Bubblewraps in the bladder

Escherichia coli-associated follicular cystitis in dogs: Clinical and pathologic characterization

Sanna J. Viitanen, Laura Tuomisto, Nina Salonen, Katariina Eskola, Kristel Kegler

Background
Follicular cystitis is characterized by the formation of tertiary lymphoid structures (TLSs) in the urinary bladder wall, associated with chronic inflammation. In humans, such formations are linked to recurrent urinary tract infections (UTIs), but their pathogenesis and clinical relevance in dogs remain poorly understood. This study aimed to describe the clinical and histopathologic features of follicular cystitis in dogs and investigate the presence of Escherichia coli (E. coli) as a potential etiologic agent.

Methods
This retrospective descriptive study included eight dogs with histologically confirmed follicular cystitis and two controls. Dogs were selected based on visible bladder mucosal follicular lesions and detection of TLSs in biopsies. Samples underwent hematology, biochemistry, urinalysis, urine and biopsy culture, and in situ hybridization (ISH) targeting E. coli 16SrRNA. Cystoscopy, ultrasonography, and computed tomography were used for anatomical and structural assessments.

Results
All eight dogs were large breed females with a history of chronic, recurrent UTIs (median duration 7 months; median 5 prior infections). Histopathology identified TLSs at varying maturation stages in all cases. ISH detected E. coli RNA in TLSs (7/8 dogs), submucosal stroma (8/8), and urothelium (3/8). Biopsy cultures confirmed E. coli presence in 5/6 cases. E. coli was also visualized intracellularly within cells morphologically consistent with macrophages or follicular dendritic cells. Control dogs showed no evidence of infection or TLSs.

Limitations
The study was limited by a small sample size and retrospective design, with inconsistencies in antimicrobial treatment and sample collection. Small biopsy size may not represent the entire bladder wall, and the RNA method used cannot distinguish viable from non-viable bacteria. Genomic profiling of E. coli strains was not performed, limiting understanding of specific pathogenic traits.

Conclusions
Findings suggest a strong association between intramural E. coli infection and follicular cystitis in dogs, implicating E. coli as a possible causative agent. The presence of bacteria in TLSs supports a role in chronic immune stimulation. Improved diagnostic methods, including ISH, may assist in identifying intramural infections when standard cultures are negative. This highlights the need for antimicrobial strategies with better tissue penetration in managing such cases.

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