"We've come so far from burned motor oil": What's new in the treatment of demodicosis (Proceedings)

Demodicosis is one of the most common and long-recognized skin diseases of animals, yet it is often overlooked, and we as a profession still struggle to find not only underlying causes but effective, safe treatments. This talk reviews the common and less known signs of demodicosis and current therapies.

Canine Demodicosis: "Check us out: Maybe we're not just your generic Demodex anymore"

Three species of Demodex mites are documented in dogs. The most common is D. canis. In the 1980's, Dr. Chesney recognized occurrence of a "stubby" Demodex (D.cornei) mite concurrent with D. canis in 6 dogs. The author has seen this short-lived mite on many occasions, always in conjunction with generalized D. canis. We believe this mite is transferred from bitch to pups similarly to D. canis; its presence does not predict etiology or prognosis.

The third mite is D. injai, recognized in the 1990's. This body (opisthosoma) of fellow is half-again longer than D. canis . D. injai can overgrow concurrent with D. canis or alone. It has a preference for the dorsum, especially of terriers, and can cause just seborrhea oleosa ± pruritus in healthy or immune suppressed adult dogs. This unusual presentation, along with low mite numbers, causes this mite to be overlooked.

There are two forms of demodicosis in dogs: localized and generalized. Tight consensus still lacks what constitutes localized v. generalized. For the most part,10 or more localized lesions, involvement of more than one body region, or complete involvement of 2 or more feet is considered generalized disease. When I see multiple stages of mites on scrapings, I believe the condition has the upper hand on the host.

Localized demodicosis is most common in dogs less than 18 months of age, causing alopecia, mild erythema, ± fine scaling, and occasionally papules / pyoderma. Face and legs are affected most often. Localized demodicosis can also present as ceruminous otitis. Adult-onset localized demodicosis is less common, but can happen (in the author's opinion) secondary to stress / change in routine and from underlying immunosuppressive disorders such as hyperadrenocorticism or hypothyroidism.

On the flip side, generalized demodicosis can be a devastating problem. Again, most cases start in dogs less than 18 months of age. The lesions are not just "more of the same" as localized D. canis. Generalized cases often have more follicular plugging and infection. Besides alopecia, these dogs have papules, erythema, scaling, comedones, and pruritus. If untreated, this progresses to furunculosis (those gross purple swellings that spew blood and pus when squeezed). Ceruminous otitis is also a feature in generalized Demodex.

Demodicosis can be diagnosed if veterinarians remember to do deep skin scrapings. In exuberant puppies, some areas, such as the periocular region, are not amenable to approach with a relatively sharp object (even a dulled scalpel blade). A hair pluck or trichogram is a safer but less sensitive technique in these patients. Scrapings may be negative in areas of dermal and epidermal thickening, such as in pododemodicosis or Shar Pei dogs; hair plucks examined in mineral oil may be more revealing. Sometimes mites are found only via biopsy. For our everyday exams, it is most thorough is to do scrapings and hair plucks.

Demodex Treatment: General concepts

Juvenile demodicosis cases rarely warrant thorough evalution beyond fecal examinations and taking a good diet history. Most cases are genetically-based. Approximately 90% of localized Demodex cases self-resolve. It is this that gives false credit to so many therapies for demodicosis. The most appropriate therapy for localized juvenile-onset demodicosis is assuring good health of the pet and assuring a "stress-free" environment. The patient and mite counts, as well as the ratios of adult to immature and live to dead mites, should be monitored every 4 weeks to assure the condition is regressing. If the dog has papules or any pruritus, topical or systemic antibiotics are justified.

For generalized juvenile cases: As above, make sure patient is as metabolically and emotionally stress-free as possible. Most cases are genetically-based and will need treatment because of the marked secondary infections that accompany the demodicosis. I stop treatment by the time the dog is 1.5 years of age and monitor for recurrence.

For adult onset generalized cases: Ruling out immune suppression (hypothyroidism, hyperadrenocortcism, underlying neoplasia) is indicated. If an underlying cause can be addressed, I will do mitacidal therapy until the mites and the underlying problem are controlled. If I cannot find a cause, I caution the owner we will be using miticidal therapy for the rest of the pet's life. It is prudent to repeat blood work, ultrasounds and chest radiographs every 6 months; often times the underlying cause comes to light later on.

Regardless of age of onset, generalized demodicosis is often accompanied by deep pyoderma. It is infection that makes generalized D. canis dogs ill. Appropriate antibiotics should be given for at least 4-6 weeks, best until mites found on scrapings are dead and few in number; otherwise infection recurs.

Miticidal Therapies: Regardless of therapy, treatment is continued for at least 4 weeks past negative scrapings!

Amitraz Dips (Mitaban): the first approved therapy, which is still at best modestly effective, especially at the label dosing (250 ppm every 2 weeks to a clipped hair coat). It is more effective applied weekly, and if concentration is doubled to 500 ppm. An alternative protocol uses 500 to 1250 ppm applied to alternating halves of the body each week. Any alternative approach increases the risk of side effects (lethargy, bradycardia, hyperglycemia). A 1:9 solution of amitraz to mineral oil is suggested for otic demodicosis. Most dermatologists skip over amitraz as a therapy unless we are concerned about avermectin or milbemycin sensitivity. It is illegal to use an EPA regulated product in any manner other than the label directions. And also remember, amitraz is an MAO-inhibitor and concurrent use with other MAO's, sedatives, antihistamines, is contraindicated.

Promeris: This monthly flea control product contains amitraz + metaflumizone and is approved for treatment of Demodex. Two studies to date with this product. Number one from the manufacturer: 16 adult dogs (mean age not given) were treated either every 2 or 4 weeks with Promeris. "Sixty-two percent of dogs in the group treated every other week were considered mite free, and 43 percent of dogs in the group receiving three monthly treatments were considered mite-free." 87% of dogs in both groups were clinically improved. Time to this assessment was not given nor was any follow up. No adverse events related to treatment were observed. Dr. Rosenkrantz treated 24 dogs with juvenile or adult onset generalized demodex with Promeris every 2 weeks until 2 negative skin scrapings. The juvenile cases had an excellent response rate with only 1/13 not responding. The adult cases were not so positive with only 45% having an excellent response and one of those cases relapsing. There were 6 reports of medically-significant adverse effects (not product odor).

I have used Promeris in a few cases of generalized Demodex with varied success and 1 adverse reaction. I find it more effective if applied every 2 weeks. Once mite counts are decreased, I switch to monthly application. Unfortunately, Promeris is associated with "not uncommon" side effects, including lethargy after application, particularly if the pet licks off any product. The most troubling side effect is a pemphigus-like drug reaction. My personal take: I find Promeris is less effective than ivermectin or milbemycin, but less expensive than Interceptor and less noxious than Mitaban dips. It has a place in avermectin-intoleratant patients.

Macrocyclic Lactones (avermectins, milbemycins): are still the "go to" therapies for generalized demodicosis. The catch is concern for breed-related and individual sensitivities to avermectins (defect in the p-glycoprotein pump) resulting in neurologic side effects ranging from mydriasis to death. We can eliminate some of apprehension by testing for MDR1 mutation via Washington State University: http://www.vetmed.wsu.edu/depts-VCPL/#Drugs. As with any laboratory test, there is worry of error and I still recommend starting at a lower dose for dogs who test normal but are of herding breed descent. This also does not account for drug interactions. For example, ketoconazole interferes with p-glycoprotein function and should not be used in dogs taking ivermectin.

Ivermectin: Still the preferred therapy of most dermatologists for treatment of Demodex. Injectable ivermectin (Ivomec, 1%) can be administered orally at reasonable cost, dosing at 0.300 – 0.60 mg/kg/d. We can "test the waters" on a patient and their sensitivity to this by starting at a low dose and working up, monitoring for side effects. I start at 0.1 mg/kg /d for 1 week and increase by 0.1 mg/kg every 4-7 days until reach 0.4-0.60 mg/kg/d). Some colleagues start even less at 0.05 mg / kg /day. As a point of reference, the heartworm preventive dose of ivermectin in 0.006 mg/kg once a month. Dogs with adult-onset generalized demodicosis often relapse if therapy is stopped unless an underlying cause is addressed. A reasonable maintenance protocol is to continue the successful miticidal dose every other to every 3rd day long term. The author has several dogs on this regime with no adverse long term effects.

Milbemycin Oxime (Interceptor): At 2 mg/kg/d, this is an effective miticide and is the first alternative for pets intolerant of ivermectin. It is also very expensive, having to dose it at 0.5 to 2 mg / kg daily. The HW preventive dose is 0.5 mg / kg / month. Some dogs with avermectin sensitivities cannot tolerate milbemycin.

Doramectin: This is an avermectin available as an injectable parasiticide for cattle (Dectomax). Weekly injections of 600 mcg/kg appear effective in one study of 23 dogs. A patient sensitive to ivermectin may have adverse reactions to doramectin as well, though one colleague (Torres) reports better tolerance in non-herding breed ivermectin-sensitive dogs.

Moxidectin: This is a milbemycin, available for small animals only as a monthly HW preventive or a monthly topical parasiticide combined with imidocloprid. There is a large animal formulation that can be used orally at 400 mcg/kg/d with the same risks as all other macrocyclic lactones. So far studies are limited to outside the US and show no greater efficacy than ivermectin or Interceptor. Anecdotally, other colleagues say it does not work well for Demodex treatment.

What doesn't work against Demodex: selamectin or topical moxidectin; lufenuron, oral selemectin. (A recent study used 24-48 mg / kg of the topical formulation of selamectin given orally to treat juvenile and adult-onset generalized demodex. In short, adverse effects were mild but it was also not very effective. And it tasted really bad.)

In summary: my preference for treatment of generalized demodex is oral ivermectin. If not tolerated, second choice is milbemycin. If owner cannot afford that, third choice is Promeris or amitraz dips; last choice is doramectin simply because of lack of experience with this drug.

Feline Demodicosis

There are 2 well-documented species of Demodex mites in cats. D. cati is morphologically similar to D. canis but is longer and thinner. It is the cause of "Follicular Demodicosis" in cats. Localized D. cati infection is rare, but can present as ceruminous otitis only. Most cases of D. cati are generalized and are associated with underlying immune suppression (FeLV / FIV infection, diabetes, hyperadrenocorticism, neoplasia). Clinical signs include alopecia, scaling, erythema, and hyperpigmentation. D. cati is usually easily found on skin scrapings.

The relatively new kid on the block is D. gatoi. This mite is significantly shorter, much harder to find, and lives in the epidermis ("Superficial Demodicosis") as opposed to the hair follicle, and acts more like scabies. This mite can cause intense pruritus (head, ventral neck, elbows, inguinal area), other signs similar to allergic dermatitis, and is believed to be contagious. Not all cats are pruritic from this mite; pruritus may reflect a hypersensitivity reaction. A negative scraping does not rule-out D. gatoi. If a cat from a multi-cat home is suspected to have D. gatoi, it may be more useful to scrape a non-affected cat, scrape areas on the affected cat not accessible to its tongue, or check a fecal float from the pruritic cat. This mite is more common in certain areas, such as the Gulf states, than other regions. Many cats diagnosed with this mite are ultimately determined to be atopic cats.

Treatment of Feline Demodicosis

D. cati: Identification of any underlying illness is essential. D. cati responds relatively well to lime sulfur dips and also daily ivermectin as described for canine patients. There is concern for potential propylene glycol toxicity from the vehicle of ivermectin used daily. Cats also appear to respond well to weekly injections of doramectin. Treatment should continue until past negative scrapings and may be needed indefinitely if underlying disease cannot be controlled.

D. gatoi presents a little challenge with treatment. Neither ivermectin nor selemectin has not been successful in treating this mite. The only published effective treatment is weekly lime sulfur dips for 5-6 weeks of ALL in contact cats. There is promise that frequent application of Advantage Multi (imidocloprid + moxidectin) for an extended time will eliminate this mite. Again, all in-contact cats must be treated.

Summary / Key Points

Scrape and pluck all derm patients, especially ones with comedones, follicular casts, or oily backs.

Assure patient is in good health and "stress-free"

Ivermectin is still first choice of treatment for dogs; watch for side effects / drug interactions. Because lime sulfur dips are not well-received by cats and their owners, I use ivermectin for cats as well.

Follow-up for assessing response to treatment and appropriate duration of antibiotic therapy important.

Selected References

Johnstone IP. Doramectin as a Treatment for Canine and Feline Demodicosis. Aust Vet Pract. September 2002;32(3):98-103.

Löwenstein C, Beck W, Bessmann W, Mueller RS. Feline demodicosis caused by concurrent infestation with Demodex cati and an unnamed species of mite. Vet Rec. September 2005;157(10):290-2.

Robson DC, Burton GG, Bassett R, Shipstone M, Mueller RS. Eight Cases of Demodicosis Caused by a Long-Bodied Demodex species (1997-2002). Aust Vet Pract. June 2003;33(2):64-74.

Oberkirchner , U, Linder, K, Olivry, T. Promeris-associated pemphigus foliaceus-like drug reactions in dogs: 22 cases. Proceedings, NAVDF 2010.

Rosenkrantz WS. Efficacy of metaflumazone plus amitraz for treatment of juvenile and adult onset generalized demodicosis in dogs: pilot study of 24 dogs. Proceedings, NAVDF, 2009.

Scott DW, Miller WH, and Griffin CE. Muller & Kirk's Small Animal Dermatology, 6th ed. Philadelpha: WB Saunders, 2001.