Canine generalized demodicosis (CGD) is considered one of the most severe canine skin disease and one of the most frustrating disease to treat and bears a guarded prognosis. Euthanasia, commonly resorted to in the past, is rarely necessary nowadays if a dedicated dog owner uses treatment currently available. With intense treatment (either with an approved protocol or with an extra-label drug), the vast majority (~ 95%) of CGD cases can be cured. Most cases of CGD have secondary bacterial infection, which requires systemic antibiotics administration for several weeks concomitantly with the acaricidal treatment.INTRODUCTION
Canine demodicosis is a parasitic skin disease characterized by an excessive proliferation of Demodex canis mites within the hair follicles and is classified as localized or generalized according to the extent of the disease.
Over the last few years, several new therapeutic options have become available for the treatment of CGD. The therapeutic efficacy of each drug varies greatly. These discrepitencies result from differences in the populations studied, in the criteria used when differentiating CLD and CGD and in defining "cure", as well as in the length in the follow-up periods.
ACARICIDAL TREATMENTS
Amitraz
Amitraz (Mitaban®, The Upjohn Company), a monoamide oxidase inhibitor, is currently the only Food and Drug Administration (FDA) approved treatment for CGD. The licensed protocol for amitraz in the United States and Canada, consisting in biweekly (q14d) 250 ppm topical solution, has reported cure rates ranging from 0 to 99%. This wide range of reported efficacy can be explained by the fact that when amitraz was introduced as a topical acaricide in the early 1980s, several reports were published stating that biweekly treatments with amitraz solution at 250 ppm were close to 100% effective in resolving CGD. However, these reports may have been misleading because the researchers defined effectiveness as a return to clinical normality, and did not pursue follow-ups to assess the long term cure. Nowadays, cure is considered if the dog remains disease free for at least a year after treatment is completed. Based on the current definition of "cure", the actual cure rate for those early studies may have been less if any of the dogs later relapsed. In any case, when cure is not achieved with the approved amitraz treatment regimen, the following options are available: euthanasia, control with amitraz dips every two to four weeks, or extra-label use of amitraz, milbemycine oxime or ivermectin.
Extra-label amitraz treatment protocols
WARNING: The following discussion is for your information only, to assist your understanding if your veterinarian recommends any of them. Under no circumstances should these products be used except by order of your veterinarian.
Although amitraz is licensed to be used as a biweekly 250 ppm topical solution, its incomplete efficacy led to the use of unlicensed protocols with more concentrated solutions applied weekly or even daily, in an attempt to increase its clinical efficacy. One study reported better success rate (75% vs 20%) by doubling the frequency of treatment to once weekly instead of the biweekly approved protocol. In Europe, weekly applications at concentrations of 500 to 1000 ppm was reported to be a very effective and a safe treatment regimen for CGD. In a study involving CGD cases resistant to the standard amitraz protocol, a 1250 ppm amitraz solution applied to half a dog's body daily was effective in 80 % of CGD cases. The mean duration of treatment was 6.5 weeks (range, three weeks to nine months). However, this more aggressive daily amitraz dip regimen never gained widespread popularity because the results were published roughly at the same time as mylbemycin and ivermectin were starting to show promising result in the treatment of this CGD.
Although the overall cure rate reported with amitraz dips, especially with the daily administration protocol, is relatively high, there are several disadvantages in its utilization in dogs with GD:
Adverse effects attributed to amitraz include sedation, pruritus, hypothermia, bradycardia, hypotension and hyperglycemia. Anorexia, polyuria, polydipsia, seizures, ataxia, and rarely death have also been reported. Interestingly, when amitraz was applied daily at five time the approved concentration (i.e. at 1250 ppm) side effects were apparently rare.
Milbemycin oxime
Recently, daily administration of milbemycin oxime (Interceptor®, Ciba-Geigy)-approved for use in dogs only as a monthly heartworm and intestinal parasite preventive at the dose of 0.5 mg/kg- was found to be effective in the treatment of CGD. The reported cure rate of CGD varied from 42 to 84.6% with an average daily dose of 1.0 mg/kg and 2.2 mg/kg respectively. The median duration of treatment with the higher daily dose was 13 weeks with a range from 9 to 26 weeks. Side effects were uncommon, but transient stupor, ataxia and trembling, that resolved after discontinuation of the treatment, have been reported. Milbemycin oxime is a very practical and relatively safe treatment in CGD. However, it is very expensive when use for this purpose.
Ivermectin
In dogs, ivermectin (Heartgard®, Merial) is only licensed for the prevention of dirofilariasis at the dosage of 6 µg/kg BW, orally once a month. Approximately 15 years ago, ivermectin was used in CGD by various investigators, at the dosage of 400 µg/kg subcutaneously, weekly, for a total of eight treatments, without any tangible benefit. However, daily administration of milbemycin oxime was subsequently found effective and, since ivermectin and milbemycin presumably have the same mode of action and spectrum of activity, the efficacy of ivermectin was re-investigated, using this time a high dosage administered daily in an adult dog with chronic GD. This initial case report showed promising results, and stimulated further research using high daily doses of ivermectin in CGD. The extra-label formulation used orally in these studies were either the 1% propylene glycol based injectable product (Ivomec® for cattle, sheep and swine, Merial) or the 1 % equine aqueous solution (Eqvalan® oral solution for horse, Merial). Ivermectin was found to be effective in up to 83.3% of adult dogs with generalized demodicosis with a daily oral dose of 300 to 600 µg/kg of body weight. Mean treatment duration typically varied from 10 and 18 weeks (based on treatment duration of one month beyond negative scrapings) with a range from 10 to 40 weeks. Transient side effects such as ataxia and mydriasis, were seen occasionally after a few days to a few weeks of treatment, subsided following withdrawal of ivermectin, or decrease of the dose administered.
The therapeutic potential of the 0.5% alcohol based pour-on formulation of ivermectin (Ivomec pour-on® for cattle, Merial) in the treatment of chronic generalized demodicosis in dogs has also been evaluated because of its presumed longer residual effect than the orally administered ivermectin in dogs. In this recent study, pour-on ivermectin was administered topically along the dorsal midline at 1,500 µg/kg (0.3 ml/kg) three times per week for up to six months. While all dogs had a substantial reduction in the severity of clinical signs and in the number of Demodex canis mites found on skin scrapings with this treatment regimen, only 1 of 12 (7%) dogs was cured. The treatment efficacy of the topical formulation may have been negatively affected by the fact that only 7 of 12 dogs completed the six-month trial. In addition, it is possible that an increased frequency of administration (i.e. 1,500 µg/kg q24h) may be more effective. However, this would render the treatment less practical and similar in cost to the more convenient daily oral ivermectin (at 600 µg/kg) treatment protocol with a reported cure rate of 83.3%, which remains a more effective and convenient formulation to use in dogs.
The extra-label use of daily oral ivermectin is therefore an effective therapeutic alternative for dogs with chronic generalized demodicosis resistant or intolerant to amitraz. It is much less expensive than milbemycin oxime and easier to administer than daily amitraz applications. However, it is also potentially more toxic and should be considered only if attempts with the conventional treatment for CGD has failed. Indeed, idiosyncratic reactions have been reported in Collies and other herding breeds such as Australian shepherds, Old English sheepdogs, Shetland sheepdogs or their outcrosses, following single dose as low as 100 µg/kg. These adverse reactions, include ataxia, behavior disturbances, tremors, mydriasis, weakness/recumbency, apparent blindness, hypersalivation, depression, and in severe cases, coma and death.
Lufenuron
Lufenuron (Program®, Ciba-Geigy), a benzoylphenyl urea, is an insect-development inhibitor for the cat flea, Ctenocephalides felis. It acts by blocking the synthesis and deposition of chitin and is both ovicidal and larvicidal. Chitin is found in Demodex spp. egg shells as well as larval, nymphal and adult exosqueletons. The efficacy of lufenuron for the treatment of CGD was recently investigated. It was found ineffective, even at the higher dosage regimen (mean dose of 15.8 mg/kg three times a week for 2 to 3 months), and despite the presence of high concentrations of lufenuron in the epidermis and dermis.
ANTIMICROBIAL TREATMENT
Systemic treatment:
Intercurrent pyoderma is present in most cases of CGD and contributes to the dog's immunosuppression. In most cases of pyodemodicosis, the bacterial component must be addressed before topical acaricidal treatment is initiated in order to make the skin less irritable and to allow better penetration of the acaricidal solution.
Antibiotic selection varies from case to case, but the oral antibiotic must be administered at proper dose and dosage interval for a minimum of 4 weeks, and for at least two weeks beyond complete healing of the sores. Typically, antibiotics are administrated for 6 to 8 weeks. Clinical normalcy may be hard to define in deep pyoderma because sterile pyogranulomatous or granulomatous components may persist making re-examinations mandatory before the antibiotic administration is stopped.
Intercurrent corticosteroid administration must be avoided.
Bacterial culture and sensitivity is often performed in the presence of a deep pyoderma associated with CGD, due to the possibility of mixed bacterial infection. In any case, a cytologic examination of the exudate from draining tracts or pustules should be performed to detect the type(s) of bacteria present.
Topical treatment
Topical treatment can be extremely beneficial, especially in the initial management of CGD cases with deep draining infections and cellulitis. The hair must be clipped (mandatory for amitraz dips) to prevent the formation of sealing crust and to allow the topical agents to come in contact with the affected skin. Hydrotherapy (whirlpool, warm water soaks, hot pack) helps to remove crust, decreases the number of bacteria, and promotes new skin formation. Magnesium sulfate (epsom salt) 30 ml/L of warm water 10-15 minute soakings, twice to 3 times daily, is a mildly hypertonic drawing solution and is usually very beneficial during the first few days of treatment. A medicated shampoo (antibacterial and/or antiseborrheic) can also be utilized as required.
CONCLUSION
Topical amitraz is the only approved treatment for CGD, however it is not always effective or tolerated. Extra-label use of amitraz, milbemycin oxime and ivermectin now offer effective therapeutic alternatives for dogs with GD resistant or intolerant to the licensed amitraz protocol. Daily oral milbemycin oxime (1 to 2 mg/kg) and ivermectin (400 to 600 µg/kg) are both very practical therapeutic options. The average duration of treatment with these treatment regimens is four months with an expected range of 12 to 40 weeks, but should be administered daily for a minimum of three months, and for at least one month after getting a series of negative skin scrapings.
Although CGD it still a disease that is not easily treated, its prognosis has improved dramatically in the past few years and CGD. However, the treatment alternatives for CGD described above are not approved by the FDA, and should only be used if your veterinarian thinks they are correct for your dog.
We hope that you will find this information helpful in understanding demodex in your pet(s). If you have any questions or comments, please call your veterinarian's office, or feel free to e-mail us.
David E. Hammett, DVM
and the Staff of All Creatures Veterinary Clinic,
PC
