Histoplasmosis and SARS-CoV-2 infection in a critically ill patient

Introduction: Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum, whose clinical manifestations range from asymptomatic to disseminated and highly fatal disease. Objective: To present the case of a patient diagnosed with disseminated histoplasmosis and SARS-CoV-2 infection. Clinical case: The case of a 79-year-old man is presented with a history of systemic arterial hypertension and type 2 diabetes mellitus. He was admitted for a week with nonproductive cough, dyspnea, and fatigue on moderate exertion, and reported having a positive antigen test for SARS-CoV-2. During hospitalization, he presented clinical deterioration, needing mechanical ventilation due to respiratory infection associated with COVID-19. Despite this, he presented lymphadenopathy, hepatosplenomegaly, and umbilicated skin-colored papules suggestive of disseminated fungal infection. Suspecting co-infection, infection by Histoplasma capsulatum was confirmed by means of mini-bronchoalveolar lavage and antifungal treatment was initiated;however, the patient presented persistent clinical deterioration and died. Conclusion: Cases of co-infections with COVID-19 in patients without chronic diseases or immunosuppressive states are rare, their diagnosis being a challenge for medical personnel and requiring consideration of pulmonary fungal infections such as cryptococcosis or histoplasmosis in associated respiratory failure. to SARS-CoV-2 infection. © 2023, Editorial Ciencias Medicas. All rights reserved.

Evidence of anti-Hcp100 antibodies in COVID-19 critically ill patients with detectable anti-histoplasmin antibodies in a highly endemic area for histoplasmosis.

Patients with severe COVID-19 are at increased risk for invasive fungal infections, which are underestimated. Histoplasmosis reactivation in endemic areas should not be overlooked in this population. In a previous study, seroconversion to anti-histoplasmin antibodies by ELISA was detected in 6/39 (15.4%) patients with severe COVID-19. In this work, samples were further investigated to detect seroconversion to antibodies against the Histoplasma capsulatum 100-kDa antigen (Hcp100) by ELISA. Seroconversion to anti-Hcp100 antibodies was detected in 7/39 patients, of whom 6 also seroconverted anti-histoplasmin antibodies. These results reinforce previous findings that show histoplasmosis as an underdiagnosed fungal entity complicating COVID-19.

This study verifies that patients with severe COVID-19 at intensive care units are at risk for histoplasmosis reactivation in endemic areas. Accurate diagnosis of this deadly fungal disease among critically ill patients with COVID-19 living in endemic areas for histoplasmosis is needed.

Chronic Cavitary Pulmonary Histoplasmosis in an Immunocompetent Patient.

Histoplasma capsulatum is a fungal organism that causes systemic histoplasmosis. It is commonly asymptomatic in healthy immunocompetent individuals. The clinical symptoms of chronic cavitary histoplasmosis are typically seen in the immunodeficient population, particularly in smokers with pre-existing structural lung disease. We report a case of chronic cavitary histoplasmosis in an immunocompetent patient from an endemic area without pre-existing structural lung pathology. She presented complaining of right hypochondrial pain and had no history of respiratory symptoms nor history suggestive of immunosuppression, tuberculosis, or recent travel. CT scan revealed a cavitary lung lesion and a hilar mediastinal mass. Biopsies obtained by bronchoscopy revealed signs of necrosis, granulomas, and the presence of fungal organisms consistent with histoplasmosis. Histoplasma antibodies by complement fixation for yeast antibodies test were positive establishing the diagnosis of chronic cavitary pulmonary histoplasmosis (CCPH). She was then started on itraconazole with good tolerance. On follow-up three months later, a chest CT done along with measurement of inflammatory markers and liver enzymes demonstrated complete clinical recovery. This case emphasizes the importance of expanding our current understanding of the clinical presentation and manifestations of histoplasmosis beyond the conventional assumption that severe disease only affects immunocompromised individuals.

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Isolated Colonic Histoplasmosis in Renal Transplant Recipient Post Covid-19 Infection

Introduction: Histoplasmosis is caused by the dimorphic fungus - Histoplasma capsulatum. The presentation of histoplasmosis is often disseminated, though primary intestinal involvement can rarely be seen in patients with cell mediated immune dysfunction like in patients with AIDS. We report a case of renal allograft recipient, who had history of COVID 19 infection and also underwent anti-rejection treatment for renal graft dysfunction, presented with chronic diarrhea and was diagnosed as a case of colonic histoplasmosis. Method(s): We report a case of 45 years old male who underwent renal transplant surgery one and a half year prior (February 2021) and was having stable graft function on tacrolimus, mycophenolate and steroid. He had history of fever and diarrhea in February 2022 and was diagnosed COVID-19 positive with RT-PCR, and was treated conservatively with intravenous dexamethasone and lowering of immunosuppressants. He had mild graft dysfunction in April 2022;renal graft biopsy had acute T-Cell mediated rejection (Banff Grade 1 B) and was treated with pulse steroids for 3 days. He had complaint of intermittent diarrhea, weight loss and intermittent fever since May 2022. He was evaluated and treated on outpatient basis with empirical oral antibiotics. He was admitted in June 2022 with complaint of high grade fever, loose stools leading to hypovolemic shock and renal dysfunction. He had marked thrombocytopenia and neutrophilic leukocytosis. He showed initial response to intravenous broad spectrum antibiotics and crystalloids, but intermittently symptoms of increased stool frequency and altered consistency were still persisting. Stool studies for ova, cyst, parasites and clostridium difficile were negative. Indian ink staining of stool sample had no evidence of Cryptococcosis. Serum PCR for cytomegalovirus was also negative. CT abdomen showed normal visualized bowel and other viscera. Upper GI endoscopy was unremarkable. Colonoscopy revealed multiple small ulcers with erythematous hue and clean base particularly in ceacum and along ascending colon. Multiple colonic biopsies were taken. Histopathology showed lymphoplasmacytic infilterate in the lamina propria. It also showed increased presence of foamy histiocytes, several of which also showed interacellular organism bearing a pseudocapsule. PAS stain also confirmed budding of these interacellular organisms which is consistent with Histoplasmosis. His HRCT chest revealed hyperinflated lungs, cylindrical bronchiectasis in left upper lobe. Urine for histoplasma antigenuria was negative. Result(s): He was treated with intravenous liposomal amphotericin B for initial two weeks followed by oral itraconazole. His symptoms responded remarkably to the treatment. In view of persisting thrombocytopenia and histoplasmosis his mycophenolate was stopped and tacrolimus was titrated as per trough levels Conclusion(s): Colonic histoplasmosis is associated with significant mortatlity and morbidity. Prolonged use of immunosuprresants, use of antirejection therapies (like high dose pulse methyl prednisolone and bortezomib) and even in some case reports COVID 19 infection have shown to increase the risk of histoplasmosis. Primary and isolated colonic histoplasmosis like in this case can be the atypical presentation which emphasizes the importance of maintaining a low threshold for consideration of histoplasmosis in renal allograft recipients. No conflict of interestCopyright © 2023

Oral Localized Lesion on the Tongue in an Immunocompetent Individual: A Report of a Rare Case With a Comprehensive Review of the Literature.

Histoplasmosis (HP) is a sporadic deep fungal disease that rarely shows oral lesions in various clinical forms. It is usually associated with immunocompromised states, but oral HP has also been reported in many immunocompetent individuals. An unusual case of focal oral HP in a 65-year-old immunocompetent male is reported from New Delhi, India (non-endemic region) presenting with oral ulcerative lesions on the floor of the mouth and lateral surface of the tongue. This case report highlights the importance of prompt diagnosis for the success of the treatment of oral HP along with a thorough review of the literature on HP in immunocompetent patients with oral manifestations. The average age of immunocompetent patients with oral HP is 49.65 years with a marked male predilection. The most common intraoral site is the tongue, followed by the gingiva. Also, five intraosseous cases of HP in immunocompetent patients are reported, among which four are seen in patients from Africa and in a much younger age group (mean: 17.25 years).

A RARE CASE OF HISTOPLASMA CAUSING OBLITERATION OF THE SUPERIOR VENA CAVA AND SUBSEQUENT DEVELOPMENT OF COLLATERAL CIRCULATION

SESSION TITLE: Critical Cardiovascular Disorders SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Physicians are educated on the traditional pathways of sanguineous return of the head and neck through the superior vena cava (SVC). There are known causes of disruption of this system such as SVC syndrome and malignancy causing compression, delayed transit or invasion of these vessels. While compensatory angiogenesis is not a new concept, it has been primarily documented in cases involving coronary artery circulation or congenital heart defects. Here, we present a rare case of the development of left-sided collateral flow in lieu of a right sided SVC with connection to the IVC as a complication of histoplasma infection. CASE PRESENTATION: Our patient was a 67-year female with a past medical history of histoplasmosis, asthma and diabetes who presented with a chief complaint of shortness of breath. Shortly following admission, she was diagnosed with COVID19. In the course of her diagnostic evaluation, she was noted to have significant abnormalities of her thoracic vasculature. More specifically, she had developed calcified granulomas that included a large old calcified granuloma of her right hilum that caused a complete obliteration of her SVC and right middle lobe airways. Her right middle lobe airways had evidence of chronic scarring with development of left sided collateral circulation. Her collateral flow went through her innominate vein into her azygos system and from there into her inferior vena cava and back to her heart. DISCUSSION: It is well established in the literature that histoplasma can lead to scarring and granulomatous changes within lung parenchyma. Our case is unique in the location where the patient developed a granuloma. The close proximity to the SVC over time led to the complete obliteration of the vessel and as a compensatory mechanism her body developed collateral circulation to the left side via her azygous vein and IVC. While we were unable to find similar cases in the literature specifically caused by histoplasma, other phenomena have led to the development of collateral circulation within the lungs. Specifically, Genta et. al. published a case report of an acute pulmonary vein occlusion leading to the development of collateral circulation through the patients' bronchial veins and into the azygous & hemiazygos system similar to our patient. One of the clinical implications for this patient during her hospitalization was the severity of her illness with COVID19. She did require treatment in the intensive care unit. This prompted a discussion among the treatment team regarding developing a plan of action for central line placement should this patient have required vasopressor support. CONCLUSIONS: This case stresses the importance of understanding primary anatomy in order to comprehend potential variants and predict future consequences for patients. It also highlights how sequela of chronic conditions can impact treatment plans. Reference #1: Yu CH, Chen MR. Clinical investigation of systemic-pulmonary collateral arteries. Pediatr Cardiol. 2008 Mar;29(2):334-8. doi: 10.1007/s00246-007-9086-y. Epub 2007 Sep 18. PMID: 17876652. Reference #2: Schaper W. Development of the collateral circulation: History of an idea. Exp Clin Cardiol. 2002 Fall;7(2-3):60-3. PMID: 19649224;PMCID: PMC2719163. Reference #3: Genta PR, Ho N, Beyruti R, Takagaki TY, Terra-Filho M. Pulmonary vein thrombosis after bilobectomy and development of collateral circulation. Thorax. 2003 Jun;58(6):550-1. doi: 10.1136/thorax.58.6.550. PMID: 12775876;PMCID: PMC1746717. DISCLOSURES: No relevant relationships by Alessandra Carrillo No relevant relationships by Chetachi Odelugo No relevant relationships by Shil Punatar No relevant relationships by Ravi Sundaram

A RARE CASE OF ACUTE PULMONARY HISTOPLASMOSIS FOLLOWING COVID-19 INFECTION

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: The most reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis. We hereby present a case of a male who developed acute pulmonary histoplasmosis (APH) after COVID-19 infection. CASE PRESENTATION: 51-year-old male with PMHx of COVID-19 infection 3 weeks ago presenting with worsening shortness of breath. Patient had a complicated hospital course with COVID-19 treated with high doses of methylprednisolone. Patient was local to Arizona and lived on a ranch with livestock. CT chest suggestive of multilobar pneumonia and bilateral pleural effusions (Image 1). Coccidiomycosis serology came back negative. Urinary Histoplasma galactomannan antigen came back positive. The diagnosis of APH after COVID-19 infection was established. Patient was started on voriconazole. His symptoms significantly improved. Patient was discharged to skilled nursing facility with outpatient infectious disease follow-up. DISCUSSION: The current literature on APH in the setting of COVID-19 infection is limited. The few proposed mechanisms are: 1. Liberal use of high dose steroids in COVID-19 leading to reactivation of latent H. Capsulatum. 2. Systemic inflammation in COVID-19 causes interstitial lung damage permitting conidia to proliferate leading to acute infection. The Histoplasma urine antigen test is highly sensitive in the diagnosis of APH, especially in immunocompromised patients like our patient. With this case we would like to increase awareness of the possibility of rare fungal infections like APH in patients with COVID-19, as timely diagnosis and appropriate management can lead to improved outcomes. CONCLUSIONS: Rare fungal infections following COVID-19 have been documented and timely diagnosis and management are imperative to improve patient outcomes. Reference #1: Macedo, Priscila M, et al. APH following COVID-19. Case Report J.Fungi 2021 DISCLOSURES: No relevant relationships by Ali Raja no disclosure on file for Yamin Saddouk;No relevant relationships by Parita Soni No relevant relationships by Lyndie Wilkins Parker

DISSEMINATED HISTOPLASMOSIS IN THE SETTING OF IMMUNOSUPPRESSION DUE TO CROHN DISEASE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus most commonly encountered as an opportunistic infection in immunosuppressed patients, particularly those with HIV/AIDS. However, patients immunosuppressed from other causes can also be at risk. Here is presented the case of a patient on multi-immunosuppressant therapy as treatment for Crohn's disease, who developed disseminated histoplasmosis. CASE PRESENTATION: A 44-year-old male with a past medical history of Crohn's disease (previously been on azathioprine, adalimumab and currently on Prednisone therapy), recently started on infliximab infusion for uncontrolled symptoms of IBD, diabetes mellitus, hypothyroidism, and COVID-19 infection (not requiring oxygen therapy) one month prior to the current admission initially presented to the hospital with chief complaints of exacerbated weakness, myalgias, fevers and diarrhea for 5 days;Symptoms of weakness, myalgias began after first infusion of infliximab and it got progressively worse after the 2nd infusion 2 weeks prior to the admission. White Blood Cell count was 1.1 K/uL, platelet count was 7 K/uL, hemoglobin was 7.9 g/dL. CRP was elevated to 142 mg/L, and ferritin was elevated to 39,000 ug/L. CT abdomen and pelvis demonstrated probable rectosigmoid colitis and splenomegaly. Subsequent chest x-ray demonstrated bilateral opacities with haziness over bilateral lung fields. Respiratory viral panel, stool panel, blastomyces antigen, cryptococcal antigen, toxoplasma antibodies, HIV antibody, CMV PCR, and blood cultures were unrevealing. Urinary histoplasma antigen was positive, and BD-glucan was elevated to over 500 ng/L. EBV panel was positive for reactivation, with EBV DNA 2.02 IU/mL. He was subsequently started on amphotericin B lipid complex, with itraconazole destination therapy. He was treated empirically for pneumocystis jiroveci pneumonia (PJP) with sulfamethoxazole-trimethoprim due to him being on chronic Prednisone therapy. Echocardiogram demonstrated left ventricular ejection fraction (LVEF) of 40%, with diffuse hypokinesis and wall motion abnormalities, posing some question of myocarditis. He was later discharged home in an improved state. DISCUSSION: Disseminated histoplasmosis in the setting of Crohn's disease on chronic immunosuppressive therapy has been very rarely reported,(1) with similar reports in patients on immunosuppressive therapy in the setting of rheumatologic disease being slightly more common.(2) The most commonly involved areas in gastrointestinal histoplasmosis are the terminal ileum and colon,(3) with this patient's rectosigmoid colitis and symptomatology being consistent with this pattern. The patient's myocarditis is also consistent with disseminated histoplasmosis infection. CONCLUSIONS: Clinicians should maintain suspicion for opportunistic infections in patients on immunosuppressive therapy in the setting of critical illness. Reference #1: Bhut, B., Kulkarni, A., Rai, V. et al. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 37, 472–474 (2018). https://doi.org/10.1007/s12664-018-0886-1 Reference #2: Wood KL, Hage CA, Knox KS, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279-1282. doi:10.1164/rccm.200206-563OC Reference #3: Galandiuk S, Davis BR. Infliximab-induced disseminated histoplasmosis in a patient with Crohn's disease. Nat Clin Pract Gastroenterol Hepatol. 2008;5(5):283-287. doi:10.1038/ncpgasthep1119 DISCLOSURES: no disclosure on file for Donald Dumford;No relevant relationships by Abhilash Bhat Marakini No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber

INCIDENCE, CLINICAL CHARACTERISTICS, AND OUTCOMES OF PATIENTS WITH COVID-19 AND FUNGAL COINFECTION

SESSION TITLE: COVID-19: Other Considerations in Management SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: To evaluate the incidence of fungal co-infections clinical characteristics, and outcomes in patients with COVID-19. METHODS: We conducted a retrospective chart review of electronic medical records of 2,639 adult patients admitted for COVID -19 to our health system from April 1, 2020 to December 31, 2021. Demographic data, comorbidities, length of hospital stay, laboratory results including fungal diagnostics, COVID therapeutics and antifungals, need for ICU admission, mechanical ventilation and in-hospital mortality were collected. RESULTS: A total of 45 of 2,639 (1.7%) COVID-19+ patients had a positive fungal test or culture of fungal pathogen and subsequently received antifungal treatment. Of these 25 (55.6%) cases of Aspergillus species were the most prominent, followed by Candida species at 12 (26.7%). Of note, there was one case each of Cryptococcus and Histoplasma (2.2%). COVID-19+ patients with fungal co-infection who survived (18;40%) were significantly younger compared to COVID-19+ patients with fungal co-infection who died (27;60%, p=0.014). Majority of COVID-19+ patients with fungal co-infection were white with average length of hospitalization of 24 days. Those patients who survived had a significantly longer length of hospitalization compared to COVID-19+ patients who died (survived 31 ± 21.5 compared to 19.6 ± 10.4 days, p<0.05). Majority of COVID-19+ patients received steroids, and remdesivir therapy for COVID-19. Antifungal treatment consisted of either voriconazole or micafungin as predominate fungal pathogens were either Aspergillus or Candida spp. CONCLUSIONS: Pulmonary aspergillosis followed by invasive candidiasis were the most common fungal co-infections in COVID-19 patients treated at our institution. In-hospital mortality from all fungal co-infections was 60%. Patients that survived were younger and hospitalized longer compared to those who expired. Need for mechanical ventilation, ICU admission and COVID therapeutics were not significantly different between the survived and expired group of COVID-19 patients with fungal co-infections. CLINICAL IMPLICATIONS: The increased risk and incidence of COVID-19 and fungal co-infection has been noted in a handful of studies with invasive aspergillosis being the most commonly reported fungal co-infection. There have been very few reports of other fungal co-infections including invasive candidiasis, mucormycosis, histoplasmosis, and cryptococcosis. Minimal incidence data has been reported on co-infection with other opportunistic fungal pathogens such as Histoplasma spp., Pneumocystis jirovecci, or Cryptococcus neoformans. This study supports previous findings of increase risk of Aspergillosis, but also show incidence of Histoplasmosis and Crytpococcal fungal infections. These fungal infections may be under reported in COVID-19 and may warrant further research. DISCLOSURES: No relevant relationships by Christopher Destache No relevant relationships by Rutendo Jokomo-Nyakabau No relevant relationships by Dorothy Kenny No relevant relationships by Paul Millner No relevant relationships by Anny Nguyen No relevant relationships by Mohammad Selim No relevant relationships by Richard Swaney No relevant relationships by Manasa Velagapudi

INVASIVE PULMONARY FUSARIOSIS WITH SUPERIMPOSED HISTOPLASMOSIS IN AN IMMUNOCOMPETENT HOST

SESSION TITLE: Complicated Chest Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Fusarium species (FS) are large filamentous fungi widely distributed in soil and plants that are well-known to cause human infections ranging from superficial to disseminated predominantly depending on the host's immune system. Histoplasma capsulatum (HC), on the other hand, is a dimorphic fungus found in soil contaminated with bird or bat droppings, such as caves, where most infections are asymptomatic or self-limited. We present a case of an immunocompetent patient who developed long-term pulmonary sequelae after a co-infection pneumonia with FS and HC. CASE PRESENTATION: 47-year-old man, non-smoker with history of Myasthenia Gravis presents to the emergency department with worsening shortness of breath and sporadic episodes of fever over the course of 3 weeks. The patient claimed to have gone cave-exploring and worked as an air-condition technician. During the previous three years, he reports progressive dyspnea on exertion, fatigue, and a constant dry cough that required multiple hospitalizations which was treated as Myasthenic Crisis. Clinical exam was remarkable for diffuse rales on bilateral lungs with a resting hypoxia of 82-84%. Laboratories showed elevated inflammatory markers with no leukocytosis or neutropenia. Chest-x-ray revealed increased pulmonary markings and chest CT demonstrated diffuse bilateral ground-glass opacities with septal thickening and innumerable millimetric pulmonary nodules of unclear distribution. Extensive infectious, immunologic, and rheumatologic workup were negative. He underwent a bronchoscopy with broncho-alveolar lavage (BAL) which showed FS and HC on cytology. Therefore, intravenous liposomal Amphotericin B was given for 2 weeks followed by a long-course of oral Voriconazole resulting in marked improvement of symptoms, yet he remained with limited physical activity due to exertional hypoxia of less than 80%. Pulmonary function tests revealed mixed obstructive-restrictive disease. DISCUSSION: To our knowledge, this case represents a novel and rare presentation of invasive pulmonary fusariosis with superimposed histoplasmosis in an immunocompetent host. Our patient had environmental exposure for years with subsequent chronic and progressive respiratory symptoms, however, with no evidence of immunosuppression. Imaging findings were non-specific which difficulted the diagnosis. Nonetheless, the patient was given directed antifungal therapy as a result of the BAL's histopathologic findings with improvement of symptoms. CONCLUSIONS: Regardless of the immunologic status, invasive fungal pneumonia should be considered in patients with prolonged environmental exposure and non-specific chest imaging abnormalities. Reference #1: Chae, S. Y., Park, H. M., Oh, T. H., Lee, J. E., Lee, H., Jeong, W. G., & Kim, Y.-H. (2020). Fusarium species causing invasive fungal pneumonia in an immunocompetent patient: a case report. Journal of International Medical Research. https://doi.org/10.1177/0300060520976475. Retrieved March 18, 2022. Reference #2: Kauffman, C. A. (2022). Diagnosis and treatment of pulmonary histoplasmosis. In Bogorodskaya, M. (Ed.), UpToDate. Retrieved March 18, 2022, from https://www.uptodate.com/contents/diagnosis-and-treatment-of-pulmonary-histoplasmosis. Reference #3: Poignon, C., Blaize, M., Vezinet, C., Lampros, A., Monsel, A., & Fekkar, A. (2020). Invasive pulmonary fusariosis in an immunocompetent critically ill patient with severe COVID-19. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 26(11), 1582–1584. https://doi.org/10.1016/j.cmi.2020.06.026. Retrieved March 18, 2022. DISCLOSURES: No relevant relationships by Juan Adams-Chahin No relevant relationships by Jorge Barletta Farias No relevant relationships by Gabriel Galindez De Jesus No relevant relationships by Camille Gonzalez Morales No relevant relationships by manuel hernandez No rele ant relationships by Enrique Leal No relevant relationships by Arelis Morales Malavé No relevant relationships by Ruth Santos Rodriguez

SUBACUTE PULMONARY HISTOPLASMOSIS DISGUISED AS COVID-19 IN A HEALTHY YOUNG MALE

SESSION TITLE: Pathology Identifying Chest Infections Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pulmonary histoplasmosis typically affects immunocompromised individuals. Symptomatic infection in immunocompetent patients is rare, however, important risk factors include living in an endemic region and the size of inoculation. We present a case of subacute pulmonary histoplasmosis in a healthy young male and discuss how availability bias during the COVID-19 pandemic may pose challenges in the diagnosis. CASE PRESENTATION: A healthy 30-year-old male presented to our hospital complaining of left flank and bilateral chest pain for one week. The patient returned from Veracruz, Mexico three weeks prior after spending two months there studying to become a chef. While in Mexico, the patient experienced low-grade fevers, night sweats, and pleuritic chest pain for which he was treated with steroids and antibiotics for presumed COVID-19 infection despite negative testing. Treatment provided the patient temporary relief, however, some of his symptoms returned prompting him to present to the emergency department. Upon presentation, the patient was afebrile and had a normal resting pulse oximetry. CT angiogram of the chest demonstrated three lung nodules and prominent mediastinal lymphadenopathy. A complete infectious and rheumatologic workup was performed. BAL, transbronchial biopsies and EBUS-TBNA were performed. Lung biopsy showed reactive pneumocytes, focal intra-alveolar fibrinous material, congestion, and hemorrhage. Lymph node cytology revealed an aggregate of necrotizing and nonnecrotizing granulomas and GMS stain was positive for yeast. Fungitell and Histoplasma antibodies returned positive. The patient was discharged on Itraconazole and followed up with infectious disease specialists two months later in stable condition. DISCUSSION: Patients with subacute pulmonary histoplasmosis and viral pneumonia may present with similar clinical and radiological findings making the diagnosis arduous. In addition, the prevalence of COVID-19 pneumonia makes clinicians susceptible to using availability bias and further obscuring diagnosis. Some clues that help differentiate subacute pulmonary histoplasmosis include a longer duration of symptoms, pulmonary nodules, and mediastinal and hilar adenopathy. CONCLUSIONS: While pulmonary histoplasmosis is an uncommon finding in immunocompetent patients, suspicion should be raised in patients from endemic regions. Despite the COVID-19 pandemic, clinicians should avoid anchoring biases and keep differential diagnoses in mind. Reference #1: Azar MM, Hage CA. Clinical Perspectives in the Diagnosis and Management of Histoplasmosis. Clin Chest Med. 2017;38(3):403-415. doi:10.1016/j.ccm.2017.04.004 Reference #2: Staffolani S, Buonfrate D, Angheben A, et al. Acute histoplasmosis in immunocompetent travelers: a systematic review of literature. BMC Infect Dis. 2018;18(1):673. Published 2018 Dec 18. doi:10.1186/s12879-018-3476-z DISCLOSURES: No relevant relationships by Steven Douedi No relevant relationships by Justin Ilagan No relevant relationships by TAIMOOR KHAN No relevant relationships by Romany Nightingale No relevant relationships by Mihir Odak No relevant relationships by Noor Salam No relevant relationships by Kameron Tavakolian

Updates on Histoplasmosis in Solid Organ Transplantation.

Purpose of Review: Histoplasmosis remains a challenging infection in solid organ transplantation. This review provides a topic update with emphasis on the changing Histoplasma epidemiology, along with new diagnostic and treatment innovations. Recent Findings: Recent years have observed expanding Histoplasma geographic distribution due to climate change, environmental disruption, and host factors. Early clinical experience also suggests a relationship between COVID-19 infection and histoplasmosis, particularly among immunocompromised individuals. Advances in diagnostic methods, such as newer enzyme immunoassays and molecular techniques, have broadened the capability for expedient and highly specific pathogen identification. Novel drug innovations, including the development of new formulations of existing antifungal agents, extended-spectrum azoles and new antifungal drug classes have expanded therapeutic options. Summary: Advances in organ transplantation have largely outpaced those for histoplasmosis. However, these emerging insights enhance our understanding of this pathogen and management of clinical infection, particularly for transplant recipients with a higher incidence and severity of disease.

AN UNUSUAL CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS ASSOCIATED WITH M.CHIMAERA OR LARGE CELL NEUROENDOCRINE CARCINOMA

CASE: 56-year-old Caucasian male presented to the hospital with worsening weakness, exertional dyspnea, dry and nonproductive cough, and a 5-pound weight loss in 2 weeks associated with loss of appetite. He has a significant medical history of mitral valve repair in July 2014, status post bioprosthetic mitral valve replacement in August 2019- culture-negative treated with ceftriaxone, vancomycin, and doxycycline for 6 weeks complicated with CVA, atrial flutter, tobacco abuse, alcohol abuse. His shortness of breath worsened quickly with O2 saturations dropping to 85% and had to be placed on BiPAP followed by high flow nasal cannula/ noninvasive ventilation and became febrile. He was then transferred to ICU for acute hypoxemic respiratory failure. Differentials could be very broad ranging from infections like visceral leishmaniasis, atypical/tuberculous mycobacteria, histoplasmosis, Ehrlichia, Bartonella, Brucella, adeno, disseminated HSV, hematological like Langerhans cell histiocytosis, multicentric Castleman disease. In this patient, differentials included hemophagocytic lymphohistiocytosis, COVID-19. Covid was negative x2. His lab abnormalities as well as diagnostic testing revealed hemophagocytic lymphohistiocytosis. He was empirically started on antibiotics and dexamethasone 20 mg to be continued for 2 weeks then taper if the patient has continued improvement. Dexamethasone was tapered over 8 weeks. On later admissions, Carious test was positive for M. chimaera, and core biopsy of the lung nodule showed large cell neuroendocrine carcinoma. IMPACT/DISCUSSION: Hemophagocytic lymphohistiocytosis (HLH) is a rare but very dangerous condition, characterized by abnormal activation of the immune system, causing hemophagocytosis, inflammation, and potentially widespread organ damage. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity, is most commonly seen in children. Secondary HLH is commonly associated with infections or malignancies. Most current information on diagnosis and treatment is based on pediatric populations. The HLH-2004 diagnostic criteria are the most commonly used diagnostic criteria and were developed for children;but used in adults as commonly as in children, although there is a gap in the knowledge. The HLH-2004 diagnosis criteria state that diagnosis of HLH can be established if either a molecular diagnosis is made consistent with HLH or diagnostic criteria for HLH is fulfilled, which includes meeting 5 of 8 criteria. These are lab and clinical findings including fever, splenomegaly, significant cytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in bone marrow/spleen or lymph nodes, low or no NK cell activity, ferritin >500 ug/L or sCD25 >2400 U/mL. CONCLUSION: HLH is a disease that needs to be diagnosed and treated promptly, it is fatal otherwise. Treatment is mostly tailored to the patient's root cause, treat the cause, and symptomatic treatment with dexamethasone and etoposide.

An Unusual Case of Secondary Hemophagocytic Lymphohistiocytosis in a Patient Diagnosed With Triple Infection: COVID-19, HIV, and Histoplasmosis.

In this study, we present a unique instance of a patient who developed hemophagocytic lymphohistiocytosis secondary to a triple infection with coronavirus disease 2019 (COVID-19), HIV, and histoplasmosis. We emphasize the proinflammatory dysregulations driving the severity of COVID-19 infection in this setting and highlight the importance of early diagnosis and targeted therapy of underlying conditions as a method to increase the chance of survival.