Differential Diagnoses for Petechial Rash

Primary Considerations

The American College of Physicians suggests that non-infectious causes, such as drug hypersensitivity reactions and viral exanthems, are the leading differentials for petechial rash with sparing of palms and soles, and prominent itchiness, in the absence of fever 1
Drug eruptions can present as fine reticular maculopapular rashes or broad, flat erythematous macules and patches, and can include petechial components, according to the American Academy of Dermatology 1, 2
The Centers for Disease Control and Prevention recommends querying the patient about any new medications within the past 2-3 weeks, particularly antibiotics, NSAIDs, or anticonvulsants, as these can cause drug hypersensitivity reactions 2
Enteroviral infections are the most common cause of maculopapular rashes and characteristically spare palms, soles, face, and scalp, as stated by the Infectious Diseases Society of America 1
The absence of fever does not exclude viral exanthems, as fever may have resolved or been mild, according to the American Academy of Pediatrics 1

The Centers for Disease Control and Prevention notes that Parvovirus B19 can cause petechial rashes in the acute phase, though "gloves and socks" syndrome typically involves palms and soles 1
The Infectious Diseases Society of America states that EBV causes maculopapular rash, especially if the patient received ampicillin or amoxicillin 1
The American College of Emergency Physicians recommends considering RMSF, which is associated with fever in virtually all cases, making this diagnosis highly unlikely given the afebrile presentation 3, 4
The Centers for Disease Control and Prevention notes that HME rash occurs in only 30% of adults and is typically associated with fever 1, 2

The American College of Physicians recommends a complete blood count with differential to evaluate for thrombocytopenia, which would suggest ITP, TTP, or hematologic causes rather than drug reaction or viral exanthem 1, 2
The Infectious Diseases Society of America suggests a comprehensive metabolic panel to assess for systemic involvement 1, 2
The American Academy of Dermatology recommends a peripheral blood smear if thrombocytopenia is present to differentiate ITP from TTP or other causes 2

The Centers for Disease Control and Prevention warns that while fever is typically present in life-threatening infectious causes, some patients may be afebrile early in disease or may have taken antipyretics 3, 4
The American College of Physicians emphasizes the importance of not overlooking drug history, as up to 40% of patients may not recall or report new medications 2
The American Academy of Dermatology notes that in darker-skinned patients, petechial rashes may be difficult to recognize, increasing risk of delayed diagnosis 5

The American College of Physicians recommends discontinuing the offending agent immediately if drug reaction is suspected, and symptomatic treatment with antihistamines for pruritus 2
The Infectious Diseases Society of America suggests supportive care with antihistamines for pruritus if viral exanthem is suspected, and monitoring for development of classic viral syndrome features 1
The American College of Emergency Physicians notes that red flags requiring immediate re-evaluation include development of fever, progression of petechiae to purpura or ecchymoses, development of systemic symptoms, and involvement of palms and soles 1, 2, 3, 4, 5