(PI) After Lung Transplantation Fahid Alghanim, MD1* Id , Janaki Deepak, MBBS1, Aldo Iacono, MD2 and Irina Timofte, MD1

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(PI) After Lung Transplantation Fahid Alghanim, MD1* Id , Janaki Deepak, MBBS1, Aldo Iacono, MD2 and Irina Timofte, MD1 ISSN: 2378-3516 Alghanim et al. Int J Respir Pulm Med 2021, 8:155 DOI: 10.23937/2378-3516/1410155 Volume 8 | Issue 2 International Journal of Open Access Respiratory and Pulmonary Medicine CASE REPORT Mycophenolate Adverse Effect Masquerading as Extensive Pneumatosis Intestinalis (PI) after Lung Transplantation Fahid Alghanim, MD1* iD , Janaki Deepak, MBBS1, Aldo Iacono, MD2 and Irina Timofte, MD1 1 Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA 2 R Adams Cowley Shock Trauma Center, Lung Transplant Program, University of Maryland School of Check for Medicine, Baltimore, MD MD 21201, USA updates *Corresponding author: Fahid Alghanim, MD, Department of Medicine, Division of Pulmonary & Critical Care Medicine, University of Maryland Medical Center, 110 S. Paca St., 2nd Floor, Baltimore, MD 21201, USA, Tel: 410-328-0177 are numerous and include pulmonary diseases, autoim- Abstract mune conditions, organ transplantation, intestinal isch- Pneumatosis Intestinalis (PI) is a rare post lung transplant emia, and medication adverse effects [1,6]. PI has been complication which is characterized by the presence of gas within the wall of the small and large intestine. PI in lung previously reported in lung and other solid organ re- transplant recipients has been previously described and is cipients and has been postulated to be associated with associated with disease of varying clinical trajectories. Here immunosuppressive medications such a corticosteroid we describe a case of PI in a lung transplant recipient that [7-10]. However, there were no previous reports that was attributed to immunosuppression with Mycophenolate Mofetil (MMF) as evidenced by the presence of increased directly implicate Mycophenolate Mofetil (MMF) with crypt epithelial apoptosis on biopsy of the duodenum and PI. In this paper, we hope to describe a case of PI in a clinical improvement with withdrawal of the offending agent. lung transplant recipient that has been associated with This case demonstrates that medication adverse effects are MMF. an important differential to consider in lung transplant recip- ients with PI. Case Description Keywords A 59-year-old man with a history of Scleroderma Pneumatosis intestinalis, Lung transplantation, Immuno- related pulmonary fibrosis who underwent bilateral or- suppression, Mycophenolate mofetil, Medication adverse thotopic lung transplantation presented three months effects post-transplant with progressively worsening diffuse abdominal pain, nausea, and bloating of 3-day dura- Introduction tion. The patient’s past medical history was notable Pneumatosis Intestinalis (PI) is defined as the pres- for hypertension, hyperlipidemia, Gastroesophageal ence of gas within the bowel wall [1]. This imaging Reflux Disease (GERD) which was treated with Nissen finding is associated with various clinical phenotypes, fundoplication, esophageal dysmotility and Raynaud’s ranging from benign to life-threatening [2]. It occurs in phenomenon. At presentation, the patient was on My- approximately 0.03% of the general population [3]. PI is cophenolate (Cellcept) 1000 mg suspension twice daily, often a clinical sign of an underlying pathology and is di- Tacrolimus 2 mg suspension once daily (trough level > vided into primary and secondary types. In the primary 12 ng/ml on admission), and Prednisone 15 mg suspen- type, PI is often benign and is associated with gas collec- sion once daily for immunosuppression. Computer To- tion in a cystic pattern. Secondary PI is due to an under- mography (CT) of the abdomen showed large amount lying pathology and is associated with linear collections of pneumoperitoneum with colonic pneumatosis (Fig- of gas within the bowel wall [4,5]. The etiologies of PI ure 1). The patient underwent emergent exploratory Citation: Alghanim F, Deepak J, Iacono A, Timofte I (2021) Mycophenolate Adverse Effect Masquerading as Extensive Pneumatosis Intestinalis (PI) after Lung Transplantation. Int J Respir Pulm Med 8:155.doi. org/10.23937/2378-3516/1410155 Accepted: May 11, 2021; Published: May 13, 2021 Copyright: © 2021 Alghanim F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Alghanim et al. Int J Respir Pulm Med 2021, 8:155 • Page 1 of 4 • DOI: 10.23937/2378-3516/1410155 ISSN: 2378-3516 Figure 1: A) Abdominal film demonstrating curvilinear lucencies suggestive of pneumatosis intestinalis; B) Coronal view of CT Abdomen/Pelvis demonstrating pneumatosis intestinalis involving the ascending and transverse colon. laparotomy which showed extensive pneumatosis of WBC count 7500 cells/mcL, and platelets were 247000/ ascending and transverse colon without bowel ischemia mcL. Sodium was 136 mmol/L, potassium 4.5 mmol/L, or areas of perforation. Symptom as well as radiolog- bicarbonate 31 mmol/L, BUN 30 mg/dL, and creatinine ical findings improved within one week of bowel rest, 1.02 mg/dL. Total bilirubin was 0.8 mg/dL, aspartate intravenous fluid administration, temporary cessation aminotransferase was 53 u/L, alanine aminotransfer- of anti-proliferative immunosuppression (MMF), as ase was 43 u/L, alkaline phosphatase was 99 u/L. Serum well as serial abdominal exams. He was discharged and lactate was 1.3 mmol/L. Tacrolimus level was 6.9 ng/ presented, three weeks later, with recurrent abdomi- mL. Clostridium difficile toxin assay was negative. EBV nal pain, weight loss, and loose dark tarry stools. At the and CMV DNA PCR were negative. Abdominal imaging time, he was only taking oxycodone and acetaminophen showed progression of previously noted PI and pneu- for pain and was avoiding Non-Steroidal Anti-Inflamma- moperitoneum (Figure 2). Gastroenterology colleagues tory Drugs (NSAIDs). He was on appropriate post-trans- were consulted and performed EGD with duodenal bi- plant antimicrobial prophylaxis as well as gastric acid opsy. The pathology is shown in the images below (Fig- suppression medications. He did not smoke, use illicit ure 3). substances, or drink alcohol. On arrival to the ED, the patient was afebrile with a heart rate of 64 beats per Discussion minute and a blood pressure of 120/87 mmHg, a respi- PI is defined as the presence of gas within the wall ratory rate of 18, and an oxygen saturation of a 100% of the small or large intestine [1]. PI in lung transplant on room air. He was alert, oriented, and non-toxic. His recipients has been previously described in the liter- cardiac examination was notable for a holosystolic mur- ature and is postulated to be associated with numer- mur at the left upper sternal border. His chest was clear ous causes with varying clinical trajectories [7-10]. The to auscultation. His abdominal examination was notable pathophysiology of PI is not well elucidated in the lit- for distention, increased tympany to percussion, and erature, but it has been hypothesized to be associated tenderness at the site of previous exploratory laparot- with three main theories in solid organ transplant recip- omy. He had a clean, dry incision, without drainage. His ients including the mechanical, bacterial or infectious, Gastro-Jejunal (GJ) tube was in appropriate position. and the atrophy of Gastrointestinal (GI) lymphoid ag- The remainder of his physical exam was normal. On lab- gregates theories [10]. The mechanical theory is routed oratory evaluation, his hemoglobin level was 9.8 mg/dL, around infiltration of bowel gas through the GI muco- Alghanim et al. Int J Respir Pulm Med 2021, 8:155 • Page 2 of 4 • DOI: 10.23937/2378-3516/1410155 ISSN: 2378-3516 Figure 2: A) Abdominal film demonstrating evidence of significant pneumoperitoneum; B) Coronal view of CT Abdomen/Pel- vis demonstrating marked pneumatosis intestinalis now involving the distal ileum and proximal colon and extending into the splenic flexure as well as pneumoperitoneum. There was no extravasation of oral contrast to suggest perforation of viscous. Figure 3: Endoscopic biopsy of duodenal mucosa showing increased crypt epithelial apoptosis indicative of Mycophenolate Mofetil induced PI. sa. This may be due to alveolar rupture in patients with jority of reported cases, PI was benign and managed obstructive lung disease or those that are mechanically conservatively. Features that may be associated with ventilated with gas dissection into the mediastinum and poor prognosis or need for invasive surgical manage- the intra-abdominal vasculature. The infectious theory ment include an amalgam of clinical, laboratory, and is related to gas formation by GI flora or infection which radiological characteristics. These include increased age may subsequently diffuse into the GI mucosa. The last (> 60 years), a toxic appearing patient with a rigid abdo- theory was thought to be due to atrophy of GI lymphoid men, elevated lactate (> 2 mm/L), elevated WBC count aggregates which causes compromised areas in GI mu- (> 12000 cells/mcL), and the presence of portal venous cosa that are more vulnerable to penetration of bowel gas on imaging. Therefore, the management of these gas. Often, PI in lung transplant recipients is localized patients should be dictated by a thoughtful multidisci- to the large intestine, namely the ascending and trans- plinary team of transplant pulmonologist and surgeons verse colon as seen in our patient [7-9]. Patients can be who are committed to observing a patient closely for completely asymptomatic or have
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