70

ranean lymphoma "malignant plasmacytoma" or at

least to postulate the origin of the tumour from B lym-phocytes.21 However, Rappaport, in his original descrip-tion of Mediterranean lymphoma,22 emphasised thatthere was no morphological evidence that the lym-phomas were histogenetically related to the diffuse plas-ma-cell infiltration, although in a more recent publica-tion23 he has claimed that the tumour cells show asimilar staining with antisera to alpha chain as the non-neoplastic plasma-cell infiltrate. We would criticise thisobservation on the grounds that the sections were nottrypsinised and the antisera were used at low dilution.Furthermore, the findings do not exclude non-specificuptake of alpha chains by the tumour cells. It is clearfrom other reports2,3 that the histology of Mediter-ranean lymphoma varies and that a significant numberof such tumours are pleomorphic "reticulum-cellsarcomas". In view of the epidemiological implications itis important to determine if some, or all, of thesetumours are of the same type as those described in this

paper.Characterisation of the specific malignant process as-

sociated with malabsorption should help to clarify therelationship between intestinal lymphoma and coeliacdisease. According to the criteria of Thompson24 andCooke and Asquith,25 a jejunal-biopsy specimen showingsevere villous atrophy and crypt hyperplasia is diagnos-tic of coeliac disease, and hence these workers would con-sider all the cases presented in this report to be adultcoeliac disease. However, if biopsy-proven gluten sensiti-vity is the accepted criterion for the diagnosis of coeliacdisease, then none of our patients qualify for that diag-nosis. The confusion is compounded by the statement ofSleisenger and Brandborg2’ that malabsorption causedby lymphoma may respond transiently to a gluten-freediet. To resolve the question of the specific relationshipbetween coeliac disease and lymphoma, patients present-ing with the type of lymphoma described here should becarefully studied for objective evidence of gluten sensiti-vity and for the presence of histocompatibility antigensHLA B8 and DW3, which are associated with coeliac dis-ease. 28,29

Non-specific chronic jejunal ulcers were present in 5of our cases, and 3 of these presented as ulcerative

jejunitis, a condition thought to be associated withcoeliac disease in much the same way as is lymphoma. In2 of these patients foci of pleomorphic lymphoma werefound only after an intensive histological search. A linkbetween ulcerative jejunitis and lymphoma has alreadybeen suggested 30,31 and our cases further support this.Moreover, characterisation of the lymphoma as malig-nant histiocytosis may explain the pathogenesis of ulcer-ative jejunitis, since the bases of ulcers not associatedwith pleomorphic tumour often contained sheets of mor-phologically normal, or only marginally atypical histio-cytes, and aggregations of similar cells were seen at in-tervals in intact mucosa. Tumour cells in malignanthistiocytosis may look deceptively benign,32 and conceiv-ably a diffuse infiltrate of malignant histiocytes, eitheralone or in association with reactive inflammation, maybe the cause of malabsorption, analogous to the "pre-lymphomatous" phase of mycosis fungoides.The characterisation of these cases of intestinal lym-

phoma as malignant histiocytosis has an important bear-ing on treatment, since local treatment, whether sur-

gery, radiotherapy, or both, will clearly not be curative.Successful chemotherapy for malignant histiocytosis hasbeen reported,33 and similar treatment is probably indi-cated when the disease affects the intestine.

Requests for reprints should be addressed to P.I.

REFERENCES

1. Fairley, N. H., Mackie, F. P. Br. med. J. 1937, i, 375.2. Al-Saleem, T., Al-Bahrani, Z. Cancer, N.Y. 1973, 31, 291.3. Nasr, K., Haghighi, P., Bakshanded, K., Abadi, P., Lahimgarzardeh, A. Dig.

Dis. 1976, 21, 313.4. Isaacson, P., Wright, D. H. Unpublished.5. Sternberger, L. A. in Immunocytochemistry; p.129. Englewood Cliff, New

Jersey, 1974.6. Huang, S, Minassian, H., More, J. D. Lab. Invest. 1976, 35, 383.7. Byrne, G. E., Rappaport, H. in Gann Monograph on Cancer Research

(edited by K. Akazaki et al.); vol. 15, p.145. Tokyo, 1973.8. Abele, D. C., Griffin, T. B. Archs Derm. 1972, 106, 319.9. Viathianathan, I., Fishkin, S., Gruben, J. E. Am. J. clin. Path. 1967, 47,

160.10. Chawla, S. K., Lopresti, P. A., Burdman, D., Sileo, A., Govoni, A. F., Smu-

lewicz, J. J. Am. J. Gastroent. N.Y. 1975, 63, 129.11. Macgillivray, J. B., Duthie, J. S. J. clin. Path. 1977, 30, 120.12. Comes, J. S. Proc. R. Soc. Med. 1967, 60, 732.13. Thompson, H. J. clin. Path. 1974, 27, 710.14. Henry, K., Farrer-Brown, G. Histopathology, 1977, 1, 53.15. Lancet, 1977, i, 1191.16. Chambers, T. J. J. Path. 1977, 122, 163.17. Mason, D. Y., Labaume, S., Preud’Homme, J. L. Clin. exp. Immun. 1977,

29, 413.18. Taylor, C. R. Eur. J. Cancer, 1976, 12, 61.19. Lukes, R. J., Collins, R. D. Cancer, N.Y. 1974, 34, 1488.20. Galian, A., Lecestre, M. J., Scotto, J., Bognel, C., Matuchansky, C., Ram-

baud, J. C. ibid. 1977, 39, 2081.21. Lewin, K. J., Kahn, L. B., Nouis, B. H. ibid. 1976, 38, 2511.22. Rappaport, H., Ramot, B., Hulu, N., Park, J. C. ibid. 1972, 29, 1502.23. Pangalis, G. A., Rappaport, H. Lancet, 1977, ii, 880.24. Thompson, H. in Current Topics in Pathology (edited by B. C. Morson);

p.49. Berlin, 1976.25. Cooke, W. T., Asquith, P. Clins Gastroent. 1974, 3, 3.26. Eidelman, S., Parkins, A., Rubin, C. E. Medicine, Baltimore, 1966, 45, 111.27. Sleisenger, M. H., Brandborg, L. L. Malabsorption; p.195. Philadelphia,

1977.28. Falchuk, Z. M., Rogentine, G. N., Stroker, W. J. clin. Invest. 1972, 51,

1602.29. Keuning, J. J., Pena, A. S., van Leeuwen, A., van Hooff, J. P., van Rood,

J. J. Lancet, 1976, i, 506.30. Hourihane, D. O’B., Weir, D. G. Gastroenterology, 1970, 59, 130.31. Whitehead, R. Gut, 1968, 9, 569.32. Rappaport, H. Atlas of Tumor Pathology; p.48. Washington, D.C., 1966.33. Stein, R. S., Morgan, E. M., Byrne, G. C. Cancer, N.Y. 1976, 38, 1083.

X-LINKED ICHTHYOSIS DUE TOSTEROID-SULPHATASE DEFICIENCY

LARRY J. SHAPIRO ROBERTA WEISS

Division of Medical Genetics, Department of Pediatrics,U.C.L.A. School of Medicine, Harbor General Hospital

Campus, Torrance, California, U.S.A.

DIANNE WEBSTER

Section of Cytogenetics, Princess Mary Laboratory, AucklandHospital, Auckland, New Zealand

JOHN T. FRANCE

Postgraduate School of Obstetrics and Gynæcology, NationalWomen’s Hospital, Auckland, New Zealand

Summary An assay of cultured skin fibroblastsidentified several individuals with

3&bgr;-hydroxysteroid-sulphate sulphatase deficiency. Allpatients with this inborn error of metabolism had clini-cally apparent ichthyosis and a family history of thisskin disorder compatible with X-linked inheritance. It isconcluded that steroid-sulphatase deficiency is the bio-

71

chemical basis of at least some cases of X-linked ich-thyosis.

Introduction

DEFICIENCY of the microsomal hydrolase 3[3-hydroxy-steroid sulphate sulphatase is an inborn error of sulpha-ted-steroid metabolism in man.1-5 Original clinical des-criptions of this entity focused on prenatal and perinatalmanifestations. Pregnancies in which the placenta wassubsequently shown to have reduced steroid-sulphataseactivity were characterised by extraordinarily lowmaternal urinary and serum cestriol concentrations. Inaddition, in many of these pregnancies there was a fail-ure of normal parturitional mechanisms and delivery bycxsarean section was not uncommon.

Placental steroid-sulphatase activity is important forthe desulphation of various steroidal precursors, a

necessary step in the biosynthesis by the placenta of thelarge amounts ofoestrogens produced in pregnancy. Thisde-conjugation seems also to be critical for the transportof these steroids among maternal, placental, and fetalcompartments. The discovery of pregnancies with verylow oestriol production due to a deficiency of placentalsteroid-sulphatase activity helped to establish theselinks. All affected pregnancies reported to date have in-volved"male infants who appeared to be clinically nor-mal after birih.We used cultured fibroblasts from the male infant in

such an affected pregnancy to demonstrate that steroid-

sulphatase deficiency in these patients affects somatictissues other than the placenta, and persists throughoutlife.3 It therefore seemed possible that some phenotypicexpression of this enzymopathy might be demonstrablepostnatally. We investigated two families in which pla-cental steroid-sulphatase activity had been abnormallylow in some pregnancies and found that several othermembers of these families were reported to have hadX-liriked ichthyosis.

Material and Methods

The first patient ever reported to have placental steroid-sul-phatase deficiency is a member of a New Zealand family(family K).’ Two other younger siblings had a similar abnor-mality.l.2 The F family in Torrance, California, in which theresults of steroid-sulphatase assays of the placenta and cul-tured skin fibroblasts have been described elsewhere,3 werealso investigated. All available members of these two familieswere seen and examined by one of us and a dermatologist.Family members also described several individuals with ich-thyosis who were dead or could not be examined. Fibroblastlines were established and maintained in conventional fash-ion.6 All assays were performed at similar passage number, celldensity, and time after subculture. Dehydroepiandrosterone-sulphate (D.H.E.A.s.)-sulphatase activity was assayed in fibro-blast homogenates as described elsewhere.3 Cholesterol sulpha-tase was assayed in these patients’ cells and there was completecorrelation with the D.H.E.A.s.-sulphatase data.7

Results

In both families (figs. 1 and 2) ichthyosis seemed tosegregate as an X-linked trait affecting males only,although autosomal dominant transmission with sex-

limited expression cannot be excluded. In those individ-uals in whom ichthyosis developed, the skin had usuallyappeared normal at birth, and first appeared abnormalat about 3 months of age. After this ichthyosis seemedto persist for life. The trunk and extensor surfaces of the

Fig. 1-K family pedigree. /’

Individuals with clinical ichthyosis are indicated by filled-in sym-bols. A slash denotes a case in which the placenta was steroid-sulpha-tase deficient. Levels of cholesterol-sulphatase activity in skin fibro-blasts for each individual tested are shown below in italics. Normallevels of steroid-sulphatase activity in this assay are 4.64:t 1.99 pmoledesulphated/mg protein/h (n= 11). -

Fig. 2-F family pedigree. l

Symbols as in fig. 1.extremities were most involved. Individual 11-5 in the F

family had a slit-lamp ophthalmological examinationand was found to have deep corneal opacities identicalwith those described by Sever et al. in patients withX-linked ichthyosis.8

All individuals with deficient fibroblast cholesterol-

sulphatase activity had clinical ichthyosis. All those withnormal levels of sulphatase activity had no skin disease.Patients n!-9 in the F family and 11-2 in the K family,although presumably obligate heterozygotes for themutant sulphatase gene, had low normal levels of choles-terol-sulphatase activity in their fibroblasts. Further-more, careful clinical examination did not disclose anypatches of discernibly ichthyotic skin as might be antici-pated in an X-linked dermatological condition with

lyonisation. Several of the sulphatase-deficient individ-uals identified through the development of ichthyosisand fibroblast studies were born after the spontaneousonset of labour and without a cxsarean section beingnecessary.

Discussion

Ichthyosis is a term which describes the clinical find-ings in a group of inherited and sporadic, non-inflamma-tory skin diseases.9 The more common inherited vari-eties of ichthyosis may exhibit dominant, autosomalrecessive, or X-linked inheritance in various families.9Clinical heterogeneity has been recognised even withinthe X-linked varieties of ichthyosis, with two and per-haps three variant forms being delineated. 10,11 X-linkedichthyosis is quite common, occurring in 1 in 6190 malesin Englandl2 and 1 in 5200 males in Israel.13 The genefor at least some varieties of X-linked ichthyosis seemsto be moderately closely linked with the gene for the Xgblood-group substance. 9

Ichthyosis is the only recognised postnatal clinical

abnormality in patients with steroid-sulphatase de-

72

ficiency. Culture of skin fibroblasts allowed us to identifyaffected individuals long after their placentas were nolonger available for study. The exact relation betweensulphated-steroid metabolism and ichthyosis in our

patients is uncertain. However, the skin is an importantorgan in steroid biotransformation in man. Whole-skinexplants from healthy people can sulphate exogenousdehydroepiandrosterone to dehydroepiandrosterone sul-phate14 and have sulphatase activity capable of hydro-lysing 3p-OH-steroid sulphates.15 It therefore seems

reasonable to suggest that diminished steroid-sulphataseactivity could alter metabolism in skin.

However, steroid-sulphatase deficiency may only befortuitously associated with ichthyosis, perhaps throughclose linkage of X-chromosomal genes. This seems un-likely for two reasons. First, ichthyosis and steroid-sul-phatase deficiency occurred together in two ethnicallyand geographically separated families and were alsofound together in one other family known to us.16 Twoother infants with placental sulphatase deficiency stu-died in the Netherlands also had ichthyosis "of theX-linked type" .17,18 A causal relation between steroid-sulphatase deficiency and ichthyosis accords with theobservation that patients with the rare autosomal reces-sive disorder of multiple sulphatase deficiency who havevery low levels of lysosomal arylsulphatase A and B,iduronate sulphatase, and heparan-N-sulphatase alsohave very low levels of steroid sulphatase.1,19,20 Many ofthese patients seem to have ichthyosis as well.21,22 There-fore it seems that steroid-sulphatase deficiency and ich-thyosis are probably causally related.We thank Dr D. M. Rowan and Dr D. A. Scolly of the Skin Clinic,

Auckland Hospital for their assistance with dermatological assess-ments and skin biopsies, and Mrs Elizabeth Torres for assistance inpreparation of the paper. This study was supported in part byN.LG.M.S. Training Grant 1T32M07414-01, National FoundationGenetics Center Grant C-114 and Basil O’Connor starter research

grant 5-6 from the National Foundation-March of Dimes.

Requests for reprints should be addressed to L. S., Division of Medi-cal Genetics, Harbor General Hospital, Torrance, California, U.S.A.

REFERENCES

1. France, J. T., Liggins, G. C. J. clin. Endocr. Metab. 1969, 29, 138.2. France, J. T., Downey, J. A., McNaught, R. W., Seddon, R. J., Liggins,

G. C. Excerpta med. int Congr. ser. 1976, no. 403, 2, 319.3. Shapiro, L. J., Cousins, L., Fluharty, A. L., Stevens, R. L., Kihara, H.

Pediat. Res. 1977, 11, 894.4. France, J. T., Seddon, R. J., Liggins, G. C. J. clin. Endocr. Metab. 1973,

36, 1.5. Fleigner, J. R. H., Schindler, I., Brown, J. B. J. Obstet. Gynæc. Br. Com-

monw. 1972, 79, 810.6. Cantz, M., Kresse, H., Barton, R. W., Neufeld, E. F. Meth. Enzymol. 1972,

28, 884.7. Shapiro, L. J., Weiss, R. Excerpta med. int. Congr. ser. 1977, no. 426, p.

57 (abstr.).8. Sever, R. J., Frost, P., Weinstein, G. J. Am med. Ass. 1968, 206, 2283.9. Goldsmith, L. A. Prog. med. Genet. 1976, 1, 185.

10. Passarge, E., Post, B., Schopt, E. in Birth Defects Original (edited by D.Bergsma); vol VII, no. 8, part XII, p.46. Baltimore, 1971.

11. Fitch, N., Segool, R., Ferenczy, A., Cohen, H. Clin. Genet. 1976, 9, 71.12. Wells, R. S., Kerr, C. B. Br. med. J. 1966,  , 947.13. Ziprkowski, L., Feinstein, H. Br. J. Derm. 1972, 86, 1.14. Gallegos, A. J., Berliner, D. L. J. clin. Endocr. Metab. 1967, 27, 1214.15. Kim, M. H., Herman, W. L. ibid. 1968, 28, 187.16. France, J. T. Unpublished.17. Jobsis, A. E., van Duuren, C. Y., de Vries, G. P., Koppe, J. G., Rijiken, Y.,

van Kempen, M. J., de Groot, W. P Ned. Tijdschr. Geneesk. 1976, 120,1980.

18. Koppe, J. G., Rijiken, Y., Jobsis, A. C., Marinkovic-Ilsen, H. Excerpta med.int. Congr. ser. 1977, no. 426, p. 57 (abstr.).

19. Murphy, J. V., Wolfe, J. H., Balzs, E. A., Moser, H. in Lipid Storage Dis-eases (edited by J. Bernsohn and H. J. Grassman); p. 67. New York, 1971.

20. Eto, Y., Wiesmann, U. N., Carson, J. H., Herschkowitz, N. N. Archs Neurol.1974, 30, 153.

21. Moser, H. W in Metabolic Basis of Inherited Disease (edited by J. B. Stan-bury, J. B. Wyngaarden, and D. S. Fredrickson); p. 668. New York, 1972.

22. Neufeld, E. F., Aylsworth, A. Personal communication.

UPRIGHT POSTURE AND THE EFFICIENCY OFLABOUR

T. J. MCMANUS A. A. CALDER

University Department of Obstetrics and Gynæcology,Glasgow Royal Maternity Hospital, Rottenrow,

Glasgow G4 0NA

Summary The claim that an upright maternalposture during labour improves the

efficiency of the uterus to the benefit of both mother andfetus has been investigated in a randomised prospectivestudy. 40 patients undergoing induction of labour wereallocated to a recumbent group or an upright group. Nodifferences were found between the groups in the lengthof labour, mode of delivery, requirements of oxytocicand analgesic drugs, or fetal and neonatal condition.Our data do not support calls to change conventionalintrapartum nursing attitudes.

Introduction

Mendez-Bauer and colleagues’ have claimed that theefficiency of labour is greatly improved if the motheradopts an upright posture. In their study, primigravidasin spontaneous labour were asked to alternate every 30minutes between the dorsal supine and the standing pos-ition. They claimed that the upright position was associ-ated with an increase in uterine activity in 50% of pa-tients, a considerable shortening of labour, and a

reduction in the mother’s need for analgesia. Dunn2 sup-ported this view and criticised the conventional obstetricpractice of nursing patients in a recumbent position dur-ing labour.We have conducted a randomised prospective study of

the influence of maternal posture on labour. The pa-tients had labour induced and consequently were in hos-pital throughout labour, making possible accurate as-sessment and data collection. We compared the results inpatients randomly allocated to a group nursed in thelateral recumbent position throughout labour and a

group who were encouraged to remain upright.

Patients and Methods

40 patients were studied, of whom 20 were primigravidasand 20 were having their second or third confinement. All gaveinformed consent to participation in the study. Within eachcategory the patients were randomly allocated to a recumbentor upright management, so that there were four groups of 10patients (table I). In every case the gestational age was 38weeks or more, and the cervical score3 was six or greater. No

multiple pregnancies or breech presentations were included.The groups were well matched for gestational age, cervical

TABLE I-DETAILS OF PATIENTS