How Can Streptococcal Infections Lead To Conditions Like Rheumatic Fever Or Glomerulonephritis?

Overview

With the seasons changing and colds going around, it is common to get infections from others. So, if you are interested in learning more about infections, specifically streptococcal infections, this article is for you.

To start, we will define streptococcal infections. These infections arise due to a common bacteria known as Group A Streptococcus (GAS), or Streptococcus pyogenes.¹ This bacterium has adapted to the human body and can cause mild to severe illnesses.² The infection affects everyone worldwide and around 1.78 million people contract this infection yearly, with around 500,000 resulting in death.²

Once infections occur it can lead to various results such as scarlet fever, impetigo, pharyngitis, type 2 necrotising fasciitis, cellulitis, and even streptococcal toxic shock syndrome.² In some cases streptococcal infections can lead to serious complications such as rheumatic fever (RF) or acute post-streptococcal glomerulonephritis (APSGN).³ Hence, it is important to understand streptococcal infections as well as the more serious forms of the disease and complications.

Mechanism of streptococcal infections

Infections of GAS occur via droplets released into the air when someone sneezes or coughs, or through contact with someone who is ill due to the same bacterium.² It can also be contracted through contaminated food or contaminated surfaces.² Sometimes, the bacteria can reside on our body (e.g. the anus, vagina, throat, or skin) without causing an illness and can use the human body as a reservoir.²

GAS has a haemolytic activity; meaning they are capable of releasing enzymes that can break down red blood cells.⁴ Additionally, some strains have a virulence factor known as M protein, which can allow the bacteria to bypass our body’s defences and cause kidney issues.⁴

As infection occurs, the body’s immune system activates and reacts accordingly, releasing antibodies to fight off the bacteria.⁴ These antibodies will detect the bacteria, attack it, and clear it out.⁴ However, sometimes our immune response can take a turn for the worse and start attacking our own tissues, which leads to autoimmunity.⁴ This immune response can lead to either rheumatic fever or APSGN.³

Rheumatic fever

What is rheumatic fever (RF)? 

RF is one of the autoimmune complications that can arise after a group A strep infection, secondary to tonsillopharyngitis.³ Although it is rare, it can occur and cause heart, brain, and skin issues along with pain in the joints.^5,6

RF usually affects children and teenagers in the range of 5-14 years old.⁷ It is interesting to note that studies have shown using antibacterial drugs to treat GAS can lead to lowering RF cases significantly.⁷ However, if left untreated, RF can progress and lead to rheumatic heart disease (RHD) and increase the risk of mortality.⁷

Pathology

RF pathophysiology is attributed to both GAS and inflammatory processes. When infected with group A strep, the bacteria can have antigens, like the M protein, on its surface that are very similar to proteins in our tissues such as in the heart, brain, or joints.⁸ This leads to our immune system having a cross reactivity with our own antigens leading to autoimmune disease.⁸ This similarity in structure is referred to as molecular mimicry.⁸

Once there is cross reactivity, inflammation takes place and can lead to valvulitis and cardiac issues.⁸

Additionally, it is worth noting that genetics can play a role in increasing your risk of having RF; for example, twins showed to have a higher risk with identical ones scoring up to 44%.⁸ Also, having a family history of RF poses a higher risk to the individual (around 5 times greater).⁸ 

Symptoms

There are multiple symptoms associated with RF and takes around 1 to 5 weeks to develop after the initial infection, some are common and some are uncommon such as:⁶

• Common symptoms:
  • Arthritis and painful joints especially in the elbows, wrists, knees, and ankles
  • Chorea which are jerky, uncontrollable body movements
  • Fatigue
  • Fever
• Uncommon symptoms:
  • Painless lumps or nodules close to the joints
  • Rash that has a clear centre with pink rings
• Cardiac symptoms:
  • Chest pain
  • Shortness of breath
  • Fast heartbeats
  • Heart murmurs
  • Enlarged heart muscle
  • Fluid surrounding the heart

If RF is not treated quickly, it can progress and lead to rheumatic heart disease where the heart valves weaken and may result in death if surgery is not done.⁶

Importance of Treatment

Early detection and treatment of strep. throat can significantly reduce the risk of rheumatic fever along with its complications. Hence, it is important to look out for the signs and symptoms of strep. throat and treat it in a timely manner.

Glomerulonephritis

What is Glomerulonephritis (GN)?

Another complication that arises from GAS is glomerulonephritis (GN in short).⁹ It is an immunological complication that affects the kidneys and is caused by a specific strain of GAS that has an affinity to the kidneys.⁹

GN is characterised by inflammation and scarring in the kidney’s filters (known as glomeruli), this causes the kidneys to lose their capability to flush out waste and excess fluid from the blood.¹⁰ GN can occur due to multiple causes but it is seen as a complication after a strep throat infection.¹⁰

GN is considered one of the most common causes of acute nephritis in kids globally, with around 500,000 new cases emerging yearly.^4,9 This disease is more common in boys (twice as much) and in children aged from 5 to 12, but can also affect people that are past 60 years old.⁹

Although GN sometimes may not show any symptoms and is picked up by urine and blood tests, it takes around 1 to 3 weeks to appear after scarlet fever, and 3 to 6 weeks after impetigo.^9,11

Pathology

When GN occurs due to GAS, the immune system ends up making antigen-antibody complexes to fight off the infection.¹² This results in the formation of IgA and C3 complement deposits that end up in the kidneys.¹² This then activates inflammatory pathways in the body which ends with the release of inflammatory cytokines that lead to glomerulosclerosis.¹²

This damage to the kidneys can lead to functional and structural changes in the organ, and as a result, can end up in a malfunctioning kidney or even failure.¹²

Symptoms

When dealing with GN, there are multiple symptoms associated:^10,12

• High blood pressure
• Swelling in the face, hands, feet and belly
• Haematuria which is the presence of blood in the urine
• Proteinuria which is the presence of protein in the urine
• Decreased urine output
• Fever
• Flu-like symptoms
• Nausea and vomiting

If GN is left untreated, it can progress into a more severe form and lead to kidney failure.¹⁰ This will require dialysis or even a transplant.¹⁰ Hence, it is important to treat GN early on to avoid more severe complications, as usually, GN presents itself in a mild manner that can be treated effectively.¹¹

Prevention and treatment

Streptococcal infections

There are multiple actions that we can take to treat and prevent the infection with GAS such as:¹³

• Having good hygiene such as cleaning hands regularly, covering sneezes and coughs
• Washing clothes and surfaces that were touched by the sick person
• Cleaning wounds and cuts
• Take antibiotics if prescribed by your healthcare provider

Rheumatic fever

To treat and prevent RF, patients can have multiple options. The best option would be to prevent RF by treating the initial step infection.¹⁴ However, this is not always the case and thus some people can take periodic antibiotics (daily or monthly) to avoid developing RF again.¹⁴ Having additional medications to treat inflammation would be beneficial to avoid heart damage.¹⁴ In some severe cases, surgery can be an option.¹⁴

Glomerulonephritis

Treatment of GN depends on the symptoms, age, and overall health of the individual.¹⁰ Some options include:¹⁰

• Medicine for blood pressure
• Corticosteroids to lower inflammation
• Diuretics to remove excess fluid from the system
• Diet changes e.g. less protein, sodium, and potassium
• Dialysis to remove waste and toxins from the blood if the kidneys have stopped functioning
• transplant

Summary

Streptococcal infections are common and can be dormant in our bodies. While they are usually self-limited, they can lead to severe complications that can have detrimental effects on our health like rheumatic fever and glomerulonephritis. Both conditions are autoimmune responses of the body trying to protect us from infection but end up attacking our own tissues due to the similarity in structures known as molecular mimicry. The best option to treat these complications is prevention. Hence, early interventions and treatment can help prevent RF and GN from occurring, such as using antibiotics to treat strep infections. Our health is valuable, and it is important for us to take care of ourselves to lead a healthy and balanced life.