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The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia
Journal of the Saudi Heart Association (2009) 21, 215– 220
King Saud University
Journal of the Saudi Heart Association www.ksu.edu.sa www.sha.org.sa www.sciencedirect.com
ORIGINAL ARTICLE
The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia Mansour Al Qurashi Al-Yamamah Hospital, P.O. Box 60989, Riyadh 11555, Saudi Arabia Available online 3 November 2009
KEYWORDS Rheumatic fever; Children; Saudi Arabia
Abstract Background: The study was carried out in Riyadh City Hospital to determine the hospital prevalence of acute rheumatic fever (ARF), its characteristics and to determine the proportion of the ARF population that have recurrent attacks. Methods: The study was an analysis of 83 children with ARF, admitted to the Children’s Hospital, Riyadh, over a 10-year period (1994–2003). The diagnosis of ARF was based on clinical features as defined in the modified Jones criteria with evidence of recent streptococcal infection. The diagnosis of recurrence of rheumatic fever in children with rheumatic heart disease was based on the presence of one major criterion apart from carditis or two minor criteria, in addition to evidence of preceding streptococcal infection. Results: The mean age at presentation was 9 years. In 31 (37%) cases, arthritis was the only major Jones criterion. In 30 (36%) others, arthritis was associated with carditis and in 3 (4%), with chorea. Cardiac involvement was documented in 44 (53%) cases; it occurred alone in 5 (6%), with arthritis in 30 (36%), and with chorea in 9 (11%) others. Among the 44 with carditis, the pattern of cardiac involvement was valvular only (mild carditis) in 30 (68%), while it was severe in the remaining 14 (32%) cases who also had heart failure. The involvement of the mitral valve alone occurred in 26 (59%) cases in the form mitral regurgitation, while both aortic and mitral valve regurgitation were present in 11 (25%) cases, and aortic valve regurgitation alone in four (9%) others. Chorea was the only major criterion of ARF in 5 children (6%), while it occurred in association with other major criteria in 12 (15%) others. Nineteen (23%) children had recurrent attacks of ARF. Conclusion: ARF continues to occur in Saudi Arabia in the period (1994–2003), despite the progress made in the socio-economic development of the country, and this is often associated with severe cardiac involvement. ª 2009 King Saud University. All rights reserved.
E-mail address: [email protected] 1016-7315 ª 2009 King Saud University. All rights reserved. Peerreview under responsibility of King Saud University. doi:10.1016/j.jsha.2009.10.004
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1. Introduction Acute rheumatic fever (ARF) is an inflammatory disease of the heart, joints, CNS, and subcutaneous tissue that develops after a pharyngeal infection by one of the group A beta-hemolytic streptococci (Streptococcus pyogenes) (Veasy and Hill, 1997). ARF has been reported previously from different regions of the kingdom (Al-Sekait et al., 1990; Al-Eissa et al., 1993;
216 Abbag et al., 1998). The last large study of the disease in Saudi Arabia was published in 1991; this showed a high prevalence of rheumatic fever of 0.3 per 1000 and the prevalence of chronic rheumatic heart disease of 2.8 per 1000, giving an overall rate of 3.1 per 1000 school children 6–15 years old (Al-Sekait et al., 1991). ARF with its attendant rheumatic heart disease continues to occur in Saudi Arabia, despite the progress made in the socio-economic development of the country and the great strides made in the delivery of sophisticated medical practice to its citizens. In order to update information on this disease, the present study was carried out to determine the hospital prevalence of rheumatic fever in Riyadh City, to verify the sociodemographic and clinical profile of the initial attacks and to compare results with those from other countries. In addition, the study had the objective of determining the proportion of the ARF population that have recurrent attacks. 2. Patients and methods A review of all patients with acute rheumatic fever (ARF) who were admitted to Suleimania Children’s Hospital, Riyadh, during the period, 1994–2003, was undertaken. The study consisted of a retrospective analysis of the medical records for the period between 1994 and 1998 and prospective study for the period 1999–2003. The patients were either referred from primary health clinics (PHC), or admitted through the emergency department of the hospital. The diagnosis of ARF was based on clinical features and evidence of recent streptococcal infection. The features were those that constitute the revised modified Jones criteria, the major ones being arthritis, carditis, chorea, erythema marginatum and subcutaneous nodules, while the minor criteria consisted of arthralgia, fever, high ESR, and prolonged PR interval (Jones, 1992). ARF with isolated arthritis was differentiated from post streptococcal reactive arthropathy (PSRA) by the clinical features such as migratory nature of arthritis or dramatic response to aspirin therapy in ARF while PSRA involves more joints including small joints of hands and feet, axial involvement, symmetrical, non migratory but more protracted and responds less to aspirin (Shulman and Ayoub, 2002; Gerber et al., 2009). Although ARF with isolated arthritis and PSRA overlap, (Jones, 1992; Keitzer, 2005; Tutar et al., 2002) children with diagnosis of PSRA were excluded from the study (13 patients). Arthritis was defined either by obvious redness, swelling and hotness of joints, or by limitation in the range of joint movement due to tenderness, and limping. All the patients had routine cultures of the throat; b-haemolytic streptococci were identified by microscopy. Erythrocyte sedimentation rates were performed by standard methods, while anti-streptolysin O titres were determined by standard techniques with commercially available reagents and a single isolated titer P400 Todd units in our lab was considered diagnostic of preceding recent streptococcal infection. The ‘‘upper limit of normal’’ value for streptococcal antibody titers depends on the population involved (AlEissa et al., 1993; Shet and Kaplan, 2002). Standard 12-lead electrocardiograms and two-dimensional (2D) and Doppler echocardiography were obtained for each patient. The valvular disease in ARF was suggested clinically by the presence of an audible murmur and confirmed by two-dimensional (2D) echocardiography and Doppler echo. Isolated Sydenham chorea was diagnosed after excluding other
M.A. Qurashi causes of chorea (Atatoa-Carr et al., 2008). The diagnosis was easier when chorea was associated with carditis or arthritis and evidence of previous group A b-haemolytic streptococcal infection, although the guidelines of the WHO, and American Academy of Cardiology specify that evidence of previous streptococcal infection is not necessary for the diagnosis of Sydenham chorea (Jones, 1992). The diagnosis of recurrence of rheumatic fever (RF) in children with rheumatic heart disease was based on the presence of one major criterion apart from carditis or two minor criteria, in addition to evidence of preceding streptococcal infection. This exception to the modified Jones criteria was based on the guidelines by the WHO and American Academy of Cardiology (Jones, 1992). 3. Results 3.1. Incidence and demographics During the 10-year period, the staff at Sulemania Children’s hospital admitted a total of 112 cases with diagnosis of ARF that satisfied the modified Jones criteria. Of the 112 cases, the full records of 83 were analysed (Table 1), while those of the remaining 29 cases were excluded either due to lack of sufficient data in the medical records (16 patients) or misdiagnoses as ARF with isolated arthritis rather than post streptococcal reactive arthropathy (13 patients). The annual number of cases was 17 in 1994 and 1995, while in 2003, only 2 cases were admitted (Table 1); the average number of cases seen per year was eight. The 83 children were aged, 4–12 years (mean 9 years; mode 11 years). There was a male preponderance (M/F ratio was 1.4:1). The number of siblings of the cases varied from 1 to 14, (mean, 5.75). Seventy-five (90%) of the 83 were from Riyadh city while 8 (10%) others from rural areas around the city. Based on the father’s occupation, income and housing, 53 (64%) children were categorized as belonging to the low socio-economic class, 28 (34%) were from the middle class and only 2 children (2%) were from the high socio-economic class. Seventy-three (88%) were Saudi nationals. 3.2. Clinical manifestations 3.2.1. Major diagnostic criteria 3.2.1.1. Arthritis. A summary of the major clinical manifestations in the patients is shown in Table 2. A single major man-
Table 1
Yearly Distribution of 83 Cases of ARF.
Year
Total per year
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
17 17 7 1 5 13 8 6 7 2
% of total 20.5 20.5 8.4 1.2 6.0 15.7 9.7 7.2 8.4 2.4
Total
83
100.0
The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia Table 2
Major manifestations of ARF in 83 children.
Manifestation
No. of cases
One major manifestation Arthritis Carditis Sydenham chorea
% of total
31 5 5
37 6 6
Two major manifestations Carditis and arthritis Carditis and chorea Chorea and arthritis
30 9 3
36 11 4
Total
83
100
ifestation was present in 41 children (49%). Arthritis alone was present in 31 children (37%), with carditis in 30 (36%) others, while arthritis with chorea was seen in only 3 children (4%). Thus, the total number of children who had arthritis was 64 (77%). In 45 (70%) of the 64 children, the arthritis involved a few large joints (less than five joints) namely, the knees, elbows, wrists, hips, ankles, and shoulders; in 15 (23%), it involved more than four joints, including 2 cases in which the small joints of the hand and feet, were also involved. Axial involvement, characterized by back pain and limitation in flexion of the spine was seen in 4 children (5%). Monoarthritis affecting large joints such as the knee, elbow, or wrist occurred in 4 children (6%). The arthritis was migratory in all 60 children with multiple joint involvement. 3.2.1.2. Carditis. Carditis, which was the second most common major diagnostic criterion, was present in 44 children (53%); it was an isolated major manifestation in 5 children (6%) only. On the other hand, carditis with arthritis was present in 30 children (36%), and together, they constituted the two most commonly associated major criteria of ARF. Carditis with Sydenham chorea was observed in 9 children (11%), 6 of whom had mitral valve regurgitation, while 3 had both mitral and aortic regurgitation. The pattern of valvular involvement in the 44 cases is shown in Table 3. Two of the children with mitral valve regurgitation and Sydenham chorea were brothers. Chorea occurred simultaneously with carditis in 4 children, while 5 in others, it occurred after intervals that varied from 3 months to 4 years. Heart failure occurred in 14 children (32%) with carditis, while pericardial effusion was present in 2 children. Silent mitral valve regurgitation, in which there was no audible murmur but only discovered on echocardiogram, was not considered as evidence of carditis (Jones, 1992; Ata-
Table 3
Pattern of valvular disease in 44 children with ARF.
Valvular lesion
No.
Mitral valve regurgitation Mitral and aortic regurgitation Aortic valve regurgitation *Others
26 11 4 3
59 25 9 7
Total
44
100
*
217
toa-Carr et al., 2008; Gupta et al., 2008). although various studies point to the importance of echographic evidence of subclinical carditis and considering it as definite rheumatic carditis, even though it is a mild form (Saxena, 2000; Veasy, 2001; Vijayalakshmi et al., 2008; Vijayalakshmi et al., 2005). 3.2.2. Sydenham chorea Rheumatic chorea occurred as isolated major manifestation of ARF in 5 children (6%); it also occurred in association with carditis in 9 (11%) others and with arthritis in 3 (4%). The total number of children with ARF who developed chorea was thus, 17 (20%). The chorea was bilateral in 16 children (94%) and unilateral in only 1 child (6%). The face was involved in 6 children (35%) while emotional lability was seen in 16 (95%). The duration of the chorea ranged from three week to 5 months. 3.2.2.1. Others. None of the cases presented with any of the two other major diagnostic criteria of ARF namely, erythema marginatum and subcutaneous nodules. 3.2.3. Minor diagnostic criteria The minor diagnostic criteria of ARF that were present are summarized in Table 4. ESR, an acute phase reactant, was recorded in 79 children; it was raised (>20 mm in the first hour) in 74 children (94%) and in the normal range in 5 children (6%), who presented with chorea. High-grade fever was present in 69 children (83%). Prolonged PR interval (more than 0.16 s on ECG), was present in 19 children (23%). Arthralgia in the absence of arthritis was noticed in 9 children (11%); it involved large joints including the knees, elbows, wrists, ankles, and shoulders. 3.3. Evidence of preceding streptococcal infection There was a history of sore throat, one to four weeks before the onset of the manifestations of ARF in 55 children (66%). Throat culture for group A b-haemolytic streptococcus was positive in only 9 (11%). Elevated anti-streptolysin O titre (>400) was present in 79 (95%) children, while it was normal in 4 with rheumatic chorea. 3.4. Treatment Isolated arthritis was treated satisfactorily with aspirin in 26 children (84%) and with naproxen in 5 (16%). Carditis (valvulitis) was treated with aspirin in 40 children (91%). These children either had carditis alone (3 (7%) children), in association with arthritis (30 (75%) children) or with chorea (7 (18%) children). Mild carditis in 26 children was treated with aspirin only. Severe carditis with heart failure was treated with prednisolone and aspirin in 14 (100%) children. Although based
%
One case each of: (a) MV and TV regurgitation; (b) MV, AV and PV regurgitation (c) MV, TV and PV regurgitation (MV = Mitral valve TV = Tricuspid valve PV = Pulmonary valve).
Table 4
Minor manifestations of ARF in 83 children.
Manifestation a
High ESR (>20 mm/h) Fever Prolonged PR interval (>0.16 s) Arthralgia a
Determined in 79 cases.
No of cases
% of total
74 69 19 9
94 83 23 11
218 on the meta-analysis, the advantage of corticosteroid treatment over salicylates in preventing rheumatic heart disease was not statistically significant (Albert et al., 1995; Cilliers, 2003). The total number of children who received aspirin was thus, 68. The side effects of aspirin observed were acute gastritis with abdominal pain and vomiting in 5 children (7%), while 1 child (1.5%) developed gastrointestinal bleeding. These side effects occurred despite the routine administration of antacid syrup to all the children on aspirin. No side effects were reported with the other medications. Rheumatic chorea was treated with Valproic acid in 15 children (88%) and haloperidol in 2 (12%). There was no mortality from ARF in our series. 3.5. Prophylaxis In line with our practice, all the children were placed on intramuscular (IM) benzathine penicillin, 1.2 million units every 21 days. Two children received daily oral penicillin as an alternative ARF prophylaxis, prescribed after rejection of IM injections. 3.6. Recurrences Nineteen children (23%) had recurrences; 7 (37%) had second attacks and 12 (63%) had more frequent attacks that ranged from 3 to 6. The interval between attacks varied from 6 months to 9 years with most (52%) being less than 1 year. The patients’ ages at the time of recurrence ranged from 5 years to 13 years (median 10 years). Compliance with longterm prophylaxis of ARF using intramuscular penicillin was poor in all the 19 children who had recurrent attacks of rheumatic fever. The major manifestation of ARF was the same in the recurrent attacks as in the preceding one in 15 patients (79%) of the 19 cases; i.e. isolated carditis in 3, isolated arthritis in 4, isolated chorea in 2 and arthritis with carditis in six. The recurrent episode differed from the initial illness in only 4 patients (21%), 3 of whom had carditis in the first attack, but developed chorea in the subsequent attacks and 1 patient who had arthritis with carditis in the first attack and developed chorea in the following attack. 4. Discussion There are various reports about the pattern of acute rheumatic fever (ARF) in the Kingdom (Al-Sekait et al., 1990; Al-Eissa et al., 1993; Abbag et al., 1998; Al-Sekait et al., 1991). However, the present report highlights our 10-year experience at the Children’s Hospital in Riyadh. The present series indicate that the incidence of ARF was high at the beginning (1994–1995) of the decade and had dropped markedly by the end (2003) as shown in Table 1. This apparent reduction in the number of new cases of ARF admitted to our hospital, probably reflects the situation in the community and may be ascribed to improved health care and primary prevention of ARF by early diagnosis of pharyngitis and adequate treatment with antibiotics. Therefore, further studies are required to identify the precise incidence of ARF in all hospitals in Riyadh city. Increased rate of ARF (64%) was seen in children from urban, low-income, and crowded areas. Crowded living conditions, which are conductive to the spread of respiratory
M.A. Qurashi infections, continue to be a predisposing factor. In addition, the associated poverty leads to a delayed access to medical care. These sociodemographic features of our patients were similar with those from other countries (Al-Eissa et al., 1993; Essop and Nkomo, 2005; Carapetis, 2007). The lack of a history of preceding pharyngitis in 28 children (34%) in this series and at similar percentage in other series (Al-Eissa et al., 1993; Gerber et al., 2009), is an important factor in the persistence of ARF in the community; this is in addition to another important factor namely, poor compliance of the patients to a full 10-day course of oral penicillin for the treatment of bacterial pharyngitis (Dajani, 1996; Gerber and Tanz, 2001). Therefore, in order to optimize primary prevention of ARF, mass education of the population in general and children in particular, is necessary using all resources available including the media. Recurrence rate of ARF in our series was high (23%); due to poor compliance with the schedule of benzathine penicillin G (BPG) administration, which was once, every 21 days. Although studies have suggested that BPG injections every 3 weeks are superior to injections every 4 weeks (Gerber et al., 2009; Lue et al., 1996), implementation of an every 3 weeks regimen can be problematic with regards to patient compliance. Currie in 1996 suggested that there may be benefits in a BPG regimen every 4 weeks with doses higher than the standard 1,200,000 U (Currie, 1996). Further studies of higher dose BPG regimens seem justified. Arthritis was the most common major manifestation of ARF in this series which was seen in 64 (77%) children, similar to that observed by other workers (Al-Eissa et al., 1993; Ravisha et al., 2003). The frequency of isolated arthritis as the presenting symptom in our series (31 children, 37%) is similar to other study (Williamson et al., 2000). Four children (6%) presented as monoarthritis, this unusual presentation was reported in a previous study (Wilson et al., 2007). In the latter situation, the diagnosis of ARF was difficult and recourse was taken to the presence of other associated major manifestation such as carditis or chorea. Although 31 (37%) children with isolated arthritis as a major criterion in association with other minor criteria such as fever and an elevated ESR plus evidence of a recent streptococcal throat infection were included in our series, such children could be labelled as post-streptococcal reactive arthritis by other physicians. The presence of migratory arthritis, involvement of large joints, prolongation of PR interval and dramatic response to aspirin therapy were considered for the likely diagnosis of ARF in this group. The 13 children who were excluded from this study did not have these features. The frequency of carditis in this series (53%), is similar to that observed by other workers (Al-Eissa et al., 1993; Martins et al., 2006). Mild carditis occurred in 30 children (68%), 3 of whom developed rheumatic heart disease (RHD) while severe carditis with heart failure occurred in 14 children (32%), 11 of whom ultimately developed RHD. A total of 14 children (32%) with carditis developed RHD, Table 5. The incidence of severe carditis was higher than reported by other workers (Al-Eissa et al., 1993). Mitral regurgitation and aortic regurgitation were the common findings in ARF while isolated mitral valve regurgitation, mitral valve regurgitation with stenosis and aortic valve regurgitation were the more common valvular disease in RHD. The profile of ARF regarding the relative frequency of valvular involvement in this series, is similar to that
The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia Table 5 Residual rheumatic heart disease pattern in 14 children. Cardiac lesion Mitral regurgitation Mitral and aortic regurgitation with mitral stenosis Mitral regurgitation and stenosis Aortic regurgitation and stenosis Mitral, aortic and pulmonary regurgitation Mitral and aortic regurgitation Mitral, tricuspid and pulmonary regurgitation Aortic regurgitation Total
No. of cases 6 2 1 1 1 1 1 1 14
observed by other workers in the Kingdom (Al-Eissa et al., 1993). PR interval prolongation is a minor criterion for the diagnosis of ARF, present in about 35–40% of children with ARF; it is useful in evaluating the patients with isolated arthritis when, if present, it makes other causes of joint involvement unlikely (Guzman-Cottrill et al., 2004; Olgun and Ceviz, 2004). In our study, it was prolonged in 19 children (23%) and only 4 (13%) children with isolated arthritis had a prolonged PR interval. In the present series, two brothers had carditis at first attack in the form of mitral valve regurgitation followed by chorea during the second attack of ARF and finally developed RHD presenting as chronic mitral valve regurgitation in addition to recurrent attacks of chorea; this suggests a genetic predisposition to form autoantibodies to specific tissue antigens which in these two brothers, were the brain and cardiac tissues. There is a similarity between streptococcal and tissue antigens that trigger autoantibody formation (Veasy and Hill, 1997; Martins et al., 2006; Bryant et al., 2009). Chorea was seen in 17 children (21%) either alone, or in combination with other major diagnostic criteria. This percentage is similar to that reported in other series (Martins et al., 2006; Oen, 2000; Al-Eissa, 1993). Diagnosis of isolated chorea was based on exclusion of other causes or chorea such as systemic lupus erythematosus, brucellosis, central neurological diseases, drug ingestion and encephalitis (Atatoa-Carr et al., 2008). Evidence of preceding streptococcal infection is not required; in fact, in our series, only one out of 5 children with isolated chorea had a high ASO titre (Jones, 1992). The profile of chorea in our series is mild, bilateral and shorter in duration compared to other studies (Al-Eissa, 1993; Dı´ az-Grez et al., 2004). Valproic acid had a high success rate in reduction of symptoms of rheumatic chorea which is similar to other study (Pena et al., 2002). All our patients who had initial attack of ARF with chorea (8 children) followed for 5 years and none of them develop valvular lesion in comparison with other study (Panamonta et al., 2007). Group A, b-haemolytic streptococcus (GAS) was isolated from throat culture in only 9 children (11%); compared to other studies in which GAS was isolated from 20% to 25% of throat cultures (Jones, 1992; Chagani and Aziz, 2003). This low yield was probably due to previous antibiotic treatment in most of our cases, 66% of whom were referred to our hospital
219
by primary care physicians. As it happened, ASO titre was left as the only available tool for confirming a preceding streptococcal infection. The overdiagnosis of PSRA in 3 children with arthritis and high ASO titre in our study, ultimately labelled as brucellosis, juvenile rheumatoid arthritis (JRA) and seronegative spondyloarthropathies (SSA) reflect high streptococcal endemicity in the community. Telmesani et al showed in a study done during 2000 a carrier rate of GAS in healthy Saudi children (3%), the occurrence of GAS among children with tonsillitis and pharyngitis was 40% (Telmesani and Ghazi, 2002). Abu-Sabaah reported only 19% of children with pharyngitis had GAS by culture (Abu-Sabaah and Ghazi, 2006). Further studies are required to assess the exact prevalence of streptococcal infection in the population; if such studies confirms that a great number of healthy children has a high ASO titre, then the diagnosis of ARF in children with isolated arthritis or the diagnosis of PSRA should be made carefully (Atatoa-Carr et al., 2008; Kaplan et al., 1998; Tucker et al., 1993; Brandt et al., 1998). 4.1. Study limitations The study was retrospective in the first 5 years from 1994 to 1998 with lacking of some data in the medical records, leading to exclusion of 16 patients with ARF from detail analysis. 5. Conclusion Acute rheumatic fever (ARF) continues to occur in Saudi Arabia, despite the progress made in the socio-economic development of the country, often associated with severe cardiac involvement. Post-streptococcal reactive arthritis is usually confused with ARF of the isolated arthritis type and differentiation can be difficult. High recurrence rate of ARF in the present study is due to poor compliance with prophylaxis regime of recommended 21-day interval for long acting penicillin (Gerber et al., 2009). The recurrence of the same major criteria in the recurrence cases strongly suggest that the genetic predisposition for rheumatic fever is tissue selective.
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M.A. Qurashi Keitzer, R., 2005. Acute rheumatic fever (ARF) and post streptococcal reactive arthritis (PSRA) – an update. Z. Rheumatol. 64 (5), 295– 307. Lue, H.C., Wu, M.H., Wang, J.K., Wu, F.F., Wu, Y.N., 1996. Threeversus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Pediatrics 97, 984–988. Martins, T.B., Veasy, L.G., Hill, H.R., 2006. Antibody responses to Group A streptococcal infections in acute rheumatic fever. Pediatr. Infect Dis. J. 25, 832–837. Oen, K., 2000. Comparative epidemiology of the rheumatic diseases in Children. Curr. Opin. Rheumatol. 12, 410–414. Olgun, H., Ceviz, N., 2004. Unusual rhythm problems in acute rheumatic fever: two patient reports. Clin. Pediatr. 43, 197–199. Panamonta, M., Chaikitpinyo, A., Auvichayapat, N., Weraarchakul, W., Panamonta, O., Pantongwiriyakul, A., 2007. Evolution of valve damage in Sydenham’s chorea during recurrence of rheumatic fever. Int. J. Cardiol. 119, 73–79. Pena, J., Mora, E., Cardozo, J., et al., 2002. Comparison of the efficacy of carbamazepine, haloperidol and valproic acid in the treatment of the children with Sydenham’s chorea: clinical followup of 18 patients. Arq. Neuropsiquiatr. 60, 374–377. Ravisha, M.S., Tullu, M.S., Kamat, J.R., 2003. Rheumatic fever and rheumatic heart disease: clinical profile of 550 cases in India. Arch. Med. Res. 34, 382–387. Saxena, A., 2000. Diagnosis of rheumatic fever: current status of Jones criteria and role of echocardiography. Indian J. Pediatr. 67, S11– S14. Shet, A., Kaplan, E.L., 2002. Clinical use and interpretation of group A streptococcal antibody tests: a practical approach for the pediatrician or primary care physician. Pediatr. Infect. Dis. J. 21, 420–426. Shulman, S.T., Ayoub, E.M., 2002. Post streptococcal reactive arthritis. Curr. Opin. Rheumatol. 14, 562–565. Telmesani, A.M., Ghazi, H.O., 2002. A study of group A streptococcal bacteria isolation from children less than 12 years with acute tonsillitis, pharyngitis and healthy primary school children. SSFCM J. 9, 2. Tucker, L.B., Goldstein-Schainberg, C., Miller, L.C., Schaller, J.G., 1993. Antistreptococcal serology in juvenile rheumatoid arthritis. In: Proceedings of the International League against Rheumatism. Congress of Rheumatology, July 1993, Barcelona. Tutar, E., Atalay, S., Yilmaz, E., Ucar, T., Kocak, G., Imamoglu, A., 2002. Post streptococcal reactive arthritis in children: is it really a different entity from rheumatic fever? Rheumatol. Int. 22 (2), 80–83 (Epub. May 8, 2002). Veasy, L.G., 2001. Time to take soundings in acute rheumatic fever. Lancet 357, 1994–1995. Veasy, L.G., Hill, H.R., 1997. Immunologic and clinical correlations in rheumatic fever and rheumatic heart disease. Pediatr. Infect Dis. J. 16 (4), 400–407. Vijayalakshmi, I.B., Mithravinda, J., Deva, A.N., 2005. The role of echocardiography in diagnosing carditis in the setting of acute rheumatic fever. Cardiol. Young 15, 583–588. Vijayalakshmi, I.B., Vishnuprabhu, R.O., Chitra, N., Rajasri, R., Anuradha, T.V., 2008. The efficacy of echocardiographic criterions for the diagnosis of carditis in acute rheumatic fever. Cardiol. Young 18 (6), 586–592. Williamson, L., Bowness, P., Mowat, A., Ostman-Smith, I., 2000. Lesson of the week: difficulties in diagnosing acute rheumatic feverarthritis may be short lived and carditis silent. BMJ 320, 362–365. Wilson, E., Wilson, N., Voss, L., Morreau, J., Lennon, D., 2007. Monoarthritis in rheumatic fever. Pediatr. Infect Dis. J. 26 (4), 369– 370.
King Saud University
Journal of the Saudi Heart Association www.ksu.edu.sa www.sha.org.sa www.sciencedirect.com
ORIGINAL ARTICLE
The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia Mansour Al Qurashi Al-Yamamah Hospital, P.O. Box 60989, Riyadh 11555, Saudi Arabia Available online 3 November 2009
KEYWORDS Rheumatic fever; Children; Saudi Arabia
Abstract Background: The study was carried out in Riyadh City Hospital to determine the hospital prevalence of acute rheumatic fever (ARF), its characteristics and to determine the proportion of the ARF population that have recurrent attacks. Methods: The study was an analysis of 83 children with ARF, admitted to the Children’s Hospital, Riyadh, over a 10-year period (1994–2003). The diagnosis of ARF was based on clinical features as defined in the modified Jones criteria with evidence of recent streptococcal infection. The diagnosis of recurrence of rheumatic fever in children with rheumatic heart disease was based on the presence of one major criterion apart from carditis or two minor criteria, in addition to evidence of preceding streptococcal infection. Results: The mean age at presentation was 9 years. In 31 (37%) cases, arthritis was the only major Jones criterion. In 30 (36%) others, arthritis was associated with carditis and in 3 (4%), with chorea. Cardiac involvement was documented in 44 (53%) cases; it occurred alone in 5 (6%), with arthritis in 30 (36%), and with chorea in 9 (11%) others. Among the 44 with carditis, the pattern of cardiac involvement was valvular only (mild carditis) in 30 (68%), while it was severe in the remaining 14 (32%) cases who also had heart failure. The involvement of the mitral valve alone occurred in 26 (59%) cases in the form mitral regurgitation, while both aortic and mitral valve regurgitation were present in 11 (25%) cases, and aortic valve regurgitation alone in four (9%) others. Chorea was the only major criterion of ARF in 5 children (6%), while it occurred in association with other major criteria in 12 (15%) others. Nineteen (23%) children had recurrent attacks of ARF. Conclusion: ARF continues to occur in Saudi Arabia in the period (1994–2003), despite the progress made in the socio-economic development of the country, and this is often associated with severe cardiac involvement. ª 2009 King Saud University. All rights reserved.
E-mail address: [email protected] 1016-7315 ª 2009 King Saud University. All rights reserved. Peerreview under responsibility of King Saud University. doi:10.1016/j.jsha.2009.10.004
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1. Introduction Acute rheumatic fever (ARF) is an inflammatory disease of the heart, joints, CNS, and subcutaneous tissue that develops after a pharyngeal infection by one of the group A beta-hemolytic streptococci (Streptococcus pyogenes) (Veasy and Hill, 1997). ARF has been reported previously from different regions of the kingdom (Al-Sekait et al., 1990; Al-Eissa et al., 1993;
216 Abbag et al., 1998). The last large study of the disease in Saudi Arabia was published in 1991; this showed a high prevalence of rheumatic fever of 0.3 per 1000 and the prevalence of chronic rheumatic heart disease of 2.8 per 1000, giving an overall rate of 3.1 per 1000 school children 6–15 years old (Al-Sekait et al., 1991). ARF with its attendant rheumatic heart disease continues to occur in Saudi Arabia, despite the progress made in the socio-economic development of the country and the great strides made in the delivery of sophisticated medical practice to its citizens. In order to update information on this disease, the present study was carried out to determine the hospital prevalence of rheumatic fever in Riyadh City, to verify the sociodemographic and clinical profile of the initial attacks and to compare results with those from other countries. In addition, the study had the objective of determining the proportion of the ARF population that have recurrent attacks. 2. Patients and methods A review of all patients with acute rheumatic fever (ARF) who were admitted to Suleimania Children’s Hospital, Riyadh, during the period, 1994–2003, was undertaken. The study consisted of a retrospective analysis of the medical records for the period between 1994 and 1998 and prospective study for the period 1999–2003. The patients were either referred from primary health clinics (PHC), or admitted through the emergency department of the hospital. The diagnosis of ARF was based on clinical features and evidence of recent streptococcal infection. The features were those that constitute the revised modified Jones criteria, the major ones being arthritis, carditis, chorea, erythema marginatum and subcutaneous nodules, while the minor criteria consisted of arthralgia, fever, high ESR, and prolonged PR interval (Jones, 1992). ARF with isolated arthritis was differentiated from post streptococcal reactive arthropathy (PSRA) by the clinical features such as migratory nature of arthritis or dramatic response to aspirin therapy in ARF while PSRA involves more joints including small joints of hands and feet, axial involvement, symmetrical, non migratory but more protracted and responds less to aspirin (Shulman and Ayoub, 2002; Gerber et al., 2009). Although ARF with isolated arthritis and PSRA overlap, (Jones, 1992; Keitzer, 2005; Tutar et al., 2002) children with diagnosis of PSRA were excluded from the study (13 patients). Arthritis was defined either by obvious redness, swelling and hotness of joints, or by limitation in the range of joint movement due to tenderness, and limping. All the patients had routine cultures of the throat; b-haemolytic streptococci were identified by microscopy. Erythrocyte sedimentation rates were performed by standard methods, while anti-streptolysin O titres were determined by standard techniques with commercially available reagents and a single isolated titer P400 Todd units in our lab was considered diagnostic of preceding recent streptococcal infection. The ‘‘upper limit of normal’’ value for streptococcal antibody titers depends on the population involved (AlEissa et al., 1993; Shet and Kaplan, 2002). Standard 12-lead electrocardiograms and two-dimensional (2D) and Doppler echocardiography were obtained for each patient. The valvular disease in ARF was suggested clinically by the presence of an audible murmur and confirmed by two-dimensional (2D) echocardiography and Doppler echo. Isolated Sydenham chorea was diagnosed after excluding other
M.A. Qurashi causes of chorea (Atatoa-Carr et al., 2008). The diagnosis was easier when chorea was associated with carditis or arthritis and evidence of previous group A b-haemolytic streptococcal infection, although the guidelines of the WHO, and American Academy of Cardiology specify that evidence of previous streptococcal infection is not necessary for the diagnosis of Sydenham chorea (Jones, 1992). The diagnosis of recurrence of rheumatic fever (RF) in children with rheumatic heart disease was based on the presence of one major criterion apart from carditis or two minor criteria, in addition to evidence of preceding streptococcal infection. This exception to the modified Jones criteria was based on the guidelines by the WHO and American Academy of Cardiology (Jones, 1992). 3. Results 3.1. Incidence and demographics During the 10-year period, the staff at Sulemania Children’s hospital admitted a total of 112 cases with diagnosis of ARF that satisfied the modified Jones criteria. Of the 112 cases, the full records of 83 were analysed (Table 1), while those of the remaining 29 cases were excluded either due to lack of sufficient data in the medical records (16 patients) or misdiagnoses as ARF with isolated arthritis rather than post streptococcal reactive arthropathy (13 patients). The annual number of cases was 17 in 1994 and 1995, while in 2003, only 2 cases were admitted (Table 1); the average number of cases seen per year was eight. The 83 children were aged, 4–12 years (mean 9 years; mode 11 years). There was a male preponderance (M/F ratio was 1.4:1). The number of siblings of the cases varied from 1 to 14, (mean, 5.75). Seventy-five (90%) of the 83 were from Riyadh city while 8 (10%) others from rural areas around the city. Based on the father’s occupation, income and housing, 53 (64%) children were categorized as belonging to the low socio-economic class, 28 (34%) were from the middle class and only 2 children (2%) were from the high socio-economic class. Seventy-three (88%) were Saudi nationals. 3.2. Clinical manifestations 3.2.1. Major diagnostic criteria 3.2.1.1. Arthritis. A summary of the major clinical manifestations in the patients is shown in Table 2. A single major man-
Table 1
Yearly Distribution of 83 Cases of ARF.
Year
Total per year
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
17 17 7 1 5 13 8 6 7 2
% of total 20.5 20.5 8.4 1.2 6.0 15.7 9.7 7.2 8.4 2.4
Total
83
100.0
The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia Table 2
Major manifestations of ARF in 83 children.
Manifestation
No. of cases
One major manifestation Arthritis Carditis Sydenham chorea
% of total
31 5 5
37 6 6
Two major manifestations Carditis and arthritis Carditis and chorea Chorea and arthritis
30 9 3
36 11 4
Total
83
100
ifestation was present in 41 children (49%). Arthritis alone was present in 31 children (37%), with carditis in 30 (36%) others, while arthritis with chorea was seen in only 3 children (4%). Thus, the total number of children who had arthritis was 64 (77%). In 45 (70%) of the 64 children, the arthritis involved a few large joints (less than five joints) namely, the knees, elbows, wrists, hips, ankles, and shoulders; in 15 (23%), it involved more than four joints, including 2 cases in which the small joints of the hand and feet, were also involved. Axial involvement, characterized by back pain and limitation in flexion of the spine was seen in 4 children (5%). Monoarthritis affecting large joints such as the knee, elbow, or wrist occurred in 4 children (6%). The arthritis was migratory in all 60 children with multiple joint involvement. 3.2.1.2. Carditis. Carditis, which was the second most common major diagnostic criterion, was present in 44 children (53%); it was an isolated major manifestation in 5 children (6%) only. On the other hand, carditis with arthritis was present in 30 children (36%), and together, they constituted the two most commonly associated major criteria of ARF. Carditis with Sydenham chorea was observed in 9 children (11%), 6 of whom had mitral valve regurgitation, while 3 had both mitral and aortic regurgitation. The pattern of valvular involvement in the 44 cases is shown in Table 3. Two of the children with mitral valve regurgitation and Sydenham chorea were brothers. Chorea occurred simultaneously with carditis in 4 children, while 5 in others, it occurred after intervals that varied from 3 months to 4 years. Heart failure occurred in 14 children (32%) with carditis, while pericardial effusion was present in 2 children. Silent mitral valve regurgitation, in which there was no audible murmur but only discovered on echocardiogram, was not considered as evidence of carditis (Jones, 1992; Ata-
Table 3
Pattern of valvular disease in 44 children with ARF.
Valvular lesion
No.
Mitral valve regurgitation Mitral and aortic regurgitation Aortic valve regurgitation *Others
26 11 4 3
59 25 9 7
Total
44
100
*
217
toa-Carr et al., 2008; Gupta et al., 2008). although various studies point to the importance of echographic evidence of subclinical carditis and considering it as definite rheumatic carditis, even though it is a mild form (Saxena, 2000; Veasy, 2001; Vijayalakshmi et al., 2008; Vijayalakshmi et al., 2005). 3.2.2. Sydenham chorea Rheumatic chorea occurred as isolated major manifestation of ARF in 5 children (6%); it also occurred in association with carditis in 9 (11%) others and with arthritis in 3 (4%). The total number of children with ARF who developed chorea was thus, 17 (20%). The chorea was bilateral in 16 children (94%) and unilateral in only 1 child (6%). The face was involved in 6 children (35%) while emotional lability was seen in 16 (95%). The duration of the chorea ranged from three week to 5 months. 3.2.2.1. Others. None of the cases presented with any of the two other major diagnostic criteria of ARF namely, erythema marginatum and subcutaneous nodules. 3.2.3. Minor diagnostic criteria The minor diagnostic criteria of ARF that were present are summarized in Table 4. ESR, an acute phase reactant, was recorded in 79 children; it was raised (>20 mm in the first hour) in 74 children (94%) and in the normal range in 5 children (6%), who presented with chorea. High-grade fever was present in 69 children (83%). Prolonged PR interval (more than 0.16 s on ECG), was present in 19 children (23%). Arthralgia in the absence of arthritis was noticed in 9 children (11%); it involved large joints including the knees, elbows, wrists, ankles, and shoulders. 3.3. Evidence of preceding streptococcal infection There was a history of sore throat, one to four weeks before the onset of the manifestations of ARF in 55 children (66%). Throat culture for group A b-haemolytic streptococcus was positive in only 9 (11%). Elevated anti-streptolysin O titre (>400) was present in 79 (95%) children, while it was normal in 4 with rheumatic chorea. 3.4. Treatment Isolated arthritis was treated satisfactorily with aspirin in 26 children (84%) and with naproxen in 5 (16%). Carditis (valvulitis) was treated with aspirin in 40 children (91%). These children either had carditis alone (3 (7%) children), in association with arthritis (30 (75%) children) or with chorea (7 (18%) children). Mild carditis in 26 children was treated with aspirin only. Severe carditis with heart failure was treated with prednisolone and aspirin in 14 (100%) children. Although based
%
One case each of: (a) MV and TV regurgitation; (b) MV, AV and PV regurgitation (c) MV, TV and PV regurgitation (MV = Mitral valve TV = Tricuspid valve PV = Pulmonary valve).
Table 4
Minor manifestations of ARF in 83 children.
Manifestation a
High ESR (>20 mm/h) Fever Prolonged PR interval (>0.16 s) Arthralgia a
Determined in 79 cases.
No of cases
% of total
74 69 19 9
94 83 23 11
218 on the meta-analysis, the advantage of corticosteroid treatment over salicylates in preventing rheumatic heart disease was not statistically significant (Albert et al., 1995; Cilliers, 2003). The total number of children who received aspirin was thus, 68. The side effects of aspirin observed were acute gastritis with abdominal pain and vomiting in 5 children (7%), while 1 child (1.5%) developed gastrointestinal bleeding. These side effects occurred despite the routine administration of antacid syrup to all the children on aspirin. No side effects were reported with the other medications. Rheumatic chorea was treated with Valproic acid in 15 children (88%) and haloperidol in 2 (12%). There was no mortality from ARF in our series. 3.5. Prophylaxis In line with our practice, all the children were placed on intramuscular (IM) benzathine penicillin, 1.2 million units every 21 days. Two children received daily oral penicillin as an alternative ARF prophylaxis, prescribed after rejection of IM injections. 3.6. Recurrences Nineteen children (23%) had recurrences; 7 (37%) had second attacks and 12 (63%) had more frequent attacks that ranged from 3 to 6. The interval between attacks varied from 6 months to 9 years with most (52%) being less than 1 year. The patients’ ages at the time of recurrence ranged from 5 years to 13 years (median 10 years). Compliance with longterm prophylaxis of ARF using intramuscular penicillin was poor in all the 19 children who had recurrent attacks of rheumatic fever. The major manifestation of ARF was the same in the recurrent attacks as in the preceding one in 15 patients (79%) of the 19 cases; i.e. isolated carditis in 3, isolated arthritis in 4, isolated chorea in 2 and arthritis with carditis in six. The recurrent episode differed from the initial illness in only 4 patients (21%), 3 of whom had carditis in the first attack, but developed chorea in the subsequent attacks and 1 patient who had arthritis with carditis in the first attack and developed chorea in the following attack. 4. Discussion There are various reports about the pattern of acute rheumatic fever (ARF) in the Kingdom (Al-Sekait et al., 1990; Al-Eissa et al., 1993; Abbag et al., 1998; Al-Sekait et al., 1991). However, the present report highlights our 10-year experience at the Children’s Hospital in Riyadh. The present series indicate that the incidence of ARF was high at the beginning (1994–1995) of the decade and had dropped markedly by the end (2003) as shown in Table 1. This apparent reduction in the number of new cases of ARF admitted to our hospital, probably reflects the situation in the community and may be ascribed to improved health care and primary prevention of ARF by early diagnosis of pharyngitis and adequate treatment with antibiotics. Therefore, further studies are required to identify the precise incidence of ARF in all hospitals in Riyadh city. Increased rate of ARF (64%) was seen in children from urban, low-income, and crowded areas. Crowded living conditions, which are conductive to the spread of respiratory
M.A. Qurashi infections, continue to be a predisposing factor. In addition, the associated poverty leads to a delayed access to medical care. These sociodemographic features of our patients were similar with those from other countries (Al-Eissa et al., 1993; Essop and Nkomo, 2005; Carapetis, 2007). The lack of a history of preceding pharyngitis in 28 children (34%) in this series and at similar percentage in other series (Al-Eissa et al., 1993; Gerber et al., 2009), is an important factor in the persistence of ARF in the community; this is in addition to another important factor namely, poor compliance of the patients to a full 10-day course of oral penicillin for the treatment of bacterial pharyngitis (Dajani, 1996; Gerber and Tanz, 2001). Therefore, in order to optimize primary prevention of ARF, mass education of the population in general and children in particular, is necessary using all resources available including the media. Recurrence rate of ARF in our series was high (23%); due to poor compliance with the schedule of benzathine penicillin G (BPG) administration, which was once, every 21 days. Although studies have suggested that BPG injections every 3 weeks are superior to injections every 4 weeks (Gerber et al., 2009; Lue et al., 1996), implementation of an every 3 weeks regimen can be problematic with regards to patient compliance. Currie in 1996 suggested that there may be benefits in a BPG regimen every 4 weeks with doses higher than the standard 1,200,000 U (Currie, 1996). Further studies of higher dose BPG regimens seem justified. Arthritis was the most common major manifestation of ARF in this series which was seen in 64 (77%) children, similar to that observed by other workers (Al-Eissa et al., 1993; Ravisha et al., 2003). The frequency of isolated arthritis as the presenting symptom in our series (31 children, 37%) is similar to other study (Williamson et al., 2000). Four children (6%) presented as monoarthritis, this unusual presentation was reported in a previous study (Wilson et al., 2007). In the latter situation, the diagnosis of ARF was difficult and recourse was taken to the presence of other associated major manifestation such as carditis or chorea. Although 31 (37%) children with isolated arthritis as a major criterion in association with other minor criteria such as fever and an elevated ESR plus evidence of a recent streptococcal throat infection were included in our series, such children could be labelled as post-streptococcal reactive arthritis by other physicians. The presence of migratory arthritis, involvement of large joints, prolongation of PR interval and dramatic response to aspirin therapy were considered for the likely diagnosis of ARF in this group. The 13 children who were excluded from this study did not have these features. The frequency of carditis in this series (53%), is similar to that observed by other workers (Al-Eissa et al., 1993; Martins et al., 2006). Mild carditis occurred in 30 children (68%), 3 of whom developed rheumatic heart disease (RHD) while severe carditis with heart failure occurred in 14 children (32%), 11 of whom ultimately developed RHD. A total of 14 children (32%) with carditis developed RHD, Table 5. The incidence of severe carditis was higher than reported by other workers (Al-Eissa et al., 1993). Mitral regurgitation and aortic regurgitation were the common findings in ARF while isolated mitral valve regurgitation, mitral valve regurgitation with stenosis and aortic valve regurgitation were the more common valvular disease in RHD. The profile of ARF regarding the relative frequency of valvular involvement in this series, is similar to that
The pattern of acute rheumatic fever in children: Experience at the children’s hospital, Riyadh, Saudi Arabia Table 5 Residual rheumatic heart disease pattern in 14 children. Cardiac lesion Mitral regurgitation Mitral and aortic regurgitation with mitral stenosis Mitral regurgitation and stenosis Aortic regurgitation and stenosis Mitral, aortic and pulmonary regurgitation Mitral and aortic regurgitation Mitral, tricuspid and pulmonary regurgitation Aortic regurgitation Total
No. of cases 6 2 1 1 1 1 1 1 14
observed by other workers in the Kingdom (Al-Eissa et al., 1993). PR interval prolongation is a minor criterion for the diagnosis of ARF, present in about 35–40% of children with ARF; it is useful in evaluating the patients with isolated arthritis when, if present, it makes other causes of joint involvement unlikely (Guzman-Cottrill et al., 2004; Olgun and Ceviz, 2004). In our study, it was prolonged in 19 children (23%) and only 4 (13%) children with isolated arthritis had a prolonged PR interval. In the present series, two brothers had carditis at first attack in the form of mitral valve regurgitation followed by chorea during the second attack of ARF and finally developed RHD presenting as chronic mitral valve regurgitation in addition to recurrent attacks of chorea; this suggests a genetic predisposition to form autoantibodies to specific tissue antigens which in these two brothers, were the brain and cardiac tissues. There is a similarity between streptococcal and tissue antigens that trigger autoantibody formation (Veasy and Hill, 1997; Martins et al., 2006; Bryant et al., 2009). Chorea was seen in 17 children (21%) either alone, or in combination with other major diagnostic criteria. This percentage is similar to that reported in other series (Martins et al., 2006; Oen, 2000; Al-Eissa, 1993). Diagnosis of isolated chorea was based on exclusion of other causes or chorea such as systemic lupus erythematosus, brucellosis, central neurological diseases, drug ingestion and encephalitis (Atatoa-Carr et al., 2008). Evidence of preceding streptococcal infection is not required; in fact, in our series, only one out of 5 children with isolated chorea had a high ASO titre (Jones, 1992). The profile of chorea in our series is mild, bilateral and shorter in duration compared to other studies (Al-Eissa, 1993; Dı´ az-Grez et al., 2004). Valproic acid had a high success rate in reduction of symptoms of rheumatic chorea which is similar to other study (Pena et al., 2002). All our patients who had initial attack of ARF with chorea (8 children) followed for 5 years and none of them develop valvular lesion in comparison with other study (Panamonta et al., 2007). Group A, b-haemolytic streptococcus (GAS) was isolated from throat culture in only 9 children (11%); compared to other studies in which GAS was isolated from 20% to 25% of throat cultures (Jones, 1992; Chagani and Aziz, 2003). This low yield was probably due to previous antibiotic treatment in most of our cases, 66% of whom were referred to our hospital
219
by primary care physicians. As it happened, ASO titre was left as the only available tool for confirming a preceding streptococcal infection. The overdiagnosis of PSRA in 3 children with arthritis and high ASO titre in our study, ultimately labelled as brucellosis, juvenile rheumatoid arthritis (JRA) and seronegative spondyloarthropathies (SSA) reflect high streptococcal endemicity in the community. Telmesani et al showed in a study done during 2000 a carrier rate of GAS in healthy Saudi children (3%), the occurrence of GAS among children with tonsillitis and pharyngitis was 40% (Telmesani and Ghazi, 2002). Abu-Sabaah reported only 19% of children with pharyngitis had GAS by culture (Abu-Sabaah and Ghazi, 2006). Further studies are required to assess the exact prevalence of streptococcal infection in the population; if such studies confirms that a great number of healthy children has a high ASO titre, then the diagnosis of ARF in children with isolated arthritis or the diagnosis of PSRA should be made carefully (Atatoa-Carr et al., 2008; Kaplan et al., 1998; Tucker et al., 1993; Brandt et al., 1998). 4.1. Study limitations The study was retrospective in the first 5 years from 1994 to 1998 with lacking of some data in the medical records, leading to exclusion of 16 patients with ARF from detail analysis. 5. Conclusion Acute rheumatic fever (ARF) continues to occur in Saudi Arabia, despite the progress made in the socio-economic development of the country, often associated with severe cardiac involvement. Post-streptococcal reactive arthritis is usually confused with ARF of the isolated arthritis type and differentiation can be difficult. High recurrence rate of ARF in the present study is due to poor compliance with prophylaxis regime of recommended 21-day interval for long acting penicillin (Gerber et al., 2009). The recurrence of the same major criteria in the recurrence cases strongly suggest that the genetic predisposition for rheumatic fever is tissue selective.
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