1. Eosinophilic diseases: “worms, wheezes and Weird diseases”
Gideon Daniel
SAIM Resident
April 9, 2013

2. Objectives
Introduction on eosinophils Eosinophilic diseases affecting the Rottweiler Feline eosinophilic diseases Eosinophlic bronchopneumopathy Other eosinophlic diseases (We will be focusing mostly on the weird diseases)

3. The Eosinophil Differences in canine vs feline eosinophils
Basophila often accompanies
Breeds predisposed to eosinophilic disease:
Rottweiler, GSD, Siberian Huskies
Alaskan Malamutes, CKCS
Diseases usually involve lungs, skin, GIT
Common 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 .

4. Diseases associated with pronounced eosinophilia: a study of 105 dogs in Sweden
Most common causes were either gastroenteritis (acute or chronic) and PIE
Dogs 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 dogs
Eosinophila 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.

5. Process involved in eosinophila
Proliferation
Adhesion and Migration
Chemoattraction
Survival and activation

6. Granules

7. Approach to drug therapy
Glucocorticoids
Interferon alpha
Cyclophilins
Leukotriene antagonists
IL12
IL5 or chemokine receptor ab
Lidocaine

8. Objectives Eosinophlic diseases affecting the Rottweiler
Introduction on eosinophils
Eosinophlic diseases affecting the Rottweiler
Feline eosinophlic diseases
Eosinophilic bronchopneumopathy
Paraneoplastic eosinophila
Other Eosinophilic diseases
(We will be focusing mostly on the weird diseases)

9. Idiopathic eosinophilic meningoencephalitis in Rottweiler dogs: three cases (1992-1997)
All 3 dogs were young male Rottweilers
All presented with neurologic symptoms (variable symptoms and duration)
Peripheral eosinophilia noted in all three
Eosinophilic pleocytosis with mild to marked increased TP on CSF taps
No infectious diseases identified- however not standardized on testing
2 of these dogs improved with steroids
1 was euthanized due to lack of improvement (but treated with 1 mcg/kg?)
Etiology- immune mediated?
Possibly infectious

10. Idiopathic 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 signs
All had marked peripheral eosinophilia, involvement in the liver, spleen and bone marrow.
Pulmonary involvement in 2 (suspected in one)
Karotype analysis normal
Marked elevations of serum IgE
Survival 1/3 (one euthanized and one died 3wks after starting treatment)
DDX: Eosinophilic leukemia
All dogs in this case series were treated with steroids
In people 1st described in 1968
1: 1mo h/o vomiting, hematocheazia and wt loss
2. 1wk h/o inappetance
3. 2mo h/o inappetance, lethargy and coughing
Liver and spleen- had either variable echotexture, was big or completely normal
Disproproritinate # 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 neoplasia
As subtle abnormalities may be missed b/c of the large # of chromosomes of ~ size and morphology
Likely not AEL (maybe CEL)

11. More on IHES Additional successful treatment- 11yo FS mix k9
Eosinophilic pancreatitis, enteritis, moderate portal hepatitis, pulmonary infiltrates and suspected thrombus within LA
Treated with pred and hydroxyruea- which were tapered over a 4mo period to lowest effect dose
Adverse effects- onychomadesis and mild anemia
Mild CS of disease during treatment
HM resolved
Hypercoagulable 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 heart
In humans- most dev cardiac, ocular or neurologic symtpoms (which were not seen here); most cats with IHES_ dev GI signs

12. Benign form of HES?
Case report of clinical remission of HES in a young Rottweiler
Presenting signs were seizure (which may have been unrelated- suspected trauma vs other)
Other to peripheral eosinophilia, eosinophilic hepatitis/abscess, lymphadenitis
BAL unremarkable, CSF normal cell count
Intestinal abnormalities on AUS (bx not done)
Tx with cyclosporine attempted (discontinued due to side effects)
Eosinophilia improved but never resolved

13. Idiopathic eosinophilic masses of the GIT in dogs
Retrospective case series- 7 dogs
Most common GI signs- hyporexia and vomiting
Peripheral eosinophilic in 6/7 dogs
Abdominal ultrasound performed in all dogs
Proceeded with endoscopy, surgery or both (1 dog)
Distinct form EE and IHES
Histo findings- moderate to severe eosinophils, often transmural fibrosis as a consistent feature
Surgery alone is inadequate (all 3 died within 4 months)
3 dogs that lived ≥ 9mo were treated with steroids
Recheck endoscopy & blood work showed improvement in 2 of these dogs
Retrospective from VM CVM
5 CM, 2 FS: 4 Rottie’s, GSD, Basset and Retriever mix
All presented with GI signs MC signs were decreaed app and vomiting (with GI hemorrhage)
These were chronic in 4 and acute in 3 dogs
3 had NNN anemia and 1 with marked reg anemia due GI bleed, hypoalb, hypochol
4 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 2dogs
colonoscopy- 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 LNs
dogs tended to be a litter older
Endoscopy rpt in 2 dogs (4 and 12wks) with improvement in signs
Also had resolution of leukocytosis, eosinophilic and hypoalb
Ulcerative, proliferative gastric and colonic lesions in one
Severe, multifocal colic masses
Both were weaned off pred over 8-12wks and were still alive 2yrs after dx

14. Objectives Feline eosinophlic diseases Introduction on eosinophils
Eosinophlic diseases affecting the Rottweiler
Feline eosinophlic diseases
Eosinophilic bronchopneumopathy
Paraneoplastic eosinophila
Other Eosinophilic diseases
(We will be focusing mostly on the weird diseases)

15. iHES in two cats middle-aged (range 8mo to 12yrs)
about 75% are female sex predilection
No specific breed predilection
GI 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 cats
Survived 48 and 91 days after presentation
Prognosis for cats is generally poor- 1wk to 3.5yrs (average 7.5wks)

16. Feline asthma
Prevalence estimate to be approximately 1% of all feline patients
Signalment: young to middle aged adults, Siamese cats appears to be predisposed
Most common clinical signs: recurrent bouts of paroxysmal coughing, wheezing and dyspnea
Radiographic signs
Prominent bronchial markings with peri-bronchial infiltration and diffuse intersisital patterns
Eosinophilia
Peripheral eosinophila in 20% from two studies
Cytology from BAL/ETW samples
Eosinophilia supportive, however up to 25% can be seen in healthy cats
Not always specific to asthma
Eosinophils may comprise up to
25% of the cells in BAL samples obtained from healthy cats,
making differentiation of asthmatic from healthy cats difficult
in some cases.35 Additionally, eosinophilic airway inflammation
may be seen in a variety of conditions including pulmonary
parasitism (which has also been documented to elicit
predominantly neutrophilic inflammation), fungal or viral
pneumonia, hypereosinophilic syndrome and dirofilariasis –
and, therefore, is not specific to asthma

17. Eosinophilic granuloma complex
AKA feline eosinophilic skin disease or eosinophilic dermatoses
Consists of indolent (or eosinophilic) ulcer, eosinophilic plaque and eosinophilic granuloma
histo features are similar
Possible etiologic triggers:
Hypersensitivity
Infectious- viral, bacterial, fungal, parasitic
Other
Treatment:
Identify and treat underlying etiology if possible
Immunosuppressive- glucocorticoids, cyclosporine

18. Indolent ulcer
Occurs unilateral or bilaterally on the upper lip at the mucocutaneous junction at the philtrum or adjacent to the upper k9 tooth
demarcated, variably sized ulcers, often crusted
pain and pruritus are rare.

19. Eosinophilic plaque
Can occur anywhere but most commonly on the ventral abdomen
well demarcated, flat-topped, erythematous elevations of the skin which are usually alopecic, eroded to ulcerated
highly pruritic

20. Eosinophilic granuloma
can occur anywhere (including oral cavity)- typically on lower lip, tongue, hard palate, hind limbs and foot pads.
Variably pruritic
well 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.

21. Objectives Eosinophilic bronchopneumopathy Introduction on eosinophils
Eosinophlic diseases affecting the Rottweiler
Feline eosinophlic diseases
Eosinophilic bronchopneumopathy
Paraneoplastic eosinophila
Other Eosinophilic diseases
(We will be focusing mostly on the weird diseases)

22. Classification of eosinophilic lower airway disorders in dogs
Idiopathic eosinophilic bronchitis or tracheobronchitis
Parasitic tracheobronchitis (Oslerus osleri)
Parenchymal disorders associated with known underlying condition
Parasitic infections
Occult heart worm disease (eosinophilic pneumonitis or eosinophilic granulomatous pneumonia)
Angiostrongylus vasorum, Filarodies hirthi
Chronic bacterial pneumonia
Idiopathic hypereosinophilic syndrome
Lung cancer
+/- Eosinophlic pulmonary vasculitis
Idiopathic parenchyma disorders
Eosinophilic granulomatous pneumonia
+/- simple eosinophilic pneumonia
Idiopathic mixed (airway & parenchyma) disorders
EBP (AKA PIE or PE)

23. ebp
Etiology remains unclear but suspected hypersensitivity to aeroallergens
Pathogenesis: dominant Th2 immune response
Increase in CD4+ T cells and decrease in CD8+ T cells
Signalment: usually young dogs (4-6yrs)
Breeds: Siberian Huskies, Alaskan Malamutes, but other small as well as large breeds
Female sex predilection (3:1)

24. Clinical signs of ebp Most common signs at time of diagnosis
Cough (95-100%)
Harsh, followed by gagging and retching
Dyspnea (91%)
Nasal discharge (52%)
Good general body condition
Lung auscultation
Normal (29%)
Increased BV sounds, wheezes or crackles have been reported
May be acute or chronic
Disease onset to diagnosis 3 weeks to 6 years

25. Diagnosis of EBP CBC: eosinophilia (50-60%)
Neutrophil, basophilia also noted
Chemistry panel usual unremarkable
Radiographs: mixed moderate to severe bronchointersitial pattern most common
Peribronchial cuffing (20% of cases)
Alveolar infiltration (up to 40%)
Bronchiectasis in chronic cases
Bronchoscopy
Moderate to large amount of yellow-green secretion (70%)
Moderate to severe thickening of mucosa with irregular or polypoid appearance
Dramatic airway hyperemia
+/- concentric airway closure during expiration (with chronicity)

26. Diagnosis (cont) Cytology Increase cell count ( > 200-400 cells/uL)
Increase % eosinophil (generally > 10%)
Bacterial culture recommended
Pulmonary function tests
ABG: mild decreased Pa02, increased A-a gradient
Tidal breathing flow volume loops
Whole body barometric plethysmorgraphy
Other
Rhinoscopy
Parsitic analysis (zinc sulfate centrifugation, Baermann, heartworm antigen)
Intradermal skin test
Normal cell counts range from cells/uL (with predominance of macrophages)
Rhinosocyp- congested/edemaotus mucosa, mucoid/MP secretion, poypoid proliferations in severe cases
ID skin- open to interpretation
Tidal breathing flow volumes- not examined with EBP

27. Treatment 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 good
Symptoms typically improve within days
Relapse of signs can occur within weeks or months after drug discontinuation
In 3 dogs, did not recur up to 2 years
Consider inhalant corticosteroids if long term steroids needed
Empirically deworming
Antibiotics if positive bacterial culture

28. Objectives Other Eosinophilic diseases Introduction on eosinophils
Eosinophlic diseases affecting the Rottweiler
Feline eosinophlic diseases
Eosinophilic bronchopneumopathy
Other Eosinophilic diseases
(We will be focusing mostly on the weird diseases)

29. Paraneoplastic Eosinophilia
Role of eosinophils and neoplasia is controversial
Promoting tissue damage vs protective role
Eosinophilia associated with MCT and LSA
Case reports of intestinal T cell lymphoma (dog and cat)
related to production of IL5, IL3 and GM-CSF by the tumors
Other tumors- mammary carcinoma, oral FSA, rectal adenomatous polyp, TCC

30. Others Eosinophilic gastroenteritis
Second most common form of idiopathic IBD
Boxer, Dobermans and GSD may be predisposed
Mucosal erosion or ulcerations may occur more frequently in EE
Eosinophilic leukemia in cats
May require immunocytochemistry and flow cytometry to different from IHES
Most reported in Felv negative cats (although recent case report in Felv positive)
Eosinophilic diseases in CKCS
Predisposed to oral eosinophilic granulomas, eosinophilic stomatitis
Eosinophilic stomatitis along with other (EBP or EE) reported

31. Questions??

32. References
Eosinophilic 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.

33. References cont
Hypereosinophilc 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 2012
Idiopathic 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. JVIM
Idiopathic eosinophilic meningoencephalitiis in Rottweiler dogs: three cases ( )
Textbook of veterinary internal medicine, 7th edition. Ettinger, Feldman: Chapter 193