Progression of ulcerative dermatitis lesions in C57BL/6Crl mice and the development of a scoring system for dermatitis lesions

Abstract

Ulcerative dermatitis (UD) is a common, spontaneous condition in mice with a C57BL/6 background. Although initial lesions may be mild, UD is a progressive disease that often results in ulcerations or debilitating fibrotic contractures. In addition, lesions typically are unresponsive to treatment. Euthanasia is often warranted in severe cases, thereby affecting study outcomes through the loss of research subjects. Because the clinical assessment of UD can be subjective, a quantitative scoring method and documentation of the likely time-frame of progression may be helpful in predicting when animals that develop dermatitis should be removed from a study. Such a system may also be helpful in quantitatively assessing success of various treatment strategies and be valuable to clinical laboratory animal veterinarians. In this 1.5-y, prospective cohort study, we followed 200 mice to monitor the development and course of UD. Mice were examined every 2 wk. A clinical sign (alopecia, pruritus, or peripheral lymphadenopathy) was not identified that predicted development of UD lesions in the subsequent 2-wk period. Once UD developed, pruritus, the character of the lesion (single or multiple crust, coalescing crust, erosion, or ulceration), and the size of the lesion were the only parameters that changed (increased) over the course of the disease. Pruritus was a factor in the rapid progression of UD lesions. We used these findings to develop a quantitative scoring system for the severity of UD. This enhanced understanding of the progression of UD and the quantitative scoring system will enhance the monitoring of UD.

Figure 1.

Lesion regions. Region 1: the head cranial to the medial pinna attachment and/or lesions affecting the mandible cranial to the sternum. Region 2: inner and outer pinna, dorsal cervical region caudal to the medial pinna attachment, dorsal and ventral thorax, and thoracic limbs. Region 3: any region caudal to the ribcage.

Figure 2.

Ulcerative dermatitis scoring system. Simplified description for (A) scratching number, (B) character of lesion, (C) length of lesion, and (D) regions affected. Scores from A, B, C, and D are used in the (E) UD scoring system formula to generate the calculated severity score.

Figure 3.

Kaplan–Meier survival analysis. Mice with a calculated severity score of 75 or greater eventually developed end-stage UD, necessitating euthanasia (red line). No mouse with a calculated severity score less than 75 necessitated early euthanasia due to UD (blue line).

Figure 4.

The typical histopathologic appearance of a (A) mild and (B) severe UD lesion in this study. (A) Mild ulcerative dermatitis consisted of relatively limited areas of ulceration (arrow) and inflammation predominantly confined to the epidermis and superficial dermis. (B) Severe ulcerative dermatitis consisted of extensive areas of ulceration (arrows) and inflammation extending into the deep dermis or subcutis or both. In both cases, although inflammation differed by extent and intensity, it was qualitatively similar (insets) consisting predominantly of neutrophils within a serocellular crust (insets) and neutrophils, mast cells, and macrophages within the dermis. Hematoxylin and eosin stain; scale bars, 500 µm.

Figure 5.

One mouse over three 2-wk examination time points. Photograph of the mouse with the examination findings and calculated severity score as determined by formula in Figure 2E.