Introduction

Definition of scarlet fever

Scarlet fever refers to the rash associated with bacterial infection with streptococcus pyogenes, a common bacterial cause of sore throat infections and skin infections such as impetigo and erysipelas. Streptococcus pyogenes is a Group A Streptococcus (GAS). The typical rash in scarlet fever is formed by small, red, raised spots with a widespread distribution. It is referred to as a “sandpaper” rash due to the texture of the affected skin. Group A streptococcus can potentially cause serious complications including acute rheumatic fever and glomerulonephritis (inflammation of the kidneys).¹ 

Modern antibiotic treatment has revolutionised the treatment of GAS and its complications, there has been a rise in invasive streptococcal infections such as necrotising fasciitis, attributed to the emergence of more aggressive strains. Whilst improved living conditions have reduced the overall incidence of streptococcal infections in industrialised nations, recently the emergence of new GAS strains has seen outbreaks of scarlet fever in both East Asia (Hong Kong and mainland China, South Korea, Vietnam) and the UK. In developing nations, the prevalence of complications of GAS infections, particularly acute rheumatic fever, and post-streptoccal glomerulonephritis, remains high.²   

Streptococcal Infections: the causative agent of scarlet fever

Group A streptococcus (streptococcus pyogenes)

The streptococcus bacteria is a circular-shaped bacterium that occurs in pairs or chains. Proteins on the bacterial surface (antigens) allow group A streptococcus to be distinguished from other streptococci via serological tests. Streptococcus pyogenes is also termed group A beta-haemolytic streptococcus (GABHS) because of its ability to completely destroy red blood cells if cultured in the laboratory on a medium containing them.³ 

GAS colonise the throat, anal and genital areas and are harboured by carriers with no symptoms ( asymptomatic carriers). During active infection GAS is spread from person to person in a variety of ways: droplet transmission via coughing and sneezing, nasal discharge (including used tissues), surfaces, and hands. GAS can also be transmitted directly from infected skin lesions such as infected wounds or impetigo. Transmission is common in crowded places such as schools and other institutions such as nursing homes or prisons.³

Mechanism of disease development in Scarlet Fever

Infection with GAS in scarlet fever is usually a result of acute pharyngitis (infection of the throat) after contact with another infected person. Less commonly, scarlet fever can be associated with streptococcal wound infections. Around 15-30% of acute throat infections in children are caused by GAS. Streptococcal bacteria proliferate and release a toxin into the bloodstream (exotoxin) which is responsible for the skin rash in scarlet fever. Not all patients infected with GAS will exhibit the rash of scarlet fever.³

Clinical manifestations of scarlet fever

Common symptoms and signs

Pharyngitis caused by GAS typically presents with a fever (usually above 38^oC), sore throat with difficulty swallowing, and swelling of the lymph nodes in the neck (“glands”). The typical rash of scarlet fever may develop 2-3 days into the infection (although in some cases the rash is a later sign, appearing up to 7 days after the initial symptoms). The rash is widespread although it does not involve the palms or soles of the feet. The spots are small, red, and raised and will blanch under direct pressure.⁴

Changes are also seen in the tongue. The appearance of the tongue in scarlet fever is termed “strawberry tongue” because of the tongue's reddish appearance and enlargement of the small bumps (papillae) on its surface that resemble a strawberry. Prior to this, the tongue is covered with a white coating. The rash becomes confluent in the skin folds giving the appearance of red lines in the skin folds known as “Pastia lines”.⁴

Clinical scoring systems such as CENTOR can help distinguish an acute sore throat caused by GAS from other common causes of sore throat. This is based on the patient's age (GAS is uncommon in children under 3), exudates on the tonsils, temperature above 38 degrees, painful, swollen lymph nodes in the neck (glands), and the absence of a cough.⁵ In the UK, the National Institute for Health and Care Excellence (NICE) recommends the use of CENTOR criteria to help identify which cases of acute sore throat may benefit from antibiotics.

Complications

Rheumatic fever

Acute rheumatic fever (ARF) results from an abnormal immune response occurring 2-4 weeks following an untreated GAS infection, most commonly pharyngitis. Whilst now rare in industrialised countries, rheumatic fever remains an important cause of morbidity due to GAS in developing countries.⁵

Proteins on the surface of GAS bacteria share similarities to those found in the body's own cells, particularly in cardiac muscle and the joints which leads the immune system to attack the body resulting in the symptoms. Symptoms are variable but Arthritis (inflammation of the joints) occurs in 60-80% of cases.

Inflammation of the heart and heart valves causes damage to the valves and over time can lead to long-term changes in the heart valves eventually progressing to rheumatic heart disease (RHD).⁶ Lesions of the skin and the brain (causing a movement disorder known as Sydenham’s Chorea) also occur in some patients.⁷ 

Treatment of acute rheumatic fever is by eradication of GAS with antibiotics, however, patients with acute disease are at risk of recurrence and progression to RHD. For this reason, long-term treatment with prophylactic antibiotics is indicated, the criteria for length of treatment being dependent on the degree of cardiac involvement.⁸

Post-streptococcal glomerulonephritis

Post-streptococcal glomerulonephritis (PSGN) is an inflammatory condition of the kidneys usually occurring 1-2 weeks following sore throat caused by GAS or 6 weeks following GAS skin infections. Immune complexes formed by antibodies to GAS bacteria and proteins found on the surface of GAS bacteria (antigens) either form or lodge in the small filtering tubules of the kidneys called glomeruli. An immune reaction to these complexes destroys the small tubules, and causes glomerulonephritis.⁹

Symtoms

• Blood in the urine(either microscopic or visible to the naked eye)
• Swelling of the legs (oedema)
• Reduction in the amount of urine passed (oliguria) 
• High blood pressure (hypertension)

In most cases, the condition will resolve with only supportive treatment and the outcome is generally good, however in a few cases there is severe deterioration in kidney function resulting in the need for dialysis.⁹ PSGN remains a significant problem in developing countries, where it represents the most common cause of acute kidney injury in children.¹⁰

Diagnosis of scarlet fever

Clinical diagnosis

The diagnosis of scarlet fever can usually be made on a clinical basis. The findings of acute pharyngitis accompanied by a characteristic “sandpaper” rash beginning on the trunk and spreading to the limbs and face (as described above) are highly suggestive of a GAS infection. Scarlet fever secondary to streptococcal wound infection, impetigo or erysipelas should also be considered.⁵ 

The CENTOR criteria mentioned earlier can be a useful adjunct to the clinical features  In the UK, NICE does not recommend routine microbiological or blood tests. However, routine practice differs in the US where the use of rapid antigen detection tests (RADT) for group A streptococcus is commonplace and recommended in the US by the CDC for children above the age of 3.

Laboratory diagnosis

The most accurate test for GAS is a throat swab sent for microbial culture, however, it has the disadvantage of taking several days to process the result, in addition to financial costs. In the UK, NICE does not recommend routine use of throat swabs but advises they be considered in certain circumstances. 

These are: if there is a localised outbreak of scarlet fever, in cases of penicillin allergy, if the patient is in contact with people with health vulnerabilities such as the immunocompromised, and if there is sufficient doubt about the diagnosis on a clinical basis.¹¹ 

Rapid antigen detection test (RADT) for GAS is used widely in the US. Whilst it is less sensitive than a throat swab, the result is instantly available in the doctor’s office and can be used to make an instant decision on antibiotic prescribing. Unlike a throat swab, the test gives no information on which antibiotics the infection is sensitive to.¹²

Serological blood tests which measure levels of the antibodies produced by GAS bacteria are not useful in treating acute infections. They have a role in detecting a recent GAS infection in cases of complications such as rheumatic fever or PSGN.

Treatment of scarlet fever

Antibiotic therapy

The wide availability of antibiotic treatment has revolutionised outcomes in scarlet fever. The standard treatment for scarlet fever is 10 days of oral penicillin V. Thus far, there are no strains of GAS resistant to penicillins. In patients allergic to penicillin, a ten-day course of clarithromycin can be used from birth upwards except in pregnancy when erythromycin is a suitable alternative.

Alternatively in non-pregnant adults and children over 6 months, a five-day course of azithromycin is suitable.¹³ These antibiotic regimes are based on the current recommendations from NICE on scarlet fever, it is appreciated that different prescribing regimes may differ slightly in other countries.

Treatment of fever and pain caused by GAS pharyngitis can be achieved with over-the-counter analgesics such as paracetamol and ibuprofen. Oral rehydration with plenty of fluids and adequate rest is also important.

How to prevent GAS infections from Spreading?

Preventing the spread of GAS infections is important, particularly in institutions like schools where localised outbreaks may occur. Prompt prescription of antibiotics reduces the spread of infection as patients are no longer infectious 24 hours following the first dose of antibiotic. This is one reason why early diagnosis and treatment is important.

If antibiotics are not taken, sufferers are infectious for between 2-3 weeks. Practicing hand washing, disposing of used tissues, covering coughs, etc., and general hygiene methods all help to lessen the spread of infectious diseases such as GAS.¹⁴ 

Scarlet fever vaccine

Research has been underway for decades aimed at developing a vaccine for GAS. This has proved challenging for several reasons, amongst them the complex immunological features of GAS and the many different strains in existence, lack of interest from developed countries, and securing funding.  Currently, no vaccines are available for GAS, the WHO (has prioritised GAS infection and rheumatic heart disease following a World Health Assembly resolution in 2018. The resulting policy documents have secured extra funding for vaccine research, with the hope of vaccines being ready for clinical trials in the next few years.¹⁵

Summary

Scarlet fever refers to the typical rash associated with group A streptococcus (GAS) infections of the throat and skin. GAS releases a toxin that precipitates a skin rash with a characteristic “sandpaper” appearance and texture. GAS accounts for 15-30% of sore throat infections in children. Once a serious cause of morbidity, owing to its complications, particularly rheumatic fever, and post-streptococcal glomerulonephritis, the treatment of GAS has been revolutionised in the modern age by antibiotics.

GAS infections and rheumatic heart disease caused by rheumatic fever remain a significant cause of morbidity in developing nations. Prompt treatment can help avoid complications and reduce spread by eradicating the carriage of GAS infection in affected people.. Prevention of GAS infections is best achieved by meticulous hand hygiene and early treatment with antibiotics. Whilst not currently available, there are hopes of a GAS vaccine being developed in the future.