Feline cutaneous histoplasmosis in a non-endemic region: diagnostic challenges and molecular confirmation of Histoplasma capsulatum in Latvia.

BACKGROUND: Feline histoplasmosis can have variable clinical presentations, it is rarely diagnosed in Europe and has not been diagnosed in Northern Europe and Baltics. We encountered a cluster of autochthonous cases of feline histoplasmosis in Latvia-a non-endemic region. In this paper we describe the diagnostic pathways, challenges and outcomes in three cats. We also report the first molecular confirmation of Histoplasma capsulatum in the Baltic region. Three domestic shorthaired cats presented with ulcerative or erosive skin lesions and were initially evaluated by cytology. Diagnostic follow-up included histopathology, immunohistochemistry (IHC), serology and in one case a polymerase chain reaction (PCR), with DNA sequencing and phylogenetic analysis. We outlined several practical challenges of performing fungal diagnostics in Europe, these can be valuable to our colleagues. RESULTS: All three cases showed organisms consistent with Histoplasma species on cytological examination. Case 1: a feline immunodeficiency virus positive shelter cat with multiple ulcerative cutaneous lesions. Histopathology and IHC confirmed fungal infection suggestive of Histoplasma species. The cat was lost to follow-up. Case 2: A 3-year-old male cat with a single erosive facial lesion. The cat fully recovered with antifungal treatment. Case 3: A 6-year-old neutered male with multiple erosive skin lesions. The cat was humanely euthanized. Diagnosis was supported by cytology while results of histopathology and IHC were suggestive of Histoplasma species. Serology (urine and serum) were positive for H. capsulatum antigen and the diagnosis was confirmed by PCR. Sequencing and phylogenetic analysis of the isolate provided the first molecular confirmation of feline histoplasmosis in the Baltic region. CONCLUSIONS: We report the occurrence of clustered autochthonous feline histoplasmosis in Latvia and expand the recognized geographic range of molecularly confirmed disease in Europe. Our cases show the advantages of cytology as an initial diagnostic tool and highlight the utility of serology and molecular methods in regions with limited access to well-established diagnostic methods for non-endemic fungal diseases. Our findings suggest that histoplasmosis may be underdiagnosed in non-endemic areas and reinforce the need for heightened clinical awareness among veterinarians across Europe.