7/22/2019

Demodicosis of the - Diagnostic Tips and Plan for today’s lecture

Updates on Treatment  Brief overview of canine  Diagnostic tips Lindsay McKay, DVM, DACVD  Updates on therapy and case management VCA- Arboretum View Hospital  “Guideline for Treatment of Canine Demodicosis” from the World Association for Veterinary Dermatology Consensus Statement (work in progress)

Demodex of the dog- 2 species Canine demodicosis injai-  Frequent and often severe parasitic disease distinct  In the USA, as many as 0.58% (or about 500,000) of species suffer from generalized form  #1 Risk Factor- BREED

Demodex canis and short bodied Demodex- morphologic variant of D. canis

• Published studies report similar treatment efficacies regardless of species of Demodex

Skin scrapings Clinical Signs  Focal (paws) to multifocal to coalescing lesions involving large areas of the body  Deep enough for capillary ooze for follicular  Locations- head, legs/paws, demodicosis neck, trunk  Follicular papules and pustules, alopecia, erythema, comedones, follicular casting, scaling  With pyoderma, see edema, crusts, patches and plaques of disease (furunculosis) Bayer  Variable pruritus, lethargy, fever Meckes, Science Source

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Hair Plucks Hair plucks- 85% sensitivity compared to scraping1  If negative, need to perform scraping  Positive trichograms are rare in dogs

 For sensitive areas that are hard to scrape  Pluck 1 cm2 (want 50-100 Courtesy of Ken Mason 1. Saridomichelakis MN, et al. Relative sensitivity of hair pluckings and exudate microscopy for the diagnosis of canine demodicosis. hairs) Vet Dermatol. 2007 Apr;18(2):138-41

Increase contrast Systematic Examination of the Slide at 10x is critical High light High condenser  For microscopy of any be sure to lower the condenser and decrease the light

Low light Low condenser

For canine demodicosis, it is important to perform accurate mite counts!

Katrine Voie, Clinician’s Brief, June 2017

Lola- 6 month old Physical exam findings •Transferred to the ER  T- 103.5, HR- 100, RR- 32, mm- pink, CRT< 2 service for fluid support  General PE- abnormalities included- increased and IV submandibular and prescrapular LN and low BCS •Demodicosis was (3/9) diagnosed by primary vet, treatment initiated with  Derm PE- cellulitis of the face with intact pustules 10 days ago present and hemopurulent discharge, deep •Two days ago, severe facial pyoderma of the chest, generalized erythema with swelling and draining a papular to pustular rash, moth eaten alopecia lesions developed

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Physical exam findings Physical exam findings

Physical exam findings Diagnostic findings and plan  CBC, Chemistry- WNL • Treatment plan  Deep skin scrapings, hair Ivermectin- 0.3 mg/kg/day pluckings- confirmed  * If seeing today, I would add demodex- 50% live an isoxazoline , all life stages, Simplicef- 7 mg/kg/day TNTC at all locations Soaks of face with dilute  Skin cytology- 4+ cocci chlorhexidine daily bacteria Twice weekly baths with  Culture- Staphylococcus medicated shampoo and pseudintermedius- conditioner sensitive to cefpodoxime Carprofen for pain relief

Why did this happen? Back to Lola- Recheck 1  Juvenile-onset demodicosis  Lola’s facial swelling is greatly reduced; no further can lead to deep pyoderma drainage and cellulitis  She is no longer febrile; she is eating, drinking and  Rupture of hair follicles laden acting more like her self with mites and bacteria lead to furunculosis and then  Progression of her hair loss, especially on her chest potentially to cellulitis  Owner reports a recurrence of red rash on groin and  Can be a deadly complication paws over the last few days of demodicosis if progresses to septicemia

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Physical exam findings Diagnostic findings and plan  Derm PE- erythema,  Deep skin scrapings- • Treatment plan hyperpigmentation, 30% live mites, more Ivermectin- 0.4 mg/kg/day- alopecia and crusting on eggs, slight decrease in also note increased weight face and chest; moth overall mite count gain! eaten hair loss on trunk  Skin cytology- 1-2+ cocci Clindamycin (11 mg/kg BID) with occasional papules; bacteria on groin Twice weekly baths with prominent papules and  Culture-methicillin- medicated shampoo and pustules on groin and resistant Staphylococcus conditioner paws; nodules and pseudintermedius- Recheck in 4 weeks plaques also present on sensitive to clindamycin groin

Lola- Recheck 2 Physical exam findings  She is much improved!  Derm PE- resolution of papular/pustular rash on paws; resolving lesions on groin, resolving alopecia, erythema and hyperpigmentation on head and trunk  DSS- all adult dead mites, 1-2 mites present on groin, trunk and front paw, BUT only 20% decrease in mite count on head  Cytology- rare # cocci bacteria present  Plan- increase ivermectin to 0.45 mg/kg/day, continue antibiotics and topicals as before

Lola- 3 months later.. Lola- Recheck 3  Lola continues to improve  Derm PE- resolution of papular rash on groin, resolving alopecia and hyperpigmentation on head, paws and trunk  DSS- significant reduction in mite numbers- 1-3 mites total on head, paw, trunk and groin; all dead adult mites  Skin cytology- negative  Plan- continue at current dose of ivermectin, continue antibiotics and topicals as before, owner to follow up with rDVM

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Juvenile-onset demodicosis Juvenile-onset demodicosis  Onset- usually 3-18 months of age  In young dogs, demodicosis has a hereditary basis and  Demodicosis is thought to be primarily due to a most likely multiple genes are involved decreased cell-mediated immunity  Do not breed dogs with generalized demodicosis  Dogs have a normal humoral immunity  Studies have shown 4X increase in certain breeds-  This is presumed to be temporary effect on immune Affenpinscher, Briard, Dogue de Bordeaux, English system in young dogs , Pit , , WHWT and

Jackson- 12 year old Beagle Jackson- 12 year old Beagle  Second opinion for licking the paws, no response to  Derm PE- alopecia, multiple courses of antibiotics and steroids hyperpigmentation,  History- owner reports over the last 6 months, Jackson comedones, draining has started to lick his paws, they occasionally drain deep pyoderma, papules bloody fluid; he also has a similar lesion on his ventral and pustules present; neck lesions on head, legs and ventrum  Owner also reports recent onset of increased thirst and urination (prior to use of steroids)  PE- mild hepatomegaly  No prior history of skin disease or medical illness  T- 103.5; HR-120; RR- 32  Current meds- prednisone and amoxicillin

Clinical photos More clinical photos…

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Diagnostic findings Therapeutic plan  CBC, Chemistry, Urinalysis- leukocytosis (13,440/ul),  Simparica (sarolaner) 40 mg tablet monthly hyperglobulinemia (5.6g/dl), elevated cholesterol (341  Simplicef (cefpodoxime)- 8 mg/kg/day mg/dl) and ALP (640 IU/L), low USG (1.010),  Twice weekly bathing with benzoyl peroxide shampoo proteinuria (3+)  Recheck in 30 days  Deep skin scrapings- numerous Demodex canis mites-  adult, juvenile and eggs, 50% live mites Plan- work up for Cushing’s at next exam  Skin cytology- 1-2+ cocci bacteria from the head, neck and legs  Skin culture- methicillin-sensitive Staphylococcus pseudintermedius-sensitive to cefpodoxime, cephalexin

Recheck exam 1  PE- improvement of clinical signs  SIMPARICA IMPORTANT SAFETY INFORMATION: Simparica is for use only in dogs, 6 months of age and older. Simparica may  Deep skin scraping- 75% reduction in mite numbers, all cause abnormal neurologic signs such as tremors, unsteadiness, dead and adult and/or seizures. Simparica has not been evaluated in dogs that are pregnant, breeding, or lactating. Simparica has been safely used in  Skin cytology- rare # cocci bacteria- legs, head/neck dogs treated with commonly prescribed vaccines, parasiticides,  ACTH stimulation test- elevated cortisol (31.6 ug/dl; and other medications. The most frequently reported adverse reactions were vomiting and diarrhea. See full Prescribing normal- 8-17 ug/dl); consistent with Cushing’s Information.  Abdominal ultrasound- bilaterally enlarged adrenal glands  SIMPLICEF IMPORTANT SAFETY INFORMATION: People with known hypersensitivity to penicillin or cephalosporins should  Endogenous ACTH- elevated, consistent with pituitary avoid exposure to SIMPLICEF. Do not use in dogs with known dependent Cushing’s allergy to penicillins or cephalosporins. See full Prescribing  PLAN- continue Simparica, Simplicef, and treat Information. Cushing’s! Follow up similar to Lola’s.

Jake- 6 year old Labrador Adult-onset demodicosis Retriever  Associated with  Previously diagnosed  Predisposing factors: o Cushing’s disease with seasonal atopic dermatitis o Hypothyroidism  Treated with o Neoplasia combination of oral o Borne diseases steroids, antihistamines o GC therapy and topical therapy o Chemotherapy  Presenting with a 2 o AD? month history of severe • Idiopathic- more than greasiness of the back 30% of cases

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Diagnostic findings  Deep skin scrapings-  Demodex injai is a long numerous Demodex injai bodied demodex mite of mites the dog. The mites  Skin cytology- occ cocci occupy the hair follicles bacteria and the sebaceous  Fungal culture- negative glands. A dog can have both D. injai and D. canis.  CS- GREASY BACK, also erythema, comedones and alopecia

Relationship between Back to Jake Demodex canis and bacteria  Steroids likely  Follow-up- 2 months of  Performing skin cytology is important contributed to Simparica and first demodicosis negative scraping  Secondary Staphylococcus infections are common  Treatment plan- treat  Good response to ASIT  If deep pyoderma is present, can also have infections with Pseudomonas and Proteus, etc. Skin culture is with Simparica, manage  NO steroids secondary infection with recommended! Simplicef  Manage secondary bacterial skin infections with both  Recommend IDT and topical and systemic therapy ASIT for management of  Benzoyl peroxide based products have advantage of his atopic dermatitis being degreasing, follicle flushing and antibacterial

Treatment of canine generalized Consensus Statements- Effective demodicosis Treatments for Canine Demodicosis  There is not a placebo controlled trial assessing treatments for demodicosis, thus the rate of  Weekly amitraz rinses at 0.025%-0.05%, long-haired spontaneous remission is not known should be clipped  The prognosis is good with the majority of cases  Oral Ivermectin at 0.3-0.6 mg/kg/day achieving long term remission. But, dogs with an  Milbemycin at 1-2 mg/kg/day incurable or poorly controlled underlying disease may never be cured and may require long term therapy  Isoxazolines- “preliminary data is very encouraging, this is a promising treatment option”  Idiopathic adult onset cases likely will need maintenance therapy  “Guideline for Treatment of Canine Demodicosis” from the World Association for Veterinary Dermatology Consensus Statement (work in progress)

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Ivermectin Ivermectin toxicity  Macrocyclic lactone, avermectin  Causes  Off label but ivermectin is an FDA approved drug o Acute overdose  Was my drug of choice, would now pair with isoxazoline o Elevated serum concentration following long term for severe cases administration  Demodicosis dose- 300-600 μg/kg/day (0.3-0.6 mg/kg) o Breed susceptibility related to ivermectin sensitivity  Start at low end of dose and increase as needed o Idiosyncratic neurotoxicity- non ivermectin-sensitive  Juvenile and adult-onset: 68% clinical and microscopic breeds remission with relapse rate of 18%1  Newer study showed 98% response rate2 1. Mueller RS, Treatment protocols for demodicosis: an evidenced based review, Veterinary Dermatology, 2004; 15 2. Paterson TE, Halliwel RE, et al. Treatment of canine-generalized demodicosis: a blind, randomized clinical trial comparing the efficacy of Advocate with Ivermectin. Vet Derm 2009; 20

Ivermectin Sensitivity  In ivermectin-sensitive herding breeds (, Shelties Ivermectin Sensitivity etc), there is deletion of gene that encodes for  Herding breeds are sensitive to the macrocyclic P-glycoprotein (MDR1 mutation) lactones above a certain dose  P-glycoprotein is a drug efflux pump found in the intestine,  Ivermectin- greater than 100μg/kg kidney, liver and the endothelial cells of the blood brain barrier  Testing can be done at Washington State Univ.  It pumps toxic xenobiotics from the body thereby preventing their access to cells/tissue  When protein is absent, ivermectin can access the brain leading to toxicity  CS- depression, mydriasis, tremors, ataxia, hypersalivation, seizures, coma, death

Updates on new treatments: Ivermectin Dosing Instructions Isoxazolines  Recommend to start with dose around 0.05 mg/kg on  MOA: inhibit Chloride Day 1, then 0.1 mg/kg Day 2, followed by incremental gated GABA channels dose increases of 0.1 mg/kg/day until final dose is  Not selective for mammalian achieved (0.3-0.6 mg/kg/day) GABA receptors  Monitor for drunken walking, change in pupil size,  Simparica (Sarolaner) lethargy, seizures or any other unusual behavior  Bravecto (Fluralaner) changes  NexGard (Afoxolaner)  Drug interactions- avoid using with other P glycoprotein substrates- ketoconazole, cyclosporine;  Credelio (Lotilaner) also reported with spinosad (Comfortis)

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What about new FDA warning? Simparica (Sarolaner)

 FDA statement: 9.21.18 “FDA is alerting…of potential  Pork liver flavored chewable tablet for neurologic adverse events in dogs and cats when  Can be given with or without food treated with drugs that are in isoxazoline class.”  Kills , for 1 month (EU label includes ear  “The FDA considers products in the isoxazoline mites, and Demodex) class to be safe and effective.”  Can be given in dogs ≥ 6 months of age and ≥ 2.8  Neurologic side effects are considered very rare- less pounds than 1 per 10,000 dogs treated  Field safety studies showed GI upset in 3.5% of dogs,  Neurologic side effects include seizures and can occur lethargy in 2.5% of dogs in pets without history of seizures  A low # of dogs in 3X and 5X study groups exhibited  This warning already existed on some product’s label- neurologic side effects, none in label dose group, there this is not really new! is precautionary statement on label

Simparica  Pilot study of 16 dogs with generalized Bravecto (Fluralaner) demodicosis, 99.8% reduction in mite counts 29  Pork flavored hydrolyzed chewable 0r topical days after treatment and 100% at 2 months1  Oral absorption is increased if given with food  Study of 53 dogs with generalized demodicosis, 95%  Kills fleas and ticks for 12 weeks reduction in mite counts after 2 months and 100%  My dosing protocol- q 1-3 months for Demodicosis 2 reduction after 5 months of treatment  Labeled for dogs ≥ 6 months of age and ≥ 4.4 pounds  No adverse effects seen  Safety studies for Bravecto- GI upset reported in about  Conclusion- Simparica is safe and effective for 5-7% of dogs demodicosis  Given to ivermectin sensitive collies at three times 1. Six RH. Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp. and Otodectes cynotis. Vet Parasit. May 2016 clinical dose and no side effects; no risk for herding 2. Becskei C. Efficacy and safety of sarolaner against generalized demodicosis in dogs in breeds with MDR1 mutation European countries: a non-inferiority study. Vet Dermatol. June 2018

Bravecto  Study of 163 dogs with generalized demodicosis (63% juvenile onset and 37% adult onset)1 NexGard (Afoxolaner)  Dogs were treated with fluralaner (25 mg/kg) orally, twice three  Beef flavored months apart. Dogs with secondary pyoderma received cephalexin (30 mg/kg BID)  Can be given with or without food  87.1% had negative skin scrapings one month after first dose. 12.9% of  Kills fleas and ticks for 1 month adult onset group needed two months after first dose to achieve  negative scrapings. The overall response to therapy was 100% at 2 Can be given in dogs ≥ 8 weeks of age, ≥ 4 pounds months. No adverse effects were observed  Field safety studies showed GI upset in 3-4% of dogs,  Study of 67 dogs (31% juvenile onset, 69% adult onset)- 100% of dry flaky skin in 3% of dogs juvenile onset negative at 2 months and 100% of adult onset negative at  3 months2 3 dogs in field study had history of seizures and 2/3  Results suggest Bravecto is an effective, safe and convenient treatment had a seizure during the course of the study option for dogs with generalized demodicosis

1. Karas-Teczca J, et al. Efficacy of fluralaner for the treatment of canine demodicosis. Vet Dermatol 2015 2. NAVDF Abstract- 2017, Duangkaew L, et al. Efficacy of oral fluralaner for the treatment of generalized demodicosis in dogs from Bangkok, Thailand.

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NexGard  Study of 102 dogs with generalized demodicosis (33% Credelio (Lotilaner) juvenile onset and 67% adult onset)1  Beef flavored  Dogs were treated with afoxolaner (2.5 mg/kg) orally, every 14 days for first 10 dogs and then monthly for remainder  Can be given with or without food  90% had negative skin scrapings 2 months after first dose  Kills fleas and ticks for 1 month  The overall response to therapy was 100% at 3 months. No  Can be given in dogs ≥ 8 weeks of age, ≥ 4.4 pounds adverse effects were observed  Label cautions using in dogs with history of seizures  1 dog needed to continue treatment every 14 days, this  Field studies show that weight loss, increased BUN, was dog with PF on immunosuppressive therapy polyuria, diarrhea occurred in low # dogs  Results suggest NexGard is an effective and safe treatment option for dogs with generalized demodicosis

1. Mueller RS, Shipstone MA. Update on the diagnosis and treatment of canine demodicosis. Advances in Veterinary Dermatology 2017.

Prognosis and Future Outlook Credelio  What does use of isoxazolines mean for the future incidence of demodicosis?  Field study of 10 dogs with generalized demodicosis,  Study of 15 bitches known to throw litters with pups 1 treated at day 0, 28 and 56 with Credelio that develop demodicosis were treated with Bravecto  9/10 dogs were mite free at day 28 10 days prior to mating and then 3 months later1  1 dog had low # of live mites at day 56, but was mite  14/15 litters did not develop demodicosis when free by day 70 followed for 12 months; 2 pups of 1 litter developed  This pilot study suggests similar efficacy of Credelio only localized demodicosis for demodicosis compared to other drugs of the class  Preventative strategy……  Still consensus is that dogs with demodicosis should not be bred 1. Snyder DE, et al. Efficacy of lotilaner, a novel oral isoxazoline against naturally occurring mite infestations in dogs caused by Demodex spp. Parasites and Vectors; 2017:10. 1. Mueller RS, Shipstone M. Update on the diagnosis and treatment of canine demodicosis. 8th World Congress of Veterinary Dermatology 2016;206-209.

What about effects on normal Last thought- maintenance flora? therapies  Demodex is part of normal cutaneous microbiota  Majority of adult-onset cases are not stable without  What is the impact of isoxazolines on this population continued maintenance therapies as it may have a role in innate defenses?  Use of isoxazolines may offer advantage of parasite  Preliminary study suggests that if healthy dogs are control for Demodex along with prevention of other treated at label doses for fleas/ticks with Bravecto and parasitic diseases including fleas, ticks, ear mites, etc. NexGard that they still maintain Demodex populations1  The future- NexGard Spectra (Afoxolaner/ Milbemycin) released in Europe for treatment of fleas,  But no studies in affected dogs, more research needs to ticks, heartworm, nematode infestation! Will be done combination lead to additive effects against Demodex? 1. ZeweCM, et al. Afoxolaner and fluralaner treatment do not impact on cutaneous Demodex populations of healthy dogs. Vet Dermatol 2017.

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