152 In

most

series

agranulocytosis

has been

an

infrequent

com-

plication of levamisole, but in Australia’ and in Finland about 10% of patients on the drug have been affected, and so we looked at HLA patterns to see if genetic constitution played a role in this drug sensitivity. The 17 patients with agranulocytosis were HLA typed and the results were compared with the antigen frequencies of 900 Finnish blood-donors. 6 patients had B8 and 6 had B27 (33%) but these figures do not differ significantly from those for controls (20 and 14%). Even less deviation was seen for the other thirty-three HLA antigens tested. 61% of patients and 54% of controls had one or two antigens of the B27 cross-reactive group (B7, B27, Bw22, B40). Thus B27-positive cancer patients, unlike patients with rheumatoid arthritis2 do not seem especially sensitive to the granulocyte-depleting effect of levamisole. Other side-effects of levamisole treatment were gastric pain (2 patients), nausea (2), headache (1) and fever without leucopenia (15). Because of the side-effects levamisole therapy was discontinued in 29 out of 174 patients (17%). Preliminary reports of levamisole have been promising, but in our experience the frequency of serious side-effects is an important consideration, especially if the survival of the patients is not strikingly improved or if other treatments prove satisfactory.

Radiotherapy Clinic, Helsinki University Central Helsinki 29, Finland

Hospital,

Finnish Red Cross Transfusion Service, Helsinki

LASSE TEERENHOVI ERKKI HEINONEN PENTTI GRÖHN PENTTI KLEFSTRÖM MAIJA MEHTONEN

ANJA TIILIKAINEN

CHRONIC LYMPHOCYTIC LEUKÆMIA AFTER

may have been fortuitous and

independent of the penicillamine may be higher in patients with rheumatoid arthritis than in the general population.’ In experiments on mice, Harris2 found a lymphocyticleukaemia-like clinical picture in animals given penicillamine for 6 months. In man, c.L.L. has never been reported as a complication to treatment with penicillamine. This may, however, be because such a complication is very rare or because most patients have not been treated long enough for the leukaemia to develop. treatment.

Furthermore, the incidence of C.L.L.

JENS E. CLAUSEN JENS C. K. ARNDAL

Department of Medicine, Ringsted Hospital, DK-4100 Ringsted, Denmark

LENNART GRAM

SINE B. KUDAHL

General Practice,

PETER FOG

Ortved, Ringsted

INCREASED HEPATIC SENSITIVITY TO PARACETAMOL

SIR,-Bonkowsky and colleagues,3 describe a patient with chronic hepatitis and liver fibrosis while taking normal therapeutic doses of paracetamol (acetaminophen). They ascribed the reaction to an unusual sensitivity to the drug. This case reminded me of a patient I saw 2 years ago. He was a 55-yearold man with alcohol abuse for a year 7 years earlier, after his wife’s death. For many years he had had backache for which, 2 weeks before admission, he had, for the first time, been prescribed a tablet containing paracetamol and chlormezanone. He took 2-7 g of paracetamol/day for a week, but because of malaise he reduced the dose to 1-35g/day for 2 days, and 0.45 g every other day three times. Because of increasing malaise,

TREATMENT WITH PENICILLAMINE

SIR,-We have seen a 58-year-old woman with rheumatoid arthritis in whom chronic lymphocytic leukaemia (C.L.L.) developed after she had taken penicillamine for 5 years. During 1959-63 the patient had had periodic attacks of arthritis. Classical rheumatoid arthritis was diagnosed in 1963. For the next 5 years the disease was controlled by salicylates and indomethacin. The arthritis then flared up, and she was treated with gold, receiving a total of 3 g ’Sanocrysin’. A remission lasting nearly 2 years was induced. In 1970 she relapsed. This time gold had no effect, but she responded to corticosteroids. In 1973, she had an exacerbation of the polyarthritis, and treatment with penicillamine was started. The dose was gradually increased to 600 mg daily. After 6 weeks she had a complete remission. Nevertheless treatment with penicillamine (600 mg daily) and prednisone (5 mg daily) was continued. When she was admitted to our hospital in 1968 and 1973, she had had no lymphadenopathy and no splenomegaly, and leucocyte and differential counts had been normal. Since 1974 her general practitioner had checked her blood every month. The white-cell count remained normal until February, 1978, but after that it rose to 45x10/1. On March 15 she was readmitted to our hospital. Her cervical, supraclavicular, axillary, and inguinal lymph-nodes

were

but there was no splenomegaly. The differential count showed 92% lymphocytes. The bone-marrow was hyperplastic with 81% lymphocytes. A minor population of the lymphocytes was larger than normal and seemed immature. Penicillamine was stopped without relapse of the arthritis. This association between rheumatoid arthritis and C.L.L.

moderately enlarged,

1. Christiansen, F.

T., Ng, K. C., Zilko, P. J, Dawkins, R. L. Lancet, 1977, i, 1111. 2. Veys, E. M., Mielants, H., Verbruggen, G. ibid, 1978, i, 148.

LIVER-FUNCTION TESTS

aspartate aminotransferase; ferase ; A.L.P.= alkaline phosphatase. A.S.A.T.=

(ON SERUM)

A.L.A.T.=

alanine aminotrans-

upper abdominal pain, yellow discoloration of the skin, and dark urine he attended the hospital. He was jaundiced and tender under the right costal margin, but had no spiders or palmar erythemas. He had normal erythrocyte-sedimentation rate and haemoglobin concentration, but only 3.6 x 109/1 white blood-cells and only 35xl0l/l platelets. The counts slowly returned to normal while the patient was in hospital. Liverfunction tests are summarised in the table. A test for HBsAg was negative. The IgG concentration was normal, the IgA was twice the upper limit of normal and the IgM marginally increased. Liver biopsy, 9 days after admission, revealed broad strands of collagenous connective tissue with few lymphocytes

1. 2.

Wintrobe,M. M.ClinicalHematology;p. 1463.Philadelphia,1975. Harris, G. Lancet, 1976, ii, 1356. 3. Bonkowsky, H. L., Mudge, G. H., McMurtry, R. J. Lancet, 1978, i, 1016.

Chronic lymphocytic leukaemia after treatment with penicillamine.

152 In most series agranulocytosis has been an infrequent com- plication of levamisole, but in Australia’ and in Finland about 10% of patients...
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