Histoplasmosis In Immunocompetent Patient Research Articles

Histoplasmosis in Non-HIV Infected Patients: Another Neglected Infection in French Guiana.

(1) Background: Only a few studies on histoplasmosis in immunocompetent patients have been reported in French Guiana. Therefore, we conducted a detailed clinical description of hospitalized patients suffering with histoplasmosis among non-HIV patients. (2) Methods: This is a single-center, retrospective study conducted at Cayenne Hospital Center between 2008 and 2022. (3) Results: Our cohort was composed of 31 (91%) adults (>18 years of age) and 3 (9%) children, with a sex ratio, M:F, of 1:2. The median age was higher among the women than among the men (70 versus 54 years). The collection of respiratory samples constituted the majority of the performed examinations (38%). Fever (>37 °C) was found in 56% of patients. Surprisingly, the histoplasmosis was disseminated in 82% of patients with an overall case fatality rate of 14.7%. However, immunosuppressive conditions were found in 52% (16/31) of the adult patients, including lymphoid hemopathies, diabetes and immunosuppressive drugs. Conclusions: This disease, though rare and usually considered a mostly benign disease in non-HIV patients, presented a relatively high mortality rate in our cohort. Thus, histoplasmosis should be suspected, screened and investigated as a first line of defense in highly endemic areas, even in immunocompetent and non-HIV patients, especially those with fever or chronic respiratory symptoms.

Disseminated Histoplasmosis in Immunocompetent Patients Presented with Fever of Unknown Origin (FUO)

Histoplasmosis is underreported although in Southeast Asia including Bangladesh is thought to be endemic considering the favorable geo-climatic conditions for the organism. Non-recognition of histoplasmosis is particularly attributed to possible misdiagnosis as tuberculosis (which is endemic here and common in Bangladesh) because histoplasmosis mimics tuberculosis in clinical presentation, imaging and histopathology. Disseminated histoplasmosis mainly occur in immunocompromised patients and rare in immunocompetent subjects. Here we are reporting two cases of disseminated histoplasmosis where both were immunocompetent and presented with FUO. Both patients visited several health centers before coming to us with no definite diagnosis and we got them in a progressive stage. Both were confirmed through bone marrow study. Unfortunately, one of them died from disease progression, sepsis and other complications and another patient gradually improved with treatment (amphotericin B and itraconazole). We are reporting these cases to highlight the fact that disseminated histoplasmosis does occur in immunocompetent patient and may occur with or without pulmonary symptoms. A high index of suspicion is required for diagnosis and delay can often be fatal. J MEDICINE 2023; 24: 59-64

Histoplasmosis of Adrenal Gland: A 5 Years' Review from a Multispecialty Diagnostic Centre.

Objective Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum . Histoplasmosis is considered to be endemic to India, especially the Gangetic belt. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients, whereas isolated adrenal involvement as the presenting manifestation in immunocompetent is uncommon. We aimed to determine the clinicopathological and radiological findings of adrenal histoplasmosis in immunocompetent patients attending a multispecialty diagnostic center referred from different clinics and hospitals. Materials and Methods All tissue samples were initially examined microscopically by performing potassium hydroxide (KOH) wet mounts, followed by culture on two tubes of Sabouraud dextrose agar and phase conversion. Histopathological correlation was done using tissue stains, hematoxylin and eosin, periodic acid-Schiff, and Gomori methenamine silver. Results We evaluated 84 clinically suspected cases radiologically for adrenal mass. The pathological and microbiological work-up was done from these suspected cases. A total of 19 cases were evident from the tissue stain and fungal culture methods. The affected population were mostly above 45 years and male. Seven patients had bilateral adrenal involvement. All these patients received amphotericin B and/or itraconazole treatment, which led to symptomatic improvement in most cases. Conclusion Diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients presenting with nonspecific symptoms, clinical signs, and laboratory and radiological features that often resemble adrenal neoplasms. Clinical specimens, together with fungal culture, must be sent for cytopathology/histopathology for a definite diagnosis and appropriate management.

S2014 Disseminated Histoplasmosis Presenting as Right Colon Lesions in HIV-Negative Patients: Report of Two Cases

Introduction: Histoplasma capsulatum is the most common endemic mycosis in the gastrointestinal tract of immunocompromised hosts. However, it can also present in immunocompetent patients. Terminal ileum and cecum are most commonly affected, recognized on endoscopic examination as inflammation, ulcerated lesions, or polypoid masses. In most patients, gastrointestinal manifestation takes a subclinical disease course. We present 2 cases of immunocompetent patients with colon lesions attributed to disseminated histoplasmosis. Case Description/Methods: First case is a 62-year-old African American woman admitted to the hospital due to abdominal pain, weight loss and poor oral intake. She was found to be anemic. CT revealed a large retroperitoneal mass with central necrosis suspicious for malignancy. Colonoscopy revealed a cecal ulcer (Figure A) with pathology reporting mucosal ulceration associated with granulomatous inflammation. GMS and PAS fungal stain showed small ovoid yeast forms, morphologically compatible with histoplasmosis (Figure B).Biopsy of the retroperitoneal mass was also positive for histoplasma. Second case is a 54-year-old Hispanic man admitted to the hospital with fluid overload secondary to acute renal failure attributed to post-infectious glomerulonephritis. He was also found to have anemia. Colonoscopy showed a 6 mm polyp in the ascending colon removed by cold snare technique (Figure C). Pathology reported polyp fragment with macrophages and numerous 2-4 micron non-budding yeast forms best seen on GMS stain, most consistent with histoplasmosis. CT scan showed prominent retroperitoneal lymphadenopathy. Both our patients were started in itraconazole and are being closely followed by the ID service. Discussion: Disseminated histoplasmosis is usually seen in immunocompromised patients such as those with HIV and medication-induced immunosuppression. GI involvement and symptoms can be diverse. Our first patient presented with a large retroperitoneal mass and cecal ulcer causing her abdominal discomfort. Second patient was much more subtle as histoplasmosis presented as a polypoid lesion. Both patients presented with significant anemia, which prompted endoscopic evaluation. Although the diagnosis of histoplasmosis in immunocompetent patients usually requires a high index of suspicion, gastroenterologists should be familiar with its variable presentations in the GI tract.Figure 1.: a) Histoplasma presenting as cecal ulcer. b) GMS stain showing Histoplasma. c) Polypoid lesion positive for Histoplasma.

P186 Disseminated Histoplasmosis in an immunocompetent patient in a tertiary care center in North India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesHistoplasmosis is a geographically restricted dimorphic fungi that causes disseminated infection in immune-competent as well as immunocompromised patients. Adrenal involvement is seen in disseminated disease but sometimes it may be the only site where then infection can be demonstrated. Early diagnosis and treatment are needed to save the patient from fatal adrenal insufficiency. We present a case of bilateral adrenal histoplasmosis in immunocompetent patient.MethodsA 63-year-old male presented to our hospital with a history of insidious onset of decreased appetite and unintentional weight loss for the last 6 months associated with generalized weakness. Patient had a history of mild to moderate intensity epigastric pain and discomfort which was intermittent in nature. Patient originally belongs to Azamgarh, Uttar Pradesh, but he was residing in Kolkata for the last 8 months.Patient had no history of fever, cough, hemoptysis, jaundice, chronic diarrhea, and steatorrhea. No history of orthostatic hypotension, salt craving, hyperpigmentation, headache, visual field disturbances, polyuria, behavioral changes, episodic headache, palpitation, diaphoresis, systemic hypertension with episodic all four-limb weakness. There was no history of abdominal striae, easy bruisability, difficulty in standing from squatting position. There was no history of tuberculosis among family members. On detailed history, it was revealed that he fed pigeons every day in the slum house where he lived in Kolkata.On the CECT abdomen it was found that there is an ill-defined hypodense enhancing lesion (72 × 52 × 77 mm) in right suprarenal region and bulky, necrosed 25 × 26 × 19 mm lesion in left suprarenal gland associated with multiple nonnecrotic paraaortic and aortic caval lymphadenopathy. He also received empirical anti-tubercular therapy for 15 days in the form of ethambutol and levofloxacin.ResultsIn all, 10% KOH wet mount of crushed smear of adrenal biopsy samples showed tissue debris and small narrow neck budding yeasts. Giemsa stain shows few small budding yeasts. Culture was put in SDA at 25°C and 37°C and incubated. On day 12, growth of colony in 25°C appears as white cottony growth with yellowish white reverse. On day 24, colony appears as buff brown with yellowish brown reverse. LPCB was done from the colony showing presence of characteristic tuberculate macroconidia (8–14) μm in diameter formed on short, hyaline, undifferentiated conidiophores and production of plenty round to pyriform microconidia (2–4 μm) in diameter, occurring on short branches and directly on the sides of the hyphae. Based on the direct microscopy and culture characteristics a diagnosis of Histoplasma capsulatum was given.ConclusionSystemic histoplasmosis is typically acquired through inhalation of microconidia or small hyphal elements in soil contaminated with bird and bat droppings leading to primary infection. This patient only manifested bilateral adrenal involvement with nonspecific symptoms.

ACUTE PULMONARY HISTOPLASMOSIS: A DIAGNOSTIC DILEMMA DURING COVID-19 PANDEMIC

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute histoplasmosis is usually a concern in immunocompromised individuals. In immunocompetent patients, histoplasmosis is generally mild or asymptomatic unless there is inhalation of a large inoculum. Below, we present a case of severe acute pulmonary histoplasmosis in an otherwise healthy, immunocompetent person and discuss the diagnostic challenges it presented during the COVID-19 pandemic. CASE PRESENTATION: A 30-year-old non-smoking Caucasian man with hypertension presented to our hospital with 1 week duration of headache, dyspnea, productive cough and high fever. He was admitted with a provisional diagnosis of COVID-19 pneumonia and started on dexamethasone and empiric antibiotics. He had elevated inflammatory markers. Chest x-ray showed diffuse bilateral interstitial and alveolar opacities. CT chest demonstrated numerous clustered ground glass nodular opacities bilaterally with mediastinal and hilar adenopathy. Subsequently, RT-PCR for SARS-CoV2 returned negative. The patient continued to deteriorate clinically over the next few days. Repeat imaging showed diffuse micronodules with mediastinal adenopathy. Upon further questioning, the patient recalled demolishing a chimney at his parents' house in Michigan 2 weeks prior to admission. The differential diagnosis was broadened to include acute hypersensitivity pneumonitis and fungal infection. BAL, transbronchial biopsies and EBUS-TBNA was performed while escalating steroids. The lung biopsy confirmed Histoplasma. Urine Histoplasma antigen returned positive. The patient was treated with itraconazole with an overlap of steroids for 2 weeks upon discharge. He was readmitted within a week with worsening hypoxia and worsening infiltrates on lung imaging. He was then treated with liposomal amphotericin with gradual clinical improvement. Follow-up 1 month post discharge revealed complete clinical and radiologic resolution. DISCUSSION: Viral pneumonia and acute pulmonary histoplasmosis have overlapping clinical and radiologic features which can make diagnosis challenging. COVID-19 pneumonia typically presents with peripheral ground glass opacities with or without superimposed consolidations. Invasive fungal pneumonia can have a similar appearance on CT usually with additional findings of hilar and mediastinal adenopathy. CONCLUSIONS: This case highlights the challenges involved in diagnosing acute pulmonary histoplasmosis in an immunocompetent individual in the midst of the pandemic. Clinicians should always maintain a wide differential diagnosis to avoid diagnostic delay. REFERENCE #1: Staffolani, S., Buonfrate, D., Angheben, A., Gobbi, F., Giorli, G., Guerriero, M., Barchiesi, F. (2018). Acute histoplasmosis in immunocompetent travelers: A systematic review of literature. BMC Infectious Diseases, 18(1). doi:10.1186/s12879-018-3476-z REFERENCE #2: Duzgun, S. A., Durhan, G., Demirkazik, F. B., Akpinar, M. G., & Ariyurek, O. M. (2020). COVID-19 pneumonia: the great radiological mimicker. Insights into imaging, 11(1), 118. https://doi.org/10.1186/s13244-020-00933-z REFERENCE #3: Klein, M., Khan, M., Salinas, J. L., & Sanchez, R. (2019). Disseminated pulmonary histoplasmosis in immunocompetent patients: A common epidemiological exposure. BMJ Case Reports, 12(3). doi:10.1136/bcr-2018-227994 DISCLOSURES: No relevant relationships by Joseph Arguinchona, source=Web Response No relevant relationships by Michael Kaster, source=Web Response No relevant relationships by Muazzam Mirza, source=Web Response No relevant relationships by Anusha Pinjala, source=Web Response no disclosure on file for Venketraman Sahasranaman;

Intestinal histoplasmosis in immunocompetent patient: An unusual cause of massive small intestine bleeding

Intestinal histoplasmosis in immunocompetent patient: An unusual cause of massive small intestine bleeding

Clinical, biochemical and imaging characteristics of adrenal histoplasmosis in immunocompetent patients in a non-endemic area: A case series

Objective: To document the clinical, biochemical and imaging phenotypes of immunocompetent patients with adrenal histoplasmosis. Methods: The clinical, biochemical and radiologic data of 18 immunocompetent patients [age: 45.00 (39.25, 56.25) years, median (IQR), m/f (16/2)] with adrenal histoplasmosis presenting in the Department of Endocrinology, BSMMU between 2014 and 2020 were retrospectively analyzed. Results: All patients were seronegative for HIV infection, and 27.8% (5/18) had well controlled diabetes mellitus. The median duration of the symptoms was 6.00 (IQR: 4.00, 11.25) months. All had significant weight loss, anorexia and weakness. Fever was present in 61.1% (11/18) patients and night sweat was present in 27.8% (5/18) cases. Hypotension and hyperpigmentation were present in 55.6% (10/18) and 66.7% (12/18) cases, respectively. Three of 18 patients presented with adrenal crisis. Hyponatremia occurred in 55.6% (10/18) cases, but none had hyperkalemia. Thirteen of 18 patients had adrenal insufficiency whereas 83.3% (15/18) had high adrenocorticotropic hormone. CT scan revealed bilateral adrenal enlargement in all cases with oval shape and regular margin. All were hypodense having radiodensity 21-90 hounsfield unit, and 11.1% (2/18) were heterogeneous in contrast enhancement. None had noticeable calcification whereas 1.1% (2/18) cases had central necrosis with peripheral rim enhancement. Hepatomegaly was present in 6 cases, splenomegaly in 3 cases and 5 patients had abdominal lymphadenopathy. Histoplasmosis were confirmed by positive fine needle aspiration cytology of adrenal tissue. Conclusions: Adrenal histoplasmosis should be considered in the list of differentials of bilateral adrenomegaly in immunocompetent individuals even living in non-endemic areas.

DISSEMINATED PULMONARY HISTOPLASMOSIS IN AN IMMUNOCOMPETENT PREVIOUSLY HEALTHY INDIVIDUAL

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Histoplasmosis infection is clinically silent in over 99% of immunocompetent individuals in endemic areas. If symptoms occur most are non-specific and self-limited. However, disseminated histoplasmosis can develop in immunocompetent patients with devastating consequences including significant mortality. CASE PRESENTATION: A previously healthy 45-year-old man presented after 2-3 weeks of worsening dyspnea, non-productive cough, and 20lb weight loss. Outpatient work up showed concern for atypical pneumonia, necessitating treatment with three escalating oral antibiotics showing no improvement prompting admission. He was transferred from an outside hospital intubated progressing toward ARDS requiring vasopressor support. On imaging there was diffuse bilateral peribronchovascular consolidation, groundglass opacities with septal thickening, hepatosplenomegaly, and retroperitoneal lymphadenopathy. Testing included respiratory viral panel positive for rhinovirus, fungitell, fungal blood cultures, urine antigens for histoplasmosis and blastomyces, and bronchoscopy. He was placed on broad spectrum antibiotics and itraconazole. The following day his fungal regimen was advanced to amphotericin B. Three days later his urine histoplasmosis antigen returned positive followed by a positive fungitell and lastly bronchoscopy cultures grew histoplasmosis. He required a month long hospital stay with aggressive ventilator support requiring tracheostomy, severe fevers requiring external cooling, and significant ATN that all slowly improved. Work up for an underlying etiology for possible immunosuppression was unrevealing. He was discharged to an extended care facility where he was liberated from the ventilator within a few days of hospital discharge with later tracheostomy decannulation. He remains on itraconazole 9 months later. He has returned to his regular activities. Most recent imaging shows mild scarring and residual consolidative and nodular opacities. DISCUSSION: Initial generalized symptoms and the rarity of disseminated histoplasmosis in immunocompetent patients can cause it to be overlooked on the differential, leading to significant delays in care. Further delays can occur as testing typically takes multiple days to result and may require bronchoscopy. In this case, a broad differential was considered with a decisive plan of starting the patient on amphotericin days prior to test results likely significantly improving overall prognosis. CONCLUSIONS: Timely diagnosis and treatment of disseminated histoplasmosis requires a broad differential diagnosis coupled with a high level of clinical suspicion. Aggressive treatment may need to begin prior to definitive diagnosis in patients with significant disease burden. Reference #1: Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev. 2007;20(1):115-132. doi:10.1128/CMR.00027-06 Reference #2: Ling Q, Zhu W, Lu Q, Jin T, Ding S. Disseminated histoplasmosis in an immunocompetent patient from an endemic area: A case report. Medicine (Baltimore). 2018;97(29):e11486. doi:10.1097/MD.0000000000011486 DISCLOSURES: No relevant relationships by Benjamin Ramser, source=Web Response No relevant relationships by Joy Wang, source=Web Response No relevant relationships by Steven Young, source=Web Response

Experience of Varied Presentation of Chronic Progressive Disseminated Histoplasmosis in Immunocompetent Patients: A Diagnostic Conundrum.

We report two cases of chronic progressive disseminated histoplasmosis with unusual and rare clinical picture in a patient with no underlying risk factor. One 50-year-old male, presented with hoarseness of voice, chronic cough, with a history of nonresponding anti-tubercular therapy, revealed mucocutaneous lesions on examination. Fungating vocal cord lesions were visualized on bronchoscopy, raised suspicion of carcinoma. The second case, a 22-year-old female, referred to hospital with suspected vasculitis, with complaints of “off and on” fever with decreased oral intake, arthralgia, who later developed generalized nodular skin eruptions. On investigation, human immunodeficiency virus test was found to be negative in both the cases. Histopathological findings of skin biopsy, adrenal and bone marrow aspirates raised suspicion, whereas fungal cultures confirmed Histoplasma infection. Although diagnosis was delayed, but both of them were successfully treated with amphotericin B.

Adrenal Histoplasmosis in Immunocompetent Patients Presenting as Adrenal Insufficiency.

Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, endemic in central and eastern states of United States, South America and Africa. India is considered to be non-endemic area for histoplasmosis. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients; whereas isolated adrenal involvement with adrenal insufficiency as the presenting manifestation of the disease is rare. Twelve patients from a non-endemic area with adrenal histoplasmosis, who were immunocompetent and diagnosed as adrenal histoplasmosis by cytology/histopathology between January 2012 to December 2014 were studied. 18F-FDG PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) was used to assess the extent of involvement. There were a total of 12 immunocompetent males (mean age: 56.9 years). Ten patients had bilateral adrenal involvement and two had a unilateral left adrenal mass. All the patients had histopathologically/cytologically proven adrenal histoplasmosis. Two patients had simultaneous histoplasmosis of other sites, one in the epiglottis and the other in the alveolus. 18F-FDG PET/CT was performed in 10 patients showing high FDG uptake in the adrenals. All these patients received Amphotericin B and/or Itraconazole treatment that led to symptomatic improvement. A diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients who present with nonspecific symptoms, clinical signs, laboratory and radiological features that can resemble adrenal neoplasms. Clinical specimens must be sent for cytopathology/histopathology together with fungal culture for a definite diagnosis and appropriate management.

Fine‐needle aspiration of histoplasmosis in the era of endoscopic ultrasound and endobronchial ultrasound

Histoplasmosis has a textbook cytologic description with numerous intracellular organisms that are readily apparent on routine stains. This is based on series and reports describing histoplasmosis in immunosuppressed patients with disseminated disease. With the advent of ultrasound-guided (US) fine-needle aspiration (FNA) techniques, a marked increase in the cytologic diagnosis of histoplasmosis in immunocompetent patients is noted. A search identified all cytology cases diagnosed with Histoplasma within the past 10 years. Cases were reviewed, along with patient demographic, clinical, and laboratory data. A total of 40 FNA cases of histoplasmosis were identified. Patients ranged in age from 15 years to 86 years. There were 23 female patients and 17 male patients; 37 were immunocompetent and 3 were immunosuppressed. Sixteen patients were being staged for primary tumors of other sites; others presented with primary pulmonary symptoms or histoplasmosis was noted incidentally. Specimens were composed of bland acellular necrosis, most commonly with granulomas (77.5%); only rare intracellular organisms were present on routine stains, and variable extracellular organisms were noted on Grocott methenamine silver stain (GMS) stain. GMS stain on direct smears was found to be more sensitive than cell block. Laboratory studies for urine antigen, yeast, and mycelial antibody (by compliment fixation), serum antibody (by immunodiffusion), and culture were positive in 11.8%, 59.1%, 4.5%, 47.6%, and 3.4% of cases, respectively. In an endemic region, histoplasmosis presents more commonly in immunocompetent patients as localized fibrocaseous disease on FNA and is often identified by high-resolution imaging. FNA is increasingly used in the diagnosis because of endoscopic ultrasound and endobronchial ultrasound. GMS stain on direct smears is more sensitive than cell block. In general, laboratory tests have low sensitivity in this patient population.

Itraconazole in Human Histoplasmosis: Itraconazol bei Histoplasmose des Menschen

A non-comparative open trial with itraconazole in progressive forms of human histoplasmosis was carried out. Thirty two patients who completed 6 months of treatment were included; 29 suffered the chronic disseminated form; 2 exhibited a chronic pulmonary histoplasmosis and one patient presented a subacute disseminated form. Thirty patients were males and 2 females; their ages ranged from 37 to 78 years old (average 56.9). The following underlying diseases were registered: hepatopathies: 12 cases; endocrinopathies and steroid therapy: 13 cases; chronic obstructive pulmonary disease: 10 patients; malignancies: 3 cases; long treatment with psychotropic drugs; 2 cases and 1 immunodeficiency of unknown origin. The therapeutic schedule applied was: 100 mg/day, orally, during 2 months, followed by 50 mg/day for another four months. Twenty-nine patients achieved clinical cure, two showed a striking improvement (both had the chronic pulmonary form) and the treatment could not be evaluated in 1 case. A follow-up of longer than a year was registered in 23 cases, one died as a consequence of mesothelioma and another due to renal impairment, and no relapses were observed. A decreasing complement fixation titer (of more than 2-fold) was observed in 19 cases; 8 of 10 patients with negative skin tests turned positive and the erythrocyte sedimentation rate was reduced to more than a half in 24 cases. Concerning side-effects, a mild, transient and asymptomatic rise of the hepatic enzymes was registered in 9 patients. It seems that itraconazole will be the drug of choice in the treatment of human histoplasmosis in immunocompetent patients.