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.     

Tepoxalin reduces pruritus and modified CADESI-01 scores in dogs with atopic dermatitis: a prospective, randomized, double-blinded, placebo-controlled, cross-over study

Thirty dogs with atopic dermatitis were given tepoxalin (Zubrin®, Intervet/Schering-Plough Animal Health, Boxmeer, the Netherlands) or placebo once daily for 4 weeks, followed by a wash-out period of 1 week before reversing the treatments. Pruritus was scored by the owners using the Edinburgh Pruritus Scale and one investigator employed a modification of the Canine Atopic Dermatitis Extent and Severity Index-01 (mCADESI-01) to score the physical lesions. After administration of tepoxalin there was a ≥ 50% reduction in pruritus and mCADESI-01 scores in 36% and 25% of the dogs, respectively, whereas following administration of the placebo there was a ≥ 50% reduction in pruritus and mCADESI-01 scores in only 25% and 16% of the dogs, respectively. Analysis of pooled data indicated that tepoxalin resulted in a significant reduction in pruritus ( P  = 0.012) and mCADESI-01 ( P  = 0.002) scores but there was no significant change after placebo. The median pruritus scores before and after tepoxalin were 2 (range 1–5) and 1 (range 0–5), respectively, and before and after placebo were 2 (range 0–4) and 2 (range 0–4), respectively. The median mCADESI scores before and after tepoxalin were 23 (range 0–68) and 16 (range 0–72), respectively, and before and after placebo were 18 (range 3–79) and 24 (range 0–65), respectively. At the dose used in this study (10.0–19.1 mg kg⁻¹), tepoxalin was well-tolerated and no adverse effects were noted.     

Interventions for atopic dermatitis in dogs: a systematic review of randomized controlled trials

The objective of this systematic review, which was performed following the guidelines of the Cochrane collaboration, was to assess the effects of interventions for treatment of atopic dermatitis (AD) in dogs. Citations identified from three databases (MEDLINE, Thomson's Science Citation Index Expanded and CAB Abstracts) and trials published by December 2007 were selected. Proceedings books from the major veterinary dermatology international congresses were hand searched for relevant citations. The authors selected randomized controlled trials (RCTs), published from January 1980 to December 2007, which reported the efficacy of topical or systemic interventions for treatment or prevention of canine AD. Studies had to report assessments of either pruritus or skin lesions, or both. Studies were selected and data extracted by two reviewers, with discrepancies resolved by a third arbitrator. Missing data were requested from study authors of recently published trials. Pooling of results and meta-analyses were performed for studies reporting similar interventions and outcome measures. A total of 49 RCTs were selected, which had enrolled 2126 dogs. This review found some evidence of efficacy of topical tacrolimus (3 RCTs), topical triamcinolone (1), oral glucocorticoids (5), oral ciclosporin (6), subcutaneous recombinant γ-interferon (1) and subcutaneous allergen-specific immunotherapy (3) to decrease pruritus and/or skin lesions of AD in dogs. One high-quality RCT showed that an oral essential fatty acid supplement could reduce prednisolone consumption by approximately half. Additional RCTs of high design quality must be performed to remedy previous flaws and to test interventions for prevention of flares of this disease.     

Clinical use of a ceramide-based moisturizer for treating dogs with atopic dermatitis

In humans, skin barrier dysfunction is thought to be responsible for enhanced penetration of allergens. Similar to conditions seen in humans, canine atopic dermatitis (CAD) is characterized by derangement of corneocytes and disorganization of intercellular lipids in the stratum corenum (SC) with decreased ceramide levels. This study was designed to evaluate the effects of a moisturizer containing ceramide on dogs with CAD. Dogs (n = 20, 3~8 years old) with mild to moderate clinical signs were recruited and applied a moisturizer containing ceramide for 4 weeks. Transepidermal water loss (TEWL), skin hydration, pruritus index for canine atopic dermatitis (PICAD) scores, and canine atopic dermatitis extent and severity index (CADESI) scores of all dogs were evaluated. Skin samples from five dogs were also examined with transmission electron microscopy (TEM) using ruthenium tetroxide. TEWL, PICAD, and CADESI values decreased (p < 0.05) and skin hydration increased dramatically over time (p < 0.05). Electron micrographs showed that the skin barrier of all five dogs was partially restored (p < 0.05). In conclusion, these results demonstrated that moisturizer containing ceramide was effective for treating skin barrier dysfunction and CAD symptoms.     

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.     

Pilot investigation of a model for canine atopic dermatitis: environmental house dust mite challenge of high-IgE-producing beagles, mite hypersensitive dogs with atopic dermatitis and normal dogs

Although canine atopic dermatitis (cAD) is common, few models are available. The aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were environmentally challenged with HDM using various doses and protocols. Similar challenge protocols were used in positive and negative control dogs: three dogs with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and three normal dogs without history of skin disease and negative IDT to HDM. All high-IgE beagles and all atopic dogs developed severe cutaneous lesions and pruritus after challenge. Lesions were erythematous papules and macules in contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They were first visible after 6 h and increased in severity over time. No normal dog developed pruritus or lesions. Biopsies of representative lesions in the high-IgE beagles were taken for histopathology and immunohistochemistry. There was superficial perivascular dermatitis with mononuclear infiltrates and spongiosis. Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that this colony of high-IgE beagles develops a dermatitis that clinically, histopathologically and immunologically resembles the naturally occurring canine disease. It is also concluded that this modality of challenge is not irritating to normal dogs but induces flare-ups in hypersensitive atopic dogs.     

Requirement for additional treatment for dogs with atopic dermatitis undergoing allergen-specific immunotherapy

Allergen-specific immunotherapy (ASIT) is one of the main treatments for atopic dermatitis in dogs, but it often requires additional treatments such as antibacterial and antifungal therapy for secondary bacterial and yeast infections, or antipruritic drugs to control the clinical signs or treat the adverse effects of the immunotherapy. Twenty-seven dogs enrolled in a study of ASIT were clinically assessed four times over a period of nine months; their requirement for treatment for secondary bacterial and yeast infections, for the administration of glucocorticoids as additional antipruritic therapy, and for the treatment of any adverse effects of the ASIT were evaluated. Twenty (74 per cent) of the dogs were treated for superficial bacterial pyoderma, 18 (66.6 per cent) required treatment for Malassezia species dermatitis on one or more occasions, eight (29.6 per cent) required treatment for otitis externa due to Malassezia species or bacteria, and eight required glucocorticoids to control their clinical signs. Five (18.5 per cent) of the dogs experienced adverse effects due to the ASIT and two required treatment with antihistamines (H1 receptor antagonists) in order to continue with the ASIT.     

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.     

Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis.

Serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly (P less than 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function.     

Results of allergen-specific immunotherapy in 117 dogs with atopic dermatitis

The success of the treatment of 117 dogs with atopic dermatitis with allergen-specific immunotherapy for up to 48 months was assessed. An excellent response (remission with exclusive immunotherapy) was recorded in 18 of the dogs, a good response (more than 50 per cent reduction in medication and improvement of clinical signs) was recorded in 57, a moderate response was recorded in 24 and a poor response in 18. The mould antigens in the allergen extract were stored in a separate vial before administration and the success rate of the immunotherapy including mould antigens was much higher than in an earlier study in which mould and pollen antigens had been stored in one vial. The success rate was not affected significantly by the age of the dogs when the disease developed, or by their age or the period for which they had shown clinical signs when the treatment began; it was also unaffected by whether pollens, moulds or dust mites were used as antigens, or by whether the offending allergens had been identified by intradermal testing or by serum testing for allergen-specific immunoglobulin E.     

Development of a clinical severity index for dogs with acute pancreatitis

Objective-To establish a clinical severity index that correlates severity of body system abnormalities with outcome in dogs with acute pancreatitis (AP) and determine the usefulness of serum C-reactive protein (C-RP) concentration as an objective measure of AP severity. Design-Retrospective cohort study. Animals-61 client-owned dogs with ultrasonographically or histologically confirmed AP. Procedures-Medical records of AP-affected dogs were reviewed, and signalment, physical examination findings, clinicopathologic data, and outcome (death or discharge from the hospital) were evaluated. The correlation of specific abnormalities in endocrine, hepatic, renal, hematopoietic, cardiovascular, and respiratory systems; local pancreatic complications; and intestinal integrity were evaluated, and a clinical severity index was developed for AP in dogs. The severity index score was compared with outcome and, for 12 dogs, with serum C-RP concentration. Results-The clinical severity index had a good correlation with outcome and interval from hospital admission until end point (days until outcome), but there was no difference in days until outcome between survivors and nonsurvivors. All 12 dogs evaluated had high serum C-RP concentration, but this variable was not related to outcome; however, within a 2-day period after onset of clinical signs, serum C-RP concentration in survivors and nonsurvivors differed significantly. Conclusions and Clinical Relevance-Among AP-affected dogs, the clinical severity index may be useful for treatment comparisons and prediction of intensive management requirements. Serum C-RP concentration was best related to AP severity within a 2-day period after onset of clinical signs, but daily measurement may be more useful for monitoring progress.     

Development and validation of the Canine Atopic Dermatitis Lesion Index,a scale for the rapid scoring of lesion severity in canine atopic dermatitis

Background – The third iteration of the Canine Atopic Dermatitis Extent and Severity Index (CADESI‐03) is the only tool rigorously validated for canine atopic dermatitis (CAD) lesion scoring. The CADESI‐03 requires 248 evaluations, limiting its widespread use. Hypothesis/Objectives – The goal of the study was to develop and validate a practical method of grading CAD lesions that requires scoring only the frequently affected body regions. Animals – Fifty‐seven privately owned atopic dogs were used in the study. Methods – The Canine Atopic Dermatitis Lesion Index (CADLI) was evaluated in an open, multicentre reliability study. Validity was assessed with expert opinion (content validity) and comparison of CADLI with existing disease severity measures (construct and criterion validity). Reliability was evaluated by analysing repeated observations of each dog. Convenience was assessed in terms of the time required to complete the scale. Results – The CADLI scores correlated with overall assessment scores (r = 0.60, P < 0.001, linear mixed model) and pruritus severity scores (r = 0.53, P < 0.001, linear mixed model), establishing construct validity. The CADLI was strongly correlated with CADESI‐03 (r = 0.84, P < 0.001, linear mixed model), establishing criterion validity. The CADLI values obtained by two observers correlated very strongly (r = 0.91, P < 0.001), as did the repeat values for the same observer (r = 0.98, P < 0.001). The mean time to complete the CADLI was less than that required for CADESI‐03 (1.9 and 12.6 min, respectively), a highly significant difference (P < 0.001). Conclusion and clinical importance – The CADLI was found to be an effective measure of CAD lesion severity, strongly correlating with CADESI‐03. The convenience of CADLI makes it suitable for use in both clinical research and practice.     

Effect of hyposensitization on atopic dermatitis in dogs

In a double-blind study, 51 dogs with clinically defined atopic dermatitis were injected with either alum-precipitated allergen solutions or a placebo. Comparing the treatment results of both groups on the basis of scores for clinical signs, a significant difference in clinical improvement was established in favor of the allergen-treated dogs (P less than 0.01). The proportional changes of scores for clinical signs in the allergen-treated group ranged between +27.3% and -100% (median, -61.5%) and in the placebo group between +36.4% and -100% (median, 0.0%) with respect to the initial scores. Immediate skin test reactivity disappeared only in the dogs with a good clinical response. Of 27 dogs treated with an allergen solution, 16 (59.3%) had an improvement of 51% or more. In the placebo group, 5 of 24 dogs (20.8%) reacted this way. There was total remission of the clinical signs in 9 and 4 dogs, respectively. In the dogs in which, after 9 months of hyposensitization, any improvement was observed, the chance for final improvement of more than 51% was calculated as 84%. Discriminant analysis revealed that evaluation of the effect of immunotherapy can be restricted to the 9-month follow-up examination.     

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.     

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.