Donor-derived endemic mycoses after solid organ transplantation: A review of reported cases.

BACKGROUND: Donor-derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor-derived infections (DDI) were included. RESULTS: Twenty-four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor-derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2-35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4-48) months after transplantation. The single reported possible donor-derived talaromycosis occurred in a man whose organ donor had at-risk travel to Southeast Asia. Collectively, the majority of donors had high-risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor-derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%). CONCLUSION: Donor-derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.

Histoplasmosis in the anal canal: case report and literature review

We herein present the case of a patient with anal condylomatosis concomitant with histoplasmosis, whose diagnosis was only possible through the collection of material and the subsequent evidence of a primary pulmonary focus. Histoplasmosis is a fungal disease whose contamination occurs through the respiratory route, and it can spread to the digestive tract, but the anus is rarely affected. It is important to have a high degree of suspicion to make the diagnosis, especially in immunosuppressed patients.

Histoplasmosis pulmonar cavitada en un paciente pediátrico: reporte de caso / Acute cavitated pulmonary histoplasmosis in a pediatric patient: a case report

La histoplasmosis es una micosis producida por el Histoplasma capsulatum. Esta condición es endémica en Estados Unidos, Suramérica, América central y África. Suele presentarse en todas las edades, pero en niños; en especial en aquellos inmunodeprimidos, se han descrito presentaciones graves o atípicas. Se presenta el caso de un paciente de 16 años con antecedentes de trasplante renal, que inicia con síntomas respiratorios inespecíficos, tos y alzas térmicas intermitentes. La radiografía de tórax mostró una imagen de condensación cavitada en el lóbulo superior izquierdo, por lo que se realiza una fibrobroncoscopia, lavado broncoalveolar y cultivos para patógenos habituales, micobacterias y hongos, lográndose aislar al Histoplasma capsulatum. EL objetivo de este trabajo es el de resaltar la consideración de histoplasmosis como diagnóstico diferencial de lesiones cavitadas en parénquima pulmonar en pacientes inmunodeprimidos con la presentación de un caso clínico.

Histoplasmosis is a mycosis caused by Histoplasma capsulatum. This condition is endemic in the United States, South America, Central America, and Africa. It usually occurs in all ages, but in children, especially those immunosuppressed, serious or atypical presentations have been described. We present the case of a 16-year-old patient with a history of kidney transplantation that began with nonspecific respiratory symptoms, cough, and intermittent fever peaks. Imaging findings suggestive of cavitation were found, which by means of a fiberoptic bronchoscopy and bronchoalveolar lavage study isolated Histoplasma capsulatum by means of a deep mycosis culture. The main interest of the case presented is the consideration of histoplasmosis in the presence of cavitated lesions in the lung parenchyma in immunosuppressed patients.

Reintroduction of immunosuppressive medications in pediatric rheumatology patients with histoplasmosis: a case series.

BACKGROUND: Children with rheumatic diseases (cRD) receiving immunosuppressive medications (IM) are at a higher risk for acquiring potentially lethal pathogens, including Histoplasma capsulatum (histoplasmosis), a fungal infection that can lead to prolonged hospitalization, organ damage, and death. Withholding IM during serious infections is recommended yet poses risk of rheumatic disease flares. Conversely, reinitiating IM increases risk for infection recurrence. Tumor necrosis factor alpha inhibitor (TNFai) biologic therapy carries the highest risk for histoplasmosis infection after epidemiological exposure, so other IM are preferred during active histoplasmosis infection. There is limited guidance as to when and how IM can be reinitiated in cRD with histoplasmosis. This case series chronicles resumption of IM, including non-TNFai biologics, disease-modifying anti-rheumatic drugs (DMARDs), and corticosteroids, following histoplasmosis among cRD. CASE PRESENTATION: We examine clinical characteristics and outcomes of 9 patients with disseminated or pulmonary histoplasmosis and underlying rheumatic disease [juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and mixed connective tissue disease (MCTD)] after reintroduction of IM. All DMARDs and biologics were halted at histoplasmosis diagnosis, except hydroxychloroquine (HCQ), and patients began antifungals. Following IM discontinuation, all patients required systemic or intra-articular steroids during histoplasmosis treatment, with 4/9 showing Cushingoid features. Four patients began new IM regimens [2 abatacept (ABA), 1 HCQ, and 1 methotrexate (MTX)] while still positive for histoplasmosis, with 3/4 (ABA, MTX, HCQ) later clearing their histoplasmosis and 1 (ABA) showing decreasing antigenemia. Collectively, 8/9 patients initiated or continued DMARDs and/or non-TNFai biologic use (5 ABA, 1 tocilizumab, 1 ustekinumab, 3 MTX, 4 HCQ, 1 leflunomide). No fatalities, exacerbations, or recurrences of histoplasmosis occurred during follow-up (median 33 months). CONCLUSIONS: In our cohort of cRD, histoplasmosis course following reintroduction of non-TNFai IM was favorable, but additional studies are needed to evaluate optimal IM management during acute histoplasmosis and recovery. In this case series, non-TNFai biologic, DMARD, and steroid treatments did not appear to cause histoplasmosis recurrence. Adverse events from corticosteroid use were common. Further research is needed to implement guidelines for optimal use of non-TNFai (like ABA), DMARDs, and corticosteroids in cRD following histoplasmosis presentation.

Combining urine antigen and blood polymerase chain reaction for the diagnosis of disseminated histoplasmosis in hospitalized patients with advanced HIV disease.

Disseminated histoplasmosis (DH) is endemic in Latin America and the Caribbean where diagnostic tools are restricted. We carried-out a 1-year prospective cohort study at a referral hospital in São Paulo, Brazil. Participants had > or =18 years old, were hospitalized due to any indication and had CD4+ < 200 cells/µl. A urine commercial monoclonal Histoplasma galactomannan enzyme-linked immunosorbent assay (IMMY, Norman, OK, USA) and 'in house' Histoplasma blood nested PCR were performed in all cases. Probable/proven DH cases were defined according to international guidelines. Conventional mycological methods were available in routine conditions to investigate suspected DH cases. Treatment of participants followed the institutional routine. One-hundred six participants were included. Median age (interquartile range [IQR]) was 39.5 years (30.0-47.3) and 80 individuals (75.5%) were males. Median (IQR) CD4 cell count was 26.5 (9.4-89.3) cells/mm3. DH was diagnosed in 8/106 patients (7.5%). Antigen assay and/or PCR were positive in 4.7% (5/106) of patients. The antigen assay and/or PCR identified 37.5% (3/8) of DH cases, which had not been diagnosed with conventional mycological methods, but had clinical manifestations compatible with HD. In conclusion, the use of Histoplasma urine antigen and Histoplasma blood PCR guided by CD4 status contributed to the diagnosis of DH in hospitalized individuals. These assays were complementary to conventional mycologic methods and are urgently needed in our setting. LAY SUMMARY: In this prospective cohort study carried-out in a referral center in São Paulo, Brazil, we found a high frequency of AIDS-related disseminated histoplasmosis (8/106, 7.5%). We used urine antigen test and blood PCR assay to improve the diagnosis of this opportunistic disease.

Concomitant onset of systemic lupus erythematosus and disseminated histoplasmosis: a case-based review.

INTRODUCTION: Concomitant infections during the debut or relapse of systemic lupus erythematosus are a common scenario, due to multiple mechanisms including the use of immunosuppressive drugs and autoimmunity per se. Invasive fungal infections are rare in systemic lupus erythematosus and are associated with profound immunosuppressed states. Disseminated histoplasmosis in patients with lupus has rarely been reported and the concomitant presentation of both entities is exceptional. METHODS: We describe a case and performed a literature review in order to identify all case reports. A literature search was carried out using in PubMed/MEDLINE, EMBASE and Google Scholar (the first 200 relevant references) bibliographic databases. All available inclusion studies from January 1968 through July 2020. All data were tabulated, and outcomes were cumulatively analyzed. RESULTS: Thirty-one additional cases were identified. Disseminated histoplasmosis was the most common clinical presentation and most cases have been reported in patients with a prior diagnosis of lupus in the setting of moderate to high steroid dose use, usually in combination with some other immunosuppressant. Description at systemic lupus disease onset was only reported in 3 cases with a high associated mortality. In our patient, severe disease activity, significant immunosuppression, malnutrition and multi-organ compromise conditioned the patient's fatal outcome. CONCLUSION: Histoplasmosis can closely mimic activity of lupus. Thus, early clinical recognition is important since a delay in diagnosis and treatment can lead to fatal outcomes.

COVID-19-Associated Histoplasmosis in an AIDS Patient.

Most reports associating fungal infections with COVID-19 have been cases of invasive aspergillosis. Here, we report a case of severe histoplasmosis and COVID-19 infections in an HIV patient in Rio Grande, Southern Brazil. Histoplasmosis must be included as a diagnostic possibility in opportunistic fungal co-infections in COVID-19 patients with AIDS, mainly in endemic areas.

Histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con virus de la inmunodeficiencia humana / Disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus

Introducción: La histoplasmosis es una micosis profunda o sistémica causada por un hongo dimórfico que se puede diseminar principalmente en pacientes con inmunosupresión, como los que tienen diagnóstico de virus de la inmunodeficiencia humana. El síndrome de reconstitución inmune consiste en un empeoramiento paradójico de una condición conocida o de nueva aparición después del inicio de la terapia antirretroviral. Objetivo: Describir un caso de histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con infección por virus de la inmunodeficiencia humana. Caso clínico: Paciente masculino de 32 años con diagnóstico de infección por virus de la inmunodeficiencia humana, con cuadro clínico de tres semanas de evolución. Este cuadro inició posterior al comienzo de la terapia antirretroviral, que consistió en pápulo-nódulos umbilicados diseminados, con compromiso pulmonar; además, tenía histopatología y cultivo positivos para Histoplasma capsulatum sl. y prueba de antigenuria para histoplasma también positiva. Se consideró un diagnóstico de histoplasmosis diseminada con presentación cutánea, fue la expresión de un síndrome de reconstitución inmune por desenmascaramiento. Se inició manejo con anfotericina B liposomal y se mantuvo la terapia antirretroviral; posteriormente se continuó el tratamiento con itraconazol durante 12 meses con mejoría de las lesiones. Conclusiones: El diagnóstico clínico, histopatológico y microbiológico fue oportuno; el paciente presentó una adecuada respuesta al tratamiento. Esta es una micosis curable e incluso prevenible, si se diagnostica a tiempo, se inicia tratamiento precoz y se mantiene la terapia retroviral(AU)

Introduction: Histoplasmosis is a deep or systemic mycosis caused by a dimorphic fungus which may disseminate mainly in immunocompromised patients, such as those diagnosed with human immunodeficiency virus. Immune reconstitution syndrome is a paradoxical worsening of a known condition or a condition appearing after the start of antiretroviral therapy. Objective: Describe a case of disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus infection. Case report: A case is presented of a male 32-year-old patient diagnosed with human immunodeficiency virus with a clinical status of three weeks' evolution. The current status developed after the start of antiretroviral therapy. It consisted in disseminated umbilicated papular nodules with pulmonary involvement, as well as positive Histoplasma capsulatum sl. histopathology and culture, and a positive histoplasma antigen test. A diagnosis of disseminated histoplasmosis with a cutaneous presentation was considered. It was the expression of immune reconstitution syndrome by unmasking. Treatment was started with liposomal amphotericin B, maintaining the antiretroviral therapy. Management was then continued with itraconazole for 12 months with improvement of the lesions. Conclusions: Timely clinical, histopathological and microbiological diagnosis was performed. The patient displayed an adequate response to treatment. This mycosis is curable and even preventable when a diagnosis is made in time, treatment is started early and the retroviral therapy is maintained(AU)

Continuous ambulatory peritoneal dialysis-associated Histoplasma capsulatum peritonitis: a case report and literature review.

BACKGROUND: Fungal peritonitis (FP) is a rare complication of peritoneal dialysis. We herein describe the second case in Asia of Histoplasma capsulatum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). CASE PRESENTATION: An 85-year-old woman with end-stage renal disease (ESRD) who had been on CAPD for 3 years and who had a history of 3 prior episodes of peritonitis presented with intermittent abdominal pain for 2 weeks and high-grade fever for 3 days. Elevated white blood cell (WBC) count and rare small oval budding yeasts were found in her peritoneal dialysis (PD) fluid. From this fluid, a white mold colony was observed macroscopically after 7 days of incubation, and numerous large, round with rough-walled tuberculate macroconidia along with small smooth-walled microconidia were observed microscopically upon tease slide preparation, which is consistent with H. capsulatum. The peritoneal dialysis (PD) catheter was then removed, and it also grew H. capsulatum after 20 days of incubation. The patient was switched from CAPD to hemodialysis. The patient was successfully treated with intravenous amphotericin B deoxycholate (AmBD) for 2 weeks, followed by oral itraconazole for 6 months with satisfactory result. The patient remains on hemodialysis and continues to be clinically stable. CONCLUSION: H. capsulatum peritonitis is an extremely rare condition that is associated with high morbidity and mortality. Demonstration of small yeasts upon staining of PD fluid, and isolation of slow growing mold in the culture of clinical specimen should provide important clues for diagnosis of H. capsulatum peritonitis. Prompt removal of the PD catheter and empirical treatment with amphotericin B or itraconazole is recommended until the culture results are known.

African histoplasmosis in a Guinea Bissau patient with HIV-2: Case report and review.

African histoplasmosis is the relatively unknown infection by Histoplasma capsulatum var. duboisii. It is endemic to Central and West Africa, generally involving the skin with potential for systemic dissemination, and has been described mainly in immunocompetent hosts. We present the case of a 30-year-old Bissau-Guinean man with HIV-2 infection known for 16 years, irregularly treated, admitted with two weeks of fever, diarrhoea and cutaneous lesions. Examination revealed multiple subcutaneous nodes, Molluscum contagiosum-like lesions, generalized lymphadenopathy and painful palpation of the left iliac fossa. Laboratory tests showed severe nonhaemolytic anaemia and CD4+ count of 9/mm3, with normal creatinine and hepatic enzymes. Chest roentgenogram was unremarkable and a research for Mycobacterium tuberculosis by GeneXpert® was negative. Nonetheless, given the lack of further diagnostic tools, a presumptive diagnosis of disseminated tuberculosis was made, and the patient was started on tuberculostatic and antiretroviral drugs. Despite initial improvement, a national shortage of antiretrovirals precluded further treatment, with worsening of the clinical picture, namely an increase in the number and dimensions of the skin lesions. An excisional biopsy of a subcutaneous nodule revealed Histoplasma capsulatum var. duboisii. Unfortunately, due to the unavailability of antifungals, the patient died one week later. To our best knowledge, this is the first confirmed case of an HIV infected patient with African histoplasmosis in Guinea-Bissau.

Laryngeal histoplasmosis in a kidney transplant recipient.

Histoplasma capsulatum is an endemic fungus that most oftenly causes a self-limiting illness but can result in severe infections in immunocompromised patients including pulmonary or extra-pulmonary disease. Rarely it can also cause a chronic progressive infection of the larynx. Herein, we report a case of laryngeal histoplasmosis in a kidney transplant patient who presented with progressive symptoms of several weeks of hoarseness, dysphagia and odynophagia. Laryngoscopic examination revealed thick plaques in the oropharynx with surrounding hyper-erythema and histopathology showed numerous intracellular yeasts forms consistent with H capsulatum. Patient was initiated on treatment with itraconazole. Infection of the larynx due to H capsulatum is highly uncommon and therefore can result in an inappropriate or delayed diagnosis. A review of literature showed four previously reported cases of laryngeal histoplasmosis in patients with solid organ transplant. This is the first case series of laryngeal histoplasmosis in transplant recipients.

Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: A multicenter study.

BACKGROUND: The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH-proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3-35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56-76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6-74.4). In 10.5% of the PDH-proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. CONCLUSIONS/SIGNIFICANCE: We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH.

Disseminated histoplasmosis in pediatric kidney transplant recipients-A report of six cases and review of the literature.

BACKGROUND: We report a case series of histoplasmosis in KTx patients in a children's hospital in an endemic area. METHODS: All KTx cases from January 1, 2002, to August 31, 2016, were reviewed to identify those with disseminated histoplasmosis. RESULTS: The attack rate of histoplasmosis among our KTx patients was 6.9 per 100 cases. The median age at the time of diagnosis was 16 years (11-18). Comorbidities included glomerulosclerosis (3), medullary cystic disease (1), and obstructive uropathy (2) and HIV (1). There were 5 deceased and 1 living-related donor transplants, and no patient had a history of rejection prior to histoplasmosis. Median time from transplant to histoplasmosis was 14.8 months (IQR 2.2-38.3) and 33% occurred in the first year after transplant. Urine and/or serum antigens were positive in all patients. They were either treated with amphotericin B and transitioned to an azole or received azole monotherapy. Most (83%) received chronic suppression with itraconazole. No patients died and relapse occurred in 1 patient after repeat transplant. CONCLUSIONS: KTx patients in endemic areas are at risk for disseminated histoplasmosis. Further study is needed to determine which factors portend the need for fungal prophylaxis in this subset of patients.

Diagnosis and treatment of histoplasmosis in solid organ transplant patients.

PURPOSE OF REVIEW: Unlike immunocompetent hosts, solid organ transplant (SOT) recipients with posttransplant histoplasmosis (PTH) often present with disseminated disease and have an attributable mortality of approximately 10%. In this review, we discuss currently available diagnostic tests and treatment strategies in PTH. RECENT FINDINGS: None of the available tests have a 100% diagnostic accuracy. Histoplasma antigen assays are the most sensitive commercially available tests. However, crossreactivity of histoplasma antigen with aspergillus galactomannan and false positive histoplasma antigen tests because of rabbit antithymocyte globulin may cause difficulty in interpreting positive test results in transplant recipients. Molecular assays such as amplification and sequencing of 'panfungal' portions of the 28S ribosomal RNA from clinical specimens appear to be promising.Lipid formulations of amphotericin B and itraconazole are the drugs of choice in the treatment of PTH. Other extended spectrum azoles also appear to be effective, but, like itraconazole, problems with drug interactions and prolongation of the QTc interval (except for isavuconazole, which shortens the QTc interval) remain. Mycophenolate therapy is associated with severe disease and should be stopped during active disease and, if feasible, calcineurin inhibitors and steroids should be reduced. SUMMARY: A combination of various tests (culture, antigen tests, nucleic amplification tests, etc.) should be used to optimize diagnostic yield. The role of unbiased next generation sequencing for early diagnosis and newer azoles in the treatment needs to be further explored.

Disseminated histoplasmosis in an immunocompetent patient - utility of skin scrape cytology in diagnosis: a case report.

BACKGROUND: Histoplasma capsulatum is a dimorphic fungus predominately found in soils enriched with bird and bat excreta. Although several cases of histoplasmosis have been reported in India, diagnosis using cytology has been done in very few cases. CASE PRESENTATION: We report here a case of disseminated histoplasmosis in a 46-year-old Indian man. CONCLUSION: Skin scrape cytology is a simple, safe, and rapid technique to establish the initial diagnosis, thus promoting early treatment and favorable outcome, in cutaneous fungal infections.

Oral Manifestations Associated to Paracoccidioidomicosis and Histoplasmosis

Objective: To determine the frequency and clinical forms of oral manifestations associated to Paracoccidioidomycosis (PCM) and Histoplasmosis. Material and Methods: 481 medical records of outpatients referred to the Medical Mycology Department were reviewed since 2009 to 2016. Data were analyzed using descriptive statistical methods. Results: 47 (9.77%) cases had oral manifestations, 29 (61.70%) were associated to PCM and 18 (38.29%) to histoplasmosis. For PCM, male-female ratio was 8:1 and 1:1 for histoplasmosis. The average age for PCM was 48 years old and 53 for histoplasmosis. All the PCM patients had more than 1 oral structure affected: 44.82% were gingival lesions and 27.58% palate. In patients with histoplasmosis, 6 (33.33%) were lesions affecting palate and 6 (33.33%) involving tongue. For both entities, painful ulcers and granulomatous-like lesions were the most prevalent clinical forms; however, we observed a wide range of other oral manifestations. Regarding PCM patient's comorbidities, 3 (10.34%) cases had HIV/AIDS, 8 (27.58%) histoplasmosis and 2 (6.89%) carcinomas. Whereas the comorbidities of patients with histoplasmosis, 2 (11.11%) had HIV/AIDS and 1 (5.55%) had carcinoma. Conclusion: In endemic countries for both mycoses, dentists must be aware of patients with mouth lesions, take advantage of epidemiologic clues that suggest risk factors and be acquainted with all the current diagnostic tests in order to make a quick diagnosis and treatment in highly suspicious cases.