Scarlet fever

This article is about disease. For Cee-Lo Green's backing band, see Scarlet Fever (band). For the song by Kenny Rogers, see Scarlet Fever (song).

Scarlet fever
Classification and external resources
ICD-10	A38
ICD-9	034.1
DiseasesDB	29032
MedlinePlus	000974
eMedicine	derm/383 emerg/402, emerg/518
MeSH	D012541

Scarlet fever is a disease caused by erythrogenic toxin (a bacterial exotoxin) released by Streptococcus pyogenes. Once a major cause of death, it is now effectively treated with antibiotics. The term scarlatina may be used interchangeably with scarlet fever, though it is most often used to indicate the less acute form of scarlet fever seen since the beginning of the twentieth century.

Scarlet fever was feared in the pre-antibiotic era, as it was associated with the late post-streptococcal complications of glomerulonephritis and endocarditis leading to heart valve disease, all of which were protracted and often fatal afflictions at the time.

Epidemiology

This disease is most common in 4-8 year olds with males and females being equally affected. By the age of 10 years most children have acquired protective antibodies and scarlet fever at this age or older is rare.

It is usually spread by the aerosol route (inhalation) but may also be spread by skin contact or by fomites.

Asymptomatic carriage may occur in 15-20% of school-age children.

The incubation period is 1-4 days.

Microbiology

The disease itself is caused by secretion of pyrogenic exotoxins by the infecting Streptococcus. Exotoxin A (speA) is probably the best studied of these toxins. It is carried by the bacteriophage T12 which integrates in to the Streptococcal genome from where the toxon is transcribed. The phage itself integrates into a serine tRNA gene on the chromosome.

The T12 virus itself has not been placed into a taxon by the International Committee on Taxonomy of Viruses. It has a double stranded DNA genome and on morphological grounds appears to be a member of the Siphoviridae.

The speA gene was cloned and sequenced in 1986. It is 753 base pairs in length and encodes a 29.244 kiloDalton (kDa) protein. The protein contains a putative 30 amino acid signal peptide: removal of the signal sequence gives a predicted molecular weight of 25.787 (kDa) for the secreted protein. Both a promoter and a ribosome binding site (Shine Dalgarno sequence) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination codon. The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1.

Streptococcal phages other than T12 may also carry the speA gene.

Symptoms and signs

Scarlet fever is characterized by:

• Sore throat
• Fever
• Bright red tongue with a "strawberry" appearance
• Characteristic rash:

fine, red, and rough-textured; it does blanch upon pressure.

• appears 12–72 hours after the fever.
• generally starts on the chest, armpits and behind the ears. It may also involve the groin.
• spares the face (although some circumoral pallor is characteristic).
• is worse in the skin folds. These Pastia lines (where the rash runs together in the armpits and groin) appear and can persist after the rash is gone.
• may spread to cover the uvula.

• Forchheimer spots (fleeting small, red spots on the soft palate) may occur

• The rash begins to fade three to four days after onset and desquamation (peeling) begins. "This phase begins with flakes peeling from the face. Peeling from the palms and around the fingers occurs about a week later." Peeling also occurs in axilla, groin and tips of the fingers and toes.

Diagnosis

Diagnosis of scarlet fever is clinical. The blood test shows marked leukocytosis with neutrophilia and conservated or increased eosinophils, high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (both indications of inflammation), and elevation of antistreptolysin O titer. Blood culture is rarely positive but the streptococci can usually be demonstrated in throat culture.

Complications

The complications of scarlet fever include septic complications due to spread of streptococcus in blood and immune-mediated complications due to an aberrant immune response. Septic complications—today rare—include ear and sinus infection, streptococcal pneumonia, empyema thoracis, meningitis and full-blown sepsis, upon which the condition may be called malignant scarlet fever.

Immune complications include acute glomerulonephritis, rheumatic fever and erythema nodosum. The secondary scarlatinous disease, or secondary malignant syndrome of scarlet fever, includes renewed fever, renewed angina, septic ear, nose, and throat complications and kidney infection or rheumatic fever and is seen around the eighteenth day of untreated scarlet fever.

An association between scarlet fever and hepatitis has been recognised for several decades. The mechanism of causation is not known.

Clinical notes

The rash is the most striking sign of scarlet fever. It usually begins looking like a bad sunburn with tiny bumps, and it may itch. The rash usually appears first on the neck and face, often leaving a clear unaffected area around the mouth. It spreads to the chest and back, then to the rest of the body. In body creases, especially around the underarms and elbows, the rash forms classic red streaks (on very dark skin, the streaks may appear darker than the rest of the skin). Areas of rash usually turn white (or paler brown, with dark complected skin) when pressed on. By the sixth day of the infection, the rash usually fades, but the affected skin may begin to peel. Usually there are other symptoms that help to confirm a diagnosis of scarlet fever, including a reddened sore throat, a fever at or above 101 °F (38.3 °C), and swollen glands in the neck. Scarlet fever can also occur with a low fever. The tonsils and back of the throat may be covered with a whitish coating, or appear red, swollen, and dotted with whitish or yellowish specks of pus. Early in the infection, the tongue may have a whitish or yellowish coating. Also, an infected person may have chills, body aches, nausea, vomiting, and loss of appetite.

When scarlet fever occurs because of a throat infection, the fever typically stops within 3 to 5 days, and the sore throat passes soon afterward. The scarlet fever rash usually fades on the sixth day after sore throat symptoms started, and begins to peel (as above). The infection itself is usually cured with a 10-day course of antibiotics, but it may take a few weeks for tonsils and swollen glands to return to normal.

In rare cases, scarlet fever may develop from a streptococcal skin infection like impetigo. In these cases, the person may not get a sore throat.

Treatment

Other than the occurrence of the diarrhea, the treatment and course of scarlet fever are no different from those of any strep throat. In case of penicillin allergy, clindamycin or erythromycin can be used with success. Patients should no longer be infectious after taking antibiotics for 24 hours. People who have been exposed to scarlet fever should be watched carefully for a full week for symptoms, especially if aged 3 to young adult. It is very important to be tested (throat culture) and if positive, seek treatment.

Note

A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin, but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, has emerged in Hong Kong in 2011, accounting for at least two deaths in that city - the first such in over a decade. About 60% of circulating strains of the Group A Streptococcus bacterium that cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, says Professor Kwok-yung Yuen, head of Hong Kong University's microbiology department. Previously, observed resistance rates had been 10-30%; the increase is likely the result of overuse of macrolide antibiotics in recent years.

History

The first description of this disease is uncertain. It is possible that Hippocrates described this in a case with a sore throat and skin ulcers but the diagnosis is not entirely clear from the description. The later physicians Avicenna, Rhazes and Ali Abbas described a measles like illness that had more a vivid colour and was more dangerous. Again it is not certain that these descriptions refer to scarlet fever.

The disease appears to have been first described in the medical literature in the book De Tumoribus praetor Naturam by the Sicilian anatomist and physician Giovanni Filippo Ingrassia where he referred to it as rossalia or rosania. It was redescribed by Johann Weyer during an epidemic in lower Germany between 1564 and 1565 who referred to it as scalatina anginosa. The first uneqivocal description of scarlet fever was published by Jean Cottyar of Poieters in his book De febre purpura epidemiale et contagiosa libri duo published on 1578 in Paris. Daniel Sennert from Wittenberg in 1572 described the classical 'scarlatinal desquamation'. He was also the first to describe the early arthritis, scarlatinal dropsy and ascites associated with the disease.

Bright in 1827 first recognised the involvement of the renal system in scarlet fever.

The association of streptococci and disease was first described in 1874 by Billroth in patients with wound infections. Billroth also coined the genus name Streptococcus. The organism was first cultured in 1883 by the German surgeon Frederich Fehleisen who cultured it from perierysipelas lesions. It received its current name (Streptococcus pyogenes) in 1884 from Rosebach.

The German physician Friedrich August Johannes Loeffler was the first in 1884 to show the presence of streptococci in the throats of patients with scarlet fever. Because not all patients with pharyngeal streptococci developed scarlet fever these finding were controversial for some time. The Austrian pediatrician Clemens von Pirquet postulated in 1906 that disease causing immune complexes were responsible for the nephritis that followed scarlet fever.

The association between streptocci and scarlet fever was confirmed by Dochez, George, and Dick in the early 1900.

Bacteriophages were discovered in 1915 by Frederick Twort. His work was overlooked and phages were later rediscovered by Felix d'Herelle in 1917. The specific association of scarlet fever with the Group A streptococcus had to await the development of Lancefield's streptococcal grouping scheme in the 1920's. The Dicks showed that cell free filtrates could induce the erythematous reaction characteristic of scarlet fever proving that this reaction was due to a toxin. Karelitz and Stempien discovered that extracts from human serum globulin and placental globulin can be used as lightening agents for scarlet fever and this was used later as the basis for the Dick test. The association of scarlet fever and bacteriophages was described in 1926 by Cantucuzene and Boncieu.

The discovery of penicillin and its subsequent widespread use has significantly reduced the mortality of this once feared disease.

The first toxin that causes this disease was cloned and sequenced in 1986 by Weeks and Ferretti.

Dick test and vaccine

The Dick test was invented in 1924 and was be used as a test to identify those susceptible to scarlet fever. A broth culture filtrate from an erythrogenic toxin producing group A streptococci was injected intracutaneously into susceptible persons. In those susceptible erythematous and oedematous skin reactions developed by 24 hours after injection. A second injection of antitoxin into the site neutralized the reactions. Non reactors were considered to have sufficient antibodies to the toxin and thus not susceptible to scarlet fever. The antitoxin was made by injecting horses with the broth filtrates and later collecting the serum from the horse.

Husband and wife Gladys Henry Dick and George Frederick Dick developed a vaccine in 1924, that was later eclipsed by penicillin in the 1940s. Broth filtrates were used as the basis for the patent the Dick's took out on their vaccine in 1924 in the United Kingdom and in 1925 in the United States.

Neither the vaccine nor the Dick test are in use presently.

In entertainment

In Act II, Scene V of Rossini's opera, The Barber of Seville, Don Basilio is terrified and sent away to bed at a very crucial point in the plot under the false persuasion that he has contracted the dreaded "febbre scarlattina" (despite the fact that he is told he has turned yellow, rather than red).

In Osmosis Jones, the main antagonist, Thrax, is a Scarlet Fever virus intent on getting himself in the medical records by overheating Frank's body in record time.

Beth, the third sister in Little Women, suffered from the effects of scarlet fever before dying.

Mary Ingalls from the Little House book and TV series lost her sight from the effects of scarlet fever.

Gene Wilder's character in See No Evil, Hear No Evil went deaf due to scarlet fever.

See also

• List of cutaneous conditions

Literature

• Rolleston JD (November 1928). "THE HISTORY OF SCARLET FEVER". British Medical Journal 2 (3542): 926–9. doi:10.1136/bmj.2.3542.926. PMC 2456687. PMID 20774279. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2456687.