Pyometra in the Cavalier King Charles Spaniel


Pyometra is a life-threatening, inflammatory bacterial infection of the uterus of mature intact female canines. The word “pyometra” literally means pus in the uterus. It is very common among purebreds, with as many as 25% of them developing the disorder before the age of 10 years. Unfortunately, cavalier King Charles spaniels and a few other breeds* are at even higher risk for developing this disease – as many as 50%, according to some studies.

*Golden retriever, Rottweiler, Bernese mountain dog, and rough-haired collie.


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What It Is

Pyometra is a hormone-induced infectious bacterial disease of the uterus, which usually occurs within a few weeks to months after the last stage of the bitch's estrous cycle (the “in heat” period). While in most breeds it typically will develop in their later years up to age ten years, in the cavalier it has been found more likely to develop at an earlier age.

Pyometra usually develops from a combination of factors, including immune system vulnerabilities, hormonal influences, and infection caused by Escherichia coli (E. coli), although other bacteria may be the culprits. These bacteria are constantly present in the dog’s vagina (and gastrointestinal tract), and they are able to ascend to the uterus during certain phases of the estrus cycle. Normally, the dog’s immune system is able to fend off the bacteria, and in those instances in which it is not, pyometra may develop.


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Symptoms

Symptoms of pyometra typically appear within weeks to four months after the completion of the bitch’s estrus cycle. The earliest signs include loss of appetite, diarrhea, excessive thirst, excessive urination, a low-grade fever, and vomiting. Such symptoms are easily attributed to other causes. She may also engage in excessive licking of the vulva.

The infected uterus will increase in size and weight, due to the buildup of pus.  In such case, the dog may exhibit  a swollen abdomen, weakness in her rear legs, and lethargy.

If the dog’s cervix is open to the vagina, there may be a bloody or mucousy vaginal discharge. If the cervix is closed, there likely will be no vaginal discharge, thereby delaying diagnosis and increasing the likelihood of complications due to the inability to eliminate any of the infectious materials. In such cases, the buildup of bacteria could cause the uterine wall to rupture and spread the pus material to the rest of the abdomen, a disorder called septic peritonitis. Bitches with closed cervix pyometra could develop signs of dehydration, shock, and collapse.

Pyometra Diagram -- Courtesy of www.bhsah.com


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Diagnosis

Pyometra is potentially life-threatening, and therefore, early recognition is crucial for a favorable outcome.

A recent estrus and the vaginal discharge, along with the typical although ambiguous clinical symptoms, would indicate the possibility of pyometra. If there is no discharge, the diagnosis becomes more difficult. The veterinarian likely will palpate the abdomen to detect an enlarged uterus. A complete blood count should show a high white cell count, high nitrogen compound levels, high protein levels, and an excess of globulin, among other indications of bacteria. X-rays should show the enlarged uterus.

An ultrasound scan of the abdomen is the preferred method for detecting pyometra. It also enables the veterinarian to discount other possible causes of the symptoms. Biomarkers for early diagnosis and predicting prognosis are being investigated. See this July 2015 article.


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Treatment

The usual treatment of pyometra is an immediate and complete ovariohysterectomy. First, however, the bitch needs to be medically stabilized and treated with antibiotics, to deal with the bacteria. This surgery can be risky, considering its extent and the condition of the very ill patient. Careful monitoring after surgery and follow-up care are very important.

A possible alternative to surgery for some young bitches with open-cervix pyometra may be medical management. Prostaglandin F2-alpha is the most commonly used medication to treat pyometra in dogs. Prostaglandins are a group of hormone-like hydroxy fatty acids that stimulate contractility of the uterine muscle and control inflammation. Dopamine agonists also have been used in combination with prostaglandins to treat pyometra.

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What You Can Do

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Veterinary Resources

Breed Risk of Pyometra in Insured Dogs in Sweden. Agneta Egenvall, Ragnvi Hagman, Brenda N. Bonnett, A°ke Hedhammar, Pekka Olson, Anne-Sofie Lagerstedt. J Vet Intern Med. 2001;15:530–538. Quote: "An animal insurance database containing data on over 200,000 dogs was used to study the occurrence of pyometra with respect to breed and age during 1995 and 1996 in Swedish bitches 10 years of age. A total of 1,803 females in 1995 and 1,754 females in 1996 had claims submitted because of pyometra. Thirty breeds with at least 800 bitches insured each year were studied using univariate and multivariate methods. The crude 12-month risk of pyometra for females 10 years of age was 2.0% (95% confidence interval 1.9–2.1%) in 1995 and 1.9% (1.8–2.0%) in 1996. The occurrence of pyometra differed with age, breed, and geographic location. The risk of developing pyometra was increased (identified using multivariate models) in rough Collies, Rottweilers, Cavalier King Charles Spaniels, Golden Retrievers, Bernese Mountain Dogs, and English Cocker Spaniels compared with baseline (all other breeds, including mixed breed dogs). Breeds with a low risk of developing the disease were Drevers, German Shepherd Dogs, Miniature Dachshunds, Dachshunds (normal size), and Swedish Hounds. Survival rates indicate that on average 23–24% of the bitches in the databases will have experienced pyometra by 10 years of age. In the studied breeds, this proportion ranged between 10 and 54%. Pyometra is a clinically relevant problem in intact bitches, and differences related to breed and age should be taken into account in studies of this disease."

New Aspects of Canine Pyometra: Studies on Epidemiology and Pathogenesis. R. Hagman. Doctoral thesis, Swedish University of Agricultural Sciences. 2004. Quote: "Pyometra is a common and lethal disease in bitches characterised by uterine bacterial infection leading to subsequent systemic illness. The objectives of the present thesis were to investigate the incidence of the disease in relation to breed and age, to assess bacteriological aspects of pyometra and to evaluate the involvement of endotoxin and prostaglandin F2α in the pathogenesis. Animal insurance data revealed age- and breed-dependent differences in the incidence of pyometra. On average 23-24% of all bitches studied experienced pyometra before 10 years of age. Data presented in this study indicate that certain breeds have a genetic pre-disposition for pyometra. ... Breeds with high risk of the development of pyometra in the present study were Collie (rough-haired), Rottweiler, Cavalier King Charles Spaniel, Bernese Mountain Dog and Golden Retriever. ... The interactions with biological age could be interpreted as that in some breeds (e.g. Rottweiler, rough-haired Collie, Golden Retriever, and Cavalier King Charles Spaniel in 1995), the risk of pyometra actually increases more and at an earlier age compared with other breeds. These breeds may carry a higher genetic predisposition for pyometra than other breeds. In general, breed differences may reflect true genetic differences or merely constitute a reflection of the different life spans in different breeds. If true genetic differences in predilection exist, the possibility of instituting breeding programmes to control the disease could be considered. ... Bacteriological genotype examinations showed that pyometra is most likely caused by Escherichia coli clones originating from the normal flora of each dog, i.e. not by clones spreading between animals. The resistance among E. coli isolates from pyometra bitches against antimicrobials commonly used in canine practice was low and not likely to cause therapy failure. Data on antimicrobial resistance of E. coli from urinary tract infections were generally not suitable for selecting antimicrobial treatment of pyometra. Systemic endotoxemia was confirmed in bitches with pyometra. The plasma levels of endotoxin were correlated with concentrations of the prostaglandin F2α metabolite (PG-metabolite). This indicates the usefulness of PG-metabolite in the diagnosis of endotoxemia in bitches. Bitches with pyometra also had increased blood concentrations of PG-metabolite compared with bitches with cystic endometrial hyperplasia (CEH). The present study revealed that in bitches with fluid in the uterus, the analysis of PG-metabolite in combination with percentage band neutrophils can distinguish between pyometra and CEH. The levels of PG-metabolite are predictive of the severity of pyometra since they were correlated to criteria of a systemic inflammatory response and also to the length of hospitalisation. In summary, this thesis provides data on breed- and age-related differences in the incidence of pyometra, which will be helpful in future studies of the disease and breeding programmes. In addition, clarification of key bacteriological and pathophysiological characteristics of the development of pyometra can improve diagnostic and therapeutic strategies and increase survival rates.

Canine pyometra. Frances O. Smith. Theriogenology. 2006;66:610–612. Quote: "Pyometra, literally meaning pus in the uterus, is a common disease entity of intact bitches. ... There is an increased risk for pyometra in some breeds, including the following: Golden Retriever, Miniature Schnauzer, Irish Terrier, Saint Bernard, Airedale Terrier, Cavalier King Charles Spaniel, Rough Collie, Rottweiler, and Bernese Mountain Dogs. ... Similar conditions occur, including hydrometra and mucometra. The exact etiology is unknown; however the repeated and prolonged response to estrogen followed by long intervals of progesterone dominance in the intact bitch leads to hormonally mediated changes in the endometrium. The endometrium changes when impacted by bacterial infiltration; changes in endometrial steroid receptors can result in the clinical syndrome described as pyometra. This paper will describe the signalment, risk factors, prevalence, proposed etiologic events, and both medical and surgical therapies. In addition, the prognosis for successful outcome and effects on future reproduction will also be described."

Determining the optimal age for gonadectomy of dogs and cats. Margaret V. Root-Kustritz. JAVMA. December 2007;231(11):1665-1675. Quote: "Pyometra-Incidence of pyometra in dogs and cats in the United States has not been reported, perhaps because of the prevalence of OHE in these species before they reach an age when they would be likely to develop pyometra. In other countries, 15.2% and 23% to 24% of bitches developed pyometra by 4 and 10 years of age, respectively. Pyometra is more common in nulliparous bitches than in bitches with a history of carrying a pregnancy successfully to term. There is a significant likelihood that cats will have clinical evidence of uterine disease when queens reach 5 years of age. Dog breeds reported to be at increased risk of developing pyometra include the Bernese Mountain Dog, Cavalier King Charles Spaniel, Chow Chow, Collie, English Cocker Spaniel, Golden Retriever, Rottweiler, and Saint Bernard. In animals with pyometra, OHE is curative, with reported _mortality rates of 0% to 17% in dogs and 8% in cats."

Investigation on the Antiendotoxic Effect of the Combination of Polymyxin E and Ampicillin in Dogs with Endotoxic Pyometra. Ayse Demirel, Şükrü Küplülü. Kafkas Univ. Vet. Fak. Derg. 2010;16(2):313-318. Quote: "The aim of this study was to determine the incidence and levels of the gram negative bacterial endotoxin, and to investigate the effects of antiendotoxemic treatment along with operation. ... Studies carried out in different regions indicated, pyometra is seen in Collie, Rottweiler, Cavalier King Charles Spaniel, Spitz, Doberman Pincher, Bernese Mountain Dog and Golden Retriever breed in the very high frequency. ... Thirty bitches with pyometra were used in this study. The bitches were randomly allocated into two groups as Group I (treated with polymyxin E-ampisillin) and Group II (treated with ampisillin). Samples for bacteriological examination were taken from vagina, vesica urinaria and uterus of all bitches. Blood samples were collected to evaluate biochemical, haematological tests and serum toxine levels before the operation and on 7 days after operation. Gelation was carried out to determine the gram negative bacterial endotoxin level with E-toxate test kit in accordance with gelation system. Gram negative bacteria were isolated 66% in Group I and 80% Group II. Escherichia coli were dominantly (63.4%) isolated from the uteri of 30 bitches with pyometra. Before the operation, serum toxin levels were found in Group I (n=10) 1.2±0.4 EU/ml and in Group II (n=12) 0.9±0.2 EU/ml. Five bitches in Group I and 3 bitches in Group II died on the third day after operation. Survival rate was a positive correlation with toxin levels (r=0.727; P<0.01) and BUN (r=0.539; P<0.01), creatinin (r=0.504, P<0.05) before operation in recovered and dead bitches. Serum toxin levels were not different between Group I (n=6; 0.14±0.02 EU/ml) and Group II (n=11; 0.19±0.01 EU/ml) 7 days after operation. Difference of toxin levels in both groups were different (P<0.05) between the preoperation period and the 7th day after operation. Before the operation and on the 7th day after the operation, in Group I difference between band neutrophil count and in Group II ALT, ALP, BUN, creatinin, RBC, WBC, Hct, band neutrophil and lenphocyte value were found significant (P<0.05). As a result, there was a positive correlation between toxin levels and BUN-creatinin values. Also, the cases that have the increased BUN and creatinin levels along with high toxin levels were trended towards to low survival rate. After operation, in cases that performed with ampicillin were acquired more effective results contrary to the hipothesis according to polymyxin E+ampicillin combination in bitches with pyometra."

Canine pyometra: Early recognition and diagnosis. Jeff Dennis, Brian Lucas Hamm. dvm360. May 2012. Quote: "Although this uterine disorder typically affects adult dogs, it can occur in intact female dogs of any age. ... Pyometra can occur in any breed of dog. Breeds thought to be predisposed to pyometra include rough-coated collies, rottweilers, miniature schnauzers, Cavalier King Charles spaniels, golden retrievers, Bernese mountain dogs, and English springer spaniels. ... Because of its nonspecific clinical signs, it may be overlooked until severe. Here's what you need to know to identify pyometra as early as possible. Canine pyometra is an infectious and inflammatory disorder of the uterus typically occurring in adult, intact bitches during or immediately after the luteal phase of the estrous cycle. The clinical signs of pyometra are often nonspecific and vary among patients depending on the chronicity of the disease and the patency of the cervical canal. Early recognition, diagnosis, and treatment of pyometra are necessary to achieve a successful outcome. In this article, we review the pathophysiology, signalment, clinical signs, and diagnosis of canine pyometra. And in the next article, we summarize the surgical and medical management options available for treating this condition."

A retrospective study of pyometra at five RSPCA hospitals in the UK: 1728 cases from 2006 to 2011. A. Gibson, R. Dean, D. Yates, J. Stavisky. Vet.Rec. October 2013;173:396. Quote: "A retrospective cross-sectional study was used to analyse pyometra cases at five RSPCA Animal Hospitals across the UK from 2006 to 2011. A total of 1728 cases of pyometra were recovered from a female dog outpatient caseload of 78,469 animals, giving a total prevalence of 2.2 per cent over the study period. There was an annual increase in the incidence of pyometra within the population, while elective ovariohysterectomy caseload has declined. There were variations in breed and age at presentation. Bullmastiffs (P<0.0001), golden retrievers (P=0.001) and dogue de Bordeaux (P=0.008) were over-represented in the pyometra population when compared with the female dog outpatient caseload. Mean age at presentation was 7.7 years. Some breeds presented at a significantly lower age, including dogue de Bordeaux (mean age 3.3 years) and bullmastiffs (mean age 5.4 years), while others presented as older dogs, including Yorkshire terriers (mean age 9.4 years) and border collies (mean age 10.3 years). Surgical mortality rate at the Greater Manchester Animal Hospital was 3.2 per cent. Pyometra is of significant welfare concern, and also has cost implications, particularly in charity practice. These results serve to highlight this condition so that future change in charity practice caseload can be anticipated and strategies can be directed to improve animal welfare."

Increased concentrations of Serum amyloid A in dogs with sepsis caused by pyometra. Supranee Jitpean, Ann Pettersson, Odd V Höglund, Bodil Ström Holst, Ulf Olsson, Ragnvi Hagman. BMC Vet. Research. 2014;10:273. Quote: "Background: Sepsis is a serious and potentially life-threatening condition and early diagnosis and appropriate treatment is crucial for survival. Pyometra is one of the most common diseases in intact female dogs. The disease often leads to sepsis (systemic inflammatory response syndrome, SIRS, caused by infection). Diagnostic markers for detecting sepsis are gaining increasing interest in veterinary medicine. Acute phase proteins (APPs) such as C-reactive protein (CRP) are useful for detecting systemic inflammation in dogs. Serum amyloid A (SAA) is another major APP in dogs that is not yet as widely used. Albumin is regarded as a negative APP and has earlier been evaluated for prediction of prognosis in septic dogs. The aim of the present study was to determine SAA, CRP and albumin concentrations in dogs with sepsis and pyometra and to evaluate whether these inflammatory markers are associated with length of postoperative hospitalization. Results: Thirty-one surgically treated bitches with pyometra were included [Cavalier King Charles Spaniel (n = 2)], whereof 23 septic (SIRS-positive) and eight non-septic (SIRS-negative). Albumin concentrations were analyzed by routine automated methods. SAA and CRP analyses were performed with previously validated commercially available assays (ELISA and immunoturbidimetric). Mean (±SE) serum concentrations of SAA were significantly higher in septic (130.8 ± 8.0 mg/L) compared to non-septic bitches (88.5 ± 12.5 mg/L). Using a cut-off value for SAA of 109.07 mg/L (n = 31 bitches), the sensitivity and specificity for detecting sepsis was 74% and 50%, respectively. Serum albumin concentrations were not significantly different in septic compared to non-septic bitches (mean ± SE, 25 ± 1 g/L and 26 ± 1 g/L, respectively). CRP concentrations were also not significantly different in septic (mean ± SE 225.6 ± 16.0 mg/L) compared to non-septic bitches (mean ± SE, 176.0 ± 27.1 mg/L). None of these inflammatory markers were associated with the outcome as measured by length of hospitalization. Conclusions: SAA concentrations were increased in dogs with sepsis induced by pyometra and may be useful as an adjunctive diagnostic marker for sepsis. To evaluate the full potential of SAA as a marker for sepsis also in other diseases, further studies are warranted."

Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions. Fabiana Azevedo Voorwald, Fabio Albuquerque Marchi, Rolando Andre Rios Villacis, Carlos Eduardo Fonseca Alves, Gilson Hélio Toniollo, Renee Laufer Amorim, Sandra Aparecida Drigo, Silvia Regina Rogatto. PLOSone. July 2015. Quote: Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

Canine pyometra - what is new? Hagman, R. 8th Int'l Symposium on Canine & Feline Reproduction. June 2016. Quote: Pyometra is a common disease, affecting in average 19% of all intact bitches before 10 years of age (1). Breed greatly influences the risk, which indicates that genetic factors may contribute to the predisposition in certain breeds. The disease is hormone-induced followed by an opportunistic bacterial uterine infection, but the pathogenesis is not completely understood despite extensively researched. Whether increased susceptibility of the bitch or the virulence of the infecting bacteria is most important has been debated, and may differ among age groups. The causative bacteria originate from the microbiota of each bitch i.e. are not derived from one clone or spread between different bitches. Certain bacterial strains, however, are more pathogenic than others. The possibility of limiting the disease by immunization against virulence factors such as Escherichia coli adhesins remains to be investigated. Pyometra is potentially life-threatening in severe cases. Early recognition of the disease and appropriate treatment is therefore crucial for a favorable outcome. Recently, biomarkers for early diagnosis and predicting prognosis has been investigated. Promising new biomarkers have been recognized, but most are not yet clinically available. Findings from clinical and laboratory examination may also be useful as indicators of prognosis. Regarding surgical treatment, laparoscopically-assisted single incision ovariohysterectomy was feasible in selected cases. Certain analgesia and anesthesia protocols may be beneficial by subduing inflammation. Inflammatory variables followed during recovery may be beneficial for detection of complications. As for medical treatment of pyometra, a new modified protocol with aglepristone administration in combination with 6 days antimicrobial therapy was highly successful, in 47 cases, and no recurrence was reported after 2 years. Advancing treatment routines for pyometra, thereby improving outcome warrants further research studies. Identifying clinically useful diagnostic and prognostic biomarkers are also interesting prospects for future investigations.

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