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Differential Diagnosis & Pitfalls

• Malaria – This infection should always be considered in a febrile patient with a compatible travel history. Thick and thin blood smears and malaria antigen testing should be performed.
• Babesiosis – Consider this in patients with compatible travel history (to the U.S. Northeast and upper Midwest). Diagnosis is made by microscopy or polymerase chain reaction (PCR).
• Colorado tick fever – Most patients recall a tick bite. As with tick-borne relapsing fever, the fever in this disease can recur. Diagnosis can be made by serology or PCR.
• Human ehrlichiosis and anaplasmosis – Tick-borne illness presenting with fever, malaise, myalgia, headache, and chills. Diagnosis is made by serology and PCR.
• Brucellosis – Fever in acute infection can sometimes last weeks. Diagnosis can be made by culture, serology, or PCR.
• Bartonella infection – In trench fever, recurrent febrile episodes can occur. Diagnosis can be made by culture, serology, or PCR.
• Tularemia – Following the initial febrile episode, the patient may experience an afebrile period lasting a few days before the fever returns. Diagnosis can be made by serology or PCR.
• Leptospirosis – This is a febrile illness caused by a pathogenic spirochete found in animal urine and contaminated water and soil. Diagnosis can be made by culture, serology, or PCR.
• Rat-bite fever – This is a febrile illness caused by Streptobacillus moniliformis or Spirillum minus. Patients typically have a rash on their extremities and polyarthritis.
• Yellow fever – This illness should be considered if there has been travel to an area of South America or Africa where transmission is known to occur. Diagnosis can be made with serology or PCR.
• Dengue fever – A minority of patients may have a relapse of fever that occurs a few days after the initial febrile episode. Diagnosis can be made by serology or PCR.
• Lymphocytic choriomeningitis virus infection – A rodent-borne viral infection that presents as aseptic meningitis. Diagnosis is by serology on acute and convalescent serum.
• Systemic juvenile idiopathic arthritis or adult-onset Still disease – Fever is a very common extra-articular manifestation of these conditions. Patients will typically lack a travel and exposure history that would be compatible with tick-borne relapsing fever. The fever will not respond to antibiotics.
• Occult malignancy – Certain malignancies including lymphoma, leukemia, and renal cell carcinoma may present with fever.

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