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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., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

A 50-year-old woman with a history of kidney transplant presented with 2 days of abdominal pain after 6 months of recurrent streptococcal pharyngitis, fevers, weight loss and a new rash on her chest and back. Her examination was notable for a unilateral tonsillar exudate and 2-3 mm pink papules with a fine scale over her chest and back. CT of the abdomen and chest demonstrated several large lymph nodes, and laboratory investigation revealed new cytopenias and elevated transaminases. Urine antigen testing for Histoplasma capsulatum was negative, but a fungal complement fixation panel was reactive for Histoplasma antibodies. Skin biopsy revealed intracellular organisms consistent with H. capsulatum She underwent treatment with liposomal amphotericin B but due to nephrotoxicity, drug interactions and worsening transaminitis, therapy was changed to itraconazole. The diagnosis and management of disseminated histoplasmosis presents multiple challenges, which are of particular importance in patients with a history of renal transplantation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The fungal pathogen Histoplasma capsulatum causes a spectrum of disease, ranging from local pulmonary infection to disseminated disease. The organism seeks residence in macrophages, which are permissive for its survival. Hypoxia-inducible factor 1α (HIF-1α), a principal regulator of innate immunity to pathogens, is necessary for macrophage-mediated immunity to H. capsulatum in mice. In the present study, we analyzed the effect of HIF-1α in human macrophages infected with this fungus. HIF-1α stabilization was detected in peripheral blood monocyte-derived macrophages at 2 to 24 h after infection with viable yeast cells. Further, host mitochondrial respiration and glycolysis were enhanced. In contrast, heat-killed yeasts induced early, but not later, stabilization of HIF-1α. Since the absence of HIF-1α is detrimental to host control of infection, we asked if large amounts of HIF-1α protein, exceeding those induced by H. capsulatum , altered macrophage responses to this pathogen. Exposure of infected macrophages to an HIF-1α stabilizer significantly reduced recovery of H. capsulatum from macrophages and produced a decrement in mitochondrial respiration and glycolysis compared to those of controls. We observed recruitment of the autophagy-related protein LC3-II to the phagosome, whereas enhancing HIF-1α reduced phagosomal decoration. This finding suggested that H. capsulatum exploited an autophagic process to survive. In support of this assertion, inhibition of autophagy activated macrophages to limit intracellular growth of H. capsulatum Thus, enhancement of HIF-1α creates a hostile environment for yeast cells in human macrophages by interrupting the ability of the pathogen to provoke host cell autophagy., (Copyright © 2019 Friedrich et al.)

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.

Heat shock proteins (Hsps) are highly conserved biomolecules that are constitutively expressed and generally upregulated in response to various stress conditions (biotic and abiotic). Hsps have diverse functions, categorizations, and classifications. Their adaptive expression in fungi indicates their significance in these diverse species, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively. This minireview focuses on the pathobiology of Hsps, with particular emphasis on their roles in the morphogenesis and virulence of Histoplasma and Paracoccidioides and the potential roles of active and passive immunization against Hsps in protection against infection with these fungi., (Copyright © 2017 American Society for Microbiology.)

Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but rarely in Japan. In recent years, however, the number of histoplasmosis patients in Japan has increased. In addition, to our knowledge, there are no previous reports of increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with histoplasmosis. We report a case series of histoplasmosis in three Japanese temporary workers in Manzanillo, Mexico. All three patients developed a persistent high fever and general fatigue. Laboratory tests showed increased C-reactive protein levels and mild liver dysfunction. All patients also showed increased soluble interleukin-2 receptor (sIL-2R) levels. Chest computed tomography revealed multiple nodules in both lung fields. All patients were positive for serum anti-Histoplasma antibodies, and two patients were positive for Histoplasma on polymerase chain reaction tests. After treatment that included antifungals, their conditions gradually improved and laboratory data normalized. Although one patient developed respiratory failure, this patient recovered with antifungal therapy in combination with methylprednisolone. Serum sIL-2R levels in all patients gradually declined to normal levels, indicating their recovery from Histoplasma infection. From our experience with these patients, sIL-2R levels may be a useful biomarker for patients with histoplasmosis., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Histoplasmosis is common among persons living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA) in Latin America, but its diagnosis is difficult and often nonspecific. We conducted prospective screening for histoplasmosis among PLWHA with signs or symptoms suggesting progressive disseminated histoplasmosis (PDH) and hospitalized in Hospital La María in Medellín, Colombia. The study's aim was to obtain a clinical and laboratory profile of PLWHA with PDH. During 3 years (May 2008 to August 2011), we identified 89 PLWHA hospitalized with symptoms suggestive of PDH, of whom 45 (51%) had histoplasmosis. We observed tuberculosis (TB) coinfection in a large proportion of patients with PDH (35%), so all analyses were performed adjusting for this coinfection and, alternatively, excluding histoplasmosis patients with TB. Results showed that the patients with PDH were more likely to have Karnofsky score ≤ 30 (prevalence ratio [PR] = 1.98, 95% confidence interval [CI] = 0.97-4.06), liver compromised with hepatomegaly and/or splenomegaly (PR = 1.77, CI = 1.03-3.06) and elevation in serum of alanine aminotransferase and aspartate aminotransferase to values > 40 mU/mL (PR = 2.06, CI = 1.09-3.88 and PR = 1.53, CI = 0.99-2.35, respectively). Using multiple correspondence analyses, we identified in patients with PDH a profile characterized by the presence of constitutional symptoms, namely weight loss and Karnofsky classification ≤ 30, gastrointestinal manifestations with alteration of liver enzymes and hepatosplenomegaly and/or splenomegaly, skin lesions, and hematological alterations. Study of the profiles is no substitute for laboratory diagnostics, but identifying clinical and laboratory indicators of PLWHA with PDH should allow development of strategies for reducing the time to diagnosis and thus mortality caused by Histoplasma capsulatum., (© The American Society of Tropical Medicine and Hygiene.)

Histoplasmosis is endemic to the Mississippi and Ohio River valley regions in the US. It usually affects patients with underlying immunodeficiency but can also be seen in immunocompetent hosts. Although gastrointestinal involvement is common in the setting of disseminated histoplasmosis, isolated gastrointestinal involvement is uncommon. We report a case of isolated pancreatic histoplasmosis in an immunocompetent patient, presenting as painless jaundice and pancreatic head mass., Competing Interests: Statement The author(s) have no conflicts of interest to disclose.

Spindle cell neoplasms are rarely reported in liver allografts; most are benign and associated with Epstein-Barr virus infection. We present a case of a malignant spindle cell neoplasm arising in a liver allograft. The patient underwent orthotopic liver transplant for cirrhosis secondary to nonalcoholic steatohepatitis. After 2 years, he presented with vague abdominal complaints. Imaging studies revealed a 10-cm right hepatic lobe mass. The patient underwent right-sided hepatectomy. The tumor displayed areas of broad, relatively hypocellular fascicles, whorls, and perivascular clustering; spindle cells with mild to moderate nuclear pleomorphism; and relatively abundant eosinophilic cytoplasm. Mitotic activity ranged from 2 to 4 mitotic figures per 20 high-power fields. Immunostaining displayed positivity for epithelial membrane antigen, vimentin, CD99, BCL2, cytokeratin, and human herpesvirus 8. Interphase fluorescence in situ hybridization findings were negative for a translocation involving the SS18 gene (18q11). We believe the tumor represents the first reported case of a novel unclassified spindle cell malignant neoplasm in a liver allograft.

We describe an imported case of histoplasmosis, whose serological profile was established by means of a protein-based microarray platform, the recently described mycoarray. Because of its peculiarities, such a novel tool greatly facilitates the rapid and multiparametric assessment of patients' serological status and lends itself to be employed as an aid in the diagnosis of primary mycoses, especially in nonendemic countries., (© 2013 International Society of Travel Medicine.)

Background: Outbreaks of histoplasmosis have been increasingly reported in association with travel to endemic areas. Multiple outbreaks have been reported following travel to the Americas, but reports of pulmonary histoplasmosis in short-term immunocompetent travelers to Africa are rare., Methods: A biology student was referred to our unit with suspected pulmonary histoplasmosis following her return from a field trip in the Ugandan rainforest. The patient informed us that several of her multinational student colleagues on the same expedition had developed a similar illness. Using an alert in ProMED-mail and a questionnaire forwarded to each of the symptomatic students, we accumulated data on the other cases involved in this apparent outbreak of pulmonary histoplasmosis., Results: Thirteen of 24 students developed respiratory symptoms following the expedition. Chest X-ray appearances were often suggestive of miliary tuberculosis but in most cases a final diagnosis of histoplasmosis was made (confirmed with serology in five cases, clinically diagnosed in six, and retrospectively suspected in two). Detailed questioning indicated that the likely source was a large hollow bat-infested tree within the rainforest., Conclusions: This is an unusual outbreak of histoplasmosis following short-term travel to Africa. Pulmonary histoplasmosis should always be considered in the differential diagnosis of an acute febrile respiratory illness in travelers returning from endemic areas or reporting activities suggesting exposure., (© 2013 International Society of Travel Medicine.)

We present a case of progressive disseminated histoplasmosis in an immunocompetent traveler. Histoplasmosis was acquired in South America; its manifestations included prolonged fever, splinter hemorrhages, erythema multiforme, arthritis, and mediastinal lymphadenopathy. To the best of our knowledge no splinter hemorrhages had previously been reported in a patient with histoplasmosis., (© 2013 International Society of Travel Medicine.)

Disseminated histoplasmosis has occasionally been documented in solid organ transplant patients in some endemic areas. Early diagnosis and treatment are associated with good outcomes. In this report the authors describe the clinical characteristics and natural history of undiagnosed disseminated histoplasmosis in a child who underwent a cadaveric renal transplant at a tertiary healthcare center in northeastern Thailand.

Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is beneficial in treating choroidal neovascularization from age-related macular degeneration, but few long-term studies have shown its efficacy in choroidal neovascularization from ocular histoplasmosis syndrome. Intravitreal anti-VEGF therapy may be effective in cases of choroidal neovascularization because of ocular histoplasmosis syndrome., Methods: Retrospective chart review of 54 eyes treated with intravitreal anti-VEGF therapy for choroidal neovascularization in ocular histoplasmosis syndrome with >1 year of follow-up after initiation of anti-VEGF treatment was performed. Previous treatment and demographic information were recorded. Visual acuity was recorded for each injection treatment and at the last follow-up visit. The anti-VEGF agent was recorded for each injection treatment. Visual acuity was recorded at the last follow-up visit., Results: Mean visual acuity improved from 20/53 to 20/26 over an average of 26.8 months. Either bevacizumab or ranibizumab were administered on an average of 4.5 injections per patient per year of follow-up. Vision loss was seen in only three eyes with loss limited to a single line of vision. Patients experienced no serious complications from treatment., Conclusion: Long-term intravitreal anti-VEGF therapy with bevacizumab or ranibizumab is beneficial in treatment of choroidal neovascularization in ocular histoplasmosis syndrome.

Purpose: To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS)., Design: Retrospective, comparative case series., Participants: Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010., Intervention: Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT)., Main Outcome Measures: Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals., Results: A total of 117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT treatment. For all patients, the average pretreatment logarithm of minimum angle of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB injections per year. There was no significant difference in initial VA, VA at 12 months, VA at 24 months, or number of eyes with a 3-line gain between the IVB monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3 lines or more, and 81.2% (84/104) of subjects had maintained or improved their starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32) follow-up. There was no increase in the proportion of subjects losing 3 lines or more over 3 years of follow-up., Conclusions: There is no significant difference in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The use of IVB alone or in combination with PDT results in significant visual stabilization in the majority of patients with CNV secondary to POHS., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: A review of the clinical presentation, diagnosis, treatment and outcomes of 30 solid organ transplant recipients (SOTRs) with histoplasmosis or blastomycosis from 3 Midwestern academic medical centers., Background: The endemic fungal pathogens, Histoplasma capsulatum and Blastomyces dermatitidis, may cause severe infection in SOTRs. In this report, we describe the clinical presentation, diagnosis, treatment, and outcomes of these endemic fungal infections (EFIs) among SOTRs at 3 academic transplant centers., Methods: A retrospective review was conducted of SOTRs with histoplasmosis or blastomycosis from 3 Midwestern medical centers in the United States. Data collected included demographics, immunosuppression, clinical presentation, method of diagnosis, antifungal treatment, response to therapy, and patient and graft survival., Results: Between 1996 and 2008, 30 transplant recipients with histoplasmosis or blastomycosis were identified, giving a cumulative incidence of infection of 0.50% (30/5989); 73% of the study patients were renal transplant recipients, and the median time to disease onset after transplantation was 10.5 months. The lungs were the most common site of infection (83%), and 60% had disseminated disease. Urine antigen testing was positive in all patients in whom it was performed (23/23). Initial antifungal therapy consisted of amphotericin B in 70%, and 87% received azoles, typically itraconazole (83%). Two patients developed relapsed infection and 7 patients had graft failure after EFI. Overall mortality was 30%, with an attributable mortality of 13%., Conclusions: As in several previous single-center studies, the incidence of post-transplant histoplasmosis and blastomycosis was <1%, but often resulted in disseminated infection. In this cohort, EFI was associated with a high rate of allograft loss and overall mortality., (© 2011 John Wiley & Sons A/S.)

Pulmonary histoplasmosis is an important cause of morbidity in the United States. Several outbreaks of acute pulmonary histoplasmosis have been linked to potentially preventable environmental exposures. Progressive disseminated histoplasmosis, which is seen frequently in the growing population of immunocompromised hosts, often presents with prominent pulmonary manifestations and is more commonly encountered in hospitalized patients than acute, subacute, or chronic pulmonary histoplasmosis. A battery of diagnostic studies including serology, antigen, cytology/histopathology, and culture should be obtained in suspected cases of histoplasmosis. The yield of antigenuria detection is highest when the multiple body fluids are tested; the level of antigenuria correlates with severity of disease. Amphotericin B is the treatment of choice for severe pulmonary or disseminated histoplasmosis, and itraconazole is effective for mild to moderately severe infection. Posaconazole exhibits promise as a salvage agent. Antifungal prophylaxis is not routinely recommended for at-risk populations. Measures to minimize environmental contamination may reduce the risk of epidemic-type acute pulmonary histoplasmosis related to high-risk exposures., (© Thieme Medical Publishers.)

Objective: Systemic bacterial and fungal infections may sometimes present local manifestations within otolaryngological district whose early detection may be useful in establishing a correct diagnosis and more appropriate treatment. This paper reviews certain systemic bacterial and fungal diseases presenting ENT manifestations in the pediatric population from an otolaryngological perspective., Methods: A medline searching for specific issues was performed in order to achieve more information as possible with regards to ENT manifestation of systemic bacterial and fungal infections. Limits for pediatric age were used. Two separate sections for bacterial and fungal disease are included. The section on systemic bacterial infections considers cat-scratch disease, Lyme borreliosis, actinomycosis, Lemierre's syndrome and congenital syphilis, and the section on systemic fungal infections includes candidiasis, aspergillosis and histoplasmosis., Conclusions: Pediatricians and ear, nose and throat (ENT) specialists, approaching head and neck disorders in children, should therefore consider them among the possible differential diagnoses. This means that physicians need to recognize the first head and neck manifestations of systemic infections promptly in order to be able to treat them efficaciously and avoid the dangerous systemic spreading of the infective process., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

The effect of methamphetamine on the host response to an opportunistic pathogen has not been extensively described. Methamphetamine is a major public health and safety problem in the United States. Chronic methamphetamine abuse is associated with a 2-fold higher risk of human immunodeficiency virus infection and, possibly, additional infections. Histoplasma capsulatum is a dimorphic fungus that is endemic in the Midwest of the United States and that causes respiratory and systemic disease, particularly in individuals with impaired immunity. We showed that methamphetamine abrogates normal macrophage function, resulting in an inability to control histoplasmosis. Methamphetamine decreased phagocytosis and killing of yeast by primary macrophages by alkalization of the phagosome. Furthermore, mice that received methamphetamine prior to H. capsulatum infection were immunologically impaired, with increased fungal burden, increased pulmonary inflammation, and decreased survival. Immunosuppression by methamphetamine may be associated with deregulation of cytokines in the lungs of infected mice, aberrant processing of H. capsulatum within macrophages, and immobilization of MAC-1 receptors on the surface of macrophages that are involved in phagocytosis. Additionally, methamphetamine inhibits T cell proliferation and alters antibody production, which are important components of adaptive immunity. With use of a murine model of histoplasmosis, this study establishes that methamphetamine may alter the immune system of the host and enhance fungal pathogenesis.

Objectives: Skin lesions, uncommon in US cases (<10%), occur in 38-85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed diagnosis, or differences in host immune response among different ethnic groups, they also could result from genetic differences changing the pathobiology of the organism. It is possible that genetic differences among strains of H. capsulatum may influence the pathogenesis and clinical manifestations of histoplasmosis., Methods: We examined the clinical features of patients with mucocutaneous manifestations of histoplasmosis and performed genetic analysis based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients. Two pairs of PCR primers were designed to develop and amplify the ITS regions of H. capsulatum, 5'-TACCCGGCCACCCTTGTCTA-3' and 5'-AGCGGGTGGCAAAGCCC-3'. These primers were based on the ITS sequence of Ajellomyces capsulatus, the ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank (accession number U18363). Eight patients attending a tertiary-care hospital in southern Brazil were enrolled into the study. All case patients had skin cultures growing H. capsulatum at the mycology laboratory., Results: Six of eight (75%) patients were HIV-positive and presented involvement of multiples organs by H. capsulatum. Two HIV-negative patients did not present evidence of involvement of other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The 2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the ITS regions. They were identical to strains of H. capsulatum isolated in patients from Colombia and Argentina, but different from strains isolated in US. Hc1 and Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV-infected and non-HIV-infected patients., Conclusions: Mucocutaneous manifestations of histoplasmosis, which are frequently seen in Brazilian patients were caused by 2 specific strains in our institution. Those strains have been isolated in patients with these particular clinical features of histoplasmosis in Latin America. Our study suggests that unique pathogenic characteristics among the Latin American species of H. capsulatum might explain its increased dermatotropism.

Histoplasma capsulatum is a common cause of fungal infection in certain geographic areas, and although most infections are asymptomatic, it is capable of causing histoplasmosis, a disseminated, life-threatening disease, especially in immunocompromised individuals. A deeper understanding of this host-pathogen interaction is needed to develop novel therapeutic strategies to counter lethal infection. Although several lines of evidence suggest that this fungus is neurotropic in HIV patients, little is known about the immunobiology of Histoplasma infection in the central nervous system [CNS]. The goal of the present study was to understand the innate neuroimmune mechanisms that recognize H. capsulatum during the initial stages of infection. Using a 293T stable cell line expressing murine Toll-like receptor 2 [TLR2], we show here that TLR2 recognizes H. capsulatum cell wall protein Yps3p and induces the activation of NF-kappaB. In further experiments, we tested the ability of Yps3p to induce signaling from TLR2 in primary microglial cells, the resident brain macrophages of the CNS. Our data show that H. capsulatum Yps3p induced TLR2 signaling in wild-type microglia, but not in microglia isolated from TLR2 KO mice, confirming that Yps3p is a ligand for TLR2. Furthermore, Yps3p-induced TLR2 signaling was suppressed by vaccinia virus-encoded TLR inhibitors. This is the first demonstration of a fungal protein serving as a TLR ligand and mediating signaling in primary brain cells.

Histoplasma capsulatum is endemic to the Ohio and Mississippi River valley regions of the United States. Infection with this fungus produces a broad range of clinical and pathologic manifestations. We report a case of laryngeal histoplasmosis, mimicking carcinoma, presenting as a manifestation of chronic disseminated histoplasmosis.

We report a case of gastrointestinal histoplasmosis in a 45-year-old HIV positive man who was misdiagnosed as a case of colonic cancer. The patient presented with low-grade fever, pain in lower abdomen, anorexia and weight loss of six months duration. On examination a lump in the left iliac fossa was detected. Colonoscopy revealed stricture and ulcerated growth in the sigmoid colon. Radiological investigations suggested malignant/inflammatory mass in the sigmoid colon with luminal compromise. Patient was operated and ulcerated tissue was sent for histopathological examination, which revealed numerous intracellular, 2-4 microm, oval, narrow-based budding yeast cells suggestive of Histoplasma capsulatum. Subsequently, the patient developed fluffy opacities on X-ray chest. Examination of sputum revealed presence of acid-fast bacilli and yeast forms of H. capsulatum. Patient was started on amphotericin B but died on the seventeenth postoperative day. The diagnosis of histoplasmosis was made retrospectively. Atypical presentation and rarity of the disease led to this diagnostic pitfall. To the best of our knowledge this is the first report of gastrointestinal histoplasmosis presenting as colonic pseudotumour from India.

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 x mm(3) 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 x mm(3) 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.

The systemic mycoses like paracoccidioidomycosis and histoplasmosis, are the main cause of adrenal insufficiency in the countries where they arc endemic. In Venezuela an elevated frequency of these mycoses has been registered. The objective of this study was to evaluate the glucocorticoid adrenal function in patients with paracoccidioidomycosis and histoplasmosis hospitalized in the University Hospital "Ruiz y Pácz" of Ciudad Bolivar (Bolivar state) and in the Hospital "Luis Felipe Rojas Guevara", of El Tigre (Anzoátegui state), Venezuela, between January 2003 and January 2004. The test of fast stimulation with synthetic adrenocorticotrophin hormone (ACTH) was applied to a total of 12 patients with diagnosis of some of these mycoses and data of epidemiologic interest were taken. The proportion men:women was of 5:1, the average age was 35.1 +/- 0.37 years, similar to the control group. Basal plasmatic cortisol levels were within the normal rank in all the patients. After the injection of synthetic ACTH, an increase of plasmatic cortisol values in the same rank for patients with a normal adrenal function was observed, but it was significantly lower than the observed for the control group. These results suggest that there is an adrenal gland functional reserve diminution in patients with either Paracoccidioidomycosis or Histoplasmosis. In patients with systemic mycoses, it is important to evaluate the response to the test of fast stimulation with ACTH due to the frequency of impairment of the glucocorticoid adrenal function in our location.

Purpose: To evaluate responsiveness of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to changes in visual acuity and to provide estimates of minimum clinically meaningful changes in NEI-VFQ scores., Methods: Data were combined from three clinical trials of submacular surgery for subfoveal choroidal neovascularization. Patients who completed NEI-VFQ interviews and visual acuity measurements at baseline and 2 years later contributed data for analysis. Data were analyzed using anchor-based (relating 2-year change in NEI-VFQ to 2-year change in visual acuity using correlation and linear regression) and distribution-based (standardized response mean) methods., Results: Of 1,015 patients enrolled, 828 patients completed NEI-VFQ interviews and had visual acuity measurements at baseline and 2 years later. Median age of patients was 75 years (range 18 to 94); all patients had subfoveal choroidal neovascularization in at least one eye. Median overall NEI-VFQ score at baseline was 69.9 (mean, 66.5). Based on anchor-based methods, a 2-line change in visual acuity of the better-seeing eye translated to a 3.4-point change in the overall NEI-VFQ score and from 2.4-point to 7.0-point changes in most subscale scores. The NEI-VFQ was sensitive to both gains and losses in visual acuity; the standardized response mean for the overall NEI-VFQ score in patients with a 2-line gain was 0.6 and for patients with 2-line loss was -0.3. In the subgroup of patients with a 2-line loss of visual acuity in the better-seeing eye, patients who had overall NEI-VFQ scores at baseline greater than the median (59.8) had an standardized response mean of -0.9 for the overall NEI-VFQ score and patients who had overall NEI-VFQ scores at baseline at or below the median had a standardized response mean of 0.2 for the overall NEI-VFQ score. A 4-point change in the overall NEI-VFQ and a 5-point change in individual subscale scores corresponded to a small clinically meaningful change., Conclusions: The NEI-VFQ was responsive to 2-year changes in visual acuity but was less responsive to changes among patients with poorer NEI-VFQ scores at baseline. Based on this analysis, a 4-point change in the overall NEI-VFQ and a 5-point change in individual subscale scores may be considered minimum clinically meaningful within-person changes in NEI-VFQ scores.

A case of disseminated histoplasmosis in a 45-year-old male patient with acquired immunodeficiency syndrome (AIDS) from Pune is reported. The patient presented with high-grade fever and pain in hypochondrium. Clinical signs were pallor and hepatosplenomegaly. Bone marrow and splenic aspirate revealed numerous intracellular oval shaped yeast forms. Histoplasma capsulatum was isolated from the bone marrow and splenic aspirate. H. capsulatum infection is an opportunistic infection usually reported from patient with AIDS in areas endemic for H. capsulatum. The present case highlights the fact that histoplasmosis could be an emerging opportunistic infection in India.

With the advent of potent immunosuppressive therapies used in solid organ transplantation, patients are more susceptible to a variety of infectious organisms. Infections may result from atypical pathogens and present in an unusual manner. We describe a case of progressive disseminated histoplasmosis presenting as cellulitis in a renal transplant recipient and review this disease.

We studied 52 patients with disseminated histoplasmosis, 30 with the acquired immunodeficiency syndrome (AIDS) (cohort 1) and 22 not co-infected with the human immunodeficiency virus (cohort 2). Demographic, clinical, laboratory, mycologic findings, as well as antifungal therapy and highly active antiretroviral (HAART), were analyzed. Skin lesions were significantly higher in cohort 1 than in cohort 2 (P = 0.001). Anemia, leukopenia, and an elevated erythrocyte sedimentation rate were also more pronounced in cohort 1 than in cohort 2 (P < 0.001). Histoplasma capsulatum was isolated more often in cohort 1 than in cohort 2 (P < 0.05) patients, but antibodies to H. capsulatum were detected more frequently in cohort 2 than in cohort 1 (P < 0.05). Itraconazole treatment was less effective in cohort 1 than in cohort 2 (P = 0.012). In cohort 1 patients, HAART improved response to antifungals when compared with individuals not given HAART (P = 0.003), who exhibited higher mortality rates (P = 0.025). Cohort 1 patients who were given dual antifungal and anti-retroviral therapies responded as well as the non-HIV patients in cohort 2, who were treated only with itraconazole. These results indicate the need to promote restoration of the immune system in patients with AIDS and histoplasmosis.

Objectives: To define the salient clinical and microbiologic characteristics and outcome of infective endocarditis caused by Histoplasma capsulatum., Methods: Case report and review of 43 literature cases., Results: Infection involved both native (36 cases) and prosthetic (7) heart valves, had a high rate of systemic embolization (58%), and a more delayed diagnosis than bacterial endocarditis. Cardiac involvement generally occurred on mitral and/or aortic valves, and almost always in the setting of disseminated disease. Antemortem diagnosis was best made by serology (serum antibody titers or urinary antigen) or culture of blood (positive in <20% of cases), bone marrow, excised valves, and other non-blood specimens. Other diagnostic methods included histopathology and immunofluorescent staining of tissue samples. Untreated infection was uniformly fatal. Prolonged antifungal therapy with amphotericin B, without surgical intervention, appeared more effective than for Candida endocarditis., Conclusions: Histoplasma endocarditis is an infrequent but important cause of left-sided, blood culture-negative endocarditis. Its true prevalence may be underestimated because of the relative difficulty in making a precise microbiologic diagnosis. Amphotericin B therapy appears more effective than for Candida endocarditis, while the role for azole treatment and secondary prophylaxis remains uncertain. Indications for surgical valve replacement are similar to those for bacterial endocarditis.

Purpose of Review: Presumed ocular histoplasmosis syndrome classically presents with atrophic choroidal scars, which are thought to progress into choroidal neovascularization in a small proportion of patients. The pathophysiology of the disease, including its underlying etiology, continues to be controversial and subject to ongoing research. Even more important is the controversy that surrounds the optimal treatment for choroidal neovascularization in patients with presumed ocular histoplasmosis, in particular that of subfoveal localization., Recent Developments: Intense efforts oriented toward defining the most beneficial therapeutic modality have resulted in some well-designed, large studies that evaluated submacular surgery, photodynamic therapies, and anti-angiogenic therapies, as well as small pilot studies exploring new therapeutic approaches for choroidal neovascularization., Summary: Important results obtained by these studies were recently made public, and the conclusions that may be drawn from them, as well as an update on findings concerning presumed ocular histoplasmosis etiology, epidemiology, and pathophysiology are presented in this report.

We report a rare case of disseminated histoplasmosis in a immunocompetent young adult person involving bone marrow, liver, spleen and oral cavity. He presented with oral ulcers, weight loss and pancytopenia. His bone marrow aspiration examination revealed Histoplasma capsulatum.

Objective: To study the clinical features and natural history of disseminated histoplasmosis(DH) in India., Methods: We retrospectively analyzed the data obtained from the in-patient medical records of adults (age > 13 years) diagnosed to have DH during the period from January 1989 to December 1999. DH was diagnosed when histologically compatible intracellular organisms were present or Histoplasma capsulatum was obtained in culture from the extrapulmonary sites., Results: Nineteen patients (18 male and 1 female) were diagnosed to have DH. Diabetes mellitus and HIV infection were the most common co-morbid conditions. Weight loss, fever and oropharyngeal ulcers were the commonest symptoms. Physical signs included hepatosplenomegaly, oropharyngeal ulcers and lymphadenopathy. The diagnosis was confirmed by histopathology and/or culture from the following sites: bone marrow, adrenal gland, lymph node, oropharyngeal ulcers, rectal mucosa and skin. Two patients were treated with Amphotericin B, 6 with various azoles and 3 had Amphotericin B followed by various azoles. Among the eleven treated, 7 were cured, 2 improved, 1 had a relapse and 1 patient died., Conclusion: DH is not uncommon in India and should be considered in the diagnosis of patients with prolonged fever, weight loss, oropharyngeal ulcers, hepatosplenomegaly, lymphadenopathy and adrenal enlargement. Correct diagnosis and treatment leads to a favourable outcome.

Purpose: To describe methods and results and to assess the value of a Traveling Vision Examiner (TVE) Program designed to provide masked vision measurements by expert vision examiners who were independent of, and traveled to, local clinical centers., Methods: The Submacular Surgery Trials (SST) Pilot Study was conducted to refine the design and methods for a set of multicenter, randomized clinical trials to evaluate submacular surgery in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) or ocular histoplasmosis (OHS), or idiopathic CNV in which the primary study outcome would be change in 2-year best-corrected vision from baseline. As part of the SST Pilot Study, the feasibility and value of a TVE Program was assessed. The goal of the program was to obtain unbiased vision measurements, according to a standard protocol, of best-corrected visual acuity, reading speed, and contrast threshold, of each patient at 2 and 4 years after enrollment., Results: Eighty-three visits by TVEs were made to 16 centers participating in the SST Pilot Study; 239 patients had at least one masked vision examination. Comparison of pairs of vision measurements of the traveling vision examiners and local vision examiners for 71 patients made on the same day showed good agreement overall (intraclass correlation coefficient > or = 0.81)., Conclusions: The proposed TVE Program was judged to be a feasible and useful method of providing standardized, unbiased, masked vision measurements. This approach was incorporated into the larger clinical trials conducted by the SST Research Group.

Objective: To evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS)., Design: Open-label, 3-center, uncontrolled clinical study., Participants: Ocular histoplasmosis syndrome patients with subfoveal CNV (N = 26) with a greatest linear dimension no larger than 5400 microm with classic or occult CNV extending under the geometric center of the fovea, and best-corrected visual acuity letter score of approximately 20/40 to 20/200., Methods: The methods were similar to those described in the 1-year results with follow-up examinations every 3 months continuing through the second year. During the second year, additional therapy was recommended if fluorescein angiography showed leakage at a scheduled visit., Main Outcome Measurements: Visual function measurements included the changes from baseline in visual acuity and contrast sensitivity scores. Lesion size and leakage from classic and occult CNV were assessed at month 12 and month 24. Safety assessments also were made., Results: A 24-month examination was completed in 22 of the 26 enrolled participants (85%). At the 24-month examination, median improvement from baseline in visual acuity of the 22 patients evaluated was 6 letters; median contrast sensitivity improved by 3.5 letters. At the 24-month examination, 10 patients (45%) gained 7 or more letters of visual acuity from baseline, whereas 4 patients (18%) lost 8 or more letters, including 2 patients (9%) who lost at least 15 letters. There was absence of fluorescein angiographic leakage from classic CNV in 17 of the 20 evaluable lesions (85%), and leakage from occult CNV was absent in all eyes. No serious ocular adverse events were reported, and no serious systemic event was considered to be associated with treatment., Conclusions: Median visual acuity improved and fluorescein angiographic leakage decreased after verteporfin therapy in this small, uncontrolled clinical study of patients with subfoveal CNV resulting from OHS. Verteporfin therapy seemed to be relatively safe in these patients. The selected cases feature fluorescein angiographic examples of CNV that are important in determining when to apply verteporfin therapy.

The usual manifestation of histoplasmosis is in the form of respiratory illness. We report the case of a 67-year-old man who presented with chronic diarrhea and did not respond to the conventional treatment, including that for Clostridium difficile. He was found to have isolated colonic histoplasmosis infection, which was treated with itraconazole. There was no evidence of any disseminated disease. His only immunocompromised state was end-stage renal disease, for which he was on chronic hemodialysis. Although it is well documented as a part of disseminated histoplasmosis, our extensive review of the literature did not reveal any reported case of isolated colonic histoplasmosis in a patient on hemodialysis.

We report four cases of cerebral histoplasmosis and discuss features of six additional cases reported in the medical literature in the past 10 years, when azoles have been available for therapy. Most patients with this disease are immunocompromised or have a history that suggests heavy exposure to Histoplasma capsulatum. Fever and other clinical findings of systemic toxicity caused by disseminated histoplasmosis may be absent; 5 of 10 patients did not manifest these findings. Although the mainstay of treatment for central nervous system histoplasmosis remains amphotericin B, 9 of the 10 patients received itraconazole or fluconazole either as initial therapy or after a course of treatment with amphotericin B.