Update on Demodicosis and other mite-caused dermatoses (Proceedings)

Canine demodicosis

Canine demodicosis is a noncontagious parasitic skin disease caused by an overpopulation of the host-specific follicular mites of the genus Demodex. Most cases of canine demodicosis are caused by Demodex canis, although two other species of demodicid mites are reported. Localized demodicosis is a common mild and benign self-limiting disease. Generalized demodicosis, in contrast, is a serious and potentially life-threatening disease. Most cases of generalized demodicosis are juvenile in onset and develop in dogs less than 1 year of age. Interestingly, yet there is no universally agreed to definition of ‘generalized', or for the term ‘adult onset ' (as opposed to juvenile). For the purposes of these notes, ‘adult onset' will be defined as any case diagnosed in a dog at over 2 years of age, and ‘generalized' will follow the suggestion of Mueller: …involvement of an entire body region, more than 5 focal areas, and/or paw involvement'.

Most cases of demodicosis are due to Demodex canis, although cases caused by D injai (a large-bodied Demodex species which lives in the hair follicle and the sebaceous glands) and an unnamed short-bodied Demodex species (which lives in the stratum corneum) have been reported.

A genetically preprogrammed immunologic defect probably is responsible for the juvenile onset, generalized demodicosis. Adult onset demodicosis has been reported to be caused by immunosuppressive treatment for neoplasias or auto-immune disorders, or be associated with diseases altering the immune response such as hypothyroidism, hyperadrenocorticism, leishmaniasis, and neoplasias. In the author's practice the most common underlying cause is the long-term use of systemic corticosteroids – these may be at relatively low doses. Perhaps 25% of the dogs have no demonstrable underlying disease.

Diagnostic tests

Diagnosis is by demonstration of the mite on deep skin scraping in a dog fulfilling the lesional and age requirements noted above. The author prefers to use a medical grade spatula (Fisherbrand* Microspatula with Flat-Ended Blade, catalogue number 21-401-20, Fisher Scientific; http://www.fisherscientific.com), as this blade is just sharp enough to scrape deep enough to the first level of capillaries (and hence deep enough to be at the follicular depth of the mites). Dogs which have very thick skin (especially on the feet) due to chronic inflammatory skin disease associated with furunculosis may need to be biopsied in order to demonstrate the mites.

For adult onset generalized demodicosis, the owner should be informed of the potential of an underlying disease, and the clinician should perform diagnostic tests searching for such an etiology. Minimum data base should include a complete blood count and biochemical profile, but depending upon the presentation of the dog (as well as the willingness of the owner to spend money) other tests such as abdominal ultrasound, thoracic radiographs, thyroid hormone panel (T4, free T4, TSH level) and ACTH stimulation test could be performed. If an underlying disease is found, the disease should be treated, as well as proceeding with appropriate miticidal treatment.

Treatment

It is important to realize that most if not all dogs with demodicosis will have a secondary pyoderma. This is usually caused by Staphylococcus intermedius, but if there is concurrent imunosuppression (for example, from exogenous corticosteroids) other bacteria may be contributing to the pyoderma. The author usually uses cephalexin at 30 mg/kg q12h (for superficial pyoderma) or q8h (for deep pyoderma). Other antibiotics which can be used are enrofloxacin 5-10 mg/kg q24 h, lincomycin 20mg/kg q12h, amoxicillin-clavulanate 13.75 mg/kg q12h or marbofloxacin 3-5 mg/kg q 24 h. Antibiotic treatment is usually continued for a minimum of 2 months.

There are several different miticidal treatments that are available to treat generalized demodicosis. In all cases the dog's mite population should be monitored by means of a deep skin scraping once monthly. The owners should be instructed to continue treatment until the dog has 2 consecutive negative scraping sessions. ‘Negative' in this instance means NO live or dead adult mites, nymphs, larva, or eggs. Thus, minimum miticidal treatment time will be 2 months. In actuality, most dogs will need to be treated for at least 4 months, although most will show improvement within the first 2 months. If the dog still has positive scrapings 6 months after continuous treatment, but is clinically normal (or dramatically improved) the owner should be informed that the disease can be controlled but that treatment is probably necessary for the rest of the dog's life.

• Ivermectin- this is the author's drug of choice for dogs, but NOT for Collies,

• Border Collies, Bearded Collies, Old English Sheep Dogs, Australian herding breeds, Shetland sheepdogs, or anything that could be considered a cross of one of these breeds. The author uses the bovine injectable 1% solution (Ivomec®: Merial) ; obviously, this is off-label usage. The usual dose is 0.3 mg/kg given ORALLY q24 h for the first week, then 0.6 mg/kg. Some dogs find this medication bitter tasting, so putting it in a small amount of food (vanilla ice cream works well!) is helpful. Adverse effects, although rare, include lethargy, edematous wheals, ataxia and mydriasis10. These effects may be seen early or late in the treatment. If the dog shows adverse effects, the drug should be stopped. Most dogs recover within 48 hours of stopping the drug. Negative outcomes (with ivermectin or moxidectin) have been associated with the use of either diazepam (or similar drugs) or barbituates to control seizures: the preferred drug is proprofol10a.

• Collies are particularly sensitive to adverse reactions of ivermectin with over 75% of Collies being either carriers or homozygous for the mutant MDR1 allele leading to neurotoxicity.10b Information on testing for this mutation can be found at http://www.vetmed.wsu.edu/depts-vcpl/ Other herding breeds such as the Shetland Sheepdog, Australian Shepherd, and Border Collie also carry or be homozygous for this allele10c. However, idiosyncratic toxicity may be seen in any breed.

• Imidacloprid & Moxidectin (Advantage Multi®, Advocate®, Bayer) -

• Label claim for demodicosis in Europe, weekly application works best, author'schoice for non-collie dogs or dogs that cannot tolerate ivermectin.

• Milbemycin oxime- formerly the author's drug of choice for the ivermectin-sensitive breeds. It would probably be the drug of choice for all breeds except it is more expensive that the bovine ivermectin solution. It is available as an oral heartworm preventative (Interceptor®: Novartis). The author uses a dose of 2 mg/kg per day. A paper from the USA supports the use of this dose11. A more recent article from Sweden suggests that lower doses (mean 0.75 mg/kg) may be effective 12. The author has had patients which eventually could be controlled (although not cured) with the lower dose, even if given q 48 h. Adverse effects are stupor, ataxia, trembling, transient vomiting, and lethargy13,14 and are generally reversible upon discontinuing the drug.

• Moxidectin, currently not approved for demodicosis in the USA, has been used as another treatment for generalized canine demodicosis. Evidence-based medicine indicates good evidence for the efficacy of moxidectin given per os (400 micrograms/kg daily).

• Doramectin (Dectomax®, Pfizer), not approved in the U.S for demodicosis. 300 micrograms/kg/day orally used successfully in Australia, New Zealand & Japan;side effects similar to those seen with ivermectin.

• Amitraz- The author has used this product as a topical 0.025% solution applied once weekly, as has been reported by others16. The hair coat should be clipped in thick-coated and long-haired dogs, and an antibacterial shampoo used to remove crusts and bacteria, then the amitraz solution applied, and NOT rinsed off. While most owners were able to perform the application at home, they were always advised to do this in a well-ventilated area wearing gloves and long-sleeved shirts, as respiratory problems have been observed in humans. In general, this is an effective treatment, but as in other treatment modalities, adult onset generalized demodicosis cases responded less favorably to therapy1 than juvenile cases, or at least required longer duration of treatment16. Most cases have to be treated once weekly for 4-6 months. Higher concentrations may have greater cure rates, but also had a greater chance of eliciting adverse effects: depression, sleepiness, ataxia, polyphagia/polydipsia and vomiting and diarrhea1. It is the impression of the author, and others6 that smaller dogs may be at greater risk of showing clinical signs. The author has noted hypoglycemia in conjunction with sleepiness or depression in some dogs following amitraz treatment: feeding the dogs a small amount of honey or similar sugar-containing food before the next treatment ameliorated or prevented signs of lethargy. This is contrary to one early experimental study which documented amitraz-induced hyperglycemia in dogs

• Two less common uses of amitraz should be noted. First, in cases of severe pododermatitis, the author and others9 have used 1ml of the 12.5% amitraz concentrate mixed in 30 ml of mineral oil for daily application. Obviously, owners should wear gloves. The other use involves a report utilizing amitraz (9%)-containing collars which were replaced every 3 weeks in 2 dogs with adult onset demodicosis19. As no follow-up period was specified, it is difficult to judge long-term efficacy.

• Finally, a recent addition to the spot-on flea-control medications, ProMerisTM for dogs, (Fort Dodge) contains amitraz in addition to metaflumizone, the anti-flea molecule). The amitraz portion has been shown to be helpful in the treatment of demodex in dogs19a. Current recommendations are to apply this product every other week. It has a somewhat unpleasant smell, which eventually dissipates over several hours. This product is in the process of being discontinued, at least in part due to it being documented as a cause of ‘Pemphigus foliaceus-like' drug reactions.

• Two other medications have recently been reported as having beneficial effect in the treatment of generalized demodicosis. Moxidectin is another milbemycin which has been evaluated either injected subcutaneously 0.200 mg/kg q7-14 days for 1 to 4 treatments, or 200-400 mcg/kg/day orally. Success rates and adverse effects were similar to milbemycin. Likewise, another avermectin, doramectin, has been evaluated for generalized demodicosis in one report; the dosage used was 0.4 – 0.6 mg/kg SQ weekly, for 5-23 weeks. Mydriasis, anorexia, weight loss, tremors have been noted at 10x this dose. The author has not yet used either of these medication, and more cases of generalized demodicosis need to be treated by these drugs before recommendations may be made.

Feline demodicosis

Two species of this parasite have been recognized: Demodex cati, which resembles an elongated Demodex canis, and Demodex gatoi which has a short, squat appearance. Demodex cati is relatively rare, is usually found in the ears or on focal areas of alopecia on the face, and is not pruritic. It is easy to find on deep skin scrapings (being a follicular mite) and when (rarely) seen as a generalized infestation, usually points to an underlying ‘immunosuppressive' disease (diabetes mellitus, hyperadrenocorticism, FeLV, or FIV infections, etc.).

Demodex gatoi, which has been conjectured as being related to rodent Demodex species, tends to cause pruritus, may be difficult to find on skin scrapings, tends to be found superficially (in the stratum corneum) and is contagious to other cats.

In Demodex cati, successful treatment has been reported using lime sulfur (Lymdyp®: DVM Pharmaceuticals, Miami, FL). 1 cup: 1 gallon, q 5 days), a dilute amitraz (Mitaban®: Upjohn, Kalamazoo, MI ) solution of 125 ppm q 7-14 days, or 300 mcg/kg of ivermectin, PO or SQ, q24h. D. gatoi seems to respond best to the topical lime sulfur protocol1. When dipping any cat, an Elizabethan collar is helpful to prevent ingestion.

Scabies

Scabies is an intensely pruritic, highly contagious, transmissible canine dermatoses caused by the epidermal mite Sarcoptes scabei var. canis. An artificial age predilection is often seen (young dogs). Clinically apparent disease may appear within one week of exposure to an affected animal. Sarcoptic mites can live up to 48 hours off a host in the environment. Although canine sarcoptic mites are fairly host specific to dogs and other canids, they may infest humans and cats as secondary hosts.

The life cycle from egg-larva-nymph-adult is 12-18 days and Adult mites live 4-5 weeks. Transmission is effected with newly fertilized female mites moving fairly rapidly on warm skin and burrow into the horny layer of the skin of their new host. The female usually lays its eggs with a few hours after burrowing. The eggs hatch within 3-8 days. Transmission is usually by direct contact with an infested dog or other canid (fox, coyotes, etc). Evidence supports clinical disease is a multi-factorial hypersensitivity reaction.

It is estimated that some member of household will have visible lesions in about 30% of the cases of canine scabies. Children are affected more commonly perhaps due to more extensive contact with the affected dog. Lesions in humans are papules, pustules and erythema most commonly on the forearms, neck, and along areas of elastic clothing contact.

Intense pruritus is the hallmark of canine scabies. Lesions on the dog are usually erythematous maculopapular eruptions with crusting, alopecia and often extreme secondary self-trauma. Crusts may be thick and yellowish. The lesions are primarily ventral in distribution with the most severe lesions affecting the pinnal margins, lateral aspects of the elbow, medial aspect of the foreleg, zygomatic arch area, and abdomen.Regional lymphadenopathy is common.

History of a rapid onset highly pruritic skin disease and possible contagion exposure as well as involvement of other dogs and people greatly increases the index of suspicion.The clinical features of scabies as noted are quite distinctive.

Diagnosis is confirmed by demonstrating via skin scrapings of the mites, eggs, and or fecal pellets. However, it is estimated that mites are found on skin scrapings in less than 50% of the cases, even after repeated scrapings. Therefore, it is essential to treat

empirically based on clinical impression. Fecal examination will sometimes show mites and eggs that were swallowed by the host during excessive grooming. A CBC with an absolute eosinophilia is suspicious (> 1300/cm). Proteinuria may be seen in the urinalysis. There is usually only partial response to previous corticosteroid treatment.

Treatment is most importantly the treatment of the dog and all in contact mammals (especially other dogs) with a scabicidal medication. Most commonly used are:

• Selamectin (RevolutionR) – Another avermectin, designed for topical application, application every 2 weeks for 3 treatments. Selamectin has the distinct advantage of having a label claim for canine scabies.

• Ivermectin (IvomecR) 20 micrograms/kg (bovine injectable product) (1/10 cc/10 lbs body weight) per os or subcutaneously, minimum of four weekly dosages. As noted with demodicosis treatment, certain dog breeds are potentially  more sensitive to ivermectin owing to differences in the blood-brain barrier. At the dosages used for scabies, this problem is of most concern for Collie Dogs and  Shetland Sheep Dogs (ABCB1-1Δ multidrug sensitivity mutation). Serious adverse neurologic reactions to ivermectin have been seen in Collie Dogs, Shetland Sheep Dogs, Border Collies, Australian Shepherds, plus a variety of other breeds idiosyncratically. Ivermectin is the most cost-effective method of treating scabies in multiple dog households or in kennels.

• Milbemycin oxime (InterceptorR) - Another avermectin, also is efficacious. Recommended dosages vary from once to twice the monthly heartworm preventative dose given once weekly for four weeks.

• Lime-Sulfur - Products include lime-sulfur at 2%. (LymDipR; DVM/TEVA; Sulfurated LimeR Dechra) – it is important to follow label directions on idlution. This traditional approach has been superseded by newer less labor-intensive methods of therapy. Lime sulfur is still used in circumstances where safety is an issue especially in very young animals.

• Amitraz (MitabanR) rinses, 3 or 4 weekly applications is an additional older choice.

In order to contain contagion, it will be helpful to

• Isolate the affected animal and clean the premises.

• Dispose of the animal's bedding or cleanse it thoroughly.

Systemic corticosteroids may be used to control pruritus during the first week. Paradoxically, pruritus may actually increase during this time because of increased antigenic load.

Notoedric acariasis

Notoedric acariasis or feline scabies is an uncommon contagious mite infestation caused by the sarcoptid mite Notoedres cati characterized by crusting with extreme pruritus.

The disease is uncommon in most regions of North America, but may be found in localized endemic areas (southern California, Chicago area, Florida Keys, western Massachusetts, parts of the Canadian prairie provinces, etc). Notoedric acariasis may be increasing in prevalence with the advent of some newer insect-specific flea control products that do not kill acarids. Notoedric acariasis is seen predominantly in cats permitted to roam. Notoedres occasionally may affect dogs, humans and other mammals. Notoedric acariasis in dogs can mimic canine scabies.

Extreme pruritus, often starting on the head/face, but in advanced cases affecting the legs and feet, and occasionally the entire body. Lesions are often thick yellowish-gray crusts, associated with alopecia and lichenification.

Diagnosis is often suspected via a history of a rapid onset highly pruritic skin disease and possible contagion exposure. This is confirmed on skin scraping as the mites are usually easily demonstrated.

Treatment is similar to treatment of canine scabies. The author especially uses:

• Selamectin (RevolutionR) – An avermectin, designed for topical application, application every 2 weeks for 3 treatments. Selamectin has the distinct advantage of regulatory  approval for topical use in cats.

• Lime-Sulfur - An insecticidal rinse every 5 days for a minimum of 6 applications.Products include lime- sulfur - 2%. (LymDipR DVM/TEVA; Sulfurated LimeR Dechra). This traditional approach has been superseded by newer less labor-intensive methods of therapy. Lime sulfur is still used in circumstances where safety is an issue especially in very young animals.

Cheyletiellosis

Cheyletiellosis or Cheyletiella dermatitis is a contagious mite infestation seen in domestic animals, wildlife and humans characterized by scaling and crusting. It may be seen more commonly in areas of the world where concerted flea therapy is not necessary or not consistent. Cheyletiella dermatitis may be increasing in prevalence on a wider basis with the advent of some newer insect-specific flea control products that do not kill acarids. Infestations have been reported in dogs, cats, rabbits, squirrels, poultry, foxes and humans. This disease may not be as uncommon as previously thought as many veterinarians in flea-active areas have a very low index of suspicion and do not look for this mite. It is reported that Cheyletiella mites may live in an animal's environment for extended periods of time (24 – 48 hours) off the host in places with optimal temperature and humidity. Cats participating in cat shows may be at highest risk for acquiring this parasite.

The causative parasites are not especially species specific: Cheyletiella yasguri (dog, cat, rabbit), C. blakei (cat), C. parasitivorax (rabbit, cat, dog). These are large mites (350-400 microns) readily easily identified by their prominent hook-like (‘Viking horn') mouth parts. The life cycle is completed on one host. The mites live on the surface and invade only the stratum corneum; Cheyletiella mites do not burrow deeper.

There may be an artificial predilection for young mammals due to increased chances of exposure (pet stores, kennels, shelters, etc).

There are definite zoonotic implications (as for scabies and notoedric mange) but less commonly suspected by MDs, despite documentation in the human medical literature. People in the house may develop visible pruritic distinctly papular lesions. It is estimated that some member of household is affected in approximately 30% of the cases. Children or others with more extensive contact with the affected animal are more likely to be affected. Lesions and sites in human are generally erythematous papules on the arms and neck, and around the belt- or bra-line. Lesions are pruritic. Cheyletiella is reported anecdotally to be self limiting in humans, once the condition is successfully treated on the pet.

Cheyletiellosis is predominantly a dorsal disease, often with dramatic scale, and .pruritus is variable and may be absent, especially in rabbits. Cats may have a dorsal miliary dermatitis (encrusted papules); there may be asymptomatic carriers. Dogs often have dorsal scaling, papules, or again may be asymptomatic carriers. Rabbits usually present with dorsal scaling and crusting.

The diagnosis may be based on history such as recent contact with other animals (cat or dog shows, pet shops, kennels, grooming establishments).  The diagnosis is confirmed via clear tape preparation - Pick up crusting debris with clear tape and use as a cover slip on a slide with mineral oil, variable as far as ease of finding. Alternatively, superficial skin scraping - mites maybe easier to find than scabies mites, but still may be difficult to demonstrate.

Treatment is as per sarcoptic mange. The author especially uses:

• Selamectin (RevolutionR) – An avermectin, designed for topical application, application every 2 weeks for 3 treatments. Selamectin has the distinct advantage of  regulatory approval for topical use in dogs and cats, and has been shown to be safe  in rabbits.

• Lime sulfur. Dogs and cats – Traditional therapy - 2% lime-sulfur (LymDipR DVM/TEVA; Sulfurated LimeR Dechra) every 5 days for 4 applications.

• Ivermectin (IvomecR) 200 micrograms/kg (bovine injectable product) (1/10 cc/10 lbs body weight) per os or subcutaneously, minimum of four weekly dosages. Certain dog breeds are potentially more sensitive to ivermectin owing to differences in  the blood-brain barrier. At the dosages used for cheyletiella, this problem is of most  concern for Collie Dogs and Shetland Sheep Dogs (ABCB1-1Δ multidrug sensitivity mutation). Serious adverse neurologic reactions to ivermectin have been seen in Collie Dogs, Shetland Sheep Dogs, Border Collies, Australian Shepherds, plus a variety of other breeds idiosyncratically. Ivermectin is the most cost-effective method of treating cheyletiella in multiple animal households or in kennels. However, experience with using ivermectin in cats is limited; caution is advised.

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