Nr. 45 Februar 2011 Magazin für Lehramtsanwärter/-innen Aus dem Inhalt: 3 Mathe unterrichten und den Lehrplanforderungen gerecht werden? 8 Kopiervorlagen aus PIK AS 11 Kreis und Winkel – eine Unterrichts- einheit für die Jahrgangsstufe 6 14 Junglehrer fordern Standards
Even if Viagra is not needed, it is possible that the doctor will be able to determine the etiology of erectile dysfunction and prescribe appropriate treatmen priligy australia it doesn't pay to forget about sexual activeness even at the first sings of malfunction.
Treatment of demodicosis in dogs: 2011 clinical practice guidelinesTreatment of demodicosis in dogs: 2011 clinical practiceguidelines Ralf S. Mueller*, Emmanuel Bensignor†, Lluı´s Ferrer‡, Birgit Holm§, Stephen Lemarie¶, ManonParadis** and Michael A. Shipstone†† *Centre for Clinical Veterinary Medicine, Ludwig Maximilian University Munich, Veterinaerstraße 13, 80539 Munich, Germany†Dermatology Referral Service, 75003 Paris, 35510 Rennes-Cesson and 44000 Nantes, France‡Department of Animal Medicine and Surgery, Universitat Autonome de Barcelona, 08193 Bellaterra, Spain§The Blue Star Small Animal Hospital, Gjutja¨rnsgatan 4, SE-417 07 Gothenburg, Sweden¶Southeast Veterinary Specialists, 3409 Division Street, Metairie, LA 70002, USA**Department of Clinical Sciences, Faculte´ de Me´decine Ve´te´rinaire, University of Montreal, CP 5000, St-Hyacinthe, Que´bec, Canada J2S 7C6††Dermatology for Animals, 263 Appleby Road, Stafford Heights, QLD 4053, Australia Correspondence: Ralf S. Mueller, Centre for Clinical Veterinary Medicine, Ludwig Maximilian University Munich, Veterinaerstraße 13, 80539Munich, Germany. E-mail: firstname.lastname@example.org Background and Objectives – These guidelines were written by an international group of specialists with the aimto provide veterinarians with current recommendations for the diagnosis and treatment of canine demodicosis.
Methods – Published studies of the various treatment options were reviewed and summarized. Where evidencein form of published studies was not available, expert consensus formed the base of the recommendations.
Results – Demodicosis can usually be diagnosed by deep skin scrapings or trichograms; in rare cases a skinbiopsy may be needed for diagnosis.
Immune suppression due to endoparasitism or malnutrition in young dogs and endocrine diseases, neoplasia andchemotherapy in older dogs are considered predisposing factors and should be diagnosed and treated tooptimize the therapeutic outcome. Dogs with disease severity requiring parasiticidal therapy should not be bred.
Secondary bacterial skin infections frequently complicate the disease and require topical and ⁄ or systemic anti-microbial therapy.
There is good evidence for the efficacy of weekly amitraz rinses and daily oral macrocyclic lactones such as mil-bemycin oxime, ivermectin and moxidectin for the treatment of canine demodicosis. Weekly application of topi-cal moxidectin can be useful in dogs with milder forms of the disease. There is some evidence for the efficacy ofweekly or twice weekly subcutaneous or oral doramectin. Systemic macrocyclic lactones may cause neurologicaladverse effects in sensitive dogs, thus a gradual increase to the final therapeutic dose may be prudent (particu-larly in herding breeds).
Treatment should be monitored with monthly skin scrapings and extended beyond clinical and microscopic cureto minimize recurrences.
Editor's Note – A brief review article by R. Mueller has been published: Evidence-based treatment of caninedemodicosis, Tierarztl Prax Ausg K Kleintiere Heimtiere 2011; 39: 419–24. This is not considered to constituteduplication of the article published here in Veterinary Dermatology.
Accepted 24 October 2011 Sources of Funding: This study is self-funded.
Objectives and explanation of this document Conflict of Interest: In the last 5 years, Ralf Mueller has obtained In humans, evidence-based medicine is not only an funding, lectured or consulted for Bayer Animal Health, Boehringer academic buzz word but has reached general practice.
Ingelheim, Dechra Veterinary Products, Intervet, Merial, NovartisAnimal Health, Pfizer Animal Health, Procter & Gamble, Royal The Cochrane Collaboration (http://www.cochrane.org/) Canin, Selectavet and Virbac. Emmanuel Bensignor has obtained provides reviews and treatment guidelines for many com- funding for studies, lectured or consulted for the following compa- mon diseases and is available at no cost worldwide to nies selling products for demodicosis: Bayer Animal Health, Novar- anyone with Internet access. In veterinary dermatology, tis Animal Health and Pfizer Animal Health. Lluı´s Ferrer has the first evidence-based medicine review was published obtained funding, lectured or consulted for Novartis, Bayer Animal in 2003 about treatments for canine atopic dermatitis.1 Health, Virbac, Merial, Intervet, Esteve Veterinaria and Elanco. Bir- This was followed with a Cochrane-type review2 and git Holm has obtained funding for studies, lectured or consulted practice guidelines publication for treatment of canine for Bayer Animal Health and Novartis Animal Health. Manon Para- atopic dermatitis in 2010.3 These guidelines are available dis has participated in a study funded by Bayer Animal Health.
in a number of different languages as open access. Other Michael Shipstone has received funding for studies and lecturesfrom Pfizer Animal Health, Schering Plough and Virbac Australia.
topics in veterinary dermatology, such as fungal infec- ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Demodicosis treatment tions, leishmaniosis or otitis caused by Pseudomonas, in a specific country and whether it was licensed for use have also been the subject of published evidence-based in dogs and, specifically, to treat canine demodicosis.
Before implementing these guidelines into practice, vet- Demodicosis is a common skin disease of the dog.
erinarians need to verify the legality of using the various Despite a number of studies evaluating pathogenesis and veterinary pharmaceutical products and treatment proto- therapeutic options, treatment of canine demodicosis is cols in their respective countries. Finally, a one-page sum- still a matter of discussion in many conferences and mary is provided at the end of this article.
continuing education courses. In October 2010, an inter-national committee was founded to establish current evi- Pathogenesis of the disease dence-based guidelines for treating canine demodicosis Demodex mites are considered to be a normal part of the in practice. The committee consisted of members with cutaneous microfauna in the dog11 and are transmitted long-standing interest in canine demodicosis as docu- from the bitch to the pups during the first days of life.12 mented by several publications in the field, namely Puppies raised in isolation after caesarean section do not (in alphabetical order) Emmanuel Bensignor (France), Lluı´s have any Demodex mites. It is assumed that immunosup- Ferrer (Spain), Birgit Holm (Sweden), Stephen Lemarie pression or a defect in the skin immune system allows (USA), Ralf S. Mueller (Germany), Manon Paradis (Canada) for mites to proliferate in hair follicles, resulting in clinical and Michael Shipstone (Australia). The aim of this commit- signs.12 In addition to the most commonly encountered tee was to develop best-practice guidelines for the treat- Demodex mite (D. canis), two other morphologically dif- ment of canine demodicosis based on published evidence ferent types have been reported.13,14 One is the long-bod- of efficacy. These guidelines are supported by the Ameri- ied D. injai, a mite commonly associated with greasy ⁄ oily can College of Veterinary Dermatology, the Asian College skin and coat.15–18 The other is a short–bodied mite13 that of Veterinary Dermatology, the Asian Society of Veterinary has been reported in association with D. canis.19,20 How- Dermatology, the Canadian Society of Veterinary Derma- ever, more recent evidence has been presented that tology, the Dermatology Chapter of the Australian College these different forms are all D. canis.21 Final determina- of Veterinary Scientists and the European Society of tion will require genetic ⁄ molecular testing. Published data indicate similar efficacy of reported treatments regardlessof the Demodex type (COE I).
In young animals, endoparasiticism,22 malnutrition and Throughout this article, recommendations for specific debilitation may lead to an immunocompromized state interventions were made based on the category of evi- that favours mite proliferation and development of skin dence (COE) described in Table 1 and on the highest evi- disease. In adult animals, chemotherapy, neoplasms, dence available at the time of writing. The categories hypothyroidism or hyperadrenocorticism, for example, have been modified from the human literature7 and a may suppress the immune system sufficiently to trigger recent evidence review of treatment options for canine proliferation of the mites.23–25 However, studies proving atopic dermatitis.2 In general, recommendations of lower a cause–effect relationship between these factors and roman numeral numbers should be considered of greater demodicosis are lacking. Many immunosuppressed dogs value than those with higher grades.
never develop demodicosis, and in many cases an under- For most of the recommendations in this article, the lying cause may not be found. In many publications, a evidence was derived from results of a recent systematic juvenile-onset and an adult-onset form of the disease are review8 (COE I) or clinical trials (COE II). There are few differentiated.23–26 However, this differentiation may be randomized controlled studies published evaluating thera- difficult in individual cases. It is more important to identify peutic options for canine demodicosis.9,10 To the authors' and correct predisposing factors (such as endoparasitism knowledge, there is not a single placebo-controlled clini- or underlying diseases) independent of age to achieve the cal trial, and the rate of spontaneous remission of dogs best possible outcome (COE IV).
with generalized demodicosis is not known. The use of Demodicosis in the dog is differentiated in a localized recommended treatments will not always result in com- versus a generalized form. Localized demodicosis has plete clinical and microscopic remission or even in a a good prognosis, with the overwhelming majority of response acceptable to the owner. Likewise, insufficient cases spontaneously resolving without miticidal treat- evidence does not imply that a specific drug is not effec- ment (COE V).27 Topical antiseptic therapy may be rec- tive but rather that there are no published studies docu- ommended to prevent or treat a secondary bacterial skin menting efficacy or lack thereof.
infection (COE V).27 Generalized demodicosis may be a Recommendations for a specific intervention did not severe and potentially life-threatening disease. The num- take into consideration whether a product was available ber of dogs with generalized demodicosis showing spon-taneous cure is unknown at this time, although evidencefor spontaneous remission in a subset of cases wasrecently presented.28 The definition of localized versus Table 1. Different categories of evidence (COE) generalized demodicosis has been a matter of debate.
Directly based on meta-analyses or systematic reviews Directly based on several studies or case series The reported lesion extent consistent with localized Directly based on at least one study or several case reports disease ranges from four lesions to 50% of the body Directly based on one case report surface.29,30 This committee considers demodicosis Directly based on expert committee reports or opinions localized if there are no more than four lesions with a Directly based on laboratory studies diameter of up to 2.5 cm (COE V).
ª 2012 The Authors. Veterinary Dermatologyª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Mueller et al.
Clinical signsMild erythema, comedones and scaling may be theonly lesions in mildly affected dogs. Partial or completealopecia may develop. Multiple coalescing foci of alopeciaand follicular papules characterize demodicosis of moder-ate severity. Follicular casts (scales adhering to the hairshafts) may be present. Follicular pustules and, in severecases, furunculosis with scales, crusts, exudation andfocal ulceration and draining tracts are observed with moreadvanced disease. Occasionally, nodules may be present.
Skin lesions often begin on the face and the forelegs and may progress to affect other body sites. Bilateral ceru-minous otitis externa occasionally may be seen with de-modicosis. Generalized demodicosis may be associatedwith lymphadenopathy, lethargy and fever. A secondarybacterial skin infection almost invariably accompaniesgeneralized demodicosis. Pedal demodicosis may beassociated with significant interdigital oedema and, partic- Figure 1. Photograph of a trichogram showing Demodex mites and ularly in larger dogs, may be distressingly painful.
eggs (arrows) in mineral oil (·100).
Diagnosis of demodicosis are difficult to scrape, such as periocular and interdigital Deep skin scrapings areas. Hairs from lesional skin are plucked with forceps in At this time, deep skin scrapings are the diagnostic test the direction of the hair growth and placed in a drop of of choice in suspect cases.31 Curettes, spatula, sharp and mineral or paraffin oil on a slide (Figure 1). The use of a dull scalpel blades can all be used to collect samples.
coverslip allows more thorough and rapid inspection of Placing a drop of mineral oil on the sampling instrument the specimen. To increase the chance of a positive tricho- and ⁄ or directly on the skin site can be helpful because gram, a large number of hairs (50–100) should be plucked.
debris adheres better to the instrument. Multiple scrap- When performed properly, trichograms have a high diag- ings (approximately 1 cm2) of affected skin are performed nostic yield. However, negative trichograms should be in the direction of the hair growth, and the skin should be followed by deep skin scrapings before ruling out demodi- squeezed during or between scrapings to extrude the cosis (COE III). Positive trichograms in healthy dogs are mites from the deep follicles to the surface. Squeezing the skin has been shown to increase the number of mitesfound with the skin scrapings (COE III).32 The best yield is achieved with primary lesions, such as follicular pap- In some rare cases, skin scrapings and trichograms may ules and pustules. Ulcerated areas should not be scraped be negative, and skin biopsies may be needed to detect because mite yields may be low in such areas. The skin is the Demodex mites in the hair follicles or in foreign body scraped until capillary bleeding occurs, which indicates granulomas in furunculosis. This may be more likely in that the scraping has reached sufficient depth. In a long- certain body locations, such as the paws, and certain dog or medium-haired dog, gently clipping the area to be breeds, such as shar-peis.
scraped will minimize the loss of the scraped material intothe surrounding hair. Debris is then transferred to a slide, Other methods of mite detection mixed with mineral or paraffin oil and examined with a Direct examination of the exudate from pustules or drain- coverslip under the microscope at low-power magnifica- ing tracts may reveal mites in some dogs. Specimens can tion (·4 and ·10 lens).
be collected by squeezing the exudate onto a glass slide Although Demodex mites are part of the normal micro- and visualized by adding mineral oil or paraffin oil and a fauna, it is uncommon to find one mite even on several coverslip. In some cases where mites are very abundant, deep skin scrapings. If a mite is found, this should raise acetate tape preparations may also reveal mites. If suspicion and additional skin scrapings should be per- affected dogs have lymphadenopathy, it is not uncom- formed. Finding more than one mite is strongly sugges- mon to find mites on fine-needle aspirates. These meth- tive of clinical demodicosis (COE V).31 Different life ods cannot be used to rule out the presence of an stages (eggs, larvae, nymphs and adults) and their num- bers should be recorded, compared from the same sitesat each visit and used to evaluate response to treatment.
Identification of bacterial infections (using clinical signs, Mites may be easier to find when the microscope con- skin cytology and culture) denser is lowered and the light decreased because this Frequently, generalized demodicosis is associated with increases the contrast in the microscope field.
secondary bacterial skin infections. In severe cases withfurunculosis, bacterial septicaemia is possible. When clin- ical signs of a possible bacterial skin infection (e.g. pap- Trichograms have been reported as an alternative to deep ules, pustules) are present, an impression smear should skin scrapings32,33 and are particularly useful in areas that be obtained, stained and evaluated for an increased num- ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Demodicosis treatment ber and ⁄ or intracellular location of bacterial organisms.
tion of 1.25%37 have been reported in dogs not respond- Most commonly, Staphylococcus pseudintermedius will ing to conventional therapies. In the latter report, dogs be present,8 but in some dogs, particularly those with were treated once with atipamezole (0.1 mg ⁄ kg intra- furunculosis, Gram-negative rods, such as Escherichia muscularly) followed by oral yohimbine (0.1 mg ⁄ kg) once coli or Pseudomonas aeruginosa, may predominate.
daily for 3 days to minimize systemic adverse effects.37These intensive protocols should be reserved for dogs Treatment of canine demodicosis failing routine treatment.
When using amitraz rinses, it is essential to clip the hair Treatment of canine generalized demodicosis is multi- coat in dogs with medium to long hair coat (COE V).40 modal. In addition to effective acaricidal therapy, treat- This needs to be repeated as needed during the treat- ment of concurrent bacterial skin infection, internal ment course. The rinse should be applied carefully with a parasitism and underlying systemic disease must be sponge and soaking the skin, and allowed to air dry with- undertaken to maximize the potential for successful treat- out rinsing. Dogs should not be allowed to get wet ment (COE V).
between rinses, to avoid washing off the amitraz. Treat-ment of pedal demodicosis with amitraz rinses may be Treatment of secondary bacterial skin infection problematic in wet environments because it is difficult to Cytology is essential in the evaluation of a dog with de- maintain the amitraz on the pedal skin in these circum- modicosis (see identification of bacterial infections above).
stances. Daily treatment of the paws27 or using other When an infection is present, it should be treated based treatment modalities may be needed (COE V). Adverse on the standard of care in each country. It is beyond the effects of amitraz reported in various studies were scope of these guidelines to detail recommendations for depression, sleepiness, ataxia, polyphagia, polydipsia, antimicrobial therapy. Ideally, a bacterial culture should be vomiting and diarrhoea.8 Amitraz anecdotally has caused performed to determine the choice of antibiotic. Culture headaches and asthma in owners, thus it is commonly and susceptibility testing are ideal in dogs with rod-shaped recommended that dogs should be washed in a well-ven- bacteria present on cytology, in cases with apparent bacte- tilated area.8,27,41 rial resistance or in very severe, potentially life-threatening Based on published studies, amitraz rinses seem to be infection (COE V). If a culture is not possible, cytological less efficacious in dogs with adult-onset demodicosis.8 determination of the bacterial type (rods or cocci) is essen- Weekly treatment is recommended (COE I). As approved tial prior to empirical antibiotic therapy, because many concentrations and treatment interval vary from country antibiotics empirically suited for Gram-positive coccal to country, veterinarians need to choose the treatment infections are ineffective for Gram-negative rods.
protocol approved in their location based on their coun- Appropriate oral antibiotic therapy and concurrent topi- try's regulatory agency guidelines.
cal antimicrobial therapy (whole-body soaks or shampoos) More recently, a spot-on preparation with 15% amitraz are recommended for all dogs with generalized demodi- and 15% metaflumizone has been used in some coun- cosis and secondary bacterial skin infection (COE V). In tries as a monthly treatment for canine demodicosis. Pilot addition to antimicrobial benefits, topical therapy contrib- studies showed promising results with administration utes to the overall wellbeing of the dog by removing monthly42 and every 2 weeks.42,43 However, pemphigus crusts and debris that may contain mites, exudate and foliaceus-like drug reactions have been reported after the inflammatory mediators. Benzoyl peroxide (2–3%) and use of the spot-on, and some dogs required long-term chlorhexidine-based shampoos (3–4%) are commonly immunosuppressive therapy for the treatment of this dis- recommended for dogs with demodicosis. They have a ease even after the use of spot-on was discontinued.44 prolonged antibacterial activity on skin.35 Benzoyl perox- The manufacturer indicated that the production of this ide is degreasing, thus drying, and may be irritant, so it spot-on is discontinued in North America at the time of may be prudent to follow up with a moisturizer to prevent writing but apparently still sold in other parts of the world.
drying of the skin.36 The frequency of topical therapy Based on the reported cases of drug-induced pemphigus depends on the dog, owner and concurrent miticidal ther- foliaceus,44 this spot-on preparation should not be rou- apy, but weekly bathing is most commonly recom- tinely used for the treatment of canine demodicosis, but (COE V). Antimicrobial should be reserved for cases not responding to other continued for 1–2 weeks beyond clinical and microscopic treatment options.
resolution of the bacterial skin infection.
Macrocyclic lactones AmitrazAmitraz as a rinse has been approved for the treatment of canine generalized demodicosis in many countries for Milbemycin oxime is licensed for the treatment of canine decades. It has been shown to be an effective treatment demodicosis in some countries at a dose of 0.5–2 mg ⁄ kg option in many studies (COE I).8 The recommended con- daily orally (p.o.). In studies from the USA and Australia, a centration varies from 0.025 to 0.06%, with a frequency clearly higher success rate was seen with a higher dose of once weekly to every 2 weeks.8 Clinical efficacy of 1–2 compared with 0.5–1 mg ⁄ kg.25,26,41 This is in con- increases with increasing concentration and shorter treat- trast to a Swedish study, where good results were ment intervals (COE II).37,38 Intensive protocols with daily achieved with the low-dose protocol,45 possibly because rinsing of alternating body halves at a concentration of most dogs in this study were diagnosed early in the dis- 0.125%39 or weekly treatment with an amitraz concentra- ease and had not previously been treated with other miti- ª 2012 The Authors. Veterinary Dermatologyª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Mueller et al.
cides. In contrast, the other studies were conducted in gradually increased (COE III) and dogs monitored for referral practices with potentially more chronically and adverse effects. If such adverse effects occur, ivermectin severely affected patients. Alternatively, a different administration should be discontinued. In some cases, it genetic base of the dogs or different susceptibilitiy of the may be indicated to attempt administering a lower dose mites to milbemycin oxime may have influenced the of ivermectin; if this is successful and clinical signs of tox- results. The success rate of milbemycin oxime was icity resolve, therapy may be continued at the lower dose.
shown to be much lower in dogs with adult-onset demod- This approach is not recommended in dogs with acute icosis (COE I).25,45 Milbemycin oxime has been adminis- toxicity within days of beginning treatment, but is often tered to collie dogs at a dose of 2.5 mg ⁄ kg daily for effective in dogs developing adverse effects after some 10 days without adverse effects,46 and there seems to weeks of therapy (COE V). Dogs of breeds known to be be a high safety margin with this drug.8 However, dogs at risk should be tested for the ABCB1-D1 gene mutation homozygous for the ABCB1-D1 (MDR-1) mutation devel- (where this is possible) or receive alternative treatments.
oped ataxia with milbemycin oxime at a dose of approxi-mately 1.5 mg ⁄ kg daily, but tolerated the drug at 0.6 mg ⁄ kg ⁄ day.47 Moxidectin has been used in a number of studies at At this time, milbemycin oxime is recommended for doses of 0.2–0.5 mg ⁄ kg ⁄ day p.o. with comparable suc- the treatment of canine generalized demodicosis at a cess to ivermectin.53,61–63 Adverse effects are similar to dose of 1–2 mg ⁄ kg p.o. daily. A lower efficacy is seen those of ivermectin,8 and a gradual dose increase similar with adult-onset demodicosis (COE I). In herding breed to that described for ivermectin was used in two of the dogs, it is advised to evaluate the ABCB1-D1 (MDR-1) studies.62,63 However, adverse effects are more com- genotype and to use lower doses or increase the dose mon. In one study, treatment was discontinued due to gradually in dogs homozygous for the ABCB1-D1 (MDR-1) lethargy, vomiting and ataxia in three of 22 dogs. In one mutation (COE V).
dog, adverse effects were noted at a dose of 0.28 mg ⁄ kgand in the other two dogs it occurred at 0.4 mg ⁄ kg. In another study, adverse effects were seen in 12 of 35 Ivermectin is not licensed for use in canine demodicosis.
dogs treated with moxidectin at 0.5 mg ⁄ kg every 72 h.
It has been used as weekly injection at a dose of The most common adverse effects were vomiting and 0.4 mg ⁄ kg subcutaneously (s.c.) with variable and incon- inappetence, but these were not severe enough to war- sistent results.48 Thus, injectable weekly treatment can- rant discontinuation of therapy.
not be recommended at this time for the treatment of Based on the published evidence, moxidectin at 0.2– canine generalized demodicosis (COE III). However, 0.5 mg ⁄ kg p.o. daily can be recommended as an effective there are a number of studies evaluating daily oral iver- therapy for canine demodicosis (COE I); an initial gradual mectin at a concentration of 0.3–0.6 mg ⁄ kg with similar dose increase and careful monitoring are recommended, outcome measures and treatment success.29,49–53 An similar to oral ivermectin.
evidence-based review concluded that oral ivermectin at Moxidectin has also become available as a 2.5% spot- a dose of 0.3–0.6 mg ⁄ kg daily can be recommended as on formulation (in combination with 10% imidacloprid).
therapy for canine generalized demodicosis (COE I).8 Iver- Initial studies evaluating the spot-on as monthly treat- mectin can cause severe neurological adverse effects, ment for generalized demodicosis were encouraging.64 such as lethargy, tremors, mydriasis and death in sensi- However, clinical use did not corroborate the findings, tive dogs (COE I). Anecdotally, blindness has also been and subsequent studies revealed that the spot-on was seen. Collie dogs and other herding breeds are most more efficacious in juvenile dogs with milder forms of the commonly affected, but other breeds have also been disease30 and that weekly therapy showed better results than twice monthly or monthly administration.9,65 Based 0.05 mg ⁄ kg on day 1 to 0.1 mg ⁄ kg on day 2, 0.15 mg ⁄ kg on these results, the label of this product was changed to on day 3, 0.2 mg ⁄ kg on day 4 and 0.3 mg ⁄ kg on day 5 is recommend weekly administration in many countries recommended in any dog treated with ivermectin where it has been approved for the treatment of canine (COE III).54 When higher daily doses are used then a fur- demodicosis. Currently, the spot-on containing 2.5% ther increase by 0.1 mg ⁄ kg ⁄ day is recommended. Other moxidectin and 10% imidacloprid can be recommended P-glycoprotein inhibitors, such as ketoconazole or ciclo- as weekly treatment for dogs with juvenile-onset and sporin, if given concurrently, increase the likelihood of mild forms of the disease (COE II). If significant improve- adverse effects (COE III).55,56 ment is not seen within the first few weeks, other ther- More recently, an ABCB1-D1 (MDR-1) mutation consid- apy may be indicated.
ered responsible for the acute toxicity in collie dogs andseveral other herding breeds has been identified.57–59 Testing for this defect is possible. However, in a recent Doramectin is also a macrocyclic lactone that has been study evaluating 28 ‘nonsensitive' breed dogs with neuro- reported as a successful treatment for canine demodico- logical adverse effects to daily ivermectin after 4 days to sis.66,67 In one study, it was administered at 0.6 mg ⁄ kg 5 weeks of therapy,60 27 dogs did not show an alteration s.c. weekly;66 in the second study, it was administered at of the ABCB1-D1 (MDR-1) gene, thus other mechanisms the same dose p.o. once weekly.67 In the latter study, of toxicity must exist. Based on published studies, iver- two dogs that did not improve clinically responded to mectin at 0.3–0.6 mg ⁄ kg p.o. daily is an effective therapy 0.6 mg ⁄ kg p.o. twice weekly, but one of them, a golden for canine demodicosis (COE I), but the dose needs to be retriever, developed ataxia and subsequently was treated ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Demodicosis treatment twice weekly with 0.3 mg ⁄ kg doramectin. The recurrence therapy (e.g. monthly amitraz rinses or weekly ivermectin rate was higher in dogs with adult-onset disease (as seen administration). Development of Demodex mite resis- with amitraz and milbemycin oxime; COE III). Based on tance against miticides has not been documented at this these two studies, there is evidence that doramectin at a point to the authors' knowledge. Whether low-dose dose of 0.6 mg ⁄ kg p.o. or s.c. weekly may be used for long-term glucocorticoid therapy for allergic disease is the treatment of demodicosis (COE III).
sufficient immunosuppression to trigger generalized The question of whether more frequent administration demodicosis has not been evaluated to the authors' increases the success rate without unacceptable adverse knowledge. The current recommendation is to avoid effects has to be evaluated by further, preferably by ran- long-term glucocorticoid therapy in dogs with a history of domized blinded trials. The effect of 1 mg ⁄ kg doramectin demodicosis (COE V).
on Ancylostoma caninum and Toxocara canis has been Based on published studies, a recurrence of the disease evaluated in pregnant beagle bitches, and no adverse in the first 1–2 years after cessation of therapy does occur effects were seen.68,69 Likewise, beagle dogs were trea- in a small number of dogs.8 The majority of these cases ted with 0.4 mg ⁄ kg s.c. doramectin for Spirocerca lupi achieve remission with a repeat of the same treatment with no adverse effects.70 However, subcutaneous dora- regimen or with another type of therapy.8 In more recent mectin at 0.2 and 0.7 mg ⁄ kg, respectively, caused severe studies, a follow-up period of 12 months is recommended neurological signs in a collie dog71 and two white Swiss to monitor for relapse. It is recommended to monitor dogs German shepherd dogs with an MDR-1 mutation72 closely for recurrence of clinical disease during the first approximately 24 h after a single administration; thus it is 12 months after treatment has been discontinued.
recommended to gradually increase the doramectin doseto identify drug-sensitive dogs in a similar manner to the How should dogs with adult-onset demodicosis be recommendations for ivermectin and moxidectin.
evaluated for underlying diseases?Adult-onset demodicosis is defined as the development Other treatment options of demodicosis in an adult dog with no known prior his- In addition to various medical treatments, it seems pru- tory of the disease. In adult animals, immunosuppressive dent, based on published information, to recommend therapy and diseases such as neoplasms, hypothyroidism good control of endoparasites, a balanced, high-quality or hyperadrenocorticism have been reported to be associ- diet and avoidance of immunosuppressive treatments if ated with generalized demodicosis.23–25 Evaluation for an at all possible (COE V).
underlying disease may include, but not be limited to, the There are a number of other reports evaluating various following tests: a complete blood count, biochemistry treatments, most of which are summarized in a published panel and urinalysis, lymph node aspirate, radiographs of review.8 A recently published study showed that treat- the chest and ultrasound of the abdomen.
ment with selamectin at a dose of 24–48 mg ⁄ kg p.o.
Hyperadrenocorticism and hypothyroidism should be once weekly or twice monthly had a low success rate in investigated; if there are no other supporting signs of hor- canine generalized demodicosis (COE III).10 monal diseases, urine cortisol creatinine ratio may be used There is insufficient evidence to recommend treatment to rule out hyperadrenocorticism (COE V). Evaluation of of canine demodicosis with amitraz collars, closantel, del- thyroid hormone concentrations can be difficult. Chronic tamethrin, vitamin E, herbal and homeopathic prepara- stress due to generalized demodicosis and secondary tions, muramyl dipeptide and phoxime.8 There is deep bacterial skin infection may influence results of evidence against the use of pour-on or injectable weekly these tests. Thyroxine concentrations may be decreased ivermectin, lufenuron, ronnel, oral selamectin and levami- due to euthyroid sick syndrome, and the urine cortisol sole (COE III).8,10 creatinine ratio may be increased. Depending on theindividual case situation, veterinarians need to consider Treatment duration, monitoring and prognosis postponing diagnostic tests for hormonal disease until the It is not sufficient to rely on clinical appearance as the bacterial skin infection is treated and the demodicosis is end-point of treatment. Clinically normal dogs may still improved or in remission. If owners of dogs showing no harbour mites on skin scrapings. Microscopic cure, other clinical signs of disease refuse further diagnostic defined as multiple negative skin scrapings, in addition to evaluation, close monitoring of the dog until development resolution of clinical signs is needed to determine the of further clinical clues should be recommended (COE V).
therapeutic end-point. In general, it is recommended to If systemic signs point to a particular disease, that disease scrape repeatedly the three to five most severely should be confirmed and treated, as evidence shows that affected areas and any new lesions monthly until all three successful treatment of an underlying cause may contrib- to five scrapings are negative. As only small areas are ute to remission of the demodicosis (COE IV).15 scraped, which may not be representative of the dog as awhole, it is recommended to continue treatment for Should dogs with demodicosis be allowed to breed? 1 month after the second negative monthly set of skin Demodicosis in young dogs is most likely to be based on scrapings. In dogs that responded very slowly to therapy, one or more genetic traits, as supported by strong breed extend treatment even further (COE V).
predispositions73 and the fact that selective breeding has The prognosis for canine demodicosis is good, with the decreased the incidence of demodicosis in breeding ken- majority of cases achieving long-term remission.8 How- nels.27 To prevent an increase in prevalence of canine ever, dogs with a incurable or poorly controlled underlying demodicosis, it is recommended not to breed from any disease may never be cured and may require long-term dog with generalized demodicosis27,74 and to neuter ª 2012 The Authors. Veterinary Dermatologyª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Mueller et al.
affected animals. This is especially important in the bitch,as oestrus cycles may trigger recurrence of clinical dis-ease (COE III),75 providing a further argument for neuter-ing these animals.
Almost 30 years ago, the American Academy of Veteri- nary Dermatology recommended that ‘the AAVD urgesveterinarians to accept for therapy only those generalizeddemodicosis patients who have been or will be neu-tered'.76 However, the definition of generalized demodico-sis is subjective and thus this recommendation may leadto different outcomes with different breeders and veteri-narians. The reported lesion extent consistent with local-ized disease ranges from four lesions to 50% of the bodysurface.29,30 There is little information on the measured le-sional area that is considered localized and whether thesize of a lesion considered localized is influenced by thesize of the dog. It is also not known whether an area with Figure 2. Photograph of the trunk of a 6-month-old West Highland papules, pustules, exudation, crusting and ulcers is com- white terrier with localized demodicosis. Note the focal alopecia, ery- parable to an area characterized by alopecia and comedo- thema, papules and small ulcers and crusts.
nes only. Thus, the authors consider that differentiation isonly of limited help to the practitioner. In addition, it isunclear whether treatment of localized demodicosis will ther progression to generalized disease or sponta- prevent the disease from becoming generalized, or if a neous remission is the recommended option.
dog predisposed to generalized demodicosis would 2 If the owner desires therapy, topical antiseptic develop it even if topical treatment were used initially on shampoos (e.g. benzoyl peroxide or chlorhexidine) the first localized lesions. Studies to answer these ques- are recommended once to twice weekly (COE V).
tions are urgently needed. The main reasons for differenti- Benzoyl peroxide is a degreasing and thus drying ating the two forms are the prognosis and the decision shampoo and may need to be followed up with a about neutering the dog to prevent breeding.
moisturizer to prevent dry, scaly and pruritic skin.
Currently, the consensus of this committee is as fol- lows. As there is no scientific basis for a clear and consis- Treatment options for scenario 1b: tent differentiation between localized and generalizeddemodicosis, ideally all dogs with demodicosis should be 1 This dog would still qualify for localized demodico- eliminated from the breeding pool. As this is not a realistic sis. Thus, initially simple monitoring of the dog for outlook for many breeds, breeding recommendations further progression to generalized disease or spon- should be based on the need for specifically treating the taneous remission is a possible option. However, dog for demodicosis. In a dog with clinical signs of de- the papules and crusts indicate a possible bacterial modicosis limited to one or few areas of the body and not secondary infection, and an impression smear is affecting the general wellbeing of the dog, it is acceptable indicated to look for the presence of bacteria. The to use antimicrobial shampoos only and refrain from mite- ideal method is an aspiration of an intact pustule.
specific therapies. However, if the disease continues to Alternatively, an impression smear can be obtained progress such that specific miticidal treatment is after rupturing a pustule. Topical antiseptic sham- required, neutering the animal to prevent breeding is poos (e.g. containing benzoyl peroxide or chlorhexi- strongly recommended (COE V).
dine) should be recommended once to twiceweekly (COE V).
Problem no. 1: treatment of localized 2 If, in addition to the presence of inflammatory cells, there is a large number of intra- and ⁄ or extracellularbacteria, an oral antibiotic may be required. Oral Case scenario no. 1 antibiotic therapy should ideally be selected based A 6-month-old female West Highland white terrier was on bacterial culture and susceptibility, particularly if presented with three small areas, approximately 5 cm2, the dog has been previously treated with antibiot- of alopecia (Figure 2). Scrapings show numerous adult ics. Alternatively, topical antiseptic therapy can be Demodex mites, larvae and eggs.
used as frequently as daily or every other day.
Scenario 1a: the alopecic areas are slightly scaly with a few comedones.
Problem no. 2: treatment of generalized Scenario 1b: papules, pustules and crusts are promi- nent in the alopecic areas.
Case scenario no. 2 Treatment options for scenario 1a: A 6-month-old male pug is presented with generalized 1 This dog would qualify for localized demodicosis.
hypotrichosis, scaling and multifocal areas of alopecia and Thus, initially simple monitoring of the dog for fur- ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Demodicosis treatment mectin or moxidectin (initially in gradually increasingdoses; COE I) or weekly doramectin (COE III).
Treatment should be chosen based on the legal con-ditions in the respective countries.
3 Monthly skin scrapings should be performed and treatment changed if either clinical signs and ⁄ ormite numbers on skin scrapings have not improvedfrom the last visit. Once clinical and, most impor-tantly, microscopic remission have been achieved,treatment should ideally be continued for a further4–8 weeks (COE V).
4 Close monitoring of dogs for recurrence is recom- mended, particularly during the first 12 months ofremission.
5 Long-term glucocorticoid therapy or other immuno- suppression should be avoided, if at all possible(COE V).
Figure 3. Photograph of the face of a 6-month-old pug with demodi-cosis. Severe alopecia, erythema, erosions, ulcers and crusts can be Treatment options for scenario 2b: 1 The situation may require administration of empiri- cal antibiotic therapy pending culture and suscepti-bility results. Cytology should determine which kindof antibacterial agent has the highest empiricalvalue. Ideally, an aspirate should be taken from anintact pustule for culture and sensitivity testingbefore empirical antibiotic therapy is begun, and acomplete blood count and biochemistry panelshould be obtained. Hospitalization of the dog andadministration of intravenous fluid and antibioticsmay be considered based on the clinical condition ofthe dog and initial laboratory investigation. Once cul-ture results are known, antibiotic therapy may haveto be adjusted. Antimicrobial therapy should be con-tinued for 1–2 weeks after clinical and microscopicresolution of the bacterial skin infection (COE V).
2 Topical antibacterial therapy is indicated to remove bacteria, crusts and inflammatory mediators from Figure 4. Photograph of the preputial area of the pug from Figure 3.
the skin surface (COE V). In some severely affected Alopecia, erythema, papules, pustules and crusts are present.
dogs, it may be necessary to delay topical therapyuntil the dog's systemic signs have improved and Scenario 2a: the alopecic areas are scaly and erythem- the stress of bathing is more easily tolerated.
atous with a few comedones.
3 Miticidal therapy is indicated. Topical amitraz rinses, Scenario 2b: papules, pustules, crusts and copious milbemycin oxime at high doses, oral ivermectin or exudation are prominent in the alopecic areas. An moxidectin (in gradually increasing doses; COE I) or exudative pododermatitis is also present. The dog weekly doramectin (COE III) may all be considered shows lethargy and an increased body temperature based on the legal situation.
(Figures 3 and 4).
4 Initially, the dog ideally should be evaluated weekly until lethargy and increased body temperature have Treatment options for scenario 2a: resolved. Treatment changes should be consideredif neither clinical signs nor mite numbers on skin 1 Cytology and culture of skin lesions should deter- scrapings have changed after a month. Thereafter, mine whether oral antibiotic therapy is needed.
monthly skin scrapings are indicated. Once clinical Even without evidence of an active infection, topical and microscopic remission have been achieved, antibacterial therapy is indicated to minimize the treatment should ideally be continued for a further chance of a secondary bacterial skin infection devel- 4–8 weeks (COE V).
5 Close monitoring of dogs for recurrence is recom- 2 Miticidal therapy is indicated. Topical moxidectin mended, particularly during the first 12 months of weekly is a convenient and safe treatment option that can be recommended for this dog (COE II).
6 Long-term glucocorticoid therapy or other immuno- Other alternatives are amitraz rinses weekly or suppression should be avoided, if at all possible every 2 weeks, oral daily milbemycin oxime, iver- ª 2012 The Authors. Veterinary Dermatologyª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Mueller et al.
20. Saridomichelakis M, Koutinas A, Papadogiannakis E et al. Adult- onset demodicosis in two dogs due to Demodex canis and a The authors would like to thank the involved presidents short-tailed demodectic mite. Journal of Small Animal Practice and board members of the many professional organiza- 1999; 40: 529–532.
tions for their time to review these guidelines and their 21. Bourdeau P. Variation in size in Demodex canis: from the longest support. They are grateful for Kinga Gortel's helpful to the shortest forms. Veterinary Dermatology 2010; 21: 213(Abstract).
suggestions regarding the manuscript.
22. Plant JD, Lund EM, Yang M. A case–control study of the risk fac- tors for canine juvenile-onset generalized demodicosis in the USA. Veterinary Dermatology 2011; 22: 95–99.
23. Duclos DD, Jeffers JG, Shanley KJ. Prognosis for treatment of 1. Olivry T, Mueller RS. Evidence-based veterinary dermatology: a adult-onset demodicosis in dogs: 34 cases (1979–1990). Journal systematic review of the pharmacotherapy of canine atopic der- of the American Veterinary Medical Association 1994; 204: 616– matitis. Veterinary Dermatology 2003; 14: 121–146.
2. Olivry T, Foster AP, Mueller RS et al. Interventions for atopic 24. Lemarie S, Hosgood G, Foil CS. A retrospective study of juvenile- dermatitis in dogs: a systematic review of randomized controlled and adult-onset generalized demodicosis in dogs (1986–1991).
trials. Veterinary Dermatology 2010; 21: 4–22.
Veterinary Dermatology 1996; 7: 3–10.
3. Olivry T, DeBoer DJ, Favrot C et al. Treatment of canine atopic 25. Miller WH Jr, Scott DW, Wellington JR et al. Clinical efficacy of dermatitis: 2010 clinical practice guidelines from the Interna- milbemycin oxime in the treatment of generalized demodicosis tional Task Force on Canine Atopic Dermatitis. Veterinary in adult dogs. Journal of the American Veterinary Medical Asso- Dermatology 2010; 21: 233–248.
ciation 1993; 203: 1426–1429.
4. Moriello KA. Treatment of dermatophytosis in dogs and cats: 26. Garfield RA, Lloyd R. The use of oral milbemycin oxime (Inter- review of published studies. Veterinary Dermatology 2004; 15: ceptor) in the treatment of chronic generalized canine demodico- sis. Veterinary Dermatology 1992; 3: 231–235.
5. Nuttall T, Cole LK. Evidence-based veterinary dermatology: a 27. Scott DW, Miller WH Jr, Griffin CE. Canine demodicosis. Muller systematic review of interventions for treatment of Pseudomo- & Kirk's Small Animal Dermatology. Philadelphia, W.B. Saun- nas otitis in dogs. Veterinary Dermatology 2007; 18: 69–77.
ders, 2001: 457–474.
6. Noli C, Auxilia ST. Treatment of canine Old World visceral leish- 28. Bruzinska-Schmidhalter R, Nett-Mettler CS. Spontaneous remis- maniasis: a systematic review. Veterinary Dermatology 2005; sion in canine generalized demodicosis – predisposing factors.
Veterinary Dermatology 2011; 22: 301 (Abstract).
7. Leung DY, Nicklas RA, Li JT et al. Disease management of ato- 29. Fondati A. Efficacy of daily oral ivermectin in the treatment of 10 pic dermatitis: an updated practice parameter. Joint Task Force cases of generalized demodicosis. Veterinary Dermatology on Practice Parameters. Annals of Allergy, Asthma & Immunol- 1996; 7: 99–104.
ogy 2004; 93: S1–S21.
30. Mueller RS, Meyer D, Bensignor E et al. Treatment of canine 8. Mueller RS. Treatment protocols for demodicosis: an evidence- generalized demodicosis with a ‘spot-on' formulation containing based review. Veterinary Dermatology 2004; 15: 75–89.
10% moxidectin and 2.5% imidacloprid (Advocate!, Bayer 9. Paterson TE, Halliwell RE, Fields PJ et al. Treatment of canine- Healthcare). Veterinary Dermatology 2009; 20: 441–446.
generalized demodicosis: a blind, randomized clinical trial 31. Mueller RS, Bettenay SV. Skin scrapings and skin biopsies. In: comparing the efficacy of Advocate! (Bayer Animal Health) with Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal ivermectin. Veterinary Dermatology 2009; 20: 447–455.
Medicine. Philadelphia, W.B. Saunders, 2010; 368–371.
10. Schnabl B, Bettenay S, Glos N et al. Oral selamectin in the treat- 32. Beco L, Fontaine F, Bergvall K et al. Comparison of skin scrapes ment of canine generalised demodicosis. Veterinary Record and hair plucks for detecting Demodex mites in canine demodi- 2010; 166: 710–714.
cosis, a multicentre, prospective study. Veterinary Dermatology, 11. Henpf Olschewski C. Hat Jeder Hautgesunde Hund Demodex- 2007; 18: 381 (Abstract).
milben? Histologische Untersuchungen von Hautproben. Berlin: 33. Bensignor E. Comparaison de trois techniques diagnostiques de Freie Universita¨t, 1988; 141.
demodecie a Demodex canis chez le chien. Pratique Medicale 12. Greve JH, Gaafar SM. Natural transmission of Demodex canis in and Chirurgicale de l'Animal de Compagnie 2003; 38: 167–171.
dogs. Journal of the American Veterinary Medical Association 34. Fondati A, De LuciaM, Furiani N et al. Prevalence of Demodex 1966; 148: 1043–1045.
canis-positive healthy dogs at trichoscopic examination. Veteri- 13. Chesney CJ. Short form of Demodex species mite in the dog: nary Dermatology 2010; 21: 146–151.
occurrence and measurements. Journal of Small Animal Practice 35. Kwochka KW, Kowalski JJ. Prophylactic efficacy of four antibac- 1999; 40: 58–61.
terial shampoos against Staphylococcus intermedius in dogs.
14. Desch CE, Hillier A. Demodex injai: a new species of hair follicle American Journal of Veterinary Research 1991; 52: 115–118.
mite (Acari: Demodecidae) from the domestic dog (Canidae).
36. Mueller RS. Topical dermatological therapy. In: Maddison JE, Journal of Medical Entomology 2003; 40: 146–149.
Page SW, Church DB, eds. Small Animal Pharmacology. Phila- 15. Hillier A, Desch CE. Large-bodied Demodex mite infestation in 4 delphia, W.B. Saunders, 2008; 546–556.
dogs. Journal of the American Veterinary Medical Association 37. Hugnet C, Bruchon-Hugnet C, Royer H et al. Efficacy of 1.25% 2002; 220: 623–627, 613.
amitraz solution in the treatment of generalized demodicosis 16. Mueller RS, Bettenay SV. An unusual presentation of generalised (eight cases) and sarcoptic mange (five cases) in dogs. Veteri- demodicosis caused by a long-bodied demodex mite in a Lake- nary Dermatology 2001; 12: 89–92.
land Terrier. Australian Veterinary Practitioner 1999; 29: 128–131.
38. Kwochka KW, Kunkle GA, Foil CS. The efficacy of amitraz for 17. Ordeix L, Bardagi M, Scarampella F et al. Demodex injai infesta- generalized demodicosis in dogs: a study of two concentrations tion and dorsal greasy skin and hair in eight wirehaired fox terrier and frequencies of application. The Compendium on Continuing dogs. Veterinary Dermatology 2009; 20: 267–272.
Education for the Practising Veterinarian 1985; 7: 8–17.
18. Robson DC, Burton GG, Bassett R et al. Eight cases of demodi- 39. Medleau L, Willemse T. Efficacy of daily amitraz therapy for cosis caused by a long-bodied Demodex species (1997–2002).
refractory, generalized demodicosis in dogs: two independent Australian Veterinary Practice 2003; 33: 64–72.
studies. Journal of the American Animal Hospital Association 19. Chen C. A short-tailed demodectic mite and Demodex canis 1995; 31: 246–249.
infestation in a Chihuahua dog. Veterinary Dermatology 1995; 6: 40. Muller GH. Amitraz treatment of demodicosis. Journal of the American Animal Hospital Association 1983; 19: 435–441.
ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Demodicosis treatment 41. Mueller RS, Bettenay SV. Milbemycin oxime in the treatment of 59. Roulet A, Puel O, Gesta S et al. MDR1-deficient genotype in Col- canine demodicosis. Australian Veterinary Practitioner 1995; 25: lie dogs hypersensitive to the P-glycoprotein substrate ivermec- tin. European Journal of Pharmacology 2003; 460: 85–91.
42. Fourie LJ, Kok DJ, du Plessis A et al. Efficacy of a novel formula- 60. Bissonnette S, Paradis M, Daneau I et al. The ABCB1-1D mutation tion of metaflumizone plus amitraz for the treatment of is not responsible for subchronic neurotoxicity seen in dogs of demodectic mange in dogs. Veterinary Parasitology 2007; 150: non-collie breeds following macrocyclic lactone treatment for gen- eralized demodicosis. Veterinary Dermatology 2009; 20: 60–66.
43. Rosenkrantz W. Efficacy of metaflumizone plus amitraz for 61. Bensignor E, Carlotti D. Moxidectin in the treatment of general- the treatment of juvenile and adult onset demodicosis in dogs: ized demodicosis in dogs. A pilot study: 8 cases. In: Kwochka pilot study of 24 dogs. Veterinary Dermatology 2009; 20: 227 KW, Willemse T, Von Tscharner C, eds. Advances in Veterinary Dermatology. Oxford, Butterworth-Heinemann, 1998; 554–555.
44. Oberkirchner U, Linder K, Dunston S et al. Metaflumizone–amit- 62. Burrows A. Evaluation of the clinical efficacy of two different raz (Promeris)-associated pustular acantholytic dermatitis in 22 doses of moxidectin in the treatment of generalized demodicosis dogs: evidence suggests contact drug-triggered pemphigus foli- in the dog. Annual Meeting of the Australian College of Veteri- aceus. Veterinary Dermatology 2011; 22: 436–448.
nary Scientists, Goold Coast, Australia, 1997.
45. Holm BR. Efficacy of milbemycin oxime in the treatment of 63. Wagner R, Wendlberger U. Field efficacy of moxidectin in dogs and canine generalized demodicosis: a retrospective study of 99 rabbits naturally infested with Sarcoptes spp., Demodex spp. and dogs (1995–2000). Veterinary Dermatology 2003; 14: 189–195.
Psoroptes spp. mites. Veterinary Parasitology 2000; 93: 149–158.
46. Sasaki Y, Kitagawa H, Murase S. Susceptibility of rough-coated 64. Heine J, Krieger K, Dumont P et al. Evaluation of the efficacy collies to milbemycin oxime. Japanese Journal of Veterinary and safety of imidacloprid 10% plus moxidectin 2.5% spot-on in Science 1990; 52: 1269–1271.
the treatment of generalized demodicosis in dogs: results of a 47. Barbet JL, Snook T, Gay JM et al. ABCB1-1D (MDR1-1D) geno- European field study. Parasitological Research 2005; 97(Suppl type is associated with adverse reactions in dogs treated with 1): S89–S96.
milbemycin oxime for generalized demodicosis. Veterinary Der- 65. Fourie JJ, Delport PC, Fourie LJ et al. Comparative efficacy and matology 2009; 20: 111–114.
safety of two treatment regimens with a topically applied combi- 48. Scott DW, Walton DK. Experiences with the use of amitraz and nation of imidacloprid and moxidectin (Advocate!) against ivermectin for the treatment of generalized demodicosis in dogs.
generalised demodicosis in dogs. Parasitological Research 2009; Journal of the American Animal Hospital Association 1985; 21: 105(Suppl 1): S115–S124.
66. Johnstone IP. Doramectin as a treatment for canine and feline de- 49. Ristic Z, Medleau L, Paradis M et al. Ivermectin for treatment of modicosis. Australian Veterinary Practitioner 2002; 32: 98–103.
generalized demodicosis in dogs. Journal of the American Veteri- 67. Murayama N, Shibata K, Nagata M. Efficacy of weekly oral dora- nary Medical Association 1995; 207: 1308–1310.
mectin treatment in canine demodicosis. Veterinary Record 50. Guaguere E. Traitement de la demodecie generalisee du chien 2010; 167: 63–64.
par l'ivermectine: a propos de 20 cas. Pratique Medicale et Chir- 68. Schnieder T, Kordes S, Epe C et al. Investigations into the urgicale de l'Animal de Compagnie 1996; 31: 31–40.
prevention of neonatal Toxocara canis infections in puppies by 51. Medleau L, Ristic Z, McElveen DR. Daily ivermectin for the treat- application of doramectin to the bitch. Zentralblatt fu¨r Veterina¨r- ment of generalized demodicosis in dogs. Veterinary Dermatol- medizin. Reihe B 1996; 43: 35–43.
ogy 1996; 7: 209–212.
69. Schnieder T, Lechler M, Epe C et al. The efficacy of doramectin on 52. Mueller RS, Hastie K, Bettenay SV. Daily oral ivermectin for the arrested larvae of Ancylostoma caninum in early pregnancy of treatment of generalised demodicosis in 23 dogs. Australian Vet- bitches. Zentralblatt fu¨r Veterina¨rmedizin. Reihe B 1996; 43: 351– erinary Practitioner 1999; 29: 132–136.
53. Delayte EH, Otsuka M, Larsson CE et al. Efficacy of systemic 70. Lavy E, Aroch I, Bark H et al. Evaluation of doramectin for the macrocyclic lactones (ivermectin and moxidectin) for the treat- treatment of experimental canine spirocercosis. Veterinary Para- ment of generalized canine demodicosis. Arquivo Brasileiro de sitology 2002; 109: 65–73.
Medicina Veterina´ria e Zootecnia 2006; 58: 31–38.
71. Yas-Natan E, Shamir M, Kleinbart S et al. Doramectin toxicity in 54. Mueller RS, Bettenay SV. A proposed new therapeutic a collie. Veterinary Record 2003; 153: 718–720.
protocol for the treatment of canine mange with ivermectin.
72. Geyer J, Klintzsch S, Meerkamp K et al. Detection of the Journal of the American Animal Hospital Association 1999; 35: nt230(del4) MDR1 mutation in White Swiss Shepherd dogs: case reports of doramectin toxicosis, breed predisposition, and 55. Hugnet C, Lespine A, Alvinerie M. Multiple oral dosing of ketoco- microsatellite analysis. Journal of Veterinary Pharmacology and nazole increases dog exposure to ivermectin. Journal of Phar- Therapeutics 2007; 30: 482–485.
macy and Pharmaceutical Sciences 2007; 10: 311–318.
73. Miller WH Jr, Wellington JR Scott DW. Dermatologic disorders of 56. Mayer UK, Glos K, Schmid M et al. Adverse effects of ketoco- Chinese Shar Peis: 58 cases (1981–1989). Journal of the Ameri- nazole in dogs – a retrospective study. Veterinary Dermatology can Veterinary Medical Association 1992; 200: 986–990.
2008; 19: 199–208.
74. Hamann F, Wedell H, Bauer J. Zur Demodikose des Hundes.
57. Mealey KL, Bentjen SA, Gay JM et al. Ivermectin sensitivity in Kleintierpraxis 1997; 42: 745–754.
collies is associated with a deletion mutation of the mdr1 gene.
75. Folz SD, Kratzer DD, Conklin RD et al. Chemotherapeutic treat- Pharmacogenetics 2001; 11: 727–733.
ment of naturally acquired generalized demodicosis. Veterinary 58. Mealey KL, Meurs KM. Breed distribution of the ABCB1-1D Parasitology 1983; 13: 85–93.
(multidrug sensitivity) polymorphism among dogs undergoing 76. Anon. Dermatologists recommend neutering of canine patients ABCB1 genotyping. Journal of the American Veterinary Medical with demodicosis. Journal of the American Veterinary Medical Association 2008; 233: 921–924.
Association 1983; 182: 1048.
ª 2012 The Authors. Veterinary Dermatologyª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Mueller et al.
Appendix 1: Summarized treatment of canine demodicosis Treatment of a dog with localized and mild to moderate disease 1 Use topical therapy with chlorhexidine or benzoyl peroxide shampoo weekly.
2 Monitor the disease progression. Many dogs will show resolution of clinical signs. Dogs with deteriorating disease should be treated as described below.
Treatment of a dog with severe generalized disease 1 Perform cytology and (with evidence of secondary bacterial skin infection) ideally a bacterial culture and sensitivity.
With inflammatory cells and bacteria present, appropriate oral antibiotic therapy is recommended.
2 Use topical therapy with chlorhexidine or benzoyl peroxide shampoo weekly to possibly twice weekly.
3 Several options exist for the treatment of the Demodex mites and which option is best will depend on the legalities pertaining to the use of veterinary pharmaceutical products in the country of residence, the finances of the owner andthe clinical situation. However, independent of the treatment specifics the dog should be neutered because dogs inneed of mite treatment should not be alllowed to breed, and the disease may relapse in cycling bitches.
a Amitraz weekly or every 2 weeks in a concentration of 0.025–0.06% can be used. Dogs with a mid to long hair coat need to be clipped, and skin should stay dry between rinses to avoid washing off the drug. Rinsing should beperformed in well-ventilated areas.
b Milbemycin oxime may be administered orally at a dose of 1–2 mg ⁄ kg ⁄ day.
c Moxidectin as a spot-on in combination with imidacloprid may be used weekly. This spot-on formulation has a markedly higher success rate in dogs with milder disease.
d Ivermectin at a dose of 0.3–0.6 mg ⁄ kg or moxidectin at 0.2–0.5 mg ⁄ kg p.o. daily are further options. With both drugs, a gradual increase from an initial dose of 0.05 mg ⁄ kg to the final dose within a few days is recommended toidentify dogs that cannot tolerate those drugs. Monitoring for neurological adverse effects should occur through-out the course of therapy.
e Doramectin weekly at 0.6 mg ⁄ kg p.o. or s.c. is a possible treatment. A gradual increase from an initial dose of 0.1 mg ⁄ kg to the final dose seems prudent to identify dogs that cannot tolerate the drug and will show neurologi-cal adverse effects.
f Dogs should be evaluated monthly, and treatment should be continued beyond negative skin scrapings.
g Factors predisposing to demodicosis, such as malnutrition, endoparasites, endocrine disease, neoplasias and che- motherapy, should be identified and corrected to maximize response to therapy.
ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Demodicosis treatment La de´mode´cie canine est fre´quente en pratique des petits animaux et il existe un certain nom- bre de traitements possible. Ces recommandations ont e´te´ e´crites par un groupe international de spe´cial-istes avec l'objectif de les fournir aux ve´te´rinaires pour le diagnostic et le traitement de cette maladie. Lese´tudes publie´es sur les diffe´rentes options de traitement ont e´te´ examine´es et re´sume´es. Lorsque lespreuves n'e´taient pas disponibles pour certaines publications, un consensus d'experts formait la base desrecommandations. La de´mode´cie est ge´ne´ralement diagnostique´e par raclages cutane´s profonds ou partrichogrammes ; dans de rares cas une biopsie cutane´e peut eˆtre requise. Les facteurs compromettants lesyste me immunitaire, tels que l'endoparasitisme ou la malnutrition chez les jeunes chiens, les dysendocri-nies, les tumeurs et la chimiothe´rapie chez les vieux chiens, sont conside´re´s comme des facteurs pre´dis-posants et devraient eˆtre diagnostique´s et traite´s afin d'optimiser les re´sultats the´rapeutiques. Les chiensdont la se´ve´rite´ de la maladie ne´cessite un traitement antiparasitaire ne devraient pas eˆtre reproduits. Lesinfections bacte´riennes cutane´es secondaires compliquent fre´quemment la maladie et ne´cessitent un trait-ement antimicrobien topique et ⁄ ou syste´mique. Dans le traitement de la de´mode´cie canine, le niveau depreuve est bon concernant l'efficacite´ de bains hebdomadaires d'amitraz a 250–500 p.p.m. et l'administra-tion orale quotidienne de lactones macrocycliques telles que la milbe´mycine oxime a 1–2 mg ⁄ kg, l'iver-mectine a 0.3–0.6 mg ⁄ kg et la moxidectine a 0.2–0.4 mg ⁄ kg. L'application hebdomadaire de moxidectinetopique peut eˆtre utile chez les chiens pre´sentant une forme mode´re´e de la maladie. Il existe certainespreuves de l'efficacite´ de la doramectine sous-cutane´e ou orale, hebdomadaire ou bihebdomadaire a 0.6 mg ⁄ kg. Les lactones macrocycliques syste´miques peuvent engendrer des effets secondaires neuro-logiques chez les chiens sensibles ; il serait prudent d'augmenter la dose progressivement jusqu'a la dosefinale the´rapeutique (en particulier chez les bergers) afin de mettre en e´vidence les chiens ne tole´rant pasces mole´cules. Le traitement doit eˆtre controˆle´ par des raclages cutane´s mensuels et doit eˆtre prolonge´ audela de la gue´rison clinique et microscopique afin de minimiser les re´cidives.
La demodicosis canina es frecuente en las consultas de pequen˜os animales y existen varias terapias posibles. Estas directrices han sido escritas por un grupo internacional de especialistas con elpropo´sito de proporcionar a los veterinarios las recomendaciones mas actuales para el diagnostico y el tra-tamiento de esta enfermedad. Se revisaron y resumieron los estudios publicados donde se exponı´an diver-sas opciones de tratamiento. En los casos en que no habı´a clara evidencia del tratamiento en forma deestudios publicados, la base de las recomendaciones fue el consenso de los expertos. La demodicosis pu-ede ser generalmente diagnosticada mediante raspados profundos de la piel o en tricogramas; y en casosraros una biopsia de la piel podrı´a ser necesaria para el diagnostico. Factores que comprometen el sistemainmune, tal como el endoparasitismo o la malnutricio´n en perros jo´venes y enfermedades endocrinas, neo-plasia y quimioterapia en perros ma´s viejos, se consideran elementos que favorecen la infeccio´n y sedeben diagnosticar y tratar para optimizar el resultado terape´utico. Los perros con enfermedad severa querequiere terapia parasiticida no deben ser utilizados con propo´sito de crı´a. Las infecciones bacterianassecundarias en la piel complican la enfermedad y requieren con frecuencia terapia antimicrobiana to´picay ⁄ o siste´mica. Hay clara evidencia al respecto de la eficacia de los lavados semanales con amitraz a250–500 p.p.m. y del tratamiento diario con lactonas macrocı´clicas orales tales como la oxima demilbemicina a 1–2 mg ⁄ kg, la ivermectina a 0.3–0.6 mg ⁄ kg y la moxidectina a 0.2–0.4 mg ⁄ kg para eltratamiento de la demodicosis canina. El uso semanal de moxidectin por vı´a to´pica puede ser u´til en perroscon formas ma´s leves de la enfermedad. Hay cierta evidencia relativa a la eficacia del semanal o dos vecesen semana de doramectina subcuta´nea u oral a dosis de 0.6 mg ⁄ kg. Las lactonas macrocı´clicas por vı´asiste´mica pueden causar efectos nocivos neurolo´gicos en perros sensibles, por lo que un aumento gradualhasta la dosis terape´utica final podrı´a ser prudente (particularmente en razas de perros pastores) paraidentificar con prontitud los perros que no toleran esos fa´rmacos. El tratamiento se debe supervisar conraspados mensuales de la piel y debe extenderse pasada la curacio´n clı´nica y microsco´pica para reducir almı´nimo las recidivas.
Die canine Demodikose ist eine ha¨ufige Erkrankung in der Kleintierpraxis mit mehr- eren Therapiemo¨glichkeiten. Diese Richtlinien wurden von einer internationalen Gruppe von Spezialistenmit dem Ziel, Tiera¨rztInnen die momentanen Empfehlungen zur Diagnose und zur Therapie der Erkrankungzur Verfu¨gung zu stellen, geschrieben. Die publizierten Studien der unterschiedlichen Behandlungsmetho-den wurden ‘reviewed' und zusammengefasst. Wo keine Evidenz in Form von publizierten Studienbestand, wurde der Consensus der ExpertInnen als Basis fu¨r die Empfehlungen herangezogen. Die canineDemodikose kann normalerweise mittels tiefer Hautgeschabsel oder Trichgramm diagnostiziert werden; inseltenen Fa¨llen ist fu¨r die Diagnose eine Hautbiopsie no¨tig. Faktoren, die das Immunsystem beeintra¨chti-gen, wie Endoparasiten oder schlechte Erna¨hrung bei Junghunden, sowie endokrine Erkrankungen,Neoplasien und Chemotherapie bei a¨lteren Hunden werden als pra¨disponierende Faktoren angesehen undsollten diagnostiziert und behandelt werden, um den Therapieerfolg zu optimieren. Mit Hunden, die dieErkrankung in einem Schweregrad aufweisen, die eine Therapie mit Antiparasitika notwendig macht, solltenicht gezu¨chtet werden. Sekunda¨re bakterielle Infektionen verkomplizieren ha¨ufig die Erkrankung underfordern eine topische und ⁄ oder systemische antimikrobielle Behandlung. Es besteht eine gute Evidenzfu¨r die Wirksamkeit von wo¨chentlichen Amitraz Ba¨dern in einer Dosierung von 250–500 p.p.m. und ta¨gli- ª 2012 The Authors. Veterinary Dermatologyª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
Mueller et al.
che orale Verabreichung von makrozyklischen Laktonen, wie Milbemycinoxim in einer Dosierung von1–2 mg ⁄ kg, Ivermectin in einer Dosierung von 0.3–0.6 mg ⁄ kg und Moxidectin in einer Dosierung von0.2–0.4 mg ⁄ kg zur Behandlung der caninen Demosikose. Eine wo¨chentliche topische Verabreichungvon Moxidectin kann bei Hunden mit einer weniger stark ausgepra¨gten Erkrankung hilfreich sein. Teilweisebesteht Evidenz fu¨r die Wirksamkeit wo¨chentlicher oder zweimal wo¨chentlicher subkutaner oder oralerVerabreichung von Doramectin in einer Dosierung von 0.6 mg ⁄ kg. Systemisch verabreichte makrozykli-sche Laktone ko¨nnen bei empfa¨nglichen Hunden neurologische Nebenwirkungen verursachen, daher istals Vorsichtsmaßnahme ein gradueller Anstieg der Dosierung bis zur letztendlich verabreichten Dosis (vorallem bei Herdenhunden) sinnvoll, um jene Hunde zu identifizieren, die diese Wirkstoffe eventuell nicht tol-erieren ko¨nnen. Die Behandlung sollte monatlich durch Hautgeschabsel kontrolliert werden und um Ru¨ck-fa¨lle zu vermeiden, u¨ber eine klinische sowie eine mikroskopische Heilung hinaus gegeben werden.
ª 2012 The Authors. Veterinary Dermatology ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 86–e21.
AAHPM Special Article Five Things Physicians and Patients ShouldQuestion in Hospice and Palliative MedicineDaniel Fischberg, MD, PhD, Janet Bull, MD, David Casarett, MD, MA, MMM,Laura C. Hanson, MD, MPH, Scott M. Klein, MD, MHSA,Joseph Rotella, MD, MBA, Thomas Smith, MD, C. Porter Storey Jr., MD,Joan M. Teno, MD, MS, and Eric Widera, MD, for the AAHPM ChoosingWisely Task ForceDepartment of Geriatric Medicine (D.F.), John A. Burns School of Medicine, University of Hawaii,Honolulu, Hawaii; Four Seasons (J.B.), Flat Rock, North Carolina; University of PennsylvaniaHealth System (D.C.), Philadelphia, Pennsylvania; Division of Geriatric Medicine and University ofNorth Carolina Palliative Care Program (L.C.H.), University of North Carolina-Chapel Hill, ChapelHill, North Carolina; Hospice and Palliative Care (S.M.K.), Visiting Nurse Service of New York, NewYork, New York; Hosparus (J.R.), Louisville, Kentucky; Johns Hopkins Medical Institutions andSidney Kimmel Comprehensive Cancer Center (T.S.), Baltimore, Maryland; American Academy ofHospice and Palliative Medicine (C.P.S.), Glenview, Illinois; Warren Alpert School of Medicine(J.M.T.), Brown University, Providence, Rhode Island; and Division of Geriatrics (E.W.), University ofCalifornia-San Francisco, San Francisco, California, USA