Cystic Endometrial Hyperplasia / Pyometra

By | February 9, 2015

Development

Pyometra is a relatively common disorder of older intact female dogs. True incidence is not known because most bitches in the United States are spayed when they are young. Pyometra is a two-step process with initial cystic endometrial hyperplasia (CEH) followed by infection.

As the name implies, CEH is a cystic thickening of the endometrium, or uterine lining (). CEH can be created experimentally by exposing uterine tissue either to estrogen or to progesterone. Cystic endometrial hyperplasia develops to a greater extent and more quickly if the uterus is first exposed to estrogen and then is exposed to progesterone. This is the normal hormonal sequence of the estrous cycle in dogs. CEH develops over time after repeated estrous cycles in the dog. There are four grades of cystic endometrial hyperplasia described by Dow: worsening in severity from type I (mild changes) to type IV (severe changes with associated inflammation and tissue destruction). As might be expected because this is a progressive disorder, mean age at diagnosis of dogs with type I CEH is younger than is mean age of dogs diagnosed with type IV CEH. By the age of 9 years, two thirds of intact bitches had some degree of cystic endometrial hyperplasia in one study.

Bitches with a history of receiving estrogen or progesterone as therapy for pregnancy termination or estrus suppression are more likely to develop cystic endometrial hyperplasia, although CEH and subsequent pyometra are not more common in bitches with a history of false pregnancy (). Dogs with CEH-pyometra do not produce higher concentrations of progesterone during diestrus, nor do they produce progesterone longer during diestrus.

The second step in the development of pyometra is infection. During proestrus and estrus, the cervix is open. This allows the normal bacterial flora of the vagina to ascend into the uterus, which occurs during every estrous cycle in bitches whether or not they are bred. In bitches with a normal uterus, bacteria are expelled from the uterus before the onset of diestrus. In bitches with CEH, bacteria colonize the thickened uterine lining and are not expelled. As diestrus begins, the cervix is closed, preventing expulsion of bacteria. Under the influence of progesterone, the uterus does not contract and the uterine glands are stimulated to produce secretions. This promotes rapid growth of the bacteria embedded in the uterine lining.

Organisms that cause pyometra are those of the normal vaginal flora. The vagina is not sterile at any time, and a large number of organisms live in balance in the uterus (Table Organisms Cultured from the Vagina of Normal Intact or Spayed Dog Compared with Organisms Cultured from Bitches with Pyometra). The most common organism associated with pyometra is Escherichia coli. It has been demonstrated that the organism causing infection in a given bitch is the same subtype of organism found in the bitch’s feces and on her skin. Dogs that develop pyometra do not do so after contracting infection from a male to which they were bred or after being exposed to a new environment or new bitch or stud dog in the kennel but instead are infected with their “own” bacteria.

Table Organisms Cultured from the Vagina of Normal Intact or Spayed Dog Compared with Organisms Cultured from Bitches with Pyometra (Listed from greatest to least prevalence)

Organisms from the Normal Vagina

  • Escherichia coli
  • Streptococcus spp.
  • Pasteurella spp.
  • Staphylococcus spp.
  • Bacillus spp.
  • Enterococcus spp.
  • Proteus spp.
  • Klebsiella spp.
  • Haemophilus spp.
  • Moraxella spp.
  • Flavobacterium
  • Pseudomonas spp.
  • Corynebacterium spp.

Organisms from Bitches with Pyometra

  • Escherichia coli
  • Streptococcus spp.
  • Staphylococcus spp.
  • Klebsiella spp.
  • Proteus spp.
  • Pseudomonas spp.
  • Corynebacterium pyogenes
  • Enterococcus spp.
  • Pasteurella spp.
  • Serratia spp.
  • Haemophilus spp.
  • Bacillus spp.

When infection develops in the uterus, discharge and white blood cells fill the uterine lumen. The bacteria float in a sea of pus within the center of the uterus, making it difficult to reach them with antibiotics, which do not diffuse into that fluid. Bacteria also may form a biofilm, a structure of proteins and sugars that supports the bacteria and prevents ready eradication. The cervix may or may not open because of the pressure of fluid against the cervix as the uterus distends.

Secondary disease conditions that may develop after pyometra is established are kidney dysfunction and suppression of the immune system. Escherichia coli and other bacteria of its class (gram-negative bacteria) release toxins from their cell wall as they die. These toxins impair the function of the kidneys. Renal damage also occurs as protein antigens from the bacteria bind to antibodies and lodge within the kidney. Damage may be irreversible. It also has been demonstrated that bitches with pyometra have decreased function of their immune cells, impairing their ability to fight off infection themselves.

Signalment

Because pyometra occurs secondary to cystic endometrial hyperplasia, which is a progressive disorder, pyometra is seen most commonly in aged bitches. However, pyometra has been reported to occur in bitches younger than 1 year of age and should always be considered a possibility when bitches present with typical clinical signs during or just after diestrus. Multiple reports have documented this disorder to be more common in aged bitches that have never borne pups; reason for this predisposition is not known. Breed predisposition is not well defined. Some studies have demonstrated no breed predisposition, whereas Saint Bernards, rottweilers, and Swedish hounds were reportedly predisposed in one study, and chow chows were reported to be predisposed in two studies.

History And Clinical Signs

The history usually is of a bitch having gone through her most recent estrus within the last 12 weeks. Clinical signs vary depending on whether or not the cervix is open. If the cervix is open, the classic clinical sign is exudation of a foul-smelling, thick discharge, often with the appearance of tomato soup. Most bitches with an open cervix have fewer and less severe clinical signs than do bitches with a closed cervix ().

Diagnosis

Diagnosis of pyometra requires demonstration of the presence of intrauterine fluid in the absence of pregnancy. Because this disorder often occurs during diestrus and may occur in bred bitches, it is important to differentiate possible pyometra from pregnancy (). This usually is best done by ultrasound (). Abdominal palpation may allow one to determine whether the uterus is enlarged but yields no other information. Radiography allows identification of uterine enlargement but does not differentiate pregnancy from pyometra until after fetal mineralization would have occurred. Ultrasound definitively differentiates the two conditions much earlier in diestrus and is the preferred imaging technique.

Bloodwork also should be performed. A complete blood count demonstrates high white blood cell (WBC) count with a preponderance of young WBCs, indicative of active infection, in most cases. The white blood cell count may be very high in dogs with closed-cervix pyometra. Anemia may be present as well. A serum chemistry profile should be evaluated for assessment of possible secondary renal disease. Urinalysis usually is not performed. Any urine sample allowed to run through the vagina for collection by free catch will be adulterated with vulvar discharge. It is dangerous to collect a sample by cystocentesis, in which a needle is placed into the bladder directly through the abdominal wall, because the large, pus-filled uterus may be hit by mistake.

Diagnosis of dogs with very subtle clinical signs may be problematic. A technique using a narrow-diameter, long endoscope to visualize the cervix and pass instruments through it to permit collection of uterine samples for culture or cytology has been described but is not routinely performed.

Treatment

The preferred treatment for all dogs with pyometra is ovariohysterectomy (OHE). Pyometra is a progressive condition that cannot be completely cured. CEH is irreversible. Physically removing the cystic endometrial hyperplasia (as in a dilatation and curettage [D&C] done in humans) has not been described in the dog and would be very invasive and unlikely to permit redevelopment of a normal endometrium. Because CEH is persistent, the dog will be predisposed to pyometra after every estrous cycle for the rest of her life. In most cases, it is in the dog’s best interest to be spayed.

An OHE is performed using the same technique as for sterilization. The bitch should be stabilized with appropriate antibiotic and fluid therapy before anesthesia is induced. Spaying is curative, and most bitches tolerate and recover from surgery well.

Surgical techniques to place drains, promoting expulsion of discharge through the cervix, are not at all routinely used. If the owner of the dog strongly desires that it not be spayed, medical therapy can be considered. I caution against the use of medical therapy for dogs with closed-cervix pyometra. Some reports have described successful medical therapy in dogs with closed-cervix pyometra, and other practitioners may be more open to the idea. Medical therapy consists of treatment with antibiotics, which control infection, and either prostaglandin, which causes uterine contractions directly, or antiprogestogens (RU486 or aglepristone), which decrease progesterone concentrations and allow spontaneous uterine contractions to occur. Prostaglandin is the drug most commonly used in the United States. The idea is that pressure of the contracting uterus and intrauterine fluid will put pressure on the internal cervical orifice, opening it. Concerns about this are (1) we cannot know how healthy the uterine tissue is and by increasing intrauterine pressure risk rupturing the uterus and causing widespread infection of the abdominal cavity (peritonitis), and (2) increased intrauterine pressure may force pus out the uterine tubes and into the abdomen, again causing peritonitis. The only reported cases of salpingitis (inflammation of the uterine tubes) in the dog were in bitches treated medically for closed-cervix pyometra. Remember that antibiotics cannot diffuse into the pool of fluid in the uterus, meaning that dogs treated medically are exposed to possible toxins from the bacteria involved until the pool of uterine fluid is cleared and all bacteria are lying against the uterine lining and exposed to the antibiotics in the bloodstream there. For dogs already showing signs of illness from endotoxins released from bacteria, such as renal dysfunction, it is not in their best interest to delay resolution of infection. Finally, it has been demonstrated that bitches that develop pyometra again after medical therapy almost invariably have the exact subtype of bacteria in both cases. This suggests that infection is not completely eradicated but just decreased to a subclinical level.

For medical therapy to be considered, the bitch should meet the following criteria:

  • • Her cervix should be open, evidenced by significant vulvar discharge.
  • • She should be young and in good body condition; there is no point trying to preserve reproductive function in a bitch that is unlikely to conceive in the best of conditions.
  • • She should be a valuable member of a breeding program. Again, there is no point trying to preserve reproductive function if the owner is not sure the bitch should be used for breeding.
  • • She has normal kidneys, evidenced by normal values on bloodwork.

For medical therapy, the bitch is stabilized with fluids and any other systemic conditions addressed. A sample of vulvar discharge is collected and submitted for culture. Antibiotic therapy is started pending culture results; a penicillin-type drug usually is used. The antibiotic chosen may need to be changed, depending on the culture and sensitivity results. The size of the uterus is determined in some repeatable way (e.g., palpation, radiographs, ultrasound). Prostaglandin is administered once or twice daily until the uterus nears normal size. The dog should continue to receive antibiotics until there is no more vulvar discharge, which in some cases may take up to a month.

Because the bitch treated medically for pyometra has cystic endometrial hyperplasia and is predisposed to pyometra at every subsequent season, it is strongly recommended that she undergo vaginal culture and receive antibiotics at every subsequent season. Bitches treated medically for pyometra should be bred the next season after treatment. Once all the desired matings have been achieved from that bitch, she should be spayed.

Prognosis

Prognosis for life with either closed- or open-cervix pyometra is good in most cases. OHE always can be performed, even if medical therapy was attempted with poor response. It is the rare bitch that dies during surgery or does not recover well after surgery, especially if care is taken to stabilize the bitch before surgery is performed.

Prognosis for fertility in bitches treated for open-cervix pyometra is fair to good. Recurrence rate reported in the literature varies from 10% to 40%, and the fertility rate after treatment averages 79%.