Two years of penicillin prophylaxis is sufficient to prevent clinically evident carditis in poststreptococcal reactive arthritis (2001)

DEAR SIR, Acute rheumatic fever (ARF) is a disease that occurs following throat infection with b-haemolytic streptococci of Lancefield group A (bHSA) [1]. Mainly children are affected and ARF manifests itself as a migratory arthritis. The most feared complication of ARF is carditis, which can result in damage to the valves, cardiac failure and death. Approximately 30–90% of first attacks of classical ARF are accompanied by carditis, and the frequency of carditis increases with subsequent attacks [2, 3]. More sensitive testing using Doppler echocardiography even shows that nearly all patients with ARF have signs of acute carditis [4]. To prevent recurrent attacks and subsequent serious complication at least 5 years of antibiotic prophylaxis has been advocated after the first attack of ARF. The incidence of carditis declines markedly with advancing age [5, 6]. Poststreptococcal reactive arthritis (PSRA) is, like ARF, a syndrome following throat infection with β-haemolytic streptococci. Recently, several reports have suggested that PSRA is a disease distinct from ARF [7–10]. PSRA occurs predominantly in middle-aged female adults, is characterized by nonmigratory type of arthritis, and has a shorter latent period between the antecedent streptococcal infection and the onset of symptoms than ARF. Furthermore, Erythema nodosum and Erythema multiforme are prevalent in patients with PSRA, whereas they seldom occur in ARF (Table 1) [5, 6, 11]. The most important clinical difference between these two syndromes is the prevalence of carditis [10]. Currently, patients are treated after the first attack of poststreptococcal reactive arthritis (PSRA) as if they have ARF; a 5-year prophylaxis has generally been recommended. It is however, not clear whether PSRA is complicated by carditis; this may have major implications for antibiotic prophylaxis [10, 12, 13]. In the present study we investigated whether a 2-year period of monthly penicillin prophylaxis, instead of 5 years, is sufficient to prevent carditis after the first attack of PSRA. Between September 1992 and September 1999, we prospectively studied 42 patients with clinically and serologically confirmed PSRA, who presented in the outpatient clinics or in the departments of Rheumatology and Internal Medicine (for further details see [10]). Briefly, patients were included only when they fulfilled the following criteria: proven arthritis following βHSA infection, exclusion of other causes of arthritis, and titres of antistreptolysine-O (ASO) and anti-deoxyribonuclease-B (anti-DNase-B) >200 U L–1. These titres have to show a significant rise in consecutive samples obtained during the next 12 weeks following infection. Serological titres were determined using a nephelometry kit from Behring (Marburg, Gemany). Recurrence of PSRA was diagnosed using the same criteria as for the first attack of PSRA. After the first attack of PSRA patients were treated with benzylpenicillin, 1.2 million units i.m. once monthly, for a total period of 2 years. All patients were regularly seen in the outpatient clinic for follow-up. An electrocardiogram was performed on all patients. The presence of carditis was detected clinically (murmurs, pericardial friction rub, signs of congestive heart failure) by electrocardiogram. An echocardiogram was performed in patients with cardiac murmurs, with a conduction block on electrocardiogram, pericardial friction rub, congestive heart failure, or other clinical signs of carditis. Forty-two patients with clinically and serologically confirmed PSRA were included in the study. There were 26 female and 16 male patients whose mean age at presentation was 49 years (range 19–74) (Table 2). The clinical symptomatology of this group of patients has been described in Ref. [10]. Initially, none of these patients had signs of carditis after the first attack of PSRA, three patients had a transient first degree atrioventricular conduction block. Thirty-six of the 42 patients received penicillin prophylaxis (Table 2). Of these 36 patients, two were treated for 1 year (stopped by their physicians), and one patient deliberately stopped prophylaxis after 2 months of treatment. So, a total of 33 patients received prophylaxis for the full 2 years (mean duration for all treated patients 21 months, range 2–24). The mean period of follow-up after stopping penicillin prophylaxis was 20 months (range 1–59). Six patients refused to use prophylaxis. No recurrence nor other problems occurred during penicillin treatment. In three of the 36 patients (8%) PSRA recurred in all after stopping the prophylaxis. None of the six patients without prophylaxis had a recurrence of PSRA. Of the patients with a recurrence of PSRA, none had signs of carditis. In two patients PSRA recurred 2 and 5 years after stopping prophylaxis, respectively. They both used prophylaxis for 2 years. The third patient had a recidive of PSRA after deliberately stopping prophylaxis after 2 months. Notably, one of the patients developed aortic arch arteritis without signs of carditis after the second attack of PSRA. Angiographic examination showed subtotal stenosis of the aortic arch and right carotid artery and complete stenosis of the left subclavian and left carotid artery. Although the patient was treated with 80 mg prednison, radial artery pulsations are still absent. This observational follow-up study shows that a 2-year period of penicillin prophylaxis is sufficient to prevent the development of clinically evident carditis after the first attack of PSRA. Prophylaxis for 2 years however, seems not sufficient to prevent a recurrence of PSRA. Acute rheumatic fever (ARF) is feared for its’ severe sequelae: carditis, congestive heart failure and increased mortality, because 30–90% of the first attacks of ARF are accompanied by carditis [2, 3]. To prevent recurrences of this potentially fatal disorder secondary antibiotic prophylaxis for 5 years or lifetime has been advocated. During the last decade poststreptococcal diseases have been commonly recognized and the prevalence has increased [10]. The ‘adult form’ of ARF might be an entity called PSRA, a syndrome that is reported to be distinct from classical ARF. In 1975, Barnert et al. [14] observed amongst 53 adult patients with PSRA that only 8 (15%) of the 53 patients had signs of carditis; the clinical picture of this carditis was mild and transient. This implies a clearly lower prevalence of severe carditis in these patients compared with classical ARF. We have previously shown that the clinical spectrum of a relatively large group of patients with PSRA was clearly different from ARF [10]: 96% of the patients had a non-migratory arthritis, 30% had Erythema nodosum, 22% Erythema multiforme and 17% had a transient cholestatic hepatitis. None of these patients had carditis. If one considers PSRA as a distinct entity with a low prevalence of carditis, the use of secondary penicillin prophylaxis seems questionable. In addition, as these intramuscular injections are very painful, patients’ compliance can be low. There is however, a large debate whether PSRA is actually different from ARF. Patients with PSRA also fulfil the Jones’ criteria of ARF (arthritis, fever, elevated erythrocyte sedimentation rate and antistreptococcal antibodies) may warrant appropriate prophylaxis [1]. The main issue of secondary prophylaxis is to prevent carditis in recurrent PSRA. The incidence of carditis in PSRA is probably low, but not well known. Ahmed et al. [15] reviewed the literature and found a prevalence of 5.8% patients who acquired valvular disease following PSRA. As these patients were mostly children and the incidence of carditis decreases with advancing age, the actual prevalence of carditis in adults may be even much lower [12, 13]. In the present study we investigated whether a 2-year (instead of 5-year) period of penicillin prophylaxis is a safe policy to prevent carditis. We investigated a group of 42 consecutive patients with PSRA, the largest number reported since 1975 [14]. Furthermore, although three patients were followed for less than 1 year, the mean follow-up period was nearly 2 years after discontinuation of prophylaxis. In none of the 36 patients with antecedent PSRA carditis occurred. Furthermore, in the six patients who refused prophylaxis no evidence of carditis was found. We conclude that a reduction of prophylaxis treatment from 5 to 2 years seems to be a safe policy after the first attack of PSRA. This period of prophylaxis is however, not sufficient to prevent recurrence of PSRA, because 3 (8%) of the 36 patients had a recurrence despite prophylaxis, several years after stopping treatment. No recurrences occurred during prophylaxis, which shows efficacy and compliance of this treatment. In one patient aortic arteritis developed after two attacks of PSRA, suggesting that recurrent streptococcal infection still may have severe sequelae similar to greater vessel vasculitis. Considering the low risk or absence of carditis in adult patients with PSRA, it is possible that PSRA is a benign disorder that warrants no antibiotic prophylaxis. To answer this question a randomized multicentre study is needed, but the absence of carditis in only six PSRA patients who received no prophylaxis is suggestive. In conclusion, a 2-year period (instead of 5 years) is a safe policy to prevent cardiac complications in adult patients with PSRA.