Transient Erythema Elevatum Diutinum Associated With HIV Viremia.

Erythema elevatum diutinum (EED) is a rare cutaneous small vessel vasculitis of unknown etiology. It is thought to be due to immune complex deposition in small vessels, resulting in complement fixation and subsequent inflammation. EED classically presents with asymptomatic, symmetric, red-brown to purple papules, plaques, and nodules overlying extensor surfaces with a lapsing-remitting course that typically resolves within five to 10 years. We discuss the case of a 47-year-old male with HIV and a new history of EED presenting after several days of missed antiretroviral medications and resolved with improved compliance with antiretroviral medications. A 47-year-old male presented with a four-week history of mildly tender violaceous plaques and nodules on the dorsal feet and posterior heels bilaterally. Medical history was significant for HIV that was well-controlled on antiretrovirals although the patient had missed two days of therapy. A punch biopsy of the lesion demonstrated leukocytoclastic vasculitis with dense dermal mixed infiltrate consisting of histiocytes, neutrophils, and eosinophils. Laboratory findings revealed the presence of HIV RNA. Prior to the initiation of Dapsone therapy, the patient's eruption cleared entirely within a month solely by restarting his antiretroviral therapy, for which he continues to remain disease-free. EED is a rare, chronic leukocytoclastic vasculitis with a poorly understood etiology. Treatment is typically aimed at treating underlying systemic disease, however, treatment of EED with Dapsone is typically first-line.

Association of Tumor Characteristics With Insurance Type Among Patients Undergoing Mohs Micrographic Surgery for Nonmelanoma Skin Cancer.

Importance: Little is known about the association between insurance type and tumor or treatment characteristics among patients undergoing Mohs micrographic surgery (MMS) for nonmelanoma skin cancer (NMSC). Objective: To investigate whether there are differences in tumor and treatment characteristics among patients undergoing MMS for NMSC by insurance type. Design, Setting, and Participants: This retrospective cohort study included patients with NMSC who presented for surgery at an academic MMS practice between May 2017 and May 2019. Main Outcomes and Measures: Preoperative and postoperative tumor diameters, number of MMS stages, type of closure, and number of high-risk tumors were compared based on insurance type among uninsured and underinsured patients and those with private insurance, Medicare, and Veterans Affairs (VA) insurance. Results: A total of 1397 patients with NMSC (978 [70%] male; mean [SD] age, 68.5 [12.4] years) underwent 1916 MMS procedures. Of these patients, 868 (45%) had Medicare, 570 (30%) had private insurance, 299 (16%) had VA insurance, and 179 (9%) were treated at a safety net clinic or were uninsured. Compared with patients with private insurance, uninsured and underinsured patients had significantly larger preoperative tumor bed diameters (difference, 28%; 95% CI, 14%-43%; P < .001) and postoperative defect sizes (difference, 28%, 95% CI, 16%-41%; P < .001). Patients with Medicare and VA insurance did not have significantly different preoperative tumor bed diameters compared with patients with private insurance. Patients with VA insurance had larger postoperative defect sizes than patients with private insurance (difference, 12%; 95% CI, 2%-23%; P = .02). The number of MMS stages and type of closure did not significantly differ based on insurance type. Conclusions and Relevance: In this cohort study of patients undergoing MMS for NMSC, larger preoperative tumor and postoperative defect sizes were associated with being uninsured or underinsured compared with privately insured. Future studies are required to determine why these differences exist to deliver optimal care to all patients.

Management of a neonate with diffuse cutaneous mastocytosis: Case report and literature review.

Mastocytosis is an accumulation of clonal mast cells within tissues, commonly caused by mutations in the KIT proto-oncogene. This report describes the management of a neonate with diffuse cutaneous mastocytosis (DCM) caused by a rare activating KIT mutation, specifically internal tandem duplication of the Ala502Tyr503 pair on exon 9, and reviews current data regarding work-up of DCM in pediatric patients.

Disseminated Syringomas of the Upper Extremities in a Young Woman.

Syringomas are benign, eccrine sweat gland tumors frequently found on the eyelids and neck in post-pubescent women and may present in healthy individuals or be associated with various medical comorbidities. We present a case of an otherwise healthy 19-year-old female with an abrupt onset of disseminated syringomas on the bilateral forearms and dorsal hands. Eruptive acral syringomas have not been previously reported in adolescents, and this diagnosis should be considered in patients presenting with a papular eruption on the hands and forearms.

The membrane type matrix metalloproteinase MMP14 mediates constitutive shedding of MHC class I chain-related molecule A independent of A disintegrin and metalloproteinases.

Engagement of tumor cell surface MHC class I chain-related molecule A (MICA) to NKG2D stimulates NK and T cell antitumor immunity. Shedding of MICA by tumor cells facilitates tumor immune evasion, which may in part contribute to tumor progression. Thus, elucidating the mechanisms by which tumors shed MIC is of great importance for therapy to reinforce NK and T cell antitumor immunity. In this study, we report that the membrane type matrix metalloproteinase (MMP)14 mediates MICA shedding. Suppression of MMP14 expression blocks MICA shedding. Concomitantly, overexpression of MMP14 enhances MICA shedding. The regulation of MICA shedding by MMP14 is independent of the activity of a disintegrin and metalloproteinases, which have been reported to mediate MICA shedding. Finally, MMP14 expression in MICA-positive tumor cells regulates the sensitivity of tumor cells to NK cell killing. These findings suggest that MMP14 may be a new target for tumor immune therapy.

An six-amino acid motif in the alpha3 domain of MICA is the cancer therapeutic target to inhibit shedding.

Expression of the MHC class I chain related molecules A and B (MICA/B) on tumor cell surface can signal the immune receptor NKG2D for tumor immune destruction. However, MIC was found to be shed by tumors in cancer patients, which negatively regulates host immunity and promotes tumor immune evasion and progression. The mechanisms by which tumors shed MIC are not well understood although diverse groups of enzymes are suggested to be involved. The functional complexity of these enzymes makes them unfeasible therapeutic targets for inhibiting MIC shedding. Here we identified an six-amino acid (6-aa) motif in the alpha3 domain of MIC that is critical for the interaction of MIC with ERp5 to enable shedding. Mutations in this motif prevented MIC shedding but did not interfere with NKG2D-mediated recognition of MIC. Our study suggests that the 6-aa motif is a feasible target to inhibit MIC shedding for cancer therapy.

Oxidative DNA damage in the prostate may predispose men to a higher risk of prostate cancer.

DNA damage has been associated with prostate cancer risk. Men who were referred for initial prostate biopsy for elevated prostate-specific antigen or abnormal digital rectal examination are often found with no cancer but have a higher risk of developing prostate cancer than the general population of men in their lifetime. In this study, we investigated whether DNA damage is one of the factors that predispose these men referred for prostate biopsies to a higher risk of prostate cancer. We found significantly elevated levels of 8-oxo-2-deoxyguanosine immunoreactivity in the prostates of the referred men (n = 50) in comparison to the control prostates of men (n = 32) with no indication for referral for prostate biopsy. Twelve of these control men were healthy middle-aged men and 20 of them were older men whose conditions were diagnosed with bladder cancer but with normal serum prostate-specific antigen and digital rectal examination and no evidence of prostate disease. In all the 8-oxo-2-deoxyguanosine-positive prostates, we detected phosphorylation of the ataxia telangiectasia mutated kinase and expression of the immune-stimulatory molecule MIC in the prostate epithelium. These data suggest that: 1) oxidative DNA damage has occurred in the "referred" but pathologically normal prostates, indicating that these prostates may be subjected to genomic instability and eventually neoplastic transformation; 2) in response to DNA damage, two surveillance pathways, represented by ataxia telangiectasia mutated phosphorylation and induction of the NKG2D ligand MIC, were activated to prevent tumorigenesis.