Melanoma is the most aggressive and deadly form of skin cancer. The current standard of care produces response rates of less than 20%, underscoring the critical need for identification of new effective, nontoxic therapies. Disulfiram (DSF) was identified using a drug screen as one of the several compounds that preferentially decreased proliferation in multiple melanoma subtypes compared with benign melanocytes. DSF, a member of the dithiocarbamate family, is a copper (Cu) chelator, and Cu has been shown previously to enhance DSF-mediated growth inhibition and apoptosis in cancer cells. Here, we report that in the presence of free Cu, DSF inhibits cellular proliferation and induces apoptosis in a panel of cell lines representing primary and metastatic nodular and superficial spreading melanoma. Both decreased cellular proliferation and increased apoptosis were seen at 50-500 nmol/l DSF concentrations that are achievable through oral dosing of the medication. In the presence of Cu, DSF caused activation of the extrinsic pathway of apoptosis as measured by caspase-8 cleavage. The addition of Z-IETD-FMK, a selective caspase-8 inhibitor, was protective against DSF-Cu-induced apoptosis. Production of reactive oxygen species (ROS) in response to DSF-Cu treatment preceded the induction of apoptosis. Both ROS production and apoptosis were prevented by coincubation of N-acetyl cysteine, a free radical scavenger. Our study shows that DSF might be used to target both nodular and superficial spreading melanoma through ROS production and activation of the extrinsic pathway of apoptosis.

According to recent data, up to 20% of patients with COVID-19 have cutaneous manifestations. Nails can also develop abnormalities during and after infection. In this article, we review the nail findings observed in patients with COVID-19.We reviewed the PubMed and Embase databases to identify all articles up to May 2021 that have described nail findings in association with COVID-19.A total of 70 studies were reviewed including 61 studies on chilblain-like lesions, which are one of the most widely identified cutaneous findings associated with the COVID-19 pandemic.Nine studies described specific nail findings (Table 1). Three of these findings [Beau lines, 1 transverse leukonychia, 1,2 and onychomadesis (Figure 1a)] are commonly seen with other systemic disease, including viral infection, and are likely the consequence of high fever and/or severe illness. One finding, paronychia, was seen in association with chilblain-like lesions, 3 and three nail findings (the red half-moon sign 4,5 (Figure 1d), the transverse orange discoloration 6 and the diffuse red-white nail bed discoloration 7 ) are novel and potentially related to the microvascular injury due to COVID-19. Of note, an orange-brownish discoloration of the nail in a transverse pattern, the most similar finding to date, has been described in patients with Kawasaki disease, which shares a similar inflammatory response component to COVID-19.COVID-19's effects on the nail blood vessels were documented by Navarro et al. in 12 pediatric patients with COVID-19-related chilblains, described in Table 1. 8 At dermoscopy of the nail fold and hyponychium, they found a red background with globules, indicative of vascular damage.We also documented dilated and tortuous capillaries at dermoscopy in a patient with transverse leukonychia after COVID-19 infection (Figure 1c).The presence of microvascular abnormalities was confirmed by a capillaroscopy study of the nails of 82 patients, enrolled during hospitalization for , or shortly after discharge. 9 Using nail video capillaroscopy (NVC), the authors observed microvascular abnormalities in all patients, which are described in detail in Table 1. Findings varied between acutely ill and discharged patients, providing visual evidence of a vascular pathogenic component to COVID-19 infection.Chilblain-like lesions are a commonly reported manifestation involving the digits. They are also known as 'COVID toes,' even

American cutaneous leishmaniasis is an important endemic zoonotic disease in the New World that comprises a spectrum of clinical manifestations. Diffuse cutaneous leishmaniasis (DCL) is a rare form of the disease characterized by antigen-specific immunodeficiency that often presents with multiple disfiguring non-ulcerated confluent nodules or plaques that involve large areas of the skin, resembling lepromatous leprosy. Relapse is invariable in advanced stages, despite aggressive chemotherapy, and a plethora of drugs has been tested with unchanging results. We report on a severe an exceptional case that resolved after treatment with amphotericin B, a drug considered only mildly effective, and discuss the therapeutic approach to this disease.

Patients experiencing homelessness (PEH) suffer from a high burden of cutaneous fungal infections. Preventative treatment is important as such infections can lead to harmful complications such as cellulitis and even osteomyelitis. There are sparse data regarding cutaneous fungal infections of homeless populations and management in low-resource settings. A MEDLINE search was conducted using the key terms "cutaneous," "fungal," "infections," "dermatophytes," and "homeless." The search included casecontrol, cohort, and randomized controlled trials published in the English language. This scoping review of studies yielded information with regard to practical treatment advice for providers in low-resource settings, including medical, hygiene, prevention, and treatment options for PEH with cutaneous fungal infections, the most common of which were tinea pedis (3-38%) and onychomycosis (1.6-15.5%). Few studies have been conducted on the differences between sheltered and unsheltered homeless patients, which can have treatment implications. Systemic antifungal therapy should be carefully considered for diffuse, refractory, or nail-based cutaneous fungal infections if there is a history of alcohol use disorder or liver disease. While PEH have a high risk of alcohol use disorder, this can make definitive treatment challenging.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms which account for less than 1% of all gastrointestinal malignancies. Of all the extra‐abdominal metastases of GIST, superficial soft tissue metastases are the rarest. Previous reports have found success with sunitinib in imatinib‐resistant GIST, but we report a certain wild‐type KIT mutation GIST with cutaneous and subcutaneous metastasis that was unresponsive to multiple tyrosine kinase inhibitor (TKI) treatments. This case illustrates that knowing the specific type of KIT mutations may uncover resistance of certain GIST's to TKIs, necessitating more targeted and alternative therapy.