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From the NEJM Image Challenge quiz

A 7-year-old girl presented with an itchy rash while taking amoxicillin for pharyngitis. Physical exam showed purulent tonsils, along with a maculopapular rash involving her face, trunk, arms, and legs.

What is the most likely diagnosis?

NOTE: out of 13,000 responses more than 60% said it was due to amoxycillin given when the disease was infectious mononucleosis 


Group A Streptococcus (GAS), also known as Streptococcus pyogenes

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Children ≥3 years, GAS pharyngitis typically has an abrupt onset. Fever, headache, abdominal pain, nausea, and vomiting may accompany the sore throat. Additional features may include exudative tonsillopharyngitis  with enlarged erythematous tonsils, enlarged tender anterior cervical lymph nodes, palatal petechiae, inflamed uvula, and scarlatiniform rash (erythematous, finely papular rash which characteristically starts in the groin and axilla and then spreads to the trunk and extremities, followed by desquamation) Symptoms usually resolve spontaneously in three to five days. (See “Complications of streptococcal tonsillopharyngitis”, section on ‘Scarlet fever’.)

Uvular oedema and erythema

Inflammation of the uvula in association with tonsillar and posterior pharyngeal involvement.
(A) Redness and vascularity of the tonsillar pillars and uvula are mild to moderate. The uvula is moderately swollen.
(B) Redness is diffuse and intense.

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The nonsuppurative complications of GAS tonsillopharyngitis include acute rheumatic fever (ARF), scarlet fever, streptococcal toxic shock syndrome, acute glomerulonephritis, and pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS).


Scarlet fever 

The scarlet fever rash first appears as tiny red bumps on the chest and abdomen that may spread all over the body. Looking like a sunburn, it feels like a rough piece of sandpaper, and lasts about two to five days.

Scarlet fever is a diffuse erythematous eruption that generally occurs in association with pharyngitis. Development of scarlet fever requires prior exposure to Streptococcus pyogenes and occurs as a result of delayed-type skin reactivity to pyrogenic exotoxin (erythrogenic toxin, usually types A, B, or C) produced by the organism. The rash of scarlet fever is a diffuse erythema that blanches with pressure, with numerous small (1 to 2 mm) papular elevations, giving a “sandpaper” quality to the skin (). (See ‘Scarlet fever’ above.)

Rash on the volar surface of the forearm.

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Early-stage diphtheritic membrane on right tonsil of 26-year-old female patient

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Viral infections

Viruses are the most common cause of acute pharyngitis  Clinical features suggestive of viral etiology include concurrent conjunctivitis, coryza, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions, viral exanthems, and/or diarrhea. Most children and adolescents with negative microbiologic tests for GAS have viral pharyngitis, which is a self-limited condition and can be treated symptomatically without additional testing.

Viruses that infect the pharynx directly

  • Epstein-Barr virus (EBV), Cytomegalovirus (CMV)
  • Human immunodeficiency virus (HIV) – Primary HIV infection
  • Herpes simplex virus types 1 and 2
  • Influenza A and B viruses
  • Adenovirus
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)*

Viruses that cause nasopharyngitis (generally do not require specific therapy or infection control measures)

  • Rhinovirus
  • Respiratory syncytial virus
  • Coronaviruses, including SARS-CoV-2*

Infectious Mononucleosis: Pharyngitis and Morbilliform Rash – LINK

A 20-year-old female on day nine of amoxicillin for a recent diagnosis of pharyngitis presented to the emergency department with a complaint of rash for two days.  The patient’s clinical course started two weeks prior and included fever, tonsillar exudates, and fatigue.  Initial vitals were temperature of 37.6oC, blood pressure 122/82, heart rate 135, respiratory rate 18, and oxygen saturation 100% on room air.

Infectious Mononucleosis

Her physical exam was significant for bilateral tonsillar exudates, cervical lymphadenopathy, and a morbilliform rash that included the palms

Laboratory testing was significant for white blood cell (WBC) count of 16.5 thous/mcl with an elevation in absolute lymphocytes of > 10 thous/mcl.  The monospot and EBV (Epstein-Barr virus) panel were positive.


A generalized, erythematous, maculopapular eruption may be seen in patients with infectious mononucleosis after the administration of amoxicillin or ampicillin.

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Infectious mononucleosis

  • Epstein-Barr virus (EBV) and cytomegalovirus account for most cases of infectious mononucleosis, a clinical syndrome that classically occurs in adolescents and is characterized by fever, severe pharyngitis (which lasts longer than pharyngitis due to GAS), and anterior and posterior cervical or diffuse lymphadenopathy, lymphocytosis, and increased aminotransferase levels.
  • Prominent constitutional symptoms include fatigue, anorexia, and weight loss.
  • Examination findings may include periorbital or palpebral edema, mild hepatomegaly, and splenomegaly. Patients who are treated with ampicillinamoxicillin, or other antibiotics may develop a characteristic rash
  • Laboratory findings may include increased aminotransferases and predominance of atypical lymphocytes in the differential blood count. (See “Infectious mononucleosis”.)
  • Unlike adolescents, who typically present with classic symptoms, younger patients with EBV infection may have a more subtle presentation that can make diagnosis difficult.
  • Patients with infectious mononucleosis and splenomegaly require activity restriction to prevent splenic rupture.

Atypical lymphocytes in infectious mononucleosis

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Slapped cheek rash of parvovirus B19

A child with the characteristic malar (“slapped cheek”) rash associated with parvovirus B19 (erythema infectiosum, fifth disease).

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Erythema infectiosum

Reticulated, blanching erythema on the extremities due to parvovirus B19. Rash is more common in children. The presence of intense erythema (a slapped cheek appearance) on the face is highly characteristic.

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Guttate Psoriasis

Guttate psoriasis is a variant of psoriasis that is characterized by the presence of small, erythematous papules and plaques on the skin. Guttate psoriasis is most frequently diagnosed in adolescents and young adults but may occur in other age groups.

Genetic and environmental factors likely contribute to the development of guttate psoriasis. The HLA-Cw*0602 allele has been strongly linked to this disorder, and streptococcal infection often precedes its development. The latency period between streptococcal infection and the appearance of skin lesions is typically two to three weeks.

The relationship between streptococcal infection and guttate psoriasis is not fully understood. Cross-reactivity between streptococcal and epidermal antigens, stimulatory effects of streptococcal superantigens, and/or the induction of an innate immune response by streptococcal components may be involve

Numerous erythematous, scaly papules on the back.

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Multiple erythematous papules with scale on the back.

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Hand-foot-and-mouth disease

Hand, foot, and mouth disease (HFMD) and herpangina occur worldwide. Most cases occur in children younger than five to seven years. However, all age groups, including adults, may be affected. 

The viruses that cause HFMD and herpangina usually are transmitted from person to person by the fecal-oral route; they also can be transmitted by oral and respiratory secretions and, in cases of HFMD, vesicle fluid. The incubation period usually is three to five days. 

HFMD presents with mouth or throat pain or refusal to eat. If present, fever generally is low grade (below 38.3°C [101°F]). The oral lesions, which may occur in isolation, usually occur on the tongue and buccal mucosa. They begin as macules and progress to vesicles, which rupture to form superficial ulcers. Oral lesions are painful and may interfere with oral intake.

The skin lesions, which may occur in isolation, are nonpruritic and nontender. They may be macular, maculopapular, or vesicular and typically involve the hands, feet, buttocks (particularly in infants and young children), and extremities. 

 

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