Febrile Neutropenia Masked a Fatal Tickborne Infection in a Child With Leukemia
A 3-year-old boy in southwestern Georgia died after Rickettsia parkeri rickettsiosis advanced under the cover of febrile neutropenia, profound cytopenias, and a broad differential that initially pointed elsewhere. The case is a blunt reminder that spotted fever group rickettsioses can be missed when a child is already hospitalized for chemotherapy-related complications and the skin findings are easy to dismiss as insect bites.
The child was receiving chemotherapy for high-risk B-cell acute lymphoblastic leukemia and was admitted in late July 2025 with fever and severe bone marrow suppression. Admission laboratory values showed leukocyte count of 110/µL, absolute neutrophil count of 20/µL, and platelets of 19,000/µL. He was in the second month of delayed intensification and had received cyclophosphamide, cytarabine, and 6-thioguanine 2 weeks earlier. On examination, the most specific clue was also the most easily overlooked: two pink papulonodules with central eschars on the left upper extremity.
Empiric cefepime began after blood cultures were obtained. Fever persisted. So did the diagnostic uncertainty.
Eschars, Rash Progression, and the Cost of a Familiar Syndrome
During the second and third hospital days, a rash appeared on the upper back and arms and then spread over the next 3 days to involve the face, trunk, and both upper and lower extremities. Some lesions developed vesicles. The parents later reported that the left arm lesions had been present for about a month before admission and had been draining clear fluid. They had assumed the lesions were insect bites because the child frequently played in grass around the family home, but they never saw an insect attached to the skin.
This is the kind of history that can push clinicians toward ordinary explanations. In a child with leukemia, however, the same skin findings can also represent a rickettsial inoculation lesion, especially when fever continues despite antibacterial therapy and blood cultures remain negative. The rash of R. parkeri infection is usually described as scattered pink macules with overlying vesicles, often with an eschar at the site of tick attachment. In this child, the eruption was broader than expected and included facial lesions, a distribution that should have raised concern for a disseminated process rather than a localized reaction.
Unbiased Sequencing Identified the Pathogen After Clinical Collapse
Because fever and cytopenias persisted, the antimicrobial regimen expanded to cover fungal and viral causes as well. Micafungin and acyclovir were added. Testing for herpes simplex virus and varicella zoster virus from an unroofed vesicle was negative. Chest computed tomography with contrast showed minimal ground glass opacities, while abdominal ultrasound revealed hepatomegaly, trace ascites, and thickened inflamed small bowel loops consistent with neutropenic enteritis.
By hospital day 7, the child had worsened into hypotension and respiratory failure and required transfer to the intensive care unit with bilevel positive airway pressure. Therapy broadened further to meropenem, vancomycin, amphotericin B, isavuconazole, and doxycycline. Despite escalation, he continued to deteriorate hemodynamically and became more hypoxic. Intubation was complicated by a 20-minute cardiac arrest, and although return of spontaneous circulation was achieved, neurologic injury became evident shortly afterward. Life-sustaining therapy was withdrawn, and he died on hospital day 8.
The decisive laboratory result arrived too late to change the outcome. Plasma microbial cell-free DNA sequencing, sent on hospital day 7, returned positive for R. parkeri with 8,374 molecules per 100 nL. Confirmatory testing at the Centers for Disease Control and Prevention found R. parkeri DNA by real-time PCR targeting the ompB gene in residual plasma. Skin biopsy sections stained by immunoalkaline phosphatase showed abundant rickettsial antigen in the lumina and endothelium of vessels, with extension into adjacent dermal tissue.
Why Immunosuppression Likely Changed the Biology of the Infection
R. parkeri rickettsiosis is usually mild to moderately severe, and most patients recover with doxycycline. The biology of this case was different. The child was profoundly lymphopenic from leukemia and chemotherapy, with an unmeasurable lymphocyte count and severe neutropenia, removing the cellular defenses that normally help contain spotted fever group rickettsiae. In vitro work has shown that CD4 and CD8 T cells matter in rickettsial control, with CD8 T cells playing a particularly important role in clearing the organism. In that setting, the usual limitation of infection to a localized eschar and limited rash likely gave way to uncontrolled vascular spread.
Pathology reinforced that concern. High concentrations of rickettsial antigen in and around dermal vessels fit the vascular tropism of the organism and support a biologic explanation for the patient’s rapid systemic decline. The article also points to experimental mouse data showing lethality with high inoculation dose, a signal that unusually heavy pathogen burden may matter when host immunity is stripped away. The combination of extreme immunosuppression and a potentially high organism load probably contributed to the severity and fatal course.
Summer Exposure in the Gulf Coast Tick Region Should Stay on the Differential
The vector for R. parkeri is the Gulf Coast tick, Amblyomma maculatum, whose range includes southwestern Georgia. Adult ticks are most active during July and August near the Gulf Coast, which matched the timing of this illness. No tick was ever seen, and no definite bite was documented, yet absence of a witnessed tick does not exclude tickborne disease. Families and clinicians alike may anchor on the visible diagnosis in front of them, in this case febrile neutropenia, while the actual exposure history remains buried in the background.
Only one prior immunocompromised patient with R. parkeri infection has been described: a kidney transplant recipient who developed a moderately severe illness that resolved with doxycycline. This pediatric case broadens the concern. Immunocompromised hosts may not mount the classic presentation, and the routine admission syndrome of chemotherapy-associated fever can obscure a treatable vectorborne infection until it is too late.
The practical lesson for bedside care is straightforward: persistent fever plus eschar lesions in a child who lives in or travels to an area where Amblyomma maculatum is present should trigger early consideration of spotted fever group rickettsiosis, even when neutropenia offers a more obvious explanation. Doxycycline remains the treatment of choice for all rickettsial infections, but sequencing-based diagnostics may be needed when standard testing is unrevealing or when the diagnosis is not suspected soon enough. In this case, the delay between clinical worsening and etiologic confirmation was fatal, and the challenge now is to recognize how easily a rare tickborne disease can hide inside a common oncologic emergency.