In this study population, approximately 25% of PMD diagnosed in patients without marijuana use were found to be non-spontaneous in nature and secondary to esophageal disruption, requiring operative intervention. In contrast, sPMD in marijuana users were all managed non-operatively and with observation, which is consistent with the more benign nature of marijuana-associated sPMD.

Esophageal imaging was obtained in 9/17 CON patients. The four that were diagnosed with esophageal disruption underwent operative intervention, as previously noted. Esophageal imaging was obtained in 7/13 THC patients. None of the THC patients underwent operative intervention, including the one patient in whom there was question of possible extraluminal contrast. There were also several patients in whom further dedicated esophageal imaging was deferred due to lack of extraluminal contrast on a non-dedicated computed tomography scan with oral contrast. Therefore, it could be argued that in this study population, esophageal imaging in marijuana-associated sPMD did not change the ultimate management of the patient.

Unfortunately, our study did not reveal any particular symptoms, vital sign abnormalities, or WBC abnormality that was able to predict whether the patient would have a leak or require intervention. The most frequently observed derangement in presenting vital signs across both groups was tachycardia, but only one of the patients requiring intervention was tachycardic at presentation. Leukocytosis was encountered in 3 of the 4 patients requiring intervention, but it was also very common across patients of both groups who did not require intervention, and is frequently encountered in PMD, even in the absence of diagnosed infection (21). Interestingly, tobacco-related leukocytosis has also been observed (22) and could be contributing to the wide-spread elevation in WBC seen across both of these study groups.

Large and moderate pleural effusions (Figure 2), however, were only found in patients who required operative intervention, and is a radiographic finding that is commonly associated with esophageal perforation (23). In patients presenting with this finding, suspicion for esophageal perforation should remain high, and dedicated esophageal imaging should not be deferred in the stable patient who does not require emergent operative intervention. Similarly, forceful and/or repeated emesis can lead to full-thickness esophageal disruption, defined as Boerhaave syndrome. As mentioned previously, marijuana use can lead to cannabinoid hyperemesis syndrome, which is relatively rare but occurs most frequently in daily long-term users (10). Only three of our THC patients reported any form of emesis, of which only one was thought to have cannabinoid hyperemesis syndrome. This patient was worked up with a CTE that showed no leak and he was managed conservatively. As illustrated with this patient, any history of forceful or repeated bouts of emesis should prompt the provider to be concerned about Boerhaave syndrome, and the patient should be worked up appropriately, regardless of marijuana use status.

Given our results and the available literature to date, we propose that marijuana-associated sPMD be classified as a separate entity from non-marijuana associated sPMD and defined as isolated PMD occurring in patients who inhale marijuana that do not have an underlying history or presenting symptoms concerning for cannabinoid hyperemesis syndrome. Ebina et al. have already demonstrated that sPMD can be safely treated on an outpatient basis without dedicated esophageal imaging or antibiotics (24). Due to the proposed mechanism of alveolar rupture and the Macklin effect in sPMD, marijuana inhalation serves as an additional risk factor for the development of sPMD without increasing the likelihood of esophageal damage in the absence of cannabinoid hyperemesis syndrome. Overall, this makes marijuana-associated sPMD much more likely to be safely managed conservatively or on an outpatient basis. One of the key points in management of this condition is cessation counselling. Our providers provide cessation counselling both at the initial encounter and in the clinic during the follow up appointment. Providers who encounter patients that smoke marijuana should be aware of the possible ramifications and strive to encourage cessation of recreational use. This is the basis for classifying marijuana-associated sPMD as a separate disease. Adding dedicated esophageal imaging would unnecessarily increase the healthcare costs of managing a condition that often can be managed conservatively, and possibly without admission to the hospital. Our results are in-line with this theory.

This study has a number of limitations. The sample size is small, and by nature of a retrospective case series, broader conclusions about the epidemiology of PMD cannot be drawn. As with much of the current literature, there are many confounding factors present within our data. A subset of our patients presented with a separate disease process associated with PMD, such as asthma (25) and diabetic ketoacidosis (26), which could have contributed to lab and vital sign abnormalities unrelated to the presence of PMD. Concurrent use of recreational drugs and tobacco, which are known to have deleterious effects on the lung (27, 28), was present in many of our THC and CON patients. There did not appear to be an association between esophageal disruption and tobacco as 50% reported use and 50% did not, and none of the esophageal perforation patients had reported other recreational drug use. PMD associated with cocaine use is an uncommon but documented phenomenon (29), and cocaine use reported by the three patients in this study group may be a confounding factor. It is also important to note that the incidence of marijuana use and other recreational drug use may be underreported in this patient population because of the fear of legal repercussions. With the relatively recent legalization within New York State, we may see a more accurate reporting of marijuana use moving forward, but many patients may still be reluctant to disclose their habits. This makes collecting specific information such as joint-years, modality of inhalation, and time-relation to presentation more difficult. During the time period from which our data was collected, there were also few objective measures of marijuana use such as drug screens, as these tests were not frequently indicated for the patient's presenting symptoms. Future prospective studies utilizing drug testing and patient questionnaires would be helpful to better understand these important data points.

Nonetheless, these results suggest that with further research, it may be safe to initially observe patients with marijuana-associated sPMD in the hospital or via close outpatient follow up, perhaps deferring dedicated esophageal imaging in the absence of clinical signs or symptoms concerning for a more ominous underlying process, such as esophageal perforation. Higher-powered studies analyzing data with minimal confounding factors such as lung disease, smoking, and other drug use would allow for better characterization of marijuana as an isolated risk factor for sPMD. This, in turn, would allow for future retrospective and prospective studies, as well as randomized control trials, to better determine the role of esophageal imaging in the management of marijuana-associated sPMD.