Histoplasmosis Capsulatum Research Articles

A rare case of Disseminated Histoplasmosis with Hemophagocytic Lymphohistiocytosis mimicking a flare of Systemic Lupus Erythematosus in a middle-aged man: A Case Report

Abstract Introduction/Objective Disseminated histoplasmosis is a progressive granulomatous disease caused by Histoplasmosis capsulatum which is an intracellular dimorphic fungus endemic to Ohio and Mississippi River valleys in the United States. The progressive spread of the infection to organs is thought to be due to the failure of the activation of the T-cell mediated immune response. Hemophagocytic lymphohistiocytosis is a rare but potentially fatal condition in which histiocytes and lymphocytes build up in and damage organs and other blood cells. Diagnosing Disseminated Histoplasmosis with Hemophagocytic Lymphohistiocytosis in a patient with Systemic Lupus Erythematosus is diagnostically challenging due to the rare presentation. Hence, we are reporting this case to alert physicians to keep a high index of suspicion in such presentations. Methods/Case Report We present a 37-year-old man with a past medical history of Systemic Lupus Erythematosus complicated by Lupus Nephritis on immunosuppressive therapy who presented to the emergency department with hypotension and was admitted for acute kidney injury. Prior to the presentation, he had persistent fever, myalgias, cough, mild shortness of breath, and back pain. CT Chest shows “eggshell” calcification and further parasitology evaluation revealed a diagnosis of histoplasmosis using a blood sample where intracellular Histoplasma organisms were identified. A diagnosis of Hemophagocytic lymphohistiocytosis was made clinically after “Clinical and Testing Criteria” was evaluated. Despite further management, he developed coagulopathy and sepsis which led to his death. Results (if a Case Study enter NA) At autopsy, we found organomegaly of the liver, spleen, and kidneys. Microscopically, these enlarged organs show old fibrotic granulomas and granulomatous inflammation with suspected fungal organisms. Periodic Acid Schiff (Fungus) and Gomori's Methenamine Silver special stain confirm these fungal organisms to be consistent with Histoplasma species (3-5 micron budding yeasts). Conclusion This case report highlights that physicians should be aware of the diagnostic challenge that Disseminated Histoplasmosis with Hemophagocytic Lymphohistiocytosis could pose in patients with Systemic Lupus Erythematosus, especially those on immunosuppression. The clinical presentation could easily mimic a flare of Systemic Lupus Erythematosus, leading to more aggressive immunosuppression. Failure to recognize the infection promptly could lead to grievous complications and sometimes death.

Prosthetic Joint Infection due to Histoplasma capsulatum in a Patient from Trinidad: Workup, Pathology, and Treatment

Histoplasma capsulatum is a rarely reported cause of prosthetic joint infections. This current case report is of a patient from Trinidad, with a history of a right total knee replacement (TKR), who underwent a successful two-stage revision due to a Histoplasmosis capsulatum periprosthetic joint infection (PJI). This case report offers a unique treatment plan to successfully treat Histoplasmosis capsulatum periprosthetic joint infections and emphasizes the importance of obtaining an accurate travel history.

S2409 Histoplasmosis Presenting as New-Onset Ascites in a Crohn’s Disease Patient on Adalimumab

Introduction: Histoplasma capsulatum is the most frequently diagnosed endemic mycosis in the United States. The majority of cases are self-limiting but infections in immunocompromised patients may result in severe pulmonary or disseminated disease. We report a rare case of disseminated histoplasmosis presenting as new- onset ascites due to granulomatous hepatitis in a patient with perianal Crohn’s Disease on Adalimumab. Case description/methods: A 39-year-old white female with perianal but no intraluminal Crohn’s Disease currently on adalimumab and azathioprine presented with cyclical fevers and rapid onset ascites. In the preceding weeks she was noted to have uptrending alkaline phosphatase (600s) with isoenzymes consistent with liver etiology, GGT 162, mildly elevated AST (53) with normal ALT and total bilirubin. Further workup included positive anti-smooth muscle (1:160) and F-actin antibodies. Anti-nuclear and anti-mitochondrial antibodies both returned negative. MRCP demonstrated a circumferential 1.9 x 1.3cm peribiliary mass with segmental biliary duct dilation. Paracentesis with peritoneal fluid analysis demonstrated a low serum-ascites albumin gradient, lymphocytic predominance, and negative cytology, acid-fast stain, tuberculosis PCR, and adenosine deaminase. Transjugular liver biopsy revealed multiple non-necrotizing granulomas surrounded by chronic inflammation, consisting predominantly of lymphocytes and eosinophils. Grocott’s methenamine sliver stain was positive for narrow-based budding yeast, with morphology suggestive of Histoplasma species. Additionally, a quantitative serum Histoplasmosis antigen returned positive at 2.53 ng/ml. Following these findings, a course of IV Amphotericin B was started with eventual transition to PO Itraconazole for 1 year. Discussion: Histoplasmosis capsulatum is a dimorphic fungus that is endemic to the United States, specifically the Ohio and Mississippi River valleys. The majority of infections are subclinical, but when diagnosed are primarily in immunocompromised patients. A high degree of clinical suspicion is required to facilitate early treatment and prevent poor outcomes. Pulmonary histoplasmosis is by far the most common clinical presentation. Progressive disseminated disease is rare, but may involve the liver, skin, adrenals, gastrointestinal tract, central nervous system, and bone marrow. With the use of immunomodulating therapies on the rise, it is important to consider opportunistic infections in patients with atypical presentations.Figure 1.: A: H&E staining at 200x magnification of liver biopsy demonstrating non-caseating granulomas. B: Liver biopsy shows narrow-based budding yeast with positive silver stain suggestive of Histoplasma.

Successful Use of Multidisciplinary Palliative Care in the Outpatient Treatment of Disseminated Histoplasmosis in an HIV Positive Child

Histoplasmosis is an uncommon opportunistic infection in human immunodeficiency virus (HIV) positive children. The most common form is primary disseminated histoplasmosis, characterized by persistent fever and failure to thrive. A 10-year-old HIV positive girl presented to the Baylor College of Medicine Children’s Foundation—Tanzania Mbeya Center of Excellence (COE) with ulcerated skin lesions and a violaceous facial rash. She also had persistent fevers, severe acute malnutrition, and severe anemia. At diagnosis, the patient was failing first line antiretroviral therapy (ART) with a cluster of differentiation 4 immune cells (CD4) of 24 cells/µL and an HIV viral load (VL) of 196,658 cp/mL. The patient was changed to a second line ART regimen (abacavir, lamivudine, and ritonavir-boosted lopinavir) and received nutritional support, blood transfusions, multiple antibiotics, and meticulous wound care. She also received comprehensive symptom management, psychosocial support, and emergency housing through the COE’s palliative care program. Biopsy of a lesion showed intracytoplasmic organisms consistent with Histoplasmosis capsulatum var capsulatum. The patient was treated with conventional amphotericin B and oral itraconazole and she achieved wound healing as well as immune reconstitution and HIV viral suppression. Amphotericin infusions were given as an outpatient despite the resource constraints of the setting in southwestern Tanzania. Histoplasmosis should be considered in the differential diagnosis of the immunocompromised host with unusual skin manifestations and persistent fever.

Presentations of Chronic Cavitary Pulmonary Histoplasmosis Mimic Infected Cystic Bronchiectasis in an Immunocompetent Host: A Case Report

BackgroundChronic cavitary pulmonary disease and laryngeal involvement are unusual manifestations of Histoplasmosis capsulatum infection, particularly in patients who are not immunocompromised. The presence of fibro-cavitary lesions has been reported as a radiologic presentation of chronic histoplasmosis in patients with pre-existing lung disease. However, there have been few reports of extensive basal predominant cavitary lesions that mimic cystic-bronchiectasis.Case presentationA 65-year-old previously healthy Thai male presented with productive cough, hoarseness, low-grade fever, and weight loss for 6 months. There was no history of significant exposure to Histoplasmosis capsulatum . Tests for HIV and anti-IFN- [[EQUATION]] antibody were negative. Chest CT revealed multifocal thick wall cavities, which were distributed in a peri-bronchial pattern, and some areas of consolidation in both basal lungs. Laryngoscopy revealed an ulcerative lesion of the false vocal cords. Histopathological study of false vocal cords and lung tissue showed granulomatous inflammation with mixed inflammatory cell infiltration and aggregation of histiocytes containing round intracytoplasmic organisms. GMS-staining was positive, but negative mucicarmine-staining was negative. A real-time PCR assay of the lung tissue was positive for Histoplasmosis capsulatum. The final diagnosis was chronic cavitary pulmonary histoplasmosis with laryngeal involvement.ConclusionChronic cavitary pulmonary histoplasmosis is rare, as is laryngeal involvement. However, there have been such cases in endemic areas, even in immunocompetent patients. Chronic histoplasmosis should be considered in patients who present with the extensive basal predominant cavitary-pulmonary lesions that mimic cystic bronchiectasis.

S2236 Disseminating Histoplasmosis Masquerading as an Inflammatory Bowel Disease Flare

INTRODUCTION: Crohn’s disease typically presents with abdominal pain, diarrhea, fatigue, and weight loss. Disease activity can be graded from mild to severe with the aid of various indices such as the Crohn’s Disease Activity Index (CDAI) and the Harvey-Bradshaw Index (HBI). Mild Crohn’s disease is typically managed with “step-up” therapy in which patients are initially trialed on a steroid taper. Mild to severe Crohn’s is managed with a “top-down” approach in which more aggressive medications such as biologics/immunomodulators are initiated with the goal of inducing remission. These medications are effective however they are also inherently immunosuppressive agents which puts patients at risk for opportunistic infection. In this case report, we examine the clinical course of a young female on chronic immunosuppression for Crohn’s disease who suffered life-threatening bowel perforation and pericardial effusion secondary to disseminated histoplasmosis. CASE DESCRIPTION/METHODS: A 32-year-old female with Crohn’s disease on adalimumab and oral prednisone was admitted to MGUH from GI clinic with tachycardia, fevers, nausea and abdominal pain concerning for Crohn’s disease flare. Two days after admission, she was taken to the operating room for the discovery of jejunal perforation. Two weeks later, she returned to OR for recurrence of bowel perforation and received a small bowel resection, ileocecectomy, and end ileostomy. Review of pathology was indicative of Crohn's disease in the jejunum and disseminated histoplasmosis in the ileocecal region. Ambisome was initiated on discovery of these findings. Tachycardia persisted despite fluid resuscitation and echocardiogram revealed pericardial effusion and RV diastolic collapse threatening impending cardiac tamponade. Pericardial fluid revealed histoplasmosis antigen confirming the diagnosis of disseminated histoplasmosis. DISCUSSION: Histoplasmosis Capsulatum is the most prevalent endemic mycosis in the United States. Macrophage and T- Cell immunity plays a crucial role in host defense against the organism hence it is the most common fungal infection seen in patients treated with TNF-alpha inhibitors. Patients with IBD presenting with an acute abdomen can present a diagnostic challenge in distinguishing whether underlying pathology is secondary to uncontrolled inflammatory disease or immunosuppressive therapy. This case reinforces that immunosuppressed patients and those on biologics should always have opportunistic infection ruled out in life threatening illness.Figure 1.: CT Abdomen/Pelvis with IV contrast demonstrates long segment jejunal enteritis and small bowel perforation given numerous loculated pockets of fluid and air within the small bowel mesentery, as well as free air within the anterior peritoneal cavity and free fluid dependently in the pelvis.Figure 2.: CT Abdomen/Pelvis without IV contrast demonstrates intestinal perforation with increasing pneumoperitoneum and ascites. Multiple small foci of free air adjacent to the ileum were also noted that indicate possible site of perforation, but this is hard to verify without the presence of intravenous contrast.Figure 3.: CT Chest without IV contrast demonstrates a moderately sized pericardial effusion, slightly increased compared to prior studies. The imaging study also indicated moderate bilateral pleural effusions with associated compressive atelectasis.

Balloon angioplasty or stent implantation for pulmonary vein stenosis caused by fibrosing mediastinitis: a systematic review.

Fibrosing mediastinitis (FM) is a very rare disease, often caused by histoplasmosis capsulatum, tuberculosis, sarcoidosis, autoimmunity and other diseases, such as IgG 4-related diseases. Fibrous structures in the mediastinum compress the pulmonary artery, pulmonary vein, superior vena cava, esophagus, trachea and cardiac vessels, leading to clinical symptoms. Drug therapeutic modality for pulmonary vein stenosis (PVS) caused by FM is palliative in essence and with limited efficacy, whereas surgical treatment causes high mortality. In recent years, catheter-based treatment to FM-caused PVS has emerged as a promising therapeutic modality, however, the safety and effectiveness of this modality remain unclear. Therefore, a systematic review on the safety and efficacy of the catheter-based treatment for PVS caused by FM was performed, in the hope to shed lights on the alternative therapeutic strategy to this fatal disease.

A Rare Case of Gastrointestinal Histoplasmosis in an Immunocompromised Host

Introduction: Histoplasmosis capsulatum (HC) is a dimorphic fungus common to the Ohio and Mississippi River valleys and is found mainly in soil enriched by avian or bat droppings. It typically presents as an asymptomatic pulmonary infection. Gastrointestinal (GI) involvement is usually unrecognized due to nonspecific symptoms and is thought to be symptomatic in only 3 to 12% of patients. The majority of GI histoplasmosis involves patients with HIV/AIDS. The most common site of GI involvement is the ileocecal region due to the presence of abundant lymphoid tissue. Case Presentation: A 64-year-old man with paroxysmal atrial fibrillation (on warfarin), end stage renal disease on hemodialysis, status post failed transplanted kidney and on chronic immunosuppression presented with a one day history of hematochezia and hematemesis and six weeks of worsening left lower quadrant abdominal pain. CT thorax with intravenous contrast revealed a right lower lobe cavitary mass and a spiculated left upper lobe nodule (Figure 1). Esophagogastroduodenoscopy with enteroscopy revealed old blood in stomach and the endoscope was advanced into the jejunum revealing multiple ulcers (Figure 2). Histopathology from jejunal biopsies was consistent with HC (Figure 3). Histoplasmosis antibodies by complement fixation for yeast and mycelia were positive as was fungal immunodiffusion for Histoplasma M antigen. Histoplasmosis serum antigen was negative. The patient was treated with intravenous amphotericin for presumed disseminated histoplasmosis. He improved clinically with resolution of symptoms and was discharged on oral itraconazole and remains therapeutic five months later.Figure: CT thorax with intravenous contrast showing (A) 21mm right lower lobe cavitary mass (B) and 19mm left upper lobe spiculated nodule.Figure: Ulcerations of proximal (A) and mid-jejunum (B).Figure: Gomori methenamine silver (GMS) stain of jejunal biopsy specimen showing budding yeast form of histoplasmosis capsulatum.Discussion: Histoplasmosis capsulatum is generally seen in immunocompromised hosts. While common at autopsy, gastrointestinal histoplasmosis (GIH) goes unrecognized during life as the symptoms are nonspecific. Patients with GIH most commonly present with abdominal pain and diarrhea, but may also have dysphagia, odynophagia, bowel obstruction or perforation. In this case, the patient presented with clinically significant gastrointestinal bleeding. Upper endoscopy with jejunal biopsies revealed HC. Both the presence of symptomatic GIH and the jejunal location are atypical. This observation in a patient without HIV is exceedingly rare.

Prosthetic Joint Infection Due to Histoplasma capsulatum Complicating a Total Knee Arthroplasty.

Histoplasmosis is a common pathogen but rarely reported in prosthetic joint infections. We present a case of Histoplasmosis capsulatum prosthetic joint infection along with a literature review revealing no guidelines or consensus on surgical and antifungal management. We chose the 2-stage management with an antifungal spacer and systemic oral itraconazole.

Unusual Presentation of Disseminated Histoplasmosis

Histoplasma capsulatum is the most common endemic mycosis in the United States and in rare cases, it could progress to disseminated histoplasmosis in immunocompromised patients. Hepatic manifestations as the primary presenting symptom are uncommon. Fever is the most common symptom in disseminated histoplasmosis, and gastrointestinal symptoms have been reported to be rare, which makes it a diagnostic challenge. We present a 61-year-old female with past medical history of rheumatoid arthritis who had been treated with Plaquenil in the past, presented with abdominal pain, jaundice, fever, chills and poor appetite. Vitals were remarkable for blood pressure of 129/63 mmhg, pulse of 111 beats per minute, temperature of 102.2 °F (oral), respiratory rate of 19 breaths per minute. Physical examination was remarkable for sclera icterus, right upper quadrant abdominal tenderness and jaundice. Her LFTs peaked at AST of 449 U/L, ALT of 745 U/L, ALP of 1045 U/L, total bilirubin of 11.6 mg/dL with direct bilirubin of 2.4 mg/dL, and GGT of 620 U/L. Negative work up included HAV, HBV, HCV, ANA, AMA, ASMA, ANCA, LKM, CMV IgM, EBV IgM, and HIV. APAP, Salicylate, CA 19-9 and CEA levels were within normal range. Abdominal ultrasound was unremarkable. CT and MRI abdomen were remarkable for mild splenomegaly. Patient was started on Vancomycin and Zosyn due to her septic picture, but symptoms did not improve. After few days blood cultures started growing Histoplasmosis Capsulatum, the histoplasma antigen was positive as well. Patient was started on Amophotericin B and Voriconazole and discharged home on Itraconzaole. Follow up appointment 2 months later showed improved LFTs and significant improvement in symptoms, with resolution of her jaundice. Disseminated histoplasmosis in our patient presented with hepatocellular jaundice and was diagnosed with acute hepatitis. Early diagnosis of disseminated histoplasmosis should be made by histoplasma antigen detection in urine and serum. In severe cases, Amphotericin B should be used initially and then it could be switched to Itraconazole due to the more desirable side effect profile. Once symptoms resolve and antigen levels return to normal, treatment can be discontinued. Prospective studies are needed to accurately assess the risk of fungal infections presenting like hepatitis in immunocompromised patients. Hence, clinicians should have a high index of suspicion for disseminated histoplasmosis in immunocompromised patients.

Intramedullary Spinal Cord Compression Caused by Histoplasma capsulatum: A Case Report and Meta-Analysis

Nine cases of intramedullar histoplasmosis have been published in the literature. In six cases, spinal cord compression was associated with brain localization or with contex of disseminated histoplasmosis. The authors are reporting here the third isolated spinal cord compression in immunocompetent 42-year-old African-rabbits breeder, a woman. This case was successfully managed with surgical removal of the lesion associated to itraconazole during 8 months. Intramedullar lesion because of the Histoplasma capsulatum was necrosis granulomatous localized at spinal conus. In conclusion, according to literature data the most frequent spinal cord compression caused by histoplasmosis capsulatum. General risk factors include residence in endemic areas as well as immunosuppression. Endemic areas include Africa, Australia, parts of Eastern Asia, and America (Mississippi, Missouri, and Ohio River valleys). Initial localization was cutaneous. Two histopathological forms reported are abscess and necrotizing granuloma. Management is mainly based on antifungus like itraconazole. Surgery is only necessary for the etiology diagnosis.

A Case of Mistaken Identity - Ocular Histoplasmosis in Florida

Ocular Histoplasmosis Syndrome (OHS) is thought to develop when Histoplasmosis capsulatum spores settle in the choroid, obstruct choroidal vessels and stimulate neovascular growth. OHS is characterized by retinal scarring and Choroidal Neovascularization (CNV). Diagnosis of OHS is usually confirmed through the presence of ‘histo’ spots and retinal swelling. The former is considered presumptive of exposure to histoplasmosis spores and the latter results from the growth of abnormal blood vessels. Multifocal Choroiditis (MFC) mimics the presentation of OHS and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory laboratory testing for H. capsulatum exposure, can avoid misdiagnosis. We report a case of MFC misdiagnosed as OHS in a patient evaluated foroccupational exposure.

Rapid In-situ Hybridization for Dematiaceous Fungi Using a Broad-spectrum Oligonucleotide DNA Probe

Dematiaceous fungi are a diverse group of "darkly" pigmented fungi, which contain melanin in their cell walls and are commonly found in soil worldwide. Although morphology and histochemical stains may aid identification in tissue sections, these means for species identification are not specific. In-situ hybridization (ISH) for abundant fungal rRNA sequences may provide a means for detecting dematiaceous fungi. In this study, a 24-base synthetic biotin-labeled oligonucleotide probe targeting rRNA sequences of a variety of dematiaceous fungi was developed. This probe was tested on a cohort of 29 patients with culture-proven cases of dematiaceous fungal-associated rhinosinusitis (26 allergic fungal sinusitis, 2 fungal ball, and 1 acute invasive fungal sinusitis). Fungal cultures were positive for Alternaria species (10), Bipolaris species (5), Curvularia species (10), Cladosporium species (1), Scedosporium prolificans (1), Scopulariopsis species (1), and dematiaceous species, not otherwise specific (1). ISH showed positivity in fungal organisms in 24 of 29 specimens. ISH was negative in culture-proven examples of Rhizopus species, Aspergillus species, Fusarium species, Paecilomyces species, Histoplasmosis capsulatum, Candida species, and Blastomyces dermatitidis. ISH with a dematiaceous-specific fungal probe may be useful for differentiating dematiaceous fungi from other filamentous fungi in tissues, particularly those responsible for fungal rhinosinusitis.

Delayed diagnosis of disseminated Histoplasmosis capsulatum var. capsulatum infection in AIDS patients in a tuberculosis high endemic country

Delayed diagnosis of disseminated Histoplasmosis capsulatum var. capsulatum infection in AIDS patients in a tuberculosis high endemic country

Pathologic quiz case: multiple cutaneous lesions in a 27-year-old woman. Cutaneous Histoplasmosis capsulatum.

Pathologic quiz case: multiple cutaneous lesions in a 27-year-old woman. Cutaneous Histoplasmosis capsulatum.

Brown-red Pigment Formation by the Mycelial Phase of a Clinical Isolate of Histoplasma capsulatum on Staib Agar : A Preliminary Report

In an HIV-positive patient, the suspected diagnosis of histoplasmosis capsulatum (being the first opportunistic infection indicating AIDS) on the basis of histopathological findings in biopsy material could be proved by culture on Staib agar (syn. Guizotia abyssinica creatinine agar, bird seed agar, etc.). On Staib agar, after 4 weeks at 26 degrees C, there was a cockade-like colony growth, consisting of a white centre, followed by a brown-red pigmented zone surrounded by a border of submerged mycelial growth of tan to brownish colour. Morphologically, there was a moderate formation of tuberculate macroconidia and a heavy formation of microconidia. On neutral Sabouraud's dextrose agar, there was a colony formation without pigment (albino type) free of tuberculate macroconidia and microconidia. Proposals for further investigation of these preliminary observations are made.

Gastrointestinal histoplasmosis presenting as hematochezia in human immunodeficiency virus-infected hemophilic patients

Two hemophiliacs infected with human immunodeficiency virus (HIV) presented with hematochezia secondary to gastrointestinal involvement with Histoplasmosis capsulatum. In one patient who was already receiving fluconazole, the diagnosis was obscured. Both patients responded to amphotericin B followed by intraconazole, with no recurrence of bleeding.

Esophageal fistula complicating mediastinal histoplasmosis: Response to amphotericin B

A 41-year-old man was admitted for evaluation of hemoptysis, dysphagia, and pleuritic chest pain associated with a mediastinal mass. Esophagraphy demonstrated a fistula between the mass and the esophagus. Results of histoplasmosis complement fixation serologic testing suggested an active infection. A methenamine silver stain of a lymph node obtained at mediastinoscopy revealed Histoplasmosis capsulatum. The patient was successfully treated with amphotericin B. This is believed to be the first reported case of an esophageal fistula as a complication of mediastinal histoplasmosis successfully treated with amphotericin B.