Recurrent Cyclical Fever Leads to a Tickborne Diagnosis in a Rituximab-Treated Patient
A 69-year-old man with indolent non-Hodgkin lymphoma developed a prolonged febrile illness that moved through multiple admissions before a tickborne bacterium was identified. The final diagnosis was Neoehrlichia mikurensis infection, an emerging intracellular pathogen that is still easy to miss when the presentation is dominated by nonspecific inflammatory symptoms rather than a classic infectious syndrome.
The case matters because the patient was immunocompromised from active lymphoma treatment, including rituximab, a CD20 monoclonal antibody that depletes B lymphocytes. In that setting, fever, night sweats, edema, chills, and a striking inflammatory response can point in several directions at once: lymphoma progression, drug toxicity, occult bacterial infection, or another opportunistic process entirely. Here, the infection sat in plain sight while standard tests remained unrevealing.
A Presentation That Looked Inflammatory Before It Looked Infectious
Treatment began in April 2024 with an R-CVP regimen consisting of rituximab, cyclophosphamide, vincristine, and prednisolone. In July, he was admitted with nonneutropenic fever, chills, night sweats, and mild bilateral leg edema. He reported hiking in a national park in the Netherlands but denied other clear infectious exposures, including a known tick bite or travel abroad.
Routine evaluation did not identify a source. Chest radiograph, urinalysis, and blood cultures were unremarkable. Even so, laboratory results showed leukocytosis of 10.1 × 10^9 cells/L and a C-reactive protein level of 124 mg/L, prompting empiric cefuroxime. The fever persisted for more than 5 days. A positron emission tomography scan showed no infectious or inflammatory focus, though it did show a good response of the lymphoma to treatment.
The pattern was clinically awkward. He felt ill during fever episodes but returned to baseline between them, a rhythm that can mislead clinicians toward intermittent inflammatory syndromes, occult malignancy, or partially treated bacterial infection rather than a tickborne intracellular organism.
Cefuroxime was stopped and he was discharged after 10 days.
Cyclical Fever, Hypotension, and a Missed Etiology
The illness did not settle. Night sweats and edema improved after discharge, but during the last two therapy cycles for lymphoma, the same cluster of symptoms returned: fever, chills, edema, and profuse sweating. He was readmitted on November 19 with a temperature of 40.3°C and received cefuroxime again.
No cardiac, renal, or protein-losing explanation emerged. Echocardiography and chest radiograph showed no right heart failure, and serum albumin and urine protein testing were unremarkable. During each admission, fever and chills triggered episodes of systemic inflammatory response syndrome with severe hypotension and tachycardia, requiring fluid resuscitation. The bedside picture was no longer a simple fever workup; it had become a hemodynamically unstable inflammatory syndrome.
Cefuroxime was discontinued after cultures remained negative and no clinical response appeared. Nonsteroidal antiinflammatory drugs started on November 25 seemed to lower the fever, and the patient was discharged three days later.
Broad-Range PCR Exposed the Pathogen Behind the Fevers
The decisive clue came after another readmission on December 31 with the same symptoms. On January 2, 2025, bone marrow biopsy showed reactive changes and did not reveal lymphoma or another malignancy. The fevers continued with a striking cyclical pattern of about 48 hours. Each episode started with chills and escalated to temperatures as high as 41.1°C, again accompanied by systemic inflammatory response syndrome.
Broad-range PCR targeting the bacterial 16S V3-V4 rRNA region followed by sequencing detected N. mikurensis DNA. A specific PCR performed on blood at the National Institute for Public Health and the Environment in the Netherlands confirmed the finding.
This is the diagnostic bottleneck with N. mikurensis: routine cultures do not help, and definitive detection depends on molecular testing that is not widely available. In a patient whose symptoms mimic fever of unknown origin, the organism can remain hidden until clinicians move beyond standard bacterial workups.
Doxycycline Rapidly Reversed the Syndrome
The patient started doxycycline on January 7 at 100 mg twice daily for 3 weeks. Fever and edema subsided within days. Blood PCR samples collected 3 and 6 months after treatment were negative.
That clinical response fits the known biology of the infection. N. mikurensis is an intracellular gram-negative bacterium transmitted by ticks, and infections are seen most often in immunocompromised people, especially those receiving B-cell–depleting therapies. The Netherlands, like other parts of western Europe where Ixodes ricinus ticks are endemic, provides the ecological conditions for exposure. Reported tick prevalence in western Europe has reached 24.2%, a reminder that the organism is more likely to be encountered where tick exposure is common and surveillance is strong.
Why This Case Should Change the Fever Workup in Immunocompromised Patients
This case illustrates a diagnostic blind spot in oncology and immunology practice. Fever, night sweats, edema, and inflammatory markers are easy to attribute to lymphoma, treatment effects, or nonspecific infection, especially when cultures stay negative and imaging is unrevealing. In patients receiving rituximab or other immunosuppressive therapies, however, the threshold for considering Neoehrlichia mikurensis should be lower, particularly when fever recurs in a cyclical pattern after possible tick exposure.
The organism’s clinical range is wider than fever alone. Published experience links it to systemic inflammation, vasculitis, and thromboembolic events, and the symptoms may not resemble the infections clinicians usually expect. B-cell depletion may impair host control of an intracellular pathogen and prolong bacteremia, which helps explain why recurrent fever can persist until targeted therapy begins.
Treatment is straightforward once the diagnosis is made: oral doxycycline for 2 to 3 weeks. Shorter courses or lower doses can allow recurrence, especially in immunocompromised patients. The clinical lesson here is not that tickborne infection is rare, but that molecular diagnostics become essential when standard evaluation fails and the inflammatory pattern keeps returning.
In the Netherlands and similar endemic regions, rising use of immunosuppressive therapy is likely to create more opportunities for this infection to appear. Prospective studies of patients who develop fever after tick exposure would help define how often N. mikurensis is missed and which clinical features should trigger early PCR testing before repeated admissions and hemodynamic instability accumulate.