Can a patient develop acute rheumatic fever or post-streptococcal reactive arthritis (PSRA) after timely treatment for Streptococcus (Strep) infection?

From the Guidelines

Timely treatment of strep throat with appropriate antibiotics significantly reduces the risk of developing acute rheumatic fever or post-streptococcal arthritis, but doesn't completely eliminate it. Patients should receive antibiotics, typically penicillin (oral penicillin V 500 mg twice daily for 10 days in adults or 250 mg 2-3 times daily for children, or a single intramuscular injection of benzathine penicillin G), within 9 days of symptom onset, as recommended by the American Heart Association 1. For penicillin-allergic patients, alternatives include cephalexin, azithromycin, or clindamycin, as outlined in the guidelines for the diagnosis and management of group A streptococcal pharyngitis 1. Even with proper treatment, there remains a small risk (less than 1%) of developing these post-streptococcal complications, as the immune response that triggers these conditions may already be activated before antibiotics are started 1. The autoimmune reaction occurs when antibodies produced against streptococcal proteins cross-react with human tissues, particularly heart valves, joints, and brain tissue. Some key points to consider include:

• The potential relationship of poststreptococcal reactive arthritis (PSRA) to acute rheumatic fever remains unresolved, as discussed in the proceedings of the Jones criteria workshop 1.
• Patients should complete the full antibiotic course even if symptoms improve and should be monitored for signs of complications like joint pain, carditis, or chorea for several weeks after infection.
• The use of antistreptococcal antibody tests, such as antistreptolysin O and antideoxyribonuclease B, can help confirm a recent GAS infection and identify patients at risk of developing rheumatic fever 1. Overall, while timely treatment with antibiotics can significantly reduce the risk of acute rheumatic fever and post-streptococcal arthritis, it is essential to monitor patients closely for signs of complications and to complete the full antibiotic course to minimize the risk of these conditions.

From the FDA Drug Label

It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever.

The patient can still get acute rheumatic fever if they have been treated for Strep in a timely manner, but the risk is reduced with at least 10 days of treatment for any infection caused by Streptococcus pyogenes. There is no information about post-streptococcal arthritis in the provided drug label 2.

From the Research

Acute Rheumatic Fever and Post-Streptococcal Arthritis

• Acute Rheumatic Fever (ARF) and Post-Streptococcal Reactive Arthritis (PSRA) are two distinct conditions that can occur after a group A streptococcal infection 3, 4, 5, 6, 7.
• Timely treatment of group A streptococcal infection can prevent ARF, and penicillin prophylaxis can prevent recurrence of ARF 5.
• However, even with timely treatment, a patient can still develop PSRA, which is characterized by inflammatory arthritis of ≥1 joint associated with a recent group A streptococcal infection in a patient who does not fulfill the Jones criteria for the diagnosis of ARF 4.
• The clinical presentation of PSRA can be similar to ARF, but it tends to occur within 10 days of a group A streptococcal infection, and can be associated with prolonged or recurrent arthritis 4.
• The distinction between ARF and PSRA is important, as the treatment and prognosis for the two conditions can differ 3, 6, 7.

Risk of Developing ARF or PSRA

• The risk of developing ARF or PSRA after a group A streptococcal infection is not entirely eliminated by timely treatment, and individual factors such as age, socioeconomic conditions, and genetic predisposition can play a role 5, 6.
• Patients who develop PSRA may not have clinical evidence of carditis during the acute disease, but can still develop cardiac complications such as mitral and aortic stenosis in the long term 3, 6.
• The frequency of HLA-B27 in PSRA does not differ from that of the normal population, which suggests that it is a separate entity from reactive arthritis (ReA) 4.

Treatment and Prevention

• Treatment of PSRA usually involves NSAIDs or corticosteroids, and most cases resolve spontaneously within a few weeks, but some cases can be recurrent or prolonged 4.
• Penicillin prophylaxis may be indicated in patients with PSRA to prevent recurrence, but this is still a topic of debate and requires further investigation 3, 6.
• Secondary prophylaxis with benzathine penicillin G has been shown to decrease the incidence of rheumatic heart disease (RHD) and is key to RHD control in patients with ARF 5.