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.     

Comparison of cyclosporine A with methylprednisolone for treatment of canine atopic dermatitis: a parallel,blinded, randomized controlled trial

Abstract The objective of this multicentre, parallel, blinded, randomized controlled study was to evaluate the efficacy and the safety of cyclosporine (CsA group, 117 dogs) in comparison with methylprednisolone (MP group, 59 dogs) in the treatment of atopic dermatitis for 4 months. Mean induction dose of both drugs (5 mg/kg CsA, 0.75 mg/kg MP) was tapered over time according to the clinical response. At the end of the study, the mean estimated percentage reduction from baseline (confidence interval) of lesion scores was 52% (44–59) and 45% (35–56), and the reduction in pruritus score was 36% (27–43) and 33% (23–43) in dogs in the CsA and MP groups, respectively. These percentages were not significantly different between groups. A significantly better overall assessment of efficacy was obtained in the CsA-treated dogs (76 vs. 63% responses excellent or good in the CsA compared with MP group). CsA-treated dogs presented a higher frequency of gastrointestinal disorders, mainly vomiting, but MP dogs tended to be more susceptible to infections. There was no remarkable change over baseline of the haematological and biochemical parameters in the two groups.     

A randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of a Chinese herbal product (P07P) for the treatment of canine atopic dermatitis

A randomized, double-blind, placebo-controlled trial of P07P, a product derived from a traditional Chinese herbal remedy, was undertaken in 50 dogs with atopic dermatitis. Owners recorded a daily itch score for 4-14 days before treatment and during treatment. Packets of powder containing P07P or placebo were added to the food once daily for 8 weeks. Dogs were assessed for erythema, surface damage, overall coat condition and seborrhoea by the same investigator, as well as for pruritus and general demeanour, at 0 (visit 2), 28 (visit 3) and 56 (visit 4) days of treatment or at withdrawal. Investigator and owner assessments of response were recorded after 28 and 56 days of treatment or at withdrawal. The predefined primary outcome measure was the owners' assessment of response at the end of treatment. Nine of the 24 dogs (37.5%) in the P07P group but only 3 of the 23 dogs (13%) in the placebo group were considered to have improved, but this difference was not statistically significant (P = 0.09). There was a significantly higher withdrawal rate due to worsening of condition in the placebo group (P = 0.04). Mean daily itch score in the second 28-day period of the study was significantly higher than baseline in the placebo group (P = 0.01) but not in the P07P group (P = 0.30). Pruritus scores showed a significant deterioration from baseline at the final visit in the placebo group (P = 0.01) but not in the P07P group (P = 1.00). There was a significant difference between the groups in change from baseline in erythema score at visit 3 (P = 0.05). There were no significant differences (P > 0.05) in surface damage, seborrhoea, overall coat condition and general demeanour scores within or between the groups throughout the study. The product was well tolerated with no severe or serious adverse events recorded. P07P may be beneficial as a novel nonsteroidal therapy for the management of dogs with atopic dermatitis.     

Cyclosporine decreases skin lesions and pruritus in dogs with atopic dermatitis: a blinded randomized prednisolone-controlled trial

During the last decade, oral cyclosporin (CsA) has proven to be effective, in randomized controlled trials, for the treatment of atopic dermatitis (AD) in human patients. The purpose of this blinded randomized controlled trial was to test the hypothesis that CsA was successful in reducing the gravity of clinical signs of AD in dogs. Thirty dogs with nonseasonal AD were randomly allocated to receive an oral solution of either NEORAL CsA (5 mg kg-1) or prednisolone (0.5 mg kg-1) once daily for 6 weeks. Before, and 3 and 6 weeks after therapy, skin lesions were graded by clinicians using the Canine AD Extent and Severity Index (CADESI). Pruritus was assessed by the owners using a visual analog scale (PVAS). In both groups, CADESI and PVAS values were significantly lower at 6 weeks post treatment than before the initiation of therapy (Friedman test, P < 0.0004). The percentage reductions in CADESI and PVAS values from baseline were not statistically different between groups (Mann-Whitney test, P > 0.3). In this experiment, the tolerability and safety of oral CsA and prednisolone appeared similar. One-fifth of dogs given oral CsA occasionally developed diarrhoea or soft stools. One dog that was given CsA developed a generalized papillomatous skin eruption during the second half of the trial. Our study provides randomized controlled trial evidence that CsA reduces the severity of clinical signs in dogs with nonseasonal AD. Moreover, the anti-allergic efficacy of CsA appears comparable with that of prednisolone. We propose that oral CsA should be considered as a valuable alternative to glucocorticoid therapy in dogs with AD.     

Double-blinded, placebo-controlled, cross-over pilot study on the efficacy of zileuton for canine atopic dermatitis

Nine dogs meeting the diagnostic criteria for canine atopic dermatitis were enrolled in a double-blind, placebo-controlled, cross-over clinical trial. In this pilot study, zileuton (a 5-lipoxygenase inhibitor) given orally at 2 mg kg(-1) three times daily for 4 weeks significantly decreased erythema in dogs with atopic dermatitis but had no effect on pruritus. Zileuton was well tolerated and no adverse clinical signs were noted. However, one dog developed mild alanine aminotransaminase elevation, which resolved within 1 week of discontinuation of therapy. Monitoring of alanine aminotransaminase may be necessary in dogs receiving zileuton. Further studies with larger number of dogs are needed to evaluate the efficacy of zileuton as treatment for canine atopic dermatitis.     

Treating canine atopic dermatitis with unsaturated fatty acids: the role of mast cells and potential mechanisms of action

Canine atopic dermatitis (CAD) is an inflammatory skin disorder that is characterized by pruritus and associated cutaneous changes. Treatment interventions include allergen avoidance, allergen‐specific immunotherapy as well as a symptomatic therapy using glucocorticoids and antihistamines. In addition, a dietary intervention using polyunsaturated fatty acids (PUFA) has been shown to alleviate symptoms in some dogs. Although the beneficial effects of PUFA in the treatment of CAD have been known for several years, their mode of action remains unclear. This review discusses the evidential basis of the therapeutic use of dietary PUFA in the treatment of CAD. Particular emphasis will be placed on the role of cutaneous mast cells. In addition, recent evidence from in vitro studies on the regulation of mast cell exocytosis will be used to build a mechanistic model of the active principle of PUFA. It is proposed that dietary PUFA are integrated into mast cell membranes resulting in a reorganization of membrane microdomains. This may then be accompanied by functional changes of membrane‐associated proteins such as the phospholipases D (PLD), enzymes having an important impact on mast cell exocytosis processes.     

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.     

A preliminary study on the effect of dietary supplementation with cod liver oil on the polyunsaturated fatty acid composition of boar semen

Eight mature Norwegian Landrace boars, of proven fertility and in routine semen production for AI, were fed individually with the same basic diet for 9 weeks. One group of 4 animals served as the control, the remaining 4 boars received a daily supplement of 75 ml cod liver oil (CLO-group). Fifteen consecutive semen samples were collected from each boar. The fatty acid composition of the semen was determined, and the content of the 15 most numerous fatty acids with a chain length longer than 12 carbon atoms was followed over time. In both groups, the proportion of 16:1n-7 decreased significantly, while 16:0 and 22:6n-3 (DHA) increased. By the end of the experiment, DHA had tended to increase and 22:5n-6 to decrease to a greater extent in the CLO-group. A significant difference between the groups was seen for onen-6 PUFA (22:4n-6), which remained unchanged in the control group but decreased in the CLO-group. No change was seen in docosapentaenoic acid (22:5n-3) and eicosapentaenoic acid (20:5n-3) was not found in any sample. These results indicate that CLO supplementation affects the fatty acid composition of boar semen. There were no significant differences in the non-return rates (4–25 days) between the two groups before, during or after the experiment.Abbreviations AA arachidonic acid - AI artificial insemination - area% each fatty acid percentage of the total area of the peaks from gas chromatographic analysis of methylated fatty acids - CLO cod liver oil - DHA docosahexaneoic acid - DPA docosapentaenoic acid - EPA eicosapentaenoic acid - LA linoleic acid - LNA linolenic acid - NR non-return rate - PUFA polyunsaturated fatty acid - T _c the temperature marking the beginning of the phase transition Fatty acid nomenclature: Example, 22:6n-3: 22=number of carbon atoms, 6=number of double bonds,n-3=position of the first double bond counted from the terminate (n or methyl end of the fatty acid chain     

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.     

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).     

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.     

A treatment study of canine symmetrical onychomadesis (symmetrical lupoid onychodystrophy) comparing fish oil and cyclosporine supplementation in addition to a diet rich in omega-3 fatty acids

Background

Treatment of symmetrical onychomadesis (symmetrical lupoid onychodystrophy) is a challenging task for dermatologists. The acute phase is characterized by sloughing of claw plates and loose claws have to be removed and secondary infections treated. The goal of long-term treatment is to allow claws to re-grow with normal quality and to achieve life-long lack of recurrence. The aim of this randomized treatment trial was to see if adding fish oil or cyclosporine to a diet rich in omega-3 could improve the treatment outcome of symmetrical onychomadesis in Gordon and English setters. All dogs were fed Eukanuba Veterinary Diets Dermatosis® exclusively during the six month treatment trial. The treatment outcome was measured as the change in number of healthy claws during treatment, as well as the long-term effect on hunting ability and recurrence of onychomadesis. The hypothesis was that cyclosporine provides a stronger and different immune modulating property than fish oil and therefore would give a better treatment outcome in dogs with symmetrical onychomadesis eating a diet rich in omega-3 fatty acids.

Results

Six Gordon setters and one English setter were treated with 5 mg/kg cyclosporine once daily for six months and seven Gordon setters were treated with 10 ml Dr Baddaky fish oil® once daily for six months. All dogs were evaluated every month and the numbers of healthy claws were recorded.There was a statistically significant improvement in the number of healthy claws after six months of treatment with a median increase of 13.5 claws for both groups. However, there was no statistically significant difference between the two treatment groups regarding the improvement in number of healthy claws, as assessed using the Wilcoxon rank-sum test (P = 0.15). Dogs in the cyclosporine group had a median increase of 10 healthy claws after six months of treatment while the median for the fish oil group was 14. Long-term cure was not achieved with either treatment.

Conclusion

Cyclosporine and fish oil appeared to be equally effective in treating symmetrical onychomadesis when the dog is fed a diet high in omega-3.     

Effects of yeast culture supplementation and the ratio of non‐structural carbohydrate to fat on growth performance,carcass traits and the fatty acid profile of the longissimus dorsi muscle in lambs

The effects of yeast culture (YC) supplementation and the dietary ratio of non‐structural carbohydrate to fat (NSCFR) on growth performance, carcass traits and fatty acid profile of the longissimus dorsi (LD) muscle in lambs were determined in a 2 × 3 full factorial experiment. Thirty‐six Small‐tailed Han lambs were randomly divided into six groups with six replicates per group. The lambs were fed one of the six pelleted total mixed rations (TMRs) for 60 days after 15 adaption days. The six rations were formed by two NSCFRs (11.37 and 4.57) and three YC supplementation levels (0, 0.8 and 2.3 g/kg dietary dry matter). The average daily gain (ADG), dry matter intake (DMI) and feed conversion ratio (FCR) data of each lamb were recorded and calculated. All the lambs were slaughtered for determining carcass traits and fatty acid profile of the LD muscle. DMI was significantly increased (p < 0.05) in a quadratic fashion with 0.8 g/kg of YC supplementation. Carcass weight (CW) and dressing percentage (DP) were significantly increased (p < 0.05) in a linear fashion with 2.3 g/kg of YC supplementation. Animals fed with high‐NSCFR diet had higher (p < 0.05) contents of myristoleic acid (C14:1), pentadecanoic acid (C15:0) and cis‐10‐heptadecenoic acid (C17:1), and lower (p < 0.05) stearic acid (C18:0) content in LD muscle than those fed with low‐NSCFR diet. Moreover, ADG, growth rate (GR), backfat thickness (BFT), percentages of crude fat (CF) and crude protein (CP), SFAs, MUFAs and PUFAs in LD muscle, were significantly affected (p < 0.05) by interaction of dietary NSCFR and supplemental YC level. Overall, YC not only improved the growth performance and carcass traits of the animals but also modified the fatty acid profile of the LD muscle. Furthermore, the effects of YC supplementation may depend on dietary compositions.