Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.     

A randomized double-blinded placebo-controlled study to evaluate an effective ciclosporin dose for the treatment of feline hypersensitivity dermatitis

Background – Hypersensitivity dermatitides (HD) are frequently suspected in cats, but there are few clinical studies on safe and effective treatments in the published literature. Objectives – To establish a safe and effective dose of ciclosporin in the treatment of feline HD. Animals – One hundred client‐owned cats with feline HD. Methods – Double‐blind study, with cats randomly assigned to receive ciclosporin at either 7.0 mg/kg once daily (n = 33) or 2.5 mg/kg once daily (n = 32) or a placebo (n = 35) for 6 weeks. Results – Mean Total Lesion Scores with 7.0 mg/kg ciclosporin were significantly lower than with 2.5 mg/kg ciclosporin (P = 0.0047) or placebo (P = 0.0003) at study end. Individual Total Lesion Scores improved by >50% in 70% of the 7.0 mg/kg group, compared with 47% in the 2.5 mg/kg group and 23% in the placebo group (P = 0.0006). The investigators’ Global Assessment of Improvement was ‘excellent’ or ‘good’ in 61% of cats treated with 7.0 mg/kg ciclosporin, compared with 47% of cats given 2.5 mg/kg and 23% given placebo. The improvement in Investigator Pruritus Scores was significantly greater in cats treated with 7.0 mg/kg ciclosporin (54%) compared with both 2.5 mg/kg ciclosporin (32%; P = 0.0232) and placebo (21%; P = 0.0063). Mild gastrointestinal disorders were the most common adverse events, but these did not require cessation of therapy. Conclusions and clinical importance – Results suggest that 7.0 mg/kg ciclosporin once daily in food or per os for 6 weeks is effective and well tolerated in feline HD.     

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.     

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.     

Canine and feline atopic dermatitis: A review of the diagnostic options

Atopic dermatitis is an inherited pruritic skin disease in dogs and cats. This pruritic skin condition is due to the animal having an allergic reaction to environmental allergens. The environmental allergens that an individual dog or cat is allergic to are specific for that individual animal. Management options for affected dogs and cats include identification of the offending environmental allergens and subsequent avoidance of that allergen, or allergen-specific immunotherapy. Several diagnostic tests are available to veterinarians to try to identify these allergens. The pros and cons of each of these diagnostic tests will be addressed.     

Detection of feline herpes virus 1 via polymerase chain reaction and immunohistochemistry in cats with ulcerative facial dermatitis, eosinophilic granuloma complex reaction patterns and mosquito bite hypersensitivity

Ulcerative dermatitis caused by feline herpes virus 1 (FHV-1) is an uncommon disease characterized by cutaneous ulcers secondary to epidermal, adnexal and dermal necrosis. Differential diagnoses for FHV-1 lesions include, but are not limited to, mosquito bite hypersensitivity and eosinophilic granuloma complex. Histopathological diagnosis of FHV-1 dermatitis is based on the detection of the intranuclear inclusion bodies. In cases where intranuclear inclusions are missing but clinical and histological findings are compatible with FHV-1 dermatitis, immunohistochemistry (IHC) and PCRs have been used. In this retrospective study, we evaluated the presence of FHV-1 by IHC and PCR in skin biopsies and compared the results of the two tests. Sixty-four skin biopsy specimens from cats with compatible lesions were reviewed and tested via PCR and IHC for evidence of FHV-1. Polymerase chain reaction was positive in 12 of 64 biopsies; PCR and IHC were positive only in two of 64 biopsies, and these cases were considered true positive cases. The higher number of PCR-positive cases was possibly attributed to amplification of viral DNA from a live attenuated vaccination, but a previous FHV-1 infection with subsequent amplification of latently inserted FHV-1 could not be excluded. If clinical signs and histopathology suggest FHV-1 infection in the absence of typical inclusion bodies, IHC is the preferred diagnostic test; PCR may be useful for initial screening, but due to false positives is not sufficient for a definitive diagnosis.     

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

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

Interaction of an intranasal combined feline viral rhinotracheitis, feline calicivirus vaccine and the FVR carrier state

Eight cats were vaccinated intranasally with a combined feline calicivirus/feline viral rhinotracheitis (FVR) virus commercial vaccine. Following intranasal challenge with a field strain of FVR virus and subsequent treatment with corticosteroid, no virus was recovered from any of the eight cats, while FVR virus was recovered following corticosteroid treatment from two of four unvaccinated and challenged controls. No evidence was found for the development of an FVR virus carrier state with the intranasal vaccine virus.     

Management of feline miliary dermatitis by supplementing the diet with essential fatty acids

Of eight cats with miliary dermatitis, six showed a good response to treatment with a dietary supplement of essential fatty acids. The analysis of serum fatty acids revealed significant abnormalities in cats with miliary dermatitis compared with normal cats.     

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.     

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.     

Relevance of feline calicivirus, feline immunodeficiency virus, feline leukemia virus, feline herpesvirus and Bartonella henselae in cats with chronic gingivostomatitis

Despite its common occurrence, the aetiology of chronic gingivostomatitis in cats remains uncertain. Aetiology is likely multifactorial, and several infectious agents may be associated with chronic gingivostomatitis. The purpose of this study was to investigate the prevalence of feline calicivirus (FCV), feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), feline herpesvirus (FHV), and Bartonella henselae (B. henselae) in cats with chronic gingivostomatitis and in an age-matched control group. In addition, other factors, e. g., environmental conditions were investigated. In 52 cats with chronic gingivostomatitis and 50 healthy age-matched control cats, the presence of FCV ribonucleic acid (RNA), and FHV deoxyribonucleic acid (DNA) (polymerase chain reaction [PCR] from oropharyngeal swabs), and B. henselae DNA (PCR from oropharyngeal swabs and blood), as well as FeLV antigen (serum), and antibodies against FCV, B. henselae, and FIV (serum) were examined. FCV RNA was significantly more common in cats with chronic gingivostomatitis (53.8%, p < 0.001) than in controls (14.0%); a significant difference was also found in the prevalence of antibodies to FCV between the cats with chronic gingivostomatitis (78.8%, p = 0.023) and controls (58.0%). Of the other infectious agents investigated, there was no significant difference in the prevalence between the cats with chronic gingivostomatitis and the controls. The results of this study allow the conclusion that FCV, but no other infectious agents, is commonly associated with chronic gingivostomatitis in cats.