|Classification and external resources|
Strawberry tongue seen in scarlet fever
Scarlet fever (also called scarlatina in older literature) is an infectious disease which most commonly affects 4-8 year old children. Symptoms include sore throat, fever and a characteristic red rash. Scarlet fever is usually spread by inhalation. There is no vaccine, but the disease is effectively treated with antibiotics. Most of the clinical features are caused by erythrogenic toxin, a substance produced by the bacterium Streptococcus pyogenes (group A strep.) when infected by a certain bacteriophage.
Before the availability of antibiotics, scarlet fever was a major cause of death. It could also cause late complications such as glomerulonephritis and endocarditis leading to heart valve disease, all of which were protracted and often fatal afflictions at the time.
It is important to recognize that strains of Group A Strep which produce the erythrogenic toxin are not inherently more dangerous than other strains which do not but are more easily diagnosed as such because of the characteristic rash.
This disease is most common in children 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.[dubious ]
It is usually spread by the aerosol route (inhalation) but may also be spread by skin contact or by fomites. Although not normally considered a food borne illness an outbreak due to chicken meat has been reported in China.
Asymptomatic carriage may occur in 15–20% of school-age children.
The incubation period is 1–4 days.
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 into the Streptococcal genome from where the toxin 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.
Scarlet fever is characterized by:
- Sore throat
- Bright red tongue with a "strawberry" appearance
- Forchheimer spots (fleeting small, red spots on the soft palate) may occur
- Characteristic rash:
- the rash is fine, red and rough-textured
- blanches 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.
- the face often shows red cheeks and a characteristic pale area around the mouth (circumoral pallor)
- 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
- 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.
The rash is the most striking sign of scarlet fever. It usually begins looking like a bad sunburn with tiny bumps and may itch. The rash usually appears first on the neck and face, often leaving a clear unaffected area around the mouth. It then spreads to the chest and back and finally to the rest of the body. In the body creases, especially around the axillae (underarms) and elbows, the rash forms the classic red streaks known as Pastia lines. 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.
Other features 
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.
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.
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.
Differential diagnosis 
Cases need to be differentiated from Far East scarlet-like fever, an infectious disease first reported in the 1950s from Russia. Because its similar clinical presentation to scarlet fever it was initially thought to be caused by a Streptococcus. It is now known to be caused by a Gram negative bacillus - Yersinia pseudotuberculosis. Kawasaki's disease is another important differential, especially in it's incomplete form. In some ways Scarlet fever looks like Kawasaki's disease, but without the eye signs or the swollen, red fingers and toes. But sometimes the signs of Kawasaki's disease may manifest over a few days, rather than all at one time. The complications of missed scarlet fever are significant but rare. The complications of missed Kawasaki's include a 1-2% death rate and coronary artery aneurysm.
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.
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.
Antibiotic resistance 
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 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.
No vaccines are currently available to protect against S. pyogenes infection, the vaccine developed by George and Gladys Dick in 1924 was discontinued due to poor efficacy and the introduction of antibiotics. Difficulties in vaccine development include the considerable strain variety of S. pyogenes present in the environment and the amount of time and number of people needed for appropriate trials for safety and efficacy of any potential vaccine.
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.
The first description of this disease is uncertain. It is possible that Hippocrates in c. 400 BC described this in a case with a sore throat and skin ulcers, but the diagnosis is not entirely clear from the description. In the 10th/11th century, the physicians Rhazes, Ali Abbas and Avicenna described a measles-like illness that had a more 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 1553 book De Tumoribus praeter 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 unequivocal description of scarlet fever was published by Jean Cottyar of Poieters in his book De febre purpura epidemiale et contagiosa libri duo published in 1578 in Paris. Daniel Sennert of Wittenberg described the classical 'scarlatinal desquamation' in 1572 and 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 Friedrich Fehleisen who cultured it from perierysipelas lesions. It received its current name (Streptococcus pyogenes) in 1884 from Rosenbach.
The German physician Friedrich 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 findings remained controversial for some time. The association between streptocci and scarlet fever was confirmed by Alphonse Dochez, George and Gladys Dick in the early 1900s.
Scarlet fever serum from horses was used in the treatment of children beginning in 1900 and reduced mortality rates significantly.
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 1920s. 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 used 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 were not susceptible to scarlet fever.
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 Dicks took out on their vaccine in 1924 in the United Kingdom and in 1925 in the United States.
Neither the vaccine or the Gladys Test are in use currently.
In fiction 
Scarlet fever has been used as a plot device in a variety of fictional settings.
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).
Beth, the third sister in Little Women, suffered from the effects of scarlet fever before dying.
In the children's book The Velveteen Rabbit, a toy rabbit's owner contracts scarlet fever and all his toys, including the rabbit, are taken to be burned.
Also in another children's book written by Enid Blyton Five Are Together Again, Joan the Kirrin family cook contracts scarlet fever and is taken away in an ambulance just as The Famous Five have arrived at Kirrin Cottage to start their school holiday.
Scarlet fever was a major plot point in American Girl's Kit Kittredge short story Kit Uses Her Head, when Kit, along with her best friends Ruthie Smithens and Stirling Howard, were diagnosed with the disease.
In Love's Everlasting Courage, Ellen Davis dies of scarlet fever.
In the movie Anne of Green Gables: The Continuing Story, Gilbert Blythe (Anne's love interest) contracts scarlet fever from the hospital while studying medicine. During this time, Anne promises to marry him, which is said to be what helped him survive.
In the 2004 movie Frankenstien, the mother dies of scarlet fever.
Persons who suffered from scarlet fever 
- Lope de Vega, the famous Spanish writer and poet died because of scarlet fever in 1635.
- Caroline Matilda of Wales (1751-1775), titular queen of Denmark, died from the disease at the age of 23.
- Johann Strauss I, composer of waltzes and other light classics, died in Vienna in 1849 from scarlet fever contracted from one of his illegitimate children.
- Myron Floren, the accordionist on The Lawrence Welk Show had scarlet fever as a child. His accordion playing saved his life, as the exertion strengthened his heart back to pre-fever performance.
- Maria Franziska von Trapp, the second daughter of Captain Georg von Trapp, suffered from scarlet fever and infected her mother Agathe Whitehead, who died from the disease. Maria von Trapp then entered the family, giving rise to the story behind The Sound of Music.
- Liu Tianhua (1895–1932), a Chinese musicologist died of scarlet fever in 1932 in Beijing.
- August Lösch (1906–1945), German economist, died of scarlet fever just after World War II ended.
- Hazel Hall (1886-1924), a poet based in Portland. She created many pieces of work, including "Curtains"
See also 
- Edward J Zabawski Jr. "Scarlet Fever". MedScape Reference.
- Czarkowski, M. P.; Kondej, B.; Staszewska, E. (2011). "Scarlet fever in Poland in 2009". Przegl Epidemiol 65 (2): 209–212. PMID 21913461.
- Czarkowski, M. P.; Kondej, B. (2010). "Scarlet fever in Poland in 2008". Przegl Epidemiol 64 (2): 185–188. PMID 20731219.
- Yang, S. G.; Dong, H. J.; Li, F. R.; Xie, S. Y.; Cao, H. C.; Xia, S. C.; Yu, Z.; Li, L. J. (2007). "Report and analysis of a scarlet fever outbreak among adults through food-borne transmission in China". J Infect 55 (5): 419–424. doi:10.1016/j.jinf.2007.07.011. PMID 17719644.
- Zabriskie, J. B. (1964). "The role of temperate bacteriophage in the production of erythrogenic toxin by Group A Streptococci". J Exp Med 119 (5): 761–780. doi:10.1084/jem.119.5.761. PMC 2137738. PMID 14157029.
- Krause, R. M. (2002). "A Half-century of Streptococcal Research: Then & Now". Indian J Med Res 115: 215–241. PMID 12440194.
- McShan, W. M.; Ferretti, J. J. (1997). "Genetic diversity in temperate bacteriophages of Streptococcus pyogenes: identification of a second attachment site for phages carrying the erythrogenic toxin A gene". J Bacteriol 179 (20): 6509–6511. PMC 179571. PMID 9335304.
- Weeks, C. R.; Ferretti, J. J. (1986). "Nucleotide sequence of the type A streptococcal exotoxin (erythrogenic toxin) gene from Streptococcus pyogenes bacteriophage T12". Infect Immun 52 (1): 144–150. PMID 262210.
- Yu, C. E.; Ferretti, J. J. (1991). "Molecular characterization of new group A streptococcal bacteriophages containing the gene for streptococcal erythrogenic toxin A (speA)". Mol Gen Genet 231 (1): 161–168. doi:10.1007/BF00293833. PMID 1753942.
- "Second HK child dies of mutated scarlet fever". Associated Press (online). 22 June 2011. Retrieved 23 June 2011.
- "Initiative for Vaccine Research (IVR) - Group A Streptococcus". World Health Organization. Retrieved 15 June 2012.
- Elishkewitz, K.; Shapiro, R.; Amir, J.; Nussinovitch, M. (2004). "Hepatitis in scarlet fever". Isr Med Assoc J 6 (9): 569–570. PMID 15373323.
- Rolleston, J. D. (1928). "The History of Scarlet Fever". BMJ 2 (3542): 926–929. doi:10.1136/bmj.2.3542.926. PMC 2456687. PMID 20774279.
- Huber, B. (2006). "100 years of allergy: Clemens von Pirquet - his idea of allergy and its immanent concept of disease". Wien. Klin. Wochenschr. 118 (19-20): 573–579. doi:10.1007/s00508-006-0701-3. PMID 17136331.
- Cantacuzène, J.; Bonciu, O. (1926). "Modifications subies par des streptocoques d'origine non scarlatineuse au contact de produits scarlatineux filtrès". CR Acad Sci Paris 182: 1185–1187.
- Dick, G. F.; Dick, G. H. (1924). "A skin test for susceptibility to scarlet fever". J Am Med Assoc 82 (4): 265–266. doi:10.1001/jama.1924.02650300011003.
- Serena Gordon (4 Feb 2013). "Mistaken Infection 'On The Prairie'?". U.S. News and World Report.
- "Johann Strauss I on Grove Music Online". Grove Music Online. Retrieved 5 October 2008.
Further reading 
|Wikimedia Commons has media related to: Scarlet fever|
- 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.
- Scarlet Fever from PubMed Health