Topical 0.1% tacrolimus for the treatment of discoid lupus erythematosus and pemphigus erythematosus in dogs

Topical 0.1% tacrolimus was used for treatment of localized lesions associated with 10 cases of discoid lupus erythematosus (DLE) and two cases of pemphigus erythematosus (PE) either as a sole therapy (n=2) or as an adjunctive treatment (n=10). Eight of 10 dogs with DLE and both dogs with PE were improved following 8 weeks of topical application. In six of the eight dogs that improved, other medications were discontinued. No adverse effects in clinical or laboratory parameters were noted throughout the study.     

P-49 Pemphigus foliaceus confined to the nails in a Hungarian short-haired pointer

The purpose of this study was to determine whether tacrolimus ointment (Protopic) decreased the severity of localized lesions of canine atopic dermatitis (AD). Twenty dogs with AD were enrolled if they exhibited skin lesions localized to both front metacarpi. Each foot was randomized to be treated either with 0.1% tacrolimus or placebo (vaseline) ointment twice daily for 6 weeks. The nature of treatment for each foot lesion was concealed from the clinician. Before, and every 2 weeks during the study, erythema, lichenification, oozing and excoriations each were graded on a 10-point scale (maximal total score: 40). The primary outcome measures consisted of the percentage reduction from baseline of lesional scores, and the number of subjects whose scores had decreased by 50% or greater by the end of the study. Intent-to-treat analyses were used. At the beginning of the study, lesional scores were not significantly different between treatment groups. After 6 weeks, the percentage reduction from baseline scores was higher for tacrolimus-treated sites [median: 63% (95% CI: 39–67)] than for placebo-treated feet [3% (-2-13)] (paired t -test; P  < 0.0001). When tacrolimus was applied, lesions decreased by 50% or greater in 15 dogs (75%), while this benchmark was not reached for any placebo-treated feet (Fisher's exact test; P  < 0.0001). Adverse drug events consisted of minor irritation in some dogs treated with tacrolimus. Results of this randomized, controlled trial suggest that the daily application of 0.1% tacrolimus ointment is useful for reducing the severity of localized skin lesions of canine AD.
Funding: Self-funded.     

P‐48 Treatment of localized lesions of canine atopic dermatitis with tacrolimus ointment: a blinded,randomized, controlled trial

The purpose of this study was to determine whether tacrolimus ointment (Protopic) decreased the severity of localized lesions of canine atopic dermatitis (AD). Twenty dogs with AD were enrolled if they exhibited skin lesions localized to both front metacarpi. Each foot was randomized to be treated either with 0.1% tacrolimus or placebo (vaseline) ointment twice daily for 6 weeks. The nature of treatment for each foot lesion was concealed from the clinician. Before, and every 2 weeks during the study, erythema, lichenification, oozing and excoriations each were graded on a 10‐point scale (maximal total score: 40). The primary outcome measures consisted of the percentage reduction from baseline of lesional scores, and the number of subjects whose scores had decreased by 50% or greater by the end of the study. Intent‐to‐treat analyses were used. At the beginning of the study, lesional scores were not significantly different between treatment groups. After 6 weeks, the percentage reduction from baseline scores was higher for tacrolimus‐treated sites [median: 63% (95% CI: 39–67)] than for placebo‐treated feet [3% (‐2‐13)] (paired t‐test; P < 0.0001). When tacrolimus was applied, lesions decreased by 50% or greater in 15 dogs (75%), while this benchmark was not reached for any placebo‐treated feet (Fisher's exact test; P < 0.0001). Adverse drug events consisted of minor irritation in some dogs treated with tacrolimus. Results of this randomized, controlled trial suggest that the daily application of 0.1% tacrolimus ointment is useful for reducing the severity of localized skin lesions of canine AD. Funding: Self‐funded.     

Treatment of localized lesions of canine atopic dermatitis with tacrolimus ointment: a blinded randomized controlled trial

This investigator-blinded randomized controlled trial was designed to determine whether tacrolimus ointment (Protopic, Fujisawa Healthcare) decreased the severity of localized lesions of canine atopic dermatitis (AD). Twenty dogs with AD were enrolled if they exhibited lesions on both front metacarpi. Each foot was randomized to be treated with 0.1% tacrolimus or placebo (vaseline) ointment twice daily for 6 weeks. Before, and every 2 weeks during the study, erythema, lichenification, oozing and excoriations each were graded on a 10-point scale (maximal total score: 40). The primary outcome measures were the percentage reduction from baseline of lesional scores and the number of subjects whose scores had decreased by 50% or greater at study end. Intention-to-treat analyses were used. At study onset, lesional scores were not significantly different between sites treated with tacrolimus or placebo. After 6 weeks, the percentage reduction from baseline scores was higher for tacrolimus-treated sites (median: 63%; 95% confidence interval: 39-67) than for placebo-treated feet (median: 3%; confidence interval: -2-13) (Wilcoxon test; P = 0.0003). When tacrolimus was applied, lesions decreased by 50% or greater in 15/20 dogs (75%); these dogs were those that completed the study. In contrast, this benchmark was not reached for any placebo-treated feet (Fisher's test; P < 0.0001). Adverse drug events consisted of minor irritation in some lesional areas treated with tacrolimus. Results of this trial suggest that the application of 0.1% tacrolimus ointment is useful for reducing the severity of localized skin lesions of canine AD.     

A case of interface perianal dermatitis in a dog: is this an unusual manifestation of lupus erythematosus?

Discoid lupus erythematosus (DLE) is a well-known autoimmune disorder described in dogs and humans. In dogs, DLE is considered the second most common immune-mediated dermatitis and is usually localized to the nasal planum. DLE does not evolve to generalized disease, however lesions may spread to the bridge of the nose and less commonly may extend to periocular region, pinnae, distal limbs, and mucocutaneous junctions (lips, oral cavity, and genital region). A 4-year-old male Bavarian Mountain Scenthound developed a chronic, erosive, cutaneous lesion located exclusively in the perianal region without facial skin involvement. Clinical signs included erythema, depigmentation, severe alopecia, crusting, and ulceration. Histologically, the hallmarks of the changes were an interface dermatitis consisting of plasma cells, lymphocytes, neutrophils, and macrophages, hydropic degeneration of basal cells, few apoptotic cells in the basal layer, pigmentary incontinence, and a focal thickening of the basement membrane, which was characterized by linear deposition of IgG. Despite the unusual localization the lesion was diagnosed as DLE based on the characteristic histologic and immunohistologic features. Following diagnosis, corticosteroid therapy resulted in a complete resolution of perianal lesions.     

Ulcerative dermatosis of the Shetland sheepdog and rough collie dog may represent a novel vesicular variant of cutaneous lupus erythematosus

A syndrome of ulcerative dermatitis (UDSSC) previously has been described as unique to the Shetland sheepdog and rough collie dog. The pathogenesis of this disease is poorly understood and it has been suggested that it may be a variant of canine dermatomyositis (DM) which is also seen in these breeds. Information on the clinical presentation and previous medical history was collected from five Shetland sheepdogs and three rough collie dogs previously diagnosed with UDSSC. Characteristic features of the disease were adult onset in the summer months with annular, polycyclic and serpiginous ulcerations distributed over sparsely haired areas of the body. Skin biopsies taken from active lesions were compared in a blinded fashion with histological sections from seven Shetland sheepdogs and one rough collie with DM. Dermatomyositis was characterized histologically as a cell poor interface dermatitis associated with follicular atrophy. In contrast, the lesional pattern of UDSSC is that of a lymphocyte-rich interface dermatitis and folliculitis with vesiculation at the dermal–epidermal junction. The authors conclude that these represent two distinct diseases and that UDSSC may be a vesicular form of cutaneous lupus erythematosus seen in the adult rough collie dog and Shetland sheepdog.     

Hereditary nasal parakeratosis in Labrador retrievers: 11 new cases and a retrospective study on the presence of accumulations of serum ('serum lakes') in the epidermis of parakeratotic dermatoses and inflamed nasal plana of dogs

We report 11 new cases of hereditary nasal parakeratosis in Labrador retrievers. The disease was first observed when the dogs were 6 months to 2 years of age, and affected dogs of either sex and all coat colours. Hyperkeratosis and depigmentation were confined to the nasal planum, and affected dogs were otherwise healthy. The principal histological findings in biopsy specimens were marked diffuse parakeratotic hyperkeratosis, multiple intracorneal serum lakes and superficial interstitial-to-interface lymphoplasmacytic dermatitis. Topical applications of propylene glycol in water or white petrolatum were often effective for treatment of the dermatosis. However, continued applications were required to maintain a beneficial response. A retrospective histological study of parakeratotic inflammatory diseases of canine haired skin and inflammatory diseases of the canine nasal planum was performed. The degree of parakeratotic hyperkeratosis and the number and size of intracorneal serum lakes were evaluated. The degree of parakeratotic hyperkeratosis was greater in hereditary nasal parakeratosis specimens than that seen in discoid lupus erythematosus and Malassezia dermatitis. There were more serum lakes in hereditary nasal parakeratosis specimens than in specimens from dogs with discoid lupus erythematosus, Malassezia dermatitis, primary seborrheic dermatitis or zinc-responsive dermatosis. Significant differences in sizes of serum lakes (if present) were not seen.     

Investigation on the clinical efficacy and safety of 0.1% tacrolimus ointment (Protopic) in canine atopic dermatitis: a randomized, double-blinded, placebo-controlled, cross-over study

Topical tacrolimus is successfully used in people with atopic dermatitis. Preliminary studies in dogs with atopic dermatitis using tacrolimus in a compounded lotion formulation indicated that tacrolimus significantly decreased erythema and pruritus according to investigator, but no significant improvement was reported by the dog owners. The objectives of this study were to evaluate the clinical efficacy and safety of the commercially available 0.1% tacrolimus ointment (Protopic) in dogs with atopic dermatitis. The study was designed as a double-blinded, placebo-controlled, cross-over study. Selected dogs were allocated to either tacrolimus or placebo for 4 weeks. After 4 weeks there was a wash-out period of 2 weeks and treatments were switched. Twelve dogs completed the study. Clinical signs were scored. Blood samples were collected for complete blood count, chemistry panels and tacrolimus levels at week 0 and 4 of each treatment. Tacrolimus ointment significantly decreased severity of symptoms for both owners and investigators at the end of the trial. When the same dogs received the placebo, there were no differences between week 0 and week 4 scores. Dogs with localized disease responded better than dogs with generalized disease. Tacrolimus was detected in the blood of animals receiving the active ingredient. Levels were below the level of toxicity and no adverse effects were reported in any of the dogs. No changes in complete blood count and chemistry parameters were detected between groups or within groups. In conclusion, tacrolimus appears to be a safe alternative treatment in dogs with atopic dermatitis, especially in those with localized disease.     

Comparison of three monoclonal and three polyclonal antibodies in the immunohistochemical diagnosis of canine autoimmune skin diseases

The aim of this study was to evaluate the utility of three monoclonal antibodies (mAbs), and two anticanine IgG and one anticanine IgM polyclonal antibodies (pAbs) for the immunohistochemical diagnosis of canine autoimmune skin diseases. Skin biopsies from 11 cases of pemphigus (7 foliaceus, 3 vulgaris and 1 erythematosus), 12 cases of discoid lupus erythematosus (DLE) and 12 cases of chronic hyperplasic dermatitis were used. The CA4E7 mAb (IgG1 + IgG2) showed similar sensitivity, but higher specificity and lower background than the two anti-IgG pAbs for the immunohistochemical diagnosis of pemphigus and DLE. The CA4F1 mAb (IgG2) and CA3H1 mAb (IgG2) showed moderate and low interepithelial reactivity, respectively, in autoimmune skin diseases, but strong staining of the cytoplasm of plasma cells of the inflammatory infiltrates. These results suggest that the CA4E7 mAb may be valuable in the immunohistochemical diagnosis of such disorders.     

Topical tacrolimus (FK506) for the treatment of feline idiopathic facial dermatitis

A 3-year-old, neutered male Persian cat with chronic ulcerative facial dermatitis was diagnosed with feline idiopathic facial dermatitis based on signalment, clinical history and diagnostic test results, including dermatohistopathological evaluation. Initial treatment started with 4 weeks of oral antifungal/antibiotic medication for severe secondary infectious dermatitis of Malassezia and bacteria. As the lesions gradually improved, the oral medication was withdrawn, leaving only 0.1% topical FK506 (tacrolimus) ointment for the remaining lesions. Topical treatment was administered just in case any new lesions developed. The patient has been managed effectively with topical tacrolimus and no side-effects were observed during treatment. Feline idiopathic facial dermatitis is known as a difficult dermatosis to manage successfully, but our experience suggests that it may respond to topical tacrolimus.     

Exfoliative cutaneous lupus erythematosus in German shorthaired pointer dogs: disease development,progression and evaluation of three immunomodulatory drugs (ciclosporin,hydroxychloroquine, and adalimumab) in a controlled environment

Six German shorthaired pointer dogs (two females, four males) with exfoliative cutaneous lupus erythematosus (ECLE) were studied in a controlled setting until disease progression necessitated euthanasia. During investigations into the heredity of disease, five dogs received immunomodulatory drugs to alleviate clinical signs (lameness, erythema, scaling, erosions/ulcers). One dog served as a control and received only baths and oral fatty acids. Four dogs received ciclosporin (5–10 mg/kg once daily) for 4.5 months to 2 years. Ciclosporin decreased erythema and arthralgia, but did not halt worsening of lesions. Three dogs received hydroxychloroquine (5–10 mg/kg once daily) for 8 weeks, 7 months, and 9 months, respectively, with no side effects. Hydroxychloroquine appeared to slow clinical progression in two dogs on extended treatment and normalized globulin levels in all three dogs while receiving the drug. Four dogs, including the control dog, were euthanized between 1 and 4.5 years of age. Two remaining male dogs received a tumour necrosis factor (TNF)‐α antagonist, adalimumab, at 0.5 mg/kg every 2 weeks for 8 weeks then weekly for 8 weeks. Serum TNF‐α levels were not significantly altered nor were quantifiable changes seen in skin lesions or lameness. Subsequently, the dogs were maintained on hydroxychloroquine for another year. This is the first study to evaluate the use of a TNF‐α inhibitor for canine lupus and the first to address the safety of long‐term administration of hydroxychloroquine, albeit in a small number of dogs. The study documents the progression of ECLE and generally poor response to therapy.     

Clinical observations of the treatment of canine perianal fistulas with topical tacrolimus in 10 dogs

Tacrolimus ointment, a potent immunosuppressive medication, was evaluated for efficacy in the treatment of perianal fistulas in dogs. Ten dogs with perianal fistulas were treated with topical tacrolimus ointment once to twice daily for 16 weeks. Full healing of the fistulas occurred in 50% and was noticeably improved in 90% of dogs.     

Focal metatarsal fistulae syndrome affecting a greyhound dog successfully treated with topical 0.1% tacrolimus ointment

Metatarsal fistulation is an uncommon cutaneous condition reported almost exclusively in German shepherd dogs and their cross‐breeds. To the best of the authors’ knowledge this is the first reported case of focal metatarsal fistulae syndrome affecting a greyhound. Remission was obtained within 6 weeks of commencing treatment using compounded 0.1% tacrolimus ointment twice daily and the dog remained stable for another 6 months with twice weekly application before treatment was discontinued. The dog remained in remission at the time of writing, which is 1 year after treatment withdrawal.     

Discoid lupus erythematosus (DLE) in a Spitz dog

A 3-year-old, female Spitz, was presented due to lack of response to therapies with a 6-month history of skin lesions characterized by diffuse erythema and scaling on the dorsal trunk. Physical examination revealed the dog was active and healthy. Skin culture isolated no fungus. Histological examination of skin biopsy specimens revealed interface dermatitis with hydropic degeneration of the basal layers, predominant plasmacytic perivascular accumulation in the dermis, and intensive plasma cell-rich interface mural folliculitis. Moderate CD3-positive lymphocytes infiltrated the superficial dermis. This report may provide unique information of canine discoid lupus erythematosus in an unusual breed with atypical cutaneous lesions.     

Subepidermal linear alignment of mast cells in inflammatory dermatoses of the dog

A recent study demonstrated that 47.7% of dogs with Malassezia dermatitis had a subepidermal linear alignment of mast cells (SLAM). A retrospective histopathological study was conducted on 419 canine skin biopsies to determine if a SLAM was present in other inflammatory diseases. Cases examined included dogs with demodicosis, sarcoptic mange, dermatophytosis, pemphigus foliaceus, pemphigus erythematosus, discoid lupus erythematosus, systemic lupus erythematosus, erythema multiforme, dermatomyositis, staphylococcal pyoderma, primary seborrhea, arthropod bites, contact hypersensitivity, flea bite hypersensitivity, atopy, and food hypersensitivity. Three cases (3/419, 0.7%) were identified with SLAM. The diagnoses for these cases were atopy (1/23, 4%) with a secondary bacterial folliculitis (1/136, 0.7%), pemphigus erythematosus (1/18, 6%), and discoid lupus erythematosus (1/16, 6%). Based on this study, SLAM is significantly more common in Malassezia dermatitis than in other inflammatory diseases.     

FC‐21 Efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs

The objective of this open pilot study was to evaluate the efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs. Seven dogs (four males, three females) were included. All subjects had a 6‐month to 2‐year history of plantar fistulae involving the plantar aspect of two to four metatarsi/metacarpi. No other skin lesions were present and the dogs appeared otherwise healthy. Before treatment with tacrolimus, all dogs received antibiotics for 4–8 weeks. Hair was clipped to visualise the lesions. The presence of erythematous papules, oedema and fistulae was recorded for each foot. All dogs served as their own controls. Dogs with four legs involved had one front and one hind leg treated. Dogs with two to three feet affected had only one foot treated. Tacrolimus 0.1% ointment (Protopic^®) was applied twice daily onto the site of lesions. Partial improvement of treated lesions was seen in all cases within 3 weeks. After 6 weeks, treated lesions were in complete remission in four dogs, while the other three subjects had palpable but invisible lesions. Signs had not improved on the untreated legs. Follow‐up varied between 4 months and 2 years. Lesion remission persisted in six dogs with the intermittent application of tacrolimus. Adverse effects of treatment were not seen. In conclusion, the application of topical tacrolimus seems to provide a safe and effective treatment option for plantar fistulae in German shepherd dogs. Funding: Self‐funded.     

FC-23 Feline plasma cell pododermatitis: a retrospective study of 26 cases

The objective of this open pilot study was to evaluate the efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs. Seven dogs (four males, three females) were included. All subjects had a 6-month to 2-year history of plantar fistulae involving the plantar aspect of two to four metatarsi/metacarpi. No other skin lesions were present and the dogs appeared otherwise healthy. Before treatment with tacrolimus, all dogs received antibiotics for 4–8 weeks. Hair was clipped to visualise the lesions. The presence of erythematous papules, oedema and fistulae was recorded for each foot. All dogs served as their own controls. Dogs with four legs involved had one front and one hind leg treated. Dogs with two to three feet affected had only one foot treated. Tacrolimus 0.1% ointment (Protopic^®) was applied twice daily onto the site of lesions. Partial improvement of treated lesions was seen in all cases within 3 weeks. After 6 weeks, treated lesions were in complete remission in four dogs, while the other three subjects had palpable but invisible lesions. Signs had not improved on the untreated legs. Follow-up varied between 4 months and 2 years. Lesion remission persisted in six dogs with the intermittent application of tacrolimus. Adverse effects of treatment were not seen. In conclusion, the application of topical tacrolimus seems to provide a safe and effective treatment option for plantar fistulae in German shepherd dogs.
Funding: Self-funded.     

A retrospective study comparing the histopathological features and response to treatment in two canine nasal dermatoses, DLE and MCP

Canine discoid lupus erythematosus (DLE) and mucocutaneous pyoderma (MCP) have overlapping clinical and histopathological changes, often making diagnosis difficult. Histopathological features of 27 nasal planum biopsies were scored to determine whether DLE and MCP were histopathologically distinguishable. Long-term follow-up, enabling assessment of clinical diagnoses, was available on 15 cases; 11/15 cases were immunomodulatory responsive (ImR) and 4/15 were antibiotic responsive (AbR). Clinical diagnosis, determined by response to treatment for 15/27 cases, was not predictable based on scoring of histopathological features. Distinct histopathological patterns were observed: 2/11 ImR cases had a lymphocyte-rich interface dermatitis. All other cases had the same histopathological changes: a band-like diffuse superficial plasmacytic to lymphoplasmacytic dermatitis +/- focal basal cell damage, but different clinical diagnoses (4/4 AbR, 9/11 ImR). German shepherd dogs/crosses were over-represented (44.4% of the cases) and tended to have more multifocal lesions (41.7% vs. 26.7% of all other breeds). Longer duration of disease was associated with a preponderance of plasmacytic infiltrate (P = 0.026).     

Vesicular cutaneous lupus erythematosus in a Border Collie in New Zealand

A 3-year-old Border Collie was initially presented for a small ulcerative lesion on the left axilla. The lesion failed to respond to conservative treatment with antibiotics, and the dog was re-presented one week later with ulcerative lesions involving the inguinal and axillary areas bilaterally. Histology of a biopsy of these lesions revealed a lymphocytic ulcerative interface dermatitis. Apoptosis and degeneration of basaloid cells was evident, with clefting along the dermo–epidermal junction. Vesicular cutaneous lupus erythematosus was diagnosed. The dog was treated with prednisone and azathioprine, resulting in complete remission of signs. However, recurrence occurred when drugs were tapered, necessitating ongoing treatment. Vesicular cutaneous lupus erythematosus has been described in North America in Rough-coated Collies and Shetland Sheepdogs. However, in Australasia, it is most commonly observed in Border Collies.     

Evaluation of four topical preparations for the treatment of cannon hyperkeratosis in a horse

The response to treatment with four topical preparations was evaluated in an 11‐year‐old Morgan horse mare with histologically confirmed quadrilateral cannon hyperkeratosis. Each limb was treated for 30 days with 0.1% tacrolimus ointment, 0.1% adapalene gel, 0.2% phytosphingosine spray or a water‐based emollient. Response to treatment was evaluated both histologically and visually. A water‐based emollient and 0.1% tacrolimus ointment produced encouraging clinical responses. Pre‐treatment histopathology identified marked, mostly compact, hyperkeratosis and follicular hyperkeratosis, most prominent in the infundibular area. Following treatment, histopathology identified a mild reduction in follicular keratin production and stratum corneum thickness.