Quality of life of dogs with skin disease and of their owners. Part 2: administration of a questionnaire in various skin diseases and correlation to efficacy of therapy

A previously validated 15-item questionnaire on dogs' life quality (QoL1) and that of their owners (QoL2) was applied in a multicentre study to owners of 200 dogs with different dermatological conditions, together with a question on the owner-perceived disease severity (S). Factor analysis was applied to the whole questionnaire. The correlation of S with QoL1 and QoL2 scores was evaluated using Spearman's rank correlation tests. Owner sex, age, educational level and willingness to pay for a potential definitive cure of the disease were recorded, and compared with quality of life (QoL) scores. In 23 atopic dogs, CADESI-03, pruritus Visual Analogue Scale and QoL scores were obtained before and after therapy, and their correlation was evaluated with linear regression. Factor analysis revealed that three factors (S, QoL1 and QoL2) explained 75% of the variance. Owner-perceived severity correlated significantly with QoL1 and QoL2 (P = 0.002 and P = 0.015, respectively). The five diseases with the worst QoL scores were scabies, pododermatitis, complicated atopic dermatitis, pemphigus foliaceus and endocrine alopecia. Pruritic diseases did not give significantly higher QoL1 or QoL2 scores compared with nonpruritic diseases (P = 0.19, Kruskall-Wallis test). Owner sex, age or educational level did not influence QoL scores. Female sex, a younger age and a higher educational level were significantly associated with more willingness to pay. In atopic dogs, all the scores decreased after therapy, but post-treatment CADESI-03 and Visual Analogue Scale scores did not correlate with QoL1 and QoL2. Questions related to the burden of maintenance therapy showed the lowest improvements in score.     

Development of a questionnaire to assess the impact of atopic dermatitis on health-related quality of life of affected dogs and their owners

Atopic dermatitis (AD) is a chronic or chronically relapsing human and canine skin disease that is known to affect the quality of life (QoL) of affected individuals. Several studies have been conducted to develop disease-specific questionnaires and assess QoL in parents of children with AD and in the children themselves. The severity of canine AD is however currently evaluated using only clinical and pruritus scores. Measurement of the QoL of affected dogs and their owners could therefore provide a new tool for assessing disease severity and treatment efficacy. Ninety-eight owners of AD-affected dogs were asked to complete two questionnaires aiming to evaluate the QoL of affected dogs and their owners on one hand and the relationship between them and their dog on the other hand. Statistical analyses were carried out in order to assess the validity of the questionnaires and to select relevant questions for future studies. These analyses resulted in the selection of 13 questions that could be used in further studies aiming at determining the QoL of affected animals and their owners.     

The glucocorticoid sparing efficacy of PhytopicaTM in the management of canine atopic dermatitis

This double-blind randomized placebo-controlled trial indicates that Phytopica™ can be an effective glucocorticoid sparing agent in canine atopic dermatitis (AD). Twenty-two dogs with perennial AD [Canine Atopic Dermatitis with Severity Index (CADESI-03) ≥ 60] were given 200 mg/kg Phytopica™ or an identical placebo in food once daily for 56 days. All dogs were initially given 0.4 mg/kg methyl-prednisolone once daily, which was then adjusted according to the daily pruritus score (0–100 mm visual analogue scale). The cumulative dose and pruritus score were lower in the Phytopica™ than the placebo group. There were statistically significant time and treatment effects for the methyl-prednisolone dose and pruritus score, but there were no significant differences between the Phytopica™ and placebo groups in the proportion of dogs that achieved a > 50% reduction in dose or pruritus scores at day 56; the mean CADESI-03 scores at days 0, 28 and 56; the numbers achieving >50% reduction in CADESI-03 at days 28 and 56; or in the owners' global efficacy score at days 28 and 56. Adverse events included diarrhoea (three Phytopica™ and one placebo treated dog), polyuria/polydipsia (three dogs in each group), and polyphagia, intermittent anorexia and panting (one dog each in the placebo group). None of these by themselves required withdrawal of treatment.     

Determination of CADESI-03 thresholds for increasing severity levels of canine atopic dermatitis

To evaluate the extent and severity of skin lesions in clinical trials enrolling dogs with atopic dermatitis (AD), the International Task Force on Canine Atopic Dermatitis recently recommended the use of the third version of the CADESI. This version of the CADESI was found to exhibit acceptable content, construct, criterion, inter- and intraobserver reliability and sensitivity to change. The current study was aimed at determining optimal CADESI-03 cut-off points to separate AD severity categories for future clinical trials. One hundred and eight dogs with AD were selected based on current diagnosis standards. At one or more visits, clinicians subjectively rated the severity of AD as 'in remission', 'mild', 'moderate' or 'severe', and a CADESI-03 score was then determined. In all, 158 CADESI-03 values were recorded and divided among the four disease severity categories. Receiver-operating characteristics (ROC) curves were generated at increasing cut-off values to determine the benchmark that would offer optimal sensitivity and specificity between adjacent categories. Cut-offs of 16, 60 and 120 are proposed at the interface of remission, mild, moderate and severe categories, respectively. Proposed intervals therefore are: remission: 0-15; mild AD: 16-59; moderate AD: 60-119; and severe AD: >/= 120. This Task Force recommends that, whenever applicable and relevant, subgroup analyses of outcome measures, based on disease severity as determined with these cut-off CADESI-03 values, be preplanned for clinical trials enrolling dogs with AD. Such subgroup analyses could help determine whether specific interventions might be more effective in a particular subset of atopic dogs.     

The effect of a spot-on formulation containing polyunsaturated fatty acids and essential oils on dogs with atopic dermatitis

Recent studies have shown that immunological aberrations and epidermal barrier defects could be important in the pathogenesis of canine atopic dermatitis (CAD) and that oral polyunsaturated fatty acids (PUFAs) might influence the epidermal barrier. The aim of this study was to evaluate the effects of a spot-on formulation containing PUFAs and essential oils on pruritus and lesions caused by CAD. Forty-eight privately owned dogs of different breeds, ages and genders diagnosed with atopic dermatitis were included in a randomized, double-blinded, placebo-controlled, multicentre clinical trial. Dogs were treated with a spot-on formulation containing PUFAs and essential oils or placebo on the dorsal neck once weekly for 8 weeks. Before and after the study, CAD extent and severity index-03 (CADESI-03) and pruritus scores were determined by veterinarians and owners, respectively.There was significantly more improvement in CADESI-03 and pruritus scores in the treatment group than in the placebo group (P = 0.011 and P = 0.036, respectively). Additionally, more dogs improved by at least 50% in CADESI-03 and pruritus scores in the treatment group than in the placebo group (P = 0.008 and P = 0.070, respectively). No adverse reactions were observed. The topical preparation containing PUFAs and essential oils was a safe treatment and beneficial in ameliorating the clinical signs of CAD.     

Evaluation of the effect of a 0.0584% hydrocortisone aceponate spray on clinical signs and skin barrier function in dogs with atopic dermatitis

The purpose of this study was to evaluate the effects of a topical spray containing 0.0584% hydrocortisone aceponate (HCA) on canine atopic dermatitis (CAD) and to evaluate the skin barrier function during the treatment of CAD. Twenty-one dogs that fulfilled the diagnostic criteria for CAD were included in this study. The HCA spray was applied once a day to the lesions of all dogs for 7 or 14 days. Clinical assessment was performed before (day 0) and after treatment (day 14), and clinical responses were correlated with changes in skin barrier function. CAD severity significantly decreased after 14 days of HCA treatment based on the lesion scores (p < 0.0001), which were determined using the CAD extent and severity index (CADESI-03) and pruritus scores (p < 0.0001) calculated using a pruritus visual analog scale. Transepidermal water loss, a biomarker of skin barrier function, was significantly reduced compared to baseline (day 0) measurements (p = 0.0011). HCA spray was shown to be effective for significantly improving the condition of dogs suffering from CAD. This treatment also significantly improved cutaneous hydration and skin barrier function in the animals.     

Validation of CADESI-03, a severity scale for clinical trials enrolling dogs with atopic dermatitis

In dogs, atopic dermatitis (AD) is a common and chronic allergic skin disease that often necessitates treatment with pharmacological interventions. In the last 30 years, numerous clinical trials testing the efficacy of anti-inflammatory drugs have been reported, but there has been a lack of consistency in the assessment of outcome measures. Several clinical scales have been employed over time, but none of these scoring systems were ever tested for validity and reliability. A committee of the International Task Force on Canine Atopic Dermatitis evaluated the currently available scales used to assess disease morbidity in humans and dogs with AD, and a third version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) was designed. This version was expanded from previous ones by redistribution and increase in body sites tested, the use of an additional lesion reflecting underlying pruritus (e.g. self-induced alopecia) and an increase in the numerical range of severity for each lesion. The CADESI-03 scale was tested for validity and reliability in a cohort of 38 dogs with AD. Overall, this revised version of the CADESI was found to exhibit acceptable content, construct, criterion, and inter- and intra-observer reliability and sensitivity to change. As a result, this scale is recommended as a validated tool for assessment of disease severity in clinical trials testing the efficacy of interventions in dogs with AD.     

The efficacy of commercially available veterinary diets recommended for dogs with atopic dermatitis

The classical treatments for dogs with atopic dermatitis have traditionally been oral antipruritic drugs, allergen-specific immunotherapy and topical therapy. Fifty dogs with atopic dermatitis were included in this multicentred, double-blinded, randomized study to compare clinical response to an 8-week period of feeding one of three commercial veterinary foods marketed for dogs with atopic dermatitis (diets A-C) or a widely distributed supermarket food (diet D). Atopic dermatitis was diagnosed using Willemse's criteria and through the exclusion of differential diagnoses. Fourteen dogs were assigned to diet A and 12 dogs each to diet B, C or D. Flea and tick control using a monthly fipronil spot-on product was administered for a minimum of 4 weeks prior to inclusion in the study and during the study period. Evaluations were made monthly. These included lesion scores, using an established scoring system (canine atopic dermatitis extent and severity index, CADESI-03) and owner evaluation of pruritus level using a visual analogue scale. After 8 weeks on the new diets, there was a significant improvement in CADESI and pruritus scores with diet B (Wilcoxon test, P = 0.043 and paired t-test, P = 0.012, respectively), in pruritus scores with diet A (paired t-test, P = 0.019) and in CADESI scores with diet D (Wilcoxon test, P = 0.037). No significant changes were detected with diet C. Based on the results of this study, in addition to the conventional therapies, changing the diet of dogs with atopic dermatitis may be a useful adjunctive therapeutic measure.     

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.     

The effects of capsaicin topical therapy in dogs with atopic dermatitis: a randomized,double-blinded,placebo-controlled,cross-over clinical trial

Abstract The efficacy of twice daily topical application of capsaicin (0.025%) for the management of pruritus in dogs with atopic dermatitis (AD) was evaluated in double-blinded, placebo-controlled study. Twelve dogs with AD were randomly assigned to either 0.025% capsaicin or vehicle lotion applied twice daily for 6 weeks. After a 4-week wash-out period, treatments were switched. Significant improvement was reported by owners ( P  = 0.0006), but not by investigators. Owners noted temporary worsening of pruritus after the first week of capsaicin therapy. Overall capsaicin was well tolerated. Substance P (SP) concentrations in the skin did not correlate with the severity of the pruritus and did not change significantly over time and between treatments. Lesional skin had less SP than nonlesional skin ( P  = 0.03). These observations suggest that topical capsaicin should be further evaluated as an adjunctive antipruritic agent in dogs with AD.     

Pilot evaluation of the efficacy of shampoo treatment with ultrapure soft water for canine pruritus

Ultrapure soft water (UPSW) is water in which calcium and magnesium ions have been replaced with sodium ions using a cation‐exchange resin. We recently demonstrated that washing with soap and UPSW reduced the clinical severity of dermatitis and improved the skin barrier function in NC/NgaTnd mice, a murine model for human atopic dermatitis. The purpose of this pilot study was to evaluate the efficacy of shampoo treatment with UPSW for dogs with pruritus. Eleven dogs with pruritus were randomly assigned to two groups depending on whether they received weekly shampoo treatment with UPSW or tap water for 4 weeks. After a washout period, the treatment protocol was switched such that each dog received both treatments. The pre‐treatment and post‐treatment values of the following were compared: pruritus scores assessed by the owners; dermatitis scores recorded by an investigator; and transepidermal water loss (TEWL). Shampoo treatment with UPSW significantly decreased pruritus and dermatitis scores in the dogs, whereas shampoo treatment with tap water did not. In addition, shampoo treatment with UPSW, but not with tap water, significantly reduced TEWL in the dogs. Adverse events due to the treatment were not observed in the dogs. Furthermore, we found that topical application of UPSW for barrier‐disrupted skin caused by tape stripping in healthy dogs decreased TEWL more rapidly than topical application of tap water. Our findings suggest that shampoo treatment with UPSW promotes skin barrier recovery and thus could be considered as a possible therapeutic option in the management of pruritus and dermatitis in dogs.     

Assessment of a correlation between Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and selected biophysical skin measures (skin hydration,pH, and erythema intensity) in dogs with naturally occurring atopic dermatitis

Atopic dermatitis is a common allergic skin disease in dogs. The aim of this study was to examine the possibility of a correlation between biophysical skin variables: skin hydration (SH), skin pH, and erythema intensity measured in 10 different body regions and both total Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and CADESI measured in a given region (CADESI L). The study was conducted using 33 dogs with atopic dermatitis. The assessment of the biophysical variables was done in 10 body regions: the lumbar region, right axillary fossa, right inguinal region, ventral abdominal region, right lateral thorax region, internal surface of the auricle, interdigital region of right forelimb, cheek, bridge of nose, and lateral site of antebrachum. Positive correlations were found between SH and CADESI L for the following regions: the inguinal region (r = 0.73) and the interdigital region (r = 0.82), as well as between total CADESI and SH on digital region (r = 0.52). Also, positive correlations were reported for skin pH and CADESI L in the lumbar region (r = 0.57), the right lateral thorax region (r = 0.40), and the lateral antebrachum (r = 0.35). Positive correlations were found in the interdigital region between erythema intensity and the total CADESI-03 (r = 0.60) as well as the CADESI L (r = 0.7). The results obtained suggest that it may be possible to use skin hydration, pH, and erythema intensity to assess the severity of skin lesion but positive correlation was only found in < 13.3% of possible correlations and usage of these measures in dogs is limited.     

Prednisolone therapy for atopic dermatitis is less effective in dogs with lower pretreatment serum 25-hydroxyvitamin D concentrations

Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in 20 dogs with atopic dermatitis prior to treatment with a standard therapeutic dosage of prednisolone (0.93-1.06 mg/kg) every other day for 5 weeks after 7 days of treatment with the same dosage once daily. The severity of their physical signs was scored before and 6 weeks after prednisolone treatment by the canine atopic dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh Pruritus Scale (EPS). The 20 dogs with atopic dermatitis that were treated with prednisolone did not have significantly lower serum concentrations of 25(OH)D than a group of 36 healthy dogs, and the physical severity of the atopic dermatitis was not correlated to pretreatment serum 25(OH)D concentrations. However, dogs which had a marked improvement of their physical signs, defined by a post-treatment EPS score of 0 and/or an 85% reduction in CADESI-03 score, had significantly higher pretreatment serum 25(OH)D concentrations than dogs with a suboptimal response (P = 0.003 and P = 0.03, respectively). Serum 25(OH)D concentrations were also measured in a previously published cohort of atopic dogs that were treated with ciclosporin. This cohort of dogs was recruited in a similar time frame to the prednisolone-treated dogs, and all samples were handled in the same way. In contrast to the prednisolone-treated dogs, there was no significant difference in 25(OH)D concentrations in dogs that responded optimally to ciclosporin compared with suboptimal responders. Additional studies are required to establish whether vitamin D has a synergistic therapeutic effect with prednisolone in dogs with atopic dermatitis.     

Further validation of a pruritus severity scale for use in dogs

A scale to assess the severity of pruritus in dogs was further validated. Comparison of the scale with one containing visible numerical markings demonstrated that owners were heavily influenced by the presence of numbers, resulting in a loss of the scale's ability to generate continuous data. The presence of a traditional visual analogue scale was therefore essential. The scale was tested on 713 owners who presented their dogs for veterinary attention. Pruritus scores in 408 dogs with skin disease covered the full range of possible values (0 to 10). In 305 dogs with no skin disease, 90 owners gave a score greater than zero. Comparison of the scores seen in pruritic dogs, and dogs with no evidence of skin disease, allowed a 'normal range' of 0–1.9 to be established. The scale was able to discriminate between conditions typically regarded as pruritic or non-pruritic. When the scale was assessed for its ability to detect changes in pruritus score following treatment, a median reduction of 4.4 points was observed. The scale was also used to determine what magnitude of response owners would expect following treatment of their pruritic dogs. Only 12% would have been satisfied with a 50% reduction, a figure that is typically quoted as a satisfactory response in clinical trials of anti-pruritic drugs. As a result, alternative methods of assessing clinical trials are proposed. This study has shown the scale to be a valuable tool for clinical assessment of patients, and for monitoring treatment responses in clinical trials.     

Validity of a health-related quality-of-life scale for dogs with signs of pain secondary to cancer

OBJECTIVE: To develop and validate a health-related quality-of-life scale for dogs with pain secondary to cancer. DESIGN: Questionnaire development. ANIMALS: 40 healthy dogs with no history or signs of pain, 20 dogs with dermatologic disease but no signs of pain other than mild pruritus, and 20 dogs with cancer. PROCEDURE: Owners of all dogs completed a questionnaire containing 12 questions with 4 options for each question, and a quality-of-life score ranging from 0 to 36 was calculated. Scores for dogs with cancer were compared with scores for healthy dogs and dogs with dermatologic disease. RESULTS: All owners indicated that the questionnaire was easy to complete. Scores for healthy dogs were significantly different from scores for dogs with cancer and scores for dogs with dermatologic disease. Scores for dogs with dermatologic disease were significantly different from scores for dogs with cancer. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a simple questionnaire may be useful in assessing health-related quality of life in dogs with pain secondary to cancer, in that dogs with cancer had significantly lower scores than did healthy dogs and dogs with dermatologic disease.     

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.     

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.     

Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis

OBJECTIVE: To develop and psychometrically test an owner self-administered questionnaire designed to assess severity and impact of chronic pain in dogs with osteoarthritis. SAMPLE POPULATION: 70 owners of dogs with osteoarthritis and 50 owners of clinically normal dogs. PROCEDURES: Standard methods for the stepwise development and testing of instruments designed to assess subjective states were used. Items were generated through focus groups and an expert panel. Items were tested for readability and ambiguity, and poorly performing items were removed. The reduced set of items was subjected to factor analysis, reliability testing, and validity testing. RESULTS: Severity of pain and interference with function were 2 factors identified and named on the basis of the items contained in them. Cronbach's alpha was 0.93 and 0.89, respectively, suggesting that the items in each factor could be assessed as a group to compute factor scores (ie, severity score and interference score). The test-retest analysis revealed kappa values of 0.75 for the severity score and 0.81 for the interference score. Scores correlated moderately well (r = 0.51 and 0.50, respectively) with the overall quality-of-life (QOL) question, such that as severity and interference scores increased, QOL decreased. Clinically normal dogs had significantly lower severity and interference scores than dogs with osteoarthritis. CONCLUSIONS AND CLINICAL RELEVANCE: A psychometrically sound instrument was developed. Responsiveness testing must be conducted to determine whether the questionnaire will be useful in reliably obtaining quantifiable assessments from owners regarding the severity and impact of chronic pain and its treatment on dogs with osteoarthritis.