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.