Cutaneous T-cell lymphoma (CTCL) is a devastating lymphoid malignancy characterised by accumulation of malignant T cells in the dermis and epidermis. Skin lesions cause serious symptoms hampering the quality of life and are entry sites for bacterial infection - a major cause of morbidity and mortality in advanced disease. What drives the pathological processes that compromise the skin barrier remains unknown. Here, we report on increased transepidermal water loss and compromised expression of skin barrier proteins filaggrin and filaggrin-2 in areas adjacent to TOX positive T cells in CTCL skin lesions. Malignant T cells secrete mediators (including cytokines such as IL-13, IL-22 and Oncostatin M) that activate STAT3 signalling and downregulate filaggrin and filaggrin-2 expression in human keratinocytes and reconstructed human epithelium. Consequently, repression of filaggrins could be counteracted by a cocktail of antibodies targeting these cytokines/receptors, by siRNA-mediated knockdown of JAK1/STAT3, and by JAK1 inhibitors. Notably, we show that treatment with a clinically approved JAK inhibitor, Tofacitinib, increases filaggrin expression in lesional skin from mycosis fungoides patients. Taken together, these findings indicate that malignant T cells secrete cytokines, which induce skin barrier defects through a JAK1/STAT3 dependent mechanism. As clinical grade JAK inhibitors largely abrogate the negative effect of malignant T cells on skin barrier proteins, our findings suggest that such inhibitors provide novel treatment options for CTCL patients with advanced disease and a compromised skin barrier.

Prurigo pigmentosa (PP) is probably underdiagnosed due to lack of awareness. Previously, it was assumed that PP primarily affected Japanese females; however, more cases are reported worldwide, and the pathogenesis is still not completely understood. In this case report, we present two healthy Danish siblings, who developed PP approximately 2 weeks after starting a ketogenic diet, suggesting that both increased levels of ketone bodies in the blood together with a genetic predisposition might play a role in the development of PP.

Merkel cell carcinoma (MCC) is a subtype of nonmelanoma skin cancer (NMSC) with increasing incidence. Clinically, MCC resembles other far less-aggressive NMSCs, and the pathogenesis is still not understood completely. Rapid diagnosis and treatment are essential to improve overall survival. We present a case report of a 74-year-old female, who had noticed a rapidly growing, oozing tumor on her right flank. She was hesitant to contact the dermatology ward where she had regular checkups as she was afraid of contracting COVID-19. This was in the beginning of the COVID-19 pandemic. At presentation, she had a large exophytic MCC on her right flank and multiple metastases. The disease was at a late stage, and palliative care was the only treatment option left. With this case, we wish to report a rather uncharacteristic location and size of an MCC tumor and suggest that fear of the pandemic and the COVID-19 lockdown has impacted dramatically on attendance of symptomatic patients.