Are You Confident of the Diagnosis?

What to be alert for in the history

Most patients develop a sudden onset of fever and sore throat and appear ill. Associated symptoms include headache, malaise, lymphadenopathy, chills, abdominal pain, nausea, vomiting, anorexia, and myalgias. The erythematous eruption appears 1 to 4 days following the onset of symptoms.

Characteristic findings on physical examination

The characteristic exanthem of scarlet fever consists of blanchable, confluent, erythematous macules and patches as well as minute papules that impart a dry, rough, sandpaper-like texture to the skin. It initially appears on the upper trunk and axillae then generalizes over days, spreading to the lower extremities last and sparing the palms and soles. There is accentuation in the flexural surfaces and dependent regions such as the buttocks.

Facial flushing with circumoral pallor is common.

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Pastia’s lines refer to the accentuation of erythema and linear petechiae in the skin folds. They tend to appear prior to the generalized eruption and may persist through the desquamative phase. Petechiae (Forschheimer spots) and erythematous macules may be present on the soft palate. Early in the course of infection, prominent, edematous papillae on the tongue are coated with a thick white membrane (“white strawberry tongue”). Within several days, a brightly erythematous tongue with prominent papillae (“red strawberry tongue”) appears as the membrane sloughs off.

The rash remits within 7 to 10 days and is followed approximately 1 week later by a fine, superficial desquamation especially marked in the skin flexures, face, palms, and soles (Figure 1). The desquamation may continue for up to 6 weeks. Depending on the severity of the illness, patients may develop late sequelae, such as Beau’s lines in the nails, and experience telogen effluvium, 3 to 4 months following infection.

Figure 1.

Acral subcorneal bullae starting to desquamate as noted in a woman with streptococcal pharyngitis

Expected results of diagnostic studies

Diagnosis can usually be made on clinical grounds Leukocytosis with a left shift is almost always present, and nasopharyngeal cultures positive for group A streptococci are confirmatory. A rapid group A streptococcus antigen test can be done and is often more convenient, although not as sensitive as a traditional culture. If the rapid test is positive, a confirmatory culture is unnecessary whereas a negative or equivocal result warrants a nasopharyngeal culture.

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are also elevated. Other laboratory tests that support the diagnosis include detection of antistreptolysin O (ASO), antihyaluronidase, antifibrinolysin, and anti-DNase B antibodies, although these are not specific to scarlet fever and are late findings. Mild albuminemia and hematuria may occur early in the infection, and urinalysis and liver function tests are helpful in assessing possible complications. Blood cultures are rarely positive in uncomplicated disease.

Biopsy is rarely warranted but specimens demonstrate engorged capillaries and dilated lymphatic vessels, most commonly in a perifollicular distribution. There is edema and a sparse polymorphonuclear perivascular infiltrate. There may be focal areas of hemorrhage. During the desquamative phase, epidermal spongiosis and prominent parakeratosis are present.

Diagnosis confirmation

The differential diagnosis of scarlet fever includes Kawasaki disease, toxic shock syndrome (TSS), staphylococcal scalded skin syndrome (SSSS), rubella, rubeola, mononucleosis, fifth disease, acute lupus erythematosis, juvenile arthritis, other viral exanthems, and drug reactions. Similar cutaneous findings can be seen with pharyngeal infections associated with Staphylococcus aureus, Arcanobacterium haemolyticum, Haemophilus influenzae, and Clostridium species.

The rash in fifth disease may resemble that seen in scarlet fever but it is rarely generalized, and the child appears clinically well.

In rubella and rubeola, the eruption progresses in a cephalocaudad spread rather than beginning on the trunk. Additionally, the triad of cough, coryza, and conjunctivitis is characteristic of rubeola.

Kawasaki disease is an important differential due to the high incidence of long-lasting cardiac sequelae if not treated appropriately. Similarly to scarlet fever, desquamation of the fingers, palms, and soles occurs in a majority of the patients 1 to 2 weeks following the onset of the fever. Asian children, most commonly in Japan, are affected. It rarely occurs in children older than 4 years of age.

Other bacteria-associated syndromes such as TSS and SSSS can be differentiated by hemodynamic instability and the sheet-like desquamation that occurs early in the course of disease, respectively. Tissue biopsy and direct immunofluorescence is helpful in further differentiating SSSS.

The various noninfectious diseases that may mimic the signs of scarlet fever should be considered and can usually be differentiated with a thorough history (ie, cutaneous drug eruption) and careful laboratory workup.

Who is at Risk for Developing this Disease?

Young children between 1 to 10 years old are most frequently affected, since by the age of 10 most develop antibodies to the pathogenic toxins, although adults may rarely be affected. The infection is most common in the late fall, winter, and spring in cooler climates.

What is the Cause of the Disease?

Scarlet fever is a toxin-mediated infection caused by the group A beta-hemolytic streptococcus (GAS) Streptococcus pyogenes. Several microbiologic factors are known to confer antigenicity and virulence to S pyogenes. Since 1933, numerous Lancefield groups have been identified, from A-T, based on the antigenic carbohydrate constituents of the bacterial cell wall. GAS is also subdivided based on the expression of M and T surface antigens.

The M-protein antigen, which is also expressed by Lancefield groups C and G, is the main virulence factor. M proteins are extracellular surface antigens that may behave like superantigens, interfering with antibody binding, complement-mediate opsinization, as well as phagocytosis by polymorphonuclear leukocytes. Currently, there are over 80 M protein types of GAS described, with various strains associated with nonsupportive poststreptococcal sequelae.

Acute rheumatic fever (ARF) is associated with M-types 1,3,5,6,18. Acute poststreptococcal glomerulonephritis (APSGN) is associated with M-types 1-4, 12, 14 (ie, nephritogenic strains). In humans, the quantity of M protein produced by the offending strain decreases throughout the course of the disease as well as with prolonged carriage, which may explain why scarlet fever is rarely seen in adults since they are likely to come into contact with the various antigens starting early in life.

The streptococcal pyrogenic (erythrogenic) exotoxins (SPE) A, B, and C are responsible for the characteristic rash. In addition, they induce lymphocyte blastogenesis, potentiate endotoxin-induced shock, produce fever, decrease antibody production, and act as superantigens. SPEA- and B-producing strains of GAS have been associated with severe cases of scarlet fever and more recently, with streptococcal toxic shock syndrome. The mechanism of SPEA is not fully understand as of yet, but it is significant in that quantities of this exotoxin produced by GAS strains are known to vary tremendously from decade to decade.

The toxins elicit a delayed-type hypersensitivity, thus requiring prior antigenic exposure for the disease to occur. This explains why scarlet fever rarely affects infants since they have not yet been exposed to the exotoxins necessary to produce anti-toxin antibodies.

Scarlet fever most commonly occurs following streptococcal pharyngitis or tonsillitis although other infectious foci such as the skin, soft tissue, surgical wounds (ie, surgical scarlet fever), burns, pelvic organs (ie, puerperal scarlet fever), and food-borne illness are also potential sources.

Systemic Implications and Complications

Complications of scarlet fever include otitis media, sinusitis, pneumonia, bacteremia, osteomyelitis, meningitis, arthritis, erythema nodosum, hepatitis, acute poststreptococcal glomerulonephritis, and acute rheumatic fever. APSGN and ARF occur approximately 10 days following pharyngeal infection.

Treatment Options

Systemic antibiotic therapy with penicillin is the treatment of choice for scarlet fever. Treatment is important in terms of quelling the symptoms, decreasing the spread to contacts, as well as avoiding future complications such as ARF and APSGN. Additionally, timely treatment within the first few days of infection is extremely important since ARF and APSGN are manifested shortly after infection and can have lasting consequences.

Treatment with antibiotics after the development of ARF and APSGN appears futile since these are immune-complex-mediated syndromes occurring post-infection. Petrolatum-based emollients are recommended for the desquamative eruption. Oral antihistamines, such as diphenhydramine or hydroxyzine, may be used if there is associated pruritus.

Optimal Therapeutic Approach for this Disease

First-line therapy: benzathine penicillin G IM in a single dose or penicillin VK orally for 10 days.

Second-line therapy: amoxicillin or first-generation cephalosporins orally for 10 days may alternatively be used.

Penicillin-allergic patients: Erythromycin orally for 10 days.

In the event that the physical or laboratory findings do not correlate with the diagnosis, further workup including bacterial and viral cultures/serologies and appropriate therapy is warranted.

Patient Management

Early diagnosis and completion of appropriate antibiotic therapy are essential to treating the infection and preventing any potential complications. With timely intervention the prognosis is excellent; most patients recover in less than 1 week and experience resolution of the cutaneous manifestations within several weeks without any lasting sequelae. Patients are recommended to follow up with their physician to ensure resolution of the primary infection and to evaluate for any signs of rheumatic fever or other complications. Urinalysis should also be done at follow-up to screen for the development of glomerulonephritis.

Unusual Clinical Scenarios to Consider in Patient Management

With the advent of antibiotic therapy, scarlet fever is no longer the significant cause of morbidity and mortality that it was historically. It usually follows a benign course with no long-term sequelae. Recognizing and treating the infection in a timely manner is essential to prevent rheumatic fever and/or poststreptococcal glomerulonephritis. Of note, it appears that acute guttate psoriasis (AGP), a nonsuppurative sequela of GAS pharyngitis, may confer protection against ARF and APSGN as there has been no reported evidence of the co-existence of these three poststreptococcal complications.

In the very rare circumstance that patients experience unlikely morbidity, it will likely be secondary to suppurative complications such as peritonsillar abscess formation, pneumonia, or meningitis. If severe odynophagia related to the pharyngitis develops, monitor for dehydration and nutritional status if the patient is unable to swallow. Extremely rarely, septic shock with multi-organ failure has been reported. In any of the above clinical scenarios, close in-patient treatment including supportive care is warranted.

What is the Evidence?

Berk, D, Bayliss, S. “MRSA, staphyloccocal scalded skin syndrome, and other cutaneous bacterial emergencies”. Pediatric Ann. vol. 39. 2010. pp. 627-33. (A review of the important pediatric bacterial skin infections and specific evaluation and treatment parameters.)

Shulman, ST, Tanz, RR. “Group A streptococcal pharyngitis and immune-mediated complications: from diagnosis to management”. Expert Rev Anti Infect Ther. vol. 8. 2010. pp. 137-50. (GAS pharyngitis from its epidemiology to diagnosis and proposed strategies for management including selective testing to avoid unnecessary testing of viral-like syndromes (cough and rhinorrhea) and appropriate management of immune-mediated sequelae such as ARF and APSGN.)

Manders, SM. “Toxin-mediated streptococcal and staphylococcal disease”. J Am Acad Dermatol. vol. 39. 1998. pp. 383-98. (Understanding the basic science and pathophysiology of how toxins and superantigens lead to the various toxin-mediated diseases and their clinical presentations.)

Krishnamurthy, K, Walker, A, Gropper, G, Hoffman, C. “To treat or not to treat? Management of guttate psoriasis and pityriasis rosea in patients with evidence of Group A streptococcal infection”. J Drugs Dermatol. vol. 9. 2010. pp. 241-50. (The role of streptococcus in the immunopathogensis of guttate psoriasis and pityriasis rosea as well as the risk of developing scarlet fever and other poststreptococcal sequelae. It is postulated that streptococcal-associated guttate psoriasis may confer protection against more severe poststreptococcal sequelae such as ARF and APSGN.)

Lancefield, RC. “Current knowledge of type-specific M antigens of group A streptococci”. J Immunol. vol. 89. 1962. pp. 307-13. (The virulence of M-proteins in type-specific antibody production in GAS.)

Robinson, JH, Kehoe, MA. “Group A streptococcal M proteins: virulence factors and protective antigens”. Immunol Today. 1992. pp. 362-7. (A review of the streptococcal M proteins and how they mediate varied streptococcal pathogenicity; 50 years after their initial classification, they still remain at the forefront of the clinicopathologic investigation.)

Barsumian, EL, Schlievert, PM, Watson, DW. “Nonspecific and specific immunological mitogenicity by group A streptococcal pyrogenic exotoxins”. Infect Immun. vol. 22. 1978. pp. 681-8. (Studies in murine and rodent models demonstrated that SPE types A, B, and C induced varied lymphocyte proliferation and responsiveness depending on the stimulation and target tissue.)

Gerber, MA, Baltimore, RS, Eaton, CB, Gewitz, M, Rowley, AH, Shulman, ST. “Prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics”. Circulation. vol. 119. 2009. pp. 1541-51. (Timely and accurate diagnosis and treatment of GAS tonsillopharyngitis is critical in preventing ARF. Patients with a history of acute rheumatic fever will need lifelong secondary prophylaxis to prevent recurrences after subsequent GAS infection.)

Bialacki, C, Feder, HM, Grand-Kels, JM. “The six classic childhood exanthems: a review and update”. J Am Acad Dermatol. vol. 21. 1989. pp. 891-903. (This review discusses the epidemiology, etiology, clinical manifestations, histologic and laboratory findings, differential diagnosis, treatment, and prevention of several classic childhood exanthems.)

Sandrini, J, Beucher, AB, Kouatchet, A, Lavigne, C. “Scarlet fever with multisystem organ failure and hypertrophic gastritis”. Rev Med Interne. vol. 30. 2009. pp. 456-9. (Scarlet fever is primarily a diagnosis of children, however; it can occur in adults as in this case report of a 62-year-old female who presented with septic shock and multiple organ failure. A positive sick contact, sand paper rash, and elevated ASO confirmed the diagnosis, and the patient was successfully treated with cefotaxime and amoxicillin.)