What are the possible infectious diseases in a patient presenting with fever for 8 days and a rash starting on the face and spreading to the trunk?

Infectious Disease Differential for 8-Day Fever with Facial-to-Trunk Rash

The most critical infectious diseases to consider immediately are Rocky Mountain Spotted Fever (RMSF) and Human Monocytic Ehrlichiosis (HME), and empiric doxycycline 100 mg twice daily must be initiated without waiting for laboratory confirmation given the 5-10% mortality risk of RMSF. 1, 2

Primary Life-Threatening Considerations

Rocky Mountain Spotted Fever (RMSF)

• RMSF typically presents with small blanching pink macules appearing 2-4 days after fever onset, initially on ankles, wrists, or forearms, then progressing to maculopapular lesions with central petechiae that spread to palms, soles, arms, legs, and trunk while characteristically sparing the face. 1
• The 8-day fever duration with facial involvement is atypical for classic RMSF presentation, but up to 20% of patients never develop the characteristic rash pattern, and less than 50% have rash in the first 3 days. 1
• The 5-10% case-fatality rate and the fact that 50% of deaths occur within 9 days of illness onset make this diagnosis critical not to miss. 1, 2
• Thrombocytopenia, increased immature neutrophils, elevated hepatic transaminases, and hyponatremia support this diagnosis, though laboratory findings may be normal early in illness. 3

Human Monocytic Ehrlichiosis (HME)

• HME presents with fever (96%), headache (72%), malaise (77%), and myalgia (68%), with rash occurring in only approximately 30% of adults, appearing later in the disease course (median 5 days after onset). 3, 1
• The rash varies from petechial or maculopapular to diffuse erythema and typically involves extremities and trunk, and can affect the face. 3
• The 3% case-fatality rate is lower than RMSF but still significant, particularly in immunosuppressed patients where mortality is substantially higher. 3, 1
• Gastrointestinal symptoms (nausea 57%, vomiting 47%, diarrhea 25%) and respiratory symptoms (28%) are common and may be prominent. 3

Meningococcemia

• Meningococcemia causes invasive disease with petechial or purpuric rash that rapidly progresses to purpura fulminans, typically appearing alongside high fever, severe headache, and altered mental status. 2
• The 8-day duration without rapid progression or systemic toxicity makes this less likely, but it cannot be excluded without further evaluation. 2

Secondary Infectious Considerations

Viral Exanthems

• Enteroviral infections are the most common cause of maculopapular rashes, characteristically presenting with trunk and extremity involvement while sparing palms, soles, face, and scalp. 1, 4
• The facial involvement in this case makes typical enteroviral infection less likely. 1
• Human herpesvirus 6 (roseola) presents with macular rash following high fever resolution, though more common in children. 1
• Parvovirus B19 presents with "slapped cheek" facial appearance with possible truncal involvement. 1
• Epstein-Barr virus causes maculopapular rash, especially if the patient received ampicillin or amoxicillin. 1

Streptococcal Infections

• Scarlet fever caused by Streptococcus pyogenes causes exanthema with characteristic tonsillopharyngitis, though atypical presentations can occur. 5
• The 8-day duration without prominent pharyngeal symptoms makes this less likely. 5

Rat-Bite Fever

• Streptobacillus moniliformis causes fever with maculopapular rash affecting palms in patients with rodent exposure. 6
• This requires specific exposure history to pet rats or other rodents. 6

Immediate Diagnostic Algorithm

Critical Red Flags Requiring Immediate Doxycycline

• Initiate doxycycline 100 mg twice daily immediately if ANY of the following are present: fever + rash + headache + tick exposure or endemic area exposure. 1
• Thrombocytopenia and/or hyponatremia are critical red flags that mandate immediate treatment. 1

Essential Laboratory Workup

• Complete blood count with differential looking for leukopenia, thrombocytopenia, or bandemia. 1, 2
• Comprehensive metabolic panel looking for hyponatremia and elevated hepatic transaminases. 1, 2
• Acute serology for Rickettsia rickettsii, Ehrlichia chaffeensis, and Anaplasma phagocytophilum. 1
• Blood cultures before antibiotics if possible, but do not delay treatment. 2
• Peripheral blood smear to look for morulae within monocytes (Ehrlichia) or granulocytes (Anaplasma). 1

Expected Clinical Response

• Clinical improvement should occur within 24-48 hours of initiating doxycycline. 1
• Lack of improvement suggests alternative diagnosis or coinfection. 1
• Severe complications including meningoencephalitis, ARDS, and multiorgan failure can occur if treatment is delayed, particularly in immunosuppressed patients. 1

Critical Pitfalls to Avoid

• Do not wait for the classic triad of fever, rash, and tick bite in RMSF, as it is present in only a minority of patients at initial presentation. 2
• Do not exclude RMSF based on facial involvement or atypical rash distribution, as up to 20% never develop characteristic rash patterns. 1, 2
• Tick exposure history is present in only 60% of RMSF cases, so absence does not exclude diagnosis. 2
• Do not delay treatment waiting for laboratory confirmation, as mortality increases significantly with each day of delay. 1, 2
• In darker-skinned patients, petechial rashes may be difficult to recognize, increasing risk of delayed diagnosis. 4