Association between skin surface pH, temperature and Staphylococcus pseudintermedius in dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

Secondary bacterial infection is a frequent complication in lesional skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP). However, the influence of skin pH and temperature in determining the composition of the cutaneous microflora at lesional sites has not been investigated. The association between ImR-LPP and pedal skin temperature, pH and Staphylococcus pseudintermedius isolates was thus evaluated. Temperature and pH were measured in 20 dogs with ImR-LPP and in 30 clinically healthy control dogs, and S. pseudintermedius was cultured from interdigital and palmoplantar swabs in both groups and scored semi-quantitatively for bacterial growth. In the ImR-LPP group, mean skin pH was slightly, but significantly, higher at both interdigital and palmoplantar sites. Staphylococcus pseudintermedius was isolated more frequently, and scores for bacterial growth were also significantly higher. However, mean skin temperatures were not significantly different from those in the control group. The isolation of S. pseudintermedius was significantly associated with ImR-LPP, with the single exception of isolates on Columbia blood agar from the palmoplantar region. However, pH and temperature were not significantly associated with the disease, and were not associated with the isolation of S. pseudintermedius at most sites sampled. Staphylococcus pseudintermedius was not isolated from all feet sampled in dogs with ImR-LPP. Taken together, these data would suggest that S. pseudintermedius infection is most likely to be a secondary phenomenon in dogs with ImR-LPP, and that changes in skin pH and temperature are not significant risk factors for this disease.

Cutaneous infiltrates and peripheral blood immune responses in dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

This study characterizes T- and B-lymphocyte responses in the peripheral blood and lesional skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP), a term previously proposed to denote a subpopulation of dogs with idiopathic pododermatitis. T-cell (CD3+, CD4+ and CD8+ ) and B-cell (CD21+) counts were significantly increased in both the epidermis and dermis of lesional ImR-LPP skin compared with that in pedal skin from healthy controls. CD3+ , CD4+, CD8+ and CD21+ cells were commonly observed in perivascular sites in the superficial dermis, periadnexally, beneath the dermal-epidermal (DE) junction and in the epidermis of lesional ImR-LPP skin. The CD8+ /CD3+ T-cell ratio in peripheral blood was significantly increased in the ImR-LPP group (0.42 versus 0.35 in controls). Serum IgA, IgG and IgM concentrations were all significantly elevated in affected dogs. Lymphocyte stimulation indices in ImR-LPP dogs were comparable with control levels except for a lower response to ionomycin (6.0 versus 11.1). Dogs with ImR-LPP had a higher incidence and mean (semi-quantitative) score for IgA, IgG and IgM deposits in the epidermis, and a significantly increased incidence of dermal IgA+, IgG+ and IgM+ mononuclear inflammatory cells. The results indicate that upregulated T- and B-lymphocyte responses may contribute to the pathogenesis of the skin lesions observed in dogs with ImR-LPP.

A study of dendritic cell and MHC class II expression in dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

The term immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP) has previously been proposed to denote a sub-population of dogs with idiopathic pododermatitis. The objective of this study was to investigate dendritic cell (DC) and MHC class II antigen expression in lesional skin of dogs with ImR-LPP (n=47). Median epidermal CD1c(+) cell counts were 37.8 and 12.5 mm(-1) in ImR-LPP dogs and healthy controls (n=27), respectively (P<0.01), while the corresponding dermal cell counts were 180.9 and 45.0 mm(-2), respectively (P<0.01). Intra-epidermal clusters of DCs were observed in 18/47 dogs with ImR-LPP. Median epidermal MHC class II(+) cell counts were 32.5 and 10.5 mm(-1) in ImR-LPP dogs and healthy controls, respectively (P<0.01), while the corresponding dermal cell counts were 216.9 and 46.9 mm(-2), respectively (P<0.01). Dermal MHC class II(+) staining was primarily associated with DCs (47/47 dogs), mononuclear inflammatory cells (45/47), fibroblast-like cells (19/47) and vascular endothelium (14/47). The DC hyperplasia and increased MHC class II expression in lesional ImR-LPP skin are consistent with enhanced antigen presentation, and suggest that both parameters may contribute to the pathogenesis of ImR-LPP through the priming and activation of CD4(+) T cells. Equally, it is possible that the enhanced DC numbers observed in this study may contribute to the immunoregulation of steady-state pathology in lesional ImR-LPP skin through additional expanded, although as yet unresolved, mechanisms.

Canine pododermatitis and idiopathic disease.

Pododermatitis is a common inflammatory skin disease of dogs. As pedal lesions are reported in many canine dermatoses, a methodical series of diagnostic tests is required to establish the underlying aetiology. However, laboratory/ancillary investigations may prove unrewarding, prompting a diagnosis of idiopathic disease. Various hypotheses have been proposed to explain the pathogenesis of idiopathic pododermatitis including pedal conformation, trauma, immunosuppression, bacterial infection, furunculosis and dermal granuloma formation. Idiopathic pododermatitis accounts for 0.5% of all dermatology referrals to the authors' clinic. A sub-group within this population is characterised histopathologically by epidermal hyperplasia, hyperkeratosis, spongiosis, dermal oedema and perivascular aggregates of lymphocytes and plasma cells. The term lymphocytic-plasmacytic pododermatitis (LPP) has previously been proposed to reflect the histological appearance of such lesions. Affected dogs, although systemically well, characteristically have pruritus, erythema, swelling, pain and alopecia of the feet. Although non-responsive to antimicrobial therapy, antiparasitic agents and elimination diets, these dogs typically respond well to immunomodulatory therapy.

Evaluation of Th1-like, Th2-like and immunomodulatory cytokine mRNA expression in the skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis.

The term immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis (ImR-LPP) has previously been proposed to denote a subpopulation of dogs with idiopathic pododermatitis. The objective of this study was to quantify the expression of mRNA encoding Th(1)-like [interferon (IFN)-gamma, interleukin (IL)-2 and IL-12], Th(2)-like [IL-4 and IL-6] and immunomodulatory cytokines [IL-10 and transforming growth factor (TGF)-beta] in lesional ImR-LPP, nonlesional ImR-LPP and healthy control pedal skin. Gene transcripts were quantified using TaqMan real-time reverse transcriptase-polymerase chain reaction assays. The skin of dogs with ImR-LPP had significant overexpression of IL-6 mRNA (P < 0.05) and significant underexpression of IL-12 mRNA (P < 0.01) compared to healthy controls. In addition, lesional ImR-LPP skin had significantly higher levels of IL-10 transcripts compared to healthy control pedal skin (P < 0.05). Although not attaining significance (P = 0.07), a trend towards reduced TGF-beta mRNA expression in lesional ImR-LPP skin was also evident. There were no significant differences in the levels of IFN-gamma or IL-2 mRNA transcripts among the three skin sample sources. IL-4 mRNA was detected in only one lesional sample. These results suggest that the pathogenesis of ImR-LPP may be associated with a T-cell-mediated inflammatory response characterized by impaired Th(1)-like, but enhanced Th(2)-like cytokine expression.

Clinical, immunological and histopathological findings in a subpopulation of dogs with pododermatitis.

Clinical, immunological and histopathological findings in 20 adult dogs of varying breeds with chronic (>or=6 months) inflammation confined to the pedal skin were compared over a 2-year period with those of a group of age-matched controls (n=20). All affected dogs were pruritic but systemically well. Lesions were present on all four feet in 18/20 cases. Affected feet were characteristically erythematous, swollen, painful and alopecic. Sinus tracts were evident in 4/20 dogs. Despite a methodical series of diagnostic tests, no underlying cause was identified. None of the dogs responded to antimicrobial therapy administered for 8 weeks, none had evidence of ectoparasitism and none satisfied the criteria for atopic dermatitis. There was no response to a dietary trial using a novel protein source. The condition was characterized histopathologically by epidermal hyperplasia, hyperkeratosis, spongiosis, dermal oedema and perivascular aggregates of lymphocytes and plasma cells. Clinical signs did not correlate with histopathological findings. Affected dogs had significantly elevated serum IgG and IgM concentrations. The results of lymphocyte proliferation assays and phenotypic studies to determine the relative percentage of CD3+, CD4+, CD8+ and CD21+ lymphocyte subsets, and the ratio of CD4+/CD8+ cells were not significantly different between groups. No age, sex or seasonal predilections were noted. All dogs subsequently responded to immunosuppressive doses of prednisolone or cyclosporin. The term immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis is proposed to denote what may be a previously unrecognized condition in some dogs with pododermatitis of undetermined aetiology.