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HEPATITIS B SURFACE ANTIGENAEMIA IN SICKLECELL DISEASE

SIR,-A survey of sickle cell disease among 10-12-year-oldchildren in Abu-Al-Khasib District of Basrah Governorate revealeda prevalence of 16% in the high-risk area compared with 2 - 5% in agroup of schoolchildren matched by age and sex from Basra itself (alow-prevalence region).1 During the survey sera were collected todetermine the frequency of hepatitis B surface antigen (HBsAg)among sickle-disease cases and controls. Haemagglutinationreaction kits, including positive control (’Hepatest’; WellcomeDiagnostic), were used.The prevalence of HBs antigenaemia among sicklers was almost

fifteen times that in the age and sex matched controls. Amongnormal Iraqi adults, the prevalence of HBsAg is not welldocumented. However, we have tested the sera of 300 consecutivevolunteer blood donors, and only 2 were positive (by hepatest).HBsAg has been found in 50% of sera from Iraqi patients withchronic hepatitis2 and in 58% of those with cirrhosis.3 In KuwaitHBsAg has been found in only 1% of volunteer blood donors whileHBsAg together with other hepatitis B markers was detected in 4%of blood donors and 37% of patients with cirrhosis and chronichepatitis.4

PREVALENCE OF HBSAgIN SERA OF SICKLERS AND CONTROLS

*Low prevalence area. tHigh prevalence area.

The only explanation for the high frequency of HBsAg in thesickle disease children is the multiplicity of injections which theyhave received; most had had attacks of bone and joint pain and somegave a history of abdominal pain severe enough to require parenteralsedation. Clinicians should be aware that jaundice in a patient withsickle cell disease may be due to hepatitis B and not a haemolyticcrisis.

Department of Pathology,Faculty of Medicine, Kuwait University,Kuwait

Department of Medicine,Faculty of Medicine, Baghdad University,Baghdad, Iraq

M. S. AL ADNANI

F. M. AL KASABF. A. AL ALUSI

DELTA INFECTION WITHOUT INCREASE INSEVERITY OF HEPATITIS

SIR,-The finding of increased morbidity of HBsAg positivehepatitis with infection by Dr Smedile and colleagues (Oct. 30, p.945) is of considerable interest to us because it is contrary to ourfindings both in 27 parenteral drug abusers with hepatitis Binfection who were examined serologically for d antigen andantibody and on whom liver biopsies were done and in 41 drugabusers with acute hepatitis B and simultaneous acute 6 infection.In our group of 27 drug-abusers with hepatitis B infection on

whom 6 serology (kindly done by Dr Rizzetto, Turin) and histologywere done, 7 had antigenaemia and 1 had anti-6 antibody. There wasno significant difference in the histological findings between 6positive and 6 negative patients; 4 of the 8 patients with 6 markershad chronic persistent hepatitis and 3 had chronic active hepatitis,while among the 19 6 negative patients 12 had chronic persistent

1. Al Kasab FM, Al-Alusi FA, Al Adnani MS, et al. The prevalence of sickle cell disease inAbu-Al-Khasib district of Southern Iraq. J Trop Med Hyg 1981; 84: 77-80.

2. Al-Balaghi SMA, Kassir A, Thewaini AJ. Hepatitis B surface antigen in various liverdiseases in Iraq. J Trop Med Hyg 1977; 80: 248.

3. Boxall EH, Flewett TN, Paton A, Rassam SW. Hepatitis surface antigen and cirrhosisin Iraq. Gut 1976; 17: 119-21.

4. Al-Nakib B, Al-Nakib W, Bayoumi A, Al-Liddawi H, Bashir AA. Hepatitis B virus(HBV) markers among patients with chronic liver diseases in Kuwait. Trans Roy SocTrop Med Hyg 1982; 76: 348-50.

hepatitis and 3 had chronic active hepatitis. Nor were there anydifferences in the clinical findings. The chronic liver disease foundwas attributable to non-A, non-B hepatitis in more than 80% ofthese patients and it preceded hepatitis B infection in more than65%.Of 254 drug-abusers with hepatitis B detected during an epidemic

of hepatitis B among them which began in 1980, 41 hadsimultaneous 6 infection. The infection was acute, as indicatedby the detection, by enzyme immunoassay, old antigen in the serumduring the acute stage of illness only. The proportion with 6antigenaemia (16%) was identical to that found by Smedile et al. intheir series of fulminant cases. None of our 41 patients with 6infection have so far shown any increase in severity of illness, suchas reported by Smedile et al. There have not been any cases offulminant hepatitis or death due to hepatitis among our group.In our study 6 infection did not adversely affect hepatic

histological or clinical findings in the initial period of infection.However, our results do not exclude long-term d-associated liverdisease.Since all but 1 of our patients with acute 6 infection were non-

Italians it may be that ethnic origin is an important factor inthe pathogenicity of the <5 agent.

Department of Medical Microbiology,University College,Dublin 4, Ireland

Charitable Infirmary,Dublin

A. G. SHATTOCK

J. F. FIELDINGYVONNE ARTHURSG. D. DOYLEM. G. KELLY

ANXIETY AND DEPRESSION IN PATIENT ONNADOLOL

SIR,-Clinically significant anxiety and depression can beinduced in patients without a previous psychiatric history. Theprobable precipitant in the case reported here was a potent&bgr;-adrenergic blocking drug prescribed for hypertension. f3-blockersaffect the central nervous system and side-effects include insomnia,hallucinations, anxiety, and, possibly, psychosis. Z-5 Propranololproduces clinical depression and exacerbates anxiety in some

patients. 2A 35-year-old man in good health and with no history of medical

or psychiatric problems felt dizzy and unwell with palpitations andarrhythmia after exercise as part of a vigorous physical exercise andweight reduction programme. Investigation revealed hypertension(170/100 mm Hg). Other tests, including the ECG, were normal.Even so the patient was prescribed nadolol 40 mg. 2 weeks later, hisblood pressure was unchanged but the pulse rate had dropped to54/min. Hydrochlorothiazide 50 mg (with potassium supplement)was then added. After a further 2 weeks, the diastolic pressure was109 mm Hg and the daily dose of nadolol was doubled to 80 mg.Within 2 days of this increase the patient experienced extremesadness which severely interfered with his social functioning and hiswork. On the fourth night, fearing he was going to commit suicide,he asked us for emergency help.The patient reported sadness, tearfulness, guilt, and difficulty

falling asleep. He expressed lack of interest in the future and felt thathe was "in quicksand slowly sinking with nothing left to hold onto". We felt that his severe depression could have been drug-induced and immediately stopped nadolol therapy. The patient didnot ascribe his feelings to the use of the drug, and did not believe ourpossible explanation.3 days after withdrawal of nadolol the patient was much

improved. He seemed cheerful and alert and accepted that the drug

1. Shattock AG, Kelly MG, Fielding JF, Arthurs Y. Epidemic hepatitis B with deltaantigenaemia among Dublin drug abusers. J Irish Med Assoc 1982; 151: 10.

2. Greenblatt DJ, Koch-Wesen J. Adverse reactions to propranolol in hospitalizedmedical patients: a report from the Boston Collaborative Drug SurveillanceProgram. Am Heart J 1973; 86: 478-84.

3. Gilman AG, Goodman LS, Gilman A, eds. The pharmacological basis of therapeutics,6th ed. New York: Macmillan, 1980: 190-95

4. Waal JH. Propranolol-induced depression. Br Med J 1967; ii: 50.5. Editorial. Beta-adrenergic blockage and anxiety. Lancet 1976; ii: 611-12.

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had probably contributed to his emotional state but also recognisedthat the drug might only have exacerbated an underlying anxietycondition. Further counselling and continued use of the diuretic hasalleviated many of the original anxiety symptoms and reduced hisblood pressure to 132/84 mm Hg.Since catecholamine-containing neurons in the central nervous

system (CNS) may be involved in mood regulation it is not

surprising that drugs which alter noradrenergic activity mayproduce the opposite effect (i.e., depression). It would therefore bedesirable for non-CNS-acting agents to be the first choice drugs.Where centrally acting j-antagonists are to be used, a briefassessment should be made to see if psychological side-effects mightbe especially disturbing. For example, the drug might exacerbatesymptoms in a patient who reports feelings of anxiety or depressionand a patient with a previous history of emotional problems mightbe susceptible to such side effects. Where j-blockers are used, thepatient must understand the possible side-effects. Our patient didnot ascribe the mood changes to the use of the drug, a findingrecorded by others.5,6 This could be dangerous for the patient whoseeks other advice without mentioning the use of the drug or whotried drastic measures to alleviate his emotional condition.A single case does not prove a point, and there are other possible

explanations for our patient’s condition-e.g., spontaneousdepression (unlikely, in view of the time course) or a diuretic-induced mood change (unlikely, since he was on a potassiumsupplement). Nonetheless we hope that our experience will helpfellow clinicians to use j-blockers more carefully.Department of Behavioral Sciences,Lincoln Institute of Health Sciences,Carlton, Victoria, Australia

Department of Psychiatry,Medical School,University of Calfornia, San Diego,and V.A. Medical Center,

San Diego, California 92161, U.S.A.

JON W. RUSSELL

MARC A. SCHUCKIT

GENERALISED ALLERGIC REACTION WITHSYNTHETIC HUMAN INSULIN

SiR,-Generalised reactions to insulin are rare. We have seen apatient who reacted in this way to highly purified beef and porkinsulin and to synthetic human insulin.A 28-year-old housewife acquired gestational diabetes during her

third pregnancy 18 months ago. ’Hypurin’ isophane insulin (highlypurified beef; Weddel) 8-10 units daily was required from 30 weeksuntil delivery. She then remained well until she presented withthirst, polyuria, and a blood glucose of 29’ 1 mmol/1 (524 mg/dl). Shehas a history of urticaria and penicillin allergy.She was treated with hypurin neutral insulin (highly purified

beef; Weddel) 6 units twice daily, and, 12 days later, had ageneralised urticarial rash 15 min after an injection. This reactiongot worse with each dose but ’Velosulin’ (highly purified porcine;Nordisk) caused a similar reaction and human insulin (emp)(’Human Actrapid’; Novo) 6 units resulted in a severe exacerbationof her urticaria and swelling of her hands and feet.Skin-patch testing was done with hypurin neutral, velosulin,

human actrapid, soluble insulin, ’Neusilin’, actrapid, and humaninsulin (crb) (’Humulin’; Lilly) with a specially prepared solution ofm-cresol 0 - 16% w/v plus phenol 0 . 065% w/v; and with a solution ofzinc sulphate 0 - 0006% w/v. Zinc, which has been implicated as acause of insulin allergy, is not in the formulation of short-actinginsulins but is present entrapped in insulin at a concentration of12-16 xg per 100 U. A positive reaction with a weal and flare of atleast 5 mm was obtained with all the insulins but subjectively therewas less irritation with humulin. No reaction was obtained withM-cresol/phenol or zinc.Desensitisation was started with humulin 0.5 5 unit daily

increasing to 3 units twice daily over 7 days. Each dose was given

6 Petries WM, Maffucci RJ, Woosley RL. Propranolol and depression Am J Psychiatry1982; 139: 1.

1 Femglos MN, Jegasoghy BV. ’Insulin’ allergy due to zinc. Lancet 1979; i: 122-24.

mixed with dexamethasone 0-05 mg. The first injection wasuncomplicated but the remaining injections resulted in a weal andflare. Desensitisation was continued without dexamethasone, thedosage increasing to 6 units twice daily, over 5 days with a gradualreduction in the local reaction.

, The clinical manifestations of insulin allergy resemble those

produced by foreign proteins, and there is usually a history ofinterrupted insulin treatment. Skin-patch testing suggested that theallergen in our patient was the insulin rather than any additive. Thiscase report indicates that a highly atopic individual may have ageneralised allergic response to synthetic human insulin after

previously being sensitised to beef insulin.

We thank Dr Peter J. Watkins, King’s College Hospital, London, for hisadvice and Weddel Pharmaceuticals Ltd, Wrexham, for the solution ofm-cresol/phenol.

Department of Medicine,War Memorial Hospital,Wrexham, Clwyd LL11 1EG

A. O. CARVETH-JOHNSONK. MYLVAGANAMD. F. CHILD

ALPHA1-ANTITRYPSIN AND OCULAR SENSITIVITYTO CROMOGLYCATE

SIR,-Dr Price (Sept. 11, p. 606) reported on a child with thecombination of alphal-antitrypsin (a I-AT) deficiency, asthma, andsensitivity to disodium cromoglycate (’Intal’). In some instances,the attacks of asthma appeared to be precipitated by the drug.Earlier this year I described two patients who had an acute chemoticreaction of the conjunctiva following the topical administration ofdisodium chromoglycate after they had previously discontinued itsuse for a short time.’ Although I did not conclusively demonstratehomocytotropic antibodies, the rapid onset of the reaction and itsfavourable response to topical adrenaline suggested that it was ananaphylactic type of response in which the "shock organ" was theconjunctiva instead of the bronchiolar tree.Continued use of disodium cromoglycate relieved the symptoms

and signs of one of the patients, suggesting that, when he usedmedication after being without it for a period of time, the drug actedas an allergen and induced degranulation of the mast cells.Continued use of the drug stabilised the mast cells resulting in reliefof the symptoms and signs.

I have now measured serum al-AT levels in these patients andhave found them to be normal (150-240 as compared with a normalrange of 111-270 in our laboratory). Although the level of a I-ATwas not determined in the tears, we have previously found it in thetears in the presence of normal serum levels.2 The findings indicatethat in my two patients, a deficiency ofa 1 -AT was playing no role inthe reaction.

Francis I. Proctor Foundationfor Research in Ophthalmology,

University of California,San Francisco, California 94143, U.S.A. H. B. OSTLER

FIRE HAZARD OF NITROGLYCERIN AEROSOL

SIR,-A manufacturer’s representative has shown me a newproduct (’Nitrolingual Spray’; Rona Laboratories) which is anaerosol preparation ofnitroglycerin designed for spraying under thetongue for the relief of angina. I was told that headache was lesscommon with this preparation than with sublingual tablets, andtried the preparation myself to test this claim. I was struck by theethereal smell of the preparation, and cautiously tested whether itwas inflammable by aiming a dose at a lit match one foot away. Theresult was a sheet of flame. Should such an inflammable preparationbe available for oral use in patients some of whom might be holding alighted cigarette during an angina attack?

Artificial Kidney Unit,Royal Infirmary,Dundee DD1 9ND MICHAEL G. BAMBER

1. Ostler HB. Acute chemotic reaction to cromolyn. Arch Ophthalmol 1982; 100: 412-13.2. Tabbara KF, Ostler HB, Biswell R, Daniels T. Chronic ulcerative conjunctivitis with

alpha, antitrypsin deficiency. Ann Ophthalmol 1982; 14: 280-82.