Dermatitis


Clinical Background

Dermatitis is an inflammatory condition of the skin often occurring as a result of exposure to ionizing radiation during radiation therapy for a variety of malignancies or exposure of the skin to irritants. Common symptoms range in severity and include redness of the skin, wet or dry desquamation, edema, and ulceration. There exists an unmet clinical need to develop treatments specific for radiation or chemically induced dermatitis. In these cases, dermatitis is often treated in the same manner as thermal burns although there are significant differences in their molecular mechanisms. Current treatments are often palliative and do not prevent recurrence. Patients are typically prescribed moisturizing creams or corticosteroids to treat dermatitis.

Preclinical Models

Model Description Length Endpoints
Acute Radiation Induced Dermatitis
Disease peaks at or around Day 12 with desquamation of approximately 50% of the irradiated area Up to 36 days Dermatitis score, histology
Fractionated Radiation Induced Dermatitis
Disease peaks at or around Day 16 with desquamation of approximately 50% of the irradiated area and evidence of skin ulceration Up to 36 days Dermatitis score, histology
Nickel Induced Contact Dermatitis
Dermatitis is evaluated in mice pre-sensitized to a nickel solution 28 days Dermatitis score, histology

 

Radiation Dermatitis

Radiation Dermatitis develops in approximately 95% of patients receiving radiation therapy for cancer treatment, most commonly associated with malignancies of the skin, head and neck and breast. Symptoms include redness of the skin, wet or dry desquamation, edema, and ulceration. These symptoms may become so severe that they are dose limiting, potentially preventing a patient from receiving the necessary radiation treatments.
Biomodels offers both an acute and fractionated model of radiation induced dermatitis. In both models, the back of the mouse is shaved and/or depilated and the skin temporarily tented such that it can be selectively targeted with radiation while the rest of the mouse is protected by a lead shield. In both models mild erythema is observed 8-10 days following radiation exposure. Disease severity peaks between Day 12-16 depending on the model/dose with desquamation of approximately 50% of the irradiated area and often ulceration of the tissue. End points in this model include dermatitis severity scores based on a standardized scale that is representative of the clinical assessment, combined with histological analysis at both peak of disease and study termination.
For an overview of these models please feel free to watch Dr. Mancini’s presentation in the “Cutaneous Issues” section of online presentations during the 2012 MASCC International Conference in NYC.http://webcasts.kenes.com/MASCC/

Acute Radiation Induced Dermatitis

Animals receive one acute dose of radiation on Day 0 of the study

Study Design

 

Mean Blinded Radiation Dermatitis Scores

*Dermatitis severity scores resulting from acute radiation exposure

 

*Representative photos of the skin of control (left) and acute irradiated (right) mice at peak disease.

 

Fractionated Radiation Induced Dermatitis

Animals receive 6 fractions of radiation on a schedule of 3 days on, 2 days off.

Study Design

 

Mean Blinded Radiation Dermatitis Scores

*Dermatitis severity scores resulting from fractionated radiation exposure

 

NR

36 Gy

48 Gy

60 Gy

*Representative photos of the skin of control and fractionated irradiated mice at peak disease.

 

NR

36 Gy

48 Gy

60 Gy

*Masson’s Trichrome staining of dermatitis at peak of disease showing inflammation, damaged epithelium and necrosis of the skin as a result of radiation exposure.

 

Nickel Dermatitis

Contact Dermatitis due to exposure to metal ions such as nickel occurs in approximately 10% of the population. Patients suffering from this allergy to nickel are unable to wear jewelry or handle metal objects. Biomodels offers a mouse model of nickel dermatitis where animals are sensitized to nickel by applying a nickel solution to the shaved abdominal region of the mouse. Mice are then challenged with an injection of a nickel solution into the rear footpad. This allows mice to be screened for nickel sensitivity. Only mice that display an inflammatory reaction to the injection of nickel are used in the study. Following this screen, the nickel solution is again applied to the abdominal region and the presence of dermatitis is scored in the following three days. This model reliably produces desquamation of 25-50% of the affected area. For a full description of this model see the publication below.

Publications

Nanoparticles reduce nickel allergy by capturing metal ions
Praveen Kumar Vemula, R. Rox Anderson, & Jeffrey M Karp
Nature Nanotechnology DOI:10.1038/NNANO.2011.37

Topical Application of the Synthetic Triterpenoid RTA 408 Protects Mice from Radiation-induced Dermatitis. Reisman SA, Lee CY, Meyer CJ, Proksch JW, Sonis ST, Ward KW.