3-year-old, female, equine French trotter (Equus caballus).For the past five months the mare showed poor condition with severe weight loss and generalized exfoliative dermatitis, easily epilated hair, and multifocal severe alopecia with pruritus. The pruritus decreased with dexamethasone treatment. In spite of treatment, the body condition of the mareremainedpoor. Clinically,asuspicionofanimmune- mediated skin disease was made. The animal was euthanized for humane reasons.
Generalized severe amyotrophy and severe weight loss (generalized cachexia) was noted at necropsy. Theexaminedanimalpresentedwithgeneralized, exfoliative dermatitis characterized by diffuse hypertrophy of skin, dry scales, serous exudates, and severe multifocal profound ulceration and alopecia involving the head, neck, flanks and hind limbs. Further, multiple deep ulcers, measuring 1 to 3 cm of diameter with fibrotic margins, were observed on the lips, upper and lower gingiva, and tongue. Two masses measuring 15 cm were observed near the duodenum and the right dorsal colon; these masses replaced the pancreas and were whitish-yellow with nodular, firm, fibrous appearance and dry cut section.
The gastric mucosa contained multifocal chronic ulcerations of the non-glandular mucosa, the fundus, and the margo plicatus and were characterized by elevated fibrous marginsand a dry appearance. Moderate hyperplasia of the mucosa was noticed in the proximal duodenum and right dorsal colon.
Moderate, diffuse, lymphadenomegaly, with a wet and whitish cut surface indicating a reactive lymphadenitis, was noticed in the gastric, pancreatic and mesenteric lymph nodes.
Macroscopic diagnoses: - Dermatitis, hyperplastic, exfoliative, and parakeratotic, diffuse, chronic, severe, with multifocal alopecia.
- Pancreatitis, sclerosing, diffuse, chronic, severe.
- Cheilitis, stomatitis and gastritis, ulcerative, multifocal, chronic, severe.
Skin: The skin lesions are characterized by focal ulceration and covered by fibrinous exudate admixed with cellular debris. The adjacent epidermis presents with parakeratotic hyperkeratosis and diffuse hyperplasia characterized by proliferation of keratinocytes (acanthosis) and formation of irregular rete ridges into the superficial dermis. Moderate multifocal lymphocytic exocytosis and multifocal vacuolar degenerationofkeratinocytesareobserved. Thesuperficial dermis is severely infiltrated by lymphocytes, plasma cells, less numerous eosinophils, and in the ulcerated areas by numerous degenerate neutrophils (suppuration); it shows moderate multifocal fibrosis, vascular congestion with lymphatic ectasia, and perivascular lymphoplasmacytic and eosinophilic infiltrates. There is a slight lymphocytic infiltration of hair follicles and sebaceous glands.
Pancreas: The architecture of the pancreatic parenchyma is completely distorted and characterized by severe, diffuse, fibrosis containing thick mature collagen fibers and few fibroblasts. Only a few pancreatic epithelial cells and islets ofLangerhansareobservedinthesections. Severeductular hyperplasia with columnar to cubioidal monostratified epithelium and abundant intraluminal amphophilic amorphous material (mucus) can be noticed. Severe multifocal infiltration by numerous non-degranulated and degranulated eosinophils, as well as lymphocytes and plasma cells, is one of the main features of this lesion. Vascular fibrosis and lymphocytic eosinophilic transcytosis are further observed features.
Colon (histoslides not submitted): The colonic crypts are separated by severe infiltration by lymphocytes, plasma cells and a few eosinophils, and are multifocally atrophic and degenerate with superficial enterocyte loss. Further, the middle sized arterioles exhibit vacuolar degeneration of the medial cells with formation of multifocal intimal and intramedial calcification foci (intimal bodies).
1. Skin: Dermatitis, interface and perivascular, lymphoplasmacytic and eosinophilic, diffuse, chronic, severe, with focal ulceration and suppuration.
2. Pancreas: Pancreatitis, eosinophilic and sclerosing, diffuse, chronic, severe with subtotal epithelial atrophy, ductular hyperplasia and moderate multifocal lymphocytic infiltration.
3. Colon: Colitis, lymphoplasmacytic and eosinophilic, diffuse, severe, chronic with superficial epithelial erosion.
(clinical pathology, microbiology, PCR, ELISA, etc.):
Complete Blood Count:
|Total bilirubin ||7.8||0-35
|GGT (Gamma glutamyl transferase) (UI/l)||23||0-40|
|Total protein (g/l)||66||56-79|
Multisystemic Epitheliotropic Eosinophilic Disease (MEED)
Equine multisystemic eosinophilic epitheliotropic disease (MEED) is a rare, sporadic disease of horses characterized by eosinophilic infiltration into several organs.(10,12) The condition is characterized by exfoliative dermatitis, ulcerative stomatitis, wasting, and infiltration of epithelial tissues by eosinophils andlymphocytes. Scalingandcrustingusuallybeginonthe face or coronary bands.(3,9) Histopathologic findings in the dermis include superficial and deep perivascular to diffuse dermatitis or granulomatous dermatitis.(4,6,9,11) Similar inflammatory lesions, often associated with varying degrees of fibrosis, are seen in other epithelial organs, especially the pancreas, salivary glands, oral mucosa, gastrointestinal tract, esophagus, biliary tracts and bronchial mucosa.(1,2,10,11) There is no breed or sex predisposition.(11) Although horses can be affected at any age, most cases involve young animals (mean age of 3 to 4 years).(12) There is no specific clinical diagnostic test for this disease.(13) The etiopathogenesis of the disease is unknown; a hypersensitivity reaction to larvae of Strongylus equinus or food allergens is suspected, as well as an epitheliotropic cell-associated virus or a genetic basis.(3,4,7,11,12) The differential diagnosis includes dermatophilosis, dermatophytosis, pemphigus foliaceous, systemic lupus erythematosus, sarcoidosis, bullous pemphigoid, pemphigus vulgaris, vasculitis, erythema multiforme, epitheliotropic lymphoma, drug eruption and various toxicoses. The definitive diagnosis is based in the histopathologic examination.(11,12) The condition is generally associated with a poor prognosis.(7,8)
Idiopathic hypereosinophilic syndrome has been reported in humans, dogs, cats, horses, and ferrets.(2,7,13) The hypereosinophilic syndrome in man is characterized by marked peripheral eosinophilic infiltrates in various organs of which the skin is the second most common. The most frequently affected organ is the heart.(8) Immunosuppressive doses of systemic glucocorticoids (dexamethasone) may be effective in horses if administered early in the course of the disease (before wasting).(3,7,11) Hydroxyurea is an orally active antineoplastic agent whose mode of action is to inhibit DNA synthesis without affecting RNA or protein synthesis; it has been used successfully for treating humans with hypereosinophilic syndrome and has been suggested for the treatment of cats. An improvement of the clinicopathological signs was noticed in a horse treated with corticosteroid and hydroxyurea and suggests that this therapy could be effective in attempts to treat this condition.(7)
1. Pancreas: Pancreatitis, sclerosing, lymphoplasmacytic and eosinophilic, diffuse, marked with ductular hyperplasia, duct ectasia, and mucinous metaplasia.
2. Haireds kinand mucocutaneous junction, lip: Dermatitis and cheilitis, lymphoplasmacytic and eosinophilic, perivascular, multifocal, mild to moderate, with ulceration, epidermal hyperplasia and parakeratotic hyperkeratosis.
Conferenceparticipantsagreedthe histopathologic findings in the submitted sections of pancreas and haired skin with lip are most consistent with the contributors diagnosis of equine multisystemic eosinophilic epitheliotropic disease (MEED). Most conference participants characterized the inflammatory pattern in the skin and lip as perivascular, rather than interface, based on the observation that most of the inflammation centers around vessels in the superficial dermis and subepithelial connective tissue. In contrast, interface dermatitis is typified by inflammatory cells that obscure the dermal-epidermal junction and associated damage to the basal layer of keratinocytes;(5) with the exception of the areas of ulceration, participants did not observe these features.
The moderator provided several useful guidelines for approaching the histologic evaluation of the tissues submitted for this case to arrive at the most accurate diagnosis. Many conference participants struggled with tissue identification for the pancreas due to the extensive fibrosis that replaces almost all of the glandular components. To address this difficulty, the moderator suggested first evaluating the section of skin to identify the histologic features of the lesion and develop a histomorphologic diagnosis. Knowledge of the key histologic features in the skin lesion then provides insight into the underlying disease process and pathogenesis, and then leads the astute diagnostic pathologist to consider the other tissues likely to be affected in equine multisystemic eosinophilic disease, such as the pancreas. The moderator noted that lymphoplasmacytic and eosinophilic pancreatitis and exfoliative dermatitis are classic lesions of MEED.
The contributor indicates the pathogenesis of MEED is unknown, and lists some potential etiologies. In addition to the etiologies listed, it has also been suggested that clonal proliferation of epitheliotropic T-lymphocytes in affected tissues results in secretion of interleukin-5, thereby attracting eosinophils. Another potential etiology is repeated type I hypersensitivity reactions that occur in response to inhaled, ingested (dietary), or parasitic antigens.5 The contributor provides excellent information on MEED. For additional information on other causes of eosinophilic dermatitis in horses the reader is referred to WSC 2009-2010, Conference 4, Case I.
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