P0650 - Karius-ity and the Cat: Diagnosing Hepatosplenic Bartonella Using Next Generation DNA Sequencing and Imaging

Case Summary:
A 23-year-old female with common variable immunodeficiency (CVID), presented with intermittent epigastric pain, which would eventually spread to her entire abdomen. She had night sweats, chills, and regular stools. She had been evaluated twice over the last two months for posterior cervical lymphadenopathy and similar abdominal symptoms, which were attributed to a possible EBV infection. Her exam was notable for diffuse abdominal tenderness, worse in the epigastric region, without rebound or guarding. Additionally, she had a non-tender fixed lymph node in the right posterior cervical chain. Her medical history is most notable for CVID, for which she receives IVIG infusions every 3 weeks with inconsistent adherence. She was not sexually active, but had a partially outdoor 2-year-old cat.

She underwent abdominal CT imaging, which revealed multifocal hepatic and splenic hypodense lesions (largest in spleen). Extensive infectious disease diagnostic work-up was unrevealing, including Bartonella serology and PCR in the blood. Histopathology after CT-guided biopsy showed normal liver tissue, as the lesions were too small to access. Ultimately, the diagnosis was made by cell-free DNA next generation sequencing (cfDNA-NGS, Karius®) test, which showed 326 molecules per microliter (reference: <10) of Bartonella henselae. She was treated with oral doxycycline 100 mg twice daily and repeat CT imaging after 5 weeks showed near-resolution of most lesions (Fig. 1).

Discussion:
Bartonella infections manifest with regional lymphadenopathy, hepatosplenic involvement, eye, neurological, musculoskeletal, endocarditis and protean manifestations. Diagnosis is usually made by serology or histopathology. The sensitivity of PCR in the blood can be as low as 30-40%. Treatment of choice is doxycycline, azithromycin+rifampin, trimethoprim/sulfamethoxazole, with the addition of gentamicin for endocarditis. CVID is a primary immunodeficiency characterized by poor B-cell differentiation and hypogammaglobulinemia. Complications often include recurrent sinopulmonary and gastrointestinal infections, granulomatous disease, polyclonal lymphocytic infiltration, autoimmune disease, and non-Hodgkin lymphomas, with an incidence of approximately 8%. This case illustrates the differential diagnosis for hepatosplenic lesions in patients with CVID, which is further complicated by limited utility of serologic assays, since such patients cannot produce their own IgG. Ultimately, diagnosis of hepatosplenic bartonellosis was made by cfDNA-NGS, a novel technology that identifies genetic material of >1200 pathogens in plasma. cfDNA-NGS been used in non-invasive prenatal testing, organ transplant rejection screening, oncologic liquid biopsies. cfDNA-NGS can be useful in challenging infectious disease cases, therefore its applicability and cost-effectiveness merit further, larger-scale investigation.

References:
Cunningham-Rundles C. Common variable immune deficiency: Dissection of the variable. Immunol Rev. 2019;287(1):145–161. doi:10.1111/imr.12728

Blauwkamp, T.A., Thair, S., Rosen, M.J. et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nat Microbiol 4, 663–674 (2019). https://doi.org/10.1038/s41564-018-0349-6