• Open Access

Acute Deterioration and Death with Necrotizing Enteritis Associated with Lawsonia intracellularis in 4 Weanling Horses


  • All work was conducted on local thoroughbred farms within 20 miles of Lexington, KY; when necessary, intensive care services were provided by ACVIM diplomates at the Hagyard Equine Medical Institute's McGee Medicine Center. All necropsies were performed at the University of Kentucky's Veterinary Diagnostic Laboratory by ACVP diplomates or board-eligible pathologists. This study has not been presented at any meeting

Corresponding author: A. Loynachan, Veterinary Diagnostic Laboratory, University of Kentucky, 1490 Bull Lea Road, Lexington, KY 40511; e-mail: alan.loynachan@uky.edu


equine proliferative enteropathy


immunoperoxidase monolayer assay


polymerase chain reaction

Case 1

An 8-month-old Thoroughbred colt was evaluated in October 2010 with a less than 1-day history of inappetence. Physical examination in the field revealed throat latch edema, lethargy, and fever (103.8°F) (ref 99–101.5°F). A complete blood count revealed leukocytosis (18.0 × 103/μL; ref 5.0–12.6 × 103/μL) with a relative neutropenia (49%; ref 55–65%) and lymphopenia (26%; ref 35–45%), as well as a toxic left shift (25% bands; ref 0–5%). Serum biochemistry abnormalities included hypoproteinemia (3.3 g/dL; ref 6–7.9 g/dL), hypoalbuminemia (1.2 g/dL; ref 3.4–4.1 g/dL), and an increased BUN (45 mg/dL; ref 11–26 mg/dL), along with other abnormalities (Table S1). Lawsonia intracellularis-induced equine proliferative enteropathy (EPE) was suspected because of the combination of hypo-proteinemia, hypoalbuminemia, inappetence, and the autumn presentation. Treatment consisted of intravenous oxytetracycline1 (6.6 mg/kg IV q24hr), flunixin meglumine2 (1 mg/kg IV q12h), oral omeprazole3 (1 mg/kg PO q24hr), dexamethasone4 (0.1 mg/kg IV q24hr), intravenous crystalloid fluids5 (10 mL/kg IV bolus once), and intravenous colloids6 (10 mL/kg IV bolus once). Despite treatment, the weanling was euthanized within 48 hours of presentation because of continued deterioration and signs of pulmonary disease characterized by nasal discharge, epistaxis, and tachypnea. Blood work submitted the morning of euthanasia revealed a worsening leukocytosis (35.4 × 103/μL) with an unchanged differential, as well as continued hypoproteinemia (3.5 g/dL), hypoalbuminemia (1.1 g/dL), and an increased BUN (59 mg/dL).

Case 2

An 8-month-old Thoroughbred filly from the same farm as case #1 presented in October 2011 with inappetence of <12 hours duration. Physical examination revealed fever (102.5°F) and an unthrifty appearance, including a poor hair coat. Examination of the serum albumin concentration at presentation revealed hypoalbuminemia (2.8 g/dL). A complete blood count the following morning revealed no significant abnormalities, but hypoproteinemia (5.1 g/dL) and a worsening hypoalbuminemia (2.5 g/dL) were seen on serum biochemistry; in addition, an L. intracellularis immunoperoxidase monolayer assay (IPMA) titer of ≥1 : 240 was reported. Other abnormalities were also noted (Table S1). On the basis of the time of year, the presence of anorexia, hypoproteinemia, hypoalbuminemia, and the weanling's positive IPMA titer, in addition to the farm's previous history, a presumptive diagnosis of EPE was made. Treatment initially consisted of oral doxycycline7 (10 mg/kg PO q12h) and flunixin meglumine7 (1 mg/kg IV q12h); however, owing to the continued decline of the weanling, the doxycycline was discontinued and intravenous oxytetracycline1 (6.6 mg/kg IV q24hr) was initiated 2 days after presentation.

The following morning (approximately 60 hours after initial signs were noted), the filly was lethargic, with a fever of 105.9°F. CBC revealed severe leukopenia (1.6 × 103/μL), neutropenia (18%), lymphocytosis (70%), and toxic left shift (12%). The serum biochemistry abnormalities included azotemia, as well as a decline in serum total protein (3.7 g/dL) and albumin (1.5 g/dL) (Table S1). Concerns about the filly's condition prompted referral for more intensive care. On arrival, the filly remained lethargic with a fever of 103.1°F. In addition, the filly was tachycardic (78 bpm; ref 20–44 bpm) and tachypneic (48 bpm; ref 8–24 bpm). Abdominal ultrasound revealed thickened small intestinal wall (6 mm; ref ≤3 mm) and free fluid in the abdominal cavity. Abdominocentesis was performed, and fluid analysis revealed a WBC count of 77,500 cells/μL (90% neutrophils and 10% mononuclear cells) (ref 0.5−5.0 × 103/μL WBC and 1 : 1 ratio of neutrophils:mononuclear cells) and total protein of 2.0 g/dL (ref 0.5–1.5 g/dL). In addition, a moderate number of short Gram-negative rods and rare Gram-positive cocci were noted, but no plant or fecal material was seen in the peritoneal fluid sample. Culture results of the abdominal fluid revealed Actinobacillus equuli. Within several hours of hospitalization, the filly became agitated, developed cyanotic mucous membranes, and exhibited agonal activity. The filly was euthanized approximately 72 hours after initial presentation at the farm.

Case 3

A 6-month-old Thoroughbred colt was evaluated on the farm in November 2011 owing to a 72-hour history of lethargy. On presentation, the colt was lethargic, tachycardic (68 bpm), and febrile (103.5°F). In addition, the colt had dark red/purple mucous membranes and delayed capillary refill time. The colt had developed diarrhea within the previous 12 hours, and severe throatlatch and preputial edema were noted. Immediately before referral to the McGee Medicine Center, treatment was initiated at the farm and included intravenous oxytetracycline1 (6.6 mg/kg IV q24hr), flunixin meglumine2 (1 mg/kg IV q12h), and synthetic colloids6 (10 mL/kg IV bolus once). A complete blood count indicated leukocytosis (31.5 × 103/μL) with neutrophilia (78%), lymphopenia (7%), and a left shift (15%). Serum biochemistry abnormalities included hypoproteinemia (2.3 g/dL) and hypoalbuminemia (0.9 g/dL), along with other metabolic abnormalities (Table S1). Abdominal ultrasound demonstrated thickening of the small intestinal wall and a preliminary diagnosis of EPE was made.

After referral, the colt remained febrile despite nonsteroidal anti-inflammatory drug (NSAID) treatment; furthermore, epistaxis developed with progressively increasing volumes of blood exiting both nostrils, ultimately leading to respiratory distress. The respiratory distress was partially alleviated with the placement of a nasotracheal tube. Spontaneous epistaxis continued and the colt also began passing dark/bloody diarrhea and blood tinged urine. Because of welfare concerns in the face of suspected disseminated intravascular coagulation (DIC), the colt was euthanized <96 hours after developing clinical signs. Blood work values collected before euthanasia revealed an increased leukocytosis (42.4 × 103/μL), as well as a progressive hypoproteinemia (1.7 g/dL) and hypoalbuminemia (0.6 g/dL) (Table S1).

Case 4

A 6-month-old Thoroughbred colt presented in late October 2011 with a fever (105°F) 5 hours before initial evaluation; the fever was immediately treated by the farm with flunixin meglumine2 (1 mg/kg IV q12h). The weanling was small for its age despite having received regular preventative health care, and physical examination revealed no other signif-icant findings. A complete blood count revealed a normal white blood cell count (7.7 × 103/dL) with neutropenia (14%) and lymphocytosis (84%). The serum biochemistry abnormalities included hypoproteinemia (3.6 g/dL) and hypoalbuminemia (1.8 g/dL) (Table S1). EPE was tentatively diagnosed, and treatment was initiated with oxytetracycline1 (10 mg/kg IV q24hr). At the time antimicrobial treatment was initiated, the colt was eating and had normal vital sign values. Four hours after examination, the colt developed peracute signs of shock and gastrointestinal crisis, including tachycardia (108 bpm), tachypnea (40–50 bpm), dark purple mucous membranes, and general signs of severe abdominal discomfort (rolling on the ground). Despite emergency intravenous fluid resuscitative care consisting of IV crystalloids5 (7 mL/kg bolus) and colloids6 (2 mL/kg bolus), the weanling quickly became recumbent and died less than 45 minutes into the crisis and approximately 24 hours after initial presentation.

Necropsy Findings

Necropsy findings involving the small intestine were similar in all 4 cases. Segments of the mucosa of jejunum, ileum, or both were thickened (cases #1–4), variably reddened (cases #1, 2, and 4), and corrugated (cases #2 and 4). Regions of ulceration and greenish-brown necrotic mucosal plaques were occasionally evident (case #3). Peyer's patches were hemorrhagic (case #4), and the intestinal lumen contained a moderate amount of dilute reddish-brown fluid (cases #1, 3, and 4). The cecal and colonic walls were moderately edematous in cases #2 and 3. Additional lesions identified at necropsy included pneumonia and gastric ulcers (case #1); cestodiasis, fibrinous peritonitis, and vegetative valvular endocarditis (case #2); multiple acute renal infarcts (case #3); and mesenteric lymphadenopathy (case #4).

L. intracellularis was associated with the small intestinal lesions in all 4 cases. L. intracellularis DNA was detected in ileal mucosal scrapings by PCR in all 4 cases. L. intracellularis-specific immunohistochemistry was performed on 2 cases (#2 and 4) and directly identified the bacterium in the necrotic lesions of both cases.

Various bacteria were cultured from the intestines and systemic organs; culture results and tetracycline antibiograms, given that tetracycline-class drugs are typically the first antimicrobial administered to animals with suspected EPE in central Kentucky,[1] are presented in Table S2. The Gram-positive cocci noted in the abdominal fluid sample of case #2 were not noted at necropsy. This could possibly be because of the administration of antimicrobials or the cocci were anaerobic and not cultured at necropsy.

Histologically, small intestinal lesions were mor-phologically diagnosed as severe subacute segmental necroulcerative enteritis (cases #1 and 4) or severe chronic segmental proliferative and necroulcerative enteritis (cases #2 and 3). All 4 cases exhibited regions of mucosal necrosis, erosion, and ulceration that were covered by mats of small amounts of fibrin, cell debris, and acidophilic proteinaceous material, low number of neutrophils and macrophages, and mixed populations of bacteria (Figs 34). The lamina propria and submucosa, subjacent to the ulcers, were edematous and infiltrated with low numbers of neutrophils, macrophages, and lymphocytes. Multifocal blood vessels contained fibrin thrombi. In addition, in cases #2 and 3, multifocal regions of the mucosa were proliferative and exhibited elongated villi, branched crypts, and crypt and glandular epithelial hyperplasia. Few crypts contained cell debris and acidophilic proteinaceous material. Tertiary findings included: necrotizing glomerulonephritis, hepatitis, and embolic pneumonia (case #1); vegetative valvular endocarditis and peritonitis (case #2); renal infarction (case #3); and renal glomerular thrombosis (case #4).

Figure 1.

Ileum, age-matched control. Villi are distinct and of normal length. H&E (40× total magnification). Bar = 1 mm.

Figure 2.

Ileum, chronic EPE. Villi are segmentally blunted and fused. Crypts are hyperplastic, elongated, and multifocally branched. H&E (40× total magnification). Bar = 1 mm.

Figure 3.

Ileum, necrotizing EPE, case 2. Villi are shortened and the crypts are mildly hyperplastic. Superficial villar tips are necrotic and covered by small amounts of cell debris. H&E (40× total magnification). Bar = 1 mm.

Figure 4.

Ileum, necrotizing EPE, case 2. Higher magnification of the necrotic villar tips. H&E (400× total magnification). Bar = 100 um.


Proliferative enteropathies induced by L. intracellularis infections have been noted to occur in a variety of species worldwide. Most notable is L. intracellularis infection in pigs where financial losses from porcine proliferative enteropathy are significant.[2] The majority of what is known with respect to L. intracellularis has been discovered from work in pigs and largely extrapolated to the horse. Porcine proliferative enteropathy exhibits several clinical entities, including the subclinical form in which affected pigs exhibit no clinical signs but shed the bacterium, the chronic form, where affected pigs fail to grow as well as littermates, and the acute form (normally referred to as porcine hemorrhagic enteritis or PHE), which is often characterized by hemorrhagic diarrhea and acute death. Whereas acute morbidity and mortality has long been recognized as a common clinical presentation of Lawsonia intracellularis infection in swine,[3] this clinical presentation has never, to the authors' knowledge, been described in multiple field cases of EPE. Here, we have presented 4 cases detailing an acute clinical entity with necrotic enteritis, which we suggest be referred to as a necrotizing form of EPE (N-EPE). This designation serves to provide not only a pathologic description but also an inference to the observed severity of clinical disease and rapid deterioration of the affected animal.

With EPE, clinical signs of anorexia, dependent edema secondary to hypoproteinemia and hypoalbuminemia, lethargy, and weight loss are typically observed during the fall and winter months (August–February)[1, 4, 5]; fever, colic, and diarrhea are less frequently seen. Ultrasonographic detection of thickened small intestinal walls in weanlings is highly suggestive of EPE, although the finding can be inconsistent.[1] Clinical cases of EPE generally develop slowly over several days, but during an EPE challenge study 1 challenged weanling developed what we termed “acute EPE” given the rapid deterioration and necrotizing enteritis that was noted in the weanling.[6] Because this was an experimental challenge study that likely failed to adequately replicate the field conditions in which L. intracellularis infection is typically contracted, we surveyed local practitioners for other, “acute EPE” cases. During the span of 13 months (October 2010–November 2011), the 4 cases detailed above were identified in the central Kentucky region. A literature review found that the 1st published description of EPE by Duhamel and Wheeldon[7] recounted the acute deterioration (5 days) and death of a foal, similar to the 24–96-hour time courses of our cases, whereas a more recent report documented the occurrence of necrotizing enteritis associated with L. intracellularis infection in 1 horse with a 10+ day history of EPE.[8] Based on the short timeframe in which we selected cases, as well as the occasional report of various facets of the N-EPE clinical entity, it is highly likely that cases of N-EPE have occurred with regularity and simply not been recognized until now. Likewise, the previous case of “acute EPE” we reported[6] should, instead, be considered a case of N-EPE based on the criteria listed above. Given that not all cases of N-EPE will expire as a result of EPE or secondary bacterial infections, practitioners may elect to diagnose surviving animals with “acute clinical EPE” and reserve N-EPE as a pathologic diagnosis.

In pigs, it has been suggested that Lawsonia-associated necrotic enteritis develops from inflammation and necrosis induced by secondary bacterial invaders.[9] The clinical signs observed with these 4 weanlings were highly unusual for EPE. Damage induced to the intestinal mucosal barrier by secondary pathogens likely predisposed these weanlings to endotoxemia or bacteremia and resulted in secondary systemic sequelae. This assertion appears to be supported by the presence of thickened mucosa associated with the necrotizing and ulcerative enteritis, suggesting that alimentary damage preceded bacterial translocation. The clinicopathologic, gross necropsy, and histologic findings in cases #1 and 2 suggest that the observed clinical signs resulted directly from secondary bacteremia. Interestingly, these 2 cases originated from the same farm but 12 months apart. Finding regular, yearly cases of EPE on certain farms has been reported previously,[4, 5] but the occurrence of 2 separate cases of N-EPE on the same farm in different years is a novel finding. This could suggest that the particular strain of L. intracellularis on this farm is potentially more virulent and that this farm should monitor diligently for reoccurrence of N-EPE. Case #3 survived the longest after initial presentation (~96 hours); however, treatment for EPE was not started until approximately 72 hours postpresentation. This weanling appeared to develop fulminant disseminated intravascular coagulation after treatment was initiated, as demonstrated by the occurrence of uncontrolled epistaxis, hematuria, melena/hematochezia, and multiple renal infarcts. Possible causes for the development of DIC in this weanling include septicemia/bacteremia, endotoxemia, or a decrease in circulating antithrombin-3 caused by hypoproteinemia. The last case, case #4, survived for the shortest amount of time (<24 hours postpresentation) and was the only weanling to die spontaneously. Based on the renal glomerular tuft thrombosis, this weanling likely died because of cardiovascular compromise initiated by acute DIC.

EPE has been a disease viewed as having a well-defined clinical presentation and a high treatment success rate when properly diagnosed.[1, 4, 10] The cases presented here provide an important repudiation to this commonly held view in that, despite the correct preliminary diagnosis and appropriate treatment, all 4 of these weanlings succumbed to complications arising from EPE. This would suggest that treatment of N-EPE cases (those with signs of secondary bacterial infection, endotoxemia, or both) should be treated aggressively with broad-spectrum antimicrobials to ensure coverage against both Gram-positive and Gram-negative bacteria, antithrombotics, and antiendotoxic measures such as low-dose flunixin meglumine,[11] intravenous polymyxin-B, or both.[12] Care must be taken, however, when administering NSAIDs, polymyxin-B, or both because of their potential nephrotoxic effects in patients with hypovolemia or in which there is a predisposition for azotemia. In addition, NSAID use could exacerbate existing mucosal compromise. Although no anaerobes were isolated from the cases presented above, practitioners should be aware of the possibility of secondary infections with anaerobic bacteria and consider metronidazole treatment if they believe it to be warranted.

More work is needed to understand the risk factors for the development of N-EPE, which could include environmental/husbandry differences, genetic polymorphisms,[13] the infectious dose, L. intracellularis strain, concurrent disease, or animal's immune status. Our previous work with an experimental challenge model seems to suggest that the host immune system likely plays the largest role in this type of clinical presentation as the infectious dose and strain used in that study was consistent across 6 challenged weanlings, yet only 1 developed N-EPE[6]; however, based on the occurrence of 2 N-EPE cases on the same farm in consecutive years, a significant role of bacterial strain cannot be ruled out. Regardless, practitioners must be cognizant of the necrotizing form of EPE as weanlings may fail to demonstrate the classic, chronic clinical signs associated with EPE (including weight loss and dependent edema) and/or require emergency treatment to prevent secondary complications such as septicemia, endotoxemia, and DIC, all of which could ultimately lead to acute death.


The authors graciously thank each of the farms that allowed for their horses to be included in this study. The authors would also like to thank Tina Elam and Katherine Short of the Hagyard Equine Medical Institute for their help with compiling the laboratory and medical records.

Conflict of Interest Declaration: Dr Page's graduate student stipend is supported, in part, by the Morris Animal Foundation and Pfizer Animal Health.

Support: None.


  1. 1

    Liquamycin LA-200, Pfizer Animal Health, New York, NY

  2. 2

    Banamine, Merck Animal Health, Summit, NJ

  3. 3

    UlcerGard, Merial Ltd, Duluth, GA

  4. 4

    Dexium, Bimeda, Le Sueur, MN

  5. 5

    Normosol-R, Hospira, Lake Forest, IL

  6. 6

    Hetastarch, Hospira

  7. 7

    Hagyard Pharmacy, Lexington, KY