Clinical and demographic characteristics of 99 episodes of rheumatic fever in Acre, the Brazilian Amazon

Abstracts

OBJETIVO: Relatar as manifestações clínicas e características demográficas de pacientes com febre reumática atendidos em serviço público no Estado do Acre. MÉTODOS: Estudo de corte transversal em pacientes atendidos consecutivamente no Ambulatório de Cardiologia da FUNDHACRE, avaliados através de questionário contendo dados demográficos, clínicos e laboratoriais. O diagnóstico de febre reumática foi realizado através da aplicação dos critérios de Jones, em associação com dados laboratoriais, eletrocardiograma, radiografia de tórax e ecocardiograma bidimensional. Excluídos portadores com outras cardiopatias, diabetes, obesidade, doenças inflamatórias, processos infecciosos, tabagismo, gestantes, uso de drogas anti-inflamatórias ou reposição hormonal. RESULTADOS: De julho/2003 a fevereiro/2004, foram avaliados 99 pacientes com febre reumática aguda (idade média de 11 anos, dp= ± 10,18) com predominância feminina (59,6%) e fenótipo racial mestiço de índio (60,6%). Excluídos 3 indivíduos, por não preencherem os critérios diagnósticos. A idade média de início foi de 9,1 anos, sendo que em 30,4% dos pacientes a doença foi diagnosticada no primeiro episódio de atividade reumática. As manifestações clínicas mais freqüentes foram cardite (69,7%), artrite (21,4%) e coréia (6,1%) e a regurgitação mitral (36,4%) a lesão mais comum seguida da associação de regurgitação mitral com aórtica (9,1%). CONCLUSÃO: Cardite reumática foi a manifestação mais freqüente de febre reumática, predominando no grupo racial mestiço de índio (60,6%), A baixa aderência à antibioticoprofilaxia contribuiu para recorrências e seqüelas cardíacas.

febre reumática; cardite; coréia

ORIGINAL ARTICLE

Clinical and demographic characteristics of 99 episodes of rheumatic fever in Acre, the Brazilian Amazon

Fátima Borges; Maria Luiza A. Barbosa; Renata Beyruth Borges; Olívia C. Pinheiro; Carlos Cardoso; Claudilson Bastos; Roque Aras

Rio Branco, AC / Salvador, BA - Brazil

Fundação Hospitalar do Acre/FUNDHACRE e Universidade Federal da Bahia

^{Correspondence}

ABSTRACT

OBJECTIVE: To report clinical manifestations and demographic characteristics of patients with rheumatic fever treated in a public hospital in the state of Acre.

METHODS: A cross-sectional study was conducted of patients consecutively seen in the Cardiology Ward at FUNDHACRE Demographic, clinical and laboratory data were assessed through a questionnaire. The diagnosis of rheumatic fever was made based on Jones' criteria, associated with laboratory data, electrocardiography, chest X-ray, and bi-dimensional echocardiography. Patients with other heart diseases, diabetes, obesity, inflammatory disease, and infections were excluded. Those who smoked, were pregnant, or used anti-inflammatory medication or hormone therapy were also excluded.

RESULTS: From July 2003 to February 2004, 99 patients with rheumatic fever were assessed (mean age, 11 years, SD= ± 10.18) with a predominance of females (59.6%), and a racial phenotype of a mixture of Caucasian and Indian (60.6%). Three individuals were excluded because they did not meet the diagnostic criteria. Mean age was 9.1 years old, and in 30.4% of the patients, the disease was diagnosed at the first episode of rheumatic fever. The most frequent clinical manifestations were carditis (69.7%), arthritis (21.4%), and chorea (6.1%). Mitral regurgitation was the most common lesion (36.4%) followed by the association of mitral regurgitation and aortic regurgitation (9.1%).

CONCLUSION: Rheumatic carditis was the most common manifestation of rheumatic fever, predominant in the group with a racial mixture of Caucasian and Indian (60.6%). Low compliance with antibiotic therapy contributed to the recurrence of the disease and to cardiac sequelae.

Key words: rheumatic fever, carditis, chorea

Rheumatic fever is a delayed inflammatory complication, nonsuppurative, with recurrent immunologic bases, frequently occurring in individuals from 5 to 15 years old, from both sexes after recurrent infections of group A streptococcal pharyngitis ¹. It is the main cause of heart disease in infancy and adolescence ². It is characterized by heart, joint, central nervous system, skin, and subcutaneous cellular tissue involvement ³.

Rheumatic fever remains a serious public health problem. About 30 million people suffer from the disease around the world⁴. In developed countries, the prevalence of the disease has decreased due to improvement in social, economic, and cultural conditions, together with the use of antibiotics for respiratory infections ⁵. In Brazil, the prevalence of rheumatic fever is 3 to 5% in children and adolescents ⁶.

This study aimed at describing the clinical manifestation of rheumatic fever, the frequency of valvular lesion, and the demographic characteristics of a hospital population in the State of Acre.

Methods

All patients with a clinical suspicion of rheumatic fever in the city of Rio Branco, Acre referred to the Cardiology and Rheumatology Ward at FUNDHACRE were consecutively assessed. The hospital is part of the federal Unique Health System (SUS/Sistema Único de Saúde) and is connected to the Medical School in Acre, which takes care of the general population of the cities and rural areas of the state.

After patients were informed about the study and gave their written consent, those from both sexes with symptoms who completed the clinical chart were included. The questionnaire contained data from the clinical history, physical examination, laboratory examinations (erythrocyte sedimentation rate, C-reactive protein, throat swab culture, mucoprotein, antistreptolysin O, blood count). Electrocardiograms, chest X-ray in posterior-anterior projections, and echocardiograms were performed, together with collection of information concerning marital status, sex, religion, occupation, family income, educational background, date of birth, weight, height, and number of people in the family. The patients who met the modified Jones' criteria were considered to have a diagnosis of rheumatic fever ⁷.

Patients with chronic inflammatory processes (osteoarthritis, collagen disease), infections, or acute inflammatory processes in the preceding 3 weeks (unrelated to rheumatic fever), use of anti-inflammatory drugs in the preceding 3 weeks, on hormone replacement therapy, diabetes mellitus, and obesity (BMI>30) were excluded. Those who were smokers and pregnant women were also excluded.

Initially, patients were assessed by a medical team comprising a cardiologist and a rheumatologist, and the diagnosis of the disease was made based on modified Jones' criteria ⁷. Fifteen milliliters of blood from the brachial artery were collected and maintained in tubes (Vacutainer) with EDTA anticoagulant for blood count and erythrocyte sedimentation rate and in tubes without anticoagulant to dose high-sensitivity C-reactive protein, mucoproteins, conventional C-reactive protein, and antistreptolysin O (AEO). The values used in the criteria adopted by the modified Jones were considered abnormal laboratory values. These were PCR up to 6mg/L; erythrocyte sedimentation rate up to 20 mm in the first hour; PCR-AS up to 0.30 mg/L; mucoproteins < 4.0 mg%, and antistreptolysin O up to 200 UI/L.

Aiming at assessing the compliance with treatment and the use of antibiotic medication as secondary prophylaxis, the following variables were added to the questionnaire: regular use of benzathine penicillin, hormonal and nonhormonal anti-inflammatory drugs, digitalis, diuretics, ACE inhibitors, calcium channel blockers, platelet inhibitors, and beta-blockers.

The Ethics and Research Committee approved the study, and it was only conducted after written informed consent was given.

Descriptive statistical analysis was used, indicating the values of means and medians. The chi-square test and Fisher's exact test were used to compare proportions, with a 95% significance level (P < 0.05).

Results

From July 2003 to February 2004, 99 patients with a diagnosis of acute rheumatic fever were assessed (mean age, 11 years SD= ± 10.18). Female sex was predominant, accounting for 59.6% of the population sample, and in the distribution according to racial group, we verified that the mixture of Caucasian and Indian was the most prevalent race (60.6%). Three patients were excluded because they did not fulfill the diagnostic criteria. Mean age at the onset of the disease was 9.1 years, and in 30.4% of the cases, the disease was diagnosed at the first episode of rheumatic activity, while 65.7% experienced 2 episodes or more. Age and sex were not associated with valvular involvement.

The most frequent clinical manifestations were carditis in 69 patients (69.7%), arthritis in 21 patients (21.4%), and chorea in 6 patients (6.1%). Of the 69 patients with active carditis, 21 patients developed heart failure, distributed according to NYHA (New York Heart Association) as follows: 9 patients were in Functional Class I, 5 patients were in Functional Class II, 4 patients were in Functional Class III, and 3 patients were in Functional Class IV. Severe secondary pulmonary hypertension was found in 1 and mild secondary hypertension was found in 3 patients. Isolated mitral regurgitation was the most common lesion (36.4%), followed by the association of mitral regurgitation and aortic regurgitation (9.1%). The presence of carditis was observed in 39 mestizo patients (Caucasian and Indian), 17 in Caucasian patients, and 13 in non-Caucasian patients.

Joint involvement was manifest by arthritis occurring in 21 patients; however, it was more prevalent in mestizo (Caucasian and Indian) (13), followed by Caucasians (6), and non-Caucasians (2). Clinical and evolvement characteristics typical of the joint picture of rheumatic fever occurred in our population, represented by 11.1% as migrating arthritis, 6.1% with additional features, and 4% monoarthritis.

Of the 99 patients studied, 70 (70.7%) had valvular lesions with a predominance of mitral failure in 36 patients (36.4%); 9 patients (9.1%) had mitral failure associated with aortic failure; 4 patients (4.0%) had a mitral prosthesis associated with aortic failure; 3 patients (3.0%) had mitral failure associated with tricuspid failure; 2 patients (2%) had mitral stenosis, tricuspid failure, mitral failure associated with aortic double lesion, mitral prostheses and mitral valvuloplasty, and 1 patient (1%) had other valvular lesions. Acute rheumatic fever was found in 30 patients (30.3%) at the first episode of the disease and in 66 patients (66.7%) with a recurrence of 2 or more episodes.

Demographic and clinical characteristics of patients are found in table I. Frequency of recurrent tonsillitis was 80.8%. Five patients (5%) underwent cardiac surgery: 2 patients (2%) received aortic bioprostheses, one patient received an aortic bioprosthesis with mitral commissurotomy, one received a mitral aortic bioprosthesis, and another patient received a mitral bioprosthesis. Sixty-one patients (61.6%) did not comply with the antibiotic prophylaxis. In our study, of 38 patients (38.4%) who used penicillin benzathine regularly, 27 (27%) had a new episode of rheumatic fever.

Serum levels of mucoproteins were increased in 61 patients (61.6%) and those of C-reactive protein in 24 patients (24.2%). Regarding antistreptolysin, we also observed an increase in 58 patients (58.8%) with rheumatic fever. VHS levels were higher in the group with arthritis with statistical significance (P< 0.026), when compared with that in the carditis group.

In the group of patients with arthritis, 16 patients (16%) had high antistreptolysin (ASLO) levels, whereas 4 patients (4%) had normal levels. Mucoproteins values were above normal in 15 patients (15%), and 4 patients had normal levels without statistical significance. C-reactive protein was normal in 11 patients (11%) and altered in 10 patients (10%) with statistically significant levels (P<0.02).

In the group of patients with carditis, the erythrocyte sedimentation rate was elevated in 37 patients (56%), which is half of the patients, but with no significant difference when compared with patients that did not have changes in the erythrocyte sedimentation rate. AEO values were increased in 41 patients (41.4%), mucoproteins in 40 patients (40.4%), and C-reactive protein in 18 patients (18.2%), with no statistically significant difference in this group.

Conduction disturbances were recorded on electrocardiograms in 30 patients (30.3%), and an increase in the P-R space was observed in 7 children (7%) with ages up to 13 years old, and in 5 children (5%) over 13 years old. Among the arrhythmias, sinus tachycardia was present in 12 patients (12.1%), followed by sinus bradycardia in 7 patients (7.1%), atrial fibrillation in 4 patients (4%), supraventricular extrasystole in 1 patient (1.0 %), and total atrial ventricular block in one patient.

In the group of patients with carditis, arrhythmias occurred in 25 patients (50.5%), and in the group with arthritis, they occurred in only 6 patients. Conduction disturbances were identified in 20 patients (20.2%) with active carditis. In 17 patients, first-degree right bundle-branch block occurred, and in 2 patients second-degree right bundle-branch block occurred.

Chest X-rays demonstrated normal pulmonary transparency in 79 patients (79.8%), and among the patients with active carditis, 25 of them (36%) had an increase in the cardiac and thoracic index, with a significance level when compared with those individuals without carditis (P < 0.031).

Discussion

Rheumatic fever is still a severe health problem in Brazil ^8-10. In our series of patients, we have observed an increased frequency of valvular lesions and carditis (69.7%), demonstrating the severity of initial attacks or of recurrences of the inflammatory activity, with heart lesion that will certainly contribute to the increase in the prevalence of heart disease in our country.

Regarding race, we observed the predominance of mestizos (Caucasian and Indian) (60.6%), a characteristic of the north region of Brazil. This population group that has not been reported on in other national publications may have some genetic predisposition to infection by streptococcus, as described in other groups of Caucasians and non-Caucasians associated with HLA Class II in different countries and ethnic groups. On the other hand, the high frequency of cardiac lesions in 42 patients (70%) of this group may be explained by the greater proportional number of the sample studied. However, when we assess the Caucasian (23.2%) and non-Caucasian (16.2%) population, we find the same severity of valvular lesions in 15 patients (65%) and 13 patients (81%), respectively. These data suggest that other factors are probably involved in addition to a genetic predisposition, such as low educational, social, and economical level; the environment in the Amazon, with a hot and humid weather, and a rainy season, which favor the infectious agent ^11-13.

Despite the low diagnostic output in carditis identification, the alterations found in the electrocardiographic records analysis are in agreement with reports in other publications ^14-16, both in the frequency of arrhythmias and in the presence of abnormalities involving the P-R interval prolonging.

Despite the increase in the number of children with pure chorea or chorea associated with carditis in recent years, this symptomatology has not been reported much in developing countries, which is different from our study where Sydenham's chorea occurred in 6.1% of patients ¹⁷.

Overall, the evidence of inflammatory activity has changed, with greater frequency in patients with arthritis. These data, which are controversial because they predict that the intensity of arthritis is related more to the inflammatory process involving the heart, were also found in our patients. C-reactive protein did not demonstrate an increase consistent with inflammatory activity, probably because of the fugacity of its elevation, which may be associated with the course of the disease and the duration of the evolvement from the collection of blood samples. When we compared values of erythrocyte sedimentation rate and C-reactive protein between the patients with arthritis and carditis, we found that the inflammation was (VHS and PCR) more elevated in the group with arthritis with statistical significance (P = 0.026).

Echocardiography has become an essential diagnostic method for the assessment of patients with rheumatic fever, because it enables a detailed analysis of the cardiac lesions and because it is more specific than clinical evaluation ¹⁸. Of the 67 patients with cardiac involvement, 36 had mitral regurgitation, without an organic murmur at clinical examination. Six patients were diagnosed with mild mitral regurgitation, demonstrated by echocardiography, and 2 had physiologic mitral regurgitation. These data are in accordance with that of other authors who identified valvular abnormalities in patients with rheumatic fever without clinical presentation of carditis, suggesting that some patients may have a subclinical course of carditis with valvular lesions ¹⁹.

In our study, a high rate of failure to comply with antibiotic prophylaxis with penicillin benzathine occurred, leading to a greater risk of recurrence and of cardiac complications, which may be explained by the lack of campaigns to educate the population, low social and economical level, and poor education of the family in the population studied.

Special attention must be paid to the primary prophylaxis of acute rheumatic fever. The upper airway infections caused by group A streptococcus b-hemolytic must be diagnosed and treated early. The population must be informed through mass media communication, giving priority to care for patients in health care units and public hospitals, enabling the needy population to have access to public health policies, thus improving compliance with the treatment. Secondary antibiotic prophylaxis is extremely necessary in this population, because of the severity of recurrence of rheumatic fever reducing lesions and valvular sequelae ²⁰.

In conclusion, we have observed that although rheumatic fever occurred more often in the racial group of mestizos (Caucasians and Indians), severe heart involvement was a factor regardless of ethnic group. A public health campaign in the region must be introduced to stop the cycle of streptococcus infection and the occurrence of rheumatic fever, in addition to the systematic use of secondary antibiotic prophylaxis.

References

Received for publication: 07/06/2004

Accepted for publication: 08/18/2004

• 1. Tanaka AC. Febre reumática: critérios diagnósticos e tratamento. In: Timerman A, César LAM, Ferreira JFM, Bertolami MC. 2. ed. Manual de Cardiologia. SOCESP, Atheneu: São Paulo 2000:271-327
• ²
  WHO Technical Report Series (community prevention and control of cardiovascular diseases report of a WHO expert community), 1986; 732.
• 3. Homer C, Shulman ST. Clinical aspects of acute rheumatic fever. J Rheumatol 1991; (suppl) 29:2-13.
• 4. Dajani AS. Current status of nonsuppurative complications of groups A streptococci. Pediatr Infect Dis J 1991; 10(Suppl):S25-7.
• 5. Murphy GE. The characteristic rheumatic lesions of striated and of nonstriated or smooth muscle cells of the heart. Genesis of the lesions known as Aschoff bodies and those myogenic components known as Aschoff cells or myocytes. Medicine 1963; 42:73-8.
• ⁶
  Ministério da Saúde. Coordenação de Doenças Crônico-Degenerativas. Incidência na febre reumática no Brasil. MS: 2003; Brasília/DF.
• 7. Dajani AS, Ayoub E, Bierman FZ. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. Guideline for the diagnosis of rheumatic fever. Jones criteria, 1992 update. JAMA 268:2069-73.
• 8. Alves Meira ZM, de Castilho SR, Lins Barros MV, et al. Prevalência da febre reumática em crianças de uma escola de rede pública de Belo Horizonte. Arq Bras Cardiol 1995; 65:331-4.
• 9. Gus I, Zaslavsky C, Seger JM, Strehl Machado R. Epidemiologia de febre reumática. Estudo local. Arq Bras Cardiol 1995; 65:321-5.
• 10. Michielin F, Pretto AA, Prataviera JC, et al. Epidemiologia e prevalência da febre reumática no Rio Grande do Sul. Arq Bras Cardiol 1994; 63:441-2.
• 11. Kaplan EL. Rheumatic fever. In: Berhman RE, Kliegman EL (ed.). Nelson Textbook of Pediatrics.14. ed. W. B. Saunders: Philadelphia 1992; 640-6.
• 12. Kaur S, Kumar D, Grover A, et al. Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients' Int J Cardiol 1998; 64: 9-14.
• 13. Guilherme L, Kalil J. Rheumatic Fever: From Sore Throat to autoimune Heart Lesions. Int Arch Allergy Imunol 2004; 134:56-64.
• 14. Bisno AL. Group A streptococcal infections and acute rheumatic fever. N Engl J Med 1991; 325:783-93
• 15. Gururaj AK; Choong KE, Arifin WA., Sharifah A. A clinical, laboratory and echocardiographic profile of children with acute rheumatic fever. Singapore Med J 1990; 31:364-7.
• 16. Clark M, Kieth J.D. Atrioventricular conduction in acute rheumatic fever. Br Heart J 1971; 33:2-15.
• 17. Goldemberg J, Ferraz MB, Hilário MO, Fonseca AS, Bastos W, Sachetti S. Increase in incidence of Sydenham' Chorea in São Paulo. J Trop Ped 1993; 39:192-3.
• 18. Grayburn PA, Smith MD, Handshoe R, Friedman BJ, DeMaria AN. Detection of aortic insufficiency by standard echocardiography, pulsed Doppler echocardiography and auscultation. Ann Intern Med 1986; 104:599-605.
• 19. Folger GM. & Hajar R. Doppler echocardiographic findings of mitral and aortic valvular regurgitation in children manifesting only rheumatic arthritis. Am J Cardiol 1989; 63:1278-80.
• 20. Ruoff GE. Recurrent streptococal pharingits. Postgrad Med 1996; 99:211-21.

Publication Dates

• Publication in this collection
  08 Mar 2005
• Date of issue
  Feb 2005

History

• Received
  06 July 2004
• Accepted
  18 Aug 2004