A pilot study on the effect of oclacitinib on epicutaneous sensitization and transepidermal water loss in a colony of atopic beagle dogs.

BACKGROUND: Dogs with atopic dermatitis are prone to sensitization to environmental allergens due to increased skin permeability; the effect of treatments on epicutaneous sensitizations is unknown. HYPOTHESIS/OBJECTIVES: To evaluate if oclacitinib (i) prevents new sensitizations and (ii) affects skin barrier function. ANIMALS: Atopic beagle dogs. METHODS: Aim 1. Ten dogs were randomly assigned to placebo or oclacitinib while exposed epicutaneously to a novel allergen. Sensitization was assessed using serum allergen-specific IgE and clinically by development of skin reactions at the site of allergen application. Time to develop dermatitis and allergen-specific IgE were compared between groups. Aim 2. Eight dogs were randomly assigned to placebo or oclacitinib for four weeks and challenged with an allergen known to trigger flares. After a four week wash-out, dogs were crossed-over and the protocol repeated. Transepidermal water loss (TEWL) was measured on days 0 and 28 of each arm. RESULTS: Aim 1. Oclacitinib significantly increased (P = 0.006) time to develop skin reactions compared to placebo. Four (of five) dogs receiving oclacitinib failed to develop skin reactions, whereas all placebo dogs developed dermatitis. There were no significant differences in allergen-specific IgE between groups. Aim 2. TEWL results were difficult to interpret. Significantly higher values were detected from the axilla in placebo compared to oclacitinib-treated dogs (P = 0.047). TEWL values were significantly higher from the inguinal area in oclacitinib (P = 0.039) treated dogs but not placebo at the end of the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinically, oclacitinib delayed development of dermatitis at the site of allergen application. TEWL results were difficult to interpret and additional studies are required for clarification.

Evaluation on the effects of 0.1% Peumus boldus leaf and Spiraea ulmaria plant extract combination on bacterial colonization in canine atopic dermatitis: A preliminary randomized, placebo controlled, double-blinded study.

Defective skin barrier characterize canine atopic dermatitis (AD). Pyoderma is the most common complication. Herbal compounds have been suggested as alternatives to control bacterial colonization for their effect on natural antimicrobial peptides (AMPs). This study evaluated the effects of 0.1% Peumus boldus leaf and Spiraea ulmaria plant extract combination on clinical signs, bacterial colonization and AMPs secretion in atopic dogs compared to placebo. Twenty privately-owned atopic dogs were randomly divided in 2 groups (treatment: n = 10; placebo: n = 10) and their abdomen was sprayed every 24 h for 4 weeks. Total and inguinal clinical scores (CADESI-03), manual bacterial count, and skin washes for AMPs (cBD3-like and cCath) were performed on days 0, 14 and 28. AMPs were detected using in-house, previously-validated, canine-specific ELISAs. Data were statistically analyzed and a p < 0.05 was considered significant. Clinical scores and AMPs secretion did not differ significantly between the two groups at any time point. A significant reduction of the clinical scores was seen in the placebo group at 14 and 28 days (p < 0.04). On days 14 and 28, a reduction in the bacterial count was seen in the treated group compared with placebo (p < 0.009 and p = 0.04, respectively). Compared to baseline, a reduction in Staphylococcus spp. was seen in the treated group after 14 days of treatment (p < 0.03). These results show the efficacy of this plant extract combination against bacterial colonization, suggesting its potential usefulness in preventing bacterial infection in atopic dogs. The influence of this compound on AMPs secretion or other mechanisms should be further evaluated.

Evaluation of the in vitro effect of Boldo and Meadowsweet plant extracts on the expression of antimicrobial peptides and inflammatory markers in canine keratinocytes.

Dogs with allergies are prone to skin infections and treatments/preventatives to boost innate immune-defenses are beneficial. The aim of this study was to evaluate the effects of Boldo and Meadowsweet extracts on the expression of ß-defensins (cBD), cathelicidin (cCath), and pro-inflammatory cytokines in canine keratinocyte. This study had two phases. Phase I evaluated mRNA expression of cBD103 and cCath, and secretion of cCath, IL-8 and TNF-α by keratinocytes harvested from healthy (n=5) and atopic (n=5) age-matched beagles exposed to Boldo (2% to 0.2%) and Meadowsweet (1% to 0.2%) extracts. Phase II focused on atopic keratinocytes (n=14) exposed to 0.2% Boldo, 0.2% Meadowsweet, and a mixture of 0.1% of both extracts. Phase I: cBD103 mRNA (all concentrations) and TNF-α secretion (2% Boldo) were increased in atopic compared with healthy keratinocytes. In atopic keratinocytes, cBD103 was increased after exposure to 1.5% and 0.2% Boldo. In healthy keratinocytes, 1% and 0.2% Meadowsweet, and 2% Boldo increased and decreased IL-8 secretion, respectively. In atopic keratinocytes, IL-8 increased after exposure to 1% and 0.4% Meadowsweet extract. Phase II: cBD103 mRNA increased after exposure to 0.2% Meadowsweet and to 0.1% mixture. cCath was increased after 0.2% Boldo, but decreased after 0.2% Meadowsweet or the 0.1% mixture. TNF-α secretion was decreased after 0.2% Boldo. It is concluded that low concentrations of both extracts and their combination may have some effects on cCath and cBD103 without stimulating an inflammatory response. However, more studies are needed to clarify the effects of these extracts on the local immunity.