Continuing Education Activity

Scarlet fever represents an acute infectious disease caused by Group A Streptococcus, characterized by fever, pharyngitis, and a diffuse erythematous rash resulting from streptococcal pyrogenic exotoxins. The condition commonly affects children but can occur in individuals of any age, with transmission facilitated by respiratory droplets or direct contact with infected secretions. Clinical features include a sandpaper-like rash, strawberry tongue, circumoral pallor, and Pastia lines, along with potential complications such as otitis media, sinusitis, pneumonia, and, in severe cases, invasive streptococcal infections. Prompt diagnosis depends on clinical recognition supported by rapid antigen detection tests and confirmatory throat cultures. Appropriate antibiotic therapy prevents transmission and reduces the risk of suppurative and non-suppurative complications, including rheumatic fever, post-streptococcal glomerulonephritis, streptococcal toxic shock syndrome, and necrotizing fasciitis. Public health measures, patient education, and adherence to antimicrobial stewardship principles remain central to reducing disease burden at both individual and community levels.

This course equips participants with a comprehensive understanding of the clinical presentation, pathophysiology, diagnostic evaluation, and evidence-based management of scarlet fever. Learners gain enhanced competence in selecting appropriate antibiotic therapy, interpreting diagnostic tests, recognizing complications early, and applying current guidelines that promote optimal outcomes. The activity emphasizes the value of collaborative practice, demonstrating how coordinated efforts among clinicians, pharmacists, nurses, and other interprofessional team members strengthen patient education, reinforce infection-control measures, and support adherence to treatment plans. Through updated knowledge, refined diagnostic skills, and a deeper appreciation for interdisciplinary communication, participants strengthen their ability to deliver high-quality, patient-centered care across diverse clinical settings.

Objectives:

• Identify the clinical signs and symptoms of scarlet fever, including the characteristic sandpaper-like rash, strawberry tongue, Pastia lines, and associated pharyngitis in patients with Group A Streptococcus infection.
• Implement timely and appropriate antibiotic therapy for scarlet fever, recognizing penicillin as the first-line treatment for non-allergic patients and selecting alternatives based on regional antibiotic resistance profiles.
• Apply appropriate diagnostic strategies by identifying and interpreting rapid antigen detection tests and throat cultures to confirm Streptococcus pyogenes infection in suspected cases of scarlet fever.
• Collaborate effectively with an interprofessional healthcare team—including pediatricians, pharmacists, infectious disease specialists, and nurses—to ensure comprehensive care, patient education, and infection control measures.

Introduction

Scarlet fever is a syndrome characterized by a blanching, erythematous, maculopapular rash often described as sandpaper-like, strawberry tongue, and exudative pharyngitis (see Image. Scarlet Fever).[1] The causative organism, Streptococcus pyogenes (Lancefield Group A Streptococcus, or Strep A), is a gram-positive bacterium adapted to humans. This organism grows in pairs and chains and is responsible for a wide spectrum of infections, ranging from superficial to deep and invasive conditions, including cellulitis, pharyngitis, erysipelas, toxic shock syndrome, and necrotizing fasciitis.[2]

Strep A produces streptococcal pyrogenic exotoxins (SPEs), which act as superantigens released during infection. These exotoxins are the primary cause of the erythematous rash associated with scarlet fever. Strep A bacterial pharyngitis and scarlet fever most commonly affect school-aged and adolescent children due to higher transmissibility in school settings. However, these infections can also occur in other age groups, particularly in crowded environments such as households and nursing homes.[3][4][5]

Scarlet fever caused by Strep A infections can occur at any age. Although it is most commonly associated with Strep A pharyngitis, it may also develop with other Strep A infections, whether invasive or noninvasive, such as erysipelas or necrotizing fasciitis. Historically, Strep A serotypes have displayed cyclic epidemiological patterns. Notably, Strep A is among the few bacteria that produce superantigen exotoxins, which are exceptionally potent T-cell activators. Strep A superantigens, also known as erythrogenic or scarlet fever toxins, are responsible for the characteristic erythematous, sandpaper-like rash and strawberry tongue observed in scarlet fever.[6] Superantigen genes, such as speA, speC, and ssa, enhance the fitness and virulence of Strep A, contributing to the development of invasive disease.[7][8]

Scarlet fever epidemics and invasive Strep A infections were common in the 19th century.[9][10] Although the prevalence of scarlet fever declined in the 20th century, a resurgence of Strep A infections occurred in the 1980s.[10] Over the past decade, more virulent epidemic strains of Strep A have emerged, leading to increased Strep A infections and scarlet fever.[10][11] Suppurative and nonsuppurative complications can arise from Strep A infections, including rheumatic heart disease and poststreptococcal glomerulonephritis. Prompt treatment of acute infections is essential to prevent these complications.

Etiology

S pyogenes is a gram-positive, non–spore-forming, and catalase- and oxidase-negative bacterium that grows in pairs and chains.[2] S pyogenes thrives on blood agar when incubated at 35 to 37 °C, with optimal growth in a 10% carbon dioxide environment. The bacterium forms smooth, moist, greyish-white colonies with clear margins, measuring over 0.5 mm.[7] The colonies are surrΟunded by a zone of complete hemolysis (β-hemolysis).[7] Strep A is a human-adapted pathogen and is not a ubiquitous environmental organism. The only known reservoirs in humans are the mucous membranes and skin. Strep A commonly causes a wide range of upper respiratory tract and skin infections, including pharyngitis, scarlet fever, impetigo, cellulitis, and erysipelas. These infections can vary in severity, ranging from mild, superficial infections to severe, invasive Group A Streptococcus (iGAS).[7][12]

Invasive infections typically occur in normally sterile sites, such as the bloodstream, cerebrospinal fluid, or the pleural space. Both Strep A and iGAS infections are increasing globally, with high morbidity and mortality rates.[7][12] In addition to acute infections, Strep A infections can trigger immune-mediated sequelae, including acute rheumatic fever, poststreptococcal glomerulonephritis, and rheumatic heart disease. Recent data suggest that in the United States, 1% to 3% of patients with untreated Strep A infections, typically Strep A pharyngitis, develop acute rheumatic fever, and nearly 60% of these cases progress to chronic rheumatic heart disease.[13]

The Lancefield classification categorizes streptococci into serological groups designated A-O, based on reactions between antisera and carbohydrate antigens on the streptococcal cell wall.[14] At least 20 serological groups have been identified, including groups A, B, and C. Strep A belongs to Lancefield group A.[15][16] Other streptococci in different Lancefield groups can cause syndromes similar to those caused by Strep A. Notably, group B Streptococcus (S agalactiae) colonizes the human gastrointestinal and genital mucosa and can cause puerperal sepsis and neonatal infections, including pneumonia, bacteremia, and meningitis.[17] 

Many virulence determinants have been identified in Strep A, enabling them to perform key processes such as adhesion, colonization, immune evasion, invasion, and dissemination within the host.[18] Prominent virulence factors include the M-protein, hyaluronic acid, streptokinase, and DNase B. Notable toxins, such as pyrogenic toxins (also known as scarlatina toxins or erythrogenic toxins), are responsible for the rash in scarlet fever. These toxins also induce mononuclear cells to produce tumor necrosis factor-α, interleukin (IL)-1, and IL-6, which may contribute to fever and shock in patients with streptococcal toxic shock syndrome.[7][19]

M-protein serotypes further classify S pyogenes based on the specific M and T antigens expressed on its surface.[14] Traditional serotyping methods for detecting these antigens have largely been replaced by sequence typing of the N-terminal region of the M-protein (emm) gene, which is now widely used for genotyping Strep A, particularly for epidemiological studies.[14][20] Whole-genome sequencing is increasingly used to identify epidemic strains.

To date, more than 250 emm types have been identified based on the M-protein gene sequence.[21] The streptococcal M-protein, encoded by the emm gene and used for epidemiologic typing, contributes to virulence and strain differentiation and holds potential as a vaccine antigen.[20][22] Emm1 strains are particularly virulent and are frequently associated with invasive infections.[23] Specific emm types, such as M1, M2, M3, M4, M6, M12, and M22, have been linked to scarlet fever outbreaks. A global resurgence of scarlet fever has been reported in regions including the United Kingdom, Hong Kong, mainland China, and Korea, often associated with the emergence of novel emm clones.[24][25]

Strep A is one of the few bacteria capable of producing superantigen exotoxins, which are among the most potent T-cell activators. These superantigens, also referred to as erythrogenic or scarlet fever toxins, are responsible for the erythematous sandpaper-like rash and strawberry tongue characteristic of scarlet fever.[6] In conditions such as streptococcal toxic shock syndrome, certain superantigenic exotoxins trigger atypical polyclonal activation of lymphocytes, leading to a rapid onset of shock and multiorgan failure with high mortality rates. Key identified superantigenic exotoxins include toxic shock syndrome toxin-1 and enterotoxins.[19][26]

Please see StatPearls' companion resource, "Streptococcus pyogenes," for further information.

Epidemiology

Epidemic scarlet fever, also known as scarlatina, is a cutaneous eruption caused by streptococcal pyrogenic exotoxins produced during Strep A infections in humans and is most commonly associated with Strep A pharyngitis. However, it can also arise from other Strep A infections. Scarlet fever is a toxin-mediated disease that tends to occur in epidemics approximately every 5 to 6 years, likely due to type-specific herd immunity. Historically, it caused significant morbidity and mortality during the 19th and early 20th centuries.[27] The prevalence of scarlet fever declined significantly in the latter half of the 20th century, likely due to the introduction of antibiotics, reducing its public health impact.[1][24] Characteristic symptoms of scarlet fever include a coarse, papular erythematous rash, a strawberry tongue, and exudative pharyngitis.[1]

Strep A exclusively infects humans and can affect many areas of the body.[2] Globally, Strep A infections are increasing, contributing to significant morbidity and mortality rates.[7][12] Transmission of Strep A occurs through respiratory secretions, fomites, and contact with infected skin, such as in impetigo. Although Strep A infections can affect individuals of any age, children, older adults, and immunocompromised individuals are at higher risk.[3] The incubation period for scarlet fever manifestations of Strep A ranges from 1 to 5 days, during which patients remain infectious and can transmit the bacteria to others.[3] Environmental factors and crowded settings, such as schools, households, and nursing homes, facilitate increased Strep A transmission.[3][4] Strep A commonly causes a variety of upper respiratory tract and skin infections, ranging from mild to severe and from superficial to iGAS.[7][12] Heavy shedding of Strep A in classrooms or other crowded spaces, even in asymptomatic individuals, can lead to outbreaks.[3]

Strep A has been reported to cause disease in young, healthy individuals, with a study's results noting its occurrence in 25% of those without risk factors.[4] Strep A may exist as an asymptomatic carrier in the pharynx or act as a pathogen causing Strep A pharyngitis. Within populations, an estimated 5% to 15% of individuals are asymptomatic carriers. Pharyngitis results from person-to-person transmission through oropharyngeal secretions and droplets from infected individuals.[18][28] Strep A infections can be categorized by location and depth, including pharyngitis, scarlet fever, impetigo (superficial keratin layer), cellulitis (subcutaneous tissue), erysipelas (superficial epidermis), and more invasive disease, including streptococcal toxic shock syndrome, myositis and myonecrosis (muscle), and necrotizing fasciitis (fascia).[29] In addition to these infections, Strep A can trigger immune-mediated sequelae, such as acute rheumatic fever and post-streptococcal glomerulonephritis, as well as direct sequelae of immune-mediated processes, such as rheumatic heart disease.[30]

The epidemiology of Strep A–related infections varies by infection type. Strep A pharyngitis most commonly affects children aged 5 to 15 and is the most common bacterial cause of acute bacterial pharyngitis in this age group. Transmissionis frequently linked to close contact with sick or asymptomatic children at school.[3][31] Strep A is the most common bacterial cause of acute pharyngitis and accounts for 5% to 15% of sore throat–related visits in adults and 20% to 30% in children who present with pharyngitis.[31][32][33]

Pharyngitis caused by Strep A typically occurs in the winter and early spring.[31] Severe illness and invasive infections exhibit a bimodal distribution, with higher rates in individuals aged 2 or younger and 50 or older.[28][34] Risk factors for increased mortality include advancing age; male sex; residence in a nursing home; chronic underlying illnesses; immunosuppression, including haemodialysis; recent surgery; septic shock; necrotizing fasciitis; concurrent viral infection; isolated bacteremia; and the presence of emm type 1 or 3 strains.[4][34]

The global prevalence of severe Strep A infections is estimated at 18.1 million cases, with 1.78 million new cases and 616 million cases of Strep A pharyngitis reported annually.[35] Severe Strep A infections are responsible for approximately 500,000 deaths globally each year, with the majority resulting from rheumatic heart disease and invasive infections.[35] The burden of iGAS is significant, accounting for approximately 663,000 new cases and 163,000 deaths annually.[35] Skin and soft tissue are the most common sites of infection, with 32% of patients presenting with cellulitis and 8% developing necrotizing fasciitis.[4]

Strep A emm1 strains are highly virulent, and the M-protein, encoded by the emm gene, serves as a key virulence factor in Strep A.[36] The resurgence of Strep A infections in the 1980s was attributed to the emergence of emm1 as the predominant cause of iGAS infections following genetic changes.[37] Strep A emm1 strains are highly virulent and associated with invasive infections.[38] Specific strains, including M1, M2, M3, M4, M6, M12, and M22, have been linked to scarlet fever outbreaks. A global reemergence of scarlet fever has been reported in countries such as the United Kingdom, Hong Kong, mainland China, and Korea, and is often associated with novel emm clones.[24][25] 

Epidemiological surveillance is crucial for monitoring epidemics, particularly given the increasing incidence and burden of Strep A infections, including iGAS, worldwide. Whole-genome sequencing plays a key role in this monitoring.[12][14][21][34][35] Since 2000, the dominant emm types in Europe and North America have been emm1 and emm3, with emm1 being the dominant type associated with invasive infections in high-income countries.[36] The 7 emm types responsible for 50% to 70% of iGAS infections are emm1, emm28, emm89, emm3, emm12, emm4, and emm6.[14][39] These emm types are collectively referred to as M1_global.[40] In contrast, in Australia, which has one of the highest rates of iGAS in the world, emm types differ according to geographical location and rates of sequelae.[41][42][43][44][45]

In 2011, a scarlet fever outbreak in Hong Kong documented a 10-fold increase in cases compared to the baseline and was associated with Strep A types emm12 and emm1. Among the isolates cultured during that year, emm12 was the dominant clone.[46] Strep A strains harboring these emm types had acquired mutations that enhanced their virulence and transmissibility.[46] Surveillance of emm types in Hong Kong revealed that these new strains exhibited increased resistance to macrolides and clindamycin, due to the acquisition of resistance genes from bacteria in the human urogenital and gastrointestinal tracts.[47] 

Following the Hong Kong outbreak, whole gene sequencing revealed an increase in scarlet fever cases in mainland China, with the expansion of emm12 clones contributing to the rise in infections.[25] Furthermore, the analysis revealed that the mobile genetic elements involved in the spread were the streptococcal toxin-encoding prophages φHKU.vir and φHKU.ssa, as well as the macrolide and tetracycline-resistant ICE-emm12 and ICE-HKU397. These findings indicate that multiclonal emm12 isolates had a significant role in expanding scarlet fever lineages both in China and globally.[25][48]

A new emm1 sublineage, termed M1_UK, was identified in 2008 in the United Kingdom and was associated with increased expression of the scarlet fever toxin and SPE-A (speA). Epidemiological surveillance during the 2014 scarlet fever outbreak in the United Kingdom revealed that regional outbreaks were caused by multiple emm types, including emm3, emm12, emm1, and emm4, as well as by various phylogenetic lineages. A significant increase in the prevalence of the ssa gene was associated with scarlet fever cases.[17] The M1_UK lineage was responsible for the rise in cases, outbreaks, and invasive infections in the United Kingdom from 2014 to 2018, eventually becoming the dominant strain in the country.[38][49][50] By 2020, the M1_UK lineage accounted for 91% of invasive emm1 isolates in the United Kingdom.[38] The incidence of scarlet fever declined during the COVID-19 pandemic.

Following the COVID-19 pandemic, 3 emerging M1_UK clades rapidly expanded across the United Kingdom, resulting in severe outcomes in children. The emergence of a new dominant clone within the emm1 genetic lineage, designated M1_UK, was first reported in the United Kingdom in 2019. This clone was associated with seasonal outbreaks of scarlet fever and an increase in invasive infections, likely driven by a 10-fold overproduction of speA superantigen, also known as erythrogenic toxin A or scarlet fever toxin.[50] The genomic structure of the M1_UK lineage differed from that of the classic M1T1 strain, having accumulated an additional 27 single-nucleotide polymorphisms that led to enhanced speA superantigen production compared to M1T1 isolates.[23] 

The M1_UK lineage appears to have outcompeted the globally dominant emm1 M1_global strain, which had been widespread since the 1980s. M1_UK strains were found to produce higher levels of the superantigenic scarlet fever toxin speA compared to contemporary M1_global strains.[38] Although declining immunity may contribute to streptococcal outbreaks, the genetic characteristics of M1_UK suggest a fitness advantage in pathogenicity and an exceptional ability to endure population bottlenecks. M1_UK is now the dominant strain in the United Kingdom. Two other lineages, M113SNPs and M123SNPs, were also identified.[36][51] GAS emm1 strains are responsible for more than 50% of invasive infections in children in the United Kingdom during the 2022 to 2023 season.[36][38] All globally sequenced M1_UK isolates (speA) can be traced back to the United Kingdom, where they caused an epidemic and have since spread into Europe and internationally.[36][52]

Pathophysiology

Many Strep A virulence determinants facilitate key processes, including adhesion, colonization, evasion of the innate immune system, invasion, and dissemination within the host.[18] Key virulence factors include the M-protein, hyaluronic acid, streptokinase, and DNase B. The M-protein allows S pyogenes to attach to epithelial cells by binding to CD46 and CD44 and stimulates the development of plasmin and fibrinogen against Strep A, harnessing these host factors to evade the adaptive immune response.[18] Hyaluronic acid also helps shield Strep A from the immune response by binding to host epithelial cells and mimicking human hyaluronic acid.[53] Streptokinase activates tissue plasminogen, leading to fibrinolysis and degradation of the extracellular matrix within host cells to facilitate infiltration.[54] The extracellular nuclease DNAse allows Strep A to degrade neutrophil DNA and suppress the toll-like receptor 9–mediated host signalling, thereby allowing it to evade and survive the host immune response.[55][56]

Notable toxins include pyrogenic toxins, also called scarlatina or erythrogenic toxins, which cause the rash observed in scarlet fever. These toxins also induce mononuclear cells to produce tumor necrosis factor α, IL-1, and IL-6, potentially contributing to fever and shock in patients with streptococcal toxic shock syndrome.[7][19][57]

The streptococcal M-protein, encoded by the emm gene and used for epidemiological typing, is also a critical virulence factor and a potential vaccine antigen.[20] Strains classified as emm1 are particularly virulent and frequently implicated in invasive infections. Specific emm types, including M1, M2, M3, M4, M6, M12, and M22, have been associated with scarlet fever outbreaks. A global resurgence of scarlet fever has been reported in countries such as the United Kingdom, Hong Kong, mainland China, and South Korea, and it is often linked to the emergence of novel emm clones.[24][25]

S pyogenes is one of the few bacteria that produce superantigen exotoxins, which are among the most potent activators of T cells. Strep A superantigens, also known as erythrogenic or scarlet fever toxins, are responsible for the erythematous sandpaper rash and strawberry tongue characteristic of scarlet fever.[6] In syndromes such as streptococcal toxic shock syndrome, certain bacterial superantigenic exotoxins cause atypical polyclonal lymphocyte activation, leading to rapid-onset shock, multiorgan failure, and high mortality. The primary superantigenic exotoxins implicated include toxic shock syndrome toxin-1 and enterotoxins.[19]

The scarlet fever rash was once believed to result from primary toxicity caused by Strep A. However, it is now understood to stem from a delayed host-acquired hypersensitivity reaction to streptococcal superantigens. Furthermore, the rash typically appears in individuals who have been previously exposed to Strep A and are thus pre-sensitized. At the same time, it is absent in those with no prior Strep A infection. The skin reactivity is likely due to rapid cytokine release and leukocyte presence, triggered by the amplified response to Strep A superantigens during secondary antigen exposure.[58][59]

Histopathology

Scarlet fever does not exhibit specific histological changes. Reported findings may include neutrophilic infiltrates, spongiosis, and parakeratosis within the epidermis.

History and Physical

Obtaining a detailed history of the presenting illness and past medical history is essential for evaluating patients with symptoms of infection. Patients may seek medical attention for complaints such as pharyngitis or cellulitis without initially noticing the rash. Scarlet fever is most commonly associated with acute pharyngitis caused by Strep A, but may also result from other manifestations of Strep A, such as erysipelas or wound infections.[58] The incubation period for Strep A ranges from 1 to 5 days. The characteristic rash of scarlet fever typically appears 24 to 48 hours after the onset of initial symptoms, most commonly Strep A pharyngitis.

The most common symptoms of Strep A pharyngitis include a sudden onset of fever and sore throat. Additional complaints may include headache, flushing around the mouth, nausea, chills, vomiting, and abdominal pain.[60] Conjunctivitis, cough, coryza, emesis, or diarrhea may be present and typically suggest a viral etiology rather than Strep A.[61] When taking a patient's history, it is common to note exposure to close contact with a Strep A infection, particularly among school-aged children or individuals residing in community settings, such as nursing homes, where close living conditions can increase the risk of transmission. 

On physical examination, findings of Strep A pharyngitis typically include generalized inflammation of the tonsils and pharynx, variable tonsillar exudates, a red and swollen uvula, and palatal petechiae. Tender cervical lymphadenopathy is also commonly palpable.[60] Physical examination of the posterior oropharynx alone is generally insufficient to differentiate Strep A from other causes of acute pharyngitis, such as viral pharyngitis, which is the most common type. Although the Centor criteria were developed to assist in the clinical diagnosis of Strep A pharyngitis, they are not reliable as a standalone tool and should be supplemented with microbiological testing for accurate diagnosis.[60][62] The score is based on 4 symptoms and signs associated with Strep A pharyngitis, including tonsillar exudates, tender anterior cervical adenopathy, absence of cough, and a history of fever >100.4 °F (38 °C). A score of 3 or higher is associated with high specificity for infection.[63]

A thorough skin examination is essential, as a fine, blanching, maculopapular erythematous rash accompanied by a strawberry tongue strongly suggests scarlet fever.[63] The rash associated with scarlet fever typically appears 2 to 3 days after the onset of infection but can be delayed for up to 7 days. The rashes generally begin on the trunk, underarms, and groin, spreading to the extremities while sparing the palms and soles.[63] The area around the mouth remains pale, creating a distinctive circumoral pallor. A characteristic strawberry tongue develops, initially presenting with a white membrane on the tongue and enlarged, protruding papillae, referred to as a white strawberry tongue. As the membrane sloughs off, the papillae persist, giving the tongue a red, strawberry-like appearance.[63] Pastia lines are linear clusters of papules observed in skin folds or pressure points, such as the neck, antecubital fossa, and groin. After the initial rash subsides, a phase of skin desquamation may occur, sometimes lasting up to 2 weeks.[63]

Evaluation

When evaluating a patient with scarlet fever, characterized by a blanching, maculopapular, sandpaper-like rash or other compatible physical findings, it is essential to identify the source of Strep A infection. Because scarlet fever is most commonly associated with Strep A pharyngitis, using the Centor criteria, combined with laboratory testing when necessary, can help confirm or rule out the diagnosis.[64][65][66] If pharyngitis is excluded, other potential primary sites of Strep A infection should be investigated, which necessitates a thorough physical examination.

Laboratory testing for Strep A pharyngitis involves a throat swab and culture, which remains the gold standard for identifying S. pyogenes. This bacterium grows readily on sheep blood agar and is both catalase- and oxidase-negative. Confirmatory identification can be performed using Lancefield grouping or more advanced methods, such as matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.[2][67] However, culture results typically take 24 hours or longer, which may delay critical decisions related to treatment, isolation, and epidemiological considerations.

A rapid antigen detection test can also be used to diagnose Strep A pharyngitis. This test has a sensitivity of approximately 85% in children, with some variability, and a specificity of 95%.[68] Given the test's high specificity in children, antibiotic therapy is recommended without a follow-up throat culture to distinguish infection from carriage. If the test result is negative, treatment decisions should follow national guidelines.[68] However, in the United States, adults typically have a lower general rate of Strep A pharyngitis, resulting in a low pretest probability. Therefore, when a negative test is obtained, confirmatory culture is generally not necessary, as a negative rapid swab strongly reduces the likelihood of Strep A infection.[61] To identify Strep A from superficial or deep body sites, such as skin, blood, wounds, or lungs, Gram staining and culture are recommended to establish a definitive diagnosis. A polymerase chain reaction test can also identify specific S pyogenes strains, particularly in complicated cases.[69]

Treatment / Management

Timely and accurate recognition of Strep A infections, particularly in patients with a scarlatiniform rash, can be challenging because many conditions may present with similar clinical features. The presence of a scarlatiniform rash accompanied by pharyngitis symptoms should strongly indicate scarlet fever as a leading diagnostic consideration. Diagnostic tests should be performed promptly, and treatment should be initiated without delay. Strep A infections are associated with increased morbidity due to the potential for invasive disease and are among the top 10 infectious causes with the highest mortality rates.[10] Culture results are crucial for tailoring antibiotic therapy and ensuring that the initial empirical antibiotic regimen covers Strep A, especially given reports of penicillin resistance and increasing resistance of Strep A to macrolides and clindamycin.[60]

β-lactam antibiotics remain consistently effective against Strep A and scarlet fever and are the preferred treatment for both noninvasive and iGAS infections. Although it is still recommended to complete a 10-day course of oral antibiotics when treating scarlet fever, the symptomatic benefit of treating uncomplicated Strep A pharyngitis is less clear.[70][71] The benefit lies in treating to limit transmission to vulnerable contacts (eg, maternal-neonatal pairs, those older than 75) and to reduce the likelihood of suppurative and non-suppurative complications, especially in high-prevalence settings.[72]

Recommended treatment regimens for scarlet fever include penicillin V or amoxicillin for 10 days, which is administered by mouth.[60] An alternative treatment is a single intramuscular dose of penicillin G benzathine, particularly for patients who may not complete the full course of oral antibiotics.[60][61] Macrolides (eg, azithromycin) or lincosamides (eg, clindamycin) can be used for patients allergic to penicillin. However, local resistance patterns should be considered, and their efficacy has not been shown to be superior to that of penicillin-based therapy.[60][70] For uncomplicated Strep A pharyngitis in high-resource, low-prevalence settings, symptomatic improvement with beta-lactam antibiotics may not be superior to placebo.[71] Once antibiotics have been commenced for 24 hours and the patient with scarlet fever has defervesced, the risk of human-to-human transmission is limited, and restrictions on usual activities can be lifted.[64][73][64] Without antibiotic treatment, infected individuals may be at risk of transmitting Strep A to others for many days to weeks.[73]

Broad-spectrum antibiotics should be initiated for severe Strep A infections, such as necrotizing fasciitis (eg, Ludwig's angina) and streptococcal toxic shock syndrome, to ensure adequate coverage while awaiting final culture results.[74] For severe infections, such as toxic shock syndrome toxin-1 and necrotizing fasciitis, clindamycin is often added to the antibiotic regimen, such as penicillin, as it may inhibit superantigen production and facilitate phagocytosis of S pyogenes by blocking M-protein production.[75] Despite some evidence suggesting the use of intravenous immunoglobulin to immunomodulate the cytokine cascade during streptococcal toxic shock syndrome, data remain conflicting, including in pediatric cases.[76][77][78][79] In addition to antibiotics, supportive measures—such as fluid resuscitation and blood pressure management with vasopressors—should also be implemented for these severe or systemic infections.[80][81]

Although there have been reports of penicillin resistance and increased minimum inhibitory concentrations to penicillin and cephalosporins, these are primarily attributed to mutations in the peptidoglycan-synthetic enzyme pbp2x gene. However, resistance rates remain low,[60][82] and penicillin remains the gold standard for treatment.[60][83] For patients allergic to penicillin, the most notable alternatives are macrolides (eg, erythromycin) and lincosamides (eg, clindamycin). However, resistance to these antibiotics has increased over the past decade, with variable prevalence of resistant S pyogenes strains observed globally.[IDSA. IDSA Clinical Practice Guideline Update on Group?A?Streptococcal (GAS) Pharyngitis][CDC. Clinical Guidance for Scarlet Fever][84] Once treatment has commenced and fevers have resolved for 24 hours, children can return to usual activities without risk of transmission to others. 

Reports from China indicate macrolide resistance rates as high as 90%, whereas some European countries report resistance rates of 20% to 40% for macrolides and up to 19% for lincosamides. In other parts of Europe and Australia, resistance rates may be as low as 2%.[44][84][85] These variations are attributed to macrolide resistance mechanisms, including those encoding the Macrolide-Lincosamide-Streptogramin B phenotype.[84][85][86] If these antibiotics are resistant, alternative antibiotics for penicillin-allergic patients can be considered. The choice of therapy should be based on the location and severity of the infection, local Strep A antibiotic resistance patterns, and the patient's allergy profile.[60] 

Differential Diagnosis

The differential diagnosis for fever and rash is broad. When a sandpaper-like rash is observed, additional clinical findings, signs, and symptoms should be evaluated to confirm the diagnosis of scarlet fever and to distinguish it from other potential causes. Key supporting features of scarlet fever include strawberry tongue and Pastia lines, which strongly suggest the diagnosis. When scarlet fever is suspected, it is vital to identify the source of the Strep A infection, such as Strep A pharyngitis, impetigo, or erysipelas.

Other conditions to consider in the differential diagnosis of a rash include rubella; rubeola; mononucleosis caused by Epstein-Barr virus or cytomegalovirus; parvovirus B19; varicella; enteroviruses, such as Coxsackie virus, causing hand, foot, and mouth disease; Arcanobacterium haemolyticum; Kawasaki disease; toxic shock syndrome; staphylococcal scalded skin syndrome; other viral exanthems, such as measles and parvovirus; and drug reactions.

Pertinent Studies and Ongoing Trials

Recent evidence for the management of scarlet fever and other Strep A infections includes insights from cutting-edge clinical trials and epidemiological studies conducted through 2024 and 2025. A notable ongoing trial is the CHIVAS-M1 project, the world's only modern S pyogenes–controlled human infection model, which studies the M1_UK strain—currently the globally dominant and highly virulent emm type linked to scarlet fever outbreaks and iGAS disease. This controlled human infection model enables a precise study of host-pathogen interactions and is instrumental for evaluating vaccine candidates by measuring protection against pharyngitis and potentially invasive complications.[NIH. A Strep Throat Controlled Human Infection Trial in Healthy Adults (CHIVAS-M1)]

Epidemiological surveillance in England for the 2024 to 2025 season reports that scarlet fever incidence is following normal seasonal patterns after the elevated rates seen in earlier years post-pandemic. Genomic studies highlight the emergence of the emm49.8 gene type, characterized by notable resistance to erythromycin and tetracycline, in contrast to prior dominant emm types, such as emm3.93, which exhibited lower resistance profiles. Penicillin remains uniformly effective against all Strep A strains.[UK Health Security Agency. Group A streptococcal infections: first update on seasonal activity in England, 2024 to 2025] Furthermore, reports following the emergence of the globally dominant M1UK strain suggest an epidemiological association between preceding respiratory infections and subsequent iGAS disease.[87][88][88]

Findings from a 2024 retrospective study have confirmed the rising incidence of iGAS infections, with a predominance of emm1 (mostly M1_UK) and emm12 genotypes. These genotypes are linked with increased severity and mortality in pediatric populations, stressing the critical need for early diagnosis and effective treatment strategies.[CDC. Severe Group A Streptococcus Infection among Children, France, 2022–2024] Older, but relevant, controlled treatment trials confirm that penicillin remains highly effective in shortening febrile periods and reducing complications in scarlet fever. At the same time, alternative regimens (shorter courses) have not shown significant differences in outcomes or adverse events.[44][89][90][91] Post-pandemic research reveals a resurgence in Strep A infections worldwide, with genetic shifts that may impact virulence and transmissibility. These data support prioritizing vaccine development and advanced molecular surveillance to curb this public health burden.

Toxicity and Adverse Effect Management

Antibiotic therapy for scarlet fever is generally well tolerated, but adverse effects can occur and require appropriate management.

Common Toxicities

• Allergic reactions to β-lactam antibiotics, including penicillin and amoxicillin, range from mild rash to severe anaphylaxis. Patients with known allergies should receive alternative agents, such as macrolides and clindamycin, with careful monitoring for hypersensitivity.[92]
• Gastrointestinal upset such as nausea, vomiting, diarrhea, and antibiotic-associated colitis may occur, particularly with macrolide or clindamycin use. Supportive care includes hydration and symptomatic treatment; severe diarrhea warrants evaluation for Clostridioides difficile infection.[93]
• Macrolide resistance has increased, potentially affecting treatment efficacy and leading to prolonged infections or complications if not identified and managed early.[44][94]

Severe Toxicities

• Toxic shock syndrome and necrotizing fasciitis are rare but life-threatening complications of iGAS infections. Early recognition and multidisciplinary management in intensive care settings are essential.
• Management involves the prompt initiation of broad-spectrum antibiotics, such as clindamycin; surgical debridement if applicable; fluid resuscitation; vasopressors; and supportive care for organ dysfunction.

Monitoring and Prevention

• Patients on antibiotics should be monitored for hypersensitivity reactions and any signs of superinfection.
• Patients and caregivers should be instructed to promptly report rash, difficulty breathing, persistent diarrhea, or signs of severe illness.
• Unnecessary antibiotic use should be avoided to minimize the development of resistance.

Prognosis

The prognosis for scarlet fever today is excellent, a significant improvement from the early 20th century. This progress is primarily attributed to the introduction of antibiotics and advances in rapid diagnosis. Once treatment begins, patients can typically resume regular activities 24 hours after their fever resolves. However, if left untreated, the condition may worsen, increasing the risk of complications related to Strep A infection. In an observational study of clinical syndromes associated with more severe pediatric iGAS presentations,  these included a positive COVID-19 diagnosis, pulmonary manifestations, streptococcal toxic shock syndrome, and meningitis or encephalitis. Other clinical factors included reduced consciousness, dyspnea, abnormal auscultatory findings, and elevated C-reactive protein.[95] Specifically, having a post–COVID-19 pandemic diagnosis was associated with higher mortality and intensive care admission rates than pre–COVID-19 pandemic cases, though it was unclear whether these cases were vaccinated against SARS-CoV-2.

Evidence indicates that diagnostic delays at the initial consultation, particularly for children aged 5 or older presenting with a sore throat, are associated with longer time to return to usual baseline activity.[96] The occurrence of scarlet fever among children in close proximity within enclosed environments, such as schools and childcare centers, increases the risk of outbreaks, with attack rates of up to 30% among susceptible children.[27]

For most patients who receive prompt treatment, the prognosis is excellent. Recovery typically occurs within 3 to 6 days, although skin symptoms may persist for 14 to 21 days. In some cases, the infection can recur. With the advent of antibiotics, the mortality rate for scarlet fever is now less than 1%. Morbidity is primarily associated with complications such as glomerulonephritis, rheumatic fever, sinusitis, and other infections, although these complications are rare.[97][98]

Complications

Historically, scarlet fever had a high complication rate and significant mortality among children. However, with the introduction of antibiotics, scarlet fever is now considered a relatively mild disease. Notably, delayed or untreated Strep A infections can still lead to severe complications, which are categorized as either suppurative or non-suppurative.

Suppurative complications typically arise from the worsening or spread of the original infection site. For instance, bacterial pharyngitis may spread to the ear, leading to otitis media; to the sinuses, causing sinusitis; or to the meninges, resulting in bacterial meningitis. In contrast, non-suppurative complications are typically immune-mediated and occur after the initial infection has resolved. Rheumatic fever, which affects the heart valves, is a notable non-suppurative complication of Strep A infections and can result in significant long-term morbidity. Although scarlet fever does not directly cause complications, Strep A infections can lead to the issues mentioned below.

Suppurative Complications 

• Peritonsillar or pharyngeal abscess [99]
• Otitis media
• Sinusitis
• Impetigo and pyoderma [100]
• Streptococcal bacteremia [44]
• Meningitis or brain abscess
• Necrotizing pneumonia and empyema [101]
• Poststreptococcal reactive arthritis [102]
• Streptococcal toxic shock syndrome
• Poststreptococcal glomerulonephritis [103]
• Sydenham's chorea
• Pediatric autoimmune neuropsychiatric disorder associated with Strep A infections (PANDAS): A condition linked to neuropsychiatric symptoms such as tic disorders and obsessive-compulsive disorder, though the exact relationship remains controversial.

Please see StatPearls' companion resources, "Streptococcal Pharyngitis," "Acute Rheumatic Fever," "Rheumatic Heart Disease," "Toxic Shock Syndrome," "Sydenham Chorea," and "Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)," for further information.

Consultations

For patients with scarlet fever, consultations may be warranted depending on disease severity, complications, and patient-specific factors.

• Infectious disease specialist: For complicated or severe iGAS infections, such as invasive disease, streptococcal toxic shock syndrome, or recurrent scarlet fever, involving an infectious disease specialist can optimize management and guide therapy adjustments, including antibiotic resistance considerations and advanced diagnostics.[104]
• Pediatrician: As scarlet fever primarily affects children, pediatric consultation ensures age-appropriate management, monitoring for complications such as acute rheumatic fever and PANDAS, referral to pediatric intensive care as required, and guidance on immunizations and follow-up care.[105]
• Otolaryngologist: Referral to ear, nose, and throat clinicians may be necessary for suppurative complications, such as peritonsillar abscess or severe pharyngitis requiring drainage or surgical intervention, and recognition of non-suppurative complications, for ongoing referral.[106][107]
• General surgeon: Early surgical consultation is required for skin and soft tissue infections outside the head and neck region in areas of high Strep A endemicity, as iGAS can rapidly progress to necrotising fasciitis without prompt antimicrobial therapy.[44]
• Nephrologist/cardiologist: In cases of suspected or confirmed non-suppurative complications such as acute glomerulonephritis or rheumatic heart disease, input from nephrology or cardiology specialists is crucial for comprehensive care and long-term management.
• Critical care/intensive care specialist: Patients with severe systemic illness, including streptococcal toxic shock syndrome or necrotizing fasciitis, require multidisciplinary critical care for hemodynamic support, surgical management, and monitoring of organ dysfunction.

Deterrence and Patient Education

Prevention of scarlet fever and other infections transmitted via fomites and respiratory droplets relies on fundamental hygiene practices, including frequent handwashing, covering coughs and sneezes, routine disinfection of commonly touched surfaces, and avoiding close contact with others when symptomatic or infected.[108][109][110] During outbreaks in school or childcare settings, affected individuals should be excluded until clinically improved or until antibiotic treatment has been commenced for at least 24 hours.[27] Public health campaigns using posters, media announcements, and community engagement are effective in reinforcing these behaviors.

Given that preceding vaccine-preventable viral infections, such as varicella-zoster virus and influenza, can predispose to Strep A infection, vaccination should be encouraged for individuals at risk.[111][112] Treatment of vulnerable close contacts of confirmed iGAS cases, such as older adults and neonates, should be considered with penicillin, cefalosporin, or macrolide therapy to reduce the risk of onward transmission.[110][113]

Public education on the prudent use of antibiotics is equally critical to addressing the growing problem of antibiotic-resistant S pyogenes strains, as there are increasing reports of clindamycin, macrolides, and tetracyclines worldwide.[44][114][115] Overuse and misuse of antibiotics contribute significantly to resistance, complicating treatment and increasing the risk of severe infections, including C difficile infection.[116] At the provider level, managing patient expectations regarding antibiotic prescriptions and promoting awareness of appropriate antibiotic use are essential to improving adherence to prescribed therapies and reducing unnecessary antibiotic exposure, particularly for self-limiting conditions such as uncomplicated otitis media and the common cold. Together, these strategies form a comprehensive deterrence and education approach to reduce scarlet fever incidence, transmission, and complications. 

Pearls and Other Issues

Pearls and Other Considerations

• Scarlet fever is a clinical diagnosis supported by the characteristic sandpaper rash, strawberry tongue, Pastia lines, and history of recent pharyngitis or other Strep A infections.
• Rapid initiation of antibiotic therapy in suppurative manifestations significantly reduces the risk of complications, curtails transmission, and enables patients to return to normal activities within 24 hours of fever resolution. However, for uncomplicated streptococcal pharyngitis, emerging evidence suggests that antibiotics may not result in clinically significant differences in fever duration or pain intensity in otherwise well children in high-resource settings. [71]
• The M-protein and its emm gene typing remain fundamental in understanding Strep A epidemiology and virulence, with emm1, particularly the M1_UK lineage, implicated in recent scarlet fever resurgence and invasive infections.[51]
• The use of rapid antigen detection tests alongside the Centor criteria improves sensitivity and specificity in diagnosing Strep A pharyngitis, which is key to timely treatment.[117][118][119]

Disposition

• Most patients with uncomplicated scarlet fever can be treated as outpatients, with clinician discretion on oral antibiotics and supportive care.[71]
• Hospitalization is indicated for patients with severe or invasive infections; complications, such as abscesses, toxic shock syndrome, and necrotizing fasciitis; or those unable to tolerate oral therapy.
• Close monitoring for complications such as acute rheumatic fever, post-streptococcal glomerulonephritis, and streptococcal toxic shock syndrome is essential, especially in high-risk populations.

Pitfalls

• Failure to recognize atypical presentations or delays in diagnosis can lead to severe suppurative and non-suppurative complications.[96]
• Overreliance on clinical criteria without confirmatory testing in ambiguous cases may lead to unnecessary antibiotic use or missed diagnoses.
• Increasing macrolide and clindamycin resistance requires awareness of local antibiograms to guide alternative treatment choices for penicillin-allergic patients.[94][114]

Prevention

• Good hand hygiene, respiratory etiquette, environmental cleaning, and exclusion from schools or workplaces during infectious periods are key to controlling outbreaks.
• Public health surveillance and genomic monitoring of Strep A strains enable early identification of epidemic clones and guide vaccine development.
• Patient and caregiver education on the importance of antibiotic adherence and the avoidance of antibiotic misuse are central to preventing resistance.

Additional Note

• There are currently no licensed vaccines for scarlet fever or Strep A infections. Still, research using controlled human infection models aims to accelerate vaccine development, offering hope for future primary prevention strategies.

Enhancing Healthcare Team Outcomes

Optimal management of scarlet fever requires a coordinated interprofessional healthcare team approach. Patient education is pivotal, with pharmacists playing a key role in reinforcing the necessity of completing the full antibiotic course to ensure eradication of Strep A, prevent recurrence, and curb antimicrobial resistance. Clinicians should work collaboratively to teach patients and caregivers about effective hand hygiene, respiratory etiquette, and environmental cleaning to prevent bacterial spread. Infection control teams can screen contacts in the hospital setting and provide chemoprophylaxis to vulnerable close contacts. Timely communication with public health units is essential to recognize and respond to emerging outbreaks of iGAS.[120] Accurate counseling on the natural history of scarlet fever, including potential skin desquamation and signs of complications, empowers patients to recognize when to seek timely medical care. Such teamwork enhances treatment adherence, reduces transmission risks, and improves overall patient outcomes in the management of scarlet fever.

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Disclosure: Sarah Sabir declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Nguyen declares no relevant financial relationships with ineligible companies.