Scarlet Fever

Scarlet fever is a clinical syndrome consisting of streptococcal pharyngitis accompanied by fever and a characteristic rash caused by pyrogenic exotoxins. Scarlet fever is a non-suppurative complication of streptococcal infection that is more commonly seen in children. Incidence peaks during the winter and spring in temperate climates. The rash begins in the 1st 24–48 hours of illness. Starting in the face or neck, the exanthem spreads to the trunk and extremities but spares the palms and soles. With the infection, the face looks flushed, accompanied by circumoral pallor and a strawberry tongue (enlarged papillae). The minute papules feel like sandpaper. Diagnosis is usually made clinically, confirmed with a rapid antigen detection test (RADT) or throat culture. Treatment is with penicillin or amoxicillin.

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Overview

Definition

Scarlet fever (also called “scarlatina”) is a diffuse erythematous eruption or rash that occurs in association with pharyngitis.

Epidemiology

  • Occurs in children > adults: Children 5–15 years of age represent the majority of cases.
  • Peak incidence: winter and spring in temperate climates
  • Develops in < 10% of streptococcal throat infection
  • Has become uncommon since the introduction of penicillin

Etiology

  • Caused by β-hemolytic, pyrogenic toxin-producing strains of Streptococcus pyogenes, also known as Group A Streptococci (GAS)
  • Key mediator of the characteristic rash: streptococcal pyrogenic exotoxins (SPEs) A, B, and C

Pathophysiology

  • Transmission of S. pyogenes is primarily via respiratory secretions.
  • Local infection occurs:
    • Bacteria adhere to the pharyngeal epithelium, causing:
      • Pharyngitis (sore throat)
      • Purulent tonsillar exudate
      • Cervical lymphadenopathy
      • Fever
  • Some strains of S. pyogenes produce pyrogenic exotoxins, which act as superantigens:
    • Antigens stimulate T cells, which release cytokines leading to an inflammatory cutaneous reaction and blood vessel dilatation.
    • Produces the characteristic rash of scarlet fever
  • While the pharynx/throat is the most common site of replication, scarlet fever may follow streptococcal skin and soft tissue infection.

Streptococcus pyogenes (GAS)

Image: “Photomicrograph of Streptococcus pyogenes bacteria” by the Centers for Disease Control and Prevention. License: Public domain.

Clinical Presentation

Symptoms

  • Initial symptoms of a child with scarlet fever will often begin with:
    • Fever
    • Headache
    • Nausea and vomiting
    • Malaise
    • Sore throat with difficulty swallowing
  • Scarlet fever rash: 
    • Rash usually appears 24–48 hours after the onset of illness.
    • Diffuse, starting at the neck/upper trunk, spreading to the rest of the trunk and extremities
    • Spares the palms and soles
    • Most pronounced in the groin and axilla
    • Can last 5 days
    • 7–10 days after the resolution of the rash: skin desquamation (especially fingers, feet)

Signs

  • Vital signs: elevated body temperature
  • General appearance:
    • Ill appearing
    • Flushed face 
  • Head:
    • Circumoral pallor
    • Bright red mucous membranes with petechiae 
    • Erythematous, edematous tonsils with a white-grayish exudate
    • “Strawberry tongue” (enlarged papillae on a coated tongue):
      • Initially (24–48 hours), tongue is covered with a whitish membrane through which papillae protrude. 
      • The membrane sloughs off, and a reddish tongue and prominent papillae are seen.
  • Neck: cervical lymphadenopathy, often tender
  • Skin:
    • Rash:
      • In the neck/trunk, axilla, groin, and extremities (palms, soles spared)
      • Begins as small, flat, erythematous macules with a sunburn appearance that blanches with pressure
      • If seen later in the disease, small papules are noted, giving a coarse “sandpaper” feel to the skin.
    • “Pastia’s lines”: accentuated rash in skin folds (e.g., axilla)

“Strawberry tongue”: early in the disease, the tongue could be covered by a white membrane or coating through which the papillae are seen. This layer sloughs off and reveals a bright red tongue with prominent papillae. A strawberry tongue results from a general inflammatory response early in the course of the disease.

Image by Lecturio.

Diagnosis and Management

Diagnosis

  • High suspicion based on symptomatology and examination
  • Streptococcal infection confirmed by:
    • Rapid antigen detection test (RADT):
      • In children and adolescents with negative RADT tests: Perform throat culture. 
      • Positive RADTs: A back-up culture is not needed.
    • Throat culture positive for S. pyogenes
  • Children < 3 years of age: No diagnostic tests are needed because acute rheumatic fever is rare in this age group.
  • Other non-specific laboratory findings (depending on the clinical picture and complication(s)) may include:
    • Complete blood count showing leukocytosis
    • Elevated inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR))

Management

Management consists of treating the causative agent of pharyngitis, Streptococcus pyogenes.

  • Goals:
    • Shorten the illness and reduce the spread of infection and suppurative complications.
    • Prevent acute rheumatic fever.
    • Prevent disease transmission.
  • Antibiotic therapy:
    • Amoxicillin or penicillin (drug of choice)
    • Cephalosporins (alternative)
    • In cases of penicillin allergy: clindamycin or macrolide (azithromycin)

Course and Complications

Usual course

  • Disease course is typically mild.
  • Clinical improvement is usually seen within days of starting antibiotics.
  • Without treatment, fever and acute illness abate by 5–7 days.
  • Desquamation occurs for up to 4 weeks and is self-limited.
  • Most cases resolve without complications.

Complications

  • Otitis media: acute inflammation of the middle ear
  • Sinusitis: acute inflammation of the paranasal sinuses
  • Peritonsillar and retropharyngeal abscesses: 
    • Local complication of pharyngitis 
    • Manifests as sore throat, localized throat/neck pain, in a toxic-appearing patient
  • Rheumatic fever: 
    • Delayed, non-suppurative, autoimmune sequelae of pharyngitis 
    • Occurs 2–4 weeks after infection
    • Major manifestations: arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum
  • Post-streptococcal glomerulonephritis:
    • Immune complex disease of the glomeruli after GAS infection (nephritogenic strain)
    • Can occur even with antibiotic treatment of preceding infection
    • Occurs 1–4 weeks after S. pyogenes infection (skin infection > pharyngitis)
    • Nephritis (proteinuria, edema, hypertension, and hematuria)
  • Bacteremia and sepsis: 
    • Severe form of S. pyogenes infection (hematogenous spread more commonly from skin and soft tissue infection) 
    • Associated with high fever, end organ damage, and marked systemic toxicity

Differential Diagnosis

  • Kawasaki’s disease: a childhood febrile vasculitis that can resemble scarlet fever by presenting with fevers, cervical adenopathy, buccal erythema, strawberry tongue, and desquamation of the skin from the fingertips. There may be conjunctival injection and erythema can be found on the palms and soles. Kawasaki’s disease often affects children < 5 years of age.
  • Measles: a maculopapular rash that begins behind the ears, hairline, and forehead. The lesions blanch on pressure. The viral illness is associated with a prodrome of fever, conjunctivitis, coryza, and cough. Koplik’s spots (small whitish or bluish papules with erythematous bases on the buccal mucosa), may be seen.
  • Staphylococcal toxic shock syndrome: an acute febrile illness, usually caused by toxin-producing S. aureus, but also occasionally by Streptococcus spp. (toxic shock-like syndrome). The rash is macular and erythematous, and involves the face, neck, axilla, and groin. The skin is tender with peeling areas of epidermis.
  • Adverse reaction to medication: morbilliform eruptions due to immune reactions to drugs. A morbilliform rash can occur in up to 5% of patients receiving drugs such as penicillins, sulfonamides, and phenytoin. The rash can be accompanied by pruritus, fever, eosinophilia, and lymphadenopathy.
Table: Comparison of common childhood rashes
NumberOther names for the diseaseEtiologyDescription
1st disease
  • Measles
  • Rubeola
  • 14-day measles
  • Morbilli
Measles morbillivirus
  • Cough, coryza, conjunctivitis
  • Koplik’s spots (blue-white spots with a red halo) on the buccal membrane
  • Maculopapular rash begins on the face and behind the ears → spreads to trunk/extremities
2nd disease
  • Scarlet Fever
  • Scarlatina
Streptococcus pyogenes
  • Sandpaper-feeling maculopapular rash that begins on the neck and groin → spreads to trunk/extremities
  • Dark, hyperpigmented areas, especially in skin creases, called Pastia’s lines
  • Strawberry tongue: coated white membrane through which swollen, red papillae protrude
3rd disease
  • Rubella
  • German measles
  • 3-day measles
Rubella virus
  • Asymptomatic in 50% of cases
  • Fine macular rash on the face (behind the ears) → spreads to the neck, trunk, and extremities (spares palms/soles)
  • Forscheimer’s spots: Pinpoint red macules and petechiae can be seen over the soft palate/uvula
  • Generalized tender lymphadenopathy
4th disease
  • Staphylococcal Scalded Skin Syndrome
  • Filatow-Dukes’ disease
  • Ritter’s disease
Due to Staphylococcus aureus strains that make epidermolytic (exfoliative) toxin
  • Some believe that 4rh disease is a misdiagnosis and, thus, nonexistent.
  • The term was dropped in the 1960s and is only used for medical trivia today.
  • Begins with a diffuse erythematous rash that usually begins around the mouth → fluid-filled bullae or cutaneous blisters → rupture and desquamate
  • Nikolsky’s sign: Applying pressure on the skin with a finger (stroking) results in sloughing off of upper layers.
5th diseaseErythema infectiosumErythrovirus or parvovirus B19 (Primate erythroparvovirus 1)
  • Facial erythema (“slapped-cheek rash”) that consist of red papules on the cheeks
  • Begins on the face → spreads to the extremities → extends to trunk/buttocks
  • Initially confluent, then becomes net-like or reticular as it clears
6th disease
  • Exanthem subitum
  • Roseola infantum
  • Rose rash of infants
  • 3-day fever
Human herpesvirus 6B or human herpesvirus 7
  • Sudden onset of high fever
  • Nagayama spots: papular spots on the soft palate/uvula
  • Rash begins as fever resolves (the term “exanthem subitum” describes “surprise” of rash after the fever subsides)
  • Numerous rose-pink, almond-shaped macules on the trunk and neck → sometimes spreads to face/extremities

References

  1. Bryant, A. E., & Stevens, D. L. (2020). Streptococcus pyogenes. In J. E. Bennett MD, R. Dolin MD, & M. J. Blaser MD (Eds.), Mandell, Douglas, and Bennett’s principles and practice of infectious diseases (pp. 2446-2461.e5). https://www.clinicalkey.es/#!/content/3-s2.0-B9780323482554001971
  2. Pichichero, M.E., & Baron, E.L. (Eds.) (2019). Complications of streptococcal tonsillopharyngitis. UpToDate. Retrieved 6 Dec 2020, from https://www.uptodate.com-streptococcal complications 
  3. Riedel, S., Hobden, J.A., Miller, S., Morse, S.A., Mietzner, T.A., Detrick, B., Mitchell, T.G., Sakanari, J.A., Hotez, P., & Mejia, R. (Eds.). (2019). The streptococci, enterococci, and related genera. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28e. McGraw-Hill.
  4. Sanders, M., & Speer, L. (2019). Scarlet fever and strawberry tongue. In Usatine, R.P., Smith, M.A., Mayeaux, Jr. E.J., & Chumley H.S. (Eds.). The Color Atlas and Synopsis of Family Medicine, 3e. McGraw-Hill.
  5. Sotoodian, B., & Rao, J. (2020). Scarlet fever. Medscape. Retrieved 6 Dec 2020, from https://emedicine.medscape.com/article/1053253-overview#a7
  6. Wald, E.R. (2020). Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis. UpToDate. Inc. Retrieved 6 Dec 2020 from https://www.uptodate.com- streptococcal tonsillopharyngitis
  7. Wessels, M. R. (2018). Streptococcal infections. In J. L. Jameson, A. S. Fauci, D. L. Kasper, S. L. Hauser, D. L. Longo, & J. Loscalzo (Eds.), Harrison’s principles of internal medicine, 20e. New York, NY: McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1160013257

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