What is the differential diagnosis for a patient with fever, maculopapular rash, polyarthralgia, and microscopic hematuria after a camping trip?

Differential Diagnosis

This presentation is most consistent with a tickborne rickettsial disease—specifically Rocky Mountain Spotted Fever (RMSF) or Human Monocytic Ehrlichiosis (HME)—and requires immediate empiric doxycycline treatment without waiting for laboratory confirmation. 1, 2

Primary Diagnostic Considerations

Tickborne Rickettsial Diseases (HIGHEST PRIORITY)

Rocky Mountain Spotted Fever (RMSF)

• The 10-day fever duration with maculopapular rash on trunk and extremities, polyarthralgia, and camping exposure creates a classic presentation for RMSF 2, 3
• RMSF initially presents as small (1-5 mm) blanching pink macules on ankles, wrists, or forearms appearing 2-4 days after fever onset, then progresses to maculopapular with central petechiae spreading to trunk 2
• Critical: RMSF carries a 5-10% case-fatality rate, and delays in diagnosis significantly increase mortality risk 2
• Less than 50% of patients have rash in the first 3 days, and up to 20% never develop a rash, making this diagnosis easy to miss 2
• The microscopic hematuria suggests systemic vasculitis from rickettsial endothelial infection 1

Human Monocytic Ehrlichiosis (HME)

• Rash occurs in only approximately 30% of adults with HME, varying from petechial to maculopapular to diffuse erythema 2, 3
• HME rash appears later in disease course (median 5 days after onset) and rarely involves palms and soles 2
• The 10-day fever duration fits the typical HME timeline better than RMSF 2
• Carries a 3% case-fatality rate 2

Anaplasmosis

• Typically presents with fever, headache, and myalgia, but rash is rare in anaplasmosis, making this less likely given the prominent rash in this patient 1
• Case-fatality rate is <1% 1
• The same tick vector (Ixodes scapularis) transmits Anaplasma phagocytophilum along with Borrelia burgdorferi and Babesia microti 1

Lyme Disease with Possible Coinfection

Borrelia burgdorferi

• Polyarthralgia involving hands, knees, and ankles is characteristic of Lyme arthritis 1
• Camping exposure in endemic areas supports this diagnosis 1
• However, the maculopapular rash on trunk/extremities does NOT fit the typical erythema migrans pattern 1
• Confirmed Anaplasma coinfection occurs in <10% of patients with Lyme disease 1
• If Lyme disease is treated with beta-lactam antibiotics in a patient with unrecognized Anaplasma coinfection, anaplasmosis symptoms could persist 1

Viral Exanthems

Enteroviral Infections

• Most common cause of maculopapular rashes with trunk and extremity involvement 2, 3
• However, 10 days of persistent fever is atypically prolonged for enteroviral infection 2
• Enteroviruses can cause petechial rashes that mimic bacterial causes 4

Epstein-Barr Virus (EBV)

• Causes maculopapular rash, especially if patient received ampicillin or amoxicillin 2, 3
• Can present with polyarthralgia 3
• Query specifically about recent antibiotic use 3

Parvovirus B19

• Presents with "slapped cheek" appearance on face with possible truncal involvement 2, 3
• Can cause polyarthralgia, particularly in adults 3

Drug Hypersensitivity Reactions

Exanthematous Drug Eruption

• Presents as fine reticular maculopapular rashes or broad, flat erythematous macules and patches 2, 3
• Query specifically about recent antibiotic use, NSAIDs, anticonvulsants, or any new medications within the past 2-3 weeks 3

Other Considerations

Tick-Borne Relapsing Fever

• Should be considered in patients with fever after staying overnight in mountain cabins in western United States 5
• Caused by Borrelia hermsii 5

Adult-Onset Still Disease

• Characterized by fever, polyarthralgia, elevated white blood cell count, and maculopapular rash 6
• However, this is a diagnosis of exclusion after ruling out infectious causes 6

Immediate Diagnostic Workup Required

Laboratory Testing (STAT)

• Complete blood count with differential looking for leukopenia, thrombocytopenia (critical red flags for rickettsial disease) 2, 3
• Comprehensive metabolic panel looking for hyponatremia, elevated hepatic transaminases (characteristic of anaplasmosis and ehrlichiosis) 1, 2, 3
• Acute serology for Rickettsia rickettsii, Ehrlichia chaffeensis, and Anaplasma phagocytophilum 2, 3
• Urinalysis already shows microscopic hematuria, consistent with systemic vasculitis 1
• Peripheral blood smear to look for morulae within granulocytes (Anaplasma) 1

Critical Management Decision

The CDC recommends initiating doxycycline 100 mg twice daily immediately if ANY of the following are present: fever + rash + headache + tick exposure or endemic area exposure. 2

Thrombocytopenia and/or hyponatremia are critical red flags that mandate immediate empiric treatment. 2

Treatment Expectations

• Clinical improvement is expected within 24-48 hours of initiating doxycycline 2
• If clinical response is delayed, consider coinfection with Borrelia burgdorferi or Babesia microti in the appropriate epidemiologic setting 1
• Severe complications (meningoencephalitis, ARDS, multiorgan failure) can occur if treatment is delayed 2

Common Pitfalls to Avoid

Do NOT wait for serologic confirmation before starting doxycycline 1, 2, 3

• Acute serology is often negative early in disease course 1
• Delay in treatment significantly increases mortality, particularly for RMSF 2

Do NOT dismiss the diagnosis because of absence of reported tick bite 1, 2

• Many patients do not recall a tick bite 1
• Camping exposure alone is sufficient epidemiologic risk 1, 5

Do NOT assume absence of palm/sole involvement rules out RMSF 2

• Classic palm/sole distribution occurs late in disease 2
• Early RMSF presents on ankles, wrists, or forearms 2

Leukopenia or thrombocytopenia in a patient being evaluated for Lyme disease should raise clinical suspicion for possible coinfection with Anaplasma phagocytophilum 1