Background Finite clinical data and understanding of COVID-19 immunopathology has led to limited, opinion-based recommendations for management of immune-mediated inflammatory disease (IMID) patients on immunosuppressive (IS) therapeutics. Objective Determine if IS therapeutic type impacts COVID-19 risk among IMID patients. Methods We conducted a retrospective cohort analysis of Henry Ford Health System (HFHS) patients tested for COVID-19 between February 1 st and April 18 th , 2020 treated with IS medication for IMID. Therapeutic class of IS medication, comorbidities, and demographic factors were combined into multivariate models to determine predictors of COVID-19 infection, admission, ventilation, and mortality. Results Of 213 IMID patients, 36.2% tested positive for COVID-19, who had no greater odds of being hospitalized or requiring ventilation relative to the general population. No IS therapeutic worsened the course of disease after multivariate correction, though multi-drug regimens and biologics predicted an increased and decreased rate of hospitalization, respectively, with the latter driven by TNFα inhibitors. Limitations A single-center study somewhat limits generalization to community-based settings. Only patients tested for COVID-19 were analyzed. Conclusion IS therapies for IMIDs are not associated with a significantly greater risk of SARS-CoV-2 or severe sequelae when controlling for other factors, and TNFα inhibitors may decrease odds of severe infection.

Keratoacanthoma (KA) is a common skin tumour that remains controversial regarding classification, epidemiology, diagnosis, prognosis and management. Classically, a KA manifests as a rapidly growing, well-differentiated, squamoid lesion with a predilection for sun-exposed sites in elderly people and a tendency to spontaneously regress. Historically, KAs have been considered a variant of cutaneous squamous cell carcinoma (cSCC) and are often reported as KA-type cSCC. However, the penchant for regression has led many to categorize KAs as biologically benign tumours with distinct pathophysiological mechanisms from malignant cSCC. The clinical and histopathological similarities between KA and cSCC, particularly the well-differentiated variant of cSCC, have made definitive differentiation difficult or impossible in many cases. The ambiguity between entities has led to the general recommendation for surgical excision of KAs to ensure a potentially malignant cSCC is not left untreated. This current standard creates unnecessary surgical morbidity and financial strain for patients, especially the atrisk elderly population. There have been no reports of death from a definitive KA to date, while cSCC has an approximate mortality rate of 1Á5%. Reliably distinguishing cSCC from KA would shift management strategies for KAs towards lessinvasive treatment modalities, prevent unnecessary surgical morbidity, and likely reduce associated healthcare costs. Herein, we review the pathophysiology and clinical characteristics of KA, and conclude on the balance of current evidence that KA is a benign lesion and distinct from cSCC.Defective mismatch repair genes (MLH1, MSH2, MSH6) leading to microsatellite instability 59,60 HPV, human papillomavirus.

Given the extremely low incidence, propensity of malignant lesions to become symptomatic and efficacy of treatment, we do not recommend routine excision of all epidermal cysts. Instead, we recommend excision and pathology for all symptomatic epidermal cysts, or those that rapidly grow, or do not respond to medical therapy.

Introduction Kohlmeier-Degos (K-D) disease is a rare obliterative vasculopathy that can present as a benign cutaneous form or with potentially malignant systemic involvement. The gastrointestinal tract is most frequently involved in systemic disease and mortality is often related to bowel perforations. Herein, we provide information to providers and patients regarding gastrointestinal K-D symptomology, pathology, treatment, and diagnosis, with a focus on the importance of timely diagnostic laparoscopy. We present three new cases of gastrointestinal K-D to highlight varying disease presentations and outcomes. Body Based on reviewed reports, perforation is preceded by at least one gastrointestinal symptom: abdominal pain/cramping, anorexia/weight loss, vomiting, diarrhea, nausea, gastrointestinal bleeding, obstipation, constipation, and abdominal fullness. Perforation most commonly occurs in the small intestine and often results in sepsis and death. Although underutilized, laparoscopy is the most sensitive and specific diagnostic technique, demonstrating serosal porcelain plaques similar to those on the skin and characteristic for K–D. The combination of eculizumab and treprostinil is presently the most effective treatment option for gastrointestinal K–D. The pathology of gastrointestinal K-D is characterized by an obliterative intimal arteriopathy eventuating in occlusive acellular deposits of mucin and collagen along with an extravascular pauci-cellular sclerosing process resembling scleroderma confined to the subserosal fat. C5b-9 and interferon-alpha are both expressed in all caliber of vessels in the affected intestine. While C5b-9 blockade does not prevent the intimal expansion, enhanced type I interferon signaling is likely a key determinant to intimal expansion by, causing an influx of monocytes which transdifferentiate into procollagen-producing myofibroblast-like cells. Conclusion Prompt laparoscopic evaluation is necessary in any K–D patient with an abdominal symptom to facilitate diagnosis and treatment initiation, as well as to hopefully decrease mortality. Those with gastrointestinal K–D should start on eculizumab as soon as possible, as onset of action is immediate.

Percutaneous cryoablation is a minimally invasive procedure for tumor destruction, which can potentially initiate or amplify antitumor immunity through the release of tumor-associated antigens. However, clinically efficacious immunity is lacking and regional recurrences are a limiting factor relative to surgical excision. To understand the mechanism of immune activation by cryoablation, comprehensive analyses of innate immunity and Her2/neu humoral and cellular immunity following cryoablation with or without peritumoral CpG injection was conducted using two Her2/neu+ tumor systems in wild type, neu-tolerant, and SCID mice. Cryoablation of neu+ TUBO tumor in BALB/c mice resulted in systemic immune priming, but not in neu-tolerant BALB NeuT mice. Cryoablation of human Her2+ D2F2/E2 tumor enabled the functionality of tumor-induced immunity but secondary tumors were refractory to anti-tumor immunity if rechallenge occurred during the resolution phase of the cryoablated tumor. A step-wise increase in local recurrence was observed in wild type, neu-tolerant, and SCID mice indicating a role of adaptive immunity in controlling residual tumor foci. Importantly, local recurrences were eliminated or greatly reduced in wild type, neu tolerant and SCID mice when CpG was incorporated in the cryoablation regimen, showing significant local control by innate immunity. For long-term protection, however, adaptive immunity was required because most SCID mice eventually succumbed to local tumor recurrence even with combined cryoablation and CpG treatment. This improved understanding of the mechanisms by which cryoablation affects innate and adaptive immunity will help guide appropriate combination of therapeutic interventions to improve treatment outcomes.