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.

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)

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.

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.

Outbreak of Severe Histoplasmosis Among Tunnel Workers-Dominican Republic, 2015.

Background: Histoplasmosis is a fungal infection associated with exposure to bat guano. An outbreak of an unknown severe febrile illness occurred among tunnel workers in the Dominican Republic, and resulted in several deaths. We conducted an investigation to confirm etiology and recommend control measures. Methods: A case was defined as fever and ≥2 symptoms consistent with histoplasmosis in a tunnel worker, July-September 2015. We interviewed workers and family members, reviewed medical records, tested serum and urine for Histoplasma antigen/antibody, and conducted a cohort study to identify risk factors for histoplasmosis and severe infection (intensive care). Results: A crew of 36 male workers removed large amounts of bat guano from tunnels without respiratory protection for a median of 24 days per worker (range, 1-25 days). Median age was 32 years (range, 18-62 years); none were immunocompromised. Thirty (83%) workers had illness that met the case definition, of whom 28 (93%) were hospitalized, 9 (30%) required intensive care, 6 (20%) required intubation, and 3 (10%) died. The median time from symptom onset to antifungal treatment was 6 days (range, 1-11 days). Twenty-two of 34 (65%) workers had laboratory evidence of infection. Conclusions: Severe illnesses and death likely resulted from exposure to large inocula of Histoplasma capsulatum spores in an enclosed space, lack of respiratory protection, and delay in recognition and treatment. Clinician education about histoplasmosis, improved laboratory capacity to diagnose fungal infections, and occupational health guidance to protect workers against endemic fungi are recommended in the Dominican Republic.

Síntomas faríngeos como primera manifestación clínica en un paciente con Histoplasmosis generalizada / Pharyngeal symptoms as first clinical manifestation in a patient with Generalized Histoplasmosis

Introducción: La Histoplasmosis es una enfermedad endémica, que presenta un comportamiento oportunista cuyo germen causal es el Histoplasma capsulatum (HC), considerado un hongo dimórfico. Objetivo: Presentar un caso con el diagnóstico de Histoplasmosis generalizada, cuyas manifestaciones faríngeas fueron el inicio de la enfermedad. Presentación del caso: Se presenta el caso de un paciente, con los síntomas faríngeos que fueron la primera manifestación de la enfermedad, en el que la biopsia permitió llegar al diagnóstico nosológico. Posteriormente presentó otras manifestaciones con aspectos clínicos-microbiológicos de diseminación progresiva. Conclusiones: La Histoplasmosis faríngea es una micosis sistémica infrecuente y de difícil diagnóstico, es preciso un buen interrogatorio y examen físico, en aquellos pacientes con factores de riesgo de enfermedades infecciosas sin diagnóstico aparente y deterioro progresivo de su estado general(AU)

Introduction: The Histoplasmosis is an endemic illness that presents an opportunist behavior in which causal germ is the Histoplasma capsulatum (HC), considered a dimorphic mushroom. Objective: To present a case with the diagnosis of Generalized Histoplasmosis in which pharyngeal manifestations were the beginning of the illness. Presentation of the case: The case of a patient is presented with the pharyngeal symptoms that were the first manifestation of the illness, in which the biopsy allowed to arrive to the diagnostic. Later the patient presented other manifestations with clinical-microbiologic aspects of progressive dissemination. Conclusions: The pharyngeal Histoplasmosis is an uncommon systemic mycosis and with a difficult diagnostic, it is necessary a good interrogation and physical exam, in those patients with factors of risk of infectious illnesses without apparent diagnosis and progressive deterioration of their general state(AU)

Case of disseminated histoplasmosis in a HIV-infected patient revealed by nasal involvement with maxillary osteolysis.

BACKGROUND: Disseminated Histoplasmosis (DH) is a rare manifestation of Acquired Immune Deficiency Syndrome (AIDS) in European countries. Naso-maxillar osteolysis due to Histoplasma capsulatum var. capsulatum (Hcc) is unusual in endemic countries and has never been reported in European countries. Differential diagnoses such as malignant tumors, cocaine use, granulomatosis, vasculitis and infections are more frequently observed and could delay and/or bias the final diagnosis. CASE PRESENTATION: We report the case of an immunocompromised patient infected by Human Immunodeficiency Virus (HIV) with naso-maxillar histoplasmosis in a non-endemic country. Our aim is to describe the clinical presentation, the diagnostic and therapeutic issues. A 53-year-old woman, originated from Haiti, was admitted in 2016 for nasal deformation with alteration of general condition evolving for at least 6 months. HIV infection was diagnosed in 2006 and classified at AIDS stage in 2008 due to cytomegalovirus infection associated with pulmonary histoplasmosis. At admission, CD4 cell count was 9/mm3. Surgical biopsies were performed and ruled out differential or associated diagnoses. Mycological cultures identified Hcc and Blood Polymerase Chain Reaction (PCR) for Hcc was positive. The patient was given daily Amphothericin B liposomal infusion during 1 month. Hcc PCR became negative in the blood under treatment, and then oral switch by itraconazole was introduced. Antiretroviral treatment was reintroduced after a 3-week histoplasmosis treatment. Normalization of naso-maxillar mucosa enabled a palatal prosthesis. CONCLUSION: Naso-maxillar histoplasmosis is extremely rare; this is the first case ever reported in a non-endemic country. Differential diagnoses must be ruled out by conducting microbiologic tools and histological examinations on surgical biopsies. Early antifungal treatment should be initiated in order to prevent DH severe outcomes.

Histoplasmosis diagnosed after arthroscopy of the knee: case report

ABSTRACTFungal arthritis is a rare complication of arthroscopic surgeries, but its possibility should always be considered due its deleterious effects on any joint. Infection caused by the fungus Histoplasma capsulatum is the most common cause of respiratory tract infections by fungi, meanwhile histoplasmosis arthritis is more rare than all other fungal infections. However, their atypical forms of arthritis and the importance of early diagnosis and treatment cannot be over-emphasized. Herein we report a case of knee monoarthritis in an immunocompetent patient with histoplasmosis arthritis following an arthroscopic meniscetomy, diagnosed by synovial biopsy and culture performed during a second arthroscopic procedure. The joint was debrided in this second intervention and the patient received itraconazole initially and fluconazole latter on. The arthritis subsided after 10 months of treatment.

Histoplasmosis diagnosed after arthroscopy of the knee: case report.

Fungal arthritis is a rare complication of arthroscopic surgeries, but its possibility should always be considered due its deleterious effects on any joint. Infection caused by the fungus Histoplasma capsulatum is the most common cause of respiratory tract infections by fungi, meanwhile histoplasmosis arthritis is more rare than all other fungal infections. However, their atypical forms of arthritis and the importance of early diagnosis and treatment cannot be over-emphasized. Herein we report a case of knee monoarthritis in an immunocompetent patient with histoplasmosis arthritis following an arthroscopic meniscetomy, diagnosed by synovial biopsy and culture performed during a second arthroscopic procedure. The joint was debrided in this second intervention and the patient received itraconazole initially and fluconazole latter on. The arthritis subsided after 10 months of treatment.

[Histoplasmosis: the multiple sides of an uncommon disease]. / Istoplasmosi: la multiforme faccia di una patologia rara.

Disseminated histoplasmosis is an invasive fungal infection documented in patients with impaired cellular immunity coming from endemic areas (America, Asia, Africa). We report two cases of disseminated histoplasmosis in AIDS patients paradigmatic of the multifaceted nature of the disease, which may be an expression either of an advanced state of immunosuppression or the immune reconstitution inflammatory syndrome (IRIS).

Chronic progressive disseminated histoplasmosis in a Mexican cockfighter.

We present illustrative images from a Mexican 58-year-old man who had the occupation of cockfighting from childhood and presented with chronic progressive disseminated histoplasmosis with primarily cutaneous manifestations.