The Use of Ciclosporin and HCA in Atopic Dermatitis and Otitis Externa

HISTORY AND CLINICAL EXAM

A 5-year-old, male, neutered, Maltese x Shih Tsu dog presented with intermittent, recurrent and chronic otitis externa; he has had since 4 months of age with the left ear being worse than the right.  In the last 12 months he had developed pedal, facial and peri-anal pruritus; there was no obvious seasonality. He had a pruritus score of 10/10 without medication and 4/10 at time of referral. The dog was receiving oclacitinib 3.6 mg BID 14 days, then SID 2+ months; this was withdrawn 7 days prior to referral appointment and resulting in rapid return of pruritus.  The dog had been in the owner’s possession since being puppy, with no known family history of skin/ear disease, was fed a commercial diet and various treats, there was no current flea or worming prevention in place, and the vaccination status was complete.  

On clinical exam, there was a moderate submandibular (SM) lymphadenomegaly with mild bilaterally symmetrical periorbital erythema / alopecia.  He had moderate interdigital erythema especially on the plantar aspects of the forefeet which were thickened with scaling skin present. He had mild erythema of the peri-anal region.  Bilateral and symmetrical erythema, scaling, and crusting of the lower lip margins was present.  

On examination of the ears, the left medial pinna had severe skin changes with occlusion of external auditory meatus, hyperplastic changes and glandular proliferation, erythema, lichenification, hyperpigmentation and malodorous exudation extending to facial skin; the right medial pinna had milder changes including erythema, lichenification, hyperpigmentation and mild ceruminous exudation (see figure 1).  Both tympanic membranes were intact on otoscopic examination.

The anal sacs were expressed, with normal contents bilaterally.

DIFFERENTIALS

• Allergic dermatitis 

  • Atopic dermatitis

  • Cutaneous adverse food reaction

  • Flea allergic dermatitis

• Secondary infections of ears and skin

• Chronic irreversible changes to left ear - may require surgical intervention

• Parasitic disease

DIAGNOSTICS

Coat brushings and flea comb were negative.  Skin scrapings were negative. Cytology was performed in several locations with the following results:

• L pinnae – Malassezia+++, cocci+, neutrophils. 

• L ear cerumen – Malassezia ++, cocci+, rods+, neutrophils.

• L face – Malassezia ++, cocci+, neutrophils.

• Interdigital webs – Malassezia++.

• R ear cerumen – Malassezia+.

• Lip margins – Malassezia ++, cocci++, neutrophils.

A blood sample was taken and sent for serological allergy testing; with positive allergens identified for meadow fescue, orchard grass, perennial rye grass, timothy grass, Kentucky blue grass, cat epithelium, birch, lambs quarter and Malassezia spp.

Bacteriology was performed on the left ear for culture and sensitivity revealing β-haemolytic Streptococcus spp., coagulase positive Staphylococcus spp., Pasteurella spp., and Malassezia spp.  All three bacteria sensitive to pradofloxacin, marbofloxacin, potentiated amoxicillin, cephalexin and cefovecin.

TREATMENT

The initial treatment plan after diagnostics included liquid ciclosporin 5mg/kg SID PO; the use of chlorhexidine / trizEDTA wipes for ears / pinnae / lip folds / interdigital skin / perineum; ear drops containing marbofloxacin, clotrimazole and dexamethasone ear drops given 10 drops once daily; oral marbofloxacin 20mg BID 21 days; and itraconazole 50mg twice weekly each week with food (off-label consent obtained).  A food trial was discussed with the owner but they felt unable to medicate without treats and tasty foods. It was recommended to use imidacloprid / moxidectin spot-on every 4 weeks along with praziquantel / pyrantel and febantel every three months.

Three weeks on, the owner reported the dog to be happier with more energy.  SM lymph nodes were bilaterally slightly enlarged. There was a significant improvement in the ears, face and perineum with minimal pruritus present (figure 2).  A moderate pedal pruritus persisted (graded 4/10). The erythema was markedly reduced (~50%) on the pinnae, interdigital skin, lip margins and peri-orbitally. Cytology was repeated from both pinnae, the face, interdigital skin and lip margins – which were all normal; the left ear cerumen had scanty cocci only with the right having no abnormalities.  At this point, two more therapies were added to the treatment plan. These were allergen specific immunotherapy and the initation of topical hydrocortisone aceponate for both ears – the pinnae was sprayed and the HCA allowed to trickle down into external ear canals, this was done 2 to 3 times weekly (off licence consent obtained).

The dog continued to be regularly checked and, seven weeks on, there was a vast improvement with a pruritus score of 0-1/10 and significant improvement in clinical signs, particularly with a reduction in the secondary changes (figure 3).  At this stage, he was continued only on oral ciclosporin SID, allergen specific immunotherapy, aural HCA and the medicated wipes.

Thirteen weeks on, and having continued to show improvement, he was continued on oral ciclosporin tapering to alternate days, medicated wipes on alternate days, aural HCA twice weekly and immunotherapy (figure 4).

DISCUSSION

This dog presented with clinical signs typical of atopic dermatitis (AD), which is a very common condition among the canine population; although true incidence is unknown, it is estimated at 3-15% of the canine population.

Otitis externa (OE) is commonly seen with AD cases and as many as 80% of atopic dogs will have chronic or recurrent OE.  OE can be the only presenting complaint in up to 20% of AD cases, which is why it is so important to perform a thorough diagnostic work up to identify the underlying disease process.²

AD is a complex, multifactorial condition with inherited, environmental, parasitic, and sometimes dietary components. It has been described as ‘a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features’ and ‘it is most commonly associated with IgE antibodies to environmental allergens’.³  AD is chronic or relapsing and is usually initially characterised by pruritus, as was the case here.⁴  In healthy skin, there is an effective barrier to prevent penetration of most bacteria, viruses and parasites; whereas AD cases can have deficiencies in the intercellular lipid barrier, the lipid composition, and the dermal lipid arrangement.^5,6  Allergens having penetrated the skin barrier trigger an IgE mediated immune allergic reaction to certain environmental allergens with a TH-2 cell dominated allergic response.⁷  This all contributes to the difficulty of treatment and the need for potent and safe treatment options.⁸  Inevitably, when presented an animal with a complex disease, a thorough history is the most important first step.  In this case, the thorough work-up and treatments were used to eliminate other differentials and lead to a diagnosis.

_{1. Rhodes, K. & Werner, A. (2011).  Atopic Dermatitis. In: Blackwell’s 5 Minute Consult. Clinical Companion. Small Animal Dermatology, Second Edition, p94-103.
2. Nuttall, T., Harvey, R.G. & McKeever, P. J. (2009).  Pruritic Dermatoses.  In: A Colour Handbook of Skin Diseases of the Dog and Cat, 2nd Edition, p24.  Mason Publishing.
3. Miller, W.H, Griffen, C.E & Campbell, K.L (2013).  Hypersensitivity Disorders.  In: Muller and Kirk’s Small Animal Dermatology, 7th Edition, p365-388. Published by Elsevier.
4. Bizikova, P., Santoro, D., Marsella, R., Nuttall, T., Eisenschenk, M. N., & Pucheu‐Haston, C. M. (2015). Review: Clinical and histological manifestations of canine atopic dermatitis, Veterinary Dermatology, 26(2), 79-83.
5. Olivry, T., Marsella, R. & Hillier, A. (2001).  The ACVD Task Force on Canine Atopic Dermatitis (XXII): Are Essential Fatty Acids Effective?, Veterinary Immunology and Immunopathology, 81, p347-362
6. Coatesworth J. (2010).  Canine Atopic Dermatitis, UK Vet Companion Animal, 15 (1), p33-37.
7. Marsella, R. (2006).  Atopy: New Targets and New Therapies, Veterinary Clinics Small Animal Practice, 36, p161-164.
8. Nuttall, T., Mueller, R., Bensignor, E., Verde, M., Noli, C., Schmidt, V. & Rème, C. (2009) Efficacy of a 0.0584% hydrocortisone aceponate spray in the management of canine atopic dermatitis: a randomised, double blind, placebo-controlled trial, Veterinary Dermatology, 20(3), p191-8.}