of 4 /4
110 from stresses which might precipitate chronic nephritis, especially when there is no evidence of permanent renal damage. JANEWAY and his colleagues ascribe the improved prognosis in their child patients with nephrosis to the control of intercurrent infections with sulphadiazine and the newer antibiotics. The avoidance of infection is the most important part of the management of these cases-the deaths from peritonitis or bacteriæmia outnumber those from uraemia. The most serious symptom requiring treat- ment is massive oedema, usually with ascites. This is a result of the hypoproteinsemia, but other factors are involved which are not yet understood. Spon- taneous remissions are common, with no rise in the plasma-protein level, and attempts to raise it by injecting plasma intravenously do not always induce diuresis. The cedema is often difficult to control, for diuretics may or may not be effective. Urea, if it works, is unlikely to harm the kidneys, but mercurial diuretics with ammonium chloride are potentially dangerous. While oedema fluid is accumulating, these patients excrete very little sodium in their urine, and the administration of salt in amounts such as are present in milk or a normal diet will quickly increase their cedema. On the other hand, cutting down their salt to less than 0-5 g. daily may not reduce the oedema or even prevent it increas- ing further. The body-fluids have an affinity for sodium, and yet Fox and MCCUNE 6 have observed . that the plasma-sodium level may be low. They also noted that the urinary losses of potassium may be high during the cedema phase, and they therefore treated some cases with 5-15 g. of both sodium and potassium acetate daily ; this treatment stimulated a diuresis. They corellated the diuretic response with a return to a normal plasma-sodium level of 140 m.eq. per litre, and a raised urinary excretion of chloride as well as sodium. Potassium losses were also high. The occurrence of spontaneous remissions makes the effects of treatment difficult to assess. However, it is important to realise that electrolyte imbalance may be present and that treatment should not be directed solely to eliminating the sodium ion. The cation resins are being widely used to control oedema by eliminating sodium via the fæces, particu- larly where the oedema is a result of cardiac failure. In this issue, Dr. PAYNE and Dr. WILKINSON show that these substances will also reduce oedema in children with nephrosis. The simplicity of the treat- ment is an obvious advantage; the resin was readily taken by these children and their appetite usually improved as they lost weight. The disadvantages are that the resin eliminates potassium as well as sodium and tends to produce metabolic acidosis and nitrogen retention. In the present series ascites did not always respond well. There must be some potential danger in allowing the serum-potassium level to fall as low as it did in some of the children, since depletion of potassium in the muscles precedes a fall in the serum level. This disadvantage could probably be overcome by giving potassium salts and the resin at widely separated times, as FRIEDMAN and others recommend. Alternatively, a mixture of cation and anion resins with potassium might 6. Fox, C. L., McCune, D. J. Amer. J. med. Sci. 1948, 216, 1. 7. Friedman, I. S., Zuckerman, S., Cohn, T. D. Amer. J. med. Sci. 1951, 221, 672. eliminate sodium without depleting the body of potassium. As McCHESNEY and colleagues 8 point out, acidosis is to be expected from resin feeding, even in normal people ; acidosis is often induced in the treatment of cedematous states and is not objection- able so long as it remains compensated. Nevertheless, an acidosis may be undesirable in renal disease because it leads to a highly acid urine and this is often associated with granular casts even in normal adults. Must a high urinary pH be included among the stresses that may precipitate irreversible changes in the kidneys in lipoid nephrosis ? And might a highly acid urine, together with a heavy proteinuria, precipitate protein in the lower parts of the nephrons and therefore be dangerous ? So long as a free flow of urine is maintained this last effect is unlikely to be a hazard. PAYNE and WILKINSON, however, are worried by the tendency of the blood-urea to rise in some patients who had received the resin for several weeks, and FRIEDMAN and colleagues 7 believe that these resins should be used cautiously if at all in patients with kidney disease or renal insufficiency. For the present, at any rate, the use of cation resins for controlling nephrotic oedema in children should be reserved for cases where day to day clinical and laboratory observations can be made, and which have not responded to other treatment. Diagnosis of Disseminated Lupus ACUTE disseminated lupus erythematosus is pre- dominantly a disease of the adolescent and young adult female, and when the characteristic skin eruption is the first sign diagnosis is fairly easy. Commonly, however, other signs appear first. TUMULTY and HARVEY 9 describe a series of 32 patients among whom the skin lesions were the first sign in only 13, though 26 developed the rash at some stage; joint manifestations were the presenting sign in 17. Unexplained fever and loss of weight, gastro-intestinal symptoms, and rarely haemorrhage may be the initial complaint ; and sometimes the renal lesion first attracts attention. Clearly a laboratory test for the diagnosis of disseminated lupus erythematosus would be very helpful; and observation of peculiar changes in the bone-marrow has led to the development of such a test, which may prove specific. In 1948 HARGRAVES et al.10 noted that in bone- marrow preparations from patients with acute dis- seminated lupus two peculiar types of cells could be seen. The first type, which they called the " tart cell," was usually a histiocyte that seemed to have a secondary nucleus-sometimes two-with the staining properties of nuclear chromatin, though the shade was different from that of the primary nucleus ; some similarly affected polymorphonuclears were also found. The " tart cell " could be found, too, in bone-marrow from severely ill patients with many diseases. The second type of cell was polymorphonuclear, or band- form granulocyte, that had phagocyted more or less degenerate nuclear material ; this nuclear material was derived from other cells, or from autolysis of one of the lobes of the cell nucleus itself. They called this the " L.E. cell " because it apparently occurred only 8. McChesney, E.W., Dock, W., Tainter, M.L. Medicine, 1951, 30, 183. 9. Tumulty, P. A., Harvey, A. M. Bull. Johns Hopk. Hosp. 1949, 85, 47. 10. Hargraves, M. M., Richmond, H., Morton, R. Proc. Mayo Clin. 1948, 23, 25.

Diagnosis of Disseminated Lupus

Embed Size (px)

Citation preview

Page 1: Diagnosis of Disseminated Lupus

110

from stresses which might precipitate chronic nephritis,especially when there is no evidence of permanentrenal damage. JANEWAY and his colleagues ascribethe improved prognosis in their child patients withnephrosis to the control of intercurrent infectionswith sulphadiazine and the newer antibiotics. Theavoidance of infection is the most important partof the management of these cases-the deaths fromperitonitis or bacteriæmia outnumber those fromuraemia. The most serious symptom requiring treat-ment is massive oedema, usually with ascites. Thisis a result of the hypoproteinsemia, but other factorsare involved which are not yet understood. Spon-taneous remissions are common, with no rise in the

plasma-protein level, and attempts to raise it byinjecting plasma intravenously do not always inducediuresis. The cedema is often difficult to control,for diuretics may or may not be effective. Urea,if it works, is unlikely to harm the kidneys, butmercurial diuretics with ammonium chloride are

potentially dangerous. While oedema fluid is

accumulating, these patients excrete very littlesodium in their urine, and the administration of saltin amounts such as are present in milk or a normaldiet will quickly increase their cedema. On the otherhand, cutting down their salt to less than 0-5 g. dailymay not reduce the oedema or even prevent it increas-ing further. The body-fluids have an affinity forsodium, and yet Fox and MCCUNE 6 have observed

. that the plasma-sodium level may be low. Theyalso noted that the urinary losses of potassium maybe high during the cedema phase, and they thereforetreated some cases with 5-15 g. of both sodium and

potassium acetate daily ; this treatment stimulateda diuresis. They corellated the diuretic response witha return to a normal plasma-sodium level of 140 m.eq.per litre, and a raised urinary excretion of chlorideas well as sodium. Potassium losses were also high.The occurrence of spontaneous remissions makesthe effects of treatment difficult to assess. However,it is important to realise that electrolyte imbalancemay be present and that treatment should not bedirected solely to eliminating the sodium ion.The cation resins are being widely used to control

oedema by eliminating sodium via the fæces, particu-larly where the oedema is a result of cardiac failure.In this issue, Dr. PAYNE and Dr. WILKINSON showthat these substances will also reduce oedema inchildren with nephrosis. The simplicity of the treat-ment is an obvious advantage; the resin was readilytaken by these children and their appetite usuallyimproved as they lost weight. The disadvantagesare that the resin eliminates potassium as well as

sodium and tends to produce metabolic acidosis andnitrogen retention. In the present series ascites didnot always respond well. There must be some

potential danger in allowing the serum-potassiumlevel to fall as low as it did in some of the children,since depletion of potassium in the muscles precedesa fall in the serum level. This disadvantage couldprobably be overcome by giving potassium salts andthe resin at widely separated times, as FRIEDMANand others recommend. Alternatively, a mixture

of cation and anion resins with potassium might6. Fox, C. L., McCune, D. J. Amer. J. med. Sci. 1948, 216, 1.7. Friedman, I. S., Zuckerman, S., Cohn, T. D. Amer. J. med. Sci.

1951, 221, 672.

eliminate sodium without depleting the body ofpotassium. As McCHESNEY and colleagues 8 pointout, acidosis is to be expected from resin feeding,even in normal people ; acidosis is often induced in thetreatment of cedematous states and is not objection-able so long as it remains compensated. Nevertheless,an acidosis may be undesirable in renal diseasebecause it leads to a highly acid urine and this isoften associated with granular casts even in normaladults. Must a high urinary pH be included amongthe stresses that may precipitate irreversible changesin the kidneys in lipoid nephrosis ? And might ahighly acid urine, together with a heavy proteinuria,precipitate protein in the lower parts of the nephronsand therefore be dangerous ? So long as a free flowof urine is maintained this last effect is unlikely tobe a hazard. PAYNE and WILKINSON, however, areworried by the tendency of the blood-urea to rise insome patients who had received the resin for severalweeks, and FRIEDMAN and colleagues 7 believe thatthese resins should be used cautiously if at all in

patients with kidney disease or renal insufficiency.For the present, at any rate, the use of cation resinsfor controlling nephrotic oedema in children shouldbe reserved for cases where day to day clinical andlaboratory observations can be made, and whichhave not responded to other treatment.

Diagnosis of Disseminated LupusACUTE disseminated lupus erythematosus is pre-

dominantly a disease of the adolescent and youngadult female, and when the characteristic skineruption is the first sign diagnosis is fairly easy.Commonly, however, other signs appear first. TUMULTYand HARVEY 9 describe a series of 32 patients amongwhom the skin lesions were the first sign in only13, though 26 developed the rash at some stage;joint manifestations were the presenting sign in 17.

Unexplained fever and loss of weight, gastro-intestinalsymptoms, and rarely haemorrhage may be the initialcomplaint ; and sometimes the renal lesion firstattracts attention. Clearly a laboratory test for thediagnosis of disseminated lupus erythematosus wouldbe very helpful; and observation of peculiar changesin the bone-marrow has led to the development ofsuch a test, which may prove specific.

In 1948 HARGRAVES et al.10 noted that in bone-marrow preparations from patients with acute dis-seminated lupus two peculiar types of cells could beseen. The first type, which they called the " tartcell," was usually a histiocyte that seemed to have asecondary nucleus-sometimes two-with the stainingproperties of nuclear chromatin, though the shadewas different from that of the primary nucleus ; somesimilarly affected polymorphonuclears were also found.The " tart cell " could be found, too, in bone-marrowfrom severely ill patients with many diseases. Thesecond type of cell was polymorphonuclear, or band-form granulocyte, that had phagocyted more or lessdegenerate nuclear material ; this nuclear materialwas derived from other cells, or from autolysis of oneof the lobes of the cell nucleus itself. They called thisthe " L.E. cell " because it apparently occurred only8. McChesney, E.W., Dock, W., Tainter, M.L. Medicine, 1951, 30, 183.9. Tumulty, P. A., Harvey, A. M. Bull. Johns Hopk. Hosp. 1949,

85, 47.10. Hargraves, M. M., Richmond, H., Morton, R. Proc. Mayo Clin.

1948, 23, 25.

Page 2: Diagnosis of Disseminated Lupus
Page 3: Diagnosis of Disseminated Lupus
Page 4: Diagnosis of Disseminated Lupus

111

in the bone-marrow of patients with disseminatedlupus erythematosus. Attempts to confirm this findingdid not always succeed until it was discovered thatL.E. cells are not seen in direct smears of bone-marrowbut only in marrow preparations that have beenmixed with an anticoagulant-heparin, citrate, or

oxalate. SUNDBERG and LICK " then showed that L.E.cells, though scanty, were visible in smears madefrom peripheral blood of patients with disseminatedlupus, provided that the blood was first mixed withanticoagulant and then centrifuged. HASERICK andBORTZ 12 found that if the buffy cellular layer fromheparinised normal marrow was mixed with cell-freeplasma from patients with disseminated lupus, L.E.

cells could be detected in smears made from thereconcentrated buffy coat ; bone-marrow from patientswith various other diseases would serve as well.HASERICK and co-workers 13 later established that theactive factor in the plasma was associated with thegamma-globulin fraction.

It was naturally asked whether this L.E. cell

phenomenon was really specific. BERMAN et al.14

reported evidence that L.E. cells could be found inother syndromes of the allied collagen-disease group,and in some quite unrelated diseases too ; but theseodd phagocytic cells were much more common inbone-marrow from cases of disseminated lupus. Theytherefore evolved a quantitative test ; the number ofL.E. cells per 500 granulocytes, including polymorpho-nuclears and band-forms, is counted ; and a count of10 or more L.E. cells per 500 granulocytes is strongevidence of disseminated lupus erythematosus. Theyalso produced L.E. cells in normal bone-marrow bymixing it with plasma from patients suspected of

having disseminated lupus; this test did provespecific, for plasma from patients with other collagendiseases gave negative results. The test was madeeasier by LEE et al., 15 who showed that L.E. cells couldbe seen in smears from the buffy coat of heparinisedperipheral blood of patients with disseminated lupus ;or more easily by mixing the buffy coat from hepari-nised normal blood, or blood from a case of chronicmyeloid leukaemia, with cell-free plasma from a

patient with disseminated lupus. They found, too,that with this sort of test plasma from patients withdermatomyositis, scleroderma, rheumatoid arthritis,and other diseases did not produce L.E. cells. Theyinvestigated the action of anticoagulants and con-

cluded that these acted by giving time for the activeplasma factor to stimulate the phagocytic activity ofthe granulocytes and other cells ; for instance, ifactive plasma from a patient with lupus erythematosuswas mixed with normal white cells, only a few L.E. cellscould be found after 2 minutes ; and the number wasgreatest only 20-30 minutes after mixing. Adminis-tration of cortisone did not abolish the activityof the plasma. Histochemical studies have also linkedthe L.E. cells with the specific pathological changes ofdisseminated lupus. KLEMPERER and his colleagues 16had shown that in the tissues of patients with dissemi-nated lupus there were hæmatoxylin-staining bodies11. Sundberg, R. D., Lick, W. B. J. invest. Derm. 1949, 12, 83.12. Haserick, J. R., Bortz, D. W. Ibid, 13, 47.13. Haserick, J. R., Lewis, L. A., Bortz, D. W. Amer. J. med. Sci.

1950, 219, 660.14. Berman, L., Axelrod, A. R., Goodman, H. L., McClaughry, R. I.

Amer. J. clin. Path. 1950, 20, 403.15. Lee, S. L., Michael, S. R., Vural, I. L. Amer. J. Med. 1951,

10, 446.16. Klemperer, P., Gueft, B., Lee, S. J. Mt Sinai Hosp. 1949, 16, 61.

composed of depolymerised nucleic acid. LEE et al.demonstrated that the inclusion bodies in the L.E.

cells are also composed of desoxyribose nucleic acid, aconsiderable proportion of which is depolymerised.From all this work it seemed that the easiest way

to use the L.E. cell phenomenon for diagnosingdisseminated lupus erythematosus was to mix cell-free plasma from the patient with buffy coat fromnormal heparinised blood, allow the mixture to standat 37°C for 30 minutes, centrifuge at 1500-2000 r.p.m.to concentrate the buffy coat, make smears from thebuffy coat, and look for L.E. cells ; if they were at allnumerous the diagnosis was settled. Recently, how-ever, MATHIS 17 has described a simple technique bywhich L.E. cells can be demonstrated in large numbersby direct examination of the peripheral blood of thepatients themselves ; no cells from another personare needed. The blood is heparinised and allowed tosettle by standing for 30 minutes. Then the plasmaand the uppermost level of the underlying cells aretransferred to a sterile centrifuge tube, allowed tostand at 37°C for 45 minutes, and centrifuged at1500-2000 r.p.m. Films are made from the buffy coatby compressing drops of material between glass slides.This test is claimed to give consistently positive resultsin disseminated lupus and consistently negative resultsin other conditions, including dermatomyositis anddiscoid lupus; and since bone-marrow cells were notused, no confusion with " tart cells " arose. Stillmore recently SCHLEICHER 18 has reported that plasmaor serum that will produce the-L.E. phenomenon willalso cause aggregation of washed group-0 Rh-positivered cells in the presence of egg-albumin, provided thatthe albumin solution and the red-cell suspension havebeen adequately cooled beforehand. This is an even

simpler test, but it has not yet been proved specificfor lupus erythematosus. Clearly, however, a rela-

tively simple laboratory test for this disorder willsoon be available.

Annotations

PORTRAIT OF A PHYSICIAN

Mr. Winston Churchill’s capacity and scope are suchthat the company at dinner in the Royal College ofPhysicians, on July 10, heard with enthusiasm his offerto serve-anyhow in emergency-as a member of ourprofession. As he pointed out, he holds the necessaryqualifications, having recently become an honoraryfellow of the College, and holding an honorary fellowshipof several years’ standing in the complementary establish-ment in Lincoln’s Inn Fields. His claim to decisionandthe ability to use a sharp edge cannot be questioned ;and his dazzling survey of modern chemotherapy wouldhave satisfied any examiner. He was presenting to LordMoran, on this occasion, the portrait of Lord Moran,painted by Pietro Annigoni, which will ultimatelyhang in the College. This fine painting, in the sitter’sown phrase, strikes the imagination and-unlike mostofficial portraits-is a work of art which will capture theattention of generations to come. Moreover the likenessis keen and lively-and will be even more so in ten years’time. It is not a College custom to have their presidentpainted ; and Lord Moran’s nine years of office were nostretch of tranquillity to be recollected with emotion.On the contrary, they were, as he said, years of contro-versy, and he was often a controversial figure. What theCollege remembers, however, is his leadership.

17. Mathis, H. B. Blood, 1951, 6, 470.18. Schleicher, E. M. Science, 1951, 113, 558.