Deep Dive
The Initial Presentation and Early Dead Ends
A 45-year-old otherwise healthy man presented with a 101°F fever and no other symptoms. Initial rapid testing for COVID and flu both came back negative, so the first doctor diagnosed viral illness and told him to return if symptoms worsened. Two days later the patient returned to Mike with a 103.5°F fever — a significant spike. Mike ran through a systematic review of systems: no respiratory symptoms, no GI symptoms, no rashes, no urinary complaints, no neurologic signs like headache or visual changes. In fact, the patient felt perfectly fine whenever he took fever-lowering medication, which actually suggested a more benign viral process. With no travel history, no risk factors, and seemingly no focal infection anywhere, Mike suspected atypical mono or EBV, but physical exam showed no lymph nodes.
The FUO Diagnosis and Initial Workup
With a high fever and no clear source despite thorough questioning, Mike was facing a case of FUO — fever of unknown origin. An FUO workup is invasive: it demands extensive bloodwork, multiple CT scans of different body regions, and significant radiation exposure. Mike chose a more measured approach because his patient felt well otherwise and could physiologically tolerate a fever for a few more days. He ordered initial labs and told the patient to call back in two days to reassess. The inflammatory markers came back elevated (CRP, ESR, ferritin), and the CBC showed scattered abnormalities — white counts slightly down, platelets slightly down, lymphocytes slightly up. This pattern still suggested a viral picture. Then the mono test returned positive along with EBV titers. The patient actually admitted he'd had mono in the past, which made reactivation seem like the obvious answer.
The Plot Twist: Fever Returns
Mike explained to his patient that the fever should resolve within five days, with the peak temperature declining each day. True to prediction, five days later the patient called back fever-free and ready to return to work. But five days after that — on a Friday evening, the worst possible time — the patient reached out again: his fever was back and now at 103°F. Mike was baffled. He had full resolution of symptoms followed by a completely normal window, and now the fever had returned at the same intensity. The next morning Mike examined the patient in clinic: normal vitals, comfortable appearance, no new symptoms, no new physical findings. Mike called two experienced ER doctors he knew for a curbside consult. They heard the case and suggested empiric doxycycline, thinking he must have a tick-borne infection like Lyme disease. Mike hesitated because he'd already tested for Lyme (negative) and had a positive mono diagnosis — he didn't think it was a true FUO.
The Diagnosis Revealed: Anaplasmosis
Rather than start doxycycline on the assumption of an unknown tick-borne illness, Mike decided to broaden the bloodwork and hunt for rare conditions. He ordered a tick-borne panel, CMV testing, and autoimmune panels he hadn't run in years. He also arranged an infectious disease consultation for early the next week. The answer came back almost immediately: anaplasmosis. Anaplasmosis is a bacterial infection spread by the same tick species that transmits Lyme disease, but it's caused by a different bacterium. Left untreated in the early phase, it can become quite serious. Mike immediately sent his patient a doxycycline prescription — exactly what Dr. Pettit had suggested — and the infectious disease doctor confirmed the diagnosis and extended the course from 10 days to two weeks. Within days of starting antibiotics, the fever disappeared. Two weeks later, all of the patient's lab work came back pristine: liver enzymes normalized, inflammatory markers dropped, CBC completely normal.
The Bigger Picture: Rising Tick-Borne Illness in the US
Mike closes with a critical public health note: tick-borne illnesses are on the rise in the United States. Summers are hotter and longer, springs arrive earlier, and winters are milder, which means less tick die-off and extended transmission seasons. This climate-driven expansion of suitable tick habitat is enabling the vector population to grow and spread more readily. Beyond climate, there are additional factors like differences in how often these diseases get diagnosed, local deer and mouse populations that serve as reservoir hosts, and geographic variation in how actively we search for these conditions. The real lesson is that anyone living in a tick-endemic area — like Mike's northeast practice — needs to think about tick-borne diseases immediately when a patient presents with unexplained fever, because they are easy to miss and can cause serious harm if left untreated.