Any acne therapyhas three goals: first, to kill the Propionibacteri-um acnes; second, to reduceinflammation; and, third, toprevent the sebaceous glandsfrom producing excess oil, clog-ging the pores and creating anenvironment that allows the P.acnes bacteria to flourish. Untilrecently most moderate tosevere acne has been treated bydermatologists with a combina-tion of antibiotics to kill thebacteria and drying agents likeAccutane and topical retinoidsto control excess oiliness.
Cheryl Lopate, MS, DVMDiplomate, American College of Theriogenologists Pyometra in the Bitch Pyometra is a condition that affects intact bitches, causing a variety of clinical signs and symptoms. Pyometra is typically pre-empted by pathologic changes in the uterus. The Greekderivation of pyometra is: pyo = pus and metra = uterus, so pyometra = an accumulation of pus inthe uterus.
As the bitch goes through the normal estrous cycle, the glands in the uterus produce secretions.
As the bitch ages (with or without repeated pregnancy), these glands may fail to empty either due toscarring around the opening of the glands which occludes them or due to failure of the muscles ofthe uterine wall to contract regularly. This failed emptying causes cyst development within the lumen(center opening) of the uterus (called cystic endometrial hyperplasia or CEH).
With each estrous cycle, as the cervix relaxes, the bacteria that normally reside in the vagina, or are introduced during mating, can enter the uterus. Ordinarily, estrogen provides protection againstinfection by promoting immune function and by stimulating uterine contractions. So, in the normalbitch, the bacteria that contaminate the uterus during estrus and mating can be cleared from theuterus before the cervix closes and as progesterone rises. In the bitch with cystic endometrialhyperplasia (CEH), uterine contractions may not be as efficient, and bacteria may remain in theuterine lumen and subsequently invade the uterine wall.
Following ovulation, progesterone concentrations rise and remain elevated for 45 – 60 days.
Progesterone is a hormone that promotes both uterine glandular secretion (for pregnancymaintenance) and bacterial growth while it suppresses uterine contractions, thereby creating anenvironment in the uterus conducive to bacterial overgrowth. In bitches with CEH, the bacteria thatare retained in or around the glands and surrounding tissues proliferate during the phase ofprogesterone production.
In the early stages of this disease, there is only inflammation in the wall of the uterus (called subacute endometritis). At this point, there are no outward signs of disease in the bitch. Withrepeated cycles, this inflammation gets worse and worse until finally there are enough bacteria andinflammation retained in the uterus that pus begins to be produced in significant quantities inside theuterine lumen.
In some bitches, there may be a stage of accumulation of mucus in the uterus prior to pus formation. In these bitches, there is glandular or lymphatic dysfunction, resulting in fluid buildup, butthere is no overgrowth of bacteria in this fluid. This condition is called mucometra. It is commonlyundiagnosed because the bitch has no outward signs of disease and any discharge present is clearto milky in color, so it either goes unnoticed or the owners are not concerned about it. Mucometratypically resolves on its own, without treatment, either during anestrous or at the onset of theensuing cycle. While CEH is present in the majority of the bitches that develop pyometra, in some cases, bitches may develop pyometra without any evidence of CEH. It is unclear at this time, why some of thesebitches develop pyometra and this variant of the disease is actively being researched. In somecases, there may be physical or anatomic defects that predispose to bacterial contamination of theuterus such as vaginal strictures or physical defects of the cervix or uterus. It is also proposed thatbacteria may be introduced into the uterus through the bloodstream, especially when the bloodsupply to the uterus is increased (during estrus).
Pyometra typically occurs 4 – 6 weeks following ovulation; however, it can occur earlier if the infection is severe enough, if bacterial numbers are very high or if the source of the infection is thebloodstream rather than the vagina. Pyometra can also occur during anestrus or estrus in theoccasional bitch. It can also occur in a portion of the uterus during pregnancy, while the rest of theuterus in unaffected.
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Cheryl Lopate, MS, DVMDiplomate, American College of Theriogenologists When pus is present and the cervix is closed the disease is termed a closed pyometra. When the cervix has opened and the uterus is draining, the disease is called an open pyometra. The severityof the signs the bitch will show is highly dependent on whether the cervix is opened or closed.
Once pyometra develops, the amount of pus may vary from just a few milliliters, to liters of fluid, depending on the size of the bitch's uterus, the rate of proliferation and the species of bacteriapresent. Generally speaking, bitches with more pus are sicker than those with lesser amounts (oftenrelated to whether the cervix is open or not). In some cases, the bacteria may be more virulent sothat the bitch may be quite ill with very little fluid present. The inflammation that results from thebuildup of pus normally causes the release of low levels of prostaglandin F2-alpha (PGF2α). Thishormone begins to cause a natural decrease in progesterone production, and promotes cervicalrelaxation and uterine contraction. Until progesterone begins to drop off, the cervix of the bitch willremain closed holding the pus within the uterus. Once the cervix opens, it allows the pus to drainout of uterus, into the vagina, and out the vulva. In some cases, significant PGF2α release may notoccur, and then progesterone will remain elevated and the cervix will remain closed. This may bedue to pathology in the uterine wall and the resultant lack of normal response to inflammation. Incertain cases of open pyometra, progesterone may already be very low or at baseline at the time ofdiagnosis.
With closed pyometra the bitch is often very depressed, with a high fever, and she quickly becomes dehydrated. Severe vomiting and diarrhea are common very early in the disease and thebitch may be drinking excessively and urinating frequently. These bitches are usually not eating well(if at all) and quickly become weak and may collapse or die. They become sick due to the toxinsproduced by the bacteria in the uterus. These toxins are excreted into the bloodstream and willquickly affect other organ systems. The most severe signs in pyometra result from the effects ofthese toxins on other body systems, a condition called the systemic inflammatory responsesyndrome (SIRS). Overwhelming bacterial infection will result in sepsis, shock and coagulationdisorders (DIC). Kidney and liver disease (acute failure) are commonly seen in patients with SIRS.
These bitches must be treated quickly and aggressively, because the toxins can rapidly overwhelmthe body's immune system resulting in collapse and death.
Bitches with open pyometra are generally not as sick as those with closed pyometra. They are usually minimally depressed, often only with low grade fever and minimal dehydration. There maybe some vomiting and increased thirst (and accompanying increase in urination) but signs areusually not as severe as with closed pyometra. Damage to the kidney and liver is usually minimal tonon-existent. These bitches may still be eating relatively normally. The degree of illness is typicallyproportional both to the amount of pus in the uterus and the toxicity of the bacteria present.
E. coli is the most common bacteria isolated from the uterus of bitches with pyometra. There are many different strains of E. coli, some more toxic than others. E. coli may have a predisposition tobind to receptors in the uterus primed with progesterone and thereby may overgrow other bacteriathat may be present.
Diagnosis of pyometra is based on clinical signs in the bitch along with some typical laboratory abnormalities. Microscopic examination of the vulvar discharge (when present) will reveal manydegenerate white blood cells and bacteria. Culture of the discharge is highly recommended toensure that the antibiotics chosen will be effective. Elevations in the peripheral white blood countare common (in bitches with closed pyometra levels may be 10x or more higher than normal, whilewith open pyometra elevations are not as severe 0.5 – 2x higher). There may also be elevations inkidney and liver enzymes depending on the amount of insult to these organs by the bacterial toxins.
Ultrasound examination of the uterus provides the definitive diagnosis and allows assessment of how much pus is actually in the uterus. The uterus may be mildly (1 - 2 cm) to markedly (6 – 8 cm,or more) distended. In advanced cases, ultrasound may reveal uterine rupture or leakage of fluidacross the uterine wall resulting in peritonitis. Ultrasound also allows assessment of areas ofthinning in the uterine wall that may indicate impending uterine rupture. If ultrasound is not 1000 Wilsonville Rd. #55 • Newberg, OR 97132 • Office: (503) 537-1123 • FAX: (503) 554-9961
Cheryl Lopate, MS, DVMDiplomate, American College of Theriogenologists available, x-rays of the abdomen may reveal an enlarged tubular structure in the abdomen (this mustbe differentiated from intestinal abnormalities or pregnancy, prior to mineralization of the fetuses).
Treatment of pyometra will depend on the type of pyometra the bitch has and the clinical signs the bitch is displaying. The treatment of choice for any pyometra is ovariohysterectomy (spaying).
Ovariohysterectomy is curative in that it removes the offending organ from the body and preventsrecurrence. In bitches that are severely ill or dehydrated, stabilization with fluids and antibiotics maybe required prior to surgery. Care must be taken during surgery to gently manipulate the fluid filleduterus as it may be predisposed to rupture. Surgery is not without risk however, and possiblecomplications include hemorrhage, peritonitis, uterine rupture, wound infection and anestheticcomplications.
In cases where the affected bitch is a valuable breeding animal, medical therapy may be selected over surgical therapy. In order for medical therapy to be a viable option, the bitch must be clinicallystable. It is preferable to have an open cervix when choosing medical therapy, but some bitcheswith closed cervix pyometra may also be successfully treated. Medical treatment involves fluid andantibiotic administration and uterine evacuation. Fluids may be given intravenously or under theskin. In some bitches, there may be little to no dehydration and they are drinking adequately so thatfluids are either minimally necessary or not required at all. Broad spectrum antibiotics should beadministered. Antibiotics will generally be continued long term after resolution of the pyometra onultrasound (typically 4 – 8 weeks after the uterus is evacuated). Uterine evacuation is the mainstay of medical therapy and is accomplished through the administration of PGF2α (the same hormone that the bitch naturally produces in the face ofinflammation in the uterus). Administration of this hormone results in smooth muscle contraction andcervical relaxation, both of which promote uterine evacuation. The uterus is made of smooth muscle(as is the GI tract and parts of the respiratory system). Because the drug will affect all smoothmuscle, side effects include GI cramping, drooling, nausea, vomiting and diarrhea. These sideeffects are transient, lasting only about 30 minutes after each injection. The bitch developstolerance to the drug as repeated doses are given, so the side effects diminish as treatmentprogresses. In order to minimize the side effects, very low doses are given early in the treatmentcourse and as the bitch adapts to the drug the dose is slowly increased. The drug is given 2 – 3times daily.
In addition to causing uterine contraction, PGF2α also causes regression of the structures on the ovaries producing progesterone (the corpora lutea) which is important to prevent further proliferationof the bacteria in the uterus. Treatment with PGF2α will be continued until the uterus is completelyevacuated (from 5 – 10 days in most cases, but up to 30 (or more) days in refractory or recurrentcases). Prior to conclusion of prostaglandin therapy, it is important to ensure that the progesteroneconcentration is basal and that it remains basal – as it has a tendency to rebound; and if it does theinfection may return.
In cases of closed pyometra, cabergoline or bromocriptine may also be administered at the onset of treatment. These medications are dopamine agonists and result in decreased prolactinproduction. Prolactin is a hormone produced by the bitch to help support the corpora lutea, so thatprogesterone production can be maintained for an extended period of time. By stopping theproduction of prolactin, cabergoline acts in concert with PGF2α to lower the progesteroneconcentration and thereby assist in cervical relaxation and uterine evacuation.
The bitch must be hospitalized while being treated with PGF2α so she can be monitored for adverse side effects and deterioration in her condition. Monitoring of the white blood count isperformed as uterine evacuation occurs and the count should drop back to normal once the infectionis effectively cleared. Sequential ultrasound examinations are performed to monitor the progressionof uterine evacuation and help determine when prostaglandin therapy may be concluded.
Any deterioration in the bitch's condition requires reassessment of the treatment plan and in some cases surgical intervention may be required if medical therapy is inadequate.
1000 Wilsonville Rd. #55 • Newberg, OR 97132 • Office: (503) 537-1123 • FAX: (503) 554-9961
Cheryl Lopate, MS, DVMDiplomate, American College of Theriogenologists Breeding bitches with a history of pyometra should be mated on the cycle following treatment using appropriate antibiotic therapy and surgical insemination (whenever possible) to minimize thecontamination brought into the uterus. The interval between estrous cycles is usually shortened (by4 - 6 weeks) following medical treatment because of the shortening of the luteal phase(progesterone secretion) resulting from prostaglandin therapy. Bitches treated medically will bepredisposed to recurrence on subsequent cycles, so should be spayed as soon as their reproductivecareers are concluded. Mated bitches must be monitored carefully after breeding for any signs ofrecurrence of the pyometra prior to (and after) diagnosis of pregnancy. Pyometra and pregnancycan occur simultaneously. Approximately 30 – 50% of bitches medically treated for pyometra can besuccessfully bred on subsequent cycles. The prognosis depends on the amount of damage to theendometrium. This is dependent on the amount of pathology in the uterus, the length of time thepyometra was present prior to diagnosis, the response to treatment and the incidence of relapse.
Prevention of pyometra is difficult, but the normal aging changes in the uterus can be slowed by placing bitches not actively being bred on mibolerone to stop cyclicity and thereby prevent theeffects of prolonged periods of progesterone dominance from acting on the endometrium andcausing pathology from occurring. The greater the number of estrous cycles the uterus is exposedto the greater the chances of pyometra occurrence. In other words, intact bitches with shortinterestrous intervals and aged bitches are more predisposed to pyometra because of the number oftimes the endometrium is exposed to prolonged progesterone production. The changes that lead up to pyometra are normal aging changes in the uterus and therefore most intact bitches, if they were to live long enough, would eventually develop pyometra. For this reason,it is recommended that any bitch not being actively used for breeding or planned future breedingsshould be spayed to prevent occurrence of this disease. Dr. Lopate is board certified in reproduction (Theriogenology). She owns and operates areproductive specialty practice providing service to companion animals and horses. Questionsregarding pyometra or other reproductive issues may be directed to Dr. Lopate at (503)537-1123,via email at [email protected] or on the web at www.reproductiverevolutions.com. 1000 Wilsonville Rd. #55 • Newberg, OR 97132 • Office: (503) 537-1123 • FAX: (503) 554-9961
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