Clinical and Histopathologic Characterization of Canine Chronic Ulcerative Stomatitis

Abstract

Canine chronic ulcerative stomatitis, also known as chronic ulcerative paradental stomatitis, is a painful condition of the oral cavity. The purpose of this study was to determine if there are commonalities in clinical and radiographic features among patients, whether the histopathologic evaluation might inform the pathogenesis, and whether the condition appears similar to human oral mucosal diseases. To do this, we prospectively collected clinical, radiographic, and histopathologic data from 20 dogs diagnosed with the disease. Clinical data were based on a clinical disease activity index, oral and periodontal examination parameters, and full-mouth dental radiographs. The histopathological and immunohistochemical data were based on oral mucosal samples obtained from erosive or ulcerated areas. Our findings revealed that canine chronic stomatitis is clinically characterized by painful oral mucosal ulcers of varying size, pattern, appearance, and distribution, most often associated with teeth with early periodontitis. Histologic examination revealed a subepithelial lichenoid band (interface mucositis) where B cells, T cells, and Forkheadbox protein 3 (FoxP3)-and interleukin-17-expressing cells were present. These cells might play a role in the underlying immune response and an immune-mediated pathogenesis is suspected. The clinical and histopathologic features of this chronic inflammatory mucosal disease in dogs resemble those of oral lichen planus in humans.

Immunopathogenesis of canine chronic ulcerative stomatitis

“…We have previously described the clinical, radiographic, clinicopathologic and histopathologic characteristics of this disease. [1] We have further provided a preliminary and qualitative characterization of the inflammatory cell infiltrate that characterizes CCUS lesions. Specifically, we showed that CCUS lesions are rich in both B and T lymphocytes, as well as IL-17 producing cells.…”

“…We have introduced a clinical scoring system, called the Canine Ulcerative Stomatitis Disease Activity Index (CUSDAI) in an attempt to quantify disease severity and response to various therapeutic regimens "S1 Table". [1] CCUS histopathology typically features a densely arrayed inflammatory cell infiltrate at the interface between the superficial mucosal epithelium and subepithelial connective tissue (lichenoid infiltrate) that is composed of B cells, plasma cells, CD3 T cell subsets (including FoxP3+), neutrophils, and fewer mast cells within the deep submucosa. [1] An initial evaluation using multi-color immunofluorescence (IF) on a small number of CCUS cases, revealed moderate numbers of infiltrating IL17 + cells; interestingly the majority of these cells were determined to be CD3 negative.…”

“…[1] CCUS histopathology typically features a densely arrayed inflammatory cell infiltrate at the interface between the superficial mucosal epithelium and subepithelial connective tissue (lichenoid infiltrate) that is composed of B cells, plasma cells, CD3 T cell subsets (including FoxP3+), neutrophils, and fewer mast cells within the deep submucosa. [1] An initial evaluation using multi-color immunofluorescence (IF) on a small number of CCUS cases, revealed moderate numbers of infiltrating IL17 + cells; interestingly the majority of these cells were determined to be CD3 negative. [1] Given the fact that CCUS patients respond poorly to current medical treatment strategies, there is a strong interest to better define the underlying pathogenesis of CCUS.…”

“…[1] An initial evaluation using multi-color immunofluorescence (IF) on a small number of CCUS cases, revealed moderate numbers of infiltrating IL17 + cells; interestingly the majority of these cells were determined to be CD3 negative. [1] Given the fact that CCUS patients respond poorly to current medical treatment strategies, there is a strong interest to better define the underlying pathogenesis of CCUS.…”

“…[7,8] In CCUS lesions, infiltrating FoxP3+ cells have been proposed to play a role in lesion pathogenesis. [1] Whether these lesion-associated Tregs are functionally deficient or play some kind of balancing role with proinflammatory IL17+ cells, awaits clarification.…”