Introduction

Did you know that you can harbour bacteria in your throat without getting sick? This is especially true if your immune system is not compromised by an infection which can cause the bacteria to show their fangs. This is what can happen in streptococcal infections which are caused by a common group of bacteria that can lead to a variety of diseases. 

Streptococcal infections are those diseases commonly caused by Group A Streptococcus (GAS) bacteria. These bacteria are usually found on the throat and skin. However, these organisms can cause infections ranging from mild to life-threatening conditions such as necrotising fasciitis, streptococcal toxic shock syndrome (STSS), pharyngitis, tonsillitis, etc. The complications of GAS infections can lead to kidney disease, rheumatic fever, rheumatic heart disease and brain problems. In this article, you will understand how streptococcal infections relate to post-streptococcal reactive arthritis (PSRA). 

What are streptococcal infections?

These are infections caused by streptococcus bacteria. Streptococcus is a gram-positive, non-motile, non-spore-forming cocci that occurs in pairs or chains.⁶ This group of bacteria is divided into three major types depending on the type of hemolysis seen on blood agar;

• 𝞪-hemolytic streptococci: This group is characterised by incomplete hemolysis and includes strains such as Streptococcus pneumoniae and Viridans streptococci
• 𝛃-hemolytic streptococci: This exhibits complete lysis of red blood cells and is further subdivided into Group A Streptococcus (GAS) and Group B Streptococci (GBS). The former include Streptococcus pyogenes while the latter include Streptococcus agalactiae⁶
• 𝞬-hemolytic streptococci: This group doesn’t show any hemolysis⁶ 

Pathophysiology of streptococcal infections

The way by which GAS causes infection is complex and involves a conglomeration of virulence factors. This is because these virulence factors contribute to its ability to cause infection in an individual. GAS secretes a variety of virulence factors that are also associated with the cell wall.¹ These exert various effects on the tissues, cells and components of the immune response to infection.¹ The surface-bound virulence factors include; M protein, hyaluronic acid capsule and S protein. These factors confer ingenious and camouflage strategies to evade immune clearance and assist with bacterial dissemination and survival in the blood.² The secreted virulence factors produced by GAS include deoxyribonucleases, immunoglobulin-degrading enzymes, streptolysins and superantigens.³

Streptococcus pyogenes is the major strain of group A Streptococci (GAS) implicated in a variety of diseases caused by this bacteria. Host-pathogen interaction occurs due to the attachment of GAS to pharyngeal or dermal epithelial cells via GAS multiple adhesion factors.⁴ These specialised adhesion mechanisms also facilitate the invasion of GAS into deeper tissues.⁴ Entry into deeper tissues leads to tissue damage and causes severe illness. 

GAS infections are common in children and can cause 3 major types of infections;

• Asymptomatic infections such as pharyngitis, scarlet fever, etc
• Mild infections like impetigo and sore throat
• Invasive group A streptococcal infections (also called iGAS infections)⁵ These include septicemia, streptococcal toxic shock syndrome, necrotising fasciitis, etc

There are about 1.8 million cases of iGAS infections worldwide with a 20% mortality rate in both young and old people. ⁵  There are also several million cases of mild GAS infections yearly.

Symptoms of streptococcal infections

The symptoms associated with streptococcal infections vary depending on the infection caused. The common symptoms include: 

• High fever
• Headache
• Enlarged tonsils
• Distended lymph nodes in the neck
• Severe muscle aches
• Malaise
• Vomiting, nausea and abdominal pain

Meaning of post-streptococcal reactive arthritis

Post-Streptococcal Reactive Arthritis (PSRA) is a condition characterised by the onset of arthritis after asymptomatic pharyngeal infection and subsequent inflammation of one or more joints and in the absence of Jones criteria for acute rheumatic fever.⁷  PSRA occurs following pharyngeal infection caused by group A 𝛃-hemolytic streptococci and symptoms start 10 days after pharyngitis.⁹

According to the Canadian Journal of Infectious Diseases, the Jones criteria for diagnosis of acute rheumatic fever (ARF) comprises the major and minor criteria. The major criteria include carditis, polyarthritis, Erythema marginatum, chorea, and subcutaneous nodules. The minor criteria include clinical features such as arthralgia and fever, elevated C-reactive protein and erythrocyte sedimentation rates in laboratory findings, prolonged PR interval, positive throat culture and antigen test. 

PSRA has a bimodal age distribution with a peak occurrence between the ages of 8-14 years and a second peak in adults between the ages of 21-37 years. The male-to-female ratio of PSRA is equal.⁸ However, PSRA has an annual incidence of 1 to 2 cases per 100,000 people.⁸ 

The connection between streptococcal infection and PSRA

PSRA is a type of arthritis associated with one or more joint inflammation that occurs after a recent group A streptococci infection in a patient. In other words, it is a streptococcal-induced arthritis that can occur in children and young adults after the underlying streptococcal infection has occurred. PSRA is chiefly characterised by a streptococcal infection of the pharynx, followed by an asymptomatic interval and, subsequently, inflammation of one or more joints. This type of arthritis does not respond to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).⁸ 

Both PSRA and Acute Rheumatic Fever (ARF) occur after pharyngitis caused by Group A Streptococci. Hence, both conditions share similar symptoms according to various studies.⁹ Therefore, there is a need to differentiate between PSRA and ARF. Here are some distinguishing features of these two conditions;

Diagnosis of PSRA

The main diagnostic criteria for PSRA are based on the following clinical presentation; 

• Onset of non-migratory arthritis which can affect any joints, can be persistent or recurrent. The arthritis doesn’t respond positively to salicylates or aspirin and can be symmetric or asymmetric. 
• Physical evidence of prior GAS infection
• Inability to attain the modified Jones criteria for the diagnosis of ARF ¹⁰
  

In order to accurately diagnose PRSA, microbiological confirmation obtained by throat culture or rapid antigen detection test (RADT) is required. The setback is that this might not differentiate between a true GAS infection and a carrier. Thus, serological tests aimed at identifying elevated anti-streptococcal antibody titers are critical in identifying a preceding GAS infection in an individual suspected of having PRSA.¹¹ 

Treatment and management of PSRA

The treatment of patients with PSRA involves the continuous use of NSAIDs until the arthritis has subsided and acute-phase reactants get back to normal. Antibiotics are prescribed to eliminate GAS from the throat and subsequently, antibiotic prophylaxis at a secondary stage. Secondary prophylaxis with antibiotics is recommended for a year with close follow-up and monitoring. This is because of the possibility of delayed onset of carditis. 

If carditis develops, the patient is classified as having ARF and should continue with the intake of antibiotic prophylaxis. According to Dr Himanshu Pathak, Department of Rheumatology, Norfolk and Norwich University, UK, antibiotic prophylaxis lasting 1-2 years for an adult without adequate evidence of PRSA can be counterintuitive, especially considering the risk of developing antibiotic resistance. Thus, this emphasises the need for proper diagnosis and undergoing echocardiography as part of follow-up. 

FAQs

How are infections caused by GAS spread? 

GAS infections are spread by direct contact with the secretions from the nose or throat of an infected individual. The risk of spread of GAS infections is increased when a person is ill and carries the bacteria asymptomatically. 

How can infection caused by Group A Streptococci be prevented?

Infections caused by GAS can be prevented by adopting appropriate hand washing and hygiene techniques, especially before preparing foods after coughing or sneezing. People diagnosed with strep throat should self-quarantine at home until 12 hours or more after taking prescribed antibiotics. This will also prevent further spread of infection. 

How long does PRSA last?

In post-streptococcal reactive arthritis (PRSA), the large and small joints and axial skeleton are involved. It can last for as long as 2 months or more depending on the severity of the infection. 

Summary

• Streptococcal infections are those diseases mostly caused by Streptococcus bacteria which can be subdivided into 𝞪,𝛃 and 𝞬-hemolytic streptococci.
• These bacteria are commonly found on the throat and the skin and can cause infection due to weakened immunity.
• The group A Streptococci (GAS), specifically Streptococcus pyogenes is the major causative organism for a variety of diseases such as pharyngitis, tonsillitis, sore throat, etc.
• Post-streptococcal reactive arthritis (PRSA) is a condition that follows after pharyngitis caused by GAS and is characterised by one or more joint inflammation.
• PRSA is diagnosed based on the absence of criteria attributed to acute rheumatic fever(ARF)
• Treatment involves continuous use of NSAIDs till the arthritis improves followed by antibiotic prophylaxis and appropriate monitoring and follow-up in case of the development of carditis.