INFLAMMATION, INFECTION, OR BOTH? ROOT CAUSES OF ENDOMETRITIS


on the inciting cause and progression of the condition. Normal mares that resolve breeding-associated inflam- mation 24 to 36hours after breeding are referred to as “resistant” to PMIE. Resistant mares are able to resolve this breeding-induced inflammation in a short time frame (96hours).4,8 “Susceptible” or “problemmares” are mares that cannot resolve the inflammatory insult of breeding within 48hours of breeding. Susceptible mares also experience prolonged inflammation, uterine fluid accumulation, and uterine fluid neutrophilia beyond 96hours.4,9–14 Additionally, these mares are unable to clear intrauterine bacterial challenge with Streptococcus equi zooepidemicus within 96hours, compared to “resist- ant”mares.15,16


3. Persistent Mating-Induced Endometritis


The diagnosis of mares with persistent mating- induced endometritis (PMIE) includes transrectal pal- pation and ultrasound findings 24hours after breed- ing that include > 2 cm of intrauterine fluid and excessive endometrial edema relative to time of ovula- tion (edema should decrease within the periovulatory window and after ovulation).14–17 Predisposing factors for mares with PMIE include anything that impedes uterine clearance and resolution of infectious or noninfectious contamination. Anatomic defects would include a pendulous uterus, a cervix that fails to relax, scar tissue that traps debris and infectious agents, and large endometrial cysts thatmechanically block uterine clearance mechanisms. Immunologic effects that predispose mares to PMIE are exacerbated proinflammatory responses (as seen in agedmares) and endocrinopathies that cause inappropriate or ineffective immune responses such as pituitary pars intermedia dysfunction and equine metabolic syndrome.16–19 The type of pathogen introduced may also affect the mare’s ability to respond effectively.20 Virulence of pathogens as enhanced by a protective biofilmmaymake the like- lihood of persistent infection and chronic endometritis more likely.20,21Additionally, degenerative changes of the endometrium such as poor lymphatic drainage, decreased normal mucus production, and impaired mucociliary apparatus can lead to an increased suscep- tibility to PMIE.19When managing a mare with a his- tory of PMIE, or that has predisposing factors (aged, poor anatomy of the reproductive tract) for PMIE, it is helpful to understand the mare’s prior reproductive his- tory. Ideally, themare is available to observe through a complete estrous cycle prior to breeding. This allows the practitioner to determine the underlying cause for failure of appropriate uterine response. Furthermore, serial examinations allowthe veterinarian to determine when the issue is occurring and to prospectively treat for optimal uterine health. For example, if the mare begins to accumulate fluid early in the cycle, ecbolic agents (oxytoxin 10IU, IM twice a day) or a prebreed- ing lavage (lactated Ringer’s solution lavage until efflux clears) can be utilized to assist in clearance.19,22 Postbreeding lavages administered 4 to 6hours after breeding help remove inflammation, debris, and


18 2022 / Vol. 68 / AAEP PROCEEDINGS


cytokines that prolong the inflammatory response.23 Antibiotics and immune modulators (dexamethasone, platelet rich plasma, mycobacterium cell wall extract) are used in some cases ofmareswith impaired anatomy or decreased immune function to help prophylactically decrease an excessive inflammatory response associ- ated with PMIE and aid in pathogen killing.24,27 With vigilant examinations, PMIE mares are often easily identified in the peribreeding period, which allows for prompt treatment. It can be challenging to diagnose the inciting cause or reason for persistent inflammation in mareswith chronic endometritis and thus, poses a chal- lenge to the practitioner. This population of mares has endometritis that developed from mating, contamina- tion, or other factors, and the clinician must identify the cause of persistent endometritis so an appropriate treatment plan can bemade.


4. Chronic Endometritis


Chronic endometritis (infectious and noninfectious) can present in a variety of ways clinically as there are many different factors that can cause the endome- trium not to be able to resolve inflammation. The di- agnosis of endometritis must be made with careful assessment of the mare’s history, systemic health, reproductive anatomy, and results from diagnostic sampling of the uterus. Differentiation of infectious versus noninfectious endometritis is traditionally made with diagnostic tools such as aerobic culture of the endometrium (swab, small-volume lavage, or bi- opsy) and cytology. The history of a mare with endo- metritis often includes decreased pregnancy rates; increased pregnancy loss before 40days of gestation; previous identification of uterine inflammation and infection on uterine cytology, culture, and/or biopsy; irregular estrous cycles; and shortened return to estrus duetoendometrial inflammation causing pre- mature luteolysis.5,14,28,29 The reproductive tract can look variable based on the inciting cause, distribution, and severity of the endometritis. Mares may have sig- nificant bacterial load and deep endometrial inflamma- tion, with few ultrasonographic signs and negative result on swab culture and cytology. In E. coli infections, it has been shown that often the endometrial cytology is negative, whereas S. equi subsp. zooepidemicus infec- tions result in more exudative reactions and endome- trial cytologies are often positive.30 Because of the variation in presentation, if one is suspicious of endome- tritis based on clinical findings, further diagnostic tests are indicated. Diagnostic sampling of the uterus is essential to determine if inflammation is present, and this is performed using uterine cytology and/or histol- ogy (biopsy). Endometrial cytology specimens are obtained with a guarded cotton-tip swab, cytobrush, or low-volume uterine lavage.30–33 Thedegreeof inflam- mation, cell types present, presence of urine crystals, mucous, debris, hyphae, yeast, and bacteria all help to understand the factors affecting the uterine environ- ment. Inflammation is generally categorized as mild (normal),moderate, or severe. The following categories


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