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.     

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.     

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.     

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.     

A randomized controlled trial of misoprostol monotherapy for canine atopic dermatitis: effects on dermal cellularity and cutaneous tumour necrosis factor-alpha

Abstract In this blinded randomized placebo-controlled trial, 20 dogs with atopic dermatitis (AD) were given placebo (8 dogs) or misoprostol (12 dogs) at 5 µg kg⁻¹, orally, three times daily for 3 weeks. Administration of the active drug, but not of placebo, led to a significant decrease in lesional and pruritus scores. The median reduction from baseline of both scores was ≈30%. Misoprostol therapy did not lead to decreases of dermal cell counts or skin tumour necrosis factor (TNF)α mRNA copy numbers that were significantly different from those of placebo. Skin TNFα protein production, assessed using indirect immunofluorescence, decreased or remained unchanged in dogs receiving misoprostol. In contrast, post treatment TNFα fluorescence scores were higher in all but two dogs given placebo. The changes from baseline of TNFα fluorescence scores did not correlate significantly with those of lesional or pruritus indices. These observations confirm the modest efficacy of misoprostol for treatment of canine AD and suggest that its mild anti-allergic effects are not associated with either inhibition of inflammatory cell emigration or TNFα production.     

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.     

P-9 CD8 and CD4 lymphocyte populations in blood from healthy dogs and dogs naturally infected with Ehrlichia canis

The purpose of this study was to determine whether doxycycline (Ronaxan) decreased the severity of localized lesions of canine acne. Dogs were enrolled if they exhibited skin lesions localized to the chin compatible with canine acne, and if cytological smears showed a bacterial invasion and bacteriological samples grew Staphylococcus intermedius colonies. Demodicosis and dermatophytosis were excluded by skin scrapings and fungal culture, respectively. Lesions (erythema, lichenification, papules, pustules and excoriations) were graded with a quantitative 4-point scale (maximal total score 15). Extent of lesion was also estimated. Pruritus was graded on a 4-point scale. Scores were given at the time of inclusion and at day 30 after treatment with doxycycline 10 mg/kg once daily. Twelve dogs (10 males and two females) representing seven breeds were included. Good improvement of both lesional (9.4 before treatment and 2.3 after treatment) and extent scores (43% before treatment and 8% after treatment) was achieved. Pruritus was also markedly improved from 2.08 before treatment to 0.42 after treatment. One dog was not significantly improved after 1 month. Results of this trial suggest that doxycyline is useful for reducing the severity of localized skin lesions of canine acne.
Funding: Self-funded.     

A randomized, double-blind, placebo-controlled study to evaluate the effect of EFF1001, an Actinidia arguta (hardy kiwi) preparation, on CADESI score and pruritus in dogs with mild to moderate atopic dermatitis

Canine atopic dermatitis (AD) is common and new therapies are beneficial. This multicentric, randomized, double-blind, placebo-controlled study tested the efficacy of Actinidia arguta (hardy kiwi) (EFF1001) in dogs with mild/moderate AD. The study was divided into two stages. Stage 1 lasted 6 weeks. In the first 2 weeks prednisolone [days 1–3: 0.2 mg/kg twice daily (BID), days 4–14: 0.2 mg/kg every other day (EOD)] was administered. Responsive dogs were placed on prednisolone 0.2 mg/kg EOD + assigned test article [either placebo or EFF1001 (30 mg/kg)] once daily for 4 weeks. Stage 1 responders were advanced to stage 2, which involved 4 weeks of just EFF1001. Clinicians scored lesions using Canine Atopic Dermatitis Extent and Severity Index (CADESI) and owners scored pruritus using a Pruritus Visual Analogue Scale. Seventy-seven dogs were enrolled, 76 were randomized on day 14, and 57 (57/76 = 75%) completed stage 1 (27 in EFF1001 and 30 in placebo). At the end of stage 1, 35 of 57 dogs (35/57 = 61%) responded (18 in EFF1001 and 17 in placebo) and advanced to stage 2. At completion of stage 1, CADESI scores did not significantly differ between groups while pruritus decreased in EFF1001 group and approached significance. At completion of stage 2, 19 dogs (19/35 = 54%) responded (15/19 = 79% had received EFF1001 and 4/19 = 21% placebo in stage 1). After completing stage 2, dogs placed on EFF1001 throughout the study were 3.5 times more likely to either maintain or improve scores than those that started it in stage 2. It is concluded that EFF1001 is beneficial adjunctive therapy after prolonged use.     

Efficacy of a 0.0584% hydrocortisone aceponate spray in the management of canine atopic dermatitis: a randomised, double blind, placebo-controlled trial

This study evaluated a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance®; Virbac SA, Carros, France) in canine atopic dermatitis (AD). Initially, dogs with a canine AD extent and severity index (CADESI-03) ≥ 50 were randomly allocated to receive HCA ( n  = 15) or placebo ( n  = 13) (two sprays from 10 cm away to treat an area of 100 cm²) once daily for 28 days. Twenty-one of the dogs then received HCA spray once daily, reducing to every other day or twice weekly over 42 days if improvement was maintained. CADESI, pruritus (14 cm visual-analogue-scale) and owner satisfaction (5-point scale) were recorded every 14 days. Haematology, biochemistry and adrenocorticotrophic hormone stimulation were performed at baseline, d28 and d70 (HCA n  = 9; placebo n  = 7). Intention-to-treat data were analysed. HCA spray significantly decreased CADESI (–61.4% versus –13.4%, P  = 0.0069) and pruritus (–38.8% versus +57.6%, P  = 0.0015) at d28 compared to placebo. Scores were significantly decreased at d14 (CADESI –50.5%, P  < 0.0021) and d28 (CADESI P  < 0.0001; pruritus P  = 0.018) compared to baseline following HCA but not placebo. At d28 11 of 15 and 7 of 15 HCA dogs had ≥ 50% reductions in CADESI and pruritus compared to 3 of 13 ( P  = 0.02) and 1 of 13 ( P  = 0.04) placebo dogs. Owner satisfaction scores were significantly higher in the HCA group (d28 P  = 0.0001). Daily 3 of the 21 dogs required daily maintenance therapy, 7 every other day, 6 twice weekly and 5 dogs required additional therapy. Coat length did not influence the results. No adverse effects or changes to blood parameters were noted. HCA spray proved safe and effective up to 70 days. It is not, however, licensed for long-term treatment.     

P‐7 Treatment of canine acne with doxycycline: an open trial

The purpose of this study was to determine whether doxycycline (Ronaxan) decreased the severity of localized lesions of canine acne. Dogs were enrolled if they exhibited skin lesions localized to the chin compatible with canine acne, and if cytological smears showed a bacterial invasion and bacteriological samples grew Staphylococcus intermedius colonies. Demodicosis and dermatophytosis were excluded by skin scrapings and fungal culture, respectively. Lesions (erythema, lichenification, papules, pustules and excoriations) were graded with a quantitative 4‐point scale (maximal total score 15). Extent of lesion was also estimated. Pruritus was graded on a 4‐point scale. Scores were given at the time of inclusion and at day 30 after treatment with doxycycline 10 mg/kg once daily. Twelve dogs (10 males and two females) representing seven breeds were included. Good improvement of both lesional (9.4 before treatment and 2.3 after treatment) and extent scores (43% before treatment and 8% after treatment) was achieved. Pruritus was also markedly improved from 2.08 before treatment to 0.42 after treatment. One dog was not significantly improved after 1 month. Results of this trial suggest that doxycyline is useful for reducing the severity of localized skin lesions of canine acne. Funding: Self‐funded.     

FC-38 Efficacy of conjugated linoleic acid and black currant seed oil in the treatment of canine atopic dermatitis: a double-blinded, randomized, placebo-controlled study

The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen-specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL-4, TNF and IL-10 was quantitated using RT-PCR. A mixture of allergen extract and liposome-DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t -test. There were significant improvements in pruritus scores ( P  = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL-4 production decreased significantly ( P  = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis.
Funding: Self-funded.     

Successful treatment of a novel generalized variant of canine discoid lupus erythematosus with oral hydroxychloroquine

Discoid lupus erythematosus (DLE) is a common canine autoimmune disease that usually manifests as a localized ulcerative and scarring nasal dermatitis. We report herein a generalized variant of canine DLE successfully treated with the antimalarial immunomodulator hydroxychloroquine (HCQ). A 9-year-old hairless Chinese crested dog was presented with annular and polycyclic hyperpigmented and scaly skin lesions with central erosions, hypopigmentation and/or scarring on the trunk, neck and lateral extremities. Associated systemic signs were not seen. The clinical diagnosis of generalized DLE was supported by the demonstration of lymphocyte-rich interface dermatitis with epidermal atrophy and dermo-epidermal deposition of immunoglobulins and activated complement. As for human DLE, treatment was initiated with HCQ at 5 mg/kg once daily along with 2 weeks of 0.1% tacrolimus ointment and restriction of sun exposure. Over the following year, complete remission was maintained with HCQ at 5 mg/kg orally once daily with the exception of three relapses; two occurred during treatment induction and the third arose when the frequency of HCQ administration was reduced to every other day. Disease flares were controlled with 0.1% tacrolimus ointment alternating with 0.1% prednicarbate cream once daily for 5-10 days. Altogether, adverse drug events were not seen with this regimen. In summary, clinically, histologically and immunologically, this dog's disease mirrored the generalized discoid variant of chronic cutaneous lupus erythematosus of humans. The apparent benefit of HCQ, its safety and low cost warrant future investigations of its use for treatment of canine cutaneous lupus variants.     

FC-41 A prospective pilot study on the use of cyclosporin on feline allergic diseases

This study evaluated the efficacy of Phytopica^TM, a proprietary blend of standardised plant extracts, in canine atopic dermatitis (AD). One hundred twenty dogs with perennial AD were recruited on the basis of history and clinical signs, and a positive intradermal allergen test or rFcεRIα serology to perennial allergens. Other pruritic dermatoses were eliminated by antimicrobial treatment, skin scrapings, Sarcoptes serology, flea control and a 6-week food trial. Exclusion criteria included antimicrobial therapy within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or cyclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days of entry into the study. Dogs [minimum Canine Atopic Dermatitis Extent and Severity Index (CADESI) = 25] were randomly allocated to receive placebo, 100, 200 or 400 mg/kg Phytopica^TM daily for 12 weeks. Their CADESI was assessed every 4 weeks. A modified intention-to-treat population was analysed. The mean reductions in CADESI scores at the end of treatment compared to baseline were 4.4% (100 mg/kg; n  = 30), 23.4% (200 mg/kg; n  = 29, P  < 0.01), 8.5% (400 mg/kg; n  = 29) and 3.9% (placebo; n  = 29). For more severely affected dogs (minimum CADESI ≥ 50 at baseline), there was significant reduction in mean CADESI score (29.3%, P  = 0.038) only in the 200 mg/kg treatment group ( n  = 14). In conclusion, this study demonstrates that Phytopica^TM is an effective nonsteroidal treatment for canine AD.
Funding: Phytopharm plc.     

Expression analysis of CCL27 and CCL28 mRNA in lesional and non-lesional skin of dogs with atopic dermatitis

Chemokines are important regulators of the selective recruitment of inflammatory cells into sites of allergic inflammation. Since canine atopic dermatitis (AD) shares many clinical features of human AD, patterns of chemokine production in dogs may also be similar with those in humans. The aim of this study was to examine mRNA expression of CCL27 and CCL28 in lesional skin of dogs with AD to demonstrate similarity of chemokine production with human counterparts. RNA was extracted from skin biopsy specimens of 12 dogs with AD. The mRNA expression of CC chemokines (CCL4, CCL19, CCL20, CCL21, CCL24, CCL27 and CCL28) was analyzed by quantitative real-time PCR and was compared between lesional and non-lesional skin. Seven types of chemokines examined were constitutively expressed in both lesional and non-lesional skin. It was found that mRNA expression levels of CCL27 and CCL28 among the chemokines were significantly different between lesional and non-lesional skin (P<0.05). Expression level of CCL27 mRNA in lesional skin was significantly lower than that in non-lesional skin. On the other hand, CCL28 mRNA expression in lesional skin was found to be higher than that in non-lesional skin. These results suggest that CCL28 but not CCL27 may play important roles in immunopathogenesis of canine AD, indicating that experimental canine study may provide additional information that can be extrapolated to human AD.     

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.     

Investigation on the use of 0.3% tacrolimus lotion for canine atopic dermatitis: a pilot study

The efficacy of 0.3% tacrolimus lotion (maximum dosage: 0.3 mg kg-1 per day) for treatment of atopic dermatitis (AD) was evaluated. Systemic absorption and effects on complete blood cell counts (CBC) and chemistry panels were also investigated. Eight dogs were assigned randomly to either a tacrolimus or a vehicle lotion treatment group. Both owners and investigator were blinded to the treatment. After 4 weeks, there was a 2-week wash-out period and treatments were reversed. Owners scored pruritus weekly while the investigator scored pruritus and erythema at the beginning and end of each treatment period. Investigator scores for pruritus in the tacrolimus group significantly decreased by the end of the study (P = 0.03). Investigator scores for erythema in the tacrolimus group were significantly lower than those in the placebo group at the end of the study (P = 0.005). There was no difference between groups with respect to owner scores for pruritus. No changes in the CBC and chemistry panels were noted. Mean blood concentrations of tacrolimus were below toxic levels.     

Expression of thymic stromal lymphopoietin in canine atopic dermatitis

Background – In humans, thymic stromal lymphopoietin (TSLP) plays a central role in the development of allergic inflammation, such as atopic dermatitis (AD), but it is unknown whether it is involved in the pathogenesis of canine AD (CAD). Hypothesis/Objectives – Our aim was to characterize canine TSLP and to assess its expression in CAD. Methods – Canine TSLP was identified based on sequence homology with human TSLP and the complementary DNA (cDNA) cloned by RT‐PCR. Real‐time quantitative RT‐PCR was established to assess the expression of canine TSLP in cultured canine keratinocytes and in skin biopsy specimens from lesional and nonlesional skin of 12 dogs with CAD and eight healthy control dogs. Results – Partial canine TSLP cDNA was cloned and characterized. It contained four exons that shared 70 and 73% nucleotide identity with human and equine TSLP, respectively, encoding the signal peptide and full‐length secreted protein. We found significantly increased TSLP expression in lesional and nonlesional skin of dogs with CAD compared with healthy control dogs (P < 0.05), whereas no difference was measured between lesional and nonlesional samples. In cultured primary canine keratinocytes, we found increased TSLP expression after stimulation with house dust mite allergen extract or Toll‐like receptor ligands lipopolysaccharide and poly I:C. Conclusions and clinical importance – Increased TSLP expression in the skin of dogs with CAD supports an involvement of TSLP in the pathogenesis of CAD similar to that in humans. Further studies should elucidate the function and therapeutic potential of TSLP in CAD.     

Low-dose recombinant canine interferon-γ for treatment of canine atopic dermatitis: An open randomized comparative trial of two doses

The purpose of this study was to investigate the minimum effective dose of recombinant canine interferon-γ (rCaIFN-γ) for the treatment of dogs with atopic dermatitis (AD). Thirty-four dogs with AD from 17 animal hospitals in Japan were administered half or one-fifth of the approved rCaIFN-γ dose of 10 000 units/kg, three times a week for 4 weeks, followed by once weekly for an additional 4 weeks. Pruritus, excoriation, erythema and alopecia were evaluated and scored by the investigators on weeks 2, 4, 6, 8 and 12. The efficacy rate (number of excellent cases + number of good cases/total number of cases) at week 8 in the 2000 units/kg group was 36.4% for pruritus, 36.4% for excoriation, 45.5% for erythema and 36.4% for alopecia. In contrast, in the 5000 units/kg group, the efficacy rate was 64.3% for pruritus, 57.1% for excoriation, 78.6% for erythema and 78.6% for alopecia. The efficacy rate of the 5000 units/kg group was high for all signs evaluated and comparable to that of the 10 000 units/kg group reported in a previous study. The results of this study showed that 2000 units/kg of rCaIFN-γ is less effective than 5000 units/kg to treat dogs with AD, and the efficacy of the 5000 units/kg dose is comparable to that of 10 000 units/kg at week 8.     

Expression of CC chemokine receptor 4 (CCR4) mRNA in canine atopic skin lesion

CC chemokine receptor 4 (CCR4) is a G protein-coupled seven transmembrane receptor that is selectively expressed on Th2 cells and plays an important role in the trafficking of Th2 cells into inflammatory sites. In this study, a full-length canine CCR4 cDNA was cloned and characterized in order to examine the potential role of CCR4 in allergic responses that produce skin lesions in canine atopic dermatitis (AD). The canine CCR4 cDNA reported in this study contained an open reading frame of 1083 nucleotides encoding 360 amino acids. The predicted amino acid sequence of canine CCR4 showed 91.9, 85.3 and 84.5% similarity with those of the human, mouse and guinea pig counterparts, respectively. Expression of CCR4 mRNA was detected in various tissues including thymus, spleen, heart, small intestine and lymph node. Furthermore, it was found that CCR4 mRNA was preferentially expressed in lesional skin of dogs with AD, together with the mRNA of thymus and activation-regulated chemokine (TARC), which is a ligand for CCR4. The present study demonstrates that CCR4 contributes strongly to the immunopathogenesis of canine AD.     

Randomized controlled trial of the efficacy of cyclosporine in the treatment of atopic dermatitis in dogs

OBJECTIVE: To evaluate efficacy of cyclosporine A, administered at either of 2 dosages, in dogs with atopic dermatitis (AD). DESIGN: Multicenter randomized controlled trial. ANIMALS: 91 dogs with AD. PROCEDURE: Dogs were assigned to receive placebo (30 dogs), cyclosporine at a low dosage (2.5 mg/kg [1.1 mg/lb], PO, q 24 h for 6 weeks; 30 dogs), or cyclosporine at a high dosage (5.0 mg/kg [2.3 mg/lb], PO, q 24 h for 6 weeks; 31 dogs). RESULTS: After 6 weeks, mean percentage reductions, compared with baseline scores, in scores of lesion severity were 34, 41, and 67% for dogs treated with the placebo, cyclosporine at the low dosage, and cyclosporine at the high dosage, respectively. Similarly, mean percentage reductions in pruritus scores were 15, 31, and 45%, respectively. Percentage reductions in skin lesion and pruritus scores were significantly higher for dogs given cyclosporine at the high dosage than for dogs given the placebo. Treatment efficacy was significantly associated with whether dogs had a history of seasonal AD. Percentage reductions in skin lesion and pruritus scores were high for dogs treated with cyclosporine at the highest dosage that had a history of nonseasonal AD. Dogs in all groups with seasonal AD improved during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that oral administration of cyclosporine at a dosage of 5.0 mg/kg once daily is effective in reducing severity of pruritus and skin lesions in dogs with AD, especially those with nonseasonal disease.