The secret lives of dermatologists

Transcription

1 1 The secret lives of dermatologists Dr Duncan Graham Animal Dermatology NZ October 2015 Royal Canin Dermatology Month webinar

2 2 The secret lives of dermatologists: breed related dermatoses and the clinical distribution of lesions. Tonight I am giving a largely anecdotal, non-evidence based presentation, because I do want to delve into the secret lives of a dermatologist, to see what we can apply to general practice. Canine dermatoses are not easy to deal with the context of the 20 minute consultation. One of the ways that people cope with this constraint is to treat most dermatological presentations as cases of infected pruritus i.e. they give corticosteroids, both injectable and oral, and a short course of antibiotics, usually clavulanic acid/amoxicillin or TMS if it s a large breed dog or an old school practitioner. (Parenthetically newer practitioners are somewhat afraid of TMS; they don t have to be unless it is a Doberman). I am okay with that as an initial approach but as soon as the dog comes in with its second presentation, we need to go into dermatology mode, still within the short consult mode. We need to start generating differential diagnoses, to be proved or disproved. One way to do this is to use the signalment, especially the breed predisposition to certain diseases, and the clinical distribution of lesions to give you a head start. In this hour tonight, I am going to give a quick insight into a few dermatoses that have breed and site predilections. Central to this approach is the concept of using response to therapy as one of the ways of proving and disproving differential diagnoses. This is the approach advocated by all dermatologists, although often it isn t made explicit. To make the diagnosis of canine atopic disease, you have to rule out flea hypersensitivity, Sarcoptes and other diseases like cutaneous adverse food reactions. The ONLY way you can rule them in or out is with response to treatment. Even if you find fleas in a dog with dorsal pruritus, the final confirmation of Flea allergy dermatitis is response to treatment. If you treat the fleas, and there is no improvement, fleas may be a contributing factor but they aren t the only cause of the pruritus. My goal in the twilight years of being a veterinarian with an interest in dermatology is to extend this idea: that the response and/or non response to treatment is part of the diagnostic work up - to the approach to other recurrent dermatological cases in the general practice setting. I know that I have spoken about this before. Now that vinyl is making a comeback, you will understand if I refer to myself as sounding a cracked record. Every consulting session I am referred dogs that have never had monotherapy; they have always had the multi-drug approach to therapy, usually corticosteroids and antibiotics, but nowadays often an antifungal is thrown in as well. It is impossible to draw any sensible conclusions from the response/non-response to treatment. I understand why you do it; the response to therapy approach to diagnosis is slow, tedious and expensive. You do have to pick your cases, but I think it should be offered. You can say to the ownerhere are differential diagnoses, we can try treating all of them at once, but if we do that, and your dog gets better and then relapses, which they often do, we are no better off. It is better to treat one thing at time, sequentially so every time there is a response or non-response it tells us something. You always guide your treatment selection by using cytology. This tool is invaluable. However you can also guide your hierarchy of differentials by using a knowledge of breed related diseases. Case study one: A one year 7 month old male Border collie presents with recurrent lesions on his ventral abdomen. The onset was at 16 months of age, with the first signs being red, sore scabs. Treatments have included Neotopic, Clavulox and Prednisone 10mg once daily with some improvement. A biopsy was done, and then Clavulox was trialed for seven days. The biopsy was compatible with a lupoid drug reaction, but no drugs had been given. Systemic lupus erythematosus was suggested. The dog has not had any contact with Tradescantia fluminensis (Wandering Jew). He was referred to me for evaluation. There was inguinal serpiginous and focal crusting in both

3 3 inguinal areas. He had minor lesions on both upper and lower lips. The lesions were reportedly more painful than pruritic. What are our differentials? Certainly pyoderma is possible although you would expect to see more of a papular eruption especially in the early stages with typical lesions. Hypersensitivity especially contact with Tradescantia fluminensis is common throughout most of New Zealand. It can present as ulcerated crusted lesions in the inguinal region certainly but is usually extremely pruritic. Other hypersensitivities including food and environmental should be considered especially if there are lesions elsewhere. Malassezia overgrowth should be looked for. The biopsy suggested a fixed drug reaction, but no drugs had been used. The biopsy was also compatible with Systemic lupus erythematosus, but there was little in the way of other systemic disease. The main differential is Vesicular cutaneous lupus erythematosus (VCLE), an ulcerative condition, mainly affecting the ventrum of Shetland sheepdogs and rough collies. In Shetlands and collies, the dermatosis is reported as usually seen in middle-aged to older dogs, and often appears in the summer, with summer exacerbation also reported. This suggests a role for UV exposure in the pathogenesis. The ventral abdomen, especially the glabrous inguinal area including the medial thighs is most often affected with focal to confluent serpiginous areas of ulceration. Additionally the mucocutaneous junctions can be affected, and the concave aspect of the pinnae and the buccal mucosa may be involved. The histology shows a cell-rich interface dermatitis with some vesiculation at the dermoepidermal junction. Apoptotic keratinocytes are often found. Response to therapy and the clinical course are quite variable. Some cases are very resistant to treatment and need high doses of corticosteroids plus or minus azathioprine. Antibiotic therapy is usually needed. In 2007 Christina Baxter presented a series of 20 Border Collies (19 from Australia, 1 from New Zealand) with clinical lesions that fit the clinical picture of VCLE. All 20 dogs had histopathology done: there was a superficial dermal lymphocytic infiltrate in 20/20 cases which varied from sparse to intense and band-like. There were apoptotic cells in 17/20 cases. The age of onset varied from 6 months to 14 years, with a mean of 3.6 years, and a median of 3 years. This is younger than the disease in Rough coat collies and Shetland sheep dogs. Five dogs had intermittent disease, with spring/summer exacerbation. The season of onset could be determined in 14 of 20 dogs: six in spring, three in summer, one in autumn and four in winter. In this retrospective study, clinically the early lesions targeted the inguinal and ventral abdominal regions in all dogs. Less commonly affected areas included the facial and peri ocular regions, the feet and foot pads, the concave surface of the pinnae, the back and tail base, the intraoral and the perioral areas, and the perianal mucocutaneous junctions. Only the back and tail base areas are somewhat atypical areas. The lesions in all dogs presented as different types of ulcers, ranging from annular to serpiginous, sometimes coalescing to plaques. Dark adherent crusting was regularly described adjacent to, or surrounding, the ulcerated areas. 13 out 20 dogs had concurrent lethargy, weakness, inappetence and/or pyrexia, which mostly resolved with treatment. Cytology was done on 16 dogs, with 15 dogs having intracellular cocci and one dog had Malassezia. Antibiotics, either cephalosporins or clavulanic acid/amoxicillin, were used in 16 of the 20 dogs, with a partial resolution or improvement in 12 of 16 dogs. Given the intracellular cocci, this isn t surprising. Immunosuppressive or immunomodulating drugs were used in 19 of the 20 dogs. The response to treatment, and the degree of treatment needed to control the dermatosis was highly

4 4 variable. This is a point I would like to stress: a minority of dogs respond to antibiotics and topical corticosteroids, the majority need ongoing immunomodulating treatment, a relapse occurs when drug doses are tapered or discontinued. Drugs that were used included Pentoxifylline in 7 cases, with persistence or later recurrence of lesions if it was used as sole treatment. Prednisolone was used as a sole agent in 3 dogs and in combination with azathioprine, pentoxifylline and/or doxycycline/ niacinamide in 11 dogs. Prednisone with azathioprine in 9 dogs gave the best response with partial to complete remission for periods of 4 weeks to at least 2 years. Topical treatment with Mometasone furoate ointment controlled the disease after initial systemic treatment in one dog. No specific disease triggers (food, drugs, or topicals) were identified in any cases. Closer to home, in 2011 Isobel Gibson presented a case in the Proceedings of the 36th Conference of the New Zealand Society for Veterinary and Comparative Pathology. A 3-year-old Border collie was initially presented for a small ulcerative lesion on the left axilla. The lesion failed to respond to conservative treatment with antibiotics, and the dog was re-presented one week later with ulcerative lesions involving the inguinal and axillary areas bilaterally. Histology of these lesions revealed a lymphocytic ulcerative interface dermatitis. Apoptosis and degeneration of basaloid cells was evident, with clefting along the dermo epidermal junction. Vesicular cutaneous lupus erythematosus was diagnosed. The dog was treated with prednisone and azathioprine, resulting in complete remission of signs. However, recurrence occurred when drugs were tapered, necessitating ongoing treatment. Back to our case study: Cytology revealed polymorph neutrophils with occasional intra cellular cocci. Because of my high index of suspicion of VCLE, I asked for a second opinion on the biopsy. While we were waiting for the second opinion, I started him on cephalosporin (Rilexine) at 22mg/kg bid for 10 days. After 5 days, some improvement was reported so these were extended. The second opinion felt that the biopsy combined with the clinical picture was very suggestive of VCLE. This is important: you must give the histopathologists a good clinical description of the lesions, especially progression, and preferably photos. The old adage of rubbish in rubbish out applies to histopathology. Basically without the history and distribution of lesions the histology of VCLE could be a severe case of DLE or mild SLE. I asked for pre-treatment bloods to be done, anticipating some heavy duty immunosuppressive treatment would be required. At the 3 week revisit, there was a % improvement to the twice daily cephalosporin, so we decided to treat topically twice daily with clobetasol cream 0.05% (Dermol, now replaced by a generic), a very potent topical corticosteroid. After 10 days, there was such a good improvement that treatment was discontinued. There was no relapse after 4 weeks. There were mild sporadic outbreaks subsequently that were managed with Dermol. Mometasome would be a good long topical if frequent application were needed. In 2013, there was a case in Veterinary Dermatology of VCLE in a Border collie that was successfully brought into remission and managed with 0.1% tacrolimus (Protopic) and Nicotinamide and Tetracycline, both 500mg tid after developing side effects with oral prednisone. After remission, the various medication were gradually discontinued and the only treatment was sun avoidance. The dog was followed for a year and had no relapse. In terms of treatment, you need to be prepared for heavy hitters, and not all dogs respond. In Tina Baxter s study 3 dogs were euthanased during treatment (3 to 16 weeks after diagnosis). Most dogs need lifelong treatment.

5 5 As a group the disease presents in Border Collies at a younger age, and may sometimes be less serious, responding to less intensive treatment. Therefore, in Border collies it be worthwhile treating any secondary infection first, and then trialling potent topical treatment and the immunomodulating medications doxycycline and nicotinic acid. Certainly these are worth trialling if there are unacceptable side effects with Prednisone and Azathioprine. Case 2: In August 2009 a 4 year old male neutered Boxer comes in for vaccination. The owner mentions that his coat seems to be thinning in the flank area. You say to keep an eye on it. Four weeks later there are bilateral areas of total alopecia in the flanks with extreme well demarcated hyperpigmentation. The dog is relatively non pruritic. It looks endocrine. You know that boxers are prone to hypothyroidism, which they are, so you check the thyroid. It is normal. This is a dermatosis with a very strong breed association. In the past it was called Canine Recurrent Flank Alopoecia, or Seasonal Flank Alopoecia or Canine cyclic flank alopecia. Now the preferred term is Canine flank alopoecia (CFA) because not all cases are seasonal, some are not cyclic or recurrent but they nearly always affect the flank area. The age of onset varies widely from 1 year or less to more than 10 years of age. One report put the median age of 3.8 years. A number of breeds can be affected, but there is a strong breed predilection with boxers highly over represented. Other breeds with increased risk are Airedales, English Bulldogs and Schnauzers of all sizes. In New Zealand, I have seen mostly Boxers with CFA, but have also seen a number of Schnauzers and Rhodesian Ridgebacks. There doesn t seem to be any sex predilection. Typically the distinictive lesions of CFA are areas of non-scarring non inflammatory non pruritic alopecia with associated severe hyperpigmentation. The lesion margins are sharply delineated giving a geographic or serpiginous look. The surrounding coat is usually normal. The most commonly affected sites are the lumbar flanks, although it can extend from shoulder to hip, and does sometimes cross the midline. It is usually bilateral but not always and may vary in intensity one side from another. Another distinctive feature is that the lesions often develop in the autumn, winter and very early spring (decreasing day length) and regress in the spring and summer (increasing day length). The progression of the dermatosis is variable from dog to dog, and even from year to year. Some years it may not reoccur, or it may reoccur with lessened severity. Hair that regrows spontaneously may be normal, or it may be a different colour and texture. Because of the distinctive nature of the lesions, you can make a tentative diagnosis of CFA based on the breed and the clinical presentation. However if it is an atypical breed, or if the hair doesn t regrow as expected, or there are complicating factors, which I will discuss below, then the best approach is to biopsy. Samples should be taken from the areas of maximum alopecia or coat change. So called witches feet or octopus-like dysplastic follicles give the biopsy a characteristic feature. Because there does not seem to be any underlying metabolic problems, benign neglect is an acceptable treatment. However, in cases where the coat doesn t regrow, most cases are severe enough that most owners request treatment. Oral melatonin 3-6 mg twice daily is used overseas where Melatonin is readily available. In New Zealand it is a section 29 drug so supply is more complicated. Based on Manon Paradis s work with melatonin implants, I routinely use, with good

6 6 results, a long acting melatonin implant called Regulin, which is licenced for use in sheep to synchronize oestrus. Some dogs only need one treatment, others need it yearly and still others need it intermittently, with several years in between. This is all relatively straight forward. However occasional dogs, usually boxers present with a secondary folliculitis so that instead of being non pruritic and non-inflammatory there are papules, crusts and a level of pruritus. I have seen this in boxers and there is definitely a degree of pruritus which seemed to respond to antibiotics. However, there are two reports, one from the ever reliable Elizabeth Mauldin, of flank alopecia with an associated interface dermatitis. Again the areas of alopecia, instead of their characteristically smooth, non-inflammatory appearance have annular lesions of crusting and scale, giving the hyperpigmented areas a moth eaten crusty appearance. She says The crusted lesions were once thought to be pyoderma until further histopathological evaluations were performed, revealing true interface dermatitis with blurring of the dermalepidermal junction with vaculolar changes and pigmentary incontinence. p 321. It seems to me that these two presentations, CFA with folliculitis and CFA with interface dermatitis, must be related, perhaps along a continuum. Again tetracyclines and nicotinamide have been used, in addition to melatonin, as you would use to treat that other interface dermatitis, Discoid lupus erythematosus. My approach if you have a case of pruritic CFA, with lesions suggesting interface dermatitis, would be to treat with melatonin, either oral or implant, and start with cephalosporins at 22mg/kg bid. If there is any residual pruritus or lesions after 3 weeks, I would start my standard DLE treatment: doxycycline at 5mg/kg bid and nicotinic acid 500mg bid (250mg bid if under 10 kg). Case 3: 6 year old male German shepherd dog presents with dorsal rump crusting, ulcers and severe pruritus. The lesions extend down the lateral thighs. There is patchy focal alopecia. In other heavily haired areas there is tenacious adherent crusting. What are our differentials? German Shepherd dog folliculitis, furunculosis and cellulitis is a heritable, familial deep pyoderma of German shepherd dogs and their crosses that is the result of immune-deficiency. Studies have shown changes in lymphocytes, especially T lymphocytes in affected dogs. These deficiencies result in an exaggerated inflammatory response, possibly to staph bacteria. Affected dog have deep skin infections that resolve slowly and recur quickly when antibacterial treatment is stopped. In some dogs an underlying problem is found but in many dogs, the problem appears in middle age, and worsens, suggesting a progressive immunodeficiency. The distribution of lesions is typical, affecting the rump, back, thighs both lateral and medial, and the ventral abdomen. In the early stages there are papules, pustules and crusts but these progress rapidly to ulcers with thick crusts, draining tracts, furunculosis, and hyperpigmentation. Haemorrhagic bullae are reportedly a hallmark of the disease, but for me they are hard to find, either rupturing early or hidden by the dense German shepherd coat. Lesions may develop quickly, forming plaques of ulcerated, eroded, friable and devitalized skin. Pruritus is often extreme leading to severe self-trauma. Early lesions may be surrounded by strikingly circular erythematous halos. Usually the bulk of the pruritus resolves with antibiotic treatment unless there is a concurrent hypersensitivity. There is usually popliteal lymphadenopathy. The disease primarily affects middleaged German Shepherds. Two studies reported a strong predilection for males.

7 7 Other causes of deep infection especially demodicosis should be ruled out. Obviously flea allergy dermatitis/ hypersensitivity is a rule out. If there is residual pruritus once the infection has been cleared, then concurrent hypersensitivity should be investigated. An adverse cutaneous food reaction should always be suspected until proven otherwise especially in a German shepherd. Some dermatologists, like Jan Declercq feel that atopy as well as genetics, bacterial reactivity and follicular micro trauma is an important part of the pathogenesis. If any underlying problems are left unaddressed, the relapsing nature of the condition is exacerbated. The diagnosis is based on the typical clinical signalment, cytology should show deep pyoderma/pyogranulomatous infection with polymorph neutrophils, macrophages, and i/c cocci. You should do a culture and sensitivity If you see rods, if the dog has had repeated courses of antibiotics, or if the resolution of lesions is incomplete. A biopsy is always indicated to confirm the clinical diagnosis particularly since the clinical management is so fraught. The major question is whether to biopsy before or after antibiotics The clinical management of this problem is extremely difficult for several reasons. Firstly it is a primary immunological problem with an exaggerated response to bacteria, so that the deep pyoderma causes the majority of the clinical lesions. Now that we are trying to restrict the use of antibiotics due to the emergence of multi drug resistant bacteria, and specifically methicillin resistant S. pseudintermedius, the options for long term management are more limited. Thirdly, there is often a large amount of scar tissue. It is a cicatricial problem with poor blood supply so antibiotic penetration is limited. Fourthly, rather than being a disease of multifactorial etiology, it may be a distinctive clinical syndrome that can be triggered by a number of diseases in susceptible animals. It is not unusual to see German shepherd recurrent furunculosis cellulitis in conjunction with perianal fistulas or metatarsal fistulation. Previously cephalosporins at 22mg/kg bid for four to eight weeks has been my usual approach. Frequent chlorhexidine shampoos or rinses can help. People have started using dilute bleach baths and products like Vetericyn to reduce our reliance on antibiotics. Ultimately we are still stuck with that ongoing dilemma: the welfare of the individual animal versus the potential welfare of the whole group. Each of us has to make that decision for themselves. Cyclosporine has been reported to be effective in managing many cases as well as being promoted for peri anal fistulas. Other authors report that dogs that have failed repeated courses of antibiotics respond to corticosteroids at antiinflammatory doses. Jan Declercq, a European dermatologist, has suggested a three stage protocol. For a 35 kg dog, he has a first Induction period of 5 weeks treating with 1. Cephalosporins at 20 mg/kg q12h 2. Rifampicin 5 mg/kg SID 1 month, starting at week 2 (total length of rifampicin 1 month) 3. Pentoxifylline 400 mg twice daily (approximately 10mg/kg) 4. Low dose daily corticosteroids, approximately 0.25mg/kg. This is followed by a second induction period of 4 weeks where the rifampicin stops but the cephalosporins continue. The pentoxifylline stays at the same dose while the corticosteroids at 0.25mg/kg are decreased to every other day. After this two stage nine week induction period, he begins a maintenance regime with pentoxifylline 400mg twice daily, every second day low dose prednisone, and decreases the cephalosporins to every other day. Eventually the cephalosporin are reduced to every third day. Adding in the rifampicin makes a lot of sense as it has good penetration into scar tissue and it combines well with cephalosporins. It has been associated with liver damage so it is worth doing a pre-treatment ALP and ALT.

8 8 Allan Bell published a protocol of weekend or pulse therapy with full dose cephalosporins twice daily 2 days out of 7 that I have used very successfully. The main point is to treat daily until all lesions, and all pruritus is fully resolved before starting the pulse treatment. Before embarking on pulse treatment, you need to be sure that the diagnosis of German shepherd recurrent furunculosis, folliculitis and cellulitis is correct. For this reason I strongly recommend a biopsy. You need to address all the underlying factors that we ve discussed. You need to be sure that it can't be controlled with topical treatment alone. Lastly you need to be certain that fewer antibiotic treatment days per year are achieved in comparison to treating infections as they recur. In other words don t go straight to pulse treatment. Treat for 4-8 weeks, and then stop and wait to see how quickly it returns. Have the owners monitor closely and restart treatment as soon as it does reoccur. Case Study 4: A 4 year 5 month neutered male wire haired fox Terrier, 8.5 kg presented with a localized 6 cm by 4 cm oily pruritic area on his dorsal midline/ back of one year s duration. The pruritus was severe. The patch was growing in size. He had always had a greasy coat according to the owners. No treatment had been given but he had been scraped several times for Demodex. He was referred for allergy testing. Assessment: What are our differentials? This was open, but the history and clinical findings were not particularly suggestive of hypersensitivity. The major rule outs were Malassezia overgrowth or atypical demodicosis. Diagnostic Plan: A cytological smear from the dorsal area was negative for Malassezia. A hair pluck was negative for Demodex. I offered to biopsy as a rational approach to diagnosis. This was declined for now. I did a deep skin scraping produced four live demodectic mites, two of which had a distinctive long tail. This long bodied mite is suggestive of Demodex injai. Demodex injai This long mite bodied mite, first described in 1996, was named Demodex injai by Desch and Hillier in It is differentiated from D. Canis by its much longer body ( µm compared with µm in D. canis) and other more subtle anatomical differences. The nymphs and eggs of D. injai are also larger than those of D. canis. Initially, there was some controversy about whether it was a different species or not; a parasitologist claimed to have been able to produce long tailed mites by altering their growth medium. However in 2012, a group under Luis Ferrar at Barcelona constructed phylogenetic trees of 3 species of canine demodex mites based on mitochondrial DNA. Using the accepted criteria that the interspecies genetic distance must be about 10 times larger than the intraspecies distance, it seems evident that D. injai is a different species from D. canis, because the mean interspecific distance is 14.5 times greater. This long bodied mite tends to reside within the sebaceous glands and this is presumably what causes the characteristic clinical presentation of D. Injai infection. Infection with Demodex canis is a relatively common dermatological problem with a typical presentation. Although small numbers of D. Canis can be found in normal dogs, under certain conditions, they can markedly increase giving rise to a clinical presentation of patchy alopoecia, papules, scaling and comedones. Secondary lesions can include crusts, erythema,

9 9 hyperpigmentation and lichenification. Pruritus is variable. Secondary folliculitis and furunculosis is common. Severe demodicosis may be associated with concurrent deep infection. In 1999, Mueller and Bettanay reported a case of demodicosis in a Lakeland terrier with an unusual presentation. In 2002, Hillier and Desch reported on Large-bodied Demodex mite in 4 dogs. In 2003, David Robson et al, from the Melbourne Referral Centre, reported on a series of 8 dogs with demodicosis associated with a long bodied Demodectic mite. In 2006 Eric Bensignor et al presented 8 cases of demodicosis due to D. injai. In 2009 Ordeix et al, reported that Demodex injai mites were detected on trichoscopic examinations and/or deep skin scrapings in eight wirehaired fox terrier dogs with dorsal greasy skin and hair. Histological examination performed in five dogs revealed marked sebaceous gland hyperplasia with lympho-plasmacytic peri-adnexal dermatitis in all of them. One mite section was observed in one patient. Seven dogs were parasitologically cured after 2 to 7 months of oral ivermectin treatment. Greasy skin and hair resolved in four dogs, was partially reduced in two dogs and persisted in the remaining dog. Skin biopsies were repeated after parasitological cure in two dogs and revealed the persistence of sebaceous gland hyperplasia with mild lympho-plasmacytic peri-adnexal dermatitis and no parasites. Based on the findings in this case series, the terrier dog breed might be at increased risk for the development of D. injai mite infestation associated with dorsal greasy skin and hair, and microscopically with sebaceous gland hyperplasia. Persistence of sebaceous gland hyperplasia after parasitological cure in some patients suggested that this histological finding may not always be resulting from Demodex infestation. Moreover, low numbers of adult mites and variable clinical responses to acaricidal therapy suggested a contributory rather than a major role of D. injai in this skin condition. The histological diagnosis of sebaceous gland hyperplasia, particularly in case of dorsal trunk specimens from terrier dog breeds, warrants the search for D. injai mites on trichoscopic examinations and/or deep skin scrapings. Nearly all cases in all 5 reports had a similar signalment and a characteristic atypical clinical presentation. Signalment and risk factors for D. injai Nearly all cases in the studies were terrier breeds with West highland whites being over represented in the Robson (4/8) and Bensignor (4/8) studies. No sex predilection was found in any study. All studies found the long bodied mite only in adult dogs. According to Robson et al, there appears to be a high incidence of concurrent disease and previous immunodulating drug use in cases with Demodex injai. Clinical presentation of D. Injai In both the Robson and Bensignor studies nearly all dogs exhibited a dorsally oriented or generalized greasiness: 8/8 and 7/8 dogs in each study respectively. Nearly all dogs showed erythema. Pruritus was variable but usually present. The lack of alopoecia was surprising, as the mite is found in follicles as well as sebaceous glands. The Bensignor study reported diffuse alopoecia in 6/8 dogs. Diagnosis of D. Injai: Robson et al felt that the number of mites on skin scraping was low; often one or less per oil immersion field. This case study similarly found a low number of mites per scraping. Because of the low number of mites, Robson et al recommended multiple biopsies in animals that fit the signalment and clinical presentation for D. injai infection but are negative on scrapings.

10 10 Sebaceous gland hyperplasia is a common histological feature (Bensignor et al), the intra sebaceous gland location of the mite presumably giving rise to hyperplasia and excessive sebum production. The Bensignor study in contrast to the Robson study felt that the mites were relatively easily found on deep skin scraping. My experience is similar to David Robson s. D. injai can be surprisingly hard to find as I found in the case study presented here. Treatment of Demodex Treatment is similar to that for D. Canis. This case was treated with oral doramectin at 3-400ug/kg every other day. (Graham D) Oral ivermectin has also been used (Robson et al) at ug/ kg once daily. In the Bensignor et al report a variety of miticidal treatments were used, including ivermectin at 400 ug/ kg once daily. Imidacloprid (10% w/v) and moxidectin (2.5% w/v) is licensed to aid in the treatment of demodicosis with a monthly application. Although it is licensed for the treatment of demodicosis, treatment failures are extremely common. In breeds with a known sensitivity to Avermectins, or in dogs that show an idiosyncratic sensitivity, the effectiveness of imidacloprid and moxidectin can be improved with repeated weekly applications. (Patterson TE et al 2008) Now as many of you no doubt know, the arrival of oral fluralaner (Bravecto) and afoxolaner (Nexgard) is dramatically changing the treatment of generalized demodicosis and potentially Sarcoptes. Most of the studies seem to be on fluralaner. Nexgard (afoxolaner) and Bravecto (fluralaner) are isoxazolines that are a novel class of parasiticides that are potent inhibitors of gamma-aminobutyric acid (GABA)-gated chloride channels (GABACls) and l-glutamate-gated chloride channels (GluCls) in both arthropods (ticks) and insects (fleas, blow/biting flies and mosquitoes. There is a lot of positive anecdotal chatter on the net, but there are two reports describing the use of these drugs to treat demodicosis. The most recent was presented at the European Dermatology meeting in Krakow in September They had 163 dogs with generalized demodicosis. Dogs were treated with fluralaner at 25mg/kg orally, twice three months apart. No other treatment against demodicosis were used. Individuals with secondary pyoderma were treated with cephalexin at 30mg/kg once daily. The dogs were divided into 2 groups: juvenile onset 2-18 months, and adult onset over 2 years of age. Skin scrapings and/or hair plucks were done at 1, 2, and 3 months after the first fluralaner dose. 87.1% had clear skin scrapings at one month. Twenty one dogs (12. (%) all from group 2 weren t clear until the second month. All dogs 100% were clear at 3 months. Case study 5: a two year old spayed female Shiz Tzu presents with intense facial pruritus. She does have a history of recurrent otitis and pododermatitis. A number of treatments had been used: anti biotics, antihistamines, glucocorticoids and Advocate. Her clinical signs are intense facial itching, with severe erythema, some trauma induced alopecia and crusting. The lesions were mainly periocular and chin, although the ears were mildly affected. Cytologically Malassezia overgrowth was present. Differentials? Obviously hypersensitivity is very possible.

11 11 However, in 2009, Forsythe et al presented a series of 10 dogs (9 Shih Tzu and one Scottish terrier) with intense facial pruritus and clinical signs as described above. Less obviously small numbers of Demodex injai were found with hair plucks and scraping under sedation. Mite numbers were typically scarce. It is so easy to go down the hypersensitivity pathway. The pruritus resolved with treatment within 2 months. Parasitological cure took 3 to 9 months, with the median time being 4 months. Case study 6. Dorsal seborrhoea in a Border terrier A 3 year old female spayed Border terrier 7.5 kg presented with a six month history of oily skin and a faint odour. There was very little pruritus. The first signs occurred on the dorsal area, appearing as greasy skin that progressively became more erythematous. Flea control was regular. There was some 50% improvement with prednisone 5mg 0.5 tablet given twice daily. The symptoms started to reoccur when the dose was dropped to once daily. Prednisone was stopped one week prior to the examination. The dog was referred for an allergy work up. Clinical findings: The entire dorsum was extremely greasy, both the coat and the skin. There was moderate erythema. The rest of the coat and body were relatively normal although there may have been slight interdigital erythema. There was minimal pruritus. The presentation was not very suggestive of hypersensitivity. A skin scraping produced small number of mites with the same characteristic long tail. Oral doramectin 1% was started every other day at 300ug/kg. At the two month revisit, there was a distinct improvement, with the skin no longer being erythematous. Dead mites were found on deep scraping. The dose of doramectin was increased slightly. At the four month revisit, no mites were found. However the skin and coat remained distinctly greasy with a seborrheic smell. Okay, so this is another case of a terrier with dorsal greasy seborrhoea with D. injai. What else is new? Well, in 2010 a group from Edinburgh showed that Border terriers suffer from an Idiopathic generalized sebaceous gland hyperplasia. (Idiopathic generalized sebaceous gland hyperplasia of the Border terrier: a morphometric study. VetDermatol.21 p.494) Five border terriers in group A presented with generalized greasiness of the skin and hair coat that was worse over the dorsal trunk and which had a typical wet appearance. This result in clumping of the hair, particularly over the dorsum, leaving a grey greasy deposit on the hands when touched. They were relatively non-pruritic. Skin biopsies from these five dogs were compared with group B, 5 Border terriers without any clinical signs of dorsal seborrhoea, and group C, 4 other Terrier breeds, 3 Staffordshire terriers, and one Yorkshire. Group A had very significantly increased numbers of sebaceous gland lobules compared to B and C. Their results indicated that the physical signs of sebaceous gland hyperplasia are caused by an increase in the number of sebaceous gland lobules and total lobular area. Border terriers may be genetically predisposed to the development of idiopathic generalized sebaceous gland hyperplasic compared with other dog breeds. Support for this idea is provided by comparing Group B (normal Borders) with Group C (non-border terriers) According to the study, there were significantly increased numbers of basal and mature sebaceous gland cells in the nonaffected Border terrier group. However we cannot rule out that the sebaceous gland hyperplasia is secondary to other dermatopathies. One of the affected Borders had previously had generalized D. injai, and two

12 12 dogs had mild atopy. However, the authors make a convincing case why the sebaceous gland hyperplasia is not secondary to other diseases. What is the clinical significance of this? Well, first of all, this is very common in Border Terriers in New Zealand. I ve seen a number of these dogs, and I am sure you have too. There is a great deal of variation as to severity. They should always be checked for Demodex. It is great if you find them, but be cautious about how much improvement the owners can expect. Some Borders clear beautifully when their Demodex injai is addressed, but others have only a partial or unimpressive improvement in terms of the greasiness. Unfortunately apart from frequent anti-seborrheic shampooing, I have no exciting helpful hints. Isotretinoin has been suggested as a way of reducing the sebaceous gland hyperplasia. Bronwyn Smits and I had been talking about setting up a study of these dogs. However she has abandoned us for the corporate life. Rob Fairley Gribbles Christchurch has indicated that he would be interested in taking up the baton. Please let me know if you have any candidates. Remember the mantra of every day dermatology. Generate differentials. Use sequential monotherapy to rule the differentials in or out.