Ovariohysterectomy is the treatment of choice for pyometra. Medical management could be considered if preserving the reproductive potential of the bitch or queen is desired. Fluids (IV) and broad-spectrum, bactericidal antibiotics should be administered. Fluid, electrolyte, and acid-base imbalances should be corrected as quickly as possible, before ovariohysterectomy is performed. The bacterial infection is responsible for the illness and will not resolve until the uterine exudate is removed. Oral antibiotics (based on the results of the culture and sensitivity) should be continued for 7–10 days after surgery.
Medical therapy with prostaglandin F2α (PGF2α) can be used for animals to be bred in the future, although prostaglandins are not approved in the USA for use in cats or dogs. PGF2α causes luteolysis, contraction of the myometrium, relaxation of the cervix, and expulsion of the uterine exudate. They should probably not be used in animals >8 yr old or in those not intended for breeding. The delay before clinical improvement and the many adverse effects of PGF2α preclude its use in a severely ill animal. PGF2α also should be used with caution in bitches or queens with a closed-cervix pyometra because of increased risk of uterine rupture. Pregnancy must be excluded, because prostaglandins can induce abortion.
Naturally occurring PGF2α (0.25 mg/kg/day, SC, for 5 days) is commonly used. Synthetic analogues (eg, cloprostenol, fluprostenol, and prostalene) are much more potent than natural PGF2α and have been used to treat pyometra in dogs. Broad-spectrum, bactericidal antibiotics, chosen on the basis of culture and sensitivity tests, should be given for ≥2 wk.
The adverse effects of PGF2α include restlessness, anxiety, panting, hypersalivation, pacing, tachycardia, vomiting, urination, and defecation. In cats, vocalization and intense grooming behavior also may be seen. These reactions disappear within 2 hr of the injection. The LD50 of PGF2α in dogs is 5.13 mg/kg. Severe ataxia, respiratory distress, and muscle tremors may be seen in queens given 5 mg/kg. If adverse effects are severe, IV fluids at rates appropriate for treatment of shock are indicated. Uterine evacuation after an injection is variable.
Other antiprogestins (eg, aglepristone) are available in some European countries. Clinicians using aglepristone report virtually no adverse effects as compared with prostaglandins. Aglepristone is also used to treat bitches with closed-cervix pyometra. In one study, a dosage of 10 mg/kg given on days 1, 2, and 8 in 15 bitches with closed pyometra led to opening of the cervix after 26±13 hr in all treated animals.
Animals should be reexamined 2 wk after completion of medical therapy. If a sanguineous or mucopurulent vulvar discharge or uterine enlargement is still present, PGF2α therapy, using the same protocol, may be repeated; however, the prognosis for recovery is much worse. After medical therapy, the prognosis for initial resolution of the pyometra is good if the cervix is open but guarded to poor if closed. Of those animals that respond, as many as 90% of bitches and 70% of queens with open-cervix pyometra may be fertile. Recurrence is likely; 70% of bitches treated medically for pyometra had recurrence within 2 yr. Therefore, the animal should be bred on the next and each subsequent cycle until the desired number of puppies or kittens has been produced, and then spayed. Prostaglandins should not be dispensed for owner administration because of the narrow safety index and the potential to trigger asthmatic events and pregnancy loss in people.
Typically, pyometra occurs in a bitch one to two months following estrus due to elevated progesterone level whether she was bred or not (Nelson and Feldman, 1986). Clinically, the bitch may present with inappetence, depression, polydipsia, lethargy and abdominal distension. She may or may not have vaginal discharge and fever and will often have an elevated White Blood Cell (WBC) count. The incidence of pyometra in dogs is approximately 24% before 10 years of age (Hagman, 2000). During this time, progesterone levels are elevated and help to create the ideal conditions for infection. This progesterone-primed condition stimulates uterine glandular secretions within the uterus, which suppresses uterine contractions (Cox, 1970) and inhibits the effect of infection-fighting blood cells in the uterus. The effects are cumulative in that each estrous cycle results in more glandular activity and higher levels of inflammatory cells and fluid or mucous within the uterus. After the establishment of a bacterial infection, which may originate from vaginal infection, urinary tract infection, or fecal contamination, the bacteria enter the uterus and multiply. In approximately 90% of cases, Escherichia coli is a main causal agent (Susi et al., 2006). This bacterium produces endotoxins (that are capable of initiating the cytokine cascade and the release of many inflammatory mediators. E. coli is thought to be the cause of the local and systemic inflammatory reactions associated with pyometra. Cystic Endometrial Hyperplasia (CEH) often precedes the disease, but can also be found in many older bitches with no signs of pyometra. The clinical manifestations of canine pyometra are well known. Some breeds are more prone to uterine infection like golden retriever, miniature schnauzer, Irish terrier, Saint Bernard, Airedale terrier, Cavalier King Charles spaniel, rough collie, Rottweiler and Bernese mountain dog and some are low susceptible to developing the disease include Drevers, German shepherds, miniature dachshunds, dachshunds (normal size) and Swedish hounds (Egenvall et al., 2001). Severe pyometra sometimes leads to fatal and systemic infection and infertility. Scientific reports on canine pyometra are not frequent in Bangladesh, but common reproductive problems in pets have been reported (Juyena et al., 2005). Different treatment methods have been applied during pymetra treatment but the popular and effective methods is ovario-hysterectomy (OHE) (Feldman and Nelson, 2004; Johnston et al., 2001). The present study was discussed about histo-pathological conditions during pyometra in a bitch.
A 9-year-old virgin German shepherd was admitted to the SA Quadery Teaching Veterinary Hospital, Chittagong Veterinary and Animal Sciences University, Bangladesh, with a several-day history of sanguinopurulent vaginal discharge was referred by a District Veterinary Hospital, Chittagong Metropolitan Area, Bangladesh. The clinical examination revealed that the dog was dull and depressed, licked her backside (vagina) and was uncomfortable. Her daily food intake was low, but other behaviors were quite normal. On physical examination, the dog was found to be quite normal with the exception of vaginal discharge and a deteriorated body condition. Systemic antibiotics in the form of Ceftriaxone (Eracef® Vet, 1 g vial, Popular Pharmaceuticals Ltd., Bangladesh) were administered, but there was no improvement. Hematological examination revealed a high WBC count (65%), indicating the presence of infection. OHE was considered to be the best treatment for pyometra with either an open or closed cervix. The most common reason given for surgical removal of the uterus and ovaries is prevention of disease recurrence.
OHE was aseptically performed according to a standard procedure. Premedication was administered in the form of intramuscular atropine sulfate (Atropine®, Techno drug, Bangladesh, 0.04 mg kg-1) and xylazine hydrochloride (Xylaxin®, Indian Immunologicals Ltd, India, 1 mg kg-1) intramuscularly. Induction and maintenance involved a diazepam (Sedil®, Square Pharmaceutical Ltd., Bangladesh) and ketamine hydrochloride (Calipsol®, Gedeon Richter Ltd., Dudapest, Hungary) combination (0.5 and 5 mg kg-1, respectively). After exposing the abdomen by laparotomy, the uterine and ovarian blood vessels were properly secured and the ovaries, uterine horns and uterus were completely removed. The abdominal wall was closed with catgut (Mersutures®, 2-0, Ethicon, Johnson and Johnson Ltd., Baddi, H.P. 173-206, India) according to a standard procedure. During the entire operative period, 5% dextrose saline was intravenously infused. Postoperatively, the broad-spectrum antibiotic ceftriaxone (Eracef® Vet, 1 g vial, Popular Pharmaceuticals Ltd., Bangladesh) was administered for 7 days and the painkiller ketoprofen BP (Ketoflam®, Opsonin Pharma, Bangladesh) was administered for 3 days.
RESULTS AND DISCUSSION
The uterine horns and ovaries were subjected to postoperative gross and histo-pathological examination. The gross examination revealed that the uterine horns were flabby the endometrial wall was thick and profuse sanguinopurulent discharge had accumulated in the uterine horn (Fig. 1). This may have been due to inflammation of the myometrium and endometrium wall. The endometrial layer was corrugated and a small cyst-like structure was found on the endometrium (Fig. 2). Some of the endometrial wall had been sloughed off. Interestingly, in the left ovary there was a persistent corpus luteum and in the right ovary there was a large ovarian cyst (Fig. 3). It seems that progesterone and estrogen had been secreted simultaneously. Generally, pyometra occurs after estrogen stimulation followed by prolonged progesterone dominance. Progesterone-primed conditions influence hyperplasia of the endometrium and endometrial glands, decrease myometrial contractions and inhibit the local leukocyte response to infection, which allows for bacterial proliferation within the uterine lumen.
|Fig. 1:||Sanguino-purulent pus was coming out from uterine horn after stabbing of canine uterine horn|
|Fig. 2:||Corrugated endometrium wall with small cyst like structure on endometrium|
|Fig. 3:||Large ovarian cyst with persistent corpus leutium (CL) (left) and only persistent CL (right) are present on ovary|
Ovarian cystic fluid also contains estradiol, which enhances the number of estrogen and progesterone receptors in the endometrium that activated the endometrium gland to secret endometrum fluid. During the early luteal phase, the increased progesterone concentration suppresses cellular immunity (Sugiura et al., 2004). E. coli is the most prevalent organism that causes pyometra in the dog and cat (Beutin, 1999; Coggan et al., 2008) and is normally present in the urine and feces of affected bitches (Tsumagari et al., 2005). Estradiol causes cervical dilation during estrous and therefore allows bacteria that are part of the normal flora of the vagina (especially E. coli and Streptococcus spp.) to ascend into the uterus. The combination of reduced local immunity and favorable uterine conditions for these pathogens allow for bacterial colonization and proliferation. Recently, it was reported that inoculation of E. coli into the uterus on days 11 to 20 and 20 to 30 after the luteinizing hormone peak caused canine pyometra, because at that time the uterus is most susceptible to infection (Smith, 2006).
Subacute endometritis followed by CEH is believed to cause pyometra. Endometrial hyperplasia is the result of cystic deformation of endometrial glands and stromal proliferation of fibroblasts with inflammatory reaction (De Bosschere et al., 2001). However, the CEHpyometra complex also develops as a consequence of an abnormal response of the uterus to repeated progestational stimulation during the luteal phase of the estrous cycle (Feldman and Nelson, 2004). CEH is also associated with mucometra; it results from endometrial thickening with the accumulation of viscid uterine fluid caused by hyperplastic and hypertrophic endometrial glands. CEH is not associated with clinical signs unless the uterine content becomes infected; this is referred to as pyometra (Barton, 1992). In the present study, histo-pathological examination of the affected uterus revealed multifocal erosions and ulcerations in the superficial epithelial layers of the endometrium, which was infiltrated with a large number of viable and degenerated neutrophils, tissue debris and extravascular erythrocytes (hemorrhage) (Fig. 4). The endometrial glands were expanded and haphazardly arranged with a hyperplastic, crowed epithelial lining, giving it the characteristic lesions of CEH. Diffuse cellular infiltration with neutrophils and extravasated erythrocytes in the endometrial stroma (Fig. 5) were correlated with the clinical presence of sanguinopurulent vaginal discharge. The cystic hyperplastic glands were the probable cause of the grossly voluminous uterine content and thickened uterine wall.
|Fig. 4:||Ulceration of the functional endometrium with diffuse hemorrhage in the mucosal surface (aero). Note the cystic endometrial hyperplasia (C) of endometrial glands|
|Fig. 5:||Cellular infiltration in the endometrial stroma with predominant neutrophils, lymphocytic cells and profuse extravasated erythrocytes|
These hyperplastic uterine glands might be involved in the secretion of more uterine fluid, which causes the voluminous uterine content.
In conclusion, OHE is usually the recommended treatment for pyometra associated with CEH in bitches. To the authors knowledge, this is the first report of CEH and endometritis in a virgin German shepherd dog in Bangladesh.