2ObjectivesIntroduction on eosinophils Eosinophilic diseases affecting the Rottweiler Feline eosinophilic diseases Eosinophlic bronchopneumopathy Other eosinophlic diseases (We will be focusing mostly on the weird diseases)
3The Eosinophil Differences in canine vs feline eosinophils Basophila often accompaniesBreeds predisposed to eosinophilic disease:Rottweiler, GSD, Siberian HuskiesAlaskan Malamutes, CKCSDiseases usually involve lungs, skin, GITCommon etiologies: allergic, parasitic, inflammatory, neoplastic/paraneoplastic, hypoadrenocorticism, idiopathic*as both are primed by IL3, which accts for concurrent elevations.in humans- skin, lungs, GIT and less commonly liver; most humans dev cardiac, ocular and neuro dz .
4Diseases associated with pronounced eosinophilia: a study of 105 dogs in Sweden Most common causes were either gastroenteritis (acute or chronic) and PIEDogs with pneumonia had the highest eosinophil counts (also had neutrophila)For dogs that were sampled more than once (49 dogs) – eosinophilia was transient in 31/49 dogsEosinophila was found in 4.8% of cats at the NYS CVM- the most common cause of eosinophia in this study was flea allergy (20%), followed by GI disease (12%), focal infection/inflammation (12%), no dx (9%), FA (9%) and EGC (5%). The highest #s were w/ FAD and EGC.
5Process involved in eosinophila ProliferationAdhesion and MigrationChemoattractionSurvival and activation
7Approach to drug therapy GlucocorticoidsInterferon alphaCyclophilinsLeukotriene antagonistsIL12IL5 or chemokine receptor abLidocaine
8Objectives Eosinophlic diseases affecting the Rottweiler Introduction on eosinophilsEosinophlic diseases affecting the RottweilerFeline eosinophlic diseasesEosinophilic bronchopneumopathyParaneoplastic eosinophilaOther Eosinophilic diseases(We will be focusing mostly on the weird diseases)
9Idiopathic eosinophilic meningoencephalitis in Rottweiler dogs: three cases (1992-1997) All 3 dogs were young male RottweilersAll presented with neurologic symptoms (variable symptoms and duration)Peripheral eosinophilia noted in all threeEosinophilic pleocytosis with mild to marked increased TP on CSF tapsNo infectious diseases identified- however not standardized on testing2 of these dogs improved with steroids1 was euthanized due to lack of improvement (but treated with 1 mcg/kg?)Etiology- immune mediated?Possibly infectious
10Idiopathic hypereosinophilic syndrome in 3 rottweilers IHES: “sustained (> 6mo) peripheral eosinophilia of > cells/uL with no apparent etiology and multiple organ involvement”Described 3 young (2 females and 1 male) Rottie’s- presented with either GI or Resp signsAll had marked peripheral eosinophilia, involvement in the liver, spleen and bone marrow.Pulmonary involvement in 2 (suspected in one)Karotype analysis normalMarked elevations of serum IgESurvival 1/3 (one euthanized and one died 3wks after starting treatment)DDX: Eosinophilic leukemiaAll dogs in this case series were treated with steroidsIn people 1st described in 19681: 1mo h/o vomiting, hematocheazia and wt loss2. 1wk h/o inappetance3. 2mo h/o inappetance, lethargy and coughingLiver and spleen- had either variable echotexture, was big or completely normalDisproproritinate # of immature cells for acute EL (so cannot r/o chornic EL).Although the presence of clonal karyotype abnormalities is diagnostic of underlying neoplasia- their absence does not r/o neoplasiaAs subtle abnormalities may be missed b/c of the large # of chromosomes of ~ size and morphologyLikely not AEL (maybe CEL)
11More on IHES Additional successful treatment- 11yo FS mix k9 Eosinophilic pancreatitis, enteritis, moderate portal hepatitis, pulmonary infiltrates and suspected thrombus within LATreated with pred and hydroxyruea- which were tapered over a 4mo period to lowest effect doseAdverse effects- onychomadesis and mild anemiaMild CS of disease during treatmentHM resolvedHypercoagulable state and risk of TE events with HES?BM, LN GIT, spleen, lungs, ksin, kidneys and peritracheal tissue.In this case- lungs, liver, pancreas, LI/SI, BM and possibly heartIn humans- most dev cardiac, ocular or neurologic symtpoms (which were not seen here); most cats with IHES_ dev GI signs
12Benign form of HES?Case report of clinical remission of HES in a young RottweilerPresenting signs were seizure (which may have been unrelated- suspected trauma vs other)Other to peripheral eosinophilia, eosinophilic hepatitis/abscess, lymphadenitisBAL unremarkable, CSF normal cell countIntestinal abnormalities on AUS (bx not done)Tx with cyclosporine attempted (discontinued due to side effects)Eosinophilia improved but never resolved
13Idiopathic eosinophilic masses of the GIT in dogs Retrospective case series- 7 dogsMost common GI signs- hyporexia and vomitingPeripheral eosinophilic in 6/7 dogsAbdominal ultrasound performed in all dogsProceeded with endoscopy, surgery or both (1 dog)Distinct form EE and IHESHisto findings- moderate to severe eosinophils, often transmural fibrosis as a consistent featureSurgery alone is inadequate (all 3 died within 4 months)3 dogs that lived ≥ 9mo were treated with steroidsRecheck endoscopy & blood work showed improvement in 2 of these dogsRetrospective from VM CVM5 CM, 2 FS: 4 Rottie’s, GSD, Basset and Retriever mixAll presented with GI signs MC signs were decreaed app and vomiting (with GI hemorrhage)These were chronic in 4 and acute in 3 dogs3 had NNN anemia and 1 with marked reg anemia due GI bleed, hypoalb, hypochol4 gastric abnormalities (gastric thickening)solitary intestinal masses in 3 dogs (10cm duo mass, 6 x 2.5 cm jejunal mass, colonic mass)4 dogs had endoscopy-severe ulcerative gastric lesions in 2dogscolonoscopy- multiple masses (ulceration), soliarty rectal mass,Histo form endoscopy- demonstrated that lesions were focal (not diffuse even when multifocal in location)In Sx Other tissues bx- pancreas, liver, spleen and mesenteric LNsdogs tended to be a litter olderEndoscopy rpt in 2 dogs (4 and 12wks) with improvement in signsAlso had resolution of leukocytosis, eosinophilic and hypoalbUlcerative, proliferative gastric and colonic lesions in oneSevere, multifocal colic massesBoth were weaned off pred over 8-12wks and were still alive 2yrs after dx
14Objectives Feline eosinophlic diseases Introduction on eosinophils Eosinophlic diseases affecting the RottweilerFeline eosinophlic diseasesEosinophilic bronchopneumopathyParaneoplastic eosinophilaOther Eosinophilic diseases(We will be focusing mostly on the weird diseases)
15iHES in two cats middle-aged (range 8mo to 12yrs) about 75% are female sex predilectionNo specific breed predilectionGI signs seem to predominate (but coughing and dyspnea are also reported).Additional findings in cats- fever, pruritus, CHF, seizures and weakness.Treatment from a recent study-Combination of hydoxycarbamide and prednisolone in 2 catsSurvived 48 and 91 days after presentationPrognosis for cats is generally poor- 1wk to 3.5yrs (average 7.5wks)
16Feline asthmaPrevalence estimate to be approximately 1% of all feline patientsSignalment: young to middle aged adults, Siamese cats appears to be predisposedMost common clinical signs: recurrent bouts of paroxysmal coughing, wheezing and dyspneaRadiographic signsProminent bronchial markings with peri-bronchial infiltration and diffuse intersisital patternsEosinophiliaPeripheral eosinophila in 20% from two studiesCytology from BAL/ETW samplesEosinophilia supportive, however up to 25% can be seen in healthy catsNot always specific to asthmaEosinophils may comprise up to25% of the cells in BAL samples obtained from healthy cats,making differentiation of asthmatic from healthy cats difficultin some cases.35 Additionally, eosinophilic airway inflammationmay be seen in a variety of conditions including pulmonaryparasitism (which has also been documented to elicitpredominantly neutrophilic inflammation), fungal or viralpneumonia, hypereosinophilic syndrome and dirofilariasis –and, therefore, is not specific to asthma
17Eosinophilic granuloma complex AKA feline eosinophilic skin disease or eosinophilic dermatosesConsists of indolent (or eosinophilic) ulcer, eosinophilic plaque and eosinophilic granulomahisto features are similarPossible etiologic triggers:HypersensitivityInfectious- viral, bacterial, fungal, parasiticOtherTreatment:Identify and treat underlying etiology if possibleImmunosuppressive- glucocorticoids, cyclosporine
18Indolent ulcerOccurs unilateral or bilaterally on the upper lip at the mucocutaneous junction at the philtrum or adjacent to the upper k9 toothdemarcated, variably sized ulcers, often crustedpain and pruritus are rare.
19Eosinophilic plaqueCan occur anywhere but most commonly on the ventral abdomenwell demarcated, flat-topped, erythematous elevations of the skin which are usually alopecic, eroded to ulceratedhighly pruritic
20Eosinophilic granuloma can occur anywhere (including oral cavity)- typically on lower lip, tongue, hard palate, hind limbs and foot pads.Variably pruriticwell demarcated, raised to nodular, alopecia and ulceration are common.Exudation can be seen in the center of ulcerated lesion.May be severe enough to require sx.
21Objectives Eosinophilic bronchopneumopathy Introduction on eosinophils Eosinophlic diseases affecting the RottweilerFeline eosinophlic diseasesEosinophilic bronchopneumopathyParaneoplastic eosinophilaOther Eosinophilic diseases(We will be focusing mostly on the weird diseases)
22Classification of eosinophilic lower airway disorders in dogs Idiopathic eosinophilic bronchitis or tracheobronchitisParasitic tracheobronchitis (Oslerus osleri)Parenchymal disorders associated with known underlying conditionParasitic infectionsOccult heart worm disease (eosinophilic pneumonitis or eosinophilic granulomatous pneumonia)Angiostrongylus vasorum, Filarodies hirthiChronic bacterial pneumoniaIdiopathic hypereosinophilic syndromeLung cancer+/- Eosinophlic pulmonary vasculitisIdiopathic parenchyma disordersEosinophilic granulomatous pneumonia+/- simple eosinophilic pneumoniaIdiopathic mixed (airway & parenchyma) disordersEBP (AKA PIE or PE)
23ebpEtiology remains unclear but suspected hypersensitivity to aeroallergensPathogenesis: dominant Th2 immune responseIncrease in CD4+ T cells and decrease in CD8+ T cellsSignalment: usually young dogs (4-6yrs)Breeds: Siberian Huskies, Alaskan Malamutes, but other small as well as large breedsFemale sex predilection (3:1)
24Clinical signs of ebp Most common signs at time of diagnosis Cough (95-100%)Harsh, followed by gagging and retchingDyspnea (91%)Nasal discharge (52%)Good general body conditionLung auscultationNormal (29%)Increased BV sounds, wheezes or crackles have been reportedMay be acute or chronicDisease onset to diagnosis 3 weeks to 6 years
25Diagnosis of EBP CBC: eosinophilia (50-60%) Neutrophil, basophilia also notedChemistry panel usual unremarkableRadiographs: mixed moderate to severe bronchointersitial pattern most commonPeribronchial cuffing (20% of cases)Alveolar infiltration (up to 40%)Bronchiectasis in chronic casesBronchoscopyModerate to large amount of yellow-green secretion (70%)Moderate to severe thickening of mucosa with irregular or polypoid appearanceDramatic airway hyperemia+/- concentric airway closure during expiration (with chronicity)
26Diagnosis (cont) Cytology Increase cell count ( > 200-400 cells/uL) Increase % eosinophil (generally > 10%)Bacterial culture recommendedPulmonary function testsABG: mild decreased Pa02, increased A-a gradientTidal breathing flow volume loopsWhole body barometric plethysmorgraphyOtherRhinoscopyParsitic analysis (zinc sulfate centrifugation, Baermann, heartworm antigen)Intradermal skin testNormal cell counts range from cells/uL (with predominance of macrophages)Rhinosocyp- congested/edemaotus mucosa, mucoid/MP secretion, poypoid proliferations in severe casesID skin- open to interpretationTidal breathing flow volumes- not examined with EBP
27Treatment Oral glucocorticoid therapy Start with 1mg/kg BID, then gradually decreased to maintenance dose (0.125 to 0.5mg/kg every other day)Response generally goodSymptoms typically improve within daysRelapse of signs can occur within weeks or months after drug discontinuationIn 3 dogs, did not recur up to 2 yearsConsider inhalant corticosteroids if long term steroids neededEmpirically dewormingAntibiotics if positive bacterial culture
28Objectives Other Eosinophilic diseases Introduction on eosinophils Eosinophlic diseases affecting the RottweilerFeline eosinophlic diseasesEosinophilic bronchopneumopathyOther Eosinophilic diseases(We will be focusing mostly on the weird diseases)
29Paraneoplastic Eosinophilia Role of eosinophils and neoplasia is controversialPromoting tissue damage vs protective roleEosinophilia associated with MCT and LSACase reports of intestinal T cell lymphoma (dog and cat)related to production of IL5, IL3 and GM-CSF by the tumorsOther tumors- mammary carcinoma, oral FSA, rectal adenomatous polyp, TCC
30Others Eosinophilic gastroenteritis Second most common form of idiopathic IBDBoxer, Dobermans and GSD may be predisposedMucosal erosion or ulcerations may occur more frequently in EEEosinophilic leukemia in catsMay require immunocytochemistry and flow cytometry to different from IHESMost reported in Felv negative cats (although recent case report in Felv positive)Eosinophilic diseases in CKCSPredisposed to oral eosinophilic granulomas, eosinophilic stomatitisEosinophilic stomatitis along with other (EBP or EE) reported
32ReferencesEosinophilic disease in two Cavalier King Charles spaniels. German et al. JSAP 2002.Investigation of hypereosinophila and potential treatments. Lilliehook et al. VCNA 2003.Eosinophilic leukaemia in cat. Sharifi, et al. JFMS 2007.Chronic eosinophilic leukemia in a cat: cytochemical and immunophenotypical features. Gelain et al. Vet Clin Path 2006.Hypereosinophilic paraneoplastic syndrome in a cat with intestinal T cell lymphosarcoma. Barrs et al. JSAP 2002.Paraneoplastic hypereosinophila in a dog with intestinal T-cell lymphoma Marchetti Vet Clin Path 2005.Eosinophila. Epstein, Rothenberg. NEJM 1998.Eosinophilic bronchopnemopathy in dogs. Clercx, et al. JVIM 2000.Canine Eosinophilic bronchopneumopathy. Clercx, et al. VCNA 2007.
33References contHypereosinophilc syndrome in two cats. Takeuchi et al. J Vet Med Sci 2008.Successful treatemnt of hypereosinophilic syndrome in a dog. Perkins et al. Aus Vet J 2001.Feline Eosinophilic Granuloma complex (itiis): some clinical clafirication. Buckley and Nuttal. JFMS 2012Idiopathic eosinophilic masses of the gastrointestinal tract in dogs. Lyles et al JVIM 2009.Clinical remission of idiopathic hypereosinophilic syndrome in a Rottweiler. James, Mansfield. Aust Vet J 2009.Diseases associated with pronounced eosinophilia: a study of 105 dogs in Sweden. Lillihook, et al. JSAP 2000.Idiopathic hypereosinophilic syndrome in 3 Rottweilers. Sykes et al. JVIMIdiopathic eosinophilic meningoencephalitiis in Rottweiler dogs: three cases ( )Textbook of veterinary internal medicine, 7th edition. Ettinger, Feldman: Chapter 193