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Background Hemophagocytic lymphohistiocytosis (HLH) is considered a rare disease with high morbidity and mortality risks. Most research on this disease is conducted in pediatric settings. Therefore, this study aimed to describe the clinical characteristics, laboratory findings, and outcomes related to HLH in people living with human immunodeficiency virus (HIV)/AIDS) and disseminated histoplasmosis. Methods A retrospective and descriptive study was conducted in a tertiary hospital in México City from January 2018 to December 2022, including people living with HIV who had disseminated histoplasmosis confirmed through direct microbiological or immunological methods with an HScore ≥169 or who met 5 of the 8 HLH-2004 criteria. Results HLH occurred in 36.1% (n = 26) of patients with HIV and disseminated histoplasmosis; the majority were men (84.9%), and their mean age (standard deviation) was 30.19 (5.6) years. The most frequent clinical manifestations were hepatomegaly (100%), fever (96.2%), and dyspnea (84.6%). The most common biochemical changes were hyperferritinemia (100%), elevated lactate dehydrogenase (100%), and bicytopenia (61.5%). Partial thromboplastin time (P =.012) and prothrombin time (P =.004) were associated with the 30-day mortality rate, and the 30-day survival rate was 65.4%. Conclusions We detected a high frequency of HLH; therefore, we encourage physicians to use diagnostic prediction tools (HLH-2004 and HScore criteria) in each reassessment for timely detection. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a fungal infection most frequently seen in immunocompromised patients. It is endemic in Central and South America and in Africa. The infection is usually asymptomatic in a healthy individual. Extrapulmonary dissemination can be seen in immunocompromised hosts. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, mimicking Crohn's disease or malignancy. We describe the case of a 36-year-old healthy man from Cameroon, living in Switzerland for 13 years and without any medical nor surgical history, who presented peritonitis not responding to antibiotics. CT-scan showed bowel obstruction and signs of peritonitis. We opted for an explorative laparoscopy, which was converted to laparotomy with extensive adhesiolysis. Diagnostic of histoplasmosis was confirmed by histology and PCR analysis on biopsy. To our knowledge, this is the first described case of peritonitis as main outcome of a disseminated histoplasmosis involving the peritoneum in an immunocompetent patient. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a granulomatous infection caused by dimorphic fungus-Histoplasma capsulatum. Ocular involvement is mainly in the form of retinal or choroidal involvement as presumed ocular histoplasmosis mostly in immunocompromised patients. Conjunctival, scleral, and adnexal involvement is rarely reported. We report a case of disseminated histoplasmosis with conjunctival lesion as the initial clinical manifestation clinching the diagnosis. [ABSTRACT FROM AUTHOR]

Background Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. Methods Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. Results A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P =.69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P =.82). Conclusions One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access. [ABSTRACT FROM AUTHOR]

Histoplasmosis is caused by Histoplasma capsulatum and, although endemic in large parts of the world, is often underrecognized in many locations. In addition to underrecognition, inadequate availability of diagnostic tests is a major contributor to poor outcomes in disseminated disease in people with HIV. For those with advanced HIV and disseminated disease, antibody testing is less useful. Culture and histopathology can be useful in this situation, but each has limitations, including variable sensitivity by site and, in the case of culture, the need for a biosafety level three laboratory and a long period of growth. Antigen testing has proven useful for disseminated histoplasmosis due to the excellent sensitivity of urine. Yet, turnaround is slower than ideal due to use in a limited number of centers. The development of lateral flow assays has the potential to make for true rapid point-of-care assays for histoplasmosis, but in order to meet that promise, the tests must be widely available and affordable. [ABSTRACT FROM AUTHOR]

Background: Since 2020 the World Health Organization (WHO) recommends Histoplasma antigen detection for the diagnosis of disseminated histoplasmosis (DH) in people living with HIV (PLHIV). Objective: Here we aimed to optimise the IMMY's Clarus® Histoplasma GM enzyme immunoassay (EIA), evaluating the best cut‐off in the semi‐quantitative (SQ‐HGM EIA), also known as 'calibrator cut‐off procedure'. Methods: The optimization was done using the quantitative standard procedure (Q‐HGM EIA), also known as 'standard curve procedure', as reference test. A retrospective study from an endemic area of DH in southern Brazil was carried out including 264 patients investigated for DH using the test. Receiver Operator Characteristic curve was plotted, and sensitivity and specificity of the SQ‐HGM EIA were calculated. Results: The study included 24 positive (values ≥ 0.20 ng/ml) and 240 negative patients by the Q‐HGM EIA. According to the manufacturer SQ‐HGM EIA protocol, the new SQ‐HGM EIA cut‐off of 0.8 EIA units was validated, resulting in sensitivity and specificity of 88% and 98.7%, respectively. Conclusion: Our study pioneers and brings important data about the optimization of the Histoplasma antigen testing for the diagnosis of DH in a population from Southern Brazil. This optimization also reduced the amount of reagents used, lowering the cost associated with testing. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis is usually considered a rapidly progressive fatal illness with poor outcomes. It is of two types: primary or familial and secondary. In patients with HIV, opportunistic infections are the secondary triggers of HLH. First line of management of infection associated HLH is treatment of the underlying infection. Here, we present a case of HLH in HIV infection due to disseminated histoplasmosis managed with liposomal amphotericin B, who required immunosuppressive therapy with intravenous immunoglobulin and dexamethasone due to nonresponse to primary therapy. [ABSTRACT FROM AUTHOR]

The Ohio and Mississippi River Valleys are endemic to histoplasmosis. It is usually self‐limiting in immunocompetent people, but it can cause morbidity and mortality if not detected early in people with an underlying autoimmune disease. Disseminated Histoplasmosis induced hemophagocytic lymphohistiocytosis (HLH) mimicking the flare of an underlying autoimmune disease, is uncommon in the published literature. Disseminated histoplasmosis (DH) can cause multiorgan involvement, especially in a patient with an underlying autoimmune disease. We present the case of a 24‐year‐old female with HLH who was initially treated as a flare of autoimmune disease but later etiology was confirmed as disseminated histoplasmosis on bone marrow histopathological examination. [ABSTRACT FROM AUTHOR]

• A biopsy that shows narrow-based budding yeast confirms the diagnosis of Histoplasmosis capsulatum. • Latent infections may trigger a strong immune response after starting combined antiretroviral therapy. • Immune reconstitution inflammatory syndrome is possible with latent H. capsulatum. • Altered mental status is an atypical presentation of disseminated histoplasmosis. Opportunistic infections, including progressive disseminated histoplasmosis (PDH), may have variable and surprising presentations in patients with AIDS. This can be either a primary infection or reactivation of a latent infection. Latent infections may occur due to being unmasked by the immune reconstitution inflammatory syndrome after the initiation of combined antiretroviral therapy. PDH can be difficult to diagnose in patients with AIDS due to its variable presentation and many overlapping symptoms with other opportunistic infections. Serum and urine antigen testing are highly sensitive and typically used as the initial diagnostic test to workup suspected PDH. However, negative antigen and antibody tests do not rule out Histoplasmosis capsulatum infection and suspicion should remain high for PDH in the right clinical context. A definitive diagnosis may require biopsy-proven narrow-based budding yeast. We present an interesting patient with AIDS who presented with worsening cognitive decline and was ultimately diagnosed with PDH based on biopsy histopathology in the setting of negative antigen and antibody testing. [ABSTRACT FROM AUTHOR]

Objectives: Disseminated histoplasmosis is a major killer of HIV‐infected persons in Latin America. Antigen detection, fungal culture and Polymerase Chain Reaction are often not available, but cytology and histology are present in most hospitals and may offer a diagnostic alternative. In this study, we review 34 years of clinical experience to describe the roles of cytology and histology in diagnosing disseminated histoplasmosis. Methods: Retrospective multicentric study of 349 patients between 1 January 1981 and 1 October 2014 with confirmed disseminated histoplasmosis. Results: Around 32/214 (14.9%) of samples were screened using cytopathology, as were 10/101 (9.9%) bronchoalveolar lavage samples and 5/61 (8.2%) of spinal fluid samples. The samples most commonly sent to pathology were liver biopsies, lower digestive tract and lymphnode biopsies; the greatest proportion of positive results were found in lower digestive tract (43/59 (72.9%) positives), lymph node (39/63 (66.1%)), and liver (38/75 (50.7%)) samples. Overall, 97.2% of bone marrow and 97% of bronchoalveolar lavage samples were directly examined by a mycologist. Positive direct examination was independently associated with death (aHR = 1.5 (95%CI = 1–2.2)). Conclusions: Opportunities for a rapid diagnosis were regularly missed, notably for bone marrow samples, which could have been examined using staining methods complementary to those of the mycologist. [ABSTRACT FROM AUTHOR]

Histoplasmosis has heterogenous clinical presentation ranging from mild and self-limiting respiratory disease to disseminated forms with high mortality. In progressive disseminated histoplasmosis (PDH), patient presents with fever, lymphadenopathy, hepatosplenomegaly, adrenal enlargement, hemophagocytic lymphohistiocytosis and non-specific mucocutaneous lesions, usually in late stage of HIV. Cutaneous involvement is upto 25% in PDH which are papules, plaques, nodules and ulcers. Forty-two year old male, recently diagnosed as HIV positive presented with complaints of multiple painful ulcerated lesions over face, neck, tongue, arms, trunk & genitalia. Skin Biopsy was suggestive of histoplasmosis. Patient showed excellent response with amphotericin B and itraconazole. Since histoplasmosis is relatively uncommon, there should be a high-index of suspicion when an HIV patient presents with disseminated skin lesions. [ABSTRACT FROM AUTHOR]

Identifying prognostic factors is important in order to guide the choice of first-line therapy for disseminated histoplasmosis. Our objective was to identify factors associated with death among a cohort of 330 patients compiled over 34 years of clinical practice in French Guiana. Survival analysis was performed with death as the failure event and date of symptom onset as the origin event. Incidence rates were and Cox proportional hazards models were computed. Overall, 330 HIV-infected patients with disseminated histoplasmosis were included in the analysis, with 126 deaths occurring. One-quarter of all patients died within 6 months of the first symptoms. Patients with dyspnea, renal failure, arterial blood pressure <90 mmHG, and a WHO performance score >2 had a greater incidence of death. Bivariate analyses showed that patients with increased LDH, low hemoglobin, low serum protein, low CD4 counts, and low platelets tended to have a greater incidence of death. After adjusting for potential confounders, patients with dyspnea, a WHO performance score >2, serum protein <60 g/L, and hemoglobin <8.9 g/dL had an increased risk of dying. The interaction terms showed that patients treated with liposomal amphotericin B had a marked reduction in death among patients with renal failure; among renal failure patients, the elevation of LDH was associated with a significant risk of death. [ABSTRACT FROM AUTHOR]

We aimed to describe the ways patients with disseminated histoplasmosis—a multifaceted and often lethal disease—present themselves and are explored. A retrospective, observational, multicentric study spanned the period between 1 January 1981 and 1 October 2014. Principal component analysis was performed for the sampling sites and for the clinical signs and symptoms. The factor loadings of the principal components were selected for eigenvalues > 1. The most frequent signs and symptoms were an alteration of the WHO general performance status, fever, digestive tract, respiratory signs and symptoms and lymphadenopathies. The most common sites sampled were bone marrow, respiratory tract, blood, lymph node and liver biopsies, with significant variations in the number of sites from which samples were taken to try to identify the pathogen. The principal component analysis clinical signs and symptoms leading to the diagnosis showed four main lines of variation. The factor loadings of the four main components were compatible with four broad types of clinical presentations and four types of exploration strategies. Extracting simple algorithms was difficult, emphasizing the importance of clinical expertise when diagnosis depends on obtaining a sample where Histoplasma can be seen or grown. Histoplasma antigen detection tests will help simplifying the algorithms. [ABSTRACT FROM AUTHOR]

Disseminated histoplasmosis is the main AIDS-defining infection of French Guiana. We aim to describe our therapeutic experience for 349 patients with disseminated histoplasmosis between 1 January 1981 and 10 January 2014 in French Guiana. Survival, delays for treatment initiation, duration of induction therapy, and associated initial treatments are described. The death rate was 14.9 per 100 person-years, with an early drop in survival. Among those who died, >1/3 died within a year of HIV diagnosis, and ¾ of all patients with histoplasmosis had been diagnosed for HIV within a year. As induction treatment, 29% received liposomal amphotericin B, 12.9% received deoxycholate amphotericin B, 54% received itraconazole alone, and 21.8% received liposomal amphotericin B and itraconazole. The median delay between symptoms-onset and hospitalization was 19.5 days (IQR = 5–105). Liposomal amphotericin B or itraconazole was initiated shortly after admission. Treatment initiation was often presumptive for liposomal amphotericin B (27%) and itraconazole (20%). The median duration of liposomal amphotericin B treatment was 7 days (IQR = 5–11 days). The present study shows that ¾ of the patients were profoundly immunocompromised and had been diagnosed for HIV within the past year. Antifungal treatment was often initiated presumptively on admission. Over time there was a significant gradual decline in early death. [ABSTRACT FROM AUTHOR]

Introduction: Histoplasmosis is the main opportunistic infection and cause of death in HIV-infected persons living with HIV in French Guiana and probably in most of Latin America. The objective of the present study was to compare cutaneomucous histoplasmosis to non-cutaneomucous histoplasmosis in French Guiana. Methods: Between 1981 and 2014 AIDS-related disseminated histoplasmosis patients followed in the three hospitals of French Guiana were retrospectively studied. Only proven incident cases of histoplasmosis, either by pathology and/or mycological analysis, were considered. Mucocutaneous histoplasmosis was ascertained by a positive mucosal or cutaneous biopsy. Results: Thirty-one patients had mucocutaneous lesions, and 318 had no mucocutaneous lesions. Patients with cutaneomucous lesions were more likely to have had prior opportunistic infections (35.5%) than those who did not have cutaneomucous lesions (19.5%). They were more likely to be very severely immunocompromised (CD4 count < 50) (90.3% versus 62.8%) and less likely to have digestive signs (32.3% versus 74.1%) and superficial adenopathies (29% versus 50.2%) than those without cutaneomucous lesions. In terms of simple biological examinations, patients with cutaneomucous lesions had fewer signs of cholestasis. The diagnosis was significantly more likely to be performed by direct examination and pathology in those with cutaneomucous lesions than in those without such lesions. On the contrary, patients with cutaneomucous lesions were less likely to be diagnosed by fungal culture than those without cutaneomucous lesions. There was a greater but non-significant risk of early death in those with cutaneomucous lesions relative to those without (OR = 2.28 (95%CI = 0.83–5.7), p = 0.056. Conclusions: Mucocutaneous forms were associated with more profound immunosuppression and perhaps risk of early death. They are easily accessible for diagnosis. [ABSTRACT FROM AUTHOR]

In this retrospective study, (1–>3)-β- d -glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common, attributing B-glucan positivity to PCP without further testing risks misdiagnosis. [ABSTRACT FROM AUTHOR]

Hypercalcemia is a common laboratory finding in patients with malignancy, as well as with granulomatous disease. We report the case of a 75‐year‐old man with multiple myeloma (MM) who presented with generalized weakness, fever, and intractable hypercalcemia. The hypercalcemia proved difficult to treat despite well‐controlled MM, as well as adequate use of bisphosphonates and calcitonin. Biopsy of sub‐centimeter mesenteric adenopathy was significant for Histoplasma capsulatum and negative for malignancy, suggesting disseminated gastrointestinal histoplasmosis as the sole etiology for uncontrolled hypercalcemia. He was successfully treated with voriconazole. Disseminated histoplasmosis can be fatal if left untreated and warrants vigilance of non‐malignant etiologies of hypercalcemia. While hypercalcemia is a common clinical manifestation of MM, our patient is an exemplar of maintaining a broader differential diagnosis in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

The incidence of Addison's disease (AD) is rare. One of the most common causes of AD in developed countries is autoimmune. On the other hand, in developing countries, infective causes still predominate. The symptoms are mostly insidious in onset and non-specific, making it challenging to diagnose AD. The delay in starting the right treatment predisposes to high mortality due to Addison's crisis. Hence, biochemical parameters play a vital role in diagnosing AD since they usually will present with prominent hyponatraemia, hyperkalaemia and hypoglycaemia. Here, we report a case of a 66-year-old man with multiple co-morbidities and disseminated histoplasmosis who presented with asymptomatic hyponatraemia and hyperkalaemia and was eventually diagnosed with Addison's disease. Although the non-specific symptoms from his multiple co-morbidities obscured the diagnosis of AD, comprehensive biochemical tests have helped in establishing the diagnosis. [ABSTRACT FROM AUTHOR]

We describe a rare and interesting case of a 37-year-old man who presented with an intermittent fever, progressive cytopenia, and hepatosplenomegaly. Histopathological examination of a bone marrow smear revealed haemophagocytes and intracellular yeast-like Histoplasma capsulatum ( H. capsulatum); thus, we prolonged the blood culture duration to detect fungi, and H. capsulatum was detected in the peripheral blood. After the diagnosis of disseminated histoplasmosis, the patient was successfully treated with amphotericin B and symptomatic therapy. This is the first case in southwest China for which H. capsulatum was cultivated in peripheral blood, illustrating that the duration of specimen culture should be lengthened if a specific pathogen infection is suspected. Moreover, this case enriches our understanding of clinical manifestations of disseminated histoplasmosis. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a relatively rare infectious disease endemic to certain geographic areas such as East Africa, eastern and central United States, western Mexico, Central and South America. Disseminated histoplasmosis has been reported mainly in immunocompromised hosts and in AIDS patients. In this paper we report on a fatal case of undiagnosed disseminated histoplasmosis presenting as fever of unknown origin (FUO) in a 43-year-old Italian woman who, although splenectomized 5 years earlier due to a motor vehicle accident, was otherwise immunocompetent. This case report highlights the fact that, even in Europe, histoplasmosis is an emerging sporadic infection which needs be considered in the differential diagnosis of given clinical scenarios. The proposed case is of blatant forensic concern as it addresses the hypothesis of professional responsibility due to a missed diagnosis of histoplasmosis. A timely diagnosis, with appropriate therapies, could have prevented death. The role of the forensic pathologist is also crucial because the post-mortem diagnosis of histoplasmosis (never considered in the differential diagnosis during prior hospitalization) highlights the importance of a meticulous and thorough autopsy to elucidate the cause of death. [ABSTRACT FROM AUTHOR]

The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control ( CDC) detected 14 (17.9%). IMMY® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis. [ABSTRACT FROM AUTHOR]

Histoplasmosis is the most prevalent endemic mycosis in the United States with the highest incidence in the Mississippi and Ohio River Valleys. Most infections are asymptomatic or self-limited. However, in immunocompromised patients, severe and progressive disseminated infection can occur. In our patient, evaluation of her cutaneous lesions was critical in making the diagnosis of acute-disseminated histoplasmosis. Because clinical manifestations of disseminated histoplasmosis can vary widely, early recognition of this infection is challenging. This case highlights the importance of considering histoplasmosis in immunocompromised patients since the untreated disease can be fatal. [ABSTRACT FROM AUTHOR]

The article explores A 61-year-old female presented with fever and diarrhea 4.5 months after liver transplant. There was no contact with any virally infected individuals, and tests for viruses including SARS-CoV-2 were negative. Computed tomography demonstrated right pleural effusion, and subsequent thoracentesis exhibited an exudative effusion with predominantly lymphocytes and essential absence of neutrophils.

Histoplasmosis is well characterized as an endemic fungal disease restricted to certain areas of the USA. In Middle Europe, most patients present with acute pulmonary symptoms after travelling to endemic areas. Here, we want to illustrate the case of a 67-year-old man who presented with persistent oral ulcers, hoarseness, dysphagia, diarrhea, and weight loss to our Department of Otorhinolaryngology in December 2014. He was a retired construction worker and had a history of soil-disruptive activities in Africa and Middle and South America during employment. A positron emission tomography-computed tomography scan revealed prominent hypermetabolic lesions in the cecum and the lung, pointing towards a malignant disease. Surprisingly, histological examination of colonic and oral biopsies revealed abundant intracellular fungal elements, highly suspicious of Histoplasma capsulatum. Diagnosis was finally confirmed by panfungal polymerase chain reaction. Upon treatment with liposomal amphotericin followed by itraconazole, the severely ill patient showed an impressive clinical response. This case describes a disseminated manifestation of H. capsulatum years after the first exposure in an otherwise immunocompetent patient descending from a nonendemic area. [ABSTRACT FROM AUTHOR]

Background. Histoplasmosis-associated hemophagocytic lymphohistiocytosis (HLH) is a relatively rare disorder for which data are limited regarding optimal treatment and clinical outcomes in adults. We describe the clinical features, treatment, and outcomes of patients with histoplasmosis-associated HLH at our institution. Methods. We performed a retrospective chart review of all inpatients at Parkland Hospital diagnosed with HLH associated with Histoplasma capsulatum from 2003 to 2013. Results. Eleven cases of histoplasmosis-associated HLH over this time period were identified. Nine of eleven cases were males (82%). Nine of these patients had human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), 1 was a renal transplant patient on immunosuppressants, and the other had no documented immunocompromise. The most common HLH criteria were splenomegaly (n = 10), fever (n = 10), and ferritin >500 ng/dL (n = 9). Urine Histoplasma antigen was positive in every patient tested (n = 9 of 9), and most antibodies for Histoplasma were positive if checked (n = 4 of 5). A majority of patients received liposomal amphotericin B (n = 9) with an average treatment duration of 11 days, and 5 patients also received prednisone, intravenous immunoglobulin (IVIG), or both. Overall, 5 patients died within 30 days (45.5%), and 7 patients died within 90 days (63.6%). Of the 5 patients that received immunosuppression, 4 died (80%), whereas in the group not given additional immunosuppression (n = 5), 2 died (40%). Conclusions. Histoplasmosis-associated HLH among adults is a lethal disease of highly immunocompromised patients, especially patients with HIV/AIDS. Clinical features such as splenomegaly, elevated ferritin, and cytopenias should prompt evaluation for HLH in this population. Further data are needed to define the role of immunosuppression, IVIG, and highly active antiretroviral therapy in treating this condition. [ABSTRACT FROM AUTHOR]

A quiz concerning the uncommon cause of fever in a pediatric renal transplant patient is presented.

Histoplasmosis is a mycotic infection caused by dimorphic fungus, Histoplasma capsulatum. The organisms are usually found within the cells (macrophages). This organism mostly affects lungs in immunocompetent individuals and disseminated forms are seen in immunocompromised cases. Here, we describe a case of disseminated histoplasmosis in an immunocompetent, 35-year-old female with lymphadenopathy diagnosed by fine-needle aspiration cytology and cell block. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a systemic fungal infection caused by dimorphic fungus, Histoplasma capsulatum. Immunocompetent individuals usually have self-limiting or localized disease whereas immunocompromised individuals develop disseminated disease. The occurrence of progressive disseminated histoplasmosis in juvenile systemic lupus erythematosus is extremely rare with only one reported case in literature showing such association. Therefore, we report a case of severe opportunistic fungal infection caused by Histoplasma in a 13-year-old girl who was diagnosed with juvenile lupus erythematosus, subsequently developed septic shock and died of the disease despite of aggressive antifungal therapy. [ABSTRACT FROM AUTHOR]

Cutaneous histoplasmosis is a rare entity, although it can be seen in a substantial portion of renal transplant recipients with disseminated disease. The prognosis of disseminated disease is worse than isolated cutaneous involvement, and significant delays in diagnosis are reported. We reviewed reports of cutaneous histoplasmosis with and without dissemination in the setting of renal transplantation to examine incidence, timing of diagnosis, clinical features, and prognosis. Remarkable morphologic variability and the non-specific appearance of skin findings suggest that tissue culture is required for definitive diagnosis. Cutaneous lesions represent an easily accessible source for early diagnosis. [ABSTRACT FROM AUTHOR]

Immunosuppressed patients are at highest risk for disseminated histoplasmosis, but only a few cases have been reported in hematopoietic stem cell transplant recipients. We report a case of disseminated histoplasmosis in an allogeneic bone marrow transplant recipient residing in a non-endemic area. Diagnosis was first suspected based on a peripheral blood smear. [ABSTRACT FROM AUTHOR]

Many relapses and deaths resulting from disseminated histoplasmosis ( DH) in acquired immunodeficiency syndrome ( AIDS) patients have been observed in an endemic area in north-eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/ AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002-2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly ( P < 0.05) associated with relapse and overall mortality (univariate analysis): non-adherence to highly active antiretroviral therapy ( HAART), irregular use of an antifungal, non-recovery of the CD4+ count and having AIDS before DH; histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non-adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population. [ABSTRACT FROM AUTHOR]

Disseminated histoplasmosis is a relentlessly progressive granulomatous disease which can mimic many other granulomatous diseases including tuberculosis. A 48-year-old male was referred to us with 11 months history of multiple subcutaneous swellings and ulcerations over the upper and lower limbs and fever for 2 months. He was evaluated outside for several months and received anti tubercular drugs for about 2 years in the past for a granulomatous infection of bone and soft tissue identified by various biopsies, without any improvement. When he was evaluated and fresh biopsies were taken, they were stained for fungus and disseminated histoplasmosis was detected. This case confirms the importance of considering fungal infections as a possibility while treating disseminated granulomatous infections, even in immune-competent patients, especially if response to treatment is inadequate. [ABSTRACT FROM AUTHOR]

The State of Ceará in north-eastern Brazil has one of the highest rates in the world of relapse and death due to disseminated histoplasmosis ( DH) in acquired immunodeficiency syndrome ( AIDS) patients. The objective of this study is to characterise the relapse and mortality of DH in AIDS cases residents in Ceará. We performed a retrospective analysis of the medical records of AIDS patients who had a first episode of DH from 2002 to 2008. We analysed the outcomes until December 31, 2010. A total of 145 patients participated in the study. The mean clinical follow-up duration was 3.38 years ( SD = 2.2; 95% CI = 3.01-3.75). The majority of the subjects were male with a mean age of 35 years ( SD = 2.2; 95% CI = 3.01-3.75) and were born in the capital of Ceará. DH was the first manifestation of AIDS in 59% of the patients. The relapse rate was 23.3%, with a disseminated presentation in 90% of these patients. The overall mortality during the study period was 30.2%. The majority of patients who relapsed or died had irregular treatment with antifungals or highly active antiretroviral therapy and did not have active clinical follow-up. High rates of recurrence and mortality were found in AIDS-associated DH in this area of the country. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is a common opportunistic fungal infection that is observed almost exclusively in immunodeficient patients, especially those with AIDS. Immunocompetent individuals that suffer from histoplasmosis are rarely reported, especially those with disseminated lesions, such as disseminated histoplasmosis. The observation of disseminated histoplasmosis with prominent gastrointestinal involvement, no respiratory symptoms (which is presumed to be the portal of infection), gastrointestinal pathological changes, and minor digestive system disorders make this case study exceedingly rare. Case presentation: We report the case of a 33-year-old immunocompetent male who presented with fever and weight loss. Based on investigations, the patient showed pancytopenia, hepatosplenomegaly, bone marrow involvement and marked colonic involvement. Finally, disseminated histoplasmosis was diagnosed and confirmed by stained smears of fine needle aspirates and biopsy from lesions in the bone marrow and colon. The patient showed appreciable regression of lesions following prompt treatment with amphotericin B deoxycholate, and was treated thereafter with oral itraconazole following discharge from hospital. Conclusion: Disseminated histoplasmosis could be underestimated in immunocompetent patients. A high degree of clinical suspicion is essential in both immunocompromised and immunocompetent patients, regardless of pulmonary symptoms, and whether in endemic or non-endemic areas. Early and accurate diagnosis is extremely important for the appropriate treatment of infection and to improve disease outcome. [ABSTRACT FROM AUTHOR]

S. Jaiswal, M. Vij, G. Chand, R. Misra and R. Pandey Diagnosis of adrenal histoplasmosis by fine needle aspiration cytology: an analysis based on five cases Background: There is limited description in the literature of the initial diagnosis of adrenal histoplasmosis by fine needle aspiration cytology (FNAC). Objective: To study the aetiology, clinical features and morphological differential diagnosis of adrenal histoplasmosis diagnosed initially by FNAC. Methods: Five cases diagnosed by ultrasound-guided FNAC from 2008 to 2010 were found in the laboratory records and reviewed. Clinical features and cytomorphological features were correlated. Results: All the patients were male and were aged 45-83 years (mean 60 years). Three patients had a history of contact with birds, one was diabetic and all were negative for human immunodeficiency virus (HIV). The commonest symptom was weight loss. On cytological smears, uniform round to oval (about 2-4 μm in diameter) budding yeasts were seen intracellularly (within histiocytes) as well as extracellularly. In three cases, an inflammatory response in the form of epithelioid cell granulomas along with multinucleated giant cells was seen. Conclusions: Adrenal histoplasmosis does occur in immunocompetent persons living in areas not endemic for the disease. Although it is not common, it needs to be considered in the differential diagnosis of bilateral adrenal enlargement. FNAC is a simple, safe technique to establish the initial diagnosis. Correct diagnosis and treatment leads to a favourable outcome. [ABSTRACT FROM AUTHOR]

An elderly patient presented with prolonged fever, gross weight loss, recurrent haemoptysis and abdominal pain. He had a background history of adrenal tuberculosis with completion of treatment without any obvious improvement. Clinically he was diagnosed as a case of adrenocotical insufficiency. Evaluation including histopathology revealed the diagnosis as disseminated histoplasmosis involving adrenal gland and lungs. The disease is a rarity without any underneath immunosuppression and hence high index of suspicion with appropriate steps for investigation is the key to achieve a diagnosis of disseminated histoplasmosis in Bangladesh. [ABSTRACT FROM AUTHOR]

U. Rappo, J.R. Beitler, J.R. Faulhaber, B. Firoz, J.S. Henning, K.M. Thomas, M. Maslow, D.S. Goldfarb, H.W. Horowitz. Expanding the horizons of histoplasmosis: disseminated histoplasmosis in a renal transplant patient after a trip to Bangladesh. Transpl Infect Dis 2010: 12: 155–160. All rights reserved Histoplasmosis is recognized to occur in the Ohio and Mississippi River Valleys of the United States, but less widely appreciated is its worldwide distribution. We report a case of disseminated histoplasmosis with disease involving skin, lungs, and epiglottis in a renal transplant patient 6 months after a trip to Bangladesh, to highlight the potential risk of acquisition of this infection in the Indian subcontinent. [ABSTRACT FROM AUTHOR]

A case of disseminated histoplasmosis in a 56-year-old apparently healthy male without any history of travel to endemic zone is described. The patient presented with fever with cough, respiratory distress and disorientation. Physical findings include fever, shortness of breath, reduced level of consciousness and hypotension. Diagnosis was confirmed by presence of Histoplasma capsulatum in bone marrow aspirate. This report illustrates the importance of recognizing the possibility of histoplasmosis in Bangladesh where mimickers of histoplasmosis like pulmonary tuberculosis and visceral leishmaniasis are extremely common. [ABSTRACT FROM AUTHOR]

Histoplasmosis, also called as Darling's disease, is caused by the dimorphic fungus, Histoplasma capsulatum. In India, several cases of histoplasmosis have been reported since 1954, but in only a few cases could the diagnosis be confirmed by fungal culture. Disseminated histoplasmosis in adults is often associated with immunosuppression, as in human immunodefi ciency virus (HIV) infection. Oral lesions are seen in 30-50% of the patients. Here, we are reporting two histoplasmosis cases, one with disseminated histoplasmosis with extensive skin and oral lesions in a known HIV-positive patient and the second case presenting with ulcer of the tongue, found to be HIV positive on investigation. It is important to consider histoplasmosis as one of the differential diagnosis of oral lesions in HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients. [ABSTRACT FROM AUTHOR]

Histoplasmosis occurs in approximately 5% of acquired immunodeficiency syndrome (AIDS) patients in endemic areas and often evolves to a disseminated picture if diagnosis is delayed and/or CD4 count falls below 150 cells × mm3 without high active antiretroviral therapy (HAART). This report presents clinical features of patients with histoplasmosis admitted from 1992 to 2005. Of the 57 individuals, 45 (79%) were male, aged 20–40 years; 30 (52.6%) presented histoplasmosis together with HIV diagnosis and 35 (61.4%) referred illness course up to 4 weeks. Fever, hepatomegaly and/or splenomegaly, dyspnea and skin lesions were noticed in 50 (87.7%), 38 (66.7%), 30 (52.6%) and 25 (43.9%) patients respectively. High levels of lactic acid dehydrogenase, X-ray lung interstitial pattern, pancytopenia and CD4 count <100 cells × mm3 were observed in 48 (84.2%), 35 (66%), 34 (59.6%) and 33 (94%) patients respectively. Mycological diagnosis was performed by one or more methods in all patients. Thirty nine (68.4%) received amphotericin B and/or itraconazole. A cure rate was observed in 76.9% and nine (23.1%) died early during therapy. Otherwise death occurred in 18 (31.6%) before diagnosis was completed. Despite free HAART disposal in public Brazilian health services, histoplasmosis still occurs as the first AIDS baseline condition in patients without antiretroviral therapy, many of whom are not receiving any medical care for HIV infection. [ABSTRACT FROM AUTHOR]

Reactive hemophagocytic syndrome (RHS) is an uncommon life-threatening disorder. It is believed to be caused by wide-spread non-neoplastic proliferation and inappropriate activation of mature macrophages, resulting in excessive cytokine activation which leads to hematophagocytosis by cells of the macrophage-monocyte lineage and multiorgan dysfunction. RHS may be associated with infections caused by bacterial, viral and fungal organisms as well as lymphoproliferative disorders, nonhematopoietic malignancies, autoimmune diseases and some therapeutic drugs. Immunosuppression is a frequent underlying condition in RHS. The following case presentation describes a patient with a history of chronic hepatitis C, cryoglobulinemia, renal failure and Staphylococcus aureus perinephric abscess and bacteremia, who, at autopsy, was found to have disseminated histoplasmosis with fungal endocarditis and RHS. [ABSTRACT FROM AUTHOR]

We present the case of a patient proceeding from the jungle of Peru with diagnosis of infection for the Human Immunodeficiency Virus (HIV) with respiratory symptoms, fever and a chest X-ray with milliary pattern. Because Tuberculosis is a prevalent disease in our country and the most frequent in patients with HIV, he received antituberculous treatment. Nevertheless, the historical information of having been in endemic zone of mycosis in some moment of his life, associated with laboratory examinations, allowed the diagnosis of Disseminated histoplasmosis, as product of the reactivation of a latent infection that appears when the level of immunity gets depressed like in infected patients by the HIV. Thehistory of diseases, trips and previous residences is a fundamental information to establish a good approximation diagnosis in patients with HIV [ABSTRACT FROM AUTHOR]

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal. [ABSTRACT FROM AUTHOR]

Background: We describe a retrospective analysis of the clinical presentation and imaging features in nine patients with adrenal histoplasmosis in nonimmunocompromised patients from a nonendemic region.Methods: Clinically, a tuberculosis-like presentation in four patients and a tumor-like presentation in five patients were seen. All patients were seronegative for the human immunodeficiency virus. Ultrasound (US) in all patients, computed tomography (CT) in six, and magnetic resonance imaging (MRI) in three showed suprarenal masses. CT-guided (in five) and US-guided (in four) biopsy and fine-needle aspiration cytology established a definite diagnosis. The work-up for malignancy and tuberculosis was negative.Results: On cross-sectional imaging, eight patients had bilateral adrenal masses and one had a unilateral adrenal mass. Imaging features were variable. All adrenal masses were hypoechoic on US, homogeneous in five, and heterogeneous in four patients. All adrenal masses were hypodense on CT, homogeneous in four, and heterogeneous in two. Heterogeneous enhancement was seen in three, homogeneous enhancement in two, and no enhancement in one patient. MRI in three patients showed that the masses were of variable signal intensity on all pulse sequences.Conclusion: Our case series showed that adrenal histoplasmosis does occur in immunocompetent persons living in areas not endemic for the disease. The imaging features were variable. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is nowadays widespread minimally invasive procedure for diagnosing a large number of benign as well as malignant lesions. We report a case of a 62-year-old immunocompetent elderly male, who presented with high-grade fever, hepatosplenomegaly and mediastinal and intra-abdominal lymph nodes. He was residing in an old haweli with bats infestation. EUS-FNA of the subcarinal and the preaortic lymph node clinched the diagnosis. A rapid on-site evaluation of the cytology material revealed organisms conforming to the morphology of Histoplasma capsulatum. The patient was immediately started on amphotericin B and itraconazole and responded well. In this case, we found the role of EUS-FNA not only in diagnosis, but also in the follow-up of the patient. [ABSTRACT FROM AUTHOR]

Objective Presentation of a case of disseminated histoplasmosis, observed in a non-endemic area, in which cutaneous lesions and fever were the dominant clinical signs of the infection. Case A 54-year-old homosexual man with acquired immunodeficiency syndrome (AIDS) related Kaposi's sarcoma presented with cutaneous lesions and fever due to disseminated histoplasmosis. The patient was successfully treated with itraconazole 200 mg/day. He died after 8 months from AIDS dementia complex: disseminated histoplasmosis relapse was not observed. Conclusion The case shows that infection with Histoplasma capsulatum must be considered by dermatologists in HIV/AIDS patients, even in non-endemic areas. [ABSTRACT FROM AUTHOR]

A case of disseminated histoplasmosis in a 62-year immunocompetent healthy male presenting as compressive myelopahty without any pulmonary involvement or travel to endemic zone is described. The patient presented with fever, dull ache pain in the back of the lower chest, weakness of both lower limbs with impairment of emptying of bowel and bladder, physical findings include raised temperature, generalized lymphadenopathy, nontender mild hepatomegaly, spastic paraplegia with sensory level up to D8 and local tenderness over D7 vertebra without any gibbus. Diagnosis was confirmed by presence of histoplasmacapsulatum in the lymph node and soft tissue from the spine. The particular interest of this paper is to present a case of disseminated histoplasmosis especially presenting as spastic paraplegia in an immunocompetent host without pulmonary involvement and illustrates the importance of recognizing the possibility of histoplasmosis in Bangladesh where mimickers of histoplasmosis like tuberculosis is extremely common. [ABSTRACT FROM AUTHOR]