Therapeutic management of canine atopic dermatitis by combination of pentoxifylline and PUFAs.

Canine atopic dermatitis (CAD) is a chronic, pruritic, andrelapsing inﬂammatory skin disease that occurs in 10–15% ofthe canine population. CAD thereby constitutes a serious medicalproblem in veterinary medicine and is reported to be one of themost common causes of canine pruritus (Saridomichelakis et al.,1999). The development and severity of the disease are related toa complex interaction between genetic, immunological, envi-ronmental, pharmacological, and physiological factors, as wellas to the functional state of skin barriers. Increased phosphodi-esterase (PDE) activity has been reported in dogs (Chan et al.,1985) and humans with AD (Haniﬁn et al., 1996), which seemsto be responsible for the deﬁciency of cAMP response in atopicpeople (Butler et al., 1983) and dogs (Butler et al., 1983; Emalaet al., 1995). Dogs with CAD may have a disorder of fatty acidmetabolism. A reduction in n6 fatty acid products of the D6- andD5- desaturases in erythrocytes of dogs with CAD in comparisonwith healthy housemates had been demonstrated by Fuhrmannet al. (2006). Symptomatic treatment modalities for CAD include gluco-corticoids, antihistamines, cyclosporine or a combination isusually tried, and fatty acid supplementation (Grifﬁn, 1993;Scott et al., 2001). Recently, several clinical studies haveproven the use of cyclosporine (Olivry et al., 2002; Steffanet al., 2004; Thelen et al., 2006; Kovalik et al., 2007; Lucaset al., 2007), azathioprine (Favrot et al., 2007), fexofanadine(Plevnik et al., 2006) and tacrolimus (Bensignor & Olivry,2005; Marsella, 2005) with varying efﬁcacy for treatment ofCAD but none has displayed substantial activity. The adverseevents of cyclosporine therapy in dogs are mainly intermittentvomiting, diarrhea (Thelen et al., 2006), and hypertension(Lucas et al., 2007). The only speciﬁc treatment for CAD isavoidance of major allergens and allergen-speciﬁc immuno-therapy. Lack of serum IgE autoantibodies speciﬁc for AD indogs with moderate and severe disease has been demonstratedby Olivry et al. (2008). Physicians should constantly attempt todecrease unnecessary glucocorticoid exposure via introductionof glucocorticoid-sparing therapies and tapering of glucocortic-oids to a minimal effective dose (McDonough et al., 2008). Spontaneous remission of clinical sign is rare, and avoidance ofmajor allergens is often impossible (Scott et al., 2001). Aller-gen-speciﬁc immunotherapy must usually be pursued formonths before an improvement in clinical signs is observed,and it is not effective in all patients (Mueller, 1993; Scott et al.,1993). Many of these dogs experience side-effects related totreatment, or do not achieve sufﬁcient control of the disease.For these reasons, symptomatic therapies are often exploredand calls for a look into new treatment strategies.Pentoxifylline (PTX) is a member of the class of drugs thatinhibit nonselectively phosphodiesterase (PDE) enzymes, referredto as PDE inhibitors (Marks et al., 2001; Scott et al., 2001). Italso decreases ﬁbronectin, reduces the production of cytokines(tumor necrosis factor-alpha, interleukin-1, interleukin -6, andinterleukin-8), decreases leukocyte response to interleukins,impairs T-lymphocyte binding to keratinocytes, decreases ﬁbro-blastic activity and with long-term use, may decrease ﬁbrosis(Samlaska & Winﬁeld, 1994; Bruyazeel et al., 1995). PTX hasbeen reported to have a steroid-sparing effect in dogs andhumans (Marsella, 2000; Marks et al., 2001). It is also a usefuladjunctive therapeutic agent in dogs receiving allergen-speciﬁcimmunotherapy (Scott & Miller, 2007). PTX is rapidly absorbedand metabolized in dogs after oral administration, and welltolerated (Marsella, 2000). Fatty acids are increasingly used incanine atopy and other canine and feline dermatoses, and theirbeneﬁcial effects are documented in several prospective, con-trolled studies (Bond & Lloyd, 1992a,b; Scarff & Lloyd, 1992;Logas & Kunkle, 1994; Mueller et al., 2004). In some atopicdogs, fatty acids alone can alleviate the clinical signs, while inothers, the use of fatty acids can reduce the amount ofglucocorticoids required to control pruritus (Bond & Lloyd,1994) or act synergistically with antihistamines (Paradis et al.,1991; Paterson, 1995). The therapeutic effects of fatty acidsoccur either through reaction of true fatty acids themselves orthrough their activated derivatives called eicosanoid (Barrett &Bigby, 1995).