554 with antigens in other helminths. Confusion will be reduced in c.F. tests if the optimal dilution of hydatid fluid is used instead of the low dilutions (1/2 or 1/4) which are selected empirically by some workers. Such low dilutions are almost certain to display all antigens present in whole hydatid fluid, where an optimal one (1/20-1/50 or greater) may reveal little more than the specific antigen. There are other possible causes of non-specific reactions: Kagan et al. 31 suggested that autoantibodies might react with host protein in hydatid antigen; but more important are the false-positive results in some patients with cancer.32 Norris33 suggested that a neoplastic condition in blood-group Plnegative subjects might be associated with an enhanced immunological response to the P substance present in hydatid fluids. Matossian and Araj34 found positive results by c.F. in three of fifty subjects who were in hospital with non-hydatid diseases. In serology it is not unusual to find antibody to a pathogenic organism in healthy persons who live and work in areas where the organism is endemic. For this reason it is not clear why H.A., a highly sensitive test, detects little or no antibody in sera from healthy persons living in areas where hydatid disease is endemic 25 32 34 36 even though specific H.A. antibodies to hydatid antigen are known to persist for a long time. This is in contrast to c.F. antibodies which, although they decline and sometimes disappear quite rapidly after infection is eradicated, are frequently reported in sera from these controls. Sometimes the c.F. antibodies may be due to infections with different parasites bearing common antigens, but this is not always the case since C.F. antibodies in control subjects were detected more often in one Welsh county where hydatid disease is common than in another where it is not,23 and the positive findings seem to be specific, since in the Welsh areas there is no likelihood of confusion from infections due to other parasites. Results of tests to detect antibodies to IgM, IgG, and IgA at different stages of the disease have been inconsistent. Matossian et al. 36 concluded that in c.F. the antigens reacted mainly with IgM antibodies and in H.A. with IgG. However, there is poor correlation between the tests which are alleged to react with the same specific immunoglobulin. Moreover, Matossian and Araj’9 could not confirm the previously reported usefulness of I.F. for detecting IgM antibodies, and no clear explanation was forthcoming. The blocking of specific IgM and IgA antibodies by high concentrations of IgG3’ is a possibility which has yet to be studied in hydatid serology. Patients are rarely investigated for hydatid disease in the early stages of infection so that, by the time symptoms arise, IgM antibodies may seldom be present. Since both H.A. and c.F. detect IgG antibodies, poor correlation in results might reflect participation in each test of different hydatid antigens. Perhaps the c.F. test applied simultaneously with H.A. (or a similar test like latex aggcross-react
31.
I. G., Norman, L., Allain, D. S., Goodchild, C. G. J. Immun. 1960, 84, 635. 32. Kagan, I. G., Bull. Wld Hlth Org. 1968, 39, 25. 33. Norris, T. J. Med. J. Aust. 1965, i, 792. 34. Garabedian, G. A., Matossian, R. M., Djanian, A. Y. J. Immun. 1957, 78,
Kagan,
269.
G., Osimani, J. J., Varela, J. C., Allain, D. S. Am. J. trop. Med. Hyg. 1966, 15, 172. 36. Matossian, R. M., Kane, G. J., Chantler, S. M., Batty, I., Sarhadian, H. Immunology, 1972, 22, 423. 37. Cohen, I. R., Norins, L. C., Julian, A. J. J. Immun. 1967, 98, 143.
35.
Kagan,
I.
lutination) would yield the highest number of true-positive results and at the same time give the best prognostic indications. At present there seems to be no in using immunofluorescence for diagnosis.
advantage
PSORIATIC ARTHRITIS THE frequency of psoriasis in the general population is believed to be around 1-2%.’The frequency of inflammatory polyarthritis in a psoriatic population has been reckoned at 6.8%.3 Patients with extensive psoriasis requiring admission to hospital may have an
unexpectedly high incidence of psoriatic arthritis-as high as 32% in one survey.4 An important follow-up5 of patients with psoriatic arthritis provides valuable information for rheumatologists and dermatologists. This paper, from the Rheumatism Research Unit, Leeds, and Stoke Mandeville Hospital, reviews 168 patients, of whom 94 have been followed for more than 10 years, The patients were divided into three types according to the pattern of their arthritis. 132 (78%) had an arthritis indistinguishable from rheumatoid arthritis; 28 (16.6%) had distal joint arthritis, affecting most commonly the distal interphalangeal joints of the fingers; and 8 (48 ! had a deforming arthritis affecting the spine, resembling ankylosing spondylitis, as well as severe involvement of peripheral joints. The sex ratio of the 168 pa tients showed a predominance of women in the
"indistinguishable" group (almost 2/1), an equal ratio in the "deforming" group, and a mild male preponderance in the "distal" group. The peak age of onset of the arthritis was between 36 and 45 years, although arthritis began three times more frequently before the age of 20 in the deforming group than in the indistinguishable group. Arthritis came on acutely in 42% of the patients, and half the patients in the deforming group had constitutional disturbances, sometimes with pyrexia. Psoriasis usually preceded the arthritis, but in 16% of patients arthritis preceded the skin lesions, often by several years. There was no consistent pattern of change in pre-existing psoriasis at the onset of arthritis As judged by the number of admissions to hospital and time off work, psoriatic arthritis was mild except in the deforming group. The distal group had the mildest arthritis, with 60% of patients not requiring admission to hospital. Certainly there was nothing to suggest that these patients are bad employment risks, and the patients with deforming arthritis made up the smallest group of all-8 most
out
of 168. It is in this last group that
complication of seronegative arthritis, was frequent, being found in a quarter of the men. It
uveitis,
a
also present in 12% of men with a distal arthritis. and in 4% of men and 9% of women with indistinguishable arthritis. On annual radiographic follow-up of the hands and feet, only a small number of joints deteriorated, and ar annual sheep-cell agglutination test (S.C.A.T.) was negative in most of the patients. However, 16% of the indistwas
1. Ingram, J. T. Lancet, 1964, i, 121. 2. Baker, H. Br. J. Derm. 1966, 78, 249. 3. Leczinsky, C. G. Acta derm-venereol., Stockh. 1948, 28, 483. 4. Little, H., Harvie, J. N., Lester, R. S. Can. med. Ass.J. 1975, 112, 31 5. Roberts, M. E. T., Wright, V., Hill, A. G. S., Mehra, A. C. Ann. rheum Dis.
1976, 35, 206.
555 group had a positive S.C.A.T. and another 10% of this group had a fluctuating S.C.A.T. result, sometimes positive, sometimes negative. The results would have been clearer if those patients with a persistently positive s.c.A.T. had been excluded. Psoriatic arthritis is characterised by a negative s.c.A.T., and a positive result suggests coincident psoriasis and rheumatoid arthritis. It is harder to say whether some of the seronegative indistinguishable group may have had seronegative rheumatoid arthritis. 27% of 57 patients responded well to phenylbutazone or oxyphenbutazone. Surprisingly the deforming group did better with these drugs than the other two groups. Antimalarials, the authors point out, worsen psoriasis and should not be used, and oral corticosteroids, although beneficial in most patients, may also severely exacerbate the skin disease. 18 patients died during the follow-up, and psoriatic arthritis or its treatment may have contributed to three of the deaths. This important study is unfortunately incomplete. It would be useful to have data on the number showing radiographic changes of ankylosing spondylitis and sacroiliitis (the annual radiographic review surprisingly does not include the spine). The histocompatibility antigens in these patients have not been examined: a threefold increase in the frequency of HLA-B13 and HLA-B17 is reported in psoriasis,6and in psoriatic arthritis HLA-B27 is said to be increased, especially if there is spondylitis.* Admittedly the link between HLA-B27 antigen and psoriatic arthropathy is not as clear as that between HLA-B27 and ankylosing spondylitis or Reiter’s syndrome. Little has been published on psoriatic arthritis in children. Work by Lambert et al. points to the existence of two main groups, one with arthritis indistinguishable from Still’s disease and the other with the patterns of adult psoriatic arthritis. Tendon-sheath involvement, most often of the flexor tendons of the hand, may be a major part of the disease. In the Leeds study,5 patients affected before the age of 20 usually had deforming arthritis, but there is no separate information about their subsequent course. Do they become more disabled than the adult psoriatic arthritic? What proportion have acquired spondylitis or sacro-iliitis, and what percentage are HLA-B27 positive ?
inguishable
PREGNANCY AFTER ORAL CONTRACEPTION
NOTHING sinister is known about pregnancies in who have completed a course of oral contraceptives, but in monitoring the effects of these widely used hormonal agents it is clearly sensible to include, as the Royal College of General Practitioners has done,’O the outcome of the first pregnancy after oral contraception has ceased. The College’s study now covers 5530 pregnancies in former pill users and twice as many controls. 13-40% of the control pregnancies and 18-82% of the women
in women who had been on oral contraceptives ended in an abortion. This gap closed considerably in the later part of the series (to 1532% and 16-93%, respectively) when spontaneous and induced abortions were recorded separately. In these smaller groups the frequency of induced abortion was 8.28% for the former pill users and 6.23% for the others. The College interprets this finding in social, not biological, terms: the higher rate was expected because "amongst women who choose the pill as a contraceptive there is likely to be a substantial proportion for whom the birth of another child would be highly undesirable." Induced abortion apart, the two groups were no different, the frequencies of ectopic pregnancy, stillbirth, multiple birth, and congenital abnormality being much the same. 136 pregnancies were in women conceiving while still taking the pill. 102 went to term, but only seven babies were abnormal and there were only two cases of congenital abnormality (imperforate anus with hydroureter, renal agenesis, and a rudimentary bladder in one and dislocation of the hip in the other). Six of these children were males. In the series as a whole there was a preponderance of males among the abnormal children born to mothers-who had taken the pill, while the sex ratio among the control infants was not unusual. The College’s study is to carry on until April, 1978, or beyond, but it now seems very unlikely that a course of oral contraception has any harmful effects on subsequent planned families.
pregnancies
TEMPORARY GLUTEN INTOLERANCE IN coeliac disease, both of adults and erance to gluten is permanent.’ But
workers report a syndrome in which gluten intolerance may be temporary.2When gluten is withdrawn, the child gets better; and, when gluten is reintroduced, the small-intestinal mucosa remains normal. As yet, no-one has done serial intestinal biopsies to obtain direct evidence of gluten intolerance, but some indirect evidence is emerging based on a test in which blood-xylose is measured 1 h after xylose.4 After gluten challenge in coeliac disease, abnormalities in xylose absorption closely reflect small-intestinal changes.5 Transient gluten intolerance commonly coexists with temporary cow’s-milk-protein intolerance, and probably both are part of a complex of food-protein intolerance. Cow’s-milk-protein intolerance has been linked with preceding gastroenteritis and with low serum-IgA concentrations at the time of diagnosis,6 and the same may well be true of transient intolerance. Rolles and McNeish7 report that HLA types are normally distributed in children who prove on reinvestigation not to have coeliac disease, whereas those with coeliac disease have a raised frequency of HLA-8; probably they are separate disorders.
Med.
1972, 287,
738.
7 White, S H., Newcomer, V. D., Mickey, M. R., Terasaki, P. I. ibid. p. 740. 8. Brewerton, D. A., James, D. C. O. Semin. Arthr. Rheum. 1975, 4, 191. 9 Lambert, J R., Ansell, B. M., Stephenson, E., Wright, V. Clin rheum. Dis. 1976, 2, 339. 10. Royal
College of General Practitioners’ Oral Contraception Study Gynœc. 1976, 83, 608.
Obstet
Br.
J.
some
Mortimer, P. E., Stewart, J. S., Norman, A. P., Booth, C. C. Br. med. J. 1968, ii, 7. 2. Visakorpi, J. K., Immonen, P. Acta pœdiat. scand. 1967, 56, 49. 3. Walker-Smith, J. A. Archs Dis. Childh. 1970, 45, 523. 4. McNeish, A. S., Rolles, C. J., Arthur, L. J. H. ibid. 1976, 51, 275. 5. Rolles, C. J., Anderson, C. M., McNeish, A. S. ibid. 1975, 50, 259. 6. Harrison, M., Kilby, A., Walker-Smith, J. A., France, N. E., Wood, C. B. S. Br. med. J. 1976, i, 1501. 7. Rolles, C J., McNeish, A. S. ibid. 1976, i, 1309. 1.
6 Russell, T. J., Schultes, L. M., Kuban, D. J. New Engl. J.
children, intol-
31.
I. G., Norman, L., Allain, D. S., Goodchild, C. G. J. Immun. 1960, 84, 635. 32. Kagan, I. G., Bull. Wld Hlth Org. 1968, 39, 25. 33. Norris, T. J. Med. J. Aust. 1965, i, 792. 34. Garabedian, G. A., Matossian, R. M., Djanian, A. Y. J. Immun. 1957, 78,
Kagan,
269.
G., Osimani, J. J., Varela, J. C., Allain, D. S. Am. J. trop. Med. Hyg. 1966, 15, 172. 36. Matossian, R. M., Kane, G. J., Chantler, S. M., Batty, I., Sarhadian, H. Immunology, 1972, 22, 423. 37. Cohen, I. R., Norins, L. C., Julian, A. J. J. Immun. 1967, 98, 143.
35.
Kagan,
I.
lutination) would yield the highest number of true-positive results and at the same time give the best prognostic indications. At present there seems to be no in using immunofluorescence for diagnosis.
advantage
PSORIATIC ARTHRITIS THE frequency of psoriasis in the general population is believed to be around 1-2%.’The frequency of inflammatory polyarthritis in a psoriatic population has been reckoned at 6.8%.3 Patients with extensive psoriasis requiring admission to hospital may have an
unexpectedly high incidence of psoriatic arthritis-as high as 32% in one survey.4 An important follow-up5 of patients with psoriatic arthritis provides valuable information for rheumatologists and dermatologists. This paper, from the Rheumatism Research Unit, Leeds, and Stoke Mandeville Hospital, reviews 168 patients, of whom 94 have been followed for more than 10 years, The patients were divided into three types according to the pattern of their arthritis. 132 (78%) had an arthritis indistinguishable from rheumatoid arthritis; 28 (16.6%) had distal joint arthritis, affecting most commonly the distal interphalangeal joints of the fingers; and 8 (48 ! had a deforming arthritis affecting the spine, resembling ankylosing spondylitis, as well as severe involvement of peripheral joints. The sex ratio of the 168 pa tients showed a predominance of women in the
"indistinguishable" group (almost 2/1), an equal ratio in the "deforming" group, and a mild male preponderance in the "distal" group. The peak age of onset of the arthritis was between 36 and 45 years, although arthritis began three times more frequently before the age of 20 in the deforming group than in the indistinguishable group. Arthritis came on acutely in 42% of the patients, and half the patients in the deforming group had constitutional disturbances, sometimes with pyrexia. Psoriasis usually preceded the arthritis, but in 16% of patients arthritis preceded the skin lesions, often by several years. There was no consistent pattern of change in pre-existing psoriasis at the onset of arthritis As judged by the number of admissions to hospital and time off work, psoriatic arthritis was mild except in the deforming group. The distal group had the mildest arthritis, with 60% of patients not requiring admission to hospital. Certainly there was nothing to suggest that these patients are bad employment risks, and the patients with deforming arthritis made up the smallest group of all-8 most
out
of 168. It is in this last group that
complication of seronegative arthritis, was frequent, being found in a quarter of the men. It
uveitis,
a
also present in 12% of men with a distal arthritis. and in 4% of men and 9% of women with indistinguishable arthritis. On annual radiographic follow-up of the hands and feet, only a small number of joints deteriorated, and ar annual sheep-cell agglutination test (S.C.A.T.) was negative in most of the patients. However, 16% of the indistwas
1. Ingram, J. T. Lancet, 1964, i, 121. 2. Baker, H. Br. J. Derm. 1966, 78, 249. 3. Leczinsky, C. G. Acta derm-venereol., Stockh. 1948, 28, 483. 4. Little, H., Harvie, J. N., Lester, R. S. Can. med. Ass.J. 1975, 112, 31 5. Roberts, M. E. T., Wright, V., Hill, A. G. S., Mehra, A. C. Ann. rheum Dis.
1976, 35, 206.
555 group had a positive S.C.A.T. and another 10% of this group had a fluctuating S.C.A.T. result, sometimes positive, sometimes negative. The results would have been clearer if those patients with a persistently positive s.c.A.T. had been excluded. Psoriatic arthritis is characterised by a negative s.c.A.T., and a positive result suggests coincident psoriasis and rheumatoid arthritis. It is harder to say whether some of the seronegative indistinguishable group may have had seronegative rheumatoid arthritis. 27% of 57 patients responded well to phenylbutazone or oxyphenbutazone. Surprisingly the deforming group did better with these drugs than the other two groups. Antimalarials, the authors point out, worsen psoriasis and should not be used, and oral corticosteroids, although beneficial in most patients, may also severely exacerbate the skin disease. 18 patients died during the follow-up, and psoriatic arthritis or its treatment may have contributed to three of the deaths. This important study is unfortunately incomplete. It would be useful to have data on the number showing radiographic changes of ankylosing spondylitis and sacroiliitis (the annual radiographic review surprisingly does not include the spine). The histocompatibility antigens in these patients have not been examined: a threefold increase in the frequency of HLA-B13 and HLA-B17 is reported in psoriasis,6and in psoriatic arthritis HLA-B27 is said to be increased, especially if there is spondylitis.* Admittedly the link between HLA-B27 antigen and psoriatic arthropathy is not as clear as that between HLA-B27 and ankylosing spondylitis or Reiter’s syndrome. Little has been published on psoriatic arthritis in children. Work by Lambert et al. points to the existence of two main groups, one with arthritis indistinguishable from Still’s disease and the other with the patterns of adult psoriatic arthritis. Tendon-sheath involvement, most often of the flexor tendons of the hand, may be a major part of the disease. In the Leeds study,5 patients affected before the age of 20 usually had deforming arthritis, but there is no separate information about their subsequent course. Do they become more disabled than the adult psoriatic arthritic? What proportion have acquired spondylitis or sacro-iliitis, and what percentage are HLA-B27 positive ?
inguishable
PREGNANCY AFTER ORAL CONTRACEPTION
NOTHING sinister is known about pregnancies in who have completed a course of oral contraceptives, but in monitoring the effects of these widely used hormonal agents it is clearly sensible to include, as the Royal College of General Practitioners has done,’O the outcome of the first pregnancy after oral contraception has ceased. The College’s study now covers 5530 pregnancies in former pill users and twice as many controls. 13-40% of the control pregnancies and 18-82% of the women
in women who had been on oral contraceptives ended in an abortion. This gap closed considerably in the later part of the series (to 1532% and 16-93%, respectively) when spontaneous and induced abortions were recorded separately. In these smaller groups the frequency of induced abortion was 8.28% for the former pill users and 6.23% for the others. The College interprets this finding in social, not biological, terms: the higher rate was expected because "amongst women who choose the pill as a contraceptive there is likely to be a substantial proportion for whom the birth of another child would be highly undesirable." Induced abortion apart, the two groups were no different, the frequencies of ectopic pregnancy, stillbirth, multiple birth, and congenital abnormality being much the same. 136 pregnancies were in women conceiving while still taking the pill. 102 went to term, but only seven babies were abnormal and there were only two cases of congenital abnormality (imperforate anus with hydroureter, renal agenesis, and a rudimentary bladder in one and dislocation of the hip in the other). Six of these children were males. In the series as a whole there was a preponderance of males among the abnormal children born to mothers-who had taken the pill, while the sex ratio among the control infants was not unusual. The College’s study is to carry on until April, 1978, or beyond, but it now seems very unlikely that a course of oral contraception has any harmful effects on subsequent planned families.
pregnancies
TEMPORARY GLUTEN INTOLERANCE IN coeliac disease, both of adults and erance to gluten is permanent.’ But
workers report a syndrome in which gluten intolerance may be temporary.2When gluten is withdrawn, the child gets better; and, when gluten is reintroduced, the small-intestinal mucosa remains normal. As yet, no-one has done serial intestinal biopsies to obtain direct evidence of gluten intolerance, but some indirect evidence is emerging based on a test in which blood-xylose is measured 1 h after xylose.4 After gluten challenge in coeliac disease, abnormalities in xylose absorption closely reflect small-intestinal changes.5 Transient gluten intolerance commonly coexists with temporary cow’s-milk-protein intolerance, and probably both are part of a complex of food-protein intolerance. Cow’s-milk-protein intolerance has been linked with preceding gastroenteritis and with low serum-IgA concentrations at the time of diagnosis,6 and the same may well be true of transient intolerance. Rolles and McNeish7 report that HLA types are normally distributed in children who prove on reinvestigation not to have coeliac disease, whereas those with coeliac disease have a raised frequency of HLA-8; probably they are separate disorders.
Med.
1972, 287,
738.
7 White, S H., Newcomer, V. D., Mickey, M. R., Terasaki, P. I. ibid. p. 740. 8. Brewerton, D. A., James, D. C. O. Semin. Arthr. Rheum. 1975, 4, 191. 9 Lambert, J R., Ansell, B. M., Stephenson, E., Wright, V. Clin rheum. Dis. 1976, 2, 339. 10. Royal
College of General Practitioners’ Oral Contraception Study Gynœc. 1976, 83, 608.
Obstet
Br.
J.
some
Mortimer, P. E., Stewart, J. S., Norman, A. P., Booth, C. C. Br. med. J. 1968, ii, 7. 2. Visakorpi, J. K., Immonen, P. Acta pœdiat. scand. 1967, 56, 49. 3. Walker-Smith, J. A. Archs Dis. Childh. 1970, 45, 523. 4. McNeish, A. S., Rolles, C. J., Arthur, L. J. H. ibid. 1976, 51, 275. 5. Rolles, C. J., Anderson, C. M., McNeish, A. S. ibid. 1975, 50, 259. 6. Harrison, M., Kilby, A., Walker-Smith, J. A., France, N. E., Wood, C. B. S. Br. med. J. 1976, i, 1501. 7. Rolles, C J., McNeish, A. S. ibid. 1976, i, 1309. 1.
6 Russell, T. J., Schultes, L. M., Kuban, D. J. New Engl. J.
children, intol-
