Pediatric pyoderma gangrenosum associated with leukocyte adhesion deficiency type 1: A case report and review of the literature.

Pyoderma gangrenosum is a rare neutrophilic dermatosis characterized by painful skin ulcers with necrotic, undermined margins. In severe cases, particularly in pediatric patients, work-up for an associated autoimmune, inflammatory, malignant, or genetic disorder should be considered based on the clinical presentation. We report a unique case of pediatric pyoderma gangrenosum with a leukemoid reaction, secondary to an autosomal recessive leukocyte adhesion deficiency type 1.

Publication Productivity Using H-Index to Evaluate Academic Success Among Fellowship-Trained Mohs Surgeons.

BACKGROUND: The h-index is a measure of research achievement using not only the number of publications of an individual, but also the impact of the publications. OBJECTIVE: The objective of this study is to evaluate the h-indices of Mohs surgeons within a variety of practice settings. MATERIALS AND METHODS: A list of all American College of Mohs Society (ACMS) members with corresponding fellowships years were collected using the ACMS membership directory. Publicly available demographic information was obtained including fellowship year, practice setting, PhD status, practice location (region), total number of publications, and h-index. Descriptive statistics were calculated to compare h-indices among the demographic data. RESULTS: A total of 1150 ACMS members were included. The Practice setting distribution was as follows: 10.6% academic, 85.7% private practice, and 3.7% combined. H-index differed significantly based on practice setting (p < .001), with higher h-indices in academic and combined settings compared with the private practice setting. Subanalysis among academic Mohs surgeons revealed higher mean h-indices among professors (23.9) > associate professors (10.6) > assistant professors (8.6) > clinical instructors (5) (p < .001). CONCLUSION: H-indices were highest among Mohs surgeons in the academic setting with increasing values correlating with higher academic rank and time since fellowship completion.

Endoscopic Coil Embolization for Refractory Intrahepatic Biliary Duct Leak.

Bile leaks may be seen after blunt and penetrating trauma, as well as iatrogenic injury from surgical procedures. There are many articles on endoscopic treatment options for the management of biliary leaks, including sphincterotomy, endoscopic stent, or nasobiliary drain placement. Data, however, are scarce regarding the management of persistent biliary leaks after the initial intervention. We present a case of endoscopic coil embolization to treat a refractory bile leak after initial endoscopic sphincterotomy and stent placement in a patient with a grade IV liver laceration due to a gunshot wound.

Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Twelve cases of acneiform eruptions while on anti-CTLA4 therapy.

We present the first detailed report of acneiform eruptions in patients on CTLA-4 inhibitor therapy. Acneiform eruptions commonly occur (up to 75-100%) as a cutaneous adverse event associated with EGFR inhibition; however, acneiform eruptions have not been highly reported as a cutaneous adverse event associated with CTLA-4 inhibitor therapy. We conducted a retrospective chart review of our institution's database to assess cutaneous adverse events associated with ipilimumab and tremelimumab, identifying 12 patients with acneiform eruptions (2 on tremelimumab and 10 on ipilimumab). The median time to onset of rash was 3 weeks after starting CTLA-4 inhibitor therapy, ranging from 0.7-45 weeks. Median time to cutaneous resolution was 6 weeks, ranging from 2 to 282 weeks. Treatment included oral and topical antibiotics, antihistamines, and oral or topical corticosteroids with four patients receiving no treatment. Acneiform eruptions are seen less commonly with CTLA-4 inhibitors than other cancer therapies, but awareness that it does occur is important for clinical practice. Better description is a necessary help to aid in early diagnosis and intervention. While EGFR inhibitor-associated acneiform eruptions are associated with clinical benefit, our sample size is too small to determine whether CTLA-4 inhibitor associated acneiform eruptions display the same correlation.

Antibody-Based Therapies for Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphomas (CTCLs) are a group of non-Hodgkin's lymphomas that present in the skin. In early-stage disease, the course is generally chronic and indolent; however, in advanced stages of disease, therapies rarely provide long-lasting responses, and the only potential curative therapy is allogeneic hematopoietic stem-cell transplantation. This has led to the search for novel targeted therapies to better treat more advanced stages of CTCLs that cannot be controlled by typical treatment regimens. One area of advancement has been the development of antibodies specifically targeted to cell types that are known to be involved in CTCL. At present, brentuximab vedotin, an antibody-drug conjugate composed of an anti-cluster of differentiation (CD)-30 antibody covalently linked to monomethyl auristatin E, is approved for the treatment of CD30+ lymphoproliferative disorders [lymphomatoid papulosis (LyP) and primary cutaneous-anaplastic large-cell lymphoma (pc-ALCL)] as well as transformed CD30+ mycosis fungoides (MF). Additionally, mogamulizumab, an anti-chemokine receptor 4 (CCR4) monoclonal antibody, is approved for patients with MF or Sézary syndrome (SS) for whom one prior systemic therapy has failed. Trials are underway looking into the use of immune checkpoint inhibitors in the treatment of CTCLs. As we continue to research CTCL, and as antibody-based therapies continue to advance, more antibody-specific targeted therapy could provide alternative treatment regimens for patients with advanced CTCL.

Retrospective Chart Review of Cutaneous Adverse Events Associated with Tremelimumab in 17 Patients.

BACKGROUND AND OBJECTIVES: Tremelimumab is a monoclonal human antibody that inhibits cytotoxic T-lymphocyte-associated antigen 4, giving rise to increased T cell activation and interleukin-2 release. While this activation of the immune system provides a mechanism to recognize and destroy cancer cells, it also leads to off-target immune-related adverse events. Ipilimumab is a US Food and Drug Administration-approved anti-cytotoxic T-lymphocyte-associated antigen 4 antibody, which has a high incidence of cutaneous adverse events. While cutaneous adverse events for ipilimumab have been extensively studied, there is a distinct lack of cutaneous adverse event data for tremelimumab. METHODS: We conducted a retrospective chart review of our institution's electronic medical records from January 2000 to March 2018 to characterize cutaneous adverse events induced by tremelimumab. Previous descriptions of tremelimumab cutaneous adverse events are limited to rash and pruritus. RESULTS: We found 17 patients treated with tremelimumab who had cutaneous adverse events including pruritus (12/17), eczematous dermatitis (8/17), morbilliform rash (5/17), vitiligo (2/17), xerosis (3/17), acneiform rash (2/17), and psoriasiform dermatitis (1/17). CONCLUSIONS: This case series demonstrates that cutaneous adverse events seen in patients taking tremelimumab overlap with those of ipilimumab. While there are some differences between rash characterizations of the two drugs, such as time to onset and clearance, the sample size of this case series is too small to draw any definite conclusions. This study addresses a gap in the descriptive knowledge on tremelimumab cutaneous adverse events and highlights the need for further large cohort prospective studies. Awareness of expected cutaneous toxicities and how best to treat these can help patients continue on immunotherapy regimens without delays or interruptions and give patients the best quality of life while receiving treatment.