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The epidemiology of drug-induced systemic lupus erythematosus.

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Arthritis and Rheumatism
o$cial journal of the gmerican Rheumatismassociation
VOL. X, NO. 5
OCTOBER, 1967
The Epidemiology of
Drug-Induced Systemic Lupus Erythematosus
By MORRISSIECEL,STANLEY
L. LEE AND NANCYS. PERESS
I
chemical agents have
been implicated in the causation of
systemic lupus-like symptoms in patients
treated for disorders unrelated to systemic
lupus erythematosus, such as essential hypertension and cardiac arrythmia. The relationship of the drug-induced disease to
idiopathic systemic lupus erythematosus
(SLE) is not clear. The clinical features
of drug-induced lupus resemble those of
SLE, with the important exception that the
symptoms generally disappear upon discontinuation of drug therapy. However,
whether the contributory factors in both
disorders are also similar is unknown. Because of its biological significance, this
question was investigated in the present
study with particular reference to host factors and time trend.
The variety of drugs implicated and the
number of drug-induced lupus cases reported constitute a problem which warrants
intensive study for clues to the underlying
mechanism in the occurrence of the spon-
taneous form of SLE.l In a review of the
numerous therapeutic agents incriminated
and the related clinical features, it was estimated that drugs were associated with
the occurrence of symptoms of lupus in
from 3 per cent to 12 percent of 1,193 investigated cases of SLE."
The cases related to the use of drugs
consisted of two broad categories: 1) the
presumably early cases of idiopathic SLE
which developed clear-cut symptoms following use of sensitizing drugs; and 2 ) all
other cases in which signs and symptoms
of lupus were first observed following drug
administration, and were apparently dependent on use of the drug. To distinguish
between these two groups of cases, comprehensive historical information on drug
therapy and clinical findings was essential.
Differentiation was particularly difficult in
cases with convulsive seizures and petit
mal, because such symptoms can occasionally be due to SLE. In these cases,
classification by the investigators was large-
From the Department of Environmental Medicine and Community Health, State University of
New York, College of Medicine at New York
City, and the Division of Hematology, Maimonides
Hospital, Brooklyn, New York.
Aided by Research Grant CD-00001 from the
Division of Chronic Diseases, Bureau of State
Services, United States Public Health Service,
Washington, D . C .
MORRIS
SIEGEL, M.D., M.P.H.: Professor, Environmental Medicine & Community Health, State
University of New York, Downstate Medical Center; Visiting Lecturer on Epidemiology, Hartiard
School of Public Health. STANLEYL. LEE, M.D.:
Director of Hematology, Maimonides Hospital,
Brooklyn; Associate Professor of Medicine, State
University of New York, Downstate Medical Center. NANCYS . PERESS,M.D.: Intern in Pathology,
Kings County Hospital, Brooklyn, N.Y.
N RECENT YEARS,
407
ARTHRITISAND RHEUMATISM,VOL. 10, No. 5 (October 1967)
408
SIEGEL, LEE, PERESS
ly based on the time relationship between
other manifestations of SLE and the use
of anti-convulsant drugs. If manifestations
subsequently appeared in other organ systems after prolonged use of such drugs,
the case was considered as drug-induced
SLE.
TREND OF DRUG-INDUCED SLE AND IDIOPATHIC SLE
NEW YORK CITY, 1957-1966
a
11M111 “ E l l MOVING AV1lAGEl
-
-
DRUG UlAJS
.METHOD
The sources of data were the records of cases in
voluntary and public hospitals, clinics and laboratories in 3 of the 5 boroughs of New York City,
Manhattan, The Bronx and Brooklyn. The hospitals included in the study had a bed capacity
of 29,182, or 62.9 per cent of the total hospital
beds in the boroughs surveyed? The relevant
clinical and epidemiological information was obtained by a public health nurse who annually
reviewed the files of hospitals and death certificates
for diagnosed cases of SLE, and communicated
every 2 weeks with laboratory personnel for newly
found cases with LE cells.
A detailed summary was then made of past
and present clinical data, with particular reference
to the temporal sequence of drug use and symptoms. The study group periodically reviewed the
clinical information, and the cases of lupus were
classified as either SLE or drug-induced SLE according to the predetermined criteria. The criteria
for a diagnosis of SLE were: involvement of at
least three organ systems; laboratory confirmation
by repeated findings of LE cells, or typical splenic
or renal microscopic lesions; and exclusion of
other diseases? The criteria for the category of
“drug-induced SLE” were symptoms consistent
with systemic lupus and confirmatory laboratory
evidence (LE cells) following use of drugs for
15 days or longer in subjects with disorders apparently unrelated to the connective tissue disease. Excluded from the drug-induced category
were cases with symptoms of connective tissue
diseases antedating the use of drugs known to be
implicated in the occurrence of drug-induced
lupus; other disorders associated with auto-immune serological manifestation, such as myasthenia gravis; cases with inadequate information
on drug therapy; and cases with obscure systemic
manifestations antedal ing drug therapy.
The present review is limited to cases of druginduced SLE following the prolonged use of 4
commonly implicated drugs, diphenylhydantoin,
isoniazid, hydralazine and procainamide. The cases
occurred among residents of New York City from
1957 to 1966, inclusive. During this 10-year
period, a total of 54 cases was identified and
0
1957
0
l9b
Id59
19W
19U
I&
1963
YEAR OF DIAGNOSIS
1964
1965
(966
Fig. 1.-Trend
of drug-induced SLE and
idiopathic SLE, N e w York City, 1957-1966
(three-year moving average).
systematically investigated for associated host and
environmental factors. A summary of the results
follows, including a comparison with data on 101
cases of SLE observed during the same study
period among residents in a defined area of New
York City with a population of 662,000 in 1960.1
Moreover, the host factor data for drug-induced
lupus are compared with the expected values.
Because the population at risk to drug therapy is
unknown, expected values are based on the
prevalence of the disorders for which the abovementioned drugs are commonly used: epilepsy,
tuberculosis, hypertension, and cardiac arrythmia
when complicating myocardial infarction.”’.’”
Adequate prevalence data by race were not obtainable for epilepsy, and so an expectancy based
on racial distribution in the population for the
commonly affected age groups was assumed. The
only specific prevalence data available for Puerto
Ricans were for tuberculosis. In estimating the
expectancy of other diseases in Puerto Ricans, the
rates for whites were applied.
RESULTS
The time trend for the occurrence of
cases of drug-induced lupus and comparative data on the incidence of SLE are
shown in Fig. 1. The annual number of
recognized drug-lupus cases rose somewhat
at first and then stayed at an even level
for several years before increasing markedly in 1965 and 1966, the last 2 years of
the study period. By contrast, data on the
incidence of idiopathic SLE showed no
significant rise in rate during the entire
period.
409
DRUG-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS
Table 1.-Drug-Induced
Year of
Diagnosis
Total
1957
1958
1959
2
2
3
1960
6
4
1961
1962
1963
1964
SLE by Year of Diagnosis and Drug Therapy, 1957-1966
Number of Cases by Implicated Drug
Diphenylhydantoin
Isoniazid
Hydralazine
1
1
1
3
3
Procainamide
1
3
2
1
1
1
1
1
2
2
1965
1966
2
5
1
13
16
3
2
2
2
1
7
3
9
Tofaat:
54
16
9
11
18
1
The relationship of the number of druginduced lupus cases diagnosed each year
to the specific drugs used is shown in
Table 1. The cases noted in the early years
of the study period were attributable to
diphenylhydantoin, hydralazine and isoniazid. The abrupt rise in 1965 was due to
procainamide hydrochloride. Over the entire period, most of the cases were related
to the use of procainamide, followed in decreasing order by diphenylhydantoin, hydralazine and isoniazid.
The many cases associated with procainamide in 1965 and 1966 were unexpected
in view of the few cases noted in previous
years. The abrupt increase in 1965 may be
due in part to greater awareness of the
complication since 1962, when it was first
reported. The increase may also be associated with the more extensive use of procainamide, as evident in a two-fold rise in
the volume of sales of this drug in 1965
and 1966.8
Analysis of the data by host factors, such
as age, sex and race, is shown in Tables
2 to 5. The distribution of cases varied
directly with age, with 5.6 per cent under
15 years of age and 55.6 per cent over 44
years of age (Table 2 ) . The average age
at time of diagnosis for all cases was 47.4
years, as compared with 35.8 years for the
101 cases of SLE observed during the same
period.
The age distribution of cases reflected
the age of the population at risk to the
drugs used. Thus, there were only 2 (12.5
per cent) of 16 epileptic patients treated
with diphenylhydantoin over 44 years of
age as against 25 (86.2 per cent) of 29
subjects on hydralazine or procainamide
for hypertensive and cardiac disorders, respectively. The average age at onset of
drug-induced lupus in the different groups
was 33.4 years for diphenylhydantoin, 40.3
for isoniazid, 53.5 for hydralazine and 60.7
for procainamide.
The distribution of drug-induced cases
by sex is given in Table 3. There was a
preponderance of female cases, 38 (70.4
per cent) as against 16 (29.6 per cent)
males, a sex ratio of 2.4. These values
were significantly different from those observed for idiopathic SLE.* Of the 101
cases of SLE under consideration, 89 (88.1
percent) were female and 12 (11.9 per
cent) male, a sex ratio of 7.4.
As shown in Table 3, the distribution of
drug-induced lupus cases by sex varied
with the drug used. Thus, the preponderance of females was marked for diphenylhydantoin, while the cases were more
equally distributed between males and females for procainamide. However, since
these differences depend on the number of
male and female subjects treated, they
* Value of P = 0.05 or less.
410
SIEGEL, LEE, PERESS
Table 2.-Age
Distribution of Drug-Induced SLE by Drug Therapy
Total
NO.
Under 15
15-24
25-34
3544
45-54
55-64
65-74
75 & over
Total:
Mean age:
%
3
5.6
5
9.2
9.2
20.4
18.5
16.7
20 4
0.0
5
11
10
9
I1
0
54
47.4
100.0
Number of Cases by Implicated Drug
Diphenylhydaiitoin
Isoniazid
Hydralazine
3
3
3
5
2
16
33.4
were compared with expected values based
on prevalence
As shown in
Table 3, the observed ratio of female to
male cases exceeded the expected ratio in
each drug category. Furthermore, the extent of the difference between observed
and expected ratios was two-fold or more,
an indication that the female may be considerably more susceptible than the male
to drug-induced lupus, unless we are to
assume that females were treated twice as
much. Specific rates by sex could not be
determined because of lack of adequate
information on the population under treatment.
The foregoing data on age and sex were
compared with case reports of drug-induced lupus published by others. The cases
considered were limited to those with a
positive LE cell test. The cumulated data
on 47 cases reported by others are shown
in Table 4 by the specific drugs under cons i d e r a t i ~ n . ~ , The
~ J ~ current study is
broadIy in agreement with the resuIts of
others. They too showed a preponderance
of cases among females, which appeared
to be most marked for hydralazine and
diphenylhydantoin. And the age at onset
was lowest for diphenylhydantoin, followed in increasing progression by hydralazine and procainarnide.
The association between drug-induced
lupus and other host factors, such as race,
Pracainamde
2
2
2
1
3
3
2
2
J"
4
7
6
9
40.3
11
53.5
18
60.7
1
CASES OF DRUG INDUCED SLE BY RACE
NEW YORK CITY, 1957-1966
501
r
a Observed
0Expected
WHITE
PUERTO
RI CAN
Number
Number
NEGRO
Fig. 2.-Cases
of drug-induced SLE by
race, New York City, 1957-1966.
was difficult to determine because of the
lack of adequate information on the number of subjects treated in each racial group.
Some indication of the relationship to race
may be evident by comparing the observed number of cases in each racial
group with the expected number as estimated from prevalence data or from the
population distribution, as described
above.5,6,? The results are summarized in
Fig. 2, which shows the observed and
expected number of cases for Negro,
Puerto Rican, and other white groups. The
observed and the expected values were
411
DRUG-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS
Table 3.-Sex
Distribution of Drug-Induced SLE by Implicated Drug
- __
Sex
Total
Number of Cases by Implicated Drug
Dlphenylhydantoiri Isoniazid
Hydralazine
Procainamide
XO.
To
Male
Female
16
38
29.6
70.4
2
14
3
6
3
8
10
Total:
54
100.0
16
9
11
18
Observed Ratio*
Expected Ratio
2.4
0.7
7.0
1.o
2.0
0.5
2.7
1.3
0.5
Observed Ratio
Expected Ratio
3.4
7.0
4.0
2.1
2.6
* Itatlo of
8
1.3
female to male cases
comparable in each racial group,
an indication that there was no apparent
racial difference in the occurrence of druginduced lupus. The failure to demonstrate
a racial difference for drug-induced lupus
was at variance with the results observed
for idiopathic SLE. As reported previously,
the prevalence of SLE was found to be
highest for non-whites, followed in descending order by the rate for Puerto
Ricans and then other whites. The morbidity rates for SLE were 2 to 3 times
greater among Negroes than whites.ll
The foregoing difference in racial characteristics between drug-induced and idiopathic lupus seems to hold for each of the
drugs under consideration (Table 5 ) . As
summarized in Table 5, the number of observed and expected cases by race and
specific drug was comparable in every instance. In Negro subjects, there was no
increase of drug-lupus for any of the drugs
incriminated thus far. This was most evident for the procainamide group, where
none of the 18 cases was a Negro. However, the expectancy among Negroes in
this drug group was only 2.0 cases, and
consequently a larger experience would be
required to determine the biological significance of these results.
The study on drug-induced lupus led to
a search for evidence of a predisposition
to the disorder as manifested by the presence of serological abnormalities before the
onset of therapy or before the appearance
of drug reactions in treated subjects. The
sera were examined for LE cells, antinuclear antibodies, direct Coombs’ reaction,
rheumatoid factor, biologic false-positive
reaction for syphilis, and for protein fractions by paper electrophoresis by methods
previously described.l
The expected frequency of serological
abnormalities was explored in a pilot study
of 80 subjects under therapy. Half of the
group had active pulmonary tuberculosis,
and the remainder were equally divided
between epilepsy and essential hypertension. The serological findings were within
normal limits except for antinuclear antibodies in 4 (10 per cent) tuberculous patients, and elevated gamma globulin levels
in 13 (34 per cent) tuberculous patients,
3 (15 per cent) hypertensives and 1 ( 5
per cent) epileptic. The average gamma
globulin level was significantly higher in
the tuberculous patients than in the others.
Following the pilot study, a prospective,
longitudinal investigation was made of serological abnormalities before and after the
onset of drug treatment for hypertension,
epilepsy and tuberculosis. Serial bleedings
were obtained shortly before or less than
1 week after onset of treatment, 1 month
later and then every 6 months thereafter.
A review of the first 50 cases in the program of which 29 were taking isoniazid for
tuberculosis, 10 taking a variety of drugs for
412
SIEGEL, LEE, PERESS
Table 4.-Neported Cases of Drug-Induced SLE by Age, Sex, and h
D w
Male
Total
Under
30
60 &
Total
Under
30
60 Bi
30
to
59
Over
to
Diphenylhydantoin
Isoniazid
Hydralazine
Procainamide
Total:
* Ratio of
6
2
4
4
16
30
59
5
1
5
g Therapy
Female
Over
1
1
4
2
8
14
0
10
2
7
3
31
13
1
1
8
1
3
14
4
12
5
Sex Ratio>
2.3
012
2.5
1.8
1.9
female to male cases.
hypertension and 11taking diphenylhydantoin or trimethadione for epilepsy, revealed
no increase in serological abnormalities attributable to drug therapy. On the contrary,
the elevated gamma globulin level in tuberculous subjects fell progressively with
treatment and clinical improvement. Nor
could the frequency of antinuclear antibodies be correlated with duration of therapy. The period af follow-up varied from
less than a year in 32 (64 per cent) cases
to 1 to 3 years in 18 (36 per cent). From
these preliminary results, the serological
abnormalities observed originally in the
pilot study appear to be largely a manifestation of the disorder treated and not
a consequence of the drugs used. It is also
apparent that the frequency of the other
serological abnormalities, which might be
attributable to drug therapy, was so low
that a very large series of patients would
be required for an adequate investigation.
DISCUSSION
In the current study, comparative epidemiological data were presented on druginduced SLE and idiopathic SLE occurring during the past decade in New York
City. The results reveal significant similarities and differences in respect to contributory factors. Thus, the preponderance of
females, so typical of SLE, was also observed for drug-lupus, although the difference was less marked.
Distinctive differences between drug-inducrd lupus and idiopathic SLE were ob-
served for such characteristics as race, age
and time trend. These may reflect significant differences in causation. Unlike SLE,
there was no evidence of an increase in
Negroes. Similar results have been noted
by Holley in Birmingham, Alabama.12
The occurrence of drug-induced lupus fluctuated over time, varying with the drugs
in popular use, and the dominant conditions and age group of the subjects treated.
On the other hand, in the past 10 years at
least, the incidence of SLE has been fairly
constant and comparable in such widely
separated areas as New York and Malmo,
Sweden.13 In addition, the disorder has
been largely concentrated in females of
child-bearing age regardless of time or
place.
The recent increase of recognized cases
of drug-induced lupus need not cause undue alarm, because it partly reflects
greater awareness of the complication and
thus earlier and more complete casefinding. Early recognition of the complication is particularly important in elderly
individuals with impaired functional capacities. The complication should be suspected in both male and female subjects
with chronic disorders under prolonged
drug therapy.
The selective action of the drugs in affecting only certain individuals under prolonged treatment reflects the presence of
predisposing host factors which might be
identified in prospective studies of drugtreated cases. In this connection, our sero-
413
DRUG-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS
Table 5.-Racial
Race
Distribution of Drug-Induced SLE by Drug Therapy
. ,
Total
Obs.
Exp.
Dinhenvlhydantoin
Obs.
Exp.
Isoniazid
Obs.
Exp.
Hydralazine
Exp.
Obs.
Procainamide
Obs.
Exp.
White
Puerto
Rican
Negro
41
6
39.0
12
2
11.7
1.7
4
2
4.5
1.3
8
4.5
1
7.6
0.7
17
1
15.2
0.8
7
10.5
2
2.6
3
3.2
2
2.7
0
2.0
Total:
54
54.0
16
16.0
9
9.0
11
11.0
18
18.0
Obs. = Observed number of cases; Exp. = Expected number of cases.
logical studies of subjects observed before
and after treatment with isoniazid, anticonvulsants and anti-hypertensive drugs
failed to reveal evidence of such a predisposition, nor evidence of an increase in
serological abnormalities following prolonged drug therapy. These results are
inconclusive because of small sample size.
They differ somewhat from a report by
others that the frequency of antinuclear
factors is higher in tuberculous patients
treated with isoniazid for one year or more
than in untreated patients14
In other studies bearing on the underlying mechanism, a relationship to hyperglobulinemia and to familial aggregation of
connective tissue abnormalities has been
reported by various investigators in an occasional drug-lupus case.15J6 The information available is only suggestive of an
association with an overactive immune
mechanism or an hereditary tendency. A
relationship to such specific processes as
the formation of antigen-antibody complexes and the release of lysosomes has not
yet been demonstrated in subjects with
drug-induced SLE.17
Whether the underlying mechanism responsible for drug induced SLE is similar
to that postulated for idiopathic SLE is
still not clear.18 Nevertheless, the fact that
different ‘chemical substances can induce
symptoms of lupus which disappear upon
withdrawal of the offending drugs makes
it reasonable to suppose that chemical or
biological agents might also be implicated
in the development of symptoms of SLE,
and that clinical remission in SLE might
follow elimination of the offending agents
or neutralization of their ill effects. This
concept is consistent with the character of
the disorder, viz, its episodic course and
protean manifestations. It emphasizes the
need for renewed efforts in search of the
specific agents involved and of methods
for counteracting their effects.
In this connection, a filterable viruslike
agent has been observed in a susceptible
crossbred strain of NZB/BL mice that develop renal disease and other manifestations resembling SLE.19v20Neonatal Swiss
mice also appeared to be susceptible to the
filterable agent, developing “features of renal and hemolytic disease” and positive
Coombs’ tests following intraperitoneal inoculation.20This finding provides new evidence for the viral etiology of auto-immune
disorders, and promises to make possible
the investigation of contributory factors
and underlying mechanism in SLE and related connective tissue diseases under laboratory conditions.
SUMMARYAND CONCLUSIONS
An increase in the incidence of druginduced SLE was observed among New
York City residents from 1957 to 1966 in
an epidemiological study of the disorder
following prolonged use of diphenylhydantoin, hydralazine, isoniazid and procainamide. The increase was partly related to
greater awareness of the complication and
414
SIECXL, LEE, PEHESS
to more widespread use of procainamide.
IIost factors associated with drug-induccd hipus varied with the d r u g used
a n d the population treated as follows: 1 )
Fernales seemed to be m o r e susceptible
than males. The extent of the difference
appeared to be a b o u t two-fold. It was
found to be somewhat greater for diphenylhydantoin t h a n for other drugs. 2 )
The m e a n age for the occurrence of druglupus varied from 33.4 years for epileptic
patients treated with diphenylhydantoin to
60.7 years for cardiac subjects treated with
procainamide. 3 ) There appeared to be no
significant racial difference in susceptibil-
ity to drug-induced lupus.
A comparison of epidemiological data o n
drug-induced SLE and idiopathic SLE ob-
served during the same period of study
revealed differences in time trend, a n d
host factors which may be of etiological
significance.
The possibility of a drug-induced disorder following prolonged d r u g therapy
should be considered in cases diagnosed
as SLE.
Drug-induced serological abnormalities
characteristic of SLE were not detected in
small groups of patients tested before a n d
after treatment for epilepsy, tuberculosis
and hypertension in a preliminary prospective study. The feasibility of a definitive
study under present conditions is questioned because of the large sample that
would be required for significant results.
SUMMARIO
IN INTERLINGUA
Comparative datos epidemiologic relative a pharmacogene lupus e a idiopathic disseminate lupus erythematose, occurrente inter 1957 e 1966, ha revelate siinilitudes e
differentias de signification biologic. Un abrupte augment0 in lupus inducite per pharaccompaniate de un simile disveloppamento
inacos occurreva in 1965 e 1966. Isto-non
con respecto a disseminate lupus erythematose-esseva
attribuibile a un plus extense
LISO de procainamida. Le characteristicas del lupus phaimacogene con respecto a1 distribution per etate e sexo del subjectos afficite dependeva in parte del popillation
tractate. Per contrast0 con disseminate lupus erythematose, lupus pharmacogene
revelava nulle evidentia de differentias racial con respecto a1 susceptibilitate.
lp
REFERENCES
1. Siegel, M., Lee, S. L., Widelock, D., Reilly,
2.
3.
4.
5.
6.
E. B., Wise, G. J., Zingale, S. B., and
Fnerst, H. T.: The epidemiology of systcmic lupus erythematosus. Preliminary results in New York City. J. Chron. Dis.
15:131-140, 1962.
Lee, S. L., Rivero., I., and Siegel, M.: Activation of systemic lupus erythematosus by
drugs. Arch. Int. Med. 117:620-626, 1966.
Hospitals and related facilities in southern
New York. Jannary 1, 1965, Hospital Review and Planning Council of Southern
New York, New York City.
Lennox, W. G.: Epilepsy and related disorders. New Ylork, Little, Brown & Co.,
1960, Vol. 1, p,, 502.
Lowell, A. M.: 'l'uberculosis in New York
City, 1961. New York Tuberculosis Association, New 'York, 1962, pp. 31-36.
National Center for Health Statistics, Division of Health Examinations Statistics:
Blood Pressure of Adults by Age and Sex,
7.
5.
9.
10.
11.
United States, 1960-G2. U. S. Dept. Health,
Education & Welfare, Public Health Service
Publication No. 1000-, Series 11-No. 4,
June 1964, p. 9.
National Center for Health Statistics, Division
of Health Examinations Statistics: Coronary
Heart Disease in Adults, United States,
1960-62. U. S. Dept. Health, Education &
Welfare, Public Health Service Publication
No. 1000-, Series 11-No. 10, Sept. 1965,
pp. 17-19.
Lavy, N. W.: Personal communication.
Kaplan, J. M., Wachtel, H. L., Czarnecki,
S. W., and Sampson, J. J.: Lupus-like illness precipitated by procainamide hydrochloride, J.A.M.A. 192:444-447, 1965.
Paine, R.: Procainamide hydrochloride and
lupus erythematosus. J.A.M.A. 194:23-26,
1965.
Siegel, M., Reilly, E. B., Lee, S. L., Fuerst,
H. T., and Seelenfreund, M.: Epidemiology
of systemic lupus erythematosus: time
DRUG-INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS
12.
13.
14.
15.
16.
trend and racial differences. Amer. J. Public
Health 54:3343, 1964.
Holley, H. L.: Personal communication.
Leonhardt, T.: Family studies in systemic
lupus erythematosus. Acta Med. Scand.
176 ( SUPPI. 416) :37-38, 1964.
Cannat, A., and Seligmann, M.: Possible induction of antinuclear antibodies by
isoniazid. Lancet 1: 185-187, 1966.
Shulman, L. E., and Harvey, A. M.: The
nature of drug-induced systemic lupus
erythematosus. Arthritis Rheum. 3:464,
1960.
Holley, H. L.: Evidence for a predisposition
to rheumatic diseases in families of patients
developing drug-induced systemic lupus
erythematosus. Arthritis Rheum. 7:684686, 1964.
415
17. Weissmann, G.: Lysosomes, New Eng. J.
Med. 273:1084-1090 and 1143-1149, 1965.
18. Conference on the immunologic aspects of
rheumatoid arthritis and systemic lupus
erythematosus. Chap. XII, Shulman, L. E.
(Chairman) : Inducing agents and relationship to other diseases. Arthritis Rheum. 6:
Suppl. 558-571, 1963.
19. Helyer, B. J., and Howie, J. B.: Renal disease
associated with positive lupus erythematosus tests in a cross-bred strain of mice.
Nature 197: 197, 1963.
20. Mellors, R. C., and IIuang, C. Y . : Immunopathology of NZB/BL mice. V.
Viruslike (filterable) agent separable from
lymphoma cells and identifiable by electron
microscopy. J. Exp. Med. 124:1031-1038,
1966.
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epidemiology, lupus, drug, induced, systemic, erythematosus
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