Canine Atopic Dermatitis

Marsella and Nicklin (2002) performed early studies on the topical use of tacrolimus for treatment of AD in dogs. In the initial pilot study, which used a 0.3% lotion formulated from the oral product, investigator scores for erythema were lower (indicating less erythema) in tacrolimus-treated dogs than in placebo-treated dogs, but owner scores for pruritus were not significantly different for the two groups. However, a subsequent randomized, double-blind, placebo-controlled crossover study using commercially available 0.1% tacrolimus ointment (Protopic) found more encouraging results (Marsella et al, 2004). In this study, treatment with topical tacrolimus was evaluated in 12 dogs that were diagnosed with AD. After 4 weeks of once-daily application, investigator scores improved significantly in the tacrolimus-treated group, whereas no significant differences between pretreatment and posttreatment signs were detected in the placebo group. When the dogs were divided based on severity of disease, those with localized disease were found to show significantly greater improvement than those with generalized disease according to both owner and investigator assessments. In conclusion, this study found that tacrolimus ointment decreased clinical signs of AD over a 4-week period with minimal adverse effects or safety concerns. A third study investigated the efficacy of 0.1% tacrolimus ointment in the treatment of localized lesions of AD on the front paws of dogs (Bensignor and Olivry, 2005). All dogs had lesions at other sites, but these were not included in either treatment or evaluation. At the end of the 6-week study the primary investigator found that all dogs that completed the study showed a more than 50% decrease in lesional scores for the evaluated areas (based on grading of erythema, lichenification, oozing, and excoriations). This study did not evaluate pruritus.

Although the results of these studies showed benefit from topical application of tacrolimus, especially for localized AD, I have noted only limited benefit in the treatment of this disease. My experience corresponds with the observation that localized lesions may improve, but progress generally is limited to decreases in erythema with less effect on pruritus. As a result, owners have not perceived a benefit substantial enough to warrant continued administration in most cases. Tacrolimus remains a potential option for treatment of localized AD, especially when the practitioner is trying to minimize the use of other treatments that raise greater concern for adverse effects (e.g., topical or systemic glucocorticoids), but at least in my practice it is not used as a sole therapy.

A recent study evaluated the tolerability and safety of a 0.1% compounded tacrolimus solution (in olive oil) applied to the external ear canals of atopic dogs with normal otoscopic findings, including intact tympanic membranes (Kelley et al, 2010). In this prospective, double-blind, placebo-controlled trial a colony of high IgE–producing beagles validated as a model for AD were studied. This tacrolimus solution was well tolerated by these dogs, with no adverse topical reactions noted and no evidence of hearing loss. However, the olive oil vehicle may have predisposed to an increase in Malassezia overgrowth and mild otitis. These results, along with favorable outcomes reported with the use of an ear wick containing 0.1% tacrolimus ointment to treat chronic noninfectious otitis in human patients, suggests that further investigation of this therapy is warranted (Harth et al, 2007).

Immune-Mediated Diseases

An open-label study was performed by my practice evaluating 0.1% topical tacrolimus in the management of immune-mediated diseases such as discoid lupus erythematosus (DLE) and pemphigus erythematosus (PE). In this study 10 dogs with DLE and 2 dogs with PE were treated with a commercially available 0.1% tacrolimus ointment (Griffies et al, 2004). All dogs had lesions localized to the nasal planum and adjacent regions of the muzzle. Owners applied 0.1% tacrolimus ointment to the affected areas every 12 hours. Each dog’s lesions were assessed for degree of erythema, crust, ulceration or erosion, depigmentation, and scarring and were evaluated 2, 4, and 8 weeks after the start of therapy. Ten of 12 dogs exhibited improvement in clinical lesions associated with PE or DLE (5 with excellent response, 5 with partial response) over the 8-week trial. Of the dogs that showed progress, 8 of 10 were treated with tacrolimus alone by the end of the study and remained in remission at 12 weeks. Two of these dogs followed for an additional 2 years continued to do well with topical tacrolimus alone.

In my practice 0.1% tacrolimus has become a first-line drug for mild to moderate DLE. In mild cases it often is used alone every 12 hours for the first 2 weeks and then decreased to every 24 hours, depending on progress. Once clinical lesions have resolved, drug application can be tapered to every other day or twice weekly in many cases. In moderate to severe cases 0.1% tacrolimus ointment often is used as adjunctive therapy in combination with tetracycline and niacinamide, vitamin E, or oral corticosteroids. In these cases the use of topical tacrolimus may allow reduction of systemic therapies and can become part of the longer-term maintenance for this chronic disease. Similarly, I use topical tacrolimus as an adjunct in managing localized lesions of pemphigus foliaceus. Topical tacrolimus is not considered a successful primary or exclusive therapy for this disease; however, it may assist in managing localized lesions, such as those remaining on the nasal planum, without necessitating an increase in or modification of systemic medications such as corticosteroids or azathioprine, provided the majority of other lesions have resolved.