BackgroundPyometra, a life-threatening bacterial infection of the uterus, is classified as open or closed depending on the functional patency of the cervix i.e. presence or absence of vaginal discharge. In closed cervix pyometra, pus and bacterial products accumulate in the uterus, which is thought to induce a more severe illness. The aim of this study was to investigate whether disease severity or outcome differed in dogs with open or closed cervix pyometra.ResultsProspectively collected data from 111 female dogs diagnosed with pyometra at the University Animal Hospital, Swedish University of Agricultural Sciences, Uppsala, intermittently during 2005–2012 was analyzed. Seventy-two dogs (65%) had open cervix, whereas 39 dogs (35%) had closed cervix. Differences between the two groups were explored by Wilcoxon Two Sample Test for continuous variables and Chi-square or Fisher’s exact test for categorical variables. P < 0.05 was considered significant.In dogs with open cervix the median age was 9.0 years and the median weight 26.0 kg. In dogs with closed cervix the median age was 9.6 years and the median weight 25.0 kg, with no significant differences between the groups (p = 0.69 and 0.24, respectively). Five dogs (4.5%) died, all with open cervix, and 16 dogs (14%) had complications.The general physical condition was moderately or severely depressed in 30% (21/71) of dogs with open cervix (severely depressed in 4 dogs, moderately depressed in 17 dogs) and in 56% (22/39) of dogs with closed cervix (severely depressed in 3 dogs, moderately depressed in 19 dogs). The general physical condition was mildly depressed in 41 dogs with open cervix and 16 dogs with closed cervix, whereas it was normal in nine dogs with open cervix and one dog with closed cervix. None of the included dogs had very severely depressed general physical condition or were non-responsive.Leukocytosis, neutrophilia, monocytosis and moderately to severely depressed general condition was more commonly found in dogs with closed cervix (p = 0.003, p = 0.008, p = 0.003 and p = 0.006, respectively).Sepsis was more commonly present in closed cervix pyometra (77%, 30/39 dogs) compared to open cervix pyometra (51%, 36/71 dogs) (p = 0.007). Presence of prolonged postoperative hospitalization did not differ significantly between the two groups.ConclusionsIn dogs with closed cervix, sepsis was more common, the general physical condition more often moderately to severely depressed and leukocytosis, neutrophilia and monocytosis more frequently found. The results showed that closed cervix was associated with a more severe illness than open cervix at admission but not with poorer outcome as measured by postoperative hospitalization. These findings may be clinically valuable for optimizing monitoring and treatments in dogs with the disease.

Sepsis is difficult to diagnose and remains a common mortality cause worldwide in both humans and animals. The uterine infection pyometra causes sepsis in more than half of affected dogs and therefore allows the natural physiological development of sepsis to be studied. To find a sepsis-specific biochemical marker that could be combined with conventional clinical criteria for a more robust and quick diagnosis of sepsis, we measured systemic concentrations of high-mobility group box 1 (HMGB1) in 23 healthy control dogs and in 27 dogs with pyometra, 74% of which had sepsis.We also measured concentrations of the major acute phase protein C-reactive protein (CRP) and an indicator for endotoxaemia, prostaglandin F 2α metabolite (PGM) to assess the relative contribution of HMGB1 to the detection of systemic inflammation and endotoxaemia. We found that HMGB1 concentrations, in line with concentrations of CRP and PGM, were significantly increased in dogs with pyometra, and that concentrations of CRP, but not HMGB1, were significantly higher in dogs with sepsis compared to dogs without sepsis. Although serum HMGB1 did not differ between dogs with or without sepsis and was not correlated with either CRP or PGM concentrations, HMGB1 was correlated with the total white blood cell counts, suggesting an independent regulation and involvement in inflammation.

Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 × 10–6, passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. Next generation sequencing and genotyping of cases and controls subsequently identified four missense SNPs within the ABCC4 gene. One missense SNP at chr22:45,893,198 (p.Met787Val) showed complete linkage disequilibrium with the associated GWAS SNPs suggesting a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene, is also potentially implicated in the development of the disease.