Cutaneous neoplasias in epidermolysis bullosa: molecular characterization and application of augmented intelligence

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Epidermolysis bullosa (EB) is a rare and serious skin condition. The skin is fragile, minor injuries lead to blisters and wounds, and patients suffer from frequent pain and infections. As a severe complication, patients with EB develop skin cancer, particularly squamous cell carcinoma (SCC). SCCs in EB occur at a young age and are aggressive, so early discovery is key. However, recognizing this cancer is difficult. In this project, we will train a computer using artificial intelligence (AI) to recognize SCC on EB skin. This method has recently proven successful in dermatology, and AI was equal to dermatologists in recognizing certain skin cancers on “normal” skin after being trained on thousands of photographs. However, EB patient cohorts and thus image collections in national centers are small. To solve this, this project joins several international reference centers to amass a large number of photographs of EB SCCs and EB skin for computer training. The goal is to create a smartphone application for both physicians and patients. Applying AI in rare skin disease is a new and important step to improve diagnostics, therapy, and patients’ quality of life.Another characteristic, but poorly understood skin finding in EB, is the EB nevus. These large pigmented spots occur in up to 14% of EB patients, grow rapidly, and show certain characteristics of melanoma, the most severe skin cancer in humans. Although EB nevi are common, they are worrisome to patients and physicians. Knowledge about EB nevi is sparse and results solely from small case studies. Why and how some patients develop EB nevi is unclear. To date, no EB nevus has transformed to melanoma, which may simply reflect the reduced lifespan of patients. It is also unknown whether EB nevi are in fact true nevi, which carry certain genetic changes in BRAF or NRAS genes; we think they are, which means they could turn into cancer.In this project, we will deepen our understanding of the clinical appearance, behavior (i.e., size, location, progression), and cause of EB nevi. For this, we will join patient cohorts of several international reference centers and collect photographs, clinical data, and tissue samples of EB nevi. From sections of tissue samples, specific markers of the pigmentary cells (melanocytes) and of the structures holding skin together that malfunction in EB will be stained and assessed. DNA will be isolated and genetic examination regarding BRAF and NRAS genes will be performed. We will then model the EB nevus in the laboratory by cultivating melanocytes and EB keratinocytes together and assessing their behavior and interaction. From this, we will better understand how EB nevi develop and what course they take.Together, both project parts will fill gaps in EB knowledge and can serve as examples for the large field of rare diseases. Most importantly, the new findings will directly benefit patients with EB.