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Corticosteroid treatment in patients with Sydenham’s chorea
Corticosteroid Treatment in Patients With Sydenham’s Chorea Judith Barash, MD*, Dov Margalith, MD†, and Abraham Matitiau, MD‡ Sydenham’s chorea occurs in approximately 10% of acute rheumatic fever and is one of its major manifestations. The disease may last for weeks or months, with a high risk of recurrence; usually only supportive treatment is recommended. This report describes five children diagnosed with Sydenham’s chorea and treated with a short course of corticosteroids. Marked improvement of the involuntary movements was observed within 24-48 hours, with complete resolution within 7-12 days after commencement of treatment; there were no relapses. Larger, possibly comparative studies are necessary, but in the meantime treatment with corticosteroids in patients with Sydenham’s chorea should be considered. © 2005 by Elsevier Inc. All rights reserved. Barash J, Margalith D, Matitiau A. Corticosteroid treatment in patients with sydenham’s chorea. Pediatr Neurol 2005;32:205-207.
Introduction
acterized by rapid, purposeless, nonrepetitive involuntary movements that disappear with sleep and may involve all except the ocular muscles. There is impaired coordination, facial grimacing, clumsiness, and difficulty in dressing and feeding. The course is variable; it may last for weeks or months, but a much longer course is reported in some cases [2]. Usually only supportive treatment is recommended; in severe cases benzodiazepine or antipsychotic drugs such as haloperidol or risperidone may be used, and there are reports about the efficacy of carbamazepine [3] or valproic acid [4]. Some of the manifestations of acute rheumatic fever (carditis and arthritis) are known to respond favorably to anti-inflammatory treatment (aspirin and corticosteroids) with prompt clinical improvement; however, concerning carditis, there is no proof of benefit in long-term prognosis. Because chorea often occurs as an isolated manifestation after the resolution of the acute phase of the disease, it was thought that there is no benefit from anti-inflammatory treatment. Nevertheless, there are some reports on corticosteroid treatment in cases with chorea. In 1978 a cohort of eight patients with chorea were reported, all of them females, who received treatment with steroids and responded relatively rapidly [5]. In another study, the medical charts of 20 children with chorea minor were retrospectively reviewed; seven of them received treatment with corticosteroids. The shortest course of chorea occurred in a patient treated with prednisone [6]. Recently, Cardoso et al. [7] reported five patients with chorea minor refractory to conventional therapy and treated successfully with pulse methylprednisolone followed by oral prednisone. This report describes five pediatric patients diagnosed with acute rheumatic fever and Sydenham’s chorea and treated successfully with a short course of corticosteroids, thus again raising the issue of such treatment.
Acute rheumatic fever is a nonsuppurative complication of group A beta-hemolytic streptococcal infection. During the second half of the twentieth century there was a steep decrease in the incidence of acute rheumatic fever in North America and Western Europe followed by a resurgence of the disease in several areas in the United States [1]. One of the major signs of acute rheumatic fever is chorea minor or Sydenham’s chorea; it occurs in approximately 10% of acute rheumatic fever cases and is char-
Over a period of 2 years, between January 2001 and December 2002, five patients with chorea minor were admitted to the pediatric division of a local primary hospital in Israel. During this period we have observed a total of 20 patients with acute rheumatic fever; five of them (25%) had chorea. Three of the five patients were males. The
From *Pediatric Rheumatology, †Pediatric Neurology, and ‡Pediatric Cardiology services, Kaplan Medical Center, Rehovot, affiliated to the Hadassah Medical School, the Hebrew University Jerusalem, Israel.
Communications should be addressed to: Dr. Barash; Pediatric Day Care; Kaplan Medical Center; Rehovot 76100, Israel. Received August 3, 2004; accepted September 22, 2004.
© 2005 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2004.09.012 ● 0887-8994/05/$—see front matter
Case Report Patients
Barash et al: Sydenham’s Chorea and Corticosteroids 205
Table 1.
Clinical data of patients with chorea minor
Patient
Onset to Diagnosis (Days)
Carditis
Arthritis
Skin
Fever
ESR
Prol P-R
Throat Culture
ASLO
1 2 3 4 5
7 5 30 7 2
Yes-moderate Yes-moderate Yes-mild No Yes-moderate
No No No No Yes-migratory
No No No No No
No No No No Yes
Normal Very high Normal Normal High
No Yes No No No
Positive Positive Negative Negative Positive
Normal High High Very high Very high
Abbrevations: ASLO ⫽ Antistreptolysin O ESR ⫽ Erythrocyte sedimentation rate Prol P-R ⫽ Prolonged P-R interval on electrocardiogram
youngest child was 4 years old; the other four were between 10 and 11 years of age as expected. All of them came from middle-class, small, urban families. The clinical data are summarized in Table 1. It is noteworthy that 4 of 5 patients were diagnosed within a few days of onset; the fifth patient (Patient 3) was referred to the hospital a month after onset of chorea, since at the beginning it was considered an emotional problem. Elevated erythrocyte sedimentation rate was documented in two patients; one of them also had fever, migratory arthritis, and moderate cardiac involvement. Carditis was diagnosed in four of the five patients, either mild or moderate. In all patients, recent streptococcal infection was confirmed either with positive throat culture (3 cases) or elevated antistreptolysin O titer (4 cases) and in two cases both of them. Because in all of the cases rheumatic chorea was considered the most probable diagnosis due to heart and joint involvement and proven recent streptococcal infection, we have done only a limited investigation to exclude other etiologies for chorea. All patients had negative antinuclear and anticardiolipin antibodies. Blood levels of ceruloplasmin were within normal limits, and eye examination by an ophthalmologist was normal.
Treatment All five patients were treated with oral penicillin for 10 days, followed by monthly injection of benzanthine penicillin. All the patients received oral prednisone, full dose (2 mg/kg/day) for the first 3 weeks, gradually tapering off for 3 further weeks. Weight, blood pressure, serum glucose and electrolytes were monitored, and none of the patients developed any adverse effects except slight, transient weight gain.
Follow-up All patients experienced marked clinical improvement within 24-48 hours after commencing steroid treatment. Complete resolution of all involuntary movements, restoration of motor skills, and emotional stability were achieved within 7-12 days. The patients were monitored for a mean of 26 months (range, 16-38). All of them are on prophylactic penicillin treatment, and none of them experienced any relapse of chorea or acute rheumatic fever.
Discussion
References
The rationale of steroid treatment in chorea minor is based upon the accumulating evidence that an immune mechanism, related to molecular mimicry between certain human tissue antigens (such as basal ganglia or myocardium) and antibasal ganglia antibody production, plays a
206
PEDIATRIC NEUROLOGY
crucial role in the pathogenesis of acute rheumatic fever and chorea in particular [8]. Although there are previous studies reporting the beneficial effect of corticosteroids in chorea minor [5-7], one of them [5] dates back to 1978 and another [7] deals with chronic chorea (mean duration 5 years) refractory to conventional treatment. Despite these publications, a review of more recent textbooks in pediatrics, pediatric rheumatology, and pediatric neurology indicates that corticosteroids are not mentioned in treatment recommendation for rheumatic chorea. This report describes five pediatric patients diagnosed with Sydenham’s chorea and treated successfully with a short course of corticosteroids. Contrary to the patients described by Cardoso [7], all our patients had acute disease and were diagnosed and treated within a short period. The commencement of treatment at this early stage may explain the rapid response and perhaps even the complete lack of recurrence. Complete resolution of all symptoms was achieved within 7-12 days, with a marked improvement within 24-48 hours, in all patients. This is a strikingly rapid response compared with the natural history of chorea minor, which may last a few months or more, or compared with other treatment protocols; for example, treatment with carbamazepine [3] in nine patients with Sydenham’s chorea resulted in improvement within 2-14 days and disappearance of symptoms within 2-12 weeks. It is also noteworthy that in our patients no relapses were seen during follow-up, contrary to other reports in which a recurrence rate of approximately 30% was seen [9]. This observation, although in a small group, cannot be attributed to coincidence and is promising enough to consider treatment with corticosteroids in patients with chorea minor as well as larger, possibly comparative studies.
Vol. 32 No. 3
[1] Ayoub EM. Resurgence of rheumatic fever in the United States: The changing picture of a preventable disease. Postgrad Med J 1992;92: 133-42. [2] Caedoso F, Vargas AP, Oliveira KD, Guerra AA, Amaral SV. Persistent Sydenham’s chorea. Mov Disord 1999;14:805-7. [3] Harel L, Zecharia A, Straussber R, Volovitz B, Amir J. Success-
ful treatment of rheumatic chorea with carbamazepine. Pediatr Neurol 2000;23:147-51. [4] Daoud AS, Zaki M, Al Saleh Q. Effectiveness of sodium valproate in the treatment of Sydenham’s chorea. Neurology 1990;40: 1140-2. [5] Green LN. Corticosteroids in the treatment of Sydenham’s chorea. Arch Neurol 1978;35:53-4. [6] Araujo AP, Padua PA, Maia-Filho HS. Management of rheumatic chorea: An observational study. Arq Neuropsiquiatr 2002;60:231-3.
[7] Cardoso F, Maia D, Cunningham MC, Valenca G. Treatment of Sydenham’s chorea with corticosteroids. Mov Disord 2003;18: 1374-7. [8] Church AJ, Cardoso F, Dale RC, Lees AJ, Thompson EJ Giovannoni G. Anti-basal ganglia antibodies in acute and persistent Sydenham’s chorea. Neurology 2002;59:227-31. [9] Berrios X, Quesney F, Morales A, Blazquez J, Bisno AL. Are all recurrences of “pure” Sydenham’s chorea true recurrences of acute rheumatic fever? J Pediatr 1985;107:867-72.
Barash et al: Sydenham’s Chorea and Corticosteroids 207
Introduction
acterized by rapid, purposeless, nonrepetitive involuntary movements that disappear with sleep and may involve all except the ocular muscles. There is impaired coordination, facial grimacing, clumsiness, and difficulty in dressing and feeding. The course is variable; it may last for weeks or months, but a much longer course is reported in some cases [2]. Usually only supportive treatment is recommended; in severe cases benzodiazepine or antipsychotic drugs such as haloperidol or risperidone may be used, and there are reports about the efficacy of carbamazepine [3] or valproic acid [4]. Some of the manifestations of acute rheumatic fever (carditis and arthritis) are known to respond favorably to anti-inflammatory treatment (aspirin and corticosteroids) with prompt clinical improvement; however, concerning carditis, there is no proof of benefit in long-term prognosis. Because chorea often occurs as an isolated manifestation after the resolution of the acute phase of the disease, it was thought that there is no benefit from anti-inflammatory treatment. Nevertheless, there are some reports on corticosteroid treatment in cases with chorea. In 1978 a cohort of eight patients with chorea were reported, all of them females, who received treatment with steroids and responded relatively rapidly [5]. In another study, the medical charts of 20 children with chorea minor were retrospectively reviewed; seven of them received treatment with corticosteroids. The shortest course of chorea occurred in a patient treated with prednisone [6]. Recently, Cardoso et al. [7] reported five patients with chorea minor refractory to conventional therapy and treated successfully with pulse methylprednisolone followed by oral prednisone. This report describes five pediatric patients diagnosed with acute rheumatic fever and Sydenham’s chorea and treated successfully with a short course of corticosteroids, thus again raising the issue of such treatment.
Acute rheumatic fever is a nonsuppurative complication of group A beta-hemolytic streptococcal infection. During the second half of the twentieth century there was a steep decrease in the incidence of acute rheumatic fever in North America and Western Europe followed by a resurgence of the disease in several areas in the United States [1]. One of the major signs of acute rheumatic fever is chorea minor or Sydenham’s chorea; it occurs in approximately 10% of acute rheumatic fever cases and is char-
Over a period of 2 years, between January 2001 and December 2002, five patients with chorea minor were admitted to the pediatric division of a local primary hospital in Israel. During this period we have observed a total of 20 patients with acute rheumatic fever; five of them (25%) had chorea. Three of the five patients were males. The
From *Pediatric Rheumatology, †Pediatric Neurology, and ‡Pediatric Cardiology services, Kaplan Medical Center, Rehovot, affiliated to the Hadassah Medical School, the Hebrew University Jerusalem, Israel.
Communications should be addressed to: Dr. Barash; Pediatric Day Care; Kaplan Medical Center; Rehovot 76100, Israel. Received August 3, 2004; accepted September 22, 2004.
© 2005 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2004.09.012 ● 0887-8994/05/$—see front matter
Case Report Patients
Barash et al: Sydenham’s Chorea and Corticosteroids 205
Table 1.
Clinical data of patients with chorea minor
Patient
Onset to Diagnosis (Days)
Carditis
Arthritis
Skin
Fever
ESR
Prol P-R
Throat Culture
ASLO
1 2 3 4 5
7 5 30 7 2
Yes-moderate Yes-moderate Yes-mild No Yes-moderate
No No No No Yes-migratory
No No No No No
No No No No Yes
Normal Very high Normal Normal High
No Yes No No No
Positive Positive Negative Negative Positive
Normal High High Very high Very high
Abbrevations: ASLO ⫽ Antistreptolysin O ESR ⫽ Erythrocyte sedimentation rate Prol P-R ⫽ Prolonged P-R interval on electrocardiogram
youngest child was 4 years old; the other four were between 10 and 11 years of age as expected. All of them came from middle-class, small, urban families. The clinical data are summarized in Table 1. It is noteworthy that 4 of 5 patients were diagnosed within a few days of onset; the fifth patient (Patient 3) was referred to the hospital a month after onset of chorea, since at the beginning it was considered an emotional problem. Elevated erythrocyte sedimentation rate was documented in two patients; one of them also had fever, migratory arthritis, and moderate cardiac involvement. Carditis was diagnosed in four of the five patients, either mild or moderate. In all patients, recent streptococcal infection was confirmed either with positive throat culture (3 cases) or elevated antistreptolysin O titer (4 cases) and in two cases both of them. Because in all of the cases rheumatic chorea was considered the most probable diagnosis due to heart and joint involvement and proven recent streptococcal infection, we have done only a limited investigation to exclude other etiologies for chorea. All patients had negative antinuclear and anticardiolipin antibodies. Blood levels of ceruloplasmin were within normal limits, and eye examination by an ophthalmologist was normal.
Treatment All five patients were treated with oral penicillin for 10 days, followed by monthly injection of benzanthine penicillin. All the patients received oral prednisone, full dose (2 mg/kg/day) for the first 3 weeks, gradually tapering off for 3 further weeks. Weight, blood pressure, serum glucose and electrolytes were monitored, and none of the patients developed any adverse effects except slight, transient weight gain.
Follow-up All patients experienced marked clinical improvement within 24-48 hours after commencing steroid treatment. Complete resolution of all involuntary movements, restoration of motor skills, and emotional stability were achieved within 7-12 days. The patients were monitored for a mean of 26 months (range, 16-38). All of them are on prophylactic penicillin treatment, and none of them experienced any relapse of chorea or acute rheumatic fever.
Discussion
References
The rationale of steroid treatment in chorea minor is based upon the accumulating evidence that an immune mechanism, related to molecular mimicry between certain human tissue antigens (such as basal ganglia or myocardium) and antibasal ganglia antibody production, plays a
206
PEDIATRIC NEUROLOGY
crucial role in the pathogenesis of acute rheumatic fever and chorea in particular [8]. Although there are previous studies reporting the beneficial effect of corticosteroids in chorea minor [5-7], one of them [5] dates back to 1978 and another [7] deals with chronic chorea (mean duration 5 years) refractory to conventional treatment. Despite these publications, a review of more recent textbooks in pediatrics, pediatric rheumatology, and pediatric neurology indicates that corticosteroids are not mentioned in treatment recommendation for rheumatic chorea. This report describes five pediatric patients diagnosed with Sydenham’s chorea and treated successfully with a short course of corticosteroids. Contrary to the patients described by Cardoso [7], all our patients had acute disease and were diagnosed and treated within a short period. The commencement of treatment at this early stage may explain the rapid response and perhaps even the complete lack of recurrence. Complete resolution of all symptoms was achieved within 7-12 days, with a marked improvement within 24-48 hours, in all patients. This is a strikingly rapid response compared with the natural history of chorea minor, which may last a few months or more, or compared with other treatment protocols; for example, treatment with carbamazepine [3] in nine patients with Sydenham’s chorea resulted in improvement within 2-14 days and disappearance of symptoms within 2-12 weeks. It is also noteworthy that in our patients no relapses were seen during follow-up, contrary to other reports in which a recurrence rate of approximately 30% was seen [9]. This observation, although in a small group, cannot be attributed to coincidence and is promising enough to consider treatment with corticosteroids in patients with chorea minor as well as larger, possibly comparative studies.
Vol. 32 No. 3
[1] Ayoub EM. Resurgence of rheumatic fever in the United States: The changing picture of a preventable disease. Postgrad Med J 1992;92: 133-42. [2] Caedoso F, Vargas AP, Oliveira KD, Guerra AA, Amaral SV. Persistent Sydenham’s chorea. Mov Disord 1999;14:805-7. [3] Harel L, Zecharia A, Straussber R, Volovitz B, Amir J. Success-
ful treatment of rheumatic chorea with carbamazepine. Pediatr Neurol 2000;23:147-51. [4] Daoud AS, Zaki M, Al Saleh Q. Effectiveness of sodium valproate in the treatment of Sydenham’s chorea. Neurology 1990;40: 1140-2. [5] Green LN. Corticosteroids in the treatment of Sydenham’s chorea. Arch Neurol 1978;35:53-4. [6] Araujo AP, Padua PA, Maia-Filho HS. Management of rheumatic chorea: An observational study. Arq Neuropsiquiatr 2002;60:231-3.
[7] Cardoso F, Maia D, Cunningham MC, Valenca G. Treatment of Sydenham’s chorea with corticosteroids. Mov Disord 2003;18: 1374-7. [8] Church AJ, Cardoso F, Dale RC, Lees AJ, Thompson EJ Giovannoni G. Anti-basal ganglia antibodies in acute and persistent Sydenham’s chorea. Neurology 2002;59:227-31. [9] Berrios X, Quesney F, Morales A, Blazquez J, Bisno AL. Are all recurrences of “pure” Sydenham’s chorea true recurrences of acute rheumatic fever? J Pediatr 1985;107:867-72.
Barash et al: Sydenham’s Chorea and Corticosteroids 207