560
WHITE
References
Or@u@u, K., HORIUCHI,M., KONDO,T., et al (1991) Is the pre disposition to neuroleptic malignant syndrome genetically
CRADD0CK,B., CRADDOCK,N. & MLLNER,0. (1991) CPK in NMS.
BritishJournalof Psychiatry,158, 130. HARSCH, H. H. (1987) Neuroleptic
malignant
physio
logical and laboratory findings in a series of nine cases. Journal of Clinical Psychiatry, 48, 328—333. IToH, H., OwrsuIcA, N., OcilTA, K., et al (1977) Malignant neuro
lepticsyndrome:its presentstatusin Japanand clinicalproblems. Folia Psychiatricaet NeurologicaJapanica,31, 565—576. KECK, P. E., HARRISON, 0.,
POPE, H. 0.,
transmitted?BritishJournal of Psychiatry, 158, 850—853. ROSEBUSH,P. & STEWART,T. (1989) A prospective analysis of 24
syndrome:
ci al (1989) Risk factors
for neuroleptic malignant syndrome. Archives of General
Psychiatry, 46, 914—918.
episodesof neurolepticmalignantsyndrome.AmericanJournal of Psychiatry,146, 717-725.
& MAzuanK,M. (1991)Serum iron and the neuroleptic malignantsyndrome.Lancet, 338, 149-151. WHITE, D. & ROBINS, A. H. (1991) Catatoma:
harbinger
of the
neurolepticmalignantsyndrome.BritishJournal of Psychiatry, 158,419—421. & —¿ (1991)Letter. British Journal of Psychiatry, 158,
858—859.
KELLAM,A. M. P. (1987) The neuroleptic malignant syndrome, so
called. A survey of the world literature. British Journal of Psychiatry, 150, 752-759. MANN, S. C., CAROFF,S. N., BLEIER,H. R., et al (1986) Lethal
Denise A. C. White, MBChB,MMecI,FFPsych,Senior
catatonia. AmericanJournal of Psychiatry, 143, 1374—1381. Psychiatrirt and Lecturer, Department of Psychiat,y,
MENZA, M. & H@is,
D. (1989) Benzodiazepines
and catatoma.
An overview. Biological Psychiatry, 26, 842-846.
Carbamazepine-Induced
University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa
Systemic Lupus Erythematosus
ST. SCHMIDT, M. WELCKER, W. GREIL and M. SCHATTENKIRCHNER
A 21-year-old woman sufferingfrom bipolaraffective disorder developed systemic kipus erythematosus (SLE) with characteristic laboratory findIngs, 18 months after starting carbamazepine maintenance treatment. SLE receded after wlthdrawel of carbemazepine and treatment with anti-Inflammatory drugs. Although both the spontaneous occurrence of SLE and the psychosis as
of this drug and treatment with corticosteroids and other anti-inflammatory drugs. To our knowledge, this is the first report of SLE in a patient with a psychiatric disorder treated with carbamazepine. This case adds strong evidence of carbamazepine induction of SLE.
a signof CNS Involvementof SLEcannotbe excluded, SLE could be considered as an adverse effect of
Case report
carbamazepine.
British Journal of Psychiatry (1992), 161, 560—561 The patient, a female student now 21 years of age, had a first severe depressive episode in 1987 with typical
Systemic lupus erythematosus
(SLE) induced by
complaints
including
depressive
mood,
anhedonia,
and
carbamazepine has been described in several case reports (Simpson, 1966; Koistee, 1983; Bateman, 1985; Lovisetto, 1985; McNicholl, 1985; Alballa,
suicidal ideas, followed by a rapid change to a manic
1987; Drory et al, 1989; Maravic, 1990; Oner, 1990; Rabinowicz et a!, 1990; De Giorgio, 1991). All patients reported suffered from neurological diseases,
during a manic episode.
in most cases epileptic disorders, been treated with carbamazepine
and usually had for one year or
longer. Despite the assumed induction by carba mazepine of SLE in these cases, seizures and other neurological symptoms could also be interpreted as signs of CNS involvement of SLE. We report here a patient with manic-depressive disorder who showed symptoms of SLE during maintenance treatment with carbamazepine. The clinical symptoms of the latter illness completely receded after withdrawal
syndrome
two months
later. Over a six-month
period,
a
rapid cycling course of depressive and manic syndromes
developed, and a first hospital admission was necessary From the beginning,depressivesyndromesweretreated with doxepine or maprotiline, in the usual doses, and manic episodes with haloperidol (up to 15 mg/day). Remarkably, extrapyramidal movement disorders (acute dystonia) occurred with doses of haloperidol as low as 4mg/day. These were treated with anticholinergics. Because of the rapid cycling course, prophylactic treatment with carbamazepine (400 mg/day) was initiated. Three months later, the patient had completely recovered from
her mood disorder and remainedstable for approximately two years. Eighteen months after initiating carbamazepine treatment, she developed arthritis of the ankle, fmgers, elbows,
CARBAMAZEPINE-INDUCED
SYSTEMIC LUPUS ERYTHEMATOSUS
and knees. Based on the following findings, systemic lupus
erythematosus was diagnosed: arthritis, positive anti nuclear-antibodies (ANA), anti-ds-DNS-antibodies 16% (normal:
up to 10¾). IgG-antibodies
against
histones
type
H1-and H2Sled to the tentativediagnosis of drug-induced SLE, in this case by carbamazepine. (C3/ C4, immune
complexes within normal range; SM-, RNP-, SS-A/B antibodies negative;no pulmonary or joint abnormalities in the X-ray examination.)
Carbamazepinewaswithdrawnand the SLEwastreated with non-steroidal anti-inflammatory drugs (for several months), corticosteroids (for about one year) and disease modifying anti-rheumatic drugs (chloroquine; up to now). The clinicalsignsof SLE subsequentlyimproved considerably within four weeksand receded completelywithin two months
(ds-DNA antibodies 10¾;ANA still remained positive; computerisedtomographyand magneticresonanceimaging of the brain normal). However, the patient had a further episode of affective instability for approximately six months and hospital admission was required three times. At this stage, a maintenance lithium treatment was begun. The chloroquine treatment was continued (for 20 months up to the present moment) to prevent a reappearance of SLE symptoms since a spontaneous SLE cannot be ruled out (see Discussion). The patient's psychiatric illness has been diagnosed as a manic-depressive (bipolar) disorder. Her course of illness is atypical, exhibiting rapid mood shifts from depression to hypomanic or manic states, from the beginning. Discussion
Just as in the previously described cases, the causalrelationship betweencarbamazepine treatment
and the occurrence of SLE in our patient is not unambiguous. However, anti-histone-antibodies, which are more often found in drug-induced SLE
(90%) than in idiopathic SLE (30—70%),constitute an important
argument
for this link.
Generally, three different interpretations are con ceivable: (a) the patient is suffering from a psychiatric disorder and additionally from carbamazepine induced SLE; (b) she exhibits an affective disorder treated with carbamazepine and independently she
developed SLE; (c) at first, she had subclinical SLE with psychiatric symptoms only, which were treated with carbamazepine, the articular manifestations
of SLE occurring later. In fact, neuropsychiatric symptoms of SLE are now being reported in up to 60% of patients, predominantly seizures, but also organic mental syndromes and sometimes functional
psychoses (Lishman, 1990).
561
However, the identification of anti-histone anti bodies strongly supports the first hypothesis, i.e. the carbamazepine-induction of the SLE in our patient. Furthermore, in agreement with the carbamazepine induced cases already described in the literature, SLE occurred during long-term treatment with
carbamazepine.
Hence, SLE has to be seriously
considered as a possible adverse effect of carbamaze pine treatment. References ALBALLA, S.,
FRITZLER, M. & DAVIS, P. (1987)
A case
of drug
induced lupus due to carbamazepine. Journal of Rheumatology, 14, 599—600. BATEMAN,
D.
E.
(1985)
Carbamazepine
induced
systemic
lupus
erythematosus: case report. British Medical Journal, 291, 632—633. DE OloRolo, C. M., RABINOWICZ, A. L. & OLIvAs, R. D. (1991)
Carbamazepine-induced antinuclear antibodies and systemic lupus erythematosus-like syndrome. Epilepsia, 32, 128—129. DRORY, V. E., Yusr,
I. & KORCZYN, A. D. (1989)
Carbamazepine
induced systemic lupus erythematosus. Clinical Neuropharma cology, 12, 115—118. KoLSTEE, H. J. V. (1983) Ben patient
met lupus erythematosus
disseminatusveroorzaaktdoor het gebruikvan carbamazepine (Tegretol).Nederlandsch Tsjdschriftvor Geneeskunde, 127, 1588—1590. LISHMAN,W. A. (1990) Organic Psychiatry:
The Psychological
Consequences of Cerebral Disorders (2nd edn 1987, reprinted 1990). Oxford: Blackwell Scientific Publications. LovisErro, P., M@iw@o, D., C*jtoNlNo, M., ci a! (1985) Su un caso di lupus farmaco-indotto.
Recenti Progressi
in Medicina,
76, 84—86. M,a@vic,
M. V., KESSLER,C., WESSEL, K., ci a! (1990) Anti
epileptic drug-induced systemic lupus erythematosus. Epilepsia,
31, 229. MCNICHOLL,
B.
(1985)
Carbamazepine
induced
systemic
lupus
erythematosus. British Medical Journal, 291, 1126. ONER, A., TOPALOOLU, R., BESMS, N., et al(1990)
Carbamazepine
induced systemic lupus erythematosus. Another warning. Clinical Neurology and Neurosurgery, 92,261-262. RABINowIcz, A.
L.,
OLIvAs, R.
D. & DEGIORGIO, C.
M.
(1990) Carbamazepine-induced SLE. Neurology, 40 (suppl. 1), 137. SIMPSON,J. R. (1966) “¿Collagen disease― due to carbamazepine (Tegretol). British Medical Journal, ii, 1434.
StephanSchmidt, MD, ResearchAssistant;5W. Greil, MD, Lecturer, Psychiatrische Klinik, University
of Munich, Nuftbaumstr. Germany; M. Welcker,
7, D-8000 Munich 2, Research Assistant;
M. Schattenkirchner, MD, Professor, Medizinische
Pollidhnik,Universityof MunichPettenkoferstr.8a, D-80% Munich 2, Germany Correspondence
Carbamazepine-induced systemic lupus erythematosus. S Schmidt, M Welcker, W Greil and M Schattenkirchner BJP 1992, 161:560-561. Access the most recent version at DOI: 10.1192/bjp.161.4.560
References Reprints/ permissions You can respond to this article at Downloaded from
This article cites 0 articles, 0 of which you can access for free at: http://bjp.rcpsych.org/content/161/4/560#BIBL To obtain reprints or permission to reproduce material from this paper, please write to [email protected] /letters/submit/bjprcpsych;161/4/560 http://bjp.rcpsych.org/ on January 11, 2016 Published by The Royal College of Psychiatrists
To subscribe to The British Journal of Psychiatry go to: http://bjp.rcpsych.org/site/subscriptions/
WHITE
References
Or@u@u, K., HORIUCHI,M., KONDO,T., et al (1991) Is the pre disposition to neuroleptic malignant syndrome genetically
CRADD0CK,B., CRADDOCK,N. & MLLNER,0. (1991) CPK in NMS.
BritishJournalof Psychiatry,158, 130. HARSCH, H. H. (1987) Neuroleptic
malignant
physio
logical and laboratory findings in a series of nine cases. Journal of Clinical Psychiatry, 48, 328—333. IToH, H., OwrsuIcA, N., OcilTA, K., et al (1977) Malignant neuro
lepticsyndrome:its presentstatusin Japanand clinicalproblems. Folia Psychiatricaet NeurologicaJapanica,31, 565—576. KECK, P. E., HARRISON, 0.,
POPE, H. 0.,
transmitted?BritishJournal of Psychiatry, 158, 850—853. ROSEBUSH,P. & STEWART,T. (1989) A prospective analysis of 24
syndrome:
ci al (1989) Risk factors
for neuroleptic malignant syndrome. Archives of General
Psychiatry, 46, 914—918.
episodesof neurolepticmalignantsyndrome.AmericanJournal of Psychiatry,146, 717-725.
& MAzuanK,M. (1991)Serum iron and the neuroleptic malignantsyndrome.Lancet, 338, 149-151. WHITE, D. & ROBINS, A. H. (1991) Catatoma:
harbinger
of the
neurolepticmalignantsyndrome.BritishJournal of Psychiatry, 158,419—421. & —¿ (1991)Letter. British Journal of Psychiatry, 158,
858—859.
KELLAM,A. M. P. (1987) The neuroleptic malignant syndrome, so
called. A survey of the world literature. British Journal of Psychiatry, 150, 752-759. MANN, S. C., CAROFF,S. N., BLEIER,H. R., et al (1986) Lethal
Denise A. C. White, MBChB,MMecI,FFPsych,Senior
catatonia. AmericanJournal of Psychiatry, 143, 1374—1381. Psychiatrirt and Lecturer, Department of Psychiat,y,
MENZA, M. & H@is,
D. (1989) Benzodiazepines
and catatoma.
An overview. Biological Psychiatry, 26, 842-846.
Carbamazepine-Induced
University of Cape Town and Groote Schuur Hospital, Observatory 7925, South Africa
Systemic Lupus Erythematosus
ST. SCHMIDT, M. WELCKER, W. GREIL and M. SCHATTENKIRCHNER
A 21-year-old woman sufferingfrom bipolaraffective disorder developed systemic kipus erythematosus (SLE) with characteristic laboratory findIngs, 18 months after starting carbamazepine maintenance treatment. SLE receded after wlthdrawel of carbemazepine and treatment with anti-Inflammatory drugs. Although both the spontaneous occurrence of SLE and the psychosis as
of this drug and treatment with corticosteroids and other anti-inflammatory drugs. To our knowledge, this is the first report of SLE in a patient with a psychiatric disorder treated with carbamazepine. This case adds strong evidence of carbamazepine induction of SLE.
a signof CNS Involvementof SLEcannotbe excluded, SLE could be considered as an adverse effect of
Case report
carbamazepine.
British Journal of Psychiatry (1992), 161, 560—561 The patient, a female student now 21 years of age, had a first severe depressive episode in 1987 with typical
Systemic lupus erythematosus
(SLE) induced by
complaints
including
depressive
mood,
anhedonia,
and
carbamazepine has been described in several case reports (Simpson, 1966; Koistee, 1983; Bateman, 1985; Lovisetto, 1985; McNicholl, 1985; Alballa,
suicidal ideas, followed by a rapid change to a manic
1987; Drory et al, 1989; Maravic, 1990; Oner, 1990; Rabinowicz et a!, 1990; De Giorgio, 1991). All patients reported suffered from neurological diseases,
during a manic episode.
in most cases epileptic disorders, been treated with carbamazepine
and usually had for one year or
longer. Despite the assumed induction by carba mazepine of SLE in these cases, seizures and other neurological symptoms could also be interpreted as signs of CNS involvement of SLE. We report here a patient with manic-depressive disorder who showed symptoms of SLE during maintenance treatment with carbamazepine. The clinical symptoms of the latter illness completely receded after withdrawal
syndrome
two months
later. Over a six-month
period,
a
rapid cycling course of depressive and manic syndromes
developed, and a first hospital admission was necessary From the beginning,depressivesyndromesweretreated with doxepine or maprotiline, in the usual doses, and manic episodes with haloperidol (up to 15 mg/day). Remarkably, extrapyramidal movement disorders (acute dystonia) occurred with doses of haloperidol as low as 4mg/day. These were treated with anticholinergics. Because of the rapid cycling course, prophylactic treatment with carbamazepine (400 mg/day) was initiated. Three months later, the patient had completely recovered from
her mood disorder and remainedstable for approximately two years. Eighteen months after initiating carbamazepine treatment, she developed arthritis of the ankle, fmgers, elbows,
CARBAMAZEPINE-INDUCED
SYSTEMIC LUPUS ERYTHEMATOSUS
and knees. Based on the following findings, systemic lupus
erythematosus was diagnosed: arthritis, positive anti nuclear-antibodies (ANA), anti-ds-DNS-antibodies 16% (normal:
up to 10¾). IgG-antibodies
against
histones
type
H1-and H2Sled to the tentativediagnosis of drug-induced SLE, in this case by carbamazepine. (C3/ C4, immune
complexes within normal range; SM-, RNP-, SS-A/B antibodies negative;no pulmonary or joint abnormalities in the X-ray examination.)
Carbamazepinewaswithdrawnand the SLEwastreated with non-steroidal anti-inflammatory drugs (for several months), corticosteroids (for about one year) and disease modifying anti-rheumatic drugs (chloroquine; up to now). The clinicalsignsof SLE subsequentlyimproved considerably within four weeksand receded completelywithin two months
(ds-DNA antibodies 10¾;ANA still remained positive; computerisedtomographyand magneticresonanceimaging of the brain normal). However, the patient had a further episode of affective instability for approximately six months and hospital admission was required three times. At this stage, a maintenance lithium treatment was begun. The chloroquine treatment was continued (for 20 months up to the present moment) to prevent a reappearance of SLE symptoms since a spontaneous SLE cannot be ruled out (see Discussion). The patient's psychiatric illness has been diagnosed as a manic-depressive (bipolar) disorder. Her course of illness is atypical, exhibiting rapid mood shifts from depression to hypomanic or manic states, from the beginning. Discussion
Just as in the previously described cases, the causalrelationship betweencarbamazepine treatment
and the occurrence of SLE in our patient is not unambiguous. However, anti-histone-antibodies, which are more often found in drug-induced SLE
(90%) than in idiopathic SLE (30—70%),constitute an important
argument
for this link.
Generally, three different interpretations are con ceivable: (a) the patient is suffering from a psychiatric disorder and additionally from carbamazepine induced SLE; (b) she exhibits an affective disorder treated with carbamazepine and independently she
developed SLE; (c) at first, she had subclinical SLE with psychiatric symptoms only, which were treated with carbamazepine, the articular manifestations
of SLE occurring later. In fact, neuropsychiatric symptoms of SLE are now being reported in up to 60% of patients, predominantly seizures, but also organic mental syndromes and sometimes functional
psychoses (Lishman, 1990).
561
However, the identification of anti-histone anti bodies strongly supports the first hypothesis, i.e. the carbamazepine-induction of the SLE in our patient. Furthermore, in agreement with the carbamazepine induced cases already described in the literature, SLE occurred during long-term treatment with
carbamazepine.
Hence, SLE has to be seriously
considered as a possible adverse effect of carbamaze pine treatment. References ALBALLA, S.,
FRITZLER, M. & DAVIS, P. (1987)
A case
of drug
induced lupus due to carbamazepine. Journal of Rheumatology, 14, 599—600. BATEMAN,
D.
E.
(1985)
Carbamazepine
induced
systemic
lupus
erythematosus: case report. British Medical Journal, 291, 632—633. DE OloRolo, C. M., RABINOWICZ, A. L. & OLIvAs, R. D. (1991)
Carbamazepine-induced antinuclear antibodies and systemic lupus erythematosus-like syndrome. Epilepsia, 32, 128—129. DRORY, V. E., Yusr,
I. & KORCZYN, A. D. (1989)
Carbamazepine
induced systemic lupus erythematosus. Clinical Neuropharma cology, 12, 115—118. KoLSTEE, H. J. V. (1983) Ben patient
met lupus erythematosus
disseminatusveroorzaaktdoor het gebruikvan carbamazepine (Tegretol).Nederlandsch Tsjdschriftvor Geneeskunde, 127, 1588—1590. LISHMAN,W. A. (1990) Organic Psychiatry:
The Psychological
Consequences of Cerebral Disorders (2nd edn 1987, reprinted 1990). Oxford: Blackwell Scientific Publications. LovisErro, P., M@iw@o, D., C*jtoNlNo, M., ci a! (1985) Su un caso di lupus farmaco-indotto.
Recenti Progressi
in Medicina,
76, 84—86. M,a@vic,
M. V., KESSLER,C., WESSEL, K., ci a! (1990) Anti
epileptic drug-induced systemic lupus erythematosus. Epilepsia,
31, 229. MCNICHOLL,
B.
(1985)
Carbamazepine
induced
systemic
lupus
erythematosus. British Medical Journal, 291, 1126. ONER, A., TOPALOOLU, R., BESMS, N., et al(1990)
Carbamazepine
induced systemic lupus erythematosus. Another warning. Clinical Neurology and Neurosurgery, 92,261-262. RABINowIcz, A.
L.,
OLIvAs, R.
D. & DEGIORGIO, C.
M.
(1990) Carbamazepine-induced SLE. Neurology, 40 (suppl. 1), 137. SIMPSON,J. R. (1966) “¿Collagen disease― due to carbamazepine (Tegretol). British Medical Journal, ii, 1434.
StephanSchmidt, MD, ResearchAssistant;5W. Greil, MD, Lecturer, Psychiatrische Klinik, University
of Munich, Nuftbaumstr. Germany; M. Welcker,
7, D-8000 Munich 2, Research Assistant;
M. Schattenkirchner, MD, Professor, Medizinische
Pollidhnik,Universityof MunichPettenkoferstr.8a, D-80% Munich 2, Germany Correspondence
Carbamazepine-induced systemic lupus erythematosus. S Schmidt, M Welcker, W Greil and M Schattenkirchner BJP 1992, 161:560-561. Access the most recent version at DOI: 10.1192/bjp.161.4.560
References Reprints/ permissions You can respond to this article at Downloaded from
This article cites 0 articles, 0 of which you can access for free at: http://bjp.rcpsych.org/content/161/4/560#BIBL To obtain reprints or permission to reproduce material from this paper, please write to [email protected] /letters/submit/bjprcpsych;161/4/560 http://bjp.rcpsych.org/ on January 11, 2016 Published by The Royal College of Psychiatrists
To subscribe to The British Journal of Psychiatry go to: http://bjp.rcpsych.org/site/subscriptions/
