Esophageal Candidiasis Research Articles

RECURRENT FUNGAL INFECTIONS FROM BIRTH TO ADULTHOOD: UNKNOWN DIAGNOSIS UNTIL GENETIC TESTING FOR STAT-1 VARIANTS

<h3>Introduction</h3> Signal transducer and activator of transcription 1 (STAT-1) is a transcription factor that plays key roles in cell viability and pathogen responses. Mutations in STAT-1 result in differing degrees of susceptibility to viral, fungal and bacterial infections, vascular alterations, failure to thrive, and autoimmunity. We report a case of STAT-1 variant presenting with a life-long history of recurrent fungal infections where the diagnosis required genetic testing. <h3>Case Description</h3> A 33-year-old man presented for an evaluation of recurrent fungal infections. He experienced oral thrush, tinea pedis, tinea corporis, and onychomycosis since infancy. He was hospitalized twice for Candida esophagitis requiring IV antifungals. He required treatments with oral antifungals every few months, as he was refractory to topical treatments. He had no bacterial or viral infections, and otherwise unremarkable past medical history. He had thorough workups through multiple specialists with no diagnosis made as his immunologic laboratory studies were normal. However, his 4-year-old son was diagnosed with chronic mucocutaneous candidiasis (CMCC) and had genetic testing showing a STAT-1 variant (c.1159A>G (p.Thr387Ala)). The patient then underwent genetic testing which revealed the same pathogenic STAT-1 variant. Further evaluation showed normal T-cell mitogen studies, total IgG/A/M/E, IgG subclass levels, and vaccine responses. Flow cytometry showed mild B-cell lymphopenia and normal T/NK cells. <h3>Discussion</h3> Patients with pathogenic STAT-1 variants can present with variable infection histories and normal immunologic testing. This case highlights the importance of genetic testing for patients presenting with CMCC regardless of normal immunologic testing to identify a specific diagnosis and defects associated with CMCC.

Prevalence and risk factors for Candida esophagitis among human immunodeficiency virus-negative individuals.

Candida esophagitis (CE) is among the commonest esophageal infections and is known as an opportunistic fungal infection mostly affecting people living with the human immunodeficiency virus (HIV). However, some medical conditions might predispose HIV-negative individuals to esophageal candidiasis. The epidemiology and associated endoscopic findings of CE among people without HIV have rarely been reported. To investigate the prevalence of CE among HIV-negative persons, and determine risk factors predicting CE. Between January 2015 and December 2018, all consecutive outpatients who underwent routine esophagogastroduodenoscopy as part of health check-ups at their own expense at the Health Check-up Center of the Kaohsiung Veterans General Hospital, Taiwan, were recruited in this study. Those with positive HIV serology results were excluded. Sociodemographic and clinical characteristics including age, gender, economic status, smoking history, alcohol consumption, tea and coffee consumption, underlying diseases, body fat percentage, body mass index, endoscopic findings, and Helicobacter pylori infection status were carefully reviewed. CE was confirmed by endoscopic biopsy and pathological assessment with hematoxylin and eosin and periodic acid-Schiff staining. To evaluate independent factors predicting the development of CE, we conducted a univariate analysis of clinical characteristics. The variables found to be significant via univariate analysis were subsequently included in a multivariable analysis of potential risk factors for CE development. A total of 11802 participants were included in this study. Forty-seven (0.4%) were confirmed as having CE by pathological examination. Univariate analysis identified older age, the presence of chronic kidney disease, alcohol consumption, and steroid use (P = 0.023, < 0.001, 0.033, and 0.004, respectively) as significantly associated with CE. Multivariable analysis revealed older age [adjusted odds ratio (OR) = 1.027; 95%CI: 1.001-1.053; P = 0.045], chronic kidney disease (adjusted OR = 13.470; 95%CI: 4.574-39.673; P < 0.001), alcohol consumption (adjusted OR = 2.103; 95%CI: 1.151-3.844; P = 0.016), and steroid use (adjusted OR = 24.255; 95%CI: 5.343-110.115; P < 0.001) as independent risk factors for CE development. The presence of dysphagia was associated with severe CE (P = 0.021). The prevalence of CE among HIV-negative persons was 0.4% in Taiwan. Independent risk factors for CE were older age, chronic kidney disease, alcohol consumption, and steroid use.

S2446 A Unique Endoscopic Finding in an HIV/AIDS Patient With Dysphagia

Introduction: There are many etiologies of dysphagia in patients with HIV/AIDS, including infection, structural issues, or medications. A broad differential is needed to properly diagnose and treat these patients. Here, we present a case of dysphagia in an HIV/AIDS patient related to esophageal intramural pseudodiverticulosis (EIPD). Case Description/Methods: A 58-year-old man with HIV/AIDS presented with a 2-week history of dysphagia. He had been non-compliant with highly active antiretroviral therapy (HAART), and his CD4 count at presentation was noted to be < 20. His past medical history was notable for hypertension, chronic kidney disease, Candida esophagitis, and Mallory-Weiss syndrome. He underwent an esophagogastroduodenoscopy (EGD), which revealed numerous outpouchings and white plaques in the mid esophagus (Figures 1a and b). Esophageal brushings confirmed Candida infection, and biopsies were positive for cytomegalovirus (CMV). A barium esophagram showed outpouchings throughout the esophagus, without any evidence of perforation (Figure 1c). No stricture was evident on EGD or barium esophagram. The patient was diagnosed with EIPD and treated with fluconazole, a proton pump inhibitor, and valganciclovir, with improvement in symptoms. Discussion: EIPD is characterized by the development of multiple small flask-shaped outpouchings in the esophagus. Patients with reflux esophagitis, Candida esophagitis, diabetes mellitus, HIV, and eosinophilic esophagitis are at higher risk for developing EIPD. There are approximately 250 published cases of EIPD in the literature, and the prevalence of EIPD is estimated to be 5-50 per 100,000 cases. Development of pseudodiverticula in the esophagus is suggested to be secondary to chronic inflammation, obstruction of the submucosal glands due to debris, or increased intraluminal pressure proximal to a luminal obstruction. The diagnosis is primarily made with EGD, barium esophagram, or computerized tomography. The treatment for EIPD includes treatment of underlying conditions and endoscopic dilation of strictures when they are present [1]. Our patient had several risk factors for development of EIPD such as Candida esophagitis, Mallory-Weiss syndrome, and HIV. However, a prior association between EIPD and CMV esophagitis has not been reported. Here, we highlight CMV esophagitis as a potential risk factor for development of EIPD.Figure 1.: EGD (a and b) and barium esophagram (c) findings.

S388 Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Utilizing the Veterans Affairs Achalasia Cohort (VA-AC)

Introduction: Achalasia is a postulated risk factor for esophageal cancer (EC) – both squamous cell carcinoma (SCC) and adenocarcinoma (AC). Evaluation of EC-associated risk factors and outcomes in achalasia are limited due to a lack of large, validated cohorts available for study. Our aim was to evaluate the risk of EC among individuals with compared to without achalasia utilizing a large, validated achalasia cohort: the Veterans Affairs Achalasia Cohort (VA-AC). Methods: We conducted a matched cohort study among US Veterans aged ≥18 years between 1999-2020. Individuals with achalasia from the VA-AC were matched to individuals without achalasia at a ratio of 1:4 on index achalasia encounter date, and by sex, year of birth, and first VA visit date +/- 180 days. Follow-up was censored at the outcome (EC), death from a non-EC related cause, or end of the study period. EC cases were ascertained from cancer registry and cause-specific mortality, with all cancer cases reviewed for verification. Descriptive statistics were performed for baseline characteristics. EC hazard functions were assessed using Cox regression models. Results: 1,866 Veterans with achalasia were matched to 7,464 Veterans without achalasia. Median age was 55 years (IQR 48-63), and 92% were male (Table). There were 17 EC cases among Veterans with achalasia (3 AC, 12 SCC, 2 unknown type) compared to 15 EC cases among Veterans without achalasia (11 AC, 1 SCC, 3 unknown). Median time from achalasia diagnosis to EC development was 3.0 years (IQR 1.3-9.1). Patients with achalasia had a 5.4-fold higher risk of EC (HR 5.4, 95% CI 2.8,10.5) compared to patients without achalasia. Higher cumulative incidence of EC (p< 0.0001, based on log-rank test; Figure) in those with vs without achalasia at 5-, 10- and 15-years follow-up was observed. In post hoc analysis, several individuals with EC also had candida esophagitis preceding their cancer diagnosis (12.5%) by median time 1.3 years (IQR 0.2-2.7). Based on univariate cox regression model, patients with vs without candida esophagitis had a 18.3-fold higher risk of EC (95% CI 6.2, 53.7). Conclusion: Using a national cohort of US Veterans, we found achalasia was associated with 5-fold increased EC risk compared to those without achalasia. Candida esophagitis exposure may also predict higher EC risk. Additional studies are needed to understand if this increased risk of EC warrants routine endoscopic surveillance in individuals with achalasia.Figure 1.: Cumulative Incidence of Esophageal Cancer Kaplan Meier curve demonstrating cumulative incidence at 5-, 10- and 15-year time points. Incidence at each time point was significantly higher for individuals with achalasia compared to individuals without achalasia. Table 1. - Achalasia ^ N = 1866 No AchalasiaN = 7464 Age, median (IQR) 55.0 (48.0 – 63.0) 55.0 (48.0 – 63.0) Males, n (%) 1725 (92.4) 6900 (92.4) Race/Ethnicity, n (%) Asian/Pacific Islander 23 (1.2) 113 (1.5) Black 378 (20.3) 1164 (15.6) Hispanic 125 (6.7) 326 (4.4) Multiracial/Other 25 (1.3) 157 (2.1) White 1208 (64.7) 4755 (63.7) Unknown 107 (10.1) 949 (12.7) BMI, median (IQR) 28.6 (25.1 – 32.9) 28.6 (25.4 – 32.6) Diabetes, n (%) 528 (28.3) 1686 (22.6) Smoking Status, n (%) Current 532 (28.5) 1592 (21.3) Former 386 (20.7) 1293 (17.3) Never 556 (29.8) 2398 (32.1) Unknown 392 (21.0) 2181 (29.2) Aspirin Exposure, n (%) 683 (36.6) 1699 (22.8) Barrett’s Esophagus, n (%) 125 (6.7) 189 (2.5) Candida Esophagitis, n (%) 64 (3.4) 7 (0.1) Esophageal Cancer, n (%) 17 (0.9) 15 (0.2) Squamous Cell Carcinoma 12 1 Adenocarcinoma 3 11 Unknown 2 3 *All variables are significant with p-value <.0001, except Age (Matched), Gender (Matched), and BMI which were not statistically significant at alpha=0.05.^Achalasia subjects were previously validated using an algorithm consisting of 3 or more ICD9 or ICD10 codes in a subject's lifetime plus a CPT code for esophageal manometry; the positive predictive value (PPV) for this algorithm to diagnose true achalasia subjects was 94% (95% confidence lower bound of 88.5%) BMI = body mass index; IQR = interquartile range.

S1043 Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series

S1043 Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series

A RARE CASE OF DISSEMINATED MYCOBACTERIUM AS THE CAUSE OF RECURRENT PNEUMOTHORAX

A RARE CASE OF DISSEMINATED MYCOBACTERIUM AS THE CAUSE OF RECURRENT PNEUMOTHORAX

S3237 Pneumocystis jirovecii Infection in Cirrhosis: A Case Report and Review of the Literature

Introduction: Pneumocystis jirovecii is a fungus that causes serious pneumonia in immunocompromised individuals most classically associated with AIDS or prolonged steroid use. Immune dysfunction is a well- nown complication of cirrhosis; however, Pneumocystis pneumonia (PCP) is not typically associated with cirrhosis as a common risk factor. We present a case of PCP in a patient with cirrhosis and review the existing cases in the literature. Case Description/Methods: A 59-year-old male with past medical history of alcoholic cirrhosis (MELD 30, Child Pugh Class C) presented with sepsis secondary to spontaneous bacterial peritonitis. He reported he was 6 months sober. He initially improved on ceftriaxone alone; he did not receive steroids. On hospital day five he developed dyspnea and hypoxia. CT-angiogram revealed extensive ground glass opacities. Despite broad spectrum antimicrobials, his condition deteriorated resulting in invasive ventilation. Bronchoalveolar lavage was significant for Pneumocystis jiroveci by polymerase chain reaction. HIV testing was negative. Due to renal impairment, therapy was initiated with clindamycin and primaquine before he expired (Figure). Discussion: This case was unique in that cirrhosis was the only identified risk factor for immunosuppression which predisposed to PCP. PCP is rare outside of risk factors including AIDS, prolonged systemic steroids and other immunosuppressive therapies, organ transplantation, hematologic malignancy, and solid tumors. There were 14 similar cases in the literature. Of the 15 total cases, 66% were male; the median age was 54. Eleven were in the setting of alcoholic hepatitis, and 9 of these received steroids. However, none of the steroid exposures were significant enough to be a classic risk factor for PCP. Common comorbidities included COPD and lymphopenia. CMV pneumonia was seen in 33% of cases. Esophageal candidiasis and Histoplasma capsulatum pneumonia were also recorded. Fatality in 87% of cases suggests that PCP in cirrhosis is associated with a poor prognosis. There are multiple possible mechanisms why these patients developed PCP. Systemic inflammation related to cirrhosis may dysregulate key inflammatory mediators required for immune response to Pneumocystis. Also, Low CD4 counts related to portal hypertension and splenic sequestration may play a role, although an effective immune response also requires interplay of B cells and natural killer cells. This case and review are important reminders of the severity of immunocompromise in cirrhosis.Figure 1.: CT-Angiogram with diffuse ground glass opacities. Table 1. - Author Date Age/sex Prior steroid exposure (duration if applicable) Etiology of cirrhosis Additional conditions Treatment for PCP Death (y/n) Ikawa 2001 40M Y (10 days and 22 days with a 7 day interim in between) alcohol abuse cytomegalovirus pneumonia, esophageal candidiasis, lymphopenia none Y Faria 2007 44F present in 6 of 7 cases (median duration: 16 days)* alcohol abuse cytomegalovirus isolated in 3 of 7 cases* trimethoprim/ sulfamethoxazole (TMP/SMX) Y 49M alcohol abuse TMP/SMX Y 50M alcohol abuse TMP/SMX Y 53M alcohol abuse TMP/SMX Y 56F alcohol abuse TMP/SMX Y 58F alcohol abuse TMP/SMX Y 61M alcohol abuse TMP/SMX Y Dodi 2010 54F Y (9 days) alcohol abuse cytomegalovirus pneumonia, hepatorenal syndrome TMP/SMX Y Yee 2017 52M N hepatitis c hepatitis c, lymphopenia primaquine, clindamycin, corticosteroids, TMP/SMX N Hadfield 2019 63M N alcohol abuse COPD TMP/SMX Y Akhter 2020 67F N hepatitis c COPD steroids, antibiotics (unspecified) N Dugan 2020 64M N NASH COPD, lymphopenia, histoplasma capsulatum pneumonia TMP/SMX Y Chung 2020 43M Y (26 days) alcohol abuse n/a TMP/SMX Y Meyers 2022 59M N alcohol abuse COPD, lymphopenia clindamycin, primaquine Y *Not specified which cases had the exposures and/or conditions.

S2316 Esophageal Pseudodiverticulosis Presenting as Chest Pain, Epigastric Pain and Nausea

Introduction: Esophageal intramural Pseudodiverticulosis (EIP) is an unusual condition manifested by tiny flask-shaped out pouches in the wall of the esophagus. We describe a case of a 68-year-old woman presenting for upper endoscopy (EGD) for an abnormal CT Scan showing esophageal thickening. Case Description/Methods: A 68-year-old woman presenting for EGD for an abnormal CT Scan showing esophageal thickening. This was seen as a finding on CT Angio Chest/Abdomen performed to rule aortic dissection as the patient complained of persistent chest pain. The chest pain was associated with epigastric discomfort and nausea. On EGD, the findings were consistent with the esophageal pseudodiverticulum located throughout the length but mainly in the distal esophagus. Accompanying the pseudodiverticulosis were whitish punctate plaques scattered throughout the length of the esophagus. The remainder of the exam on EGD was normal. The biopsy findings were consistent with esophagitis, in the areas where multiple esophageal psuedodiverticuli were found. The PAS stain was negative for fungal infection. The patient was prescribed Omeprazole 40 mg daily for esophagitis and was also offered treatment for Esophageal Candidiasis due to findings of white punctate plaques in the esophagus (Figure). Discussion: Esophageal Intramural Pseudodiverticulosis is an uncommon condition first described by Mendl et al. in 1960. EIP is mainly a disease of older age with a 3:2 male to female ratio. In 90% of the cases of EIP, esophagitis is found as in our patient. Esophageal Candidiasis is commonly associated with EIP. These Intramural Pseudodiverticulosis are dilated excretory ducts of the deep esophageal mucosal glands. Treatment is required in about 90% of the patients. Treatment mainly consists of PPI therapy in cases of esophagitis and dilatation in Esophageal Strictures. Antifungal therapy is indicated in suspected Esophageal Candidiasis cases as candida infection is also associated with EIP.Figure 1.: In this image, whitish plaques are seen. We can also see pseudodiverticula (marked by arrows).

S2438 A Rare Cause of Esophageal Varices

Introduction: Esophageal varices (EV) are classified as downhill or uphill varices. Uphill varices are common and found in the distal esophagus that develop secondary to portal hypertension. Downhill esophageal varices (DEV) are rare and found in the proximal and mid esophagus and most commonly develop from obstructed venous blood flow in the superior vena cava (SVC). Case Description/Methods: A 74-year-old White male with past medical history of ESRD who was on hemodialysis for 5 years before a renal transplant was performed, COPD Gold Stage II, and obstructive sleep apnea presented to clinic with weight loss and dysphagia for the past year. The patient had no history of liver disease, physical examination was unremarkable, and his labs were normal. An esophagogastroduodenoscopy (EGD) revealed one large non-bleeding esophageal varix (EV) in the mid-esophagus and whitish plaques later confirmed by pathology to be Candida esophagitis. The patient was placed on IV micafungin and his dysphagia resolved. A CT Abdomen showed a normal liver and spleen. To further assess the DEV, a CT angiogram of the chest was obtained and revealed significant narrowing of SVC. (Figure). To evaluate the cause of SVC stenosis, an echocardiogram was ordered which revealed moderate to severe dilation of the right ventricle and evidence of pulmonary hypertension deemed to be likely secondary to his COPD and OSA. Of note, the patient had a prior chronic hemodialysis (HD) indwelling catheter in his SVC. After discussion with cardiology and CT surgery, the patient was referred to cardiology for an SVC venogram and right heart catheterization to measure pulmonary pressures. Discussion: DEV are formed when there is an obstruction in the SVC causing retrograde blood flow into the right atrium through collateral channels. The proximal and mid esophageal veins drain into the collaterals and the increased pressure result in DEV. The most common etiology is thrombosis of the SVC, but DEV can also be caused by severe pulmonary hypertension, thyroid tumors, and complications with HD catheters. In our case, the patient’s prior chronic HD catheter likely caused narrowing of the SVC lumen, along with long-standing pulmonary hypertension. Currently, there are no guidelines for screening or management of DEV. Physicians should be aware of unusual causes of varices and the management of DEV involves a multidisciplinary approach to treat the underlying cause of the SVC obstruction.Figure 1.: Significant narrowing of SVC (red arrow) on CT chest.

S2440 A Rare Cause of Dysphagia: Esophageal Stricture Due to Lichen Planus

Introduction: Esophageal lichen planus (ELP) is an unusual and under-recognized cause of dysphagia. Timely diagnosis is crucial for effective treatment as ELP has been associated with increased risk for development of squamous cell carcinoma. Case Description/Methods: A 72-year-old man presented with esophageal dysphagia to solids. Past medical history included oral lichen planus (LP) and osteoporosis with use of alendronate. He underwent endoscopy (EGD) which showed a proximal esophageal stricture for which balloon dilation ranging from 8 to 15 mm was done. Biopsy of the stricture showed esophageal mucosa with increased intraepithelial eosinophils (Figure). The working diagnosis was peptic stricture with possible eosinophilic esophagitis (EoE). He was started on pantoprazole 40 mg twice daily. He underwent 2 more EGDs with dilation for recurrent stricture and on the 2nd EGD, biopsy of the stricture showed numerous intraepithelial lymphocytes and focal apoptotic squamous cells (Civatte bodies) compatible with ELP. Budesonide slurry 1 mg twice daily was instituted and an EGD 6 months later showed near resolution of the stricture. The patient no longer requires dilations or antiacid therapy and is asymptomatic currently. He had Candida esophagitis 1 month after initiation of budesonide which was treated with fluconazole. Discussion: ELP is prevalent in patients with mucocutaneous forms of LP, most often oral LP. It is rarely seen in males with a case series by Franco et al describing the female to male ratio as 5:1. The endoscopic differential diagnosis for ELP should distinguish findings of esophagitis and stricture secondary to EoE, reflux esophagitis or esophageal Candidiasis. A low threshold should be kept for suspecting ELP in a patient with dysphagia and mucocutaneous LP. If histology is inconclusive but a high index of suspicion remains, particularly in patients with mucosal LP, repeating biopsies may be warranted for diagnosis as is highlighted in this case. A co-relation between longer duration of disease with severity of inflammation has been proposed with case series reporting strictures. Treatment includes serial dilations, topical and/or systemic steroids. Recurrence has been described despite topical steroid therapy with requirement of additional dilations. Successful use of immunomodulators such as cyclosporine, mycophenolate has been described. There is paucity of data regarding surveillance and optimal treatment for ELP, and thus further studies are needed for better understanding of this disease.Figure 1.: Esophageal biopsy showing esophageal squamous mucosa with basal cell hyperplasia, intraepithelial lymphocytes, and 2 apoptotic keratinocytes (Civatte or colloid bodies). Findings are compatible with esophageal lichen planus.

S2323 First Known Case of Esophageal Parakeratosis Associated With a Severe SARS-CoV-2 Infection

Introduction: Esophageal parakeratosis is a rare, benign condition that is associated with vitamin deficiencies as well as squamous cell carcinoma of the head and neck or upper gastrointestinal tract. Symptoms include dysphagia, odynophagia, and heartburn. Here we describe a patient diagnosed with esophageal parakeratosis in the setting of a recent, severe SARS-CoV-2 infection as his only associated condition. Case Description/Methods: A 79-year-old man presented for an outpatient endoscopy for history of a gastric mass. He had been worked up for this presumed gastrointestinal stromal tumor (GIST) with endoscopic and surgical biopsies that were unrevealing. During that time he developed a severe case of SARS-CoV-2 with prolonged hospitalization and was started on anticoagulation for bilateral pulmonary emboli. He developed hematemesis and endoscopy revealed a large ulcer at the same site of the previous noted mass instead of the previously. He was now presenting for endoscopic workup with EGD as an outpatient for follow up. Endoscopy revealed only chronic gastritis but no evidence of mass or ulcer. However, the entire esophageal mucosa was abnormal with diffuse sloughing. Brushings were taken and he was empirically started on antifungals for presumed candida esophagitis as well as proton pump inhibitor twice daily. Histology revealed esophageal parakeratosis without dysplasia without candida. He returned for a repeat EGD and was found to have a normal esophagus at that time. All vitamin levels checked were within normal range including zinc at 78 ug/dL. There were no other known active malignancies at the time and imaging revealed no residual evidence of mass. His only other association during this time was the recent, severe SARS-CoV-2 infection (Figure). Discussion: Esophageal parakeratosis needs to be differentiated from other conditions such as candida and eosinophilic esophagitis. It should raise suspicion for head and neck malignancies and has been found in the nearby esophageal mucosa of 90 percent of patients with esophageal cancer in one study. Other associated conditions with esophageal parakeratosis include tylosis and alcohol abuse. The temporal relationship of the severe SARS-CoV-2 infection likely causing some degree of immunosuppression in this patient could have been the precipitating factor that led to the development of his esophageal parakeratosis. More studies are needed to elucidate the relationship between the immunocompromised state during SARS-CoV-2 infection and esophageal parakeratosis.Figure 1.: Esophageal Parakeratosis.

S2409 A Case of Esophago-Pulmonary Fistula From Esophageal Candidiasis Diagnosed on Endoscopy

Introduction: Esophago-pulmonary fistulas (EPFs) are abnormal connections between the esophagus and lungs that are rarely seen despite the proximity of the 2 structures. They are associated with high morbidity and mortality. Fistulization between the esophagus and lungs is a known complication of pneumonectomy procedures, but other causes include malignancies and infection. Case Description/Methods: A 61-year-old male with a history of tobacco and alcohol use disorder, diabetes mellitus, and esophageal candidiasis, with both Candida glabrata and Candida albicans isolated on biopsies from an otherwise normal endoscopy 4 months prior presented with presumed septic shock and melena. Blood cultures were positive for C. glabrata. Esophagogastroduodenoscopy (EGD) was done and revealed a fistulous tract leading to a bronchial bifurcation consistent with an esophago-pulmonary fistula with necrotic and friable tissue surrounding it (Figure A and B), in addition to grade D esophagitis. Subsequent CT chest showed definite right and possible left esophago-pleural fistulization with associated right loculated pleural effusion and small left pleural effusion (Figure C). No evidence of pulmonary malignancy or pulmonary tuberculosis was noted on imaging. Serum interferon gamma release assay and 3 sets of sputum acid fast bacillus testing for tuberculosis testing were negative. Thoracic Surgery were consulted but the procedure offered was multistage and did not align with patient's goals of care. The patient continued to decline despite antifungal and antibiotic treatment and was ultimately transitioned to hospice care. Discussion: While formal tissue diagnosis was not obtained in this case due to patient’s tenuous condition, the etiology of EPF was presumed to be invasive esophageal candidiasis infection, especially in the absence of malignancy on imaging and recent EGD. Interestingly, fistulas related to empyema were commonly reported in the pre-antibiotic era. A CT scan of the chest is useful for early diagnosis of EPF. While different modalities help establish the diagnosis of EPF, clinical suspicion remains key in initiating appropriate investigation.Figure 1.: A and B: Lower third of esophagus with necrotic tissue surrounding esophago-pleural fistula (arrows). C: (Axial CT showing an air-fluid level within the distal esophagus with loss of the fat plane between the esophagus (arrow) and the loculated right pleural effusion (dashed arrows), compatible with an esophago-pleural fistula).

S932 Active Tuberculosis and Opportunistic Infections: Pooled Safety Analysis of Ustekinumab Through up to 5 Years Across All Approved Indications

Introduction: Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment. Methods: Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or >16 weeks after the last UST dose for UST pts who switched to PBO. Results: Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a CD pt 10 months after receiving UST 130 mg IV) and UST pts (n=1) (Table). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1). Conclusion: Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 years with 13807 PYs of follow-up and not higher in UST pts vs PBO, suggesting no increased risk of OI with long-term UST treatment. Table 1. - Opportunistic infections (OIs) and active tuberculosis (TB) in Inflammatory Bowel Disease (CD, UC) and Psoriatic studies (PsO, PsA) through up to 5 yrs; numbers of events per 100 patient-years (PYs) of follow-up Inflammatory Bowel Disease Indications a Psoriatic Indications a All Approved Indications Pooled Placebo b (n=1389) Ustekinumab c (n=2575) Placebo d (n=1112) Ustekinumab e (n=4135) Placebo b,d (n=2501) Ustekinumab c.e (n=6710) Total PYs of follow-up 916 3960 327 9847 1244 13807 Average duration of follow-up (weeks) 34.31 79.97 15.30 123.83 25.86 107.00 All OIs, event rates per 100 PYs [n] 0.55 [5] 0.33 [13] 0.00 [0] 0.01[1] 0.40 [5] 0.10 [14] OIs excluding TB 0.33 [3] 0.30 [12] 0.00 [0] 0.01 [1] 0.24 [3] 0.09 [13] TB 0.22 [2] 0.03 [1] 0.00 [0] 0.00 [0] 0.16 [2] 0.01 [1] aPsoriatic (PsO and PsA) trials evaluated subcutaneous ustekinumab (UST) 45/90 mg or placebo (PBO), generally at week 0 and 4, then every 12 weeks (q12w). IBD (CD and UC) trials generally evaluated a single intravenous UST dose (130 mg or weight range-based dosing of ∼6 mg/kg) or PBO induction dose at week 0, followed by subcutaneous UST 90 mg at week 8, then q8w or q12w.bCD and UC: includes data up to the first UST dose for patients who were initially treated with PBO; includes data at or after 16 weeks from the first UST dose onward, up to the dose adjustment if patients had a dose adjustment, for patients who crossed-over or re-randomized to PBO maintenancecCD and UC: includes data up to 16 weeks from the first UST dose for patients who crossed-over or re-randomized to PBO maintenance, and from the dose adjustment onward if patients had a dose adjustment from subcutaneous PBO to subcutaneous UST 90 mg q8wdPsoriatic diseases: includes data up to the time of early escape or crossoverePsoriatic diseases: includes data from the first UST dose onward for patients who early escaped or crossed-over from PBO

S2322 Esophageal Intra-Mural Pseudo-Diverticulosis With Candidiasis

Introduction: Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disorder of idiopathic etiology characterized by the presence of multiple small outpouchings protruding from the esophageal lumen. Diagnosis is typically made through radiological imaging or with esophagogastroduodenoscopy (EGD). While asymptomatic by itself, symptoms arise from associated conditions including candidiasis, esophageal stricture, and chronic esophagitis. It has a male predominance and dysphagia secondary to esophageal stricture is the most common presenting complaint. Treatment is directed at associated symptomatic conditions and whether or not the diverticula disappear post treatment has no impact on the patients' clinical outcome. Case Description/Methods: This is a case of a 38-year-old male with human immunodeficiency virus (HIV) on anti-retroviral therapy. He was evaluated for a chronic history of dysphagia and odynophagia, associated with nausea, vomiting, heart burn, and weight loss. He underwent EGD which revealed pseudo-diverticula along the entirety of the esophagus with superimposed esophageal candidiasis. Patient was prescribed fluconazole 100 mg oral daily for 2 weeks and will be re-evaluated post treatment (Figure). Discussion: Dysphagia is a common presenting symptom for numerous GI conditions. Though cases of EIPD are uncommon, it is important for clinicians to keep this diagnosis in their differential. The diagnosis of EIPD may not always be apparent through EGD, as the diverticula may be small enough to miss. If a high clinical suspicion remains, radiological imaging with contrast should be considered as it has enhanced sensitivity for detecting these smaller diverticula. EIPD has been associated with Candidiasis, however it is uncertain whether it causes or is a result of the infection. In our case, we were unable to confirm whether EIPD was the cause or result of a Candida infection. Additionally, patient education is important when it comes to dysphagia. Our patient had been experiencing symptoms for 6-7 months before a diagnosis was made. It is important to educate patients that dysphagia is an abnormal symptom and should be further evaluated to determine causal etiology. There is scarce literature available regarding discussion of EIPD, therefore clinicians should continue to report cases to improve our understanding of this rare pathology.Figure 1.: Esophagogastroduodenoscopy images demonstrating esophageal intramural diverticula indicated by yellow arrows, and showing generalized esophageal candidiasis plaques present throughout the entirety of the esophagus.

S2447 “Outpouchings in the Esophagus”: A Rare Case of HIV-Associated Esophageal Intramural Pseudodiverticulosis in the Absence of Esophageal Candidiasis

S2447 “Outpouchings in the Esophagus”: A Rare Case of HIV-Associated Esophageal Intramural Pseudodiverticulosis in the Absence of Esophageal Candidiasis

S3705 A Case of Multifocal Burkitt Lymphoma in an Immunocompromised Patient

Introduction: Primary non-Hodgkin’s lymphoma (NHL) of the GI tract accounts for less than 0.9% of all gastrointestinal tumors. 30-40% of all extranodal manifestations occur in the stomach during secondary involvement, however this is less common in non-endemic Burkitt lymphoma (BL). Primary BL of the GI tract is very rare, including involvement of the stomach, duodenum and pancreas, accounting for less than 1% of all NHL tumor growth, even in secondary disease. BL is associated with HIV and EBV, however in those with HIV/AIDS, the CD4 count is typically greater than 200 without presence of concomitant opportunistic infections. Case Description/Methods: A 52 YO M PMH HIV, AIDS, HCV, IV drug abuse presented with acute L sided back and abdominal pain. On arrival he was hypotensive, cachectic with temporal wasting and severe, diffuse abdominal tenderness and tenderness of his L paraspinal muscles and lumbar spine. Labs were significant for leukocytosis, normocytic anemia, AKI, elevated ALP, LDH and ESR, and UDS positive for cocaine and opiates. CT A/P showed a fracture of the L 9th rib and asymmetry of the gastric wall. MRI revealed multifocal osteomyelitis with an epidural abscess spanning T7-T9. He underwent I & D and pathology of the epidural abscess and ribs revealed Burkitt Lymphoma. ERCP/EUS findings included esophageal candidiasis, multiple masses and nodules within the stomach, duodenum, and pancreas with strictures throughout the CBD and lower third of the main bile duct. A biliary sphincterotomy was performed and biopsies of all specimens were positive for Burkitt Lymphoma. His hospitalization was complicated by a subdural hemorrhage, initially thought to be CNS involvement however MRI brain and CSF flow cytometry did not reveal brain metastasis. A bone scan showed increased uptake in the distal shaft of the L humerus and femur, and a CT chest revealed a 4 mm nodule, all concerning for metastasis. He also developed SBO for which he was treated with R-CODOX/R-IVAC chemotherapy to reduce tumor burden. G-CSF and intrathecal methotrexate were administered. His SBO resolved and he was discharged home to follow up with Oncology for further management. Discussion: We present an HIV patient with low CD4 counts who was diagnosed with BL of the bone, lymph nodes, duodenum, stomach, pancreas and small intestine. The primary site of BL is ultimately unknown due to his complex presentation, however primary and/or secondary involvement of the duodenum, pancreas, stomach and intestine is very rare in non-endemic BL.

P482 Burden of serious fungal infections in India

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Fungal disease is frequent in India but its incidence and prevalence are unclear. Literature searches yielded over 2900 papers; 434 papers with incidence/prevalence/proportion data were analyzed. Deterministic modeling allowed annual incident and prevalence estimates for multiple life and sight-threatening infections with significant morbidity. An estimated 55 916 148 of 1 393 400 000 people in India (4.01/100 000) suffer from a serious fungal disease. The prevalence (in millions) of recurrent vulvovaginal candidiasis is 24.3, allergic bronchopulmonary aspergillosis (ABPA) is 2.0, tinea capitis in school-age children is 25, severe asthma with fungal sensitization of 1.36, chronic pulmonary aspergillosis of 1.75 and chronic fungal rhinosinusitis of 1.52. The annual incidence of Pneumocystis pneumonia (58 400), invasive aspergillosis (250 900), mucormycosis (195 000), esophageal candidiasis in HIV (266 600), candidemia (18 800), fungal keratitis (1 017 100) and cryptococcal meningitis (11 300) were also determined. Histoplasmosis, talaromycosis, mycetoma, and chromoblastomycosis are less frequent. India's fungal burden is high and under-appreciated in clinical practice.See Figures below.

Signet Ring Cell Esophageal Adenocarcinoma: A Rare Histologic Variant

A 68-year-old man with a history of heavy smoking presented with 3 weeks of dysphagia to solids. Endoscopy revealed erythema in the lower esophagus with scattered white plaques covering umbilicated nodules (Figure A); on gastric retroflexion, these lesions extended beyond the esophagogastric junction (Figure B). Infectious esophagitis, specifically esophageal candidiasis or herpes esophagitis, was suspected, but surprisingly the biopsies revealed squamous mucosa with infiltrating adenocarcinoma containing copious signet ring cells (SRC) (Figure C: low [left] and high [right] magnification; arrows indicate SRC with large intracellular mucin-containing vacuoles displacing nuclei to the cell periphery). SRC comprised >50% of the tumor mass. Immunostaining detected overexpressed programmed death-ligand-1 (PD-L1) but not human epidermal growth factor receptor-2 (HER-2). Positron emission tomography/computed tomography revealed distal esophageal wall thickening with mild metabolic uptake but no enlarged, metabolically active lymph nodes. Endoscopic-ultrasonography revealed an irregular circumferential mucosal mass extending 36 cm from the incisors to 1 cm distal to the esophagogastric junction, invading the adventitia but not regional lymph nodes (Figure D). The cancer progressed despite neoadjuvant chemoradiotherapy, esophagectomy, and adjuvant immunotherapy; the patient died 8 months after presentation. SRC adenocarcinoma accounts for <10% of esophageal adenocarcinomas and portends a worse outcome. Clearly, the presence of esophageal skip lesions should not exclude the possibility of neoplasia. The prevalence and prognostic value of PD-L1 and HER-2 overexpression in esophageal SRC adenocarcinoma are unknown.

A six-year hospital-based surveillance study on burden of esophageal candidiasis in Gangtok, Sikkim.

Esophageal candidiasis once thought to be restricted amongst immunocompromised patients is being increasingly reported among non-immunocompromised individuals. It is debilitating and if not treated well may cause chronic long-lasting infections. The objective of this study was to identify the various species of Candida causing esophageal candidiasis and analyse their antifungal susceptibility pattern. This was an observational, prospective study. Total of 108 patients who attended the Gastroenterology Department of Sir Thutob Namgyal Memorial Hospital, Govt of Sikkim, Gangtok, India between July 2012 - May 2018 were included in the study. They had complaints of upper gastrointestinal disturbances and chronic dyspeptic symptoms that required an endoscopy. Esophageal biopsy and brushings were taken and were transported to Microbiology Department. They were subjected to microscopic observation, fungal culture on Sabourauds dextrose agar. Preliminary species identification was done by chlamydospore formation and growth characteristics on CHROMagar Candida. Species confirmation and antifungal susceptibility testing was done on VITEK 2 system at Microbiology Department, Kasturba Medical College and Hospital, MAHE, Manipal, Karnataka, India. A total of 108 patients were screened among which 73 samples were positive for Candida species and species identification and antifungal susceptibility was performed. Forty fiveisolates were found to be C. albicans, 8 were C. glabrata, 4 were C. tropicalis, 3 were C. lusitaniae 2 were C. krusei, 2 were C. lipolyticaand 1 was C. parapsilosis. Eight isolates could not be identified and were recorded as Candida spp. C. albicans isolates were predominantly sensitive strain with susceptibility of 95% for both amphotericin B and fluconazole and 100% for caspofungin. C. glabrata showed high resistance to fluconazole with one isolate showing intermediate resistance to caspofungin. Upper gastrointestinal symptoms even in non-immunocompromised patients need to be screened by endoscopy to rule out esophageal candidiasis. With the emergence of drug resistant non albicans Candida species diagnostic testing laboratories should include Candida species identification and antifungal susceptibility testing facility to provide effective patient care.

The spectrum of opportunistic fungal infections in relation with ART in HIV patients

Recent years have witnessed a phenomenal increase in prevalence as well as severity of opportunistic fungal infection (OFIs) despite of availability of different therapeutic options. This could be attributed to various reasons including increased prevalence of immunocomprised patients. Awareness of spectrum of fungal infections in immunocompromised conditions and their epidemiological changes is critical for early diagnosis and proper management. Method: A total of 277 clinical samples were collected from 216 HIV patients suspected of OFI. Sample processing and identification of fungi carried out by standard conventional methods. Result: Out of 216 patients, 30% (65) showed positive fungal etiology with single or multiple system involvement. Oral candidiasis ranked highest (46%) followed by Cryptococcal meningitis (35%), Candidial pneumonia (10%), Oesophageal candidiasis (7%), Dermatophytoses (6%), Pulmonary aspergillosis (4%), Systemic candidiasis (4%), Pneumocystis pneumonia (3%) etc. Discussion: As most of opportunistic fungi (OF) are part of the normal human microbial flora, clinical significance of fungal isolates must be confirmed by standard criteria laid down such as repeated isolation, supportive clinical findings and radiographical evidences. Although Antiretroviral Therapy for minimum 6 months duration provides protection against OFI by maintaining CD4 count, compliance to treatment important.