Measurement of serum Interleukin 34 (IL-34) and correlation with severity and pruritus scores in client-owned dogs with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of dogs. Interleukin (IL)-34 is a monocyte/macrophage growth factor, produced mainly by keratinocytes, that has been implicated in several human inflammatory conditions including human AD. HYPOTHESIS: Canine serum IL-34 concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores. ANIMALS: Forty seven client-owned dogs diagnosed with AD and 25 healthy, unaffected control dogs. METHODS AND MATERIALS: A commercially available IL-34 ELISA was optimized for the measurement of IL-34 in canine serum samples. Information regarding treatment, clinical lesion scores [Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04)] and pruritus Visual Analog Score (pVAS) were recorded for each dog at the time of serum collection. RESULTS: Dogs with AD had significantly increased serum IL-34 concentrations compared to controls. There was a significant positive correlation between IL-34 concentrations and CADESI-04 and pVAS scores. Concentrations of IL-34 remained increased in dogs with AD receiving steroids or the JAK1 inhibitor, oclacitinib, compared to unaffected control dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum IL-34 concentrations are increased in dogs with AD and are correlated with clinical severity and pruritus. IL-34 may be a suitable candidate therapeutic target for canine AD.

Measurement of serum macrophage migration inhibitory factor (MIF) and correlation with severity and pruritus scores in client owned dogs with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of dogs. Macrophage migration inhibitory factor (MIF) initiates pro-inflammatory cytokine release in human AD and serum concentrations are correlated with disease severity. HYPOTHESIS: Canine serum MIF concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores. ANIMALS: Client owned dogs (n = 49) diagnosed with AD and 17 healthy, unaffected control dogs were used for the study. METHODS AND MATERIALS: A commercially available MIF ELISA was optimized for the dog and serum from clinical cases used. Information regarding treatment, Canine Atopic Dermatitis Extent and Severity Index, (CADESI-4) and pruritus Visual Analog Scale (pVAS) were recorded for each dog at the time of serum collection. RESULTS: Dogs with AD which had not received steroid therapy and those treated with oclacitinib had significantly elevated serum MIF concentrations compared to controls. Concentrations of MIF were not significantly different in AD dogs receiving steroids compared to controls. There was no significant correlation between MIF concentrations and clinical scores (CADESI-4 or pVAS). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum MIF concentrations are increased in dogs with AD and MIF might be a target for therapy.

Dose tapering for ciclosporin in cats with nonflea-induced hypersensitivity dermatitis.

BACKGROUND: Little information is available on the ciclosporin dose-tapering regimen and clinical response in the treatment of feline hypersensitivity dermatitis. HYPOTHESIS/OBJECTIVES: To test a dose-tapering regimen and assess efficacy and clinical safety for up to 18 weeks. ANIMALS: Eighty-eight client-owned cats with feline hypersensitivity dermatitis. METHODS: Cats that received either a placebo or ciclosporin at 2.5 mg/kg or 7 mg/kg daily for 6 weeks were given 7 mg/kg ciclosporin daily for 4 weeks. Depending on the clinical response, the dose was tapered from daily to every other day over the next 4 weeks and further to twice a week for an additional 4 weeks. RESULTS: After all cats received 7 mg/kg for 4 weeks, the dose could be tapered to every other day for the next 4 weeks in 70% of cats remaining in the study. During the next 4 weeks, 57, 15 and 22% of cats remaining in the study could be treated at twice a week, every other day or daily, respectively. After the first 4 weeks, the mean lesion score and owner-assessed pruritus improved over baseline by 69 and 61%, respectively, and remained stable during the following 8 weeks. Approximately 65% of the cats in the study were reported to have an adverse event (AE), very often mild and resolving spontaneously. The most frequent AEs were gastrointestinal and included primarily vomiting and diarrhoea. Eighty per cent of AEs occurred when cats were on daily treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that the induction dose of 7 mg/kg ciclosporin can be tapered as soon as 4 weeks without deterioration of the clinical response. Establishment of the lowest effective dosing regimen of ciclosporin reduced the frequency of AEs.

The effectiveness of systemic antimicrobial treatment in canine superficial and deep pyoderma: a systematic review.

AIM: To identify and evaluate existing evidence for the effectiveness of systemic antimicrobial treatments for naturally occurring superficial and deep canine pyoderma. METHOD: Electronic searches of PubMed, MEDLINE and CAB Direct were carried out (25 May 2011) without date or language restrictions. Proceedings of ESVD/ECVD, AAVD/ACVD, NAVDF and WCVD annual congresses were searched. Unpublished studies were sought via the Veterinary Dermatology discussion list and Veterinary Information Network. RESULTS: Seventeen full-length, peer-reviewed controlled trials reporting clinical outcomes of systemic antimicrobial treatment for canine pyoderma were identified. Outcomes specific to superficial or deep pyoderma were reported in nine and five studies, respectively. Five studies reported outcomes only for nondifferentiated pyoderma depth. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. A good level of evidence was identified supporting the high efficacy of subcutaneously injected cefovecin in superficial pyoderma and for oral amoxicillin-clavulanic acid in deep pyoderma. A fair level of evidence was identified for moderate to high efficacy of oral amoxicillin-clavulanic acid, clindamycin, cefadroxil, trimethoprim-sulphamethoxazole and sulfadimethoxine-ormetoprim in superficial pyoderma and oral pradofloxacin, oral cefadroxil and subcutaneously injected cefovecin in deep pyoderma. Eleven trials reported observations of adverse effects in treated pyoderma cases by intervention group; four dogs were withdrawn owing to the severity of adverse effects. CONCLUSIONS: There is a need for greater numbers of adequately sized, blinded, randomized controlled trials evaluating systemic antimicrobial interventions for canine pyoderma. Improved differentiation between superficial and deep pyoderma in outcome reporting, outcome measure standardization and association of outcomes with causative bacterial species and their resistance patterns are required.

Ciclosporin 10 years on: indications and efficacy.

Ciclosporin is a lipophilic cyclic polypeptide with powerful immunosuppressive and immunomodulatory properties that has been used in veterinary medicine for two decades. It is a calcineurin inhibitor whose principal mode of action is to inhibit T cell activation. The drug is principally absorbed from the small intestine and is metabolised in the intestine and liver by the cytochrome P450 enzyme system. Ciclosporin is known to interact with a wide range of pharmacological agents. Numerous studies have demonstrated good efficacy for the management of canine atopic dermatitis and this has been a licensed indication since 2003. In addition to the treatment of atopic dermatitis, it has been used as an aid in the management of numerous other dermatological conditions in animals including perianal fistulation, sebaceous adenitis, pododermatitis, chronic otitis externa and pemphigus foliaceus. This article reviews the mode of action, pharmacokinetics, indications for use and efficacy of ciclosporin in veterinary dermatology.

Adherence of Staphylococcus intermedius to corneocytes of healthy and atopic dogs: effect of pyoderma, pruritus score, treatment and gender.

Staphylococcal pyoderma occurs commonly in atopic dogs. Some studies have suggested that adherence of staphylococci to corneocytes of atopic dogs and humans is higher than to corneocytes of healthy individuals. This hypothesis and possible differences resulting from the presence or absence of pyoderma, the severity of pruritus or the effect of treatment or gender, were studied. Adherent bacteria (Staphylococcus intermedius) were quantified by computerized image analysis on corneocytes collected from healthy or atopic dogs using double-sided adhesive tape. The adherence of S. intermedius to the corneocytes of atopic dogs was significantly greater than to those of healthy dogs (P=0.005). Furthermore, adherence was significantly greater in dogs with high levels of pruritus compared to those with low scores. No significant differences were found between atopic dogs with no history of pyoderma, atopic dogs with a history of pyoderma and atopic dogs with pyoderma at the time of sampling (P=0.068), suggesting that factors other than adherence are necessary for clinical pyoderma to develop. Treatment did not generally influence the adherence of S. intermedius to corneocytes of atopic dogs and there was no gender difference in adherence in either healthy or atopic dogs.

Species specificity in the adherence of staphylococci to canine and human corneocytes: a preliminary study.

Staphylococcal pyoderma is rarely contagious between dogs and humans, or humans and dogs. This study investigated the hypothesis that there are species differences in adherence of Staphylococcus intermedius (the most common isolate from dogs) and Staphylococcus aureus (the most common isolate from humans) to canine and human corneocytes. Sheets of corneocytes were collected from the ventral abdomen of 10 dogs and the medial forearm of 10 humans (all healthy and without any history or physical signs of skin disease) using double-sided tape. Staphylococcus intermedius from a case of canine bacterial pyoderma and a human strain of S. aureus were prepared in phosphate buffered saline (PBS) and applied in duplicate, respectively, to the canine and human corneocyte-covered tapes using PBS as negative control. After incubation, rinsing, and staining with crystal violet, quantification of the adherent bacteria was carried out blindly by computerized image analysis. Staphylococcus intermedius was found to adhere significantly more to canine corneocytes than S. aureus (P = 0.0006), whereas S. aureus showed greater adherence to human corneocytes than S. intermedius (P < 0.0001). In addition, the pattern of adherence differed between the two organisms, with S. intermedius adhering to the entire surface and S. aureus adhering mainly to the periphery of both canine and human corneocytes. Preference for adherence to these two hosts may explain, in part, why S. intermedius and S. aureus are uncommonly isolated from human and canine skin infections, respectively.

Use of computerized image analysis to quantify staphylococcal adhesion to canine corneocytes: does breed and body site have any relevance to the pathogenesis of pyoderma?

An optimized system of computerized image analysis was used to investigate variations in the adherence of Staphylococcus intermedius to canine corneocytes from four different breed groups and six different anatomical sites. S. intermedius showed significantly greater adherence to the head and neck compared with the dorsum, but adherence to the limb, axilla and groin did not differ from other sites. Furthermore, there was significantly greater adherence of S. intermedius to corneocytes from the dorsum, forelimb, axilla and groin of Boxers and Bull Terriers than Spaniels and Hounds. S. intermedius, and also Pseudomonas aeruginosa, exhibited abundant adherence, which was significantly greater than Staphylococcus aureus, Streptococcus canis, Klebsiella pneumoniae and Escherichia coli. In addition, S. intermedius adherence demonstrated a sigmoid dose-response curve with increasing bacterial concentration. These results suggest that S. intermedius adheres to canine corneocytes by a specific receptor-ligand interaction and adheres to the skin of some breeds more avidly than others. However, variations in adherence between body regions would not account for the predilection sites of canine bacterial pyoderma.