808 BRITISH MEDICAL JOURNAL VOLUME 283 26 SEPTEMBER 1981 Br Med J (Clin Res Ed): first published as 10.1136/bmj.283.6295.808 on 26 September 1981. Downloaded from istic globules of an amorphous material which are resistant to at presentation. Nor is the damage likely to result from diastase and positive for periodic-acid-Schiff. Immuno- accumulation of alpha,-antitrypsin in the liver, since patients fluorescence studies have shown that these globules are without liver damage have periodic-acid-Schiff-positive immunologically similar to alpha1-antitrypsin; they may be the globules. Further studies from different geographical areas are result of accumulation of a precursor of alpha,-antitrypsin needed to find out whether there is a true association between which cannot be released from the hepatocytes possibly the PiMZ phenotype and liver disease or whether liver damage because of a modification in its structure. The material is secondary to unknown associated environmental or genetic extracted from the globules contains no sialic acid-part of factors. the circulating alpha,-antitrypsin molecule.3 The association between deficiency of and 'Pierce JA, Eradio B, Dew TA. Antitrypsin phenotypes in St Louis.7AMA alpha1-antitrypsin 1975;231 :609-12. childhood cirrhosis was first described in 19764 and since 2 Talamo RC, Langley CE, Reed CE, Makino S. x-Antitrypsin deficiency: confirmed in numerous studies in both children and adults. In a variant with no detectablex,-antitrypsin. Science 1973;181 :70-1. I Jeppsson J-O, Larsson C, Eriksson S. Characterization of ac,-antitrypsin in childhood, liver disease associated with alpha1-antitrypsin the inclusion bodies from the liver in a,-antitrypsin deficiency. N Engi deficiency usually presents in the first four months of life as J Med 1975 ;293:576-9. an acute hepatitis with conjugated hyperbilirubinaemia and 1 Sharp HL. The current status of a,-antitrypsin, a protease inhibitor, in gastrointestinal disease. Gastroenterology 1976;70:611-21. often follows directly neonatal physiological jaundice. The 5 Talbot IC, Mowat AP. Liver disease in infancy: histological features and characteristic periodic-acid-Schiff-positive globules within the relationship to x,-antitrypsin phenotype. 7 Clin Pathol 1975;28:559-63. hepatocytes are rarely seen before 12 weeks of age, despite 6 Psacharopoulos HT, Mowat AP, Cook JJL, Rodeck C. Familial factors and the severity of liver disease in genetic deficiency of alpha-l-anti- florid liver damage.5 The clinical severity of the hepatitis is trypsin (PiZZ). British Paediatric Association, 53rd annual meeting, variable. About one-quarter of the children presenting with York. Arch Dis Child (in press). neonatal hepatitis die from cirrhosis the Sveger T. Liver disease in alpha,-antitrypsin deficiency detected by by second decade of screening of 200 000 infants. N EnglJ Med 1976 ;294:1316-21. life, one-quarter have cirrhosis, one-quarter have persistently 8 Berg NO, Eriksson S. Liver disease in adults with alpha,-antitrypsin abnormal liver function values, and one-quarter seem to deficiency. N Engl3r Med 1972 ;287:1264-7. Triger DR, Millward-Sadler GH, Czaykowski AA, Trowell J, Wright R. recover completely.6 Not all PiZ infants develop clinical Alpha,-antitrypsin deficiency and liver disease in adults. QJ7 Med 1976; features of neonatal hepatitis. A comprehensive epidemio- 45:351-72. in Sweden found that of infants with 0 Lieberman J. Emphysema, cirrhosis, and hepatoma with alpha,-anti- logical study 110", trypsin deficiency. Ann Intern Med 1974;81 :850-2. alpha1-antitrypsin deficiency developed prolonged cholestatic Palmer PE, Wolfe HJ. a,-Antitrypsin deposition in primary hepatic jaundice; 60 ' had subclinical hepatitis in infancy without carcinoma. Arch Pathol Lab Med 1976 ;100 :232-6. jaundice; and 350 ' had minor abnormalities of liver function.7 12 Kueppers F, Dickson ER, Summerskill WHJ. Alpha,-antitrypsin pheno- types in chronic active liver disease and primary biliary cirrhosis. Mayo Why only some PiZ infants develop liver disease is not known. Clint Proc 1976;51 :286-8. Possibly the liver is unable to control a damaging process 3 Fisher RL, Taylor L, Sherlock S. a-l-Antitrypsin deficiency in liver disease: the extent of the problem. Gastroenterology 1976;71 :646-5 1. caused by environmental or associated genetic factors, which Morin T, Martin J-P, Feldmann G, Rueff B, Benhamou J-P, Ropartz C. would have been adequately controlled had normal inhibitors Heterozygous alpha,-antitrypsin deficiency and cirrhosis in adults, a of bacterial, viral, or inflammatory cell proteases been present. fortuitous association. Lancet 1975 ;i :250-1. Theodoropoulos G, Fertakis A, Archimandritis A, Kapordelis C, Angel- In adults the association between the homozygous ZZ opoulos B. Alpha,-antitrypsin phenotypes in cirrhosis and hepatoma. phenotype and liver disease is even less clear, and the incidence Acta Hepatogastroenterol (Stuttg) 1976;23:114-7. 9 16 Eriksson S, Moestrup T, Hagerstrand I. Liver, lung and malignant of such an association varies considerably.8 Furthermore, disease in heterozygous (PiMZ) oc-antitrypsin deficiency. Acta Med there are appreciable differences in the prevalence of hepatic Scand 1975;198:243-7. fibrosis, cirrhosis, or hepatocellular carcinoma in different 17 Hodges JR, Millward-Sadler GH, Barbatis C, Wright R. Heterozygous MZ alpha,-antitrypsin deficiency in adults with chronic active hepatitis geographical areas.10-13 and cryptogenic cirrhosis. N EnglJl Med 1981 ;304 :557-60. http://www.bmj.com/ Whether an association exists between liver disease and the heterozygous PiZ state remains uncertain. No association was found when patients were screened by measuring serum levels of alpha,-antitrypsin'3 or by phenotyping the Treatment of seasonal and patients.14 15 In contrast, an association was seen when only patients with the characteristic periodic-acid-Schiff-positive perennial rhinitis inclusions in the hepatocytes were studied.'6 Hodges et al'7 have recently reported the results of a five-year prospective Hyperreactivity ofthe nasal mucosa causes a range of disorders on 2 October 2021 by guest. Protected copyright. study of liver biopsy specimens from 1055 adults with liver whose main symptoms are sneezing, itching, rhinorrhoea, disease. Phenotyping of the 34 patients whose specimens nasal congestion, and blockage. These symptoms are usually contained characteristic hepatocyte inclusions showed pheno- labelled as seasonal or perennial allergic rhinitis when there is type MZ in 25 of them. The other phenotypes found were ZZ, a recognised provoking antigen and as vasomotor (or non- SZ, MS, and MM. Twenty-one per cent of patients with allergic) rhinitis when there is not. Since some patients with cryptogenic cirrhosis and 205% of those with chronic active seasonal allergic rhinitis (hay fever) may have nasal symptoms hepatitis negative for hepatitis B surface antigen had pheno- all the year these disorders may prove to be a continuum type MZ, whereas this was found in only 3 5°k, of patients with rather than separate diseases.' alcoholic cirrhosis and 2 60" of those with other types of Allergic rhinitis, whether seasonal or perennial, is mainly cirrhosis. Hodges et al 7 also suggested that the patients with due to a type 1 allergic reaction. Specific IgE immunoglobulins chronic active hepatitis and phenotype MZ might have become attached to the surface of the mast cells, and when the distinctive clinical features. patient is re-exposed to the antigen these cells release histamine The mechanism of liver damage in such patients remains to and other chemical mediators, causing sneezing, nasal itching, be explained. It does not seem to be correlated with low serum rhinorrhoea, and nasal congestion. Effective treatment depends activities of alpha,-antitrypsin; 420% of the heterozygous on either preventing the release of mediators or blocking their patients with chronic active hepatitis or cryptogenic cirrhosis pharmacological effects. reported by Hodges et al had values within the normal range In contrast, the mechanisms underlying vasomotor and BRITISH MEDICAL JOURNAL VOLUME 283 26 SEPTEMBER 1981 809 Br Med J (Clin Res Ed): first published as 10.1136/bmj.283.6295.808 on 26 September 1981. Downloaded from non-allergic rhinitis are not fully understood. Among the drugs4 administration once or twice daily may control symptoms factors that may be concerned are, firstly, stimulation of and reduce unwanted effects. Two newer antihistamines, cholinergic receptors ("autonomic imbalance"), which renders astemizole and terfenadine, seem free of sedative effects at the nasal mucosa hyperreactive to non-specific stimuli (such doses which adequately antagonise the Hl-receptor5-7 and are as cold air, chemical irritants, and dust); secondly, type 3 under evaluation. allergy; and, finally, other non-immunological reactions such Oral decongestant sympathomimetics (such as pseudo- as sensitivity to salicylates and indomethacin. In these cases ephedrine and phenylpropanolamine) are available alone or in treatment is largely empirical. combination tablets with antihistamines-a combination which When an allergic aetiology is proved or appears likely on has been shown to have a synergistic effect.8 Nevertheless, oral clinical grounds the initial management should be directed at sympathomimetics should be prescribed with care since an controlling the allergens-simple in theory but often a problem appreciable rise in blood pressure has been reported in even in practice. Household pets should be removed when these are young normotensive individuals9 and interactions may occur the source of antigen. House dust and the house-dust mite are with adrenergic-neurone-blocking antihypertensive drugs, more difficult problems, but attempts should be made to monoamine-oxidase inhibitors, indomethacin,10 and a com- minimise dust, especially in bedrooms. Avoidance of exposure bination of methyldopa and oxprenolol." Treatment with oral to pollen is virtually impossible, but air filtration is a useful steroids should be reserved for patients with severe symptoms means of controlling pollen exposure indoors, though uncontrolled by conventional topical treatment. The potentially costly. serious adverse effects should limit use of steroids to short Topical treatment is preferable to systemic drug administra- periods only and at doses not exceeding 10 mg of prednisolone tion in the management of rhinitis since a useful therapeutic daily. Depot injections of methylprednisolone are considered effect can be obtained with minimum side effects. Disodium valuable treatment by some doctors, but they probably give cromoglycate is the only drug available for the treatment of no better results than equivalent doses of oral prednisolone. rhinitis which prevents degranulation of the mast cells. It is Treatment by injection has two advantages, however: it allows administered intranasally in powder or as a 2% solution. medical staff to control treatment on an intermittent basis and Reports of its use in seasonal and perennial allergic rhinitis and so avoids manipulation of treatment by the patient; and high- conjunctivitis since 1970 have mostly described a good clinical dose, short-duration treatment often produces rapid symptom- response but additional treatment has often been required. The atic relief which may outlast the pharmacological effects of the main disadvantage of treatment with cromoglycate is that it injection. In some patients who respond poorly to topical needs to be given four times a day. Topical sympathomimetic steroids a course of oral steroids or a single depot injection (alpha-agonist) agents are effective in relieving nasal congestion may establish whether the rhinitis is sensitive or resistant to but should be reserved for acute infective rhinitis, since their steroids. prolonged use is associated with rebound hyperaemia, local Immunotherapy (hyposensitisation) should be reserved for irritation, and, finally, rhinitis medicamentosa. Topical steroid patients with a clearly defined allergy in whom exposure to the preparations (such as beclomethasone dipropionate or fluniso- antigen is unavoidable and where other treatment has failed, lide) are especially effective in seasonal allergic rhinitis, but they since the treatment carries a risk of provoking anaphylaxis. It have also proved beneficial in allergic and non-allergic peren- has been used particularly in seasonal and perennial rhinitis nial rhinitis. There is a clear dose-response effect. Most due to pollens and house-dust mite. Symptoms are usually patients require 400 ,ug beclomethasone daily to induce im- reduced by about half, but the duration of benefit is unknown. provement, though the maintenance dose may be lower than When medical treatment has failed specific types of nasal obstruction (deviated septum or enlarged turbinates) can be this. Nasal polyps tend to shrink during treatment with topical http://www.bmj.com/ steroids but this is no substitute for surgical polypectomy. relieved by surgical techniques. Patency of the nasal passages Topical beclomethasone has no real adverse effects apart from will be improved but usually incompletely. In severe cases of minor nasal bleeding in fewer than one in 20 users,2 and watery rhinorrhoea, removal of most of the parasympathetic systemic absorption of the steroids is negligible. Eye symptoms innervation of nasal mucosa by sectioning the Vidian nerve are unaffected by nasal application of beclomethasone and may be effective, though the surgical technique is difficult. require separate management. Nasal polyps and recurrent sinusitis often occur in patients Oral drugs which have been used in the treatment of rhinitis with seasonal or perennial rhinitis, and these problems, too, include Hl-receptor antagonists (antihistamines), sympatho- may need surgical management. on 2 October 2021 by guest. Protected copyright. mimetics, and steroids. Antihistamines antagonise the action of histamine released by mast cells, but their anticholinergic Hendeles L, Weinberger M, Wong L. Medical management of non- infectious rhinitis. Am 7 Hosp Pharm 1980;37:1496-504. effects have an important subsidiary action. They relieve 2 Mygind N. Nasal allergy. Oxford: Blackwell Scientific Publications, 1978. sneezing, rhinorrhoea, nasal itch, and conjunctivitis but have 3Nicholson AN. Effect of the antihistamines brompheniramine maleate and little effect on nasal Used in seasonal triprolidine hydrochloride on performance in man. Br3r Clin Pharmacol obstruction. mainly 1979;8:321-4. allergic rhinitis, they are most effective if administered before 4Cook Tj, MacQueen DM, Wittig HJ, Thornby JI, Lantos RL, Virtue CM. antigen exposure. Their use is limited by the high incidence of Degree and duration of skin test suppression and side effects with antihistamines. 7 Allergy Clin Immunol 1973;51:71-7. adverse effects: sedation is the main problem and is potentiated 5Clarke CH, Nicholson AN. Performance studies with antihistamines. BrJ by alcohol and other central nervous system depressants. In Clin Pharmacol 1978;6:31-5. allergic rhinitis symptoms are often most troublesome at night 6 Kulrestha VK, Gupta PP, Turner P, Wadsworth J. Some clinical pharma- cological studies with terfenadine, a new antihistamine drug. Br 7 Clin and on rising in the morning, and sustained-release anti- Pharmacol 1978 ;6 :25-9. histamine preparations taken at night may be effective in 7Nicholson AN, Stone BM. Performance studies in man with the H1 controlling the symptoms and avoid daytime drowsiness.3 histamine receptor antagonists, astemizole and terfenadine. Br J Pharmacol (in press). Anticholinergic effects (dry mouth, constipation, and difficulty 8 Aschan G. Decongestion of nasal mucous membranes by oral medication with micturition) may also be troublesome. Since there is some in acute rhinitis. Acta Otolaryngol (Stockh) 1974;77:433-8. 9 Horowitz JD, Lang WJ, Howes LG, et al. Hypertensive responses evidence that the therapeutic effects (measured by weal-and- induced by phenylpropanolamine in anorectic and decongestant flare response) are much longer than the half lives of these preparations. Lancet 1980;i:60-1. 810 BRITISH MEDICAL JOURNAL VOLUME 283 26 SEPTEMBER 1981 Br Med J (Clin Res Ed): first published as 10.1136/bmj.283.6295.808 on 26 September 1981. Downloaded from 0 Lee KY, Beilin LJ, Vandongen R. Severe hypertension after ingestion of siting of the consultants' contracts. In Patients First'0 the an appetite suppressant (phenylpropanolamine) with indomethacin. Lancet 1979;i:1110-1. DHSS proposed that contracts should be held by DHAs: the 1 McLaren EH. Severe hypertension produced by interaction of phenyl- BMA strongly opposed this, arguing that they should be held propanolamine with methyldopa and oxprenolol. Br Med 7 1976;ii: at region, which is where all but teaching hospital consultants' 283-4. contracts are held at present. No final decision has been made, and presumably the Government hopes that by deferring one until the DHAs are set up the switch could be quietly intro- duced by individual health authorities, who will understand- NHS some ably see a district-held contract as being administratively tidy reorganisation: and a boost to their power. But consultants will not meekly hazards for doctors give way, because they regard this issue as one that affects standards of care. On 1 April 1982 193 district health authorities will be taking The arguments for retaining contracts at region are powerful. over the running of the NHS in England from 90 area health One of the NHS's successes has been the countrywide authorities. Scotland,' Wales,2 and Northern Ireland3 each provision of a good standard of hospital care. This has largely has its own NHS reorganisation plans, which do not include been a result of regional planning, which includes control over the formation of districts, and separate timetables. For the appointment of consultants. Districts might well adopt a England, the Secretary of State for Social Services has, after parochial or even a political stance, both in deciding the range consultation, decided on the district boundaries for the of local consultant services and in the consultant appointments reorganised Health Service and he is now appointing chairmen. themselves. This could hinder the promised expansion of the The appointment ofstaffhas been delayed because the National consultant grade, prove needlessly contentious and uneconomic, Whitley Council's Reorganisation Committee took longer than and create unacceptable variations in standards of hospital expected to agree on terms for the staff affected by reorganisa- care. A substantial proportion of consultants will have duties tion.4 But appointments will soon be taking place. and the extending beyond a single district, so the proposed change BMA, as well as warning its divisions to take an active part in would mean either introducing complicated administrative the reorganisation,5 has also urged doctors to ensure that "it arrangements for sharing contracts between DHAs-several really is patients first in the new NHS." In particular, consul- in the case of regional specialties-or requiring individual tants in the new district management teams have been asked consultants to hold several small-session contracts. Finally, by Mr D E Bolt, chairman of the Central Committee for senior staff in RHAs have developed the knowledge and Hospital Medical Services, to look "very critically at proposals experience to handle two sensitive aspects of consultant for purely administrative posts at district level." One of the employment-discipline and the sick doctor-and in general Government's aims in the reorganisation is to save money- they have won the respect and confidence of the profession. District staff would have to acquire this experience, and £30m is the target-and to use these administrative savings to improve patient care. Administrators may be sceptical of because they would be responsible for many fewer consultants any oversimplification of the problems of slimming such a might not achieve the level of skill now available at regional complex institution as the NHS,j but those NHS staff dealing level. This would be detrimental to the NHS at a time when with patients' clinical needs will be disappointed if the changes patients show an increasing tendency to complain about their turn out to be a game of administrative musical chairs and the treatment. savings illusory. On 28 July the Secretary of State for Social Services told Parliament that he had received over 800 representations on Many doctors will not be personally affected by reorganisa- http://www.bmj.com/ tion, but for some doctors in community medicine this will be the question of consultant contracts being held at region, the second time in a decade that their professional lives will mostly from individuals or groups of consultants. Given the have been disrupted.7 Given the recruitment difficulties in reluctance of working doctors to participate personally in community medicine, it is unlikely that there will be unemploy- medicopolitics, this represents a formidable strength of feeling ment in this craft. Even so, the next few months will be a among consultants. The BMA's Annual Representative worrying time for these doctors, and to acquaint the new Meeting at Brighton also showed the strength of the DHA chairmen with the tasks of community physicians the profession's feelings by voting overwhelmingly in favour of Central Committee for Community Medicine has just sent contracts being held by RHAs. The new Secretary of State, on 2 October 2021 by guest. Protected copyright. them an explanatory booklet,8 which among other things Mr Norman Fowler, should waste no time in endorsing that declares that "no district will require less than two community policy decision by the profession. physicians (the district medical officer and one other) to provide the essential services." The CCCM's next sentence, Scottish Home and Health Department. Structure and management of the that "this should be regarded as a minimum" (the committee's NHS in Scotland. 1981(Gen)14. Edinburgh: SHHD, 1981. 2 Anonymous. Br Med3 1981;283:86. italics), would seem to be an unremarkable statement of the 3Anonymous. Br MedJ7 1981;283:86. obvious were it not for the genuine concern among community Department of Health and Social Security. NHS reorganisation: implemen- tation of General Whitley agreements. London: DHSS, 1981. physicians that some DHAs might confine their appointments a British Medical Association. The BMA division in the nezw Health Service. to the one district medical officer defined among the seven London: BMA, 1981. "prescribed" management posts in the reorganisation circular.9 6 Anonymous. Hippocratic humbug. Health and Social ServiceJournal 1981; 4 September:1065. All other appointments will be at the discretion of the 7 Miles DPB. Community physicians and NHS reorganisation in England. authorities, and community medicine doctors will be looking Br Medy 1981 ;283:743-4. for support from their colleagues in the to ensure 8 Central Committee for Community Medicine. Community medicine at profession district in the re-organised NHS 1981-1982. London: British Medical that this branch of medicine is appropriately staffed in the Association, 1981. reorganised service. 9 Department of Health and Social Security. Health Service development: structure and management. HC(80)8. London: DHSS, 1980. Consultants, for their part, will welcome their colleagues' u0 Department of Health and Social Security. Patients first. London: support in another unresolved issue in reorganisation: the HMSO, 1979.