P. Prélaud, H.T. Power Atopic dermatitis syndrome Canine atopic dermatitis (CAD) is a camman chronic prurtic dermattis, the definition of which causes much controversy. Only the defritions proposed by the European Academy of Alergy and Cinical immunology’ AAC), adopted recently by the WHO, and thase by the International Task Force on Canine Atopic Dermatitis (TFCAD) {are to be used (Table 15.). CAD is, therefore, a chronic pruritic dermatitis ofthe face and limbs, responsive to glucocorticoids and linked toa predisposition to develop allergic reactions to environmental allergens. This def- ition can include food hypersensitvty as Its impossible to distinguish atopic dermatitis caused by food aller- {gens from atopic dermattis caused by aeroallergens®. When there is no demonstrable evidence of allergy, or more precisely, atopy, despite a cinical history consistent with this condition, the term “atopic dermatits-ike" is some- times used, The mutiplcity of cinica forms and causes of CAD is such that today in human medicine, the term “atopic dermatitis syndrome" is used’. Such variety algo exists in the dog and we have chosen to use the term canine atopic dermatitis syndrome. The incidence of CAD in the dog is unknown, although most authors cite an incidence of 10% of the canine population’. Table15.1: Definition of terms used in clinical immunology. Hypersensitivity: reproducible clinical signs, triggered by exposure to a stimulus which, at the same dose, produces no effect in a normal individual. Allergy: hypersensitity of immunological origin ‘Atopy: predisposition to develop allergic reactions Canine atopic dermatitis: a geneticaly-predisposed pruritic dermatitis characterised by particular pattems of lesion cistrbution and frequent association with allergy to aeroallergens. Aetiopathogenesis as ‘CAD has long been thought to involve alergy to aeroalergens. Atthough this i important, the condition is mutifac- torial invohing bot intrinsic factors, unique to the animal, and extrinsic factors, relating to both the environment and ‘cutaneous microenvironment. A thorough understanding ofthese factors is needed if the condition is to be mana- ‘ged successfully Intrinsic factors Genetic predisposition Genetic predisposition is exoressed inthe breed and line. Lines of atopic dogs have been selected for exper ‘mental reseerch. Some present spontaneously with sttong IgE responses to experimental sensitisation (ler {ons injected wth an advent), some show a strong spontaneous response to house dust mites or food allergens and others develop clinical atopic dermatitis Breed predispositions are very significant but vary from one country to another. Breeds commonly cited in ‘America, Europe and Japan include the Shar pei, Fox trier, Jack Russell erie, Labrador retriever, French bull. dog, West Highland White terier, Boxer and Dalmatian. The risk of a Labrador retriever puppy, born of atopic parents, developing atopic dermatitis is close to 0.56. Genetic predisposition is probably muti-alllc. Studies invohing lines of atopic dogs or dogs that have been artificially sensitised, show that the allergen-specific IgE response, total IgE concentration and the clinical expression of CAD depend on different genes*, 209Immune response Each atopic inivdual evokes an IgE immune response to environmental antigens, This abnormal is due to {deviation in the cetar immune response, thought tobe a Th2 response, characterised by production of yo kines that favour the allergic response: increased IgE production, expression of high-afnity receptors by ant- gen-presenting cells Langerhans’ cals) and mast cel pre-activation. This creates a vicious circle perpetuating the allergic response. The IgE laden antigen-presenting cell present a large quantity of epitopes to lymaha- cfs, favouring an IgE response, Pre-actvated mast cells are very really activated by immunological and nen- immunological stiruiation Surface hydrolipid barrier and keratinisation abnormalities In the atopic dog, surface hydolipid barrier abnormalities lead to increased water loss and greater adherence Of infectious agents such as staphy/ococe’ and Malassezia spp. in breeds such as the West Highland White terrier and Shar pei, Keratinisation disorders sometimes dominate the clinical picture’. Extrinsic factors ‘Atopic individuals can be allergic to both aeroallergens and food allergens. Aeroallergens House dust mites In every continent, house dust mites are the most commonly encountered aeroallerens'®. The most alerganic in the dog is Dermatophagoides farinae (Df. Sensitivities to other pyroglyphid mites, D. pteronyssinus (Op) and 'D. microcera, are a lot less common. The diference in sensitivity to that seen in the human population sharing the same habitat, is probably explained by the fact that the major allergens in dogs and people are diferent (Table 15:1). The house dust mite, Eurogyphus mayne! may also cause sensitisation in the dog. Inthe topics, the house dust mite fs Blomia tropicals" ‘Table15.1l: Major aeroallergens isolated in the dog and their equivalent allergens in human medicine Allergen Major allergen for man Major allergen forthe dog Dermatophagoides farinae Der f 1, Der {2 Der { 15, Der 2, Der f 18 Dermatophagoides pteronyssinus | Der 0 1, Der p 2 z Chat Fold : Ragweed Rog 1 - ‘Cryptomeria japonicum oyit Onyit orage (storage) mites The incidence of forage mite sensitity is high in atopic dogs. iis dificult to know if this apparent sensiiity Is due to cross reactivity with Dermatophagoides mites or a genuine sensitty in is own right, The qualty of some forage mite extracts is not always that high and test results may be unreliable. ntradermal reactions to Tyrophagus are impossible to interpret as they are often postive in both normal and atopic dogs, at every dilution” Hair and scale ‘The importance of allergies to hair and epithelia, human or animal, is unclear in the dog. Apparent senstvtos do occur but their signiicance and the importance of including hair and epithelial allergens in an ant-llergen vaccine is unknown, Cockroaches Cases of cockroach sensitivity have been reported in Europe", They have always been associated with pyro ‘lyphid mite allergy and the inclusion of cockroach allergen in anti-allergen vaccines has never been found to be worthwhile, 23015: Atopic dermatitis syndrome Other components of house dust (Other components af house dust, formerly included in intradermal tests, are now known to be non-allergenic in the dog and therefore obsolete. They inctude linen, woo, cotton and kapok Pollens ‘The allergenic pollens are, as in human medicine, anemophlous pollens. ‘Tree pollens are a heterogeneous group of species which vary with latitude and continent. They are often ineri- rminated in towns and cities. The most common causes of allergy are birch pollen in Northern Europe, cypress in the Mediterranean region’” and Cryptomera japonicum (Jepanese Cedar in Japan’, for which the major aller- ‘gen and specific epitopes in the dog have been characterised (Table 15.1). Grass pollens are highly antigenic", the most important allergenic pollens in temperate regions. The presence of ‘grass pollens in the soll may explain non-seasonal allergies to these pollens in the dog. Weed pollens belong to various families. The most allergenic of als that of ragweed in North America and much ‘of Europe. Plantain, mugwort, goosefoot and wall pelitory may cause senstisation especially in dry regions and in the countryside" ‘Moulds Mould spores are often incriminated. Although allergenic mould extracts often cause both positive intradermal test reactions and raised specific IE tres", sensitisation appears not to be spectic and ther importance in anti- allergen vaccines has never been demonstrated. Food allergens. Food allergens are important in the atopic dog. In one of few prospective studies involving elimination diets in atopic dogs, signs were controled after an olimination dit in 20% of cases". Although foods most commonly incriminated in food hypersensthity studies in the dog are meat (beef, chicken and lamb), egg, dairy products ‘and soya, any dietary protein is potentially allergenic, Our knowledge of which allergens are important is far from ‘complete. “The main allergens for the dog in beet and cow's milk may be heavy immunoglobulin G chains”. There may be cross reactions between cow's mik and beef in the dog, Allergy to casein in cow's milk has also been demons ‘vated in models of animals with spontaneous food allergies", Muscle enzymes (e.g. phosphoglucomutases) com- ‘mon to many mamaian species may explain the cross reactions between lamb and beet”. “The vast majo of alergens identified inthe dog are high molecular weight proteins, 40-70 KD. Cross reactions between foods and pollens are very rare in the dog. The ony case reported is between tomato and cypress polen'. Ctenocephalides felis ‘topic dogs are not predisposed to developing fea allergy dormaits but fea bites may cause fares, ether via ‘a summation effector via the effects of salivary superantigens™. The extent to which flea bites tigger CAD flares, is currently unknown. Staphylococcus intermedius ‘Staphylococcus intermedtus is highly incriminated in CAD flares. in dogs with CAD, staphylococcal adherence is ‘enhanced, with increased mutiplcation causing pyoderma or surface bacterial proliferation. Staphylococcal ente- rotoxins may have superantigen effects exacerbating the allergic reaction. Protein A, produced by most ‘Staphylococcus intermedius strains, can activate cutaneous mast oats (Diagram 15.1). Malassezia spp. ‘Atopic dermatitis is the main cause of Matassezia dermatitis. Yeasts readily colonise the skin of atopic dogs, espe- Cialy whan there is a concurrent keatinisation disorder. Atopic dogs also develop an IgE response to yeast anti- {gens which enhances both prutitus and lesions*, 231\ Practical Guide To Canine Dermatology Diagram 15.|: Vicious circle of staphylococc| inflammatory reaction in atopic dermatitis SSAs. <= gO eo e= 10 staniylococci and stapnyecoceal antigens @ Protein WC Aeroalergens ‘SSAs: staphylocoscal suporantigens Vasoactive amine release favours penetration by staphylococci. Proten G, aeroallergans and staphylococcal antigens provoke IgE-dependent mast cal activation. SSA trigger an immune response leading to mast col ‘pre-activation, Clinical signs _ eae tm Cinical signs appear between 6 months and 3 years in 75% of cases". There ar las of ciferent patterns or forms of atopic dermatitis. Signs seer to show breed variation in severity and clstrbution, although no studies, have actualy shown ths. Typical form ‘Skin lesions involve localised pruritus of the face (ears, li, per-palpebral region) (Fig. 15:1-8), and/or dts (Fig. 15:9-12) and/or anil, inguinal and perineal regions (Fig. 15:13-21). Primary lesions include erythema ‘and papules and some salvary staining of hairs induced by licking. This is the form most readily identifiable, In chronic cases, most lesions, excoriation, alopecia, ichenffication and hyperpigmentation, arise from sei trauma, Most atopic dogs veer towards this form if untreated. Not many dogs go on to develop a serious, ‘generalised condition, Generalised (severe) form In chronic cases or ithere is a marked concurrent keratinisation disorder, severe pruritus and lesions may affect the whole body (Fig. 15:21,23,24). Surface bacterial and/or fungal (Malassezia spp.) proliferation (Fig. 16:9,11,16,19), bacterial folicultis and even furunculosis may develop. This form carries a more guarded pro- 232)161: Atopic dermatitis #1 @ mer mize 163: Atopic dermatis renfcation and ex ‘pic dermatitis syndrome 15.2: Atope dermatitis a French bullog: facial igo aesooated with Malasseza ina Fronch bulldog: facial rpigmentation fo derma retriever: Ovonic oh 233Practical Guide To Carine Derma gnosis, ‘The dog may be affected systemically Atypical forms. ‘Atypical forms are often poorly understood. They are basically localised: isolated otitis externa, bilateral podo- dermatitis, hyperkeratosis around the nipples. These isolated manifestations occur long before pruritus has beco- me bad enough to warrant consultation, Even moderate pruritus may not be noticed by the owner. It is important 10 identity these unusual forms in animals of predisposed breeds so that the owner can be prepared forthe possibilty that the dog may develop more extensive clinical signs (typical form), ‘Some animals have non-lesional pruritus with only seltinduced wel-crcumscribed bilaterally symmetrical alo- ppecia. In our experience, such hair loss is typically seen around the elbow, hock, stile and flanks. it seems to bbe associated more with pollen than with house dust mite allegies. Recurrent pyotraumatic dermatitis and pyotraumatic follcultis and furuncuiosis can be a manifestation of CAD, especially in densely-coated dogs. Diagnosis Clinical diagnosis \Various systems of diagnostic crtera have been proposed for cinical diagnosis. They have been derived mainly ‘rom human dermatology” and are sometimes superfuous (positive intradermal reactions and raised specific gE levels), not explct enough (facial lesions) or non-specific (ryperhydross, hock lesions). Only one study has tes- tad the diagnostic strength of these criteria by comparing them in atopic dogs and non-atopic prurtic dogs. This study enabled minor and major criteria to be defned (Table 16:l). The presence of atleast three mejor ofteria ‘ves a 79% sensitivity and an 81% specify. Most minor erteria, .9. hypertydrosis, are very specific but rot very sensitive (Table 15.1), ‘Table15.ll: Diagnostic criteria for canine atopic dermatitis (Prélaud and colleagues”) - Onset of cnical signs between 6 months and 3 years Pruitus sensitive to glucocorticoids - Bilateral erythematous pododermatitis affecting anterior interdgital region Medial pinnal erythema Cheitts = Prodisposed breed or family history - Chronic relapsing dermatitis of over two year's duration + Lacklustre coat ~ Hock lesions Aral lick dermatitis ~ Hyperhydrosis - History of urticaria or angio-oedema - Seasonal exacerbation of tnical signs = Exacerbation of clinical signs when walking through grass - Variation in clinical signs according to habitat Differential diagnosis ‘The differential diagnosis includes all pruritic dermatoses. As CAD is a condition ofthe young adut, ferential include ectoparasitic infestations, skin infections, other types of allergic dermatitis (Table 151V) and causes of rnon-lesional pruritus such as behavioural disorders, ois media and syringomyelia (facial distribution 23618: Atopic dermatitis syndrome 15.105 16.1: Atgpe demmatiue in a Labrador retriever: ventral pedal ‘entoma, har ascolouration and brownish deposit Maassexa 1613: Aloo dermattis in a Fox terior cross: ventral carpal236 Table15.V : Ditferental diagnosis of CAD ‘Skin condition ‘Simlatos with CAD Diagnosis ‘Sarcoptic mange Prurtus ‘Skin serapings Distribution ace, cstal lbs) Serological testing Fesponse to sterid therapy Response to therapy Demodicosis Prunus es frequent) ‘Skin scrapings. Distribution imoling fet and lips Precisposed breeds (eg. Cavalier King Charles spaniel, West Hghland White terior and English bul trier) Bacterial overgrowth Pruttus, distrbution Cytology, response to therany syndrome (806) (axllae and inguinal gions) Malassezia dermatitis’ | Prutus and identical cstibution Cytology response to therapy Bacterial folicults" ruts, cistbuton Cytology response to therapy (exile and inguinal regions) ‘Contact dermatitis Prutus, distribution fips and dts) ‘Argon avoidance ‘Mucooutaneous Teal mphoma Pruitus, cistrbution Cytology, skin biopsies ips, alae and inguinal regions) ‘Syringomyelia Facial or neck prurtus MF Behavioural problems ‘Anal king Demonstration of habit or substitution activity Allergy testing Contrary to afar too widely held eke, diagnosis isnot based solely onthe results of alergy testing. Alergy test resuts shoud only be interpreted in the light of eporprate tory and clrical signs. About 20-80% of atop dogs produce negative alery test results whereas a sindar ar even greater percentage (<50%) of normal dogs may test postive Cross reactions between house dust mites and paraste mites (¢.9, Sarcoptes, Chey, Trombicua and Otodectes) ‘can oocur Dogs infested wth these parasites may, therefore, test postive to pyreghphid mtes®™ ‘The aim of alergy testing is nat to confrm a diagnosis of CAD but to select appropriate therapy (e.g. ant-allergen ‘vaccination. I can also help calm anxious owners by identiying the alergies affecting their dog. History The most important questions to ask the owner relate to diet, stools, in-contact animals, habitat, seasonal var tion and changes when the animal is taken to another location. Elimination diet {An elimination diet must be carried out and followed stictl. A third of atopic dogs can be controled with cet” ‘but compliance is not always perfect. Dietary history {A dietary history must be taken and al items listed. This is not easy given the abundance of food sources. Any supplements, scraps, treats or hidden extras must be noted. if necessary, the owner should be asked to keep 1 diary of al items consumed within a fortnight, Including all supplements and medications containing favour enhancing proteins (.g. pig Iver Selecting an elimination diet Protein in an elimination diet, protein must be restricted to sources never previously eaten by the animal. Duck, horse15: Atopic dermatitis syndrome 16.17: Atop ina French buldog: erythema, papules, the ventral neck rmatis ina Sharpe: enthema and lchenication 16.20: Atopic dermattls na Shar pet: anal mucosal erosions and abdomen and medal hind imbs perineal erythema 18.21 Atopic damatits (severe form) ina French buldog: ventral 15.22: Atopic dermatts in a Fox tere: sefncuced bata ank thama,Ichenifeation, enlarged feats and markod cxythema and ofthe nippes 3 Atopic dermatitis (severe form) in a Labrador retriever: 3 erthema and papules with largo areas of fehenication erythema, lehenifcaton, hyperpigmentation and skin ridging 237A Prectical Gudde To Canina Darrnatelogyy 238 ‘and white fish are often appropriate. Hycrotysed proteins are low in molecular weight and allergenicity, highly igestible and can be used whatever thelr origin. Most hydrolysed diets are poultry- or soye-based. Home-prepared diets Home-prepared diets should include just one source of protein and one source of carbohydrate. The advanta: {98 of these diets lies with the owner having control overall basi ingredients. For dogs used to home-prepa- red diets, they are often more palatable than commercial dry diets (Table 15.V). On the downside, they ae ess practical, especially for large dogs. Any imbalances for puppies or dogs requiring the diet for more than two ‘months, can easly be corrected. However, additional constraints associated with these diets can lead to ower compliance (Table 15.V), ‘Table1$.\: Examples of protein and carbohydrate sources in a home-prepared clet. Protein Carbohydrate Horse ice White fish Maize Duck Tapioca (cassava) Chicken Potato Lamb ‘Sweet potato Rabott Banana In puppies, calcium and a source of vitamin D should be added (Zima D2, 1 drop per 10 kg body weight) * 0.25 g CaCO,/kg body weight (<20 ka) * 0.5 g CaCO,/kg body weight (>20 kg) Commercial diets “There is a mutituce of commercial diets marketed as ‘hypoallergenic’ or ‘for skin allergies’. These cet fi nto three categories: ‘protein coming mostly from specific sources. These diets cannot be considered suitable as elimination diets 1a the protein source is too varied. + protein coming entraly from specific sources (e.g. ostrich, Kangaroo and duck). These diets are suitable but ‘may contain hidden traces of food allergens. + hydrolysed protein, These cts are theoretically less Ikely to be allergenic than non-hydrolysed diets, Hycrosis reduces protein into smal, low molecular weight peptides. Hydrolysed dlets are therefore the most practical ‘commercial preparations, Hydrolysis effectively reduces the molecular weight and intinsic antigenic of the food and also makes it more digestible. These two factors combine to provide low stimulation to the gas ‘ro-intestnal immune system, ‘The advantage of commercial diets Is their ease of use (Table 15.\Vl). However, this should not lead the owner ‘to underestimate the diftcuities of sticking to such a cet. A commercial dst should be fed as strictly as a home: prepared diet in relation to amount and timing of feeding, preventing other foods being eaten, checking for gas- tro-intestnal side-effects. and monitoring the animal's weight. Concurrent therapy ‘Therapy, usually antibiotics or glucocorticoids, may need to be given alongside an elimination let. Such there- by must be stopped for 6 waeks before the efficacy of the elimination diet can be determined. If pils must be given with food, all protein sources, including butter, cheese, ice cream, meat and animal treats must be avo dod. Honey is preferable. Monitoring ‘The patient must be monitored to ensure good compliance. Potential side-etfects such as weight loss / gain ‘and gastro-intestinal problems, or practical dificules such as refusing to eat or behavioural changes can aso be spotted. To reduce the lkelincod of gastrointestinal problems, the elimination diet should be introduced gr dualy, over at least 4 days, alongside the familar diet. Ifthe dog loses weight, the diet must be adjusted (for ‘example, protein intake increased) Length of diet ‘Six to eight weeks is considered optimal by most dermatologists. Continuing beyond this time is pointess i there has hitherto been no benefit15: Atopic derma syndrome ‘Table15.VE Ingredients of home-prepared diets (G. Blanchart, ENVA, personal communication) 3 desert spoons EE Se ey ann ee a anes wma ‘Table 18.VIl; Advantages and disadvantages of home: prepared and commercial diets Practical Wel balanced, highly cgestibie Low allergenicity / hycrolysed Palatabity Preparation time consuming ‘No control over proten sources (ten to0 ich in protein tives [Need to balance the dit for growing dogs Large range o foods Sido-etocts Cost Platabity Patatabity Interpretation ‘Athough spectacular clinical improvement is, natural, easy to appreciate, partial improvement is harder to reco- rise. Keeping labelled photographs and a log of pruritus scores (Table 16.Vl) can be very helpful Tablet$.Vill: Prurtus scoring No prutus Mid prurtus, not reported spontaneously by the owner, or under an hour per day Moderate pruitus, reported spontaneously by the owner, 1-8 hours per day Marked pruritus, 3-6 hours per day Severe, unremiting prutus, cbserved during the consultation; césturbed sleep 239240 ‘Socing a marked improvement is insufficient to attriute dietary involvement in a case of CAD. Some dogs do not relapse when the previous diet is reintroduced. All dogs need, therefore, to be challenged with thelr old cst before any frm conclusions can be drawn about the effects of the elimination det. In the absence of any impro- ‘yement, compliance and strict adherence to the diet must be verified before dietary hypersensitivity is rejected Challenge There are two options: 4) challenge with the complete previous diet 2) introduction of one new protein source every 1-2 weeks, ‘The latter option allows individual foods responsibie for producing hypersensitivity to be identi. Intradermal testing “The aim of intradermal testing is to reproduce locally the hypersensitivity phenomenon by injectng indivi alr. ‘gens. Intradermal testing has only been validated for aeroallergens. Selection of test extracts ‘Some allergenic extracts are useless, ether because they are too complex in their composition and inoonsis- tent in their quality, or because they are not realy aeroalleygens. For example, house dust, Kapok and textes {inen, cotton etc...) are really mite habitats. Extracts must be tallored to the requirements of each region. Most allergenic extract producers make veterinary Kits with this in mind (Table 15.00. Alternatively, each clinician may make up his own kit with concentrates diluted as required with 1/100 physiological saine™. ‘Animals unsuited to intradermal testing “There are numerous constraints on the use of intradermal testing which can affect reliably + Age of animal ‘Negative intradermal test results are common in atopic dogs under a year old. It is therefore reasonable to delay the procedure unti a dog is a year or 18 months of age. In older animals with chronic GAD, prolonged Used of glucocorticoids makes it very unikely that meaningful results wil be obtained. Lesions In chronic cases, skin lesions may be generalised and involve the test site, Intradermal testing such animals is not practical without fst controling secondary pyoderma, Malassezia dermatitis and keratis- tion disorders. ‘Skin pigmentation Intradermal test reactions are impossible to read in pigmented skin, erythema being slight or invisible (Fg. 15:32) ‘+ Drug interference To avoid false negative resus, all drugs capable of interfering with intradermal test reactivity must be avo ded prior to the test (Table 15.X), Glucocorticoids (even topical) and antihistamines are mast commonly incr rminated (Fig. 15:28-29), Controls are needed to ensure that there is no initant effect associated withthe extract diiuent and no interie- rence from ant-inflammatory medication on the results. The negative control is the allergen divent (0.4% phe ric physiological saline) and the positive control a 1/10,000 wi histamine solution. 1/100,000 w/v soitions do not give reproducible results, Preparing the animal ‘An area of skin, about 20 x 15 cm (or larger depending on the number of alergens to be used), is cipped over the lateral thorax, with the animal in lateral recumbency. Cipping must be thorough but non-iritating. The skin must not be washed or disinfected. After clipping, injection sites are marked with a permanent ftp pen, ans spaced at least 3 cm apart, The order of injections is not important although the histamine extract should rot bbe placed next to commonly reacting extracts like house dust mites (Fig, 15:26). Anaesthesia and sedatives ccan be used if necessary Intradermal testing procedure 10.05 mlis injected intradermally, quite deep. I the injection is too superficial, a whitish halo appears inthe cent of the swalng. If it is to0 deep, a sweling develops with no change in the appearance of the skin. Neither the ‘owner nor the animal must touch the reactions for 15 minutes atter the lat injection.5 Syndr dermatve atopique ‘Table15.1X: Intradermal test extracts suitable for use in Norther Europe (for Mediterranean region, add lve, wall pelitory and cypress pollens) ‘Non-seasonalallewgens Polens Dermatophagoldes farinae Grasses (in) Dermatophagoides pteronyssinus Planian Cat epithelia Mugwort Human eptnela Plane Altrnara sop. Bich Cladosporum spp. Hazol False Acacia ‘Complementary ist “ACanIS sO aah Gyojpnagus destructor Oak Tyrophagus putrescentiae Pooler Ewrogyphus maynei Ragweod, Goosefoot (Cockroach TTable15.X: Drugs able to interfere with intradermal testing Drug ‘Withdrawal period required prior to intradermal test Glucocorticoids ‘rl (eednisolone « 1 marks) 2 wooks repeated oral or high dose > 2 wooks repeated topical > 2 wooks Jong-actng injection > 6 woeks Long-acting progestogen 4 months Antihistamines most 2 cays astemizoe 2 months cetrizine, lratcire 1 week Ketotifen 2 wocks Ketoconazole Cyclosporin A Essential fatty acids Reading the test Controls, after 15 minutes For the test to continue, the negative control reaction must be non-erythematous and measure fess than § mm, {and the histamine reaction erythematous and larger than 10 mm (Fig. 15:27,28,30,33}. I these conditions are not ‘met, the test cannot be considered roliable (Fig. 18:90-31). A weak histamine reaction may be due to recent glu- ‘cocorticoids, antihistamines or svess (photo 15,29). An erythematous negative control may be due to dermato~ cgraphism, extract contamination or poor injection technique Test extracts, after 15 minutes ‘Subjective and objective assessments can be performed. Any reaction occurring within § minutes ofthe intra {dermal injection must be disregarded, The test must be read after 15 to 20 minutes. Whatever the size of the reaction, the result must be considered positive if there is erythema, For objective assessment, the wheal diameter, or preferably the average ofthe two diameters (down and across) of each contro is measured. Any erythematous reaction with a diameter greater than the average diameter of 2athe two controls is considered positive. However, this simplistic interpretation néed not be folowed to the le ter. In practice, it can be difficult to decide to the milimetre if @ reaction is postive or negative. It is better to trust your eye and personal experience than rely solely on a ruler. Other factors need to be considered such as ‘volume injected {which can affect the resulting reaction size, the possibilty that some extracts may induce sight irtant reactions and the fact that histamine reactwvty can vary from one individual to another. In practice, sub- jective assessment is sufficient. Except for very obvious reactions, intradermal test interpretation varies Cons erably from one clinician to anather (25% of results fang totaly") Delayed reading, after 6-48 hours Delayed reading (6-48 hours) is possible but dificult and does not improve diagnosis™. Errors in reading and interpretation of results “There are numerous causes of reading and interpretation ertors (Table 15!) ears + Drug interference *# Extracts to dite + Extract mix (> 4 allergens) leading to excessive sion + Extracts out-of-date « Extracts contaminated + Subcutaneous ijecton + Inadequate volume (ar bubbes) False postive reactions + Extracts 100 concentrated “Exact ertant + tracts contaminated + Volume njcted > 0.05 mi + Extract injected too close to postive conto! + Cross reaction between mits: false postive eactons to Dermataphagoces in cheyletilsis, | sarcoptie mange, Otadectes infestation or ombicuoss + Dermatograohism + Haemorrhage Serological testing for aeroallergens Serological testing can be used to demonstrate aeraallergen allergy. The type of reagents used (polylonal or ‘monoclonal antibodies, human recombinant FcAR1 ) has litle affect on the raliabity of these techniques" Kis better fo use techniques employing standardised procedures and high thresholds to ensure good speciicty™, Under these conditions, interpretation of results is identical to that of intradermal testing. The use of screening tests with allergen mixes has no agnostic valve. Treatment eA ‘CAD is a multfactoral condition and treatment must take into account potential ficulties in owner compan eas wall as aleray test results Table 15.XI). Basic hygiene measures, applicable to every atopic dog, will convo punts and lesions in most mild cases and reduce the need for drugs in more serious cases, 242.1: Atopic dermatitis syndrome 1625: Inradermal fast reaotons after 15 minutes: histamine reaction (top left) overlgping with reaction undemeath rendering lerpreation ofthis allergen impossibie 1627; Inradormal test reactions after 15 minutes: athough the testa conductod on skin with iesions fepiermal collet), the test was easy to read and interpret (contots located at tap let) 1629: Iaderma test reactions after 15 minutes: results are lmaossble to interpret. The positve contol reaction (top let) i= rat erythematous 1831: inraderal test reactions after 15 minutes: reading reactions on white skn is easy whereas recognising erythema in mented ars impossibie 15.26: Intradermal test reactions after 15 minutes: controls located top left ith definte postive reactions farge erythematous wneals to house dust mites 16.28: intradermal test nan Avgontinian mast receiving lucacoricais for tho last 5 days (reactions after 15 minutes): postive results can be determined but the wheels ae smaller than 15.90: Intradermal fest reactions after 15 minutes: cermatographism in a Shar pe with enthematous reactions at al Inection sites 16,32: intradermal test reactions after 15. minutes: multiple Sonstivias demonstrated by reactions to several polen miss uring intial testing. Anther area has Deen cippod 10 test for inaivual potas 243A Practical Guide To Canine Dermatology a Table1§.Xil: Treatment of citferent clinical forms of CAD. EFA = essential fatty acids, ant-ht = antihistamines ‘A minima ‘Monthly flea control, elimination dit, therapeutic emolients Benign form “Topical glucacortcoids or tacrolimus, EFAS, ant-nt ‘Typical form with transient fares Antibiatics, antifungals and/or glucocorticoids | ‘Typical relapsing form Antibiotics, anitungals and/or glucocorticoids | + ant-allergen vaccination and cyclosporin necessary Serious, permanent Prolonged, thorough antimicrobials, cyclosporin and antialergen vaccination Routine measures Certain simple steps can significantly reduce the development of CAD lesions and should always be adopted Flea control ‘As fleas can aggravate CAD, strict, permanent flea control is essential. This idea is often dtfcut to sel to ‘owners and needs to be put across not as fea conto! in itself but as a preventative measure for an allergic an mal. Owners must be involved in the formulation of flea control measures which take into account the atopic dog, in-contacts and the nature of the animal's environment. Flea control must not be compromised by other treatments such as frequent shampoos and may need to be given more frequently if dog is having reguer baths Feeding a well-balanced diet Diet plays a major role in the management of CAD. Even if there has been litle response to an elimination det, itis important to feed a well-balanced, high quality, easily digestible det. Easily digestible food reduces the rok of developing a food hypersensiity and optimises nutrient availabilty. Home-prepared diets are often deficient in essential fatty acids. A very effective and cheap way of countering this is to add rape seed cil (Table 16.) Shampoos and emollients Emolient shampoos are uselul for two reasons, Firstly, they help to remove infectious and allergeric paces ‘rom the skin surface. Secondly, they help to restore the integrity of the surface hydrolipd fim. Shampoos ae ‘normaly given twice weekiy®. The aim of emolient and/or moisturising products isto avoid epidermal ying and to restore surface protection to a level comparable to that provided by the superficial pd fl, They can ao be soothing, lubricating and even antiseptic. Lactic acid, for example, reduces bacterial proliferation. Each type of product has a diferent mode of action. Emollients prevent skin drying by filing intercorneocyte spaces with lipid droplets. Examples include vegetable «ils (eg. olve, sesame, coconut and peanut}, animal-derived ols from sheep wool lanolin) and mineral ais iui paraffin, Vaseline). There are no specific veterinary emolient preparations, ‘Moisturisers are hygroscopic agents that attract water in the superficial epidermal layers, thereby rehytating the corneal layer without the need for oll substances. Also called non-lpid emollients, they include mainly lac: tic acid, urea, glycerin and propylene glycol. The last three are soluble, high molecular weight substances which ccover and protect the entire skin surface. Occlusive dressings reduce transepidermal water loss and increase the amount of water in the corneal ayer ‘They are not used in veterinary dermatology because of the increased risk of maceration. Emollient emulsifiers are fatty acid polyesters with emulsifiers that cisperse the oly emollient in water, there by prolonging its moisturising etfect on the skin, Stearic acid, sterol, lecithin and PEG-4 ciiaurate are the most commonly used examples. Optimal beneftis obtained when these products are sprayed onto damp skin after rinsing, or incorporated into the shampoo in the form of muftlamellar structures (novasomes, spherulte) for gradual release, They can aso be mixed directly into the water used for rinsing. Many lotions now contain emolients (typically glycerin) con- bined with other active ingredionts. 26615: Syndrome dermatiteatopique Grooming Daily grooming with soft brushes (avoiding metal brushes and currycombs which can cause skin microtrauma) helps reduce the allergenic load on the skin surface, removes hair and debris and promotes sebum production. {Grooming atopic dogs is essential, especially densely-coated dogs with lots of ear and interdigital har. Regular ‘olpping of the interdigtal spaces and ventral paw is particularly indicated and enables more effective topical therapy. Hair plucking in wie-coated breeds is, however, not advised because ofthe possibilty of inducing micro- trauma, Topical ear products Ear treatments are viel to avoid the development of otis externa. Cleaners, adapted to protect the ear and restore a suitable environment, are indicated once or twice week. They are sometimes combined with ant septics. At the onset of each episode of inflammation, topical glucocorticoid and antimicrobial products are given inne with cytological findings. The ears must be checked at every re-examination. Antimicrobial treatment Antibiotics ‘Antibiotic therapy is the major component of CAD treatment (on a par with flea contro}, not surprising, given the high incidence of bacterial proliferation syndrome and associated pyoderma, it can be instituted routinely ‘evon in the absence of abvious signs of pyoderma'® (chapter 5). Correct dosing and duration of treatment must bbe respected, Systemic antifungal treatment ‘The incidence of Malassezia dermatitis is also very high and systemic antifungal therapy is often required (chap- tor 9). Ketoconazole (5-10 mg/kg/d) and itraconazole (5 mg/kg/d) both give excellent results; treatment lasts about 3 or 4 weeks. If elapse is frequent, treatment may be given intermittently on about 2 or 3 consecutive days per week. As with antibiotic therapy, some authors recommend routine use of ketoconazole rather than ralying on low sensitivity tests for Malassezia. However, such a recommendation is debatable. Systemic anti- fungal treatment should be reserved for very pruritic cases of Malassezia dermatitis or cases where response to topical therapy (antiseptic and antifungal shampoos) is inadequate. Antiseptic and antifungal shampoos ‘Antiseptic (@.9. chlorhexidine), antitungal e.a. Ketoconazole and miconazol) and emolient shampoos can be Used twice weekiy to accelerate heaing of superficial pyoderma lesions or Malassezi dermatitis. However, regu: lac washing shouid not interfere with flea Control nor cause excessive maceration, especialy inthe ear canal, intercgital spaces, alae or inguinal regions. Topical anti-inflammatory agents Glucocorticoids ‘Topical glucocorticoids (and topical emoliants) are the mainstay of atopic dermatitis treatment in man. Although a haity coat limits their usefulness in the dog, topical steroids can be used in hairless areas for well-crcum- seribed non-infected lesions. Irtialy, a more potent, class 3 glucocorticoid (e.g. dexamethasone or betame- thasone) is needed, Subsequently, or for more prolonged treatment, a class 1 product, such as hydracortisone, ‘can be used. Daily or twice dally administration is recommended. Low concentration triamcinolone sprays (0.01595) can be useful but must only be used for short periods (about a week, always striving to fin the lowest possible effective dose (for example, a maintenance dose of one application per week} Tacrolimus ‘Tacrolimus is a calcneurn inhibitor given systemically in man to prevent graft rejection and topicay for human ato- pic dermatitis. A 0.1% tacrolimus gel can be used n localised CAD to bring about a significant reduction (more than 50%) in lesion severity When treatment is fst started, inition may increase. The product shoud at frst be ‘applied daly before the frequency is gradually educed over several months, Other topical agents Various non-steroidal antiprurtic sprays end shampoos can also be beneficial. Often complex, these products contain various active ingredients emollents such as glycerin, antiseptcs such as chorhexidine and piroctone ‘lamine, analgesics, antinistamines, essential fatty acids, antioxidants such as vitamin , and ant-prurtic agents such as colloidal oatmeal or tea tree oll. They have to be used very frequently (daly for benefit to be obtained. 205Practical Guise To Canine Dermatology Allergen avoidance Diet ‘Arypoallergenic dit can be continued beyond the time needed to diagnose a food hypersensitity but the pos- sibily ofthe patent developing a hypersensitity to an item inthe hypoallergenic det cannot be discounted. Aeroallergens ‘Aeroallergen avoidance conoeins mainly hause dust mites and for it be effective, the mites must be klled or have thei ife cycle broken. In addition, proteins in their cuticle and faeces must be denatured. In human med cing, the efficacy of such measures is highly controversial; studies are very susceptible to recruitment and ‘assessment bias. Inthe dog, an open study (using benzyl benzoate to ebminate potently rich sources ofhovso dust mites, such as mattresses and cushions, involving dogs with CAD demonstrated complete contol of CAD in half the animals, Athough these results are very encouraging, they need to be backed up by controled stu dies in which important influences (such as the insecticidal actiity of products used) are taken into considera- tion ‘Anti-allergen vaccination (desensitisation, specific immunotherapy] [Anti-allergen vaccination invoWes the reguar subcutaneous administration of allergenic extracts to which the ‘animal is allergic. tis indicated whenever alergen avoidance does not produce significant improverent; ony aecoallergens are indicated, The modes of ation remain uncertain but is thought to bring about an immuno rmaduiation towards a Tht type response" Initial measures tts essential to obtain the full co-operation of the owner who must be told exactly what is involved regarding treatment logistics, ikely nature of any improvernent, length of treatment and cost. Tis information must not bbe given solely in the form of an impersonal handout, and time must be taken to explain each point fully. Points may need repeating at folow-up appointments. & diary is a useful means of motivating the ower and docu ‘menting an animal's progress. Allergen selection ‘Allergen selection is based on allergy test results, intradermal or in vitro. Poor quality extracts or those tor wich, in the dog, there is no evidence of benefit in ant-allergen vaccination (e.g, dust, epithelia and moulds) should be avoided. If there is a disorepancy between allergy test results and the animal's history, the clinical histoy should be glven prioty, If there is a discrepancy between intradermal and serological test results, the clinica history should again be decisive. However, i the in vitro test is very sensitive and not very spectic (low post ve threshold), resus wil nt be very reliable, In Europe, laboratories produce longer-acting extracts, using aluminium hydroxéde or calcium phosphate ad vvants, whereas in North America, aqueous extracts are more commonly employed. Aqueous extracts do not keep 80 well and require more frequent injection (Table 15.Xl). Only four tens can be included in extracts produced in Europe, due to the influence of human medicine regu: lations. In North America, there are no such restrictions and the composition is very variable, Protocols ‘Al treatment protocols stert with a vary low dose which then increases gradually, the amount of allergen dou bling with each injection, until a maximum dose, usualy between 10,000 and 20,000 PNU or 100 U or 10 IR, Is given. There is considerable variation in the type of extract used, the therapeutic response obtained and the ‘experience of the clinician (Table 15.XIl), Utra-rapid immunotherapy can be used to avoid errors linked to Cchanges in dose during the induction phase. However, this approach is commonly associated with aggravation Of cinical signs and must, therefore, be carried out under strict medical supervision“. Low-dose protocols do not seem any less effective than standard protocols. Monitoring Associated treatments Forthe animals andthe owne's sake, symptomatic treatments can be given longside immunotherapy. Hower, io study has been conducted on the long-term effects cf eter glucocorticoids or eyclosporin Length of treatment ‘Antalergen vaccination shou last, accorcing to some authors, beween one and three years, Howe, prac- tice, abrupt cessation, even after prolonged treatment, can lead to relapse. Life-long treatment is, thereto, recommended. 266__________—15: Atopic dermatitis syndrome Table1$.Xill: Current ant-allergen vaccination protoco's ae eee =\|5 ——- lee Jos fo | ee = nee CS s12__| 20000 then one injection par month Side-effects Injection site reactions are extremely rare and due to fauity injection {intramuscular or intradermal). ‘An aggravation of clinical signs is seen in between 5 and 20% of cases using adjuvanted extracts and more frequently in cases using aqueous extracts. Athough not serious, it is stil worrying forthe animal's owner. It nearly always involves generalised pruritus on the day after the injection, persisting for 2 or 3 days. Less com- ‘monly, urticaria or angio-oedema may develop in the hours folowing the injection. There is no case of fatal shock in the veterinary Sterature. If there is an aggravation in clinical signs, various steps can be taken such as com- 267bining an antinistamine with the ant-alergen vaccination, rush therapy, ie. an ultre-rapid protocol in 6 hours with the animal hospitalised, and increasing the dose a lot more slowly, Efficacy ‘There is often an element of contusion with regard to the definition of improvement or success of anti-alergen vaccination. In some studies, assessment is made merely by asking the owner questions over the telephone. In others, treatment is considered effective only if clinical or lesion score is reduced by at least 60%. After 9-18. ‘months, 10-20% of animals show complete cure and 50-80% of animals show significant improvement. Its important to explain to owners that improvement may take the form of longer intervals between flares, a less extensive cistrbution, reduced lesion severity or a marked reduction in drug consumption detailed in the diay discussed above. Factors influencing prognosis ‘Age: age of onset of clinical signs or atthe start of treatment does not significantly atfect prognosis. Nor does the duration ofthe conditon**™. ‘Alergens: the best results are obtained with mite and pollen extracts. Insect, epithelia and mould spore extra cts have not been found to give good resuts. The number of allergens to which the animal is sensitised is not a significant prognostic factor" (Overall reatment: there is a Ink between length of the intial consultation and treatment eficacy, underining the importance of good overall reatment in the long-term management of CAD, Systemic ant Antihistamines ‘The etfcacy of antihistamines is similar to that of a placebo". First generation antihistamines (chlorpheniram ne, cyproheptadine and dexchlorpheniramine) have sedative effects and can be helpful in managing night tme pruritus, Amitriptyline is also used for ts anxiolytic activity in atopic dogs whose prurtus can be reinforced by substitution activities (Table 15.XIM), inflammatory treatment Table18.XIV; Antihistamines used currently in the dog Common name Dose ‘Amiiptylng 1a makoid ‘Astomizole 1 make 2810 ceatrzine 0.25-1 marks (Crlohenramine 05-2 mgikg 3071 Coainzine 025-5 mgkg/ Cyproheptadine 0.4 mgikg 1D Dexchlorpheniemine 0.1 mg/kgi Diphentycramine 2-4 mg/kg STI Mydronaine 2 mg/Kg WTO Loratidine somes Mequitazine 0,25 mares Promethazine 2mahkg v8. Glucocorticoids Precnisolone (0.5-1 mg/kg/d), prednisone and methyiprednisolone (0.4-0.8 mg/kg/d) are the steroids of cho Ce for short-term treatment (3-7 days). Neither withdrawal nor alternate-day dosing is necessary, For more po- longed treatment, a minimum effective dose must be sought. Glucocorticoid usage must be limited if topical steroids are already being prescribed, and avoided if bacterial or fungal infections are present, I steroids ae sed long-term, regular monitoring is essential to spot the early onset of side-effects or urinary or skin infec tions (e.g. steroid-induced pyoderma). 248)15: Atopic dermatitis syndrome Cyclosporin A (Cyclosporin A (CsA) is one of the few products licensed for CAD treatment. It inhibits the activation of cels ‘capable of inducing (T hmphocytes and Langerhan's cells) and effecting (mast cells and eosinophils the aller- ic inflammatory response; it, therefore, inhibits immediate hypersensitivity and delayed, celular infitration reac- tions at the sites of cutaneous inflammation. CsA is used at a dose of 5 mg/kg/d on an empty stomach. At two weeks, is effcacy is comparable to that of ‘lucocorticoids®, However, as in man, signs may reappear on cessation of treatment. Two types of protocol ‘can be considered: ‘© 5 mg/kg/d for 4-6 months followed by cessation until relapse ‘+ 5 mg/kg/d for 1-2 months folowed by gradual dose reduction every 1-2 months. The ease with which the dose can be reduced depends on the length of the induction phase™. ‘Side-effects are mainly gastrointestinal (vomiting and soft faeces in 25% of cases) and usually transiont®, Loss ‘commonly, other side-effects (e.g. hyperrichosis and gingival hyperplasia) can be seen after several months. “Teatment falures are usually due to infection (pyoderma, Malassezia dermatitis) CsA is very effective in the long-term treatment of CAD but limited in use by it high cost. It should be reser- ved for severe cases of CAD where pruritus is inadequately controlled by standard antiprurtic treatments or where pruritus can be controlled only with long-term glucocorticoids. Infection must be wel-controlled. Nutraceuticals Essential fatty acids Essential fatty acids (EFAs) (n or omega 8 and n or omega 6) (chapter 28) have been used extensively in the ‘treatment of GAD over the last 20 years or so, although few studies have demonstrated significant effects. They ‘may inhibit LTB4 production or restore the surface hydrolpid barrier ‘Most studies adopt very varied protocols (dase, duration of treatment), demonstrate very disparate results and do not take into account fatty acid levels inthe patients’ diet’, In cross-over studies (animals act as their own ‘contros). which avoid this problem to some extent, the dose of omega 3 was found to vary between O and 116 mg/kg/d and that of omega 6 from 0 to 138 mg/kg/d (the omega 6:omega 3 rato varied between 9 and 20 when combined), The effect on prurtus was low improvement in more than 60% in 5-16% of cases) whe- reas improvement in global or lesion scores was significant in 40-80% of cases. Response may vary according to the presenting form and chronicity of the CAD. In one study using an omega 6, omega 3 combination, the response atter 2 months was significantly better in dogs with atopic dermatitis of more recent onset”. In another study, EFA administration enabled the dose of glucocorticoids to be reduced significantly in atopic dogs. EFAs can, therefore, be used in the treatment of atopic dermatitis, ether to improve skin and coat condition or 10 reduce the amount of steroid needed in dogs requifing long-term glucocorticoid therapy. EFA supplementa- tion needs to be given for 1-2 months before significant effects become apparent Vitamins and trace elements No wtarnin supplements have been found to bring about significant cinica improvement. Vitamin E has been used as en antioxidant alongside essential fatty acd preparations. It stabilses mast cell in vio but has not been found to be uselul in CAD. Chinese herbs |A product based on Chinese herbs is commercially avaliable fr the treatment of CAD. In one randomised, mul- ticentrc study, lesion score was improved in 30% of atopic dermatitis cases after 4 months of treatment™ 209A Practical Guide Te Canine Dermatology) 250 References 1 10. 1" 12 14, 15. 17 18, 19. 2 22. 23, 24. 25, 26. 2 Johansson SGO, Bieber T. New diagnostic classification of alergic skin csorders. Current Opinion in ‘Allergy and Cinical Immunology 2002:2:4086. ly T, DeBoer Ou, Grifin CE ot al. The ACVD task force on canine atopic dermatitis: forewords and lexicon Veterinary Immunology and immunopathology 2001;81:143°6. bier A, Grifin CE. The ACVD task force on canine atopic dermatitis (1s there a relationship between ‘canine atopic dermatitis and cutaneous adverse food reactions ? Veterinary Immunology and Immunopathology 2001;81:227-31 Hiller A, Grin CE. The ACVD task force on canine atopic dermatts (I: incidence and prevaense. 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