Equine multisystemic eosinophilic epitheliotropic disease: A case report and review of literature

CASE HISTORY: A 2-year-old Standardbred gelding presented with a history of fever over 1 week, anorexia and skin lesions on all four legs. The lesions were associated with severe pruritus and oedema, and there was no response to therapy.

CLINICAL FINDINGS: The horse was in poor body condition, was lethargic and severely pruritic. Skin lesions consisted of diffuse alopecia and crusting of the distal extremities. Initially it was slightly febrile, but subsequently its temperature increased up to 40°C. Ten days after admission it developed profuse watery diarrhoea and the skin lesions progressed. Skin biopsies revealed superficial and deep perivascular dermatitis with lymphoplasmacytic and eosinophilic predominance. Based on the poor prognosis the horse was subject to euthanasia.

PATHOLOGICAL FINDINGS: The most notable lesions included ulcerative gastritis, typhlitis and colitis with prominent oedema of the intestines, marked subcutaneous oedema and severe thickening of the large bile ducts. Histopathology showed marked eosinophilic and lymphoplasmacytic infiltration of various tissues including the skin, gastrointestinal tract, mesenteric lymph nodes, large bile ducts, pancreatic duct and kidney. Immunohistochemistry revealed a clear predominance of CD3-positive cells in the lymphocytic infiltrations.

DIAGNOSIS: Based on the clinical findings and histopathology a diagnosis of multisystemic eosinophilic epitheliotropic disease (MEED) was made.

CLINICAL RELEVANCE: Multisystemic eosinophilic epitheliotropic disease is rare in horses, and usually chronic. In the current case the horse showed an apparently acute onset with high fever and rapid clinical deterioration. A diagnosis of MEED should be considered in horses presenting with weight loss and skin lesions with or without fever. A final diagnosis is based on histological results of biopsy specimens from affected organs.     

Feline eosinophilic conjunctivitis

Objective To review 12 cases of histologically confirmed feline eosinophilic conjunctivitis, their clinical, cytologic, histologic and electronmicroscopic findings, results on PCR for FeHV‐1, treatment and outcome. Animals studied Twelve naturally occurring cases presented during a period of 26 months. Procedures Thorough ophthalmologic examination, conjunctival scrapings performed with the cytobrush method; histologic samples from the palpebral conjunctiva; PCR for FeHV‐1 on Schirmer Tear Test (STT) strips; saliva and nasal swabs, and retrospective evaluation of all results. Results The breed most commonly affected was the Domestic Shorthair (n = 8), followed by Persians (n = 2), Somali (n = 1) and Siamese (n = 1). Age at presentation was 1–15 years with a mean age of 7.2 years. Nine cats were castrated males; three cats were females: two of them were spayed. Unilateral (n = 7) or bilateral (n = 5) involvement with depigmentation and erosions of lid margin, blepharospasm, swelling and redness of conjunctiva and third eyelid were the most common clinical findings. Frequency of eosinophils in cytologic samples was more than 10% in every patient. PCR for FeHV‐1 on STT was negative in all cases. Histologically, eosinophils, lymphocytes, plasma cells, mast cells and macrophages were involved. On electronmicroscopy, viral particles were not detected. Ten cases needed long‐term anti‐inflammatory treatment. Conclusions The 12 reviewed cases suggest that feline eosinophilic conjunctivitis is a chronic inflammatory uni‐ or bilateral disease of the adult cat. Typically the lid margin was also involved, and was thickened, depigmented and erosive. Cytological examination of conjunctival scrapings was a valuable tool for detecting eosinophilic conjunctivitis. The cytological findings correlated well with the histopathological findings in our patients. Topical or systemic anti‐inflammatory drugs resolved the clinical symptoms in our cases within a short period of time. Neither electronmicroscopy nor PCR were able to detect involvement of FHV1 in the represented cases. The etiopathogenic role of FeHV‐1 remains undetermined.     

Inflammatory bowel disease characterized by multisystemic eosinophilic epitheliotropic disease (MEED) in a horse in Saskatchewan,Canada

A 3-year-old Quarter Horse gelding was evaluated for chronic weight loss, diarrhea, and pruritus. Physical examination revealed several ulcerative lesions on the skin and mucosal membranes. Diagnostic imaging findings were consistent with enteritis, typhlitis, and colitis. Multisystemic eosinophilic epitheliotropic disease (MEED) was diagnosed upon necropsy. This disease may be considered a form of equine inflammatory bowel disease complex which can be challenging to diagnose, requiring histological assessment, and in some cases, the use of immunohistochemical markers.Key clinical message:Multisystemic eosinophilic epitheliotropic disease is challenging to diagnose but should be considered in horses with chronic weight loss that fail to respond to conventional treatment for concurrent diarrhea and skin lesions.     

Chronic idiopathic inflammatory bowel diseases of the horse

A review of reported cases of inflammatory bowel diseases (IBDs) of horses for which no etiology was identified included cases of granulomatous enteritis (GE), multisystemic eosinophilic epitheliotropic disease (MEED), lymphocytic-plasmacytic enterocolitis (LPE), and idiopathic eosinophilic enterocolitis (EC). The terms EC and MEED were both used to describe a disease in horses characterized by infiltration of intestine and extraintestinal tissues with eosinophils. We use EC to describe IBD characterized by only intestinal infiltration by eosinophils. Horses with GE, MEED, or LPE are usually examined because of weight loss and depression, but horses with EC are usually examined because of signs of abdominal pain. Typically, horses with IBD have low concentrations of serumal proteins, especially albumin, and fail to adequately absorb glucose or xylose. Antemortem diagnosis of IBD can only be made by histologic examination of affected intestine. In some cases, antemortem diagnosis is made from histologic examination of rectal mucosa obtained by biopsy. Suspected causes of IBD in the horse include abnormal immune response to bacterial, viral, parasitic, or dietary antigens. Most horses with IBD do not survive, but horses with EC are more likely than those with LPE, MEED, or GE to respond to treatment. Successful treatments of horses with IBD include resection of grossly affected intestine and administration of corticosteroids.     

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF EOSINOPHILIC PULMONARY GRANULOMATOSIS IN FIVE DOGS

Canine pulmonary eosinophilic granulomatosis is a rare inflammatory pulmonary disease characterized by formation of eosinophilic granulomas that tend to obliterate the normal pulmonary architecture. The purpose of this retrospective study was to describe the CT characteristics of confirmed idiopathic pulmonary eosinophilic granulomatosis in a group of dogs. Five dogs met inclusion criteria. All patients were young adult dogs of variable breeds. No dog had concurrent occult heartworm disease. Computed tomographic characteristics most commonly included pulmonary masses and nodules of variable size, and lesions were most commonly located in the caudal lung lobes. Four dogs had large pulmonary masses with or without additional nodules and one dog had nodular lesions disseminated throughout the entire lung parenchyma. All large eosinophilic granulomas were smoothly margined, heterogeneous pulmonary masses displaying heterogeneous contrast enhancement. A honeycomb‐like enhancement pattern was observed in all but one mass and consisted of multiple hyperattenuating rims delineating central hypoattenuating areas, suggestive of bronchiectatic lung with peripheral enhancing airway walls and fluid‐filled, necrotic bronchial lumen. One dog had evidence of tracheobronchial lymphadenopathy. Findings indicated that canine eosinophilic pulmonary granulomatosis should be included as a differential diagnosis for dogs with CT characteristics of multiple pulmonary masses and/or nodules in caudal lung lobes, and a honeycomb‐like enhancement pattern in masses after intravenous administration of iodinated contrast medium.     

A case of idiopathic eosinophilic pneumonia in a Quarter Horse gelding

A 16-year-old Quarter Horse gelding was presented to the Kansas State Veterinary Health Center for acute onset of diffuse, nonpruritic, generalised and coalescing urticaria. A single dose of dexamethasone resulted in resolution of the urticaria within 24 h; however, 48 h after discharge, he presented with mild colic. The patient was febrile and thoracic ultrasound was abnormal, evidenced by bilateral pleural echogenic irregularities, mild pulmonary consolidation and slight unilateral pleural effusion. Thoracic radiographs also revealed caudoventral soft tissue opacity in the same region of the ultrasonographic abnormalities. Transtracheal wash was performed and broad spectrum antimicrobials initiated. Poor clinical response to therapy and marked peripheral eosinophilia resulted in the necessity for bronchoalveolar lavage, which revealed a predominance of pulmonary eosinophils. A diagnosis of acute idiopathic eosinophilic pneumonia was made. Treatment included a tapering dose of dexamethasone over 4 weeks. Due to incomplete disease resolution, the patient was moved to an alternate environment which resulted in disease resolution.     

Characterisation of the inflammatory reaction in equine idiopathic focal eosinophilic enteritis and diffuse eosinophilic enteritis

REASONS FOR PERFORMING STUDY: Idiopathic focal eosinophilic enteritis (IFEE) and diffuse eosinophilic enteritis (DEE) are primary eosinophilic intestinal conditions without a known cause that are associated with an increasing number of surgical colic cases. Histology may be helpful in defining disease aetiology and pathogenesis. OBJECTIVES: To characterise further the inflammatory infiltrate in equine IFEE and to compare the condition with DEE. METHODS: Twenty-three IFEE cases and 5 DEE cases were examined by light microscopy including immunohistology to identify infiltrating leucocytes. Inflammatory infiltrates in mucosa and submucosa were characterised in IFEE lesions (Group 1), the intestine distant from the lesions in IFEE (Group 2) and DEE (Group 3). RESULTS AND CONCLUSIONS: IFEE lesions represented an accumulation of leucocytes in submucosa and muscularis, with dominance of eosinophils and macrophages and smaller numbers of lymphocytes, plasma cells and neutrophils. T cells represented the dominant lymphocytes. The mucosa overlying the lesion and both mucosa and submucosa in IFEE nonlesion sites and in DEE exhibited a similar composition, with different prevalence of various cell types. Macrophages were significantly more prevalent in the mucosal and submucosal infiltrates in IFEE nonlesion sites than in DEE, and lymphocytes significantly more prevalent in the mucosa in DEE than in IFEE nonlesion sites. The findings confirm IFEE as a primary eosinophilic intestinal disorder and indicate that IFEE represents a focally exacerbated inflammatory reaction in horses with DEE, possibly due to functional changes in the macrophage and T cell components, with subsequent excessive recruitment of both eosinophils and macrophages.     

Limbal conjunctival plaques and idiopathic eosinophilic conjunctivitis

A 4‐year‐old Welsh pony crossbred gelding was examined for acute onset of blepharospasm, epiphora and corneal oedema. Ophthalmic examination identified 2 conjunctival plaques located near the superior limbus of the left eye. The plaques did not resolve following treatment with topical triple antibiotic ointment, topical atropine ointment and oral flunixin meglumine and therefore a conjunctival biopsy was performed. Histology of the biopsy resulted in a diagnosis of eosinophilic conjunctivitis, which was treated with a topical corticosteroid ointment. Plaques resolved after 73 days of therapy but lesions did not improve with concurrent treatment with anthelmintics early in the course of therapy. Failure to identify an aetiological agent led to a diagnosis of idiopathic eosinophilic conjunctivitis. The conjunctival plaques have not recurred in the 10 months following discontinuation of therapy.     

Severe eosinophilic cholangiohepatitis due to fluke infestation in a pony in Scotland

Fasciola hepatica infestation is reported as a cause of severe eosinophilic cholangiohepatitis in a 28‐year‐old Warmblood cross pony gelding. The gelding presented initially for investigation of acute laminitis found to be secondary to pars pituitary intermedia dysfunction (PPID). Six weeks of treatment including administration of pergolide achieved good control of the laminitis but there was a marked general clinical deterioration over this period with notable weight loss, tachycardia, anorexia and ventral oedema. Hepatobiliary enzymes were increased significantly and there was mild elevation of plasma bile acid concentration. An eosinophilia in both blood and peritoneal fluid specimens and histopathological confirmation of an eosinophilic cholangiohepatitis on examination of liver biopsies supported a primary parasitic aetiology. The pony was treated for Fasciola hepatica with triclabendazole 12 mg/kg bwt but clinical signs continued to progress. Due to poor clinical response the pony was subjected to euthanasia and post mortem examination revealed an overwhelming infestation of the biliary tracts with Fasciola hepatica and a secondary chronic and severe cholangiohepatitis with marked fibrosis. To the authors' knowledge this is the first equine report demonstrating the relationship between the clinical disease syndrome, eosinophilic cholangiohepatitis and hepatic fluke infestation. Depending on geographical location, fasciolosis should be considered as a differential diagnosis for equine hepatopathies and can result in severe disease.     

Extreme eosinophilia with disseminated eosinophilic granulomatous disease in a horse

Extreme eosinophilia with disseminated eosinophilic granulomatous disease is described in a 4-year-old Arabian mare. Clinical signs included weight loss, coughing, jugular distention, and ventral edema. Cutaneous lesions were not observed. Eosinophilic inflammation was observed in cytologic specimens from the respiratory tract, body cavities, and lymph nodes. At necropsy, a 20-cm diameter intrathoracic mass was observed. Smaller nodules were present in the lymph nodes, liver, spleen, adrenal glands, pancreas, and skeletal muscle. Histologically, these masses and nodules were characterized by infiltrates of eosinophils, macrophages, and multinucleated giant cells, reactive fibroplasia; and multifocal eosinophilic coagula. Microscopically, mild eosinophilic infiltrates were observed in sections of stomach, small intestine, colon, and pleura; however, gross lesions were not observed in these tissues at necropsy. The etiology of the extreme eosinophilia and disseminated eosinophilic granulomatous disease in this horse was not determined.     

Chronic eosinophilic leukemia in a cat: cytochemical and immunophenotypical features

A 3-year-old, male, domestic shorthaired cat was presented with a 3-day history of anorexia and depression. The cat was moderately dehydrated, had pale, slightly icteric, mucous membranes, oral ulcerations, and mild hepatosplenomegaly. A feline leukemia virus (FeLV) antigen test was positive. CBC results obtained at initial presentation included severe normocytic, normochromic, nonregenerative anemia, severe thrombocytopenia, and marked leukocytosis (>100,000/microL) with 77% eosinophils. After 15 days of treatment with prednisone and doxycycline, the cat had persistent severe nonregenerative anemia (HCT 3.4%), thrombocytopenia (28,000/microL), and extreme eosinophilia (total eosinophils, 123.1 x 10(3)/microL; segmented 103.0 x 10(3)/microL; immature 20.1 X 10(3)/microL). Cytologic examination of aspirates from bone marrow, liver, lymph nodes, and spleen revealed a predominance of mature and immature eosinophils, many with dysplastic changes. The M:E ratio was 96.4. On histopathologic examination, multiple organs were infiltrated by eosinophilic granulocytes. Neoplastic cells in blood and bone marrow stained positive for alkaline phosphatase and were negative for myeloperoxidase, chloroacetate esterase, and alpha-naphthyl acetate esterase. On flow cytometric analysis of peripheral blood, the neoplastic cells were positive for CD11b and CD14. These findings were consistent with chronic eosinophilic leukemia. To our knowledge, this is the first report of chronic eosinophilic leukemia in a cat associated with naturally acquired FeLV infection, in which flow cytometry was used to characterize the neoplastic cells.     

Bovine nasal eosinophilic, granuloma with blood eosinophilia caused by Nocardia species.

OBJECTIVE: To describe a case of nocardial nasal granuloma in a Holstein heifer. CLINICAL FEATURES: The heifer showed laboured respiration and occasional coughing with granulomatous excrescences on the bilateral nasal mucosa, and a marked leucocytosis with eosinophilia. NECROPSY: Severe granulomatous inflammation with eosinophils, epithelioid cells, giant cells and Nocardia sp obstructed both nasal passages completely. CONCLUSION: This lesion resulted from chronic infection with Nocardia sp and is distinct from other forms of bovine nasal granuloma, also called atopic rhinitis or chronic granular rhinitis, which we propose should be classified as bovine allergic granular rhinitis. The most appropriate name for the present disease is bovine nasal eosinophilic granuloma.     

Multisystemic eosinophilic epitheliotropic disease (MEED) in a horse

Extract

A 6-year-old Thoroughbred-cross gelding was presented with ulcerative coronitis and sloughing of chestnuts and ergots. The horse was mildly lame and its faeces were soft and formless. Laboratory findings included a mild eosinophilia, mild hyperglobuli-naemia and a marked elevation of gamma glutamyl transferase and glutamate dehydrogenase. There was a general deterioration of the horse's condition over a 3-week period and the dermatitis became generalised and the diarrhoea severe. It was euthanised. At necropsy, the pancreas was pale, multinodular and firm. The liver had a lobular appearance and there was generalised thickening of the descending colon. Histologically, there was a marked, predominantly eosinophilic infiltrate of the pancreas, liver and colon. There was a superficial and deep perivascular dermatitis of the coronet, characterised by dense infiltrates of eosinophils in association with marked acanthosis and hyperkeratosis. The combination of clinical findings, haematology, serum biochemistry and gross changes in conjunction with the histology confirmed MEED. The aetiology of MEED has not been established.     

Severe pulmonary disease due to multisystemic eosinophilic epitheliotropic disease in a horse

Multisystemic eosinophilic epitheliotropic disease was diagnosed histologically in a 17-year-old Quarter Horse intact mare that was presented with a chronic history of respiratory distress. At necropsy, the lungs were poorly collapsed and the pulmonary parenchyma contained innumerable, discrete, spherical nodules in a miliary pattern. A few similar nodules were scattered in the liver and the renal lymph nodes. Histologically, these nodules consisted of fibrosing eosinophilic granulomas. Based on histologic findings and the absence of an etiologic agent, a diagnosis of multisystemic eosinophilic epitheliotropic disease was made.     

Three cases of idiopathic eosinophilic enteritis with chronic obstinate diarrhea in Japanese Black fattening cattle

Eosinophilic enteritis (EOE) is a type of inflammatory bowel disease and is characterized clinically by chronic obstinate diarrhea. Three Japanese Black (JB) fattening cattle (2 males and 1 female) on different cattle farms presented with chronic episodic diarrhea without fever or dehydration. Soft reddish spherical carneous tissues (1−3 cm) were occasionally excreted within the diarrheic feces. Administration of antibiotics, antidiarrheal drugs and vermicides had no therapeutic effect, but dexamethasone improved the fecal characteristics. The symptoms persisted until the animals were slaughtered at 27–30 months of age. Histopathological examination of the intestines revealed marked eosinophilic infiltration in the lamina propria and submucosa. From these findings, we diagnosed these cattle as the first cases of EOE in JB cattle.     

Clinical and histopathological features of pemphigus foliaceus with and without eosinophilic infiltrates: a retrospective evaluation of 40 dogs

The importance of cellular infiltrates in tissues has been investigated as a diagnostic tool, mechanism of pathogenesis, and prognostic indicator in certain human diseases. Eosinophils, in particular, have a distinct role in the development of cutaneous lesions in human autoimmune diseases. Identification of an eosinophilic infiltrate can aid the diagnosis of immunobullous disease in the early stages of the disease process. In canine pemphigus foliaceus, eosinophils are present to a variable degree within lesional tissue. This study retrospectively evaluated 40 dogs with pemphigus foliaceus, and examined clinical and histologic features and final outcomes in cases with and without eosinophilic infiltrates. Twenty‐five of 40 dogs (63%) had an eosinophilic infiltrate in either the pustules/crust, follicular infundibulum or dermis. There was no statistically significant difference in clinical distribution or appearance of dermatological lesions, response to treatment, or disease outcome in dogs with or without an eosinophilic infiltrate. However, dogs with concurrent disease were significantly more likely to have an eosinophilic infiltrate (P = 0.01). Dogs with adverse effects associated with immunosuppressive therapy were significantly more likely to have an eosinophilic infiltrate (P = 0.05). Fifteen of 40 dogs (38%) had a history of allergic disease and a significantly higher proportion of these dogs had an eosinophilic infiltrate (P = 0.04). An eosinophilic infiltrate was found in more than half of the dogs in this study. These findings justify further studies to investigate the role of eosinophils in the pathogenesis, therapy and prognosis in dogs with pemphigus foliaceus.     

Treatment of proliferative feline eosinophilic keratitis with topical 1.5% cyclosporine: 35 cases

Objective  Proliferative feline eosinophilic keratitis is a chronic keratopathy caused by a suspected immune mediated response to an unknown antigenic stimulus. The purpose of this study is to demonstrate the efficacy of topical 1.5% cyclosporine solution in proliferative feline eosinophilic keratitis.
Methods  Thirty-five cats were treated topically with 1.5% cyclosporine A between 1997 and 2007. Eosinophilic keratitis was diagnosed by clinical appearance and evidence of eosinophils and/or mast cells in corneal cytology. The patients were treated with topical cyclosporine (1.5%) twice (26 of 35, 74.3%) and three times (9 of 35, 25.7%) daily. The minimum period for follow-up was 5 months.
Results  The age of the patients ranged from 2 to 13 years with a mean age of 6.0 years. Twenty-two were neutered males, and 13 were females. The represented breeds were 30 DSH, 3 DLH, one Siamese and one Maine Coon. Cytologic examination of a corneal scrape revealed the presence of eosinophils in 34 of 35 specimens, and mast cells in 25 of 35 specimens. Improvement in the treated eyes was seen in 31 cats (88.6%). Four animals (11.4%) did not respond to the treatment with topical cyclosporine. Recurrences were seen in seven (22.6%) cases. Blepharitis was noted as an infrequent side effect.
Conclusion  Based on our findings, topical cyclosporine (1.5%) is an effective treatment of proliferative feline eosinophilic keratitis in the vast majority of cases. Recurrences were mainly associated with poor owner compliance. Chronic, often lifelong therapy with medications is thus recommended.     

Clinical and histological evaluation of an analogue of palmitoylethanolamide, PLR 120 (comicronized Palmidrol INN) in cats with eosinophilic granuloma and eosinophilic plaque: a pilot study

Fifteen cats with eosinophilic granuloma or eosinophilic plaque were given PLR 120 at the dosage of 10 mg kg⁻¹ twice daily for one month. PLR-120 down-modulates mast cell degranulation via a receptor-mediated mechanism. No other drugs were permitted and cats were kept free of parasites throughout the study. A clinical evaluation and skin biopsies were performed before and after the treatment. Clinical improvement was assessed at 15 and 30 days. Mast cell numbers were counted and their granular content was assessed by densitometric analysis on toluidine blue-stained sections before and after the treatment. Ten of 15 (67%) cats showed clinical improvement of signs and lesions. There was no significant difference between mast cell numbers in skin biopsies taken before and after the trial, whereas the number of granules was significantly increased ( P < 0.009). This pilot study suggests that PLR-120 might be a useful drug for the treatment of eosinophilic granuloma and eosinophilic plaque.     

Chronic eosinophilic dermatitis: a manifestation of a multisystemic, eosinophilic, epitheliotropic disease in five horses

A generalized, chronic, progressive, exfoliative dermatitis in five horses is described. Histologically, the lesion is characterized by a superficial and deep perivascular dermatitis which is eosinophil-rich with a marked lymphocytic and plasmacytic component, accompanied by marked acanthosis and hyperkeratosis. More severe cases progress to a lichenoid pattern with the same cellular composition with focal eosinophilic spongiosis and eosinophilic subcorneal pustules. Clinically, the disease is associated with chronic, severe weight loss and is fulminating. The skin lesions are accompanied by lymphoplasmacytic and eosinophilic infiltrates and formation of eosinophilic granulomas in other epithelial organs, most noticeably the pancreas, in which a chronic, fibrosing pancreatitis develops. Other epithelial organs involved to various degrees are salivary glands, the gastrointestinal system, including the oral cavity and esophagus, biliary epithelium and bronchial epithelium. The etiology of this disease is unknown.