TREATING LOCALIZED CANINE DEMODICOSIS
Fortunately, juvenile-onset localized demodicosis resolves spontaneously within one or two months in most dogs. Thus, miticidal
therapy is not required unless the disease generalizes. It is important not to use mite-specific therapy in cases of localized
disease in order to determine which patients progress to generalized disease. By not treating localized cases with miticidal
therapies, dogs developing generalized disease can be identified and eliminated from breeding programs given the genetic basis
of this disease. Furthermore, mite-specific therapy has potential side effects and presents an unnecessary risk in patients
with potentially self-curing disease.
Localized demodectic lesions may benefit from topical antimicrobial agents such as mupirocin, benzoyl peroxide, chlorhexidine,
or ethyl lactate when secondary pyoderma is present. The use of any glucocorticoid-containing product is contraindicated and
could favor disease generalization. Evaluate the patient's overall health with special consideration to conditions affecting
the immune system such as poor husbandry, poor nutrition, inoculation status, and internal parasitism. A clinical examination
with skin scrapings two to four weeks after initial diagnosis is indicated to monitor for disease resolution or progression.
TREATING GENERALIZED CANINE DEMODICOSIS
Generalized demodicosis can be one of the most frustrating skin diseases you will ever treat (Table 1). Counsel owners on the time (possibly up to a year or longer) and financial commitment required to treat this potentially
life-threatening dermatosis. Premature treatment cessation by owners is a central reason for treatment failure. Since clinical
signs often improve before parasitologic cure, it is paramount owners understand the need for regularly scheduled follow-up
visits to ensure a successful outcome. A client handout may be helpful in educating clients about demodicosis.
Table 1: Treatment Summary for Generalized Demodicosis in Dogs
Clinical and microscopic observation
Some dogs less than 1 year of age with mild generalized disease may spontaneously recover. Clinical and microscopic observation
over several weeks with no mite-specific therapy is an option if signs are mild. Elective sterilization to avoid disease propagation
in the gene pool can be performed once any secondary pyoderma is controlled; however, the stress of anesthesia and surgery
may promote disease progression.8
If clinical signs progress or mite numbers increase, miticidal therapy is indicated. A complete blood count, serum chemistry
profile, and urinalysis are useful, particularly in adult dogs to exclude predisposing conditions or when deep pyoderma is
a confounding factor. This minimum database taken in context with presenting clinical signs may lead to other diagnostic testing
such as hormonal assays and stimulation studies. Treatment success is directly related to identifying and controlling underlying
conditions. Nevertheless, demodicosis may precede an undiagnosed predisposing disease.
Antibiotic therapy for pyoderma
Superficial staphylococcal pyoderma is treated empirically by using a beta-lactamase-stable antibiotic for a minimum of four
weeks (Table 2). In dogs with unresponsive superficial pyoderma or deep pyoderma or when rod-shaped bacteria are identified on cytologic
examination, select antibiotic therapy based on bacterial culture and antimicrobial sensitivity testing. Continue antibiotic
therapy until the pyoderma is clinically and cytologically resolved.
Table 2: Recommended Antibiotic Therapy for Staphylococcal Skin Infection in Dogs
Adjunctive topical therapy with an antibacterial shampoo may hasten clinical resolution. Common antibacterial shampoo ingredients
include benzoyl peroxide, chlorhexidine, and ethyl lactate. Benzoyl peroxide-based shampoos are often recommended because
of their keratolytic and supposed follicular flushing activity.9
All recognized Demodex mites in dogs appear to respond similarly to mite-targeted therapy. Treatment failure is rarely due to resistant mites. More
frequent causes of treatment failure in canine demodicosis include poor pyoderma control, premature discontinuation of therapy,
unsuccessful control of underlying conditions, and the use of concomitant glucocorticoids (Table 3). However, if a patient does not respond to the initial miticide, switch to another treatment option.10
Table 3: Reasons for Treatment Failure in Dogs with Demodicosis
According to a review of treatment protocols for canine demodicosis, amitraz, ivermectin, milbemycin oxime, moxidectin, and
doramectin are all recommended for treating canine demodicosis.10 This same review found evidence that ronnel, lufenuron, and levamisole should not be used to treat canine demodicosis. Improper
study design factors including patient selection, age of onset stratification, definition of cure, time to cure, and follow-up
time were major limiting factors in evaluating the efficacy of some treatments. Thus, there was insufficient evidence for
or against the use of many other treatments. Because of the safer therapeutic options available, organophosphates should not
be used to treat demodicosis.
Amitraz. Topical amitraz is FDA-approved for treating generalized demodicosis in dogs older than 4 months of age. Amitraz, a miticide
and insecticide, is a monoamine oxidase inhibitor (MAOI), prostaglandin synthesis inhibitor, and an alpha2-adrenergic agonist.10 Per the product label, amitraz liquid concentrate (Mitaban—Pfizer Animal Health) is to be used as a 0.025% (250 ppm) dip
every two weeks for three to six topical treatments until no live mites are found.
Not all dogs can be cured with amitraz administered per the label protocol. Consequently, investigators have found greater
cure rates by using various regimens of increased dip concentrations or frequencies.10,11 Overall, topical amitraz at 0.025% to 0.05% every seven to 14 days is recommended. A suggested protocol for amitraz is listed
in Table 4.
Table 4: Protocol to Maximize Amitraz Dip Efficacy in Dogs
Pododemodicosis and demodectic otitis can be treated with an extralabel mixture of amitraz and mineral oil (1:9), although
this mixture may irritate the otic epithelium in certain individuals.12 Before using an extralabel protocol, it is important to recognize that amitraz is a pesticide registered with the Environmental
Protection Agency (EPA). This status makes it a federal violation to use amitraz in a manner contrary to its label. If the
label protocol proves to be ineffective, it may be more acceptable to use a macrocyclic lactone instead of extralabel amitraz.
Amitraz collars are not recommended for treating demodicosis.10
Amitraz dips are not without risk to dogs and their handlers. Many patients experience mild toxicosis seen as excessive lethargy
for one or two days after dipping.8 More overt signs of toxicosis are similar to those seen with the use of alpha2-adrenergic agonists, including sedation, hypothermia, bradycardia, and hyperglycemia. Hyperglycemia is a potential concern
in diabetic dogs and clients.13 The use of alpha2-adrenergic antagonists can reverse signs of toxicosis and can be used before dipping in patients with a history of adverse
effects.13,14 Atipamezole (50 µg/kg intramuscularly) can reverse the signs of toxicosis within 10 minutes.13 Avoid antidepressants and MAOIs, such as selegiline, in dogs receiving amitraz. Animal handlers administering amitraz should
wear protective clothing and apply it in a well-ventilated area. Personnel should be aware of the potential risk for drug
interactions. Those with respiratory problems or diabetes should not use amitraz.15
A new spot-on formulation containing metaflumizone and amitraz (ProMeris—Fort Dodge Animal Health) is available in the United
States to control fleas and ticks on dogs. This product was recently evaluated as a topical treatment for generalized demodicosis
in a small study involving 16 dogs older than 1 year of age.16 Dogs were divided into two equal groups and treated with the spot-on at the proposed minimum dose rate (20 mg/kg of both
metaflumizone and amitraz, 0.133 ml/kg) on days 0, 28, and 56 or days 0, 14, 28, 42, 56, and 70. Five sites were scraped for
mites throughout the study. Clinical signs improved and mite numbers decreased for both treatment groups. For dogs that received
three treatments every 28 days until day 56, 42.9% had negative test results for live mites and eggs. For dogs that received
six treatments every 14 days until day 70, 62.5% had negative test results for live mites and eggs. Although the spot-on did
improve clinical signs and reduce mite numbers, the study excluded dead mites and mite segments from evaluation. It is also
unknown whether dogs cleared of mites relapsed after the study because skin scrapings were not obtained after the treatment
was discontinued. The use of a spot-on is an exciting concept, but more critically evaluated trials are needed to substantiate
this drug's efficacy in the long-term control of generalized demodicosis. It is important to recognize that ProMeris is registered
with the EPA. This status makes it a federal violation to use it in a manner inconsistent with its label.
Macrocyclic lactones. Macrocyclic lactones include the avermectins (ivermectin and doramectin) and milbemycins (milbemycin oxime and moxidectin).
This class of drugs selectively binds to glutamate-gated and gamma-aminobutyric acid (GABA)-gated chloride channels in the
mite's nervous system, resulting in cell hyperpolarization, mite paralysis, and, finally, death. Macrocyclic lactones do not
readily cross the mature mammalian blood-brain barrier.17 Safety in mammals is due to the lack of glutamate-gated chloride channels in the peripheral nervous system and the restriction
of GABA to the central nervous system.
The ease of oral administration compared with dips makes macrocyclic lactones the first line of therapy for many dermatologists
(Table 5). Unfortunately, the use of macrocyclic lactones for generalized demodicosis is considered extralabel, and there is no antidote
to the potentially serious and life-threatening side effects. Also, dogs should have negative heartworm disease test results
before macrocyclic lactone therapy is implemented. When using macrocyclic lactones for generalized demodicosis, the owner
must understand its extralabel use and potential for side effects. Some dermatologists will have the owner sign a consent-to-treat
form outlining this information before macrocyclic lactones use.
Table 5: Macrocyclic Lactone Dosages for Generalized Demodicosis in Dogs
—For generalized demodicosis, the injectable form of ivermectin is given orally at a dose of 300 to 600 µg/kg/day.10,12 The aqueous formulations may be more palatable than are the propylene glycol-based products. Adverse events are sporadic
and include lethargy, edematous wheals, mydriasis, muscle tremors, and ataxia. The main concern is the development of signs
attributable to severe neurotoxicosis including depression, stupor, coma, ataxia, and seizures; death can also result. Blindness
has also been reported in dogs.18
To better identify ivermectin-sensitive dogs, one report recommends initially dosing ivermectin at 50 µg/kg/day and then incrementally
increasing the dose by 50 µg/kg during the first days of treatment until the target dose is achieved.19 Another way to gradually increase the dose of ivermectin is to calculate the target dose and corresponding volume, and then
give 25%, 50%, and 75% of the total volume for several days before reaching the therapeutic volume (Table 6). Because of the long half-life of the drug, ivermectin serum concentrations increase for weeks with daily dosing. Thus,
patients need to be monitored for side effects during the first several weeks to months of therapy.10 The pour-on formulation of ivermectin is not effective in treating generalized demodicosis.10
Table 6: Example of Incrementally Increasing the Dose of Ivermectin in a Dog
Signs of ivermectin toxicosis can occur in any breed but are most common in ivermectin-sensitive breeds such as collies and
other herding breeds.20,21 Ivermectin sensitivity is derived from a frameshift deletion mutation of the multidrug resistance gene (MDR1; the most recent
nomenclature is ABC±), resulting in a severely truncated, nonfunctional protein product. The product of the MDR1 gene, P-glycoprotein,
is a large ATP-dependent transmembrane protein transporter found in the blood-brain barrier among other tissues.22 P-glycoprotein pumps substrates (e.g. ivermectin and loperamide) within the brain back into the blood. Dogs homozygous for this mutation (MDR1-1 delta) display
an ivermectin-sensitive phenotype, developing severe neurotoxicosis after a single dose of ivermectin.22 When ivermectin is deemed necessary for a dog, testing for the MDR1-1 delta genotype before its use is available through
Washington State University's Veterinary Clinical Pharmacology Laboratory (
http://www.vetmed.wsu.edu/vcpl/). Dogs without an ivermectin-sensitive genotype can still show signs of toxicosis if ivermectin is given in conjunction with
P-glycoprotein inhibitors (Table 7).
Table 7: Selected P-Glycoprotein Inhibitors*
Recently, the FDA issued a safety warning stating that some dogs have developed signs of ivermectin toxicity when high extralabel
doses of ivermectin are used concurrently with spinosad (Comfortis—Eli Lilly).23 Additional information can be found in the Lilly Companion Animal Health Technical Bulletin (http://elms.xh1.lilly.com/10788_03_tech_Bulletin.pdf). Thus, dogs receiving ivermectin for the treatment of demodicosis should not receive concurrent treatment with spinosad.
—Oral milbemycin oxime (Interceptor—Novartis Animal Health) is recommended at a dose of 1.5 to 2 mg/kg/day, although dose
ranges of 0.5 to 3.1 mg/kg/day have been used.10,24,25 Cure rates vary but are better with higher doses. Ivermectin-sensitive breeds generally tolerate milbemycin oxime at the
doses outlined above.26 Side effects of daily milbemycin oxime administration are similar to those of ivermectin and include depression, stupor,
coma, ataxia, and seizures. The major limitation of this drug is expense.
We have treated demodectic otitis topically with a commercial solution containing 0.1% milbemycin oxime (MilbeMite Otic Solution—Novartis
Animal Health); this use is considered extralabel.
—Few studies are available, but moxidectin (Cydectin injectable—Fort Dodge) given orally at 400 µg/kg/day can be effective
in treating generalized demodicosis.10,27,28 Moxidectin can be started at a lower dose and then gradually increased to 400 µg/kg/day similar to ivermectin, as outlined
above. Consider treatments other than moxidectin for ivermectin-sensitive breeds.29
Recently, an imidacloprid (10% w/v) and moxidectin (2.5% w/v) spot-on (Advantage Multi—Bayer Animal Health) was introduced
in the United States as a heartworm, intestinal parasite, and flea preventive. A similar European product (Advocate—Bayer
HealthCare) is labeled to treat and prevent flea infestation, treat ear mite infestation, treat sarcoptic mange, treat demodicosis
(caused by D. canis), prevent heartworm disease, and treat gastrointestinal nematodes. This spot-on product was evaluated in the treatment of
generalized demodicosis through a multicenter, randomized, blinded field trial during the registration process in Europe.30 Another group of dogs with generalized demodicosis was treated with daily milbemycin oxime and served as the control group.
Dogs were treated with the spot-on two to four times, at four-week intervals, with the test product at the recommended dose
of at least 0.1 ml/kg. Up to five body sites were scraped each month to look for Demodex species mites. Treatment was discontinued when two subsequent monthly skin scrapings were negative for living mites or at
the last examination on day 84. At study end, 87% of the treated dogs and 88% of the control dogs had no live mites on skin
scrapings with no difference in clinical response between the groups.
A limitation of the study is the exclusion of dead mites and mite segments from evaluation. It is also unknown whether dogs
cleared of mites relapsed after the study because skin scrapings were not obtained after treatment discontinuation. Although
this moxidectin spot-on appears to be equally effective when compared with milbemycin oxime in the treatment of generalized
demodicosis using the criteria of this study, more long-term studies with stricter evidence for parasitologic cure are needed
to corroborate these findings. Based on the experience of our European colleagues, treatment failures with this product are
—Doramectin, another avermectin, has been used in a study involving 23 dogs that received weekly subcutaneous injections of
600 µg/kg.10,31 None of the animals showed adverse effects with doramectin; however, this drug should not be used in ivermectin-sensitive
breeds of dogs. More research is needed to evaluate doramectin for treating demodicosis.10
Clinical signs and microscopic examination of skin scrapings are used to guide treatment for generalized demodicosis. Repeat
skin scrapings every two to four weeks during treatment. Sample at least four to six affected body sites including the face
and paws at each recheck. Obtain samples from the same body areas to consistently monitor the mite population. Once all scrapings
are negative for mites at any developmental stage, including dead mites or mite fragments, a parasitologic cure can be declared.8,12
If eggs or immature mite numbers do not decrease over four to eight weeks, consider altering the dose or frequency of the
given treatment. Miticidal treatment continues until two consecutive negative skin scrapings collected two to four weeks apart
are obtained. Chronic cases benefit from an additional month of therapy beyond the two negative scrapings. A complete cure
is declared if no relapses occur within 12 months from the time of treatment discontinuation.12