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The striking association between lupus anticoagulant and fetal loss in systemic lupus erythematosus patients.

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and non-glucocorticoid-treated postmenopausal RA patients
may be that the bone resorbing influences of the disease
itself and the menopausal state have left little to be depleted
by glucocorticoids.
Integrating the present knowledge of the effects of
glucocorticoids on RA patients, it seems wise to prescribe
these drugs carefully, to use a low dose, to give postmenopausal patients estrogen-progestogen substitution therapy,
and finally, to not ignore the potential hazards of these drugs
when prescribed for premenopausal RA patients as well.
Anders Gotfredsen, MD
Orla Skibsted Als, MD
Claus Christiansen, MD
Glostrup Hospital
University of Copenhagen
Glostrup, Denmark
1. Als OS, Gotfredsen A, Christiansen C: The effect of glucocorti-
coids on bone mass in rheumatoid arthritis patients: influence of
menopausal state. Arthritis Rheum 28:369-375, 1985
Gotfredsen A, Als OS, Tjellesen L, Nilas L, Borg J, Christiansen
C . Clinical applicability of in vivo estimation of total body bone
mineral by dual photon absorptiometry: measurements on normals and osteopenic patients. J Comput Assist Tomogr 19558-559,
Als OS, Gotfredsen A, Riis BJ, Christiansen C: Are disease
duration and degree of functional impairment determinants of
bone loss in rheumatoid arthritis? Ann Rheum Dis 44:406411,
Steinbrocker 0, Traeger CH, Batterman RC: Therapeutic criteria
in rheumatoid arthritis. JAMA 140:659-662, 1949
Nagant de Deuxchaisnes C, Devogelaer JP, Esselinckx W,
Bouchez B, Depresseux G, Rombouts-Lindemans C, Huaux JP:
The effect of low dosage glucocorticoids on bone mass in
rheumatoid arthritis: a cross-sectional and a longitudinal study
using single photon absorptiometry. Adv Exp Med Biol
171:209-239, 1984
Salville PD, Kharmosh 0: Osteoporosis of rheumatoid arthritis:
influence of age, sex and corticosteroids. Arthritis Rheum
10:423-430, 1967
Zanzi I, Roginsky MS, Ellis KJ, Blau S, Cohn SH: Skeletal mass
in rheumatoid arthritis: a comparison with forearm bone mineral
content (abstract). AJR 126:1305-1306, 1976
mass :metaphyseal mass (DM :MM) ratios, which can specifically detect the loss of bone mineral induced by
glucocorticoid therapy, one must wonder whether the measurement of bone mineral mass at a single site or total body
bone mineral measurement, which they did use, are sufficiently sensitive in small numbers of patients, to make this
The question of the effect of glucocorticoids on
premenopausal females is far more novel. Observations by
Nagant de Deuxchaisnes note significant loss of bone mineral density at distal and midshaft sites of the radius in
premenopausal women who receive glucocorticoids, as compared with controls. Since a greater loss at the distal site,
characteristic of glucocorticoid-induced osteopenia, was
also observed, one must wonder whether studies with larger
numbers of premenopausal patients would have supported a
finding of bone loss aggravated by glucocorticoids in some
premenopausal women.
Obviously, it is difficult to detect glucocorticoidinduced bone mineral loss in rheumatic disease patients,
without using specific measures such as DM:MM ratios, or
without large numbers of patients. Method of detection must
be emphasized. Results of various studies using different
methodologies have indicated that glucocorticoids have a
detrimental effect on bone mass in 1 or more groups of
subjects. Our recent study (Dykman TR, Gluck OS, Murphy
WA, Hahn TJ, Hahn BH: Evaluation of factors associated
with glucocorticoid-induced osteopenia in patients with
rheumatic diseases. Arthritis Rheum 28:361-368, 1985),
which used specific measurements for detecting glucocorticoid-induced osteopenia, suggested that various glucocorticoid regimens contribute to osteopenia in all patients with
rheumatic diseases. Common findings suggest that glucocorticoids have a measurable effect on all patient groups,
although differences in patient selection and the methodology used for detection may complicate detection.
Thomas R. Dykman, MD
Fayetteville Diagnostic Clinic
Fayetteville, AR
The striking association between lupus anticoagulant
and fetal loss in systemic lupus erythematosus patients
Reply to Nagant de Deuxchaisnes
To the Editor:
As Nagant de Deuxchaisnes et al demonstrate and
appropriately emphasize, osteopenia and fractures are aggravated by glucocorticoid therapy in postmenopausal females who have rheumatic disease. Als et a1 disagree with
this observation (Als OS, Gotfredsen A, Christiansen C: The
effect of glucocorticoids on bone mass in rheumatoid arthritis patients: influence of menopausal state. Arthritis Rheum
28:369-375, 1985). Proving that glucocorticoids contribute to
osteopenia in this group of women is not easy, since factors
such as menopausal status, race, and immobility also contribute to osteopenia. Since Als et al failed to use diaphyseal
To the Editor:
It is generally accepted that in pregnant women who
have systemic lupus erythematosus (SLE), the prevalence of
fetal wastage due to spontaneous abortion and intrauterine
fetal death (IUFD) is higher than the average of 10% in the
general population (1-3). A pathogenetic role for several
immunologic mechanisms has been suggested by several
investigators. These mechanisms are: inadequate production
of blocking antibodies (4), immune complex deposition in the
trophoblast basement membrane (9,lymphocytotoxic antibodies cross-reacting with trophoblastic antigens (6),
transplacental passage of anti-Ro antibodies (7), and recently, the lupus anticoagulant (LAC) (8).
The evidence of an association between LAC and
fetal wastage is based upon isolated reports of selected
patients (8). Therefore, we studied the presence of LAC in
32 randomly assigned SLE patients with histories of pregnancy and in a heterogeneous group of patients with a
variety of connective tissue diseases (CTD): progressive
systemic sclerosis, 7 patients; primary Raynaud’s disease, 5
patients; discoid LE, 3 patients; rheumatoid arthritis, 3
patients; polymyositis, 3 patients; Sjogren’s syndrome, 3
patients; Takayasu’s syndrome, 2 patients. The results of the
LAC assay were related to the outcomes of pregnancies (9).
The presence of LAC is determined by a prolonged
clotting time of platelet-poor plasma tested in phospholipiddependent coagulation tests, in the presence of normal
activities of individual clotting factors. It is caused by
antiphospholipid antibodies interfering with the activation of
coagulation factors in the presence of phospholipids (9,lO).
LAC was found in 9 of 32 SLE patients, but was
fourtd in none of the 26 women with other CTD. The 32 SLE
patients accounted for 63 pregnancies: 26 pregnancies in 9
LAC positive patients and 37 pregnancies in 23 LAC negative patients. A total of 28 pregnancies in 15 SLE patients
(including 5 patients with LAC) had occurred before the
onset of SLE. Among the 9 LAC positive SLE patients, 7
pregnancies (5 occurring before SLE onset) ended with a live
birth, 18 pregnancies ended with IUFD (4 pregnancies
occurring before SLE onset), and there was 1 extrauterine
pregnancy (occurring before SLE onset). This results in a
73.1% rate of fetal wastage in the LAC positive patients.
Of the 37 pregnancies in 23 LAC negative SLE
patients, 30 (14 pregnancies occurring before SLE onset)
ended with a live birth, 5 (3 pregnancies occurring before
SLE onset) ended with IUFD, 1 ended by induced abortion
(before SLE onset), and 1 was an extrauterine pregnancy
(after SLE onset). This results in an 18.9% rate of fetal
wastage for LAC negative SLE patients. In the 26 patients
with other CTD, 63 pregnancies were recorded; 52 of these
ended with a live birth, 7 ended with IUFD, 3 ended by
induced abortion, and 1 was actually a hydatid mole (a 17.5%
rate of fetal wastage).
The 41.3% fetal wastage in the 32 SLE patients was
significantly higher than the 17.5% wastage in patients with
other CTD ( P < 0.01; Figure 1). Within the group of SLE
patients, fetal wastage was associated significantly with the
presence of LAC (P < 0.001; Figure 1). There was no
statistically significant difference between the fetal wastage
in LAC negative SLE patients and that in patients with other
From our observations, we conclude that the high
prevalence of fetal loss in SLE is strikingly associated with
the presence of LAC. However, the pathogenetic mechanism of antiphospholipid antibodies in pregnancy remains to
be clarified.
R. H. W. M. berksen, MD
B. N. Bouma, PhD
L. Kater, MD
University Hospital
Utrecht, The Netherlands
. -
women( n1
26 37
9 23
other CTD
Figure 1. Fetal wastage in women with systemic lupus erythematosus (SLE) or other connective tissue diseases (CTD), according to presence (+) or absence (-) of the lupus anticoagulant
1 . UCLA Conference, Fine LG (moderator): Systemic lupus
erythematosus in pregnancy. Ann Intern Med 94:667477, 1981
2. Mor-Yosef S, Navot D, Rabinowitz R, Schenker JG: Collagen
diseases in pregnancy. Obstet Gynecol Surv 39:67-84, 1984
3. Novak ER, Woodruff JD: Gynecologic and Obstetrics Pathology, with Clinical and Endocrine Relations. Seventh edition.
Philadelphia, WB Saunders Co., 1974, p 581
4. Rocklin RE, Kitzmiller JL, Carpenter CB, Garovoy MR, David
JR: Paternal fetal relation: absence of an immunologic blocking
factor from the serum of women with chronic abortions. N Engl
J Med 295:1209-1233, 1976
5. Grennan DM, McCormick JN, Wojtacha D, Carty M, Behan W:
Immunological studies of the placenta in systemic lupus
erythematosus. Ann Rheum Dis 37: 129-134, 1978
6. Bresnihan B, Oliver M, Grigor RR: Immunological mechanism
for spontaneous abortion in systemic lupus erythematosus.
Lancet 2: 1205-1207, 1977
7. Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott 0, Skinner
RP: Connective-tissue disease, antibodies to ribonucleoprotein,
and congenital heart block. N Engl J Med 309:209-212, 1983
8. Scott JS: Connective tissue disease antibodies and pregnancy.
Am J Reprod Immunol6:19-24, 1984
9. Green D, Hougie C, Kazmier FJ: Report of the working party
on acquired inhibitors of coagulation: studies of the “lupus”
anticoagulant. Thromb Haemost 49:14&146, 1983
10. Bvron MA: The clottine defect in SLE. Clin Rheum Dis
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loss, lupus, strikingly, patients, associations, systemic, erythematosus, anticoagulant, fetal
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