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with blood vessels (Fig 3) (Riek 1953a,b; Baker and Quinn 1978; Kleider and Lees 1984; Kurotaki et al. 1994).
Peripheral blood eosinophils are variably increased in horses with IBH and may be phenotypically distinct. An increase in PBEs was a consistent finding in one population of horses with chronic IBH (Kleider and Lees 1984), while another had increased circulating CD4+ and CD5+ T-cells, and monocytes, but no difference in eosinophils (McKelvie et al. 1999). In susceptible horses, PBEs are higher in the summer, peaking later in the day (Riek 1953a). Protein kinase C isotypes in PBEs from ponies with IBH differ from normal animals, but the functional significance of this has not been determined (Greenaway et al. 2003).
Tissue eosinophilia is a prominent feature of IBH, particularly in the acute phase. Biopsies from active lesions show extensive eosinophil infiltration in all layers of the dermis (Baker and Quinn 1978), and a majority of horses with chronic IBH have significant dermal infiltration of eosinophils (Kleider and Lees 1984). Experimental infiltration of Culicoides extract produces eosinophils in all layers of the skin, notable at 20 min and most prominent at 60 to 90 min (Baker and Quinn 1978). Increased numbers of CD3+CD4+ lymphocytes may also be found in the superficial and deep dermis of affected horses (McKelvie et al. 1999), though in one study lymphocytes were not seen in the youngest affected animals (Baker and Quinn 1978). Degranulated mast cells may be seen, and MHC class II-positive dendritic cells are increased in developing lesions (Kurotaki et al. 1994). Platelet-activating factor and histamine may play a role in eosinophil recruitment, and eotaxin is upregulated in lesions harbouring eosinophils (Foster et al. 1995a,b; Foster et al. 1998; Benarafa et al. 2002).
Eosinophil-associated diseases Eosinophil-associated diseases (EAD) are those in which the eosinophil plays a major, though often enigmatic, role. Rare but debilitating, these conditions are a research priority in human medicine (Bochner et al. 2012; Khoury et al. 2018; O’Sullivan and Bochner 2018). Horses suffer from EADs, including those that affect isolated body systems (Dixon et al.
1992; Lankveld 2001; Uhlhorn et al. 2006; Climent et al. 2007; Loibl et al. 2013; Archer et al. 2014; Lassaline-Utter et al. 2014; Luethy et al. 2017; Trimble et al. 2017), as well as multisystemic eosinophilic epitheliotropic disease (MEED), which affects multiple body systems simultaneously (Bosseler et al. 2013). Lesions can occur in the gastrointestinal tract, skin, liver, pancreas, lymph nodes, kidney, bile ducts and respiratory tract (Bosseler et al. 2013; Pucheu-Haston and Del Piero 2013). Published literature on these conditions is limited to case reports and reviews of individual conditions without consideration given to equine EADs as a whole. The underlying aetiologies of these conditions, and how they may relate to each other or to the diseases reviewed above, are unknown, but a diagnosis typically is made only when there is no direct or temporal evidence of parasites (Ramsey et al. 1994; Yamagata et al. 1996; Edwards et al. 2000; Schumacher et al. 2000; Brooks 2004; Archer et al. 2006; Perez Olmos et al. 2006; Wolfe et al. 2010; Lassaline-Utter et al. 2014; de Bont et al. 2018).
Focal eosinophil-associated diseases in the horse have emerged newly or increased in occurrence since the early 1990s, with MEED appearing in the literature a decade earlier. Eosinophilic disease confined to the intestine (EDCI) (Schumacher et al. 2000) has increased in several countries since the late 1990s (Edwards et al. 2000; Archer et al. 2006; Proudman and Kipar 2006; Archer et al. 2014). This includes cases previously reported as idiopathic focal eosinophilic enteritis (IFEE), diffuse eosinophilic enteritis (DEE) and segmental eosinophilic
colitis (SEC). Eosinophilic
keratoconjunctivitis (KE) has been reported in the literature since the early 1990s (Knickelbein et al. 2019), and is considered an emerging disease (Gonzalez-Medina 2019). Periodic reports of MEED have appeared in the literature since the first published case in 1982 (Pucheu-Haston and Del Piero 2013).
Occurrence of equine EADs is often seasonal. Idiopathic focal eosinophilic enteritis has been reported most commonly between late spring and early fall (Southwood et al. 2000; Archer et al. 2006; Archer et al. 2014). In only one study did this pattern not hold (Perez Olmos et al. 2006). A similar distribution is reported for eosinophilic keratitis, with the greatest clustering in summer months (Lassaline-Utter et al. 2014; Gonzalez-Medina 2019; Knickelbein et al. 2019). In a MEED series, cases occurred in April and October (Nimmo Wilkie et al. 1985).
Equine EADs may occur more often in younger animals. Idiopathic focal eosinophilic enteritis is reported most commonly in horses aged 5 years and younger, and risk decreases with age (Archer et al. 2014). Large colon lesions do not follow this pattern (Edwards et al. 2000; de Bont et al., 2018). In one series of EK cases, all affected horses were aged 5 years and under (Yamagata et al. 1996) but two others showed no age predisposition (Lassaline-Utter et al. 2014; Knickelbein et al. 2019). Nearly two-thirds of individual MEED cases reported in the literature are in horses aged 5 years and under (Bosseler et al. 2013).
20 µm
Fig 3: Degranulating eosinophils are identified in a skin biopsy from a donkey with insect bite hypersensitivity. Image courtesy of Dr Jason Struthers.
© 2020 EVJ Ltd
Evidence for a breed predilection is inconsistent. No breed predilection is noted in EDCI of the small intestine (Archer et al. 2006) or small colon (de Bont et al., 2018). Warmbloods were overrepresented in one EK series (Knickelbein et al.
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