptococcal, shunt, bacterial endocarditis, Goodpasture’s, mesangio-capillary, serum sickness, systemic lupus erythematosus. Polymyositis, polyneuritis, multiple sclerosis, myasthenia gravis, post-infective/postimmunisation encephalitis. Atopic eczema, milk and food allergy, juvenile chronic

Rheumatology

INTRODUCTION

for

SIZE AND SCOPE OF THE PROBLEM

Respiratory medicine Dermatology

Department of Immunology, University Hospital, Nottingham

*Chairman, British Society Immunology.

’

SELECTED EXAMPLES OF IMMUNOLOGICALLY MEDIATED DISEASE

W. G. REEVES*

Despite major

created such a considerable communications gulf that it is not surprising that many doctors do not understand what it is all about.

Survey

DEVELOPMENT OF CLINICAL IMMUNOLOGY AND ALLERGY IN THE UK—COMMON PROBLEMS AND SOLUTIONS

Summary

did not receive any or adequate teaching of immunology as undergraduates or postgraduates and those that did may well find it out of date. This deficiency, in conjunction with the formidable literature generated by basic immunologists, has

arthritis, Henoch-Schonlein

purpura.

Rheumatoid arthritis,

systemic lupus, dermatomyositis, widespread vasculitis.

Some clinicians have a specific interest in adverse reactions airborne, ingested, or other materials derived from the surrounding environment8,9-a grouping often designated as "allergy". Disorders such as allergic rhinitis, allergic asthma, and adverse reactions to foods and drugs are extremely common, although where the line should be drawn between disorders that are undoubtedly associated with an immunological response and other kinds of adverse reaction to

722

always clear. Those who have investigated "hypersensitivity" to foods or drugs will be only too aware of is

not

the

various

forms

of adverse

reaction

which

develop-immunological hypersensitivity being only

can

one

of

.

them. 10-13

With the considerable growth in awareness and interest of the general public in environmental agents as a cause of acute symptoms and disease some clinicians find themselves under pressure to provide clear answers to all sorts of aetiological proposals. In the absence of adequate training in immunology may also find it difficult to refute an allergic basis for their patients’ problems. The tendency for patients to ascribe all their current symptoms and problems to a particular cause-often arbitrarily-is common and undoubtedly fostered by fears concerning the safety of our complex and often artificial environment. These considerations receive avid encouragement from the media, who give such fears their ultimate expression by the use of phraseology such as "total allergy syndrome" or "allergy to the 20th century". 14

they

Allergy was originally defined by Von Pirquet as a state of "changed reactivity" following vaccination. He did not seek to distinguish between an adverse or beneficial outcome.15 The Victorian view that microbes were "bad" and the host response essentially "good" has gradually been modified by knowledge concerning various immunological factors which govern the severity of response to pathogenic organisms. 16-18

Exactly the same principles apply to immunological reactions to inanimate material, and restriction of the term "allergy" to conditions induced by inanimate material has only served to isolate the subject from the mainstream of clinical immunology. 19 Separation of some immunological disorders, for example, those of an atopic nature, from the rest is both contrived and arbitrary and will not advance our understanding of disorders characterised by immunological responses to environmental immunogens. Such advancement will be made only by defining the mechanisms involved and their distinction from other non-immunological events. THE CHANGING FACE OF IMMUNOLOGY

An enormous amount of immunological research has been conducted in the past quarter of a century, much of it analysing the component parts of the immune system and the way they interact in the mature organism to control responses to foreign material and maintain the integrity of "self’ . 20 The immune system has turned out to be at least as complex as some of the earlier theoretical proposals had suggested, but our present understanding of the mechanisms of immunoregulation, genetic control of the immune response, and development and maintenance of self-tolerance, and the characterisation of thymic hormones, interleukins,

interferons, and inflammatory mediators, has led to new and exciting possibilities for manipulating disease states.2l-24 This, in conjunction with major technological advances-for example, recombinant DNA synthesis25 and hybridoma that the next decade is likely to see innovations of an immunological nature.

technology26—means many

therapeutic

IMPORTANCE OF ACADEMIC UNITS

A prerequisite for bridging the gulf between basic immunology and clinical medicine is the existence of academic units in clinical immunology. These have an important function in teaching both undergraduate and postgraduate students the relevance of immunology to

medicine as well as serving as a source of knowledge for other specialists. Those working on clinical immunological problems need to be actively involved in immunological research and familiar with its terminology and literature as well as to have experience of the medical disorders they study. Immunology has often been seen as a bandwagon on which disorders previously described as "idiopathic" become "immunological" after the results of a few laboratory tests, but it has hatched from its descriptive shell and has much to say about the pathogenesis of many common diseases.27 These prospects for the development of clinical immunology will only be realised through properly conducted clinicopathological studies and clinical trials with carefully

designed protocols.24

.

Remarkably few academic departments of clinical immunology have been established though their existence is vital if developments in basic immunology are to be exploited speedily and effectively Academic developments in clinical immunology are particularly appropriate for support by the University Grants Committee’s "new blood" scheme designed to assist academic initiatives for developing and applying new technology. 28 DEPLOYMENT OF CLINICAL SERVICES

development of clinical immunology in the United Kingdom lags far behind the way in which immunology has The

developed as a basic science and, more importantly, is woefully under-provided for in terms of the contribution it should be making to the diagnosis and management of disease. The National Health Service districts and regions vary remarkably in the clinical immunological facilities that they possess.29 It needs more consultant appointments to focus interest and rationalise and develop services. The Working Party of the British Society for Immunology has recently considered the functions and training of the clinical immunologist29 and concluded that there is an urgent need for more appropriately trained laboratory-based immunologists to develop, coordinate, and manage clinical immunological services. The National Health Service has more than 40 consultants in immunopathology,3o but many of them hold honorary contracts and not all carry much service commitment. Some consultant immunologists received their initial postgraduate training as physicians and it is likely that recruits to the specialty will continue to be a mix of those who train initially in pathology or medicine.

Laboratory-based consultants-depending

on

qualifications

and experience-will usually require their own outpatient sessions or joint clinics with colleagues in other specialties, and it is customary for them to provide consultative advice on the wards for clinical colleagues.

The Working Party also recommended that an obligatory immunological component should be included within the higher specialist training of organ-based specialties commensurate with the importance of immunology to the specialty concerned, and this has recently been implemented for respiratory medicine.31 Some organ-based consultants will maintain an interest in immunology and conduct appropriate research, but the provision of an adequate and comprehensive clinical immunology service should not rely solely on this random commitment to clinical immunology. Since clinical specialties are now well developed on organbased lines, it does not seem wise to encourage the spread ofaa separate species-the clinical immunologist with day-to-day

723

inpatient care which crosses specialty addition, a commitment to laboratory with, not conflict with the importance of This does immunology. academic units of clinical immunology, which may well focus on problems that transcend specialty barriers. Clinical immunology departments and their laboratories are best located sub-regionally to cater for several health districts, the optimum catchment population being 0’5-1 million. The appointment of a consultant immunologist to

responsibility

boundaries

for

in

coordinate and rationalise services prevents

progressive

fragmentation and improves cost-effectiveness ofaservice. In teaching centres service departments should be associated with to academic units. Joint departments of this kind are ideally placed to launch and investigate therapeutic innovations of an immunological nature. FUNCTIONS OF THE CONSULTANT IMMUNOLOGIST

These should be tailored to suit the needs and interest of a particular locality but generally should include:

(i) Provision of laboratory investigation relevant to several, and sometimes all, of the following prime areas: immunodeficiency-both primary and secondary; allergy-ie, responses to environmental antigens; autoimmunity, including connective tissue diseases; lymphoproliferative disease including myeloma, immunological manipulations including immunisation and immunotherapy; and transplantation It is assumed that the use of immunological methods for other purposes-eg, blood transfusion serology, microbial serology, and radioimmunoassay of hormones, will remain the preserve of the other relevant departments.

(ii) Provision of consultative advice on the wards (sometimes in the form of "combined" ward rounds) and in outpatient clinics (often in conjunction with colleagues in organ-based

specialties). (iii) Quality control, interpretation of results, and test evaluation.32,33 (iv) Teaching of clinical immunology. (v) Application of developments in basic immunology to clinical practice. (vi) Providing a repository of knowledge and advice for the locality with particular reference to clinical research, clinical trials, and ethical considerations. (vii) Recruiting and training medical laboratory scientific officers, scientific officers, and junior medical staff. TRAINING THE CONSULTANT IMMUNOLOGIST

Medical graduates need to acquire the MRCP or part I of the MRCPath before specialising, usually at senior registrar

level, in immunopathology. During the period of higher specialist training the individual should become competent in the execution of laboratory methods in each of the main areas which form part of current practice. Additionally, a sound basis in immunobiology and immunochemistry is obligatory as well as experience in the clinical aspects of a number of different specialties in which immunology plays a significant part. The latter is probably best obtained by rotational attachments to clinical firms and/or experience in joint clinics during a four year training period. The trainee should also have an opportunity to undertake research and project work. At the end of the higher specialist training period in immunopathology the individual should be competent to

develop and administer a comprehensive clinical immunology service catering for all the major specialties

paediatric medicine. Science graduates enter a career in immunopathology via a research post in immunology, usually followed by the acquisition of a PhD. The specialist training period lasts for at least five years and should be undertaken in departments recognised by the Royal College of Pathologists. In either case, acquisition of the MRCPath in immunopathology will usually occur before appointment to the consultant (or equivalent) grade. within adult and

Some of the material presented here is derived from the report of the the British Society for Immunology on Clinical The remainder should be attributed to me and does not necessarily reflect the views of the British Society for Immunology or its Working Party. I have, nevertheless, to thank many colleagues for stimulating discussion which I hope will be enhanced rather than diminished by this article.

Working Party of

Immunology.29

REFERENCES 1. Golub ES. The cellular basis of the immune response. Boston: Sinauer Associates, 1981. 2. Glynn LE, Steward MW, eds. Immunochemistry: an advanced textbook. Chichester:

John Wiley, 1977. RL, eds. Comprehensive immunogenetics. Oxford: Blackwell, 1981. 4. Fougereau M, Dausset J, eds. Fourth International Congress of Immunology. Immunology 80. Progress in Immunology IV. London: Academic Press, 1980. 5. Samter M, ed. Immunological diseases, 3rd ed. Boston: Little, Brown, 1978. 6. Lachmann PJ, Peters DK, eds. Clinical aspects of immunology, 4th ed. Oxford: Blackwell, 1982. 7. Holborow EJ, Reeves WG, eds. Immunology in medicine: a comprehensive guide to clinical immunology. 2nd ed. London: Grune and Stratton, 1983. 8. Patterson R. Allergic diseases: diagnosis and management, 2nd ed. Philadelphia: J. B. Lippincott, 1980. 9. Lessof MH, ed. Immunological and clinical aspects of allergy. Lancaster: MTP Press, 3. Hildemann WH, Clark EA, Raison

1981. 10.

Reeves WG, Trounce JR. The problem of drug hypersensitivity. Guy’s Hosp Rep 1971;

11.

Brostoff J, Challacombe SJ, eds. Food allergy: Clinics in immunology and allergy. Vol II, no 1. Eastbourne: Saunders, 1982 Lessof MH, ed Clinical reactions to food. Chichester: John Wiley, 1983. Pearson DJ, Rix KJB, Bentley SJ. Food allergy: how much in the mind? A clinical and psychiatric study of suspected food hypersensitivity. Lancet 1983; i: 1259-61. Nixon PGF. "Total allergy syndrome" or fluctuating hypocarbia? Lancet 1982; i:

120: 245-68.

12. 13. 14.

404. 15. Von Pirquet

CF, Klinische Studien veber Vaccination und Vaccinale Allergie. Mu Med W, 1906, 53: 457. 16. Dick G, ed. Immunological aspects of infectious diseases. Lancaster: MTP Press, 1979. 17. Cohen S, Warren KS, eds. Blackwell, 1982.

Immunology

of

parasitic infections,

2nd ed. Oxford:

18. Mims CA. The pathogenesis of infectious disease, 2nd ed. London: Academic Press, 1982. 19. Reeves WG, Holborow EJ. General introduction. In: Holborow EJ, Reeves WG, eds. Immunology in medicine. 2nd ed. London: Grune and Stratton, 1983. 20. Klein J. Immunology: the science of self-nonself discrimination. Chichester: John Wiley, 1982.

21. Chedid L, Miescher PA, Mueller-Eberhard HJ, eds. Immunostimulation. Amsterdam: Springer-Verlag, 1980. 22. NIAID study group report. New initiatives in immunology. US Department of Health and Human Services, 1981. 23. Salaman JR. Immunosuppressive therapy. Lancaster: MTP Press, 1981. 24. Reeves WG. Therapeutic manipulation of the immune response. In: Holborow EJ, Reeves WG, eds. Immunology m Medicine. London: Grune and Stratton, 1983. 25. Williamson R. Genetic engineering. London: Academic Press, 1983. 26. McMichael AJ, Fabre JW. Monoclonal antibodies in clinical medicine. London: Academic Press, 1982. 27. Cohen S, Ward PA, McCluskey RT, eds. Mechanisms of immunopathology. Chichester: John Wiley, 1979. 28. New Scientist, December 23/30, 1982. 29. Report of British Society for Immunology Working Party on Clinical Immunology. Functions and training of the clinical immunologist. Clin Exp Immunol 1983; 52: 702-05. 30. DHSS Medical and dental staffing prospects in the NHS in England and Wales. Hlth Trends 1982; 15: 35-39. 31. Joint Committee on Higher Medical Training. Amendment to Regulations for Higher Specialist Training in Respiratory Medicine. JCHMT, 1980. 32. Dawkins RL, Peter JB. Laboratory tests in clinical immunology: A critique. Am J Med

1980; 68: 3-5. 33. WHO Memorandum. Use and abuse of eight widely-used diagnostic clinical immunology. Clin Exp Immunol 1981; 46: 662-76.

procedures

in