Friday, March 21, 2014

Three things I learned: treatment of demodex in dogs

This is Jen. No, she doesn't suffer from demodex, but she does like to cool off in her shell pool.

As a companion animal veterinarian I see demodex mange (aka demodicosis) reasonably commonly in practice, so it was nice to hear an update on treatment and drug interactions by dermatologist Rob Hilton during another fantastic webinar this week.

He talked about demodex in dogs and cats but the key things I learned really relate to demodex in dogs.

It is caused by three species: D. canis, D. injai (much harder to diagnose and sometimes can only been seen on biopsy) and D. cornei which is probably a morphological variant of D. canis

The first thing I learned is that the juvenile form (localised or generalised) probably has a genetic basis but it is the mites and the bacteria associated with them via secondary infection which produce byproducts that induce immunosuppression. So the immunosuppression is reversed when you treat the bacterial infection and the mites.

Adult onset demodicosis is associated with an acquired immunodeficiency, but it can be difficult to identify an underlying cause in many cases.

The cornerstones of treatment are the macrocyclic lactones and amitraz, but no treatment is 100 per cent successful in clearing mites and no demodicosis can be considered cured unless it has been twelve months without relapse.
Adult cases where there is an uncontrolled, undiagnosed primary cause are very hard to treat.

The second thing I learned is the key reasons for treatment failure.
  1. Not treating for long enough – dogs should be treated for three negative skin scrapes 3-4 weeks apart.
  2. Resistance or refractory infestation – where 6 weeks after treatment commences, there are large numbers of mites, nymphs and eggs on skin scrapes/hair plucks
  3. Poorly stored medications – especially the macrocyclic lactones, they don’t like being exposed to air or light
  4. Not getting the treatment dose right
  5. Not treating secondary infections (Dr Hilton recommends cephalexin 25mg/kg BID for a minimum of three weeks or 10-14 days from clinical resolution; or cefovecin fortnightly for two doses SC; as well as use of a chlorehexidine shampoo twice a week followed by a leave in conditioner).
  6. Inability to treat the underlying cause
  7. Immune system collapse

The third thing I learned is around minimising the risk of toxicity when treating dogs with the macrocyclic lactones.

Dr Hilton discussed the different drug doses he used, but the main point is that he uses a “build up protocol” in ALL animals, not just those with reported susceptibility to toxicity (usually commencing at 50micrograms/kg until the final dose is reached). The main reason for this is that while collies and shelties and select other breeds possess the MDR delta-1 gene defect (involved in the coding for P-glycoprotein), 1-2 per cent of any breed can have it…and some dogs WITHOUT the genetic defect will be susceptible to toxicity.

[P glycoprotein is present in lots of cells, and occurs in intestinal lining and the CNS vascular endothelium. It pumps out noxious agents from cells. Macrocyclic lactones are highly lipid soluble and readily enter the CNS, but P glycoprotein defects mean that these drugs can accumulate in the CNS].

Thus while genetic tests can prove that the drug is UNSAFE in a particular dog, they cannot prove that the drug is SAFE in that dog. He offers genetic tests for the gene in all patients where macrocyclic lactones may be used to treat demodicosis, but insists if there is any chance the animal may be related to a herding breed.

And he puts all animals through a build-up protocol even when the test is negative for the genetic defect.

There are a lot of drugs that should not be used in dogs on these medications and it all depends on whether they compete with P glycoprotein. These include antifungal azoles, some antibiotics and anti-emetics, numerous chemotherapeutic agents, anaesthetics and antihistamines.

Dr Hilton also talked about the use of amitraz in the treatment of demodicosis. Currently this is only available off label in Australia and there are some human safety issues that make its use rather challenging (e.g. potential health risks to diabetic pets and owners, ditto owners with asthma, owners and pets on MOAIs and SSRIs etc.)