Sunday, July 14, 2019

Adventures in Canine Dermatology

Once Humphrey's eye issues finally resolved, the next issue to tackle is his coat and skin.

About a year ago, Humphrey's coat began thinning, starting on the hind legs, and gradually affecting the tail, and the lower half of his body. Wearing the cone of shame also led to hair loss and skin damage on the back of his neck. Luckily, the front of his body remains fine (for now).
Despite alopecia, Humphrey is currently looking good and feeling great!


Extensive diagnostic testing revealed no medical explanation. Blood tests sought answers, especially thyroid/hormonal irregularities (such as Cushings) that are often associated with symmetric patterns of hair loss like Humphrey experienced. His blood tests have remained clear for a full year.

He was checked for parasites (such as dermodex mites), infections, and yeast/fungus. Scrapings and a lab culture revealed nothing wrong. Initially, an examination under a Woods Lamp revealed an excess of possible yeast. So, for  a year, he endured Nizoral baths, with the hope that the active ingredient (the antifungal ketokonazole) would eliminate any excess yeast. For periods of time, he was bathed every 2 days, otherwise weekly. He was also prescribed several courses of antibiotics to help with management. It made little difference.

This is a fantastic overview of dog hair loss by Dr. Karen Campbell, a veterinarian and Professor Emeritus at the University of Missouri, titled "The Bald Patient" - with photos and all!

With everything else ruled out, it appears that Humphrey may be suffering from an autoimmune disorder called sebaceous adenitis - but this is a tentative diagnosis of exclusion. Lucky for Humphrey, sebaceous adenitis does not pose any health risks, and the resulting alopecia and skin dryness is purely cosmetic.

Beginning this summer, Humphrey will undergo some interventions to see if the hair loss can be stopped, and perhaps even regrown! The best overviews of the affliction and its treatment, upon which the following is based, are:

Treatment of sebaceous adenitis can be pharmacological/systemic (with cyclosporine, tetracycline, and oral retinoids), supplement-based (essential fatty acids, vitamin A, zinc, biotin), or topical (a combination of mineral oil, topical essential fatty acids, moisturizers, and salicylic acid cleansers). Research suggests that topical treatment can be as effective as pharmacological/systemic while avoiding the dire potential side-effects of immunosuppressants (oral cyclosoporine) or heavy-duty antibiotics and retinoids (tetracycline).

Here's an overview of the recommended, non-systemic treatments.

Supplements (should be monitored by a veterinarian)

  • Melatonin has been shown to work on various alopecias (hair loss) in animals. The dose should be 1 mg for dogs under 10 lbs, and 2mg or 3mg for dogs 10 to 20 lbs (larger doses for larger dogs) for a period of 8 to 12 weeks. Melatonin is widely used to treat dogs with various anxiety disorders.  Melatonin can be applied topically - and topic treatment has been shown to be effective in humans.
  • Biotin can improve alopecia in cases where a dog has a biotin deficiency. The recommended dose is 5mg per 10 kg of body weight for 4 to 6 weeks. In a study of 119 cases, all responded to some degree, but only about half achieved significant improvement.
  • Vitamin A, 1000 IU per kg of weight, not to exceed 20,000 IU 
  • Omega 3 essential fatty acids, 180mg per 5 kg of mody weightin in a formulation of EPA and DHA. Ascenta/NutraSea is a widely available,cost-effective option formulated for dogs. 
  • In some cases, Zinc supplementation may be warranted, where the skin quality shows signs of possible Zinc deficiency (and Zinc also helps to keep Vitamin A in one's system). Dosing of Zinc depends on the type: Zinc sulfate: 10mg/kg; Zinc guconal/gluconate, 2mg/kg.
Topical Washes
  • SALICYLIC ACID WASH. For at least 4 weeks, shampooing with a salicylic acid shampoo after a few hours of intense moisturization (mineral oil or baby oil) is recommended. The salicylic acid removes excess topical oil, but also de-scales and exfoliates dead and dry skin that can block hair growth. Widely available options include Sebcur and Neutrogena T/Sal.

Topical Ointments and Oils (all are recommended, to work together to heal the skin)
  • MINERAL OIL. A first line of defense is a weekly, 2 hour soak with baby oil or another mineral oil. The purpose of this is to moisturize the top layer of the skin, which is typically dried out  in cases of sebaceous adenitis. After applying oil to the whole body (which is sometimes recommended in a 50% water dilution), the excess can be washed away. Upon results in 4 to 8 weeks, the frequency of this step can be decreased.
  • ESSENTIAL FATTY ACIDS (EFAs). In between the intense baby oil soaks, less oily but constant moisturization is recommended. First is using topical essential fatty acids (EFAs), which are widely available in beauty products in the form of botanical oils. For instance, sunflower oil, chia oil, and others are effective EFAs. Many are available at low cost. The Ordinary offers a pure chia oil for under $8 Canadian. Peas in a Pod offers Bottoms Up "bum spray" for babies that contains various EFAs and other moisturizing agents. Finally, Verb Ghost Dry Oil and Briogeo Farewell Frizz (a leave-in conditioner) both provide spray-on formulations that contain EFAs without too much mess. Studies published in medical journals on humans as well as on rats reveal that EFAs have benefits for healing and preventing lesions that far exceed mineral oil (e.g., those prone to pressure ulcers). For those with sebaceous adenitis, EFAs provide moisture to heal the skin and possibly hair follicles.
  • MOISTURE-LOCKING TOPICALS. The research on sebaceous adenitis also recommends applying a moisture-locking preparation daily - usually a propylene glycol spray. This does not replace EFAs (which moisturize), but rather locks the moisture into skin and hair. Commercially, Naked Manicure Hydrating Hand and Body Serum is a non-greasy, propylene glycol solution. Alternately, there may be value in using a hyaluronic acid preparation to lock moisture into the skin and hair, such as The Ordinary's Hyaluronic Acid 2%.
  • ANTI-INFLAMMATORY TOPICALS (E.G., PHYTOSPHINGOSINE). Research suggests value in applying phytosphingosine, which has anti-inflammatory properties and is part of the skin's natural lipd layer. It often appears in ceramide-based cosmetic creams for humans (since phytosphingosine is part of the ceramide structure) which can be used. It is a main ingredient in the Douxo Calm line for dogs (e.g., the Douxo Calm Mousse). A multi-tasking product from The Ordinary called Natural Moisturizing Factors + HA contains ceramides as well as hyaluronic acid may be a good substitute for the much more costly Douxo products (though may be more difficult to apply than the Douxo spray or mousse)
  • MELATONIN is sometimes applied topically.
Other interventions may contribute to managing sebaceous adenitis that should be further explored. These include:
  • Red light therapy, that is effective in human dermatology and hair loss.
  • Microneedling (AKA, the Kim Kardashian Vampire Facial) has been effective in treating dogs with alopecia X that are resistant to other treatments. In addition to a study published in a veterinary journal, it is now practiced at Colorado State University's veterinary school (check out the dramatic before-and-after photos on their site). Nobody in Canada is currently practicing microneedling on dogs.  
  • Urea-based creams that moisturize and may contribute to gentle exfoliation and de-scaling.
  • Vitamin A topicals that could assist with  exfoliation and skin quality, such as Mad Hippie Vitamin A Serum (it is all natural and contains EFAs) or The Ordinary's Retinol 1% in Squaline (a bargain at $6!). Vitamin A is harsh on the skin - so must be used in small quantities and definitely not more than once weekly to start. However, since topical Vitamin A (Retinol) cause skin renewal, it might be beneficial for the exfoliation process, and avoids the dangers of oral retinoids which are sometimes prescribed to dogs. One caution is that topical Vitamin A causes sun sensitivity, so the skin to which it is applied should be covered when outdoors.
  • Various essential fatty acid (EFA) masks and leave in treatments, such as Kiehl's Ginger Leaf and Hibiscus Firming Mask, or Weleda's Skin Food, could enhance the skin's moisure. These are rich oil-based pastes, so may pose some challenge in application on a dog with a dense coat.
  • Omega 6 promotes dermal healing, both topically and orally (see Silva et al., 2018). While the earlier research emphasizes Omega 3 supplementation, it may be beneficial to also supplement Omega 6 (topically, sunflower oil is perhaps the best source of Omega 6). 
  • Peppermint and rosemary essential oils (diluted in a carrier base of sesame and sweet almond oils) stimulate hair follicles and deliver moisture when massaged.
So now, we apply lotions and potions, and wait a month or two. Fingers crossed that these work!

UPDATE: 4 months later, Humphrey is experiencing some hair regrowth! The regrowth remains patchy, but the vet and the groomer commented on it without prompting.  It seems that his progress may be related to the following:
- 0.25 mg melatonin, orally, every night. This is about 1/12 the recommended dose for a dog his size experiencing Alopecia X, but it seems to work. Biotin supplements had no effect and were tried for about 6 weeks before melatonin.
- Oral Omega 3 supplement for dogs daily as directed on packaging.
- Weekly shampooing with Nizorol and a salicylic shampoo (a good option is LaRoche-Posay), and if necessary a wipe down with Clean & Clear's lemon exfoliating wipes.
- Weekly serum treatment with Elizabeth Arden ceramide pods on the affected areas right after bathing. The Elizabeth Arden pods (even when used mid-week) seem to cause immediate exfoliation of any dark spots that materialize. They also seem to deliver more sustained moisture to the skin than other products (perhaps this has to do with ceramides which purport to be identical to the skin).
- Daily moisturizing with a rotation of  Avene Cicalfate (it contains zinc, moisturizes without being gooey, and is a good barrier cream for bare skin in harsh weather), the sesame oil tincture containing peppermint essential oil, and an EFA treatment with Yves Rocher creme riche. It seems that Humphrey's skin's needs changed based on the weather, so his treatments are adjusted from day to day with this group of products.
- Occasional red light therapy using the now-defunct Tanda Luxe device (other options remain on the market). Humphrey does not love sitting still long enough to do a proper treatment, but it's a harmless process that probably yields some benefit to the skin if not hair follicles. The vet wondered if this wasn't the deal-maker in his progress.

On a related note, we have spoken with the vet about microneedling, and he is fascinated but (not surprisingly) unwilling to try. Presently, no local vets in Canada nor US locations surrounding Humphrey's home offer it. Depending on Humphrey's progress, we may attempt a DIY with the help of women who are skilled at doing their own (human) microneedling at home and swear it is not uncomfortable.

Treating dry eye - a work in progress

Humphrey's ophthalmologist has initiated some treatment for dry eyes. Keratoconjunctivitis sicca (or keratitis sicca) is chronic, bilateral desiccation of the conjunctiva and cornea due to an inadequate tear film. Humphrey has typically shown low-normal tear production on the Schirmer tear test (STT), but his values were never quite low enough to warrant formal treatment. Even after his recent corneal ulcers, his STT is unclear.

Humphrey's delighted expression the moment he learned his ulcer was healed and the cone was off for good!

Nonetheless, his STT history suggests he may benefit from attempting to increase tear production, as well as adding artificial lubrication. For the past 10 days, he has received OptixCare with hyaluron lubricating gel in his eyes multiple times a day, and it gives him immediate relief. In fact, he signals discomfort every so often by trying to paw at his face, and immediately stops when the gel is administered.

The next intervention recommended is the introduction of topical cyclosporine or tacrolimus. Often taken orally or intravenously, cyclosporine is an immunosuppressant used to treat rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, and in organ transplants to prevent rejection. But in ophthalmology, it is used topically in drops or gel to stimulate tear production.  Fun fact: ophthalmologic cyclosporine was originally developed for use in dogs, then adapted for humans as Restasis. Tacrolimus is typically also used as an anti-rejection medication when prescribed orally, but in veterinary ophthalmology it is applied topically to stimulate tear production.

In humans, a preparation of 0.05% cyclosporine is sufficient to stimulate tear production for people who suffer from dry eyes, but the proportion is different for dogs. veterinary A product called Optimmune® is widely available (and inexpensive compared to the human preparation!) at 0.2%, but Humphrey's ophthalmologist is considering up to a 2% preparation. However, Humphrey discovered that small dogs who received 2% experienced suppression of systemic lymphoblastogenesis, but not with 0.2%, suggesting that a lower concentration might be safer for a fellow his size.

Humphrey's opthalmologist prescribed tacrolimus 0.02% in an olive oil suspension - and it has worked extremely effectively. Upon his first dose, his scleritis (inflammation/redness of the sclera or whites of the eye) resolved! He will continue on EDTA as well, to manage mineral deposits that arrive in his eyes.

By the middle of July, as predicted, Humphrey's corneal lesions seem to have resolved - the scar tissue seems to be mostly gone, and his vision is restored, even in the bright sun!

This is a fantastic resolution to a very long and difficult healthcare journey!

Plasma for the eyes

Humphrey has benefited from ophthalmologic plasma drops in his eyes. He's decided to do a little further research to understand why, and if he might benefit from longer-term use of plasma.

Plasma has been used in ophthalmology for about 20 years, because plasma allows for a variety of therapeutic benefits based on its composition. An outstanding summary in Acta Ophthalmologica provides a comprehensive description of components, but  highlights include:

  • epidermal growth factor (EGF) and transforming growth factor‐β (TGF‐β) which promotes tissue growth 
  • fibromectin and fibroblas growth factor B (BFGF), which promote healing
  • albumin
  • a high concentration of vitamin A that reduces degradation of cytokines and growth factors
  • nerve growth factor (NGF) that helps to restore the function of injured neurons
Plasma is are used to treat corneal problems and substitute for natural tears in some cases where the body cannot sufficiently produce tears according to he Review of Ophthalmology., as well as for lesions and healing after LASIK surgery.

In humans, autologous plasma (meaning the patient's own) is used, as well as donor plasma where the source is a blood bank. The UK's Queen Victoria Hospital produced an excellent informational document on the collection, preparation and use of autologous plasma for corneal disease, including dry eye.

According to the Review of Ophthalmology, ophthalmologic plasma can be pure, or diluted with sterile saline to contain 20%, 25% or 50% plasma serum to saline. In that article, a physician interviewed estimates about half of patients who try plasma receive sufficient benefit to continue with the costly drops.

So far, Humphrey has benefited from plasma obtained from the animal blood donor clinic, but his vet is able to create autologous serum for him for a cost of around $100. The latter, as far as he knows, would not be diluted.

2021 UPDATE: Humphrey needed plasma for his eyes in 2021, but could not get an appointment with an ophthalmologist in time to get sufficient plasma for every-two-hour instillation! No vets in the area carried it. So, he put his crack research skills to work and determined that it could indeed be ordered (by a vet) from the Canadian Animal Blood Bank in Alberta. For ophthalmologic use, the product is Canine Neonate Plasma, 5 ml for $20 in 2021 plus shipping. It shipped in 24 hours frozen, and each 5ml vial was sufficient for 2 or 3 days of drops instilled every 2 hours. We used fine-tipped glass eyedropper which we sterilized every day. Once unfrozen, the plasma is good for about 3 days (though one ophthalmologist told us it can be used for up to 5 days). If kept in the freezer, the vials are good indefinitely.



Thursday, July 11, 2019

Humphrey's angelic look-a-like

A friend of Humphrey's remarked that he bore an uncanny resemblance to actor Michael Sheen in "The Good Fight." True enough (with the defiant grin, on a day he refused to come inside), but perhaps he resembles Sheen's angelic incarnation in "Good Omens" even more closely? You be the judge...