EQUINE VETERINARY EDUCATION / AE / NOVEMBER 2020
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Tissue eosinophilia is not a prominent feature of airway wall histology in horses with active disease. Significantly greater numbers of eosinophils are identified intraluminally and in epithelial and smooth muscle layers in control horses compared with those with heaves, defined in this study as airway inflammation and laboured breathing at rest upon exposure to mouldy hay (Dubuc and Lavoie 2014). This is notable as other studies have shown that normal horse lung contains few eosinophils and lacks eotaxin (Benarafa et al. 2000).
Respiratory secretions and histopathologic diagnoses are poorly correlated. Horses with diffuse or focal eosinophilia histopathologically can have similar eosinophil counts in their respiratory secretions (Larson and Busch 1985). Notable are horses with exercise-induced pulmonary haemorrhage (EIPH), in which eosinophils typically are not identified in tracheal or BAL fluid samples (Dixon et al. 1995), but in post-mortem studies, about one-third of horses’ lungs show eosinophils associated with areas of haemorrhage. A role in neovascularisation is hypothesised (O’Callaghan et al. 1987; Gunson et al. 1988).
Specific clinical signs are inconsistently associated with eosinophils. Eosinophils are not consistently associated with coughing (Bedenice et al. 2008). Clinical signs did not differ in IAD cases with and without eosinophilic BALF in one study (Moore et al. 1995), although a period of exercise intolerance coincided with transient increases in BALF eosinophils and PBEs in horses sampled during training (Riihimaki et al. 2008).
Eosinophils are associated with changes in lung
function.In horses with poor performance, eosinophils in BALF were significantly correlated with the impulse oscillometry system test results irrespective of their IAD classification, with IAD diagnosed as BALF cytology having >10% neutrophils, >2% mast cells or >1% eosinophils (Richard et al. 2009). Horses with exercise intolerance and BALF eosinophils >5% had significantly different respiratory scores, and tidal volume and respiratory rate at 20 h post-exercise, than controls, and
eosinophil count was correlated with respiratory score and histamine response in all horses. The respiratory score measures clinical characteristics such as respiratory rate and effort, nasal and airway secretion, auscultation and cough, and results suggest BALF eosinophilia may modify some of these parameters and the histamine response. The reason for a change in lung mechanics was uncertain, but this change potentially mitigated the observed histamine responsiveness (Hare and Viel 1998).
Long-term exposure to allergens may result in airway eosinophilia. A radiolabelling study of horses with a diagnosis of obstructive airway disease in remission showed increased lung eosinophils in only two of seven horses following a 7-h hay challenge (Fairbairn et al. 1993) but a 28-day challenge resulted in significant increases in BALF eosinophils in a group of clinically normal horses, and eosinophils correlated with respirable particles (Ivester et al. 2014). Platelet-activating factor (PAF) may play a role in airway eosinophilia, as horses receiving PAF following injection of radiolabelled eosinophils showed transient increases in pulmonary eosinophils irrespective of airway disease status (Fairbairn et al. 1996). Platelet-activating factor is known to attract eosinophils and other cell types that contribute to the clinical signs of allergic airway disease such as bronchoconstriction (Asmis and Jorg 1990).
Allergic skin disease
Eosinophils are absent from normal skin, but abundant in dermatologic conditions in horses and human subjects such as atopic dermatitis, urticaria, autoimmune disease, drug reactions, larval migrans and ectoparasites (Mathison 1995; Hinden et al. 2012; Wilson 2014; de Graauw et al. 2015). Type I hypersensitivity is the underlying mechanism for many of these conditions, involving aberrant production of IgE, secretion of Th2 cytokines, sensitisation and activation of mast cells, and eosinophil recruitment and degranulation (Mak 2006). Eosinophils may play a role in fibrosis or immunoregulation, (de Graauw et al. 2015) and are present during wound healing in human subjects (Lopez et al. 2014). Many hypersensitivity reactions have been reported in the horse (Nixon et al. 1984; Madison and Ziemer 1993; Turnquist et al. 2001; Spoormakers et al. 2003; Palm et al. 2008; Cocchia et al. 2012) with the best described being insect bite sensitivity.
Magnification: 100 x 5 µm
Fig 2: Eosinophils, characterised by their large granules, are identified in the bronchoalveolar lavage fluid of a horse with inflammatory airway disease. Image courtesy of Dr Theresa Rizzi.
Insect bite hypersensitivity in the horse Insect bite hypersensitivity (IBH) is an allergic condition that has been described in the literature since the nineteenth century. It is a type I hypersensitivity reaction to proteins in the saliva of Culicoides spp. (McKelvie et al. 2001; van der Haegen et al. 2001; Schaffartzik et al. 2012; Wilson 2014; Woodward et al. 2014). The disease occurs globally, variably referred to as sweet itch, Queensland itch and kasen. Occurrence is seasonal, from late spring or early summer through early fall. Clinical signs include pruritus, alopecia, scaling, papules and excoriation, and older horses may be more severely affected. Histological findings include oedema, tortuous vessels and perivascular cuffing. Eosinophils are consistently the predominant cell type, with extensive infiltration through all layers of the skin, and often associated
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