INTRODUCTION:Levamisole is a contaminant present in street cocaine. It has been associated with a number of clinical side effects, including vasculitis. We present a case of a patient with acute pulmonary, cutaneous and Musculoskeletal symptoms following cocaine use who was found to have an overlap features of Granulomatosis with Polyangiitis (GPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA). CASE PRESENTATION:A 31 year old male with no past medical history presented with fatigue, polyarthralgia, generalized body ache and scattered blisters over the upper and lower extremities. Days prior to presentation, he used injected cocaine. His vital signs were notable for tachycardia (140s). Exam was notable for swollen hand joints, scabbed lesions over the arms and legs. WBC was 21 with Absolute Eosinophil count 8.23 . Serum IgE was 1500. Urine toxicology was positive for cocaine metabolites. CXR showed multiple bilateral infiltrates. During hospitalization, he continued to have severe polyarthralgia. He developed worsening cough with small volume hemoptysis. CT of the chest showed bilateral patchy peripheral infiltrates. Bronchoscopy with Bronchoalveolar Lavage (BAL) revealed bloody secretions not meeting criteria for DAH. BAL sample had 107 cells with 80% eosinophils. Extensive infectious, hypersensitivity and autoimmune workup was sent. Results returned positive for C-ANCA and Anti-PR3. He underwent left lung wedge biopsy which revealed Active Interstitial Pneumonitis with marked intra-alveolar and interstitial eosinophilia that was more consistent with Eosinophilic Granulomatosis with Polyangiitis. This lead to a diagnosis overlap syndrome of GPA and EGPA that was likely Levamisole induced. DISCUSSION: Our case illustrates drug induced systemic ANCA vasculitis with overlap features of Granulomatosis with Polyangiitis (GPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA) following cocaine use . Levamisole is a synthetic imidazothiazole analogue that has immunomodulatory properties. It is currently being used as an anthelmintic agent in veterinary medicine. It is a frequent contaminant of street cocaine. It has been associated with a number of side effects including vasculitis. Our patient presented with Pulmonary, cutaneous and musculoskeletal manifestations after cocaine use. Elevated C-ANCA along with presence of peripheral eosinophilia, marked IgE elevation and lung tissue biopsy finding of eosinophilic interstitial pneumonitis lead to a diagnosis of drug induced GPA/EGPA overlap syndrome. Rare reports of similar syndrome were rported but none of which were drug induced.CONCLUSIONS: This case highlights the importance of considering substance induce Autoimmune conditions in patients presenting with multisystem syndrome with pulmonary involvement. Levamisole which is a contaminant present in cocaine can induce ANCA associated vasculitis with variable manifestations.

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Positive End Expiratory Pressure (PEEP) is a fundamental ventilator setting selected by critical care providers and is thought to mitigate atelectasis and atelectotrauma. Optimal PEEP is often studied in the setting of ARDS, but there have been few investigations on the selection of initial PEEP in its absence. Five cm H 2 O is believed to be a physiologic level and is often set as a standard starting point for intubated patients. We sought to explore if an initial use of PEEP$7.5 cmH 2 O compared to lower initial levels of PEEP may reduce the incidence of Ventilator Associated Events (VAE). METHODS:We retrospectively reviewed charts of patients who received mechanical ventilation in 3 Intensive Care Units staffed by the same group of critical care providers. Consecutive cases were reviewed from September 2017 through September 2018. Exclusion criteria included a ventilator course of less than 3 calendar days, inpatient ventilation with alternate facilities or services prior to transfer, or the use of home ventilation prior to arrival. A total of 146 patients met inclusion criteria and data were recorded in a standardized format. Potential VAE were verified by the most senior reviewer using strict CDC criteria. Two cohorts were delineated, those who received an initial PEEP$7.5 cmH 2 O and those initiated on <7.5 cmH 2 O. The initial PEEP was defined as the first setting that was sustained for a period of 8 hours. Fisher's Exact and Wilcoxon Rank Sum tests were used to assess for differences of dichotomous and nonparametric continuous variables, respectively. The primary outcome was the rate of VAE. Secondary outcomes included ICU and hospital mortality, ventilator days, and ICU and hospital days. Multivariate logistic regression analysis was performed to evaluate for any confounders noted in baseline characteristics.RESULTS: Of the 146 cases reviewed, 106 received higher initial PEEP and 40 received lower initial PEEP. Baseline characteristics between groups were similar, though an exception favoring the higher PEEP group was hypoxia as the reason for intubation (67% vs 35%, p¼0.001). The cohort with PEEP$7.5 had fewer VAE (9% vs 23%, p¼0.04) and lower ICU mortality (48% vs 65%, p¼0.02) compared to the lower PEEP cohort. Median number of ventilator days also trended towards significance in the former group (7 vs 11, p¼0.07). Controlling for BMI and reason for intubation, PEEP$7.5 independently reduced VAE 4-fold (OR 0.2, p¼0.01) and ICU mortality 3-fold (OR 0.3, p¼0.01). BMI$30 also increased VAE 3-fold (OR 3.2, p¼0.03) regardless of initial PEEP but had no effect on ICU mortality. CONCLUSIONS:The rates of VAE and ICU mortality were lower in patients who received an initial PEEP$7.5 cmH 2 O compared to lower levels of initial PEEP. This observation was persistent after controlling for differences in baseline characteristics between groups. Obesity was an independent risk factor for VAE. A trend towards reduction of ventilator days was also seen among patients receiving higher levels of initial PEEP.CLINICAL IMPL...

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