JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

September 2024

D-M02 (NP)

 

HISTORY (JPC #1902492): Tissue from a 4-year-old quarter horse with a 5-month history of diarrhea and progressive weight loss.

 

MICROSCOPIC DESCRIPTION: Duodenum: Diffusely and circumferentially, the intestinal wall is expanded up to 8mm; the submucosa is expanded diffusely up to 2.5mm. The submucosa and to a lesser extent the lamina propria are infiltrated and expanded by large numbers of lymphocytes, plasma cells, eosinophils, and fewer macrophages and neutrophils admixed with eosinophilic cellular and karyorrhectic debris (necrosis), scattered hemorrhage, fibrin, and mild edema with ectatic submucosal lymphatic vessels. This inflammation invades through and multifocally replaces the discontinuous muscularis mucosa. Multifocally within the submucosa, dense, round to oval, 0.5-1.5mm, aggregates of brightly eosinophilic necrotic debris are surrounded by epithelioid macrophages, eosinophils, rare multinucleated giant cells, and concentric rings of collagen (eosinophilic granulomas). The submucosa also contains increased small caliber blood vessels and reactive, haphazardly arranged, hypertrophied fibroblasts surrounded by abundant edematous collagen (granulation tissue). Multifocally, submucosal glands (Brunner’s glands) are mildly dilated and frequently filled with or obscured by nodular aggregates of degenerate eosinophils, necrotic cellular debris (necrosis), and abundant pale basophilic fibrillar material (mucin). Within the lamina propria, lacteals are multifocally dilated and contain moderate numbers of lymphocytes with fewer eosinophils admixed with eosinophilic proteinaceous fluid (lymphangiectasia). The mucosa is characterized by blunting and fusion of villi with erosion. There are occasional crypt abscesses, and rare crypt herniation in foci of discontinuous muscularis mucosae. The previously described inflammatory infiltrate extends multifocally into the tunica muscularis. Multifocally, the serosa and outer layer of the tunica muscularis are expanded by increased clear space and dilated lymphatics (edema). Within the intestinal lumen, there is an exudate composed of hemorrhage and fibrin admixed with sloughed epithelial cells, cellular debris, and moderate numbers of eosinophils, lymphocytes, plasma cells, macrophages and few neutrophils.

 

MORPHOLOGIC DIAGNOSIS: Small intestine: Enteritis, eosinophilic and lymphohistiocytic, diffuse, severe, with eosinophilic granulomas, mucosal erosion and granulation tissue, quarter horse, equine.

 

GENERAL:

• Chronic eosinophilic enteritis

• Described as part of a distinct multisystemic epitheliotropic syndrome sometimes referred to as multisystemic eosinophilic epitheliotropic disease (MEED)
• Uncommon condition characterized by both nodular and diffuse eosinophilic enteritis with other inflammatory cells that can affect all layers and all portions of the gastrointestinal tract; other organs most commonly affected are skin, pancreas, common bile duct, and lungs
• Young horses 3-4 years of age, Standardbreds/thoroughbreds overrepresented

• Idiopathic focal eosinophilic enteritis: 

• Separate entity from multisystemic eosinophilic syndrome
• Has been described as a part of the equine inflammatory bowel disease (IBD) complex
• Associated with obstructive colic; resection of the affected intestinal portion is typically curative

 

PATHOGENESIS:

• Chronic eosinophilic enteritis:

• Unknown specific cause, eosinophils suggest type I hypersensitivity reaction 

• One case has been associated with pythiosis
• Other suggestions include hypersensitivity to migrating parasites, inhaled or ingested allergens, viruses, and toxins

• Disease is associated with upregulation of Th2 lymphocytes and increased IL-5 production

• One suggestion for etiology is an undiagnosed T-cell lymphoma elaborating IL-5

• In horses and humans, the lymphoplasmacytic infiltrates in this condition are precursors to lymphoma
• Chronic mucosal inflammation may explain protein loss and hypoproteinemia

• Idiopathic focal eosinophilic enteritis:

• Part of the IBD complex and/or associated with enteric parasitism

 

TYPICAL CLINICAL FINDINGS:

• Chronic eosinophilic enteritis:

• Weight loss 
• Soft to diarrheic stools (not present if large bowel lesions are not present)
• +/- peripheral eosinophilia according to one reference, absent eosinophilia according to another
• With the exception of rare cases in which a specific etiologic agent is diagnosed, horses die
• Protein losing enteropathy leading to hypoalbuminemia, pitting edema

• Idiopathic focal eosinophilic enteritis:

• Has been associated with intestinal obstruction and colic

 

TYPICAL GROSS FINDINGS:

• Chronic eosinophilic enteritis:

• Gastrointestinal tract:

• Mucosal and sometimes transmural thickening at any level of the alimentary tract, segmental to diffuse
• Mucosa is thrown into thick, turgid, transverse folds or occasionally fissured and roughened
• Focal or diffuse ulcers may be present
• Hyperkeratosis of squamous mucosa of esophagus and stomach
• Caseous lesions up to 1.5cm diameter in the intestinal submucosa and common bile duct

• Pancreas: enlarged, fibrotic
• Skin (see I-M11): Exfoliative and exudative dermatitis (especially of the face, limbs, ventral abdomen); ulcerative coronitis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Chronic eosinophilic enteritis:

• Gastrointestinal tract: 

• Eosinophilic and lymphoplasmacytic infiltrates in both nodular and diffuse accumulations in all layers and portions of the gastrointestinal tract
• Caseous foci in mucosa and submucosa: central masses of eosinophils +/- surrounded by macrophages, giant cells, and fibrous connective tissue
• Moderate to severe villus atrophy is common
• Lamina propria fibroplasia
• Muscularis mucosa hypertrophy

• Other organs: Additional eosinophilic infiltrates and granulomas have been described in biliary and pancreatic ducts, pancreas, salivary glands, capsule and cortex of mesenteric lymph nodes, and periportal regions of liver
• Skin: Variable inflammatory pattern (perivascular, lichenoid interface, interstitial, diffuse, and granulomatous) with predominance of eosinophils, lymphocytes, and plasma cells; marked acanthosis and hyperkeratosis, epitheliotropic eosinophils and lymphocytes are common, apoptotic keratinocytes may be prominent

• Idiopathic focal eosinophilic enteritis:

• Focal infiltration of large numbers of eosinophils and macrophages focused on the submucosa and tunica muscularis, often with increased lamina propria lymphocytes, plasma cells, and macrophages with fewer eosinophils

 

DIAGNOSIS:

 

DIFFERENTIAL DIAGNOSIS:

 

COMPARATIVE PATHOLOGY:

• Donkeys can rarely also be affected; eosinophilic granulomas in multiple organs, chronic weight loss, exfoliative dermatitis, peripheral eosinophilia; all euthanized (Paraschou et al., J Comp Pathol, 2023)
• Multisystemic eosinophilic disease (hypereosinophilic syndrome): reported in dogs, cats, ferrets and humans; usually with peripheral eosinophilia
• Feline enteric eosinophilic syndrome is often progressive and fatal 
• Human and canine enteric eosinophilic syndromes tend to be nonprogressive and controllable

 

REFERENCES:

1. Mauldin EA, Peters-Kennedy, J. Integumentary System. In: Maxie MG. ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier Saunders; 2015:695. 
2. Paraschou G, Vogel PE, Lee AM, Trawford RF, Priestnall SL. Multisystemic eosinophilic epitheliotropic disease in three donkeys. J Comp Pathol. 2023;201:105-108.
3. Spagnoli ST, Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:396-485. 
4. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Saunders; 2015:96.

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