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PubMed1985

Histoplasmosis in the acquired immune deficiency syndrome.

This report describes the experience with disseminated histoplasmosis in seven of 15 patients with the acquired immune deficiency syndrome (AIDS) diagnosed in Indianapolis since 1981. Three were homosexual, two were intravenous drug addicts, one was the spouse of another patient with AIDS and disseminated histoplasmosis, and the seventh was a hemophiliac. Six had associated infections: candidiasis in three, Pneumocystis carinii pneumonia, recurrent mucocutaneous herpes simplex infection, and disseminated Mycobacterium avium infection in two each, and disseminated infection with an unidentified mycobacterium in one. Clinical diseases suggested sepsis in four. Histoplasma fungemia occurred in five, but the diagnosis was established first by visualization of organisms in blood or bone marrow in three. Results of Histoplasma serologic tests were positive in each. Three died before receiving 50 mg of amphotericin B, three had prompt improvement with amphotericin B, and one was treated with ketoconazole to prevent dissemination. However, two of the three patients treated with amphotericin B had relapses after a 35 mg/kg course, and the third died within a month following therapy. Disseminated histoplasmosis is a major opportunistic infection in patients with AIDS from endemic areas. AIDS should be strongly considered in otherwise healthy persons with disseminated histoplasmosis, especially if risk factors for AIDS are present. Amphotericin B is not curative in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effect of successful treatment with amphotericin B on Histoplasma capsulatum variety capsulatum polysaccharide antigen levels in patients with AIDS and histoplasmosis.

PURPOSE: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. PATIENTS AND METHODS: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. RESULTS: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment. CONCLUSIONS: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the effectiveness of fluconazole for suppression of relapse of histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective, nonrandomized, open trial. SETTING: Multicenter at two university referral centers and in five private practices. PATIENTS: Seventy-six patients with AIDS and disseminated histoplasmosis who completed induction treatment with amphotericin B, itraconazole, or fluconazole and maintained on treatment with fluconazole to prevent relapse. INTERVENTIONS: Fluconazole was given at dosages of 100 to 400 mg per day. Patients were followed by their primary physicians, who completed questionnaires collecting information about treatment and relapse status. Blood and urine specimens were submitted periodically for Histoplasma capsulatum var. capsulatum antigen determination. MEASUREMENTS AND MAIN RESULTS: Nine of the 76 patients relapsed during fluconazole therapy and another was removed from the study because of allergic rash. Survival after initiation of therapy for histoplasmosis was 94 weeks, ranging from 74 weeks for those who received less than 1 g of amphotericin B for induction and none for maintenance therapy to 156 weeks for those who received greater than 1 g for induction and additional amphotericin B for maintenance therapy before beginning fluconazole (P < 0.02). Antigen levels fell at rates of 0.05 units/week in urine and 0.02 units/week in serum in patients who were successfully maintained in remission and increased by > or = 2 units/week in 4 of 6 patients who relapsed. CONCLUSIONS: Fluconazole > or = 200 mg daily is a reasonable choice for chronic suppressive therapy of histoplasmosis in patients who cannot take itraconazole because of drug interactions, malabsorption, or side effects.

AIDS-Related Opportunistic Infections↗
PubMed1980

Association of HLA-DRw2 antigen with presumed ocular histoplasmosis.

Patients with presumed ocular histoplasmosis syndrome were typed for HLA-A, B, C, and DR antigens. It was found that 21 (81%) of 26 of the presumed ocular histoplasmosis syndrome patients with disciform macular scarring and 8 (62%) of 13 of the presumed ocular histoplasmosis syndrome patients with peripheral atrophic spots typed for DRw2. The frequency of DRw2 in normal blood donors was 28%. The 77% (20 patients) frequency of B7 in 26 of the presumed ocular histoplasmosis syndrome patients with disciform scarring was also significantly higher than the 25.6% frequency of B7 in normal blood donors. In contrast, no significant differences were observed in any HLA antigen frequency for patients with disciform scarring of degenerative choroidopathy. These observations suggest that an association with DRw2 may play a role in the pathogenesis of the eye lesions after Histoplasma capsulatum infection.

Choroid↗
PubMed1990

Sclerosing mediastinitis: improved management with histoplasmosis titer and ketoconazole.

Recognition that many patients with benign sclerosing mediastinitis have smoldering disease responsible for failure of surgical procedures or for development of collateral circulation in patients with superior vena caval obstruction has markedly improved management of these difficult patients. Histoplasmosis complement fixation titers have been used to detect unsuspected subacute disease and to follow the therapeutic adjunctive management with ketoconazole, an oral antifungal agent. Twenty-two patients with benign sclerosing mediastinitis demonstrated a variety of symptoms relating to the area of compression: superior vena cava, 13; esophagus, 3; pulmonary artery and pericardium, 3; and trachea, 3. Histoplasmosis was documented in 12 patients. Operation is used initially for diagnosis, to rule out carcinoma, and to treat the complications: superior vena caval reconstruction, 6; tracheal decompression, 2; right middle lobectomy, 1; esophageal decompression, 2; division of tracheoesophageal fistula, 1; and release of pericardial effusion and cardiac tamponade, 1. Postcardiotomy syndrome occurred in 1 patient and wound infection in another. No deaths resulted. In 6 cases of histoplasmosis, symptoms recurred in 100% of patients and were successfully managed with ketoconazole treatment, and then clinical progress was monitored with serial histoplasmosis complement fixation studies. One patient had four superior vena caval reconstructions at an outside hospital, each 1 year apart, with symptoms recurring each time. With ketoconazole therapy alone, she has been asymptomatic for more than 2 years. Vigorous search for a fungal cause may even obviate the necessity for surgical intervention. If an operation is necessary, preoperative and postoperative use of ketoconazole has assured success.

Adult↗
PubMed2004

Endobronchial histoplasmosis: a masquerade of primary endobronchial neoplasia--a clinical study of four cases.

BACKGROUND: Histoplasma capsulatum is a dimorphic fungus with both hyphal and microconidial elements and is endemic in certain areas of the central United States. Most clinically recognized syndromes are self-limited, presenting in more than 80% of cases as an influenza-like acute pulmonary illness. We encountered four patients with an endobronchial presentation of histoplasmosis masquerading as a bronchogenic malignancy. METHODS: The patient files from one of the authors (PR) uncovered four patients diagnosed with, and treated for, endobronchial histoplasmosis; all cases were referred for a presumptive diagnosis of endobronchial neoplasia. RESULTS: The case study group comprised three women, ages 52, 68, and 81 years, respectively, and one man age 29 years, all presenting with recurrent hemoptysis. An obstructing adherent lesion was apparent on bronchoscopy in three, involving the right upper lobe bronchus in two, and right mainstem bronchus in one. In one patient, blood was observed in the bronchus intermedius; there was no gross lesion. Recurrent hemoptysis necessitated a right upper sleeve lobectomy in one, a right upper lobe lobectomy and right lower wedge resection in one, a right middle lobectomy in one, and wedge resection of the right upper lobe in one. CONCLUSIONS: Endobronchial histoplasmosis may mimic primary bronchogenic carcinoma, presenting as a fixed obstructing endobronchial lesion associated with hemoptysis; the latter potentially necessitating surgical intervention. Endobronchial histoplasmosis should be considered in the differential diagnosis of obstructing endobronchial lesions associated with hemoptysis, especially when prior and(or) concurrent biopsies fail to disclose malignancy.

Adult↗
PubMed2005

Histoplasmosis and penicilliosis: comparison of clinical features, laboratory findings and outcome.

INTRODUCTION: Histoplasmosis and penicilliosis are infections caused by the dimorphic fungi, Histoplasma capsulatum and Penicillium marneffei, respectively. The aim of this study was to compare the clinical presentation, laboratory and radiologic findings and outcome of these infections at Srinagarind Hospital, Khon Kaen, Thailand. METHODS: The medical records of patients who had positive cultures for Histoplasma capsulatum and Penicillium marneffei during 1996-2002 were reviewed. The data were compared and analyzed by the Chi-square and Fisher's exact tests. RESULTS: There were 32 and 36 medical records of patients with H. capsulatum and P. marneffei infection, respectively, available for review. The most common underlying disease of patients with histoplasmosis and penicilliosis was acquired immunodeficiency syndrome (AIDS), which accounted for 90.6% and 91.7%, respectively. The most common clinical findings in both infections were fever, weight loss, cough, anemia, lymphadenopathy, hepatomegaly and splenomegaly. Frequencies of skin lesions were not statistically different between either group (P=0.20). Laboratory findings were similar between the two infections, except hyperbilirubinemia, which was more common in the penicilliosis group (P=0.02). There were similar abnormal X-ray findings in both groups with interstitial infiltration the most common abnormality. CONCLUSIONS: Histoplasmosis and penicilliosis had similar clinical presentations, laboratory findings and chest X-ray abnormalities. Itraconazole is recommended as secondary prophylaxis in HIV-infected patients who have histoplasmosis or penicilliosis.

AIDS-Related Opportunistic Infections↗
PubMed2006

Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay.

Antigen detection is a useful adjunct for the diagnosis of histoplasmosis. The purpose of this study was to evaluate antigen detection in bronchoalveolar lavage (BAL) fluid using an improved second-generation Histoplasma antigen assay. Antigen was detected in 16 of 19 (84%) cases of histoplasmosis and 5 of 6 (83.3%) blastomycosis cases using the second-generation assay vs. 13 of 19 (68%) and 4 of 6 (66.7%), respectively, in the original assay. Ten-fold concentration permitted detection of antigen in an additional case of histoplasmosis and another with blastomycosis, for an overall sensitivity of 23 of 25 (92.0%). Specificity was 98.2% in both assays in controls with other pulmonary infections. These findings support the diagnostic utility of the second-generation assay in patients with pulmonary histoplasmosis and blastomycosis.

Antigens, Fungal↗
PubMed2006

Histoplasmosis in two aboriginal patients from Australia's tropical Northern Territory.

Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the tropical Northern Territory, nor in Aboriginal Australian patients. We report one suspected and one confirmed case of severe disseminated histoplasmosis in Aboriginal Australians from the Northern Territory. Underlying illness included chronic cardiac disease and Type 1 diabetes mellitus, respectively, and neither patient was infected with HIV. The clinical presentations resembled malignancy. Diagnosis of histoplasmosis was made on the basis of bowel histology in Case 1, demonstrating characteristic yeasts, and lymph node histology and culture in Case 2. Histoplasmosis should be considered in relevant clinical situations, even in HIV-negative patients who have not left Australia.

Adult↗
PubMed1997

Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group.

PURPOSE: This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study. CONCLUSIONS: Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse.

AIDS-Related Opportunistic Infections↗
PubMed1979

Histoplasmosis simulating lymphoma in children.

The experience of two Mineapolis hospitals with histoplasmosis over a 10-yr period was reviewed. Six of eleven pediatric patients with histoplasmosis presented with systemic symptoms, a mediastinal mass, and no pulmonary infiltrates. A clinical diagnosis of lymphoma was made in each case. Immediate radiation therapy for respiratory compromise was considered in one patient before pathologic diagnosis revealed primary histoplasmosis of the mediastinum. Although immediate therapy with steroids or irradiation is often considered in patients who have acute respiratory embarrassment caused by a mass, histologic confirmation of the diagnosis is always indicated before such therapy is instituted. Primary histoplasmosis of the mediastinum may be more common than previously thought.

Adolescent↗
PubMed1993

Disseminated histoplasmosis with glomerulonephritis mimicking Wegener's granulomatosis.

Renal complications of disseminated histoplasmosis include chronic recurrent abcesses of the interstitium and urogenital tract. To our knowledge, glomerulonephritis has never been reported in histoplasmosis. We describe a case of proven histoplasmosis presenting with oral granulomatous ulceration and segmental glomerulonephritis that mimicked Wegener's granulomatosis (WG). All symptoms and renal parameters remitted under itraconazole treatment alone. In conclusion, glomerulonephritis may complicate the course of chronic disseminated histoplasmosis. Since it can masquerade as WG, systematic tissue staining for intracellular microorganisms should be done when WG is suspected.

Diagnosis, Differential↗
PubMed2005

Imported and autochthonous histoplasmosis in Italy: new cases and old problems.

In the past the Italian soil was considered as a low-endemic pabulum for H. capsulatum var. capsulatum and only few autochthonous cases of histoplasmosis were reported in Italy, especially in the Po valley. The aim of the paper was to evaluate this possibility by reviewing the literature and providing our own personal data. Four additional cases of histoplasmosis were observed during 1999-2003 in AIDS immigrant or in Italian citizens, and in travellers to endemic areas. One of the AIDS patients was an autochthonous case of histoplasmosis. The Italian literature was reviewed. Recent cases and literature data confirm the possible autochthonous presence of histoplasmosis in Italy, especially in the Northern regions.

AIDS-Related Opportunistic Infections↗
PubMed2002

Disseminated cutaneous histoplasmosis in patients infected with human immunodeficiency virus.

BACKGROUND: In the pre-AIDS era disseminated histoplasmosis was rare and the cutaneous manifestations thereof were reported infrequently. A range of unusual clinical manifestations of disseminated cutaneous histoplasmosis (DCH) in AIDS patients has been documented, but the cutaneous histopathological descriptions are short and incomplete. In addition, the histopathological spectrum of AIDS-associated DCH is poorly recognized. METHODS: This is a prospective 32-month study of all HIV positive patients diagnosed with histoplasmosis in the Departments of Anatomical Pathology and Dermatology, Nelson R. Mandela School of Medicine and King Edward VIII Hospital, Durban, South Africa. Clinical distribution and morphology of the individual skin lesions and CD4+ lymphocyte counts in the peripheral blood were analysed in relation to the histopathological features of biopsied lesional tissue. Ultrastructural examination of tissue retrieved from the wax blocks of three cases that exhibited dermal karyorrhexis and collagen necrosis was undertaken. Fungal culture of lesional skin tissue was undertaken in all patients. RESULTS: Twenty-one biopsies of papules (7), nodules (4), plaques (5), erythema multiforme-like lesions (2), vasculitic lesions (2) and exfoliative dermatitis (1) from 14 patients were examined. Of four biopsies (CD4 range: 120-128 cells/mm3) one and three demonstrated necrotizing and non-necrotizing granulomatous inflammation with a paucity of intrahistiocytic microorganisms. Seven biopsies (CD4 range: 2-56 cells/mm3) demonstrated diffuse dermal and intravascular accumulation of histiocytes densely parasitized by Histoplasma capsulatum var. capsulatum. Vasculitis, karyorrhexis or collagen necrosis was not present. Ten biopsies (CD4 range: 2-72 cells/mm3) demonstrated diffuse dermal karyorrhexis, collagen necrosis and interstitial, extracellular H. capsulatum var. capsulatum. Histiocytic disintegration and nuclear fragmentation and release of intact microorganisms and intact and ruptured lysosomes were identified ultrastructurally. Leucocytoclastic vasculitis was present in two biopsies of vasculitic clinical morphology. Microbiological culture confirmed histoplasmosis in all cases. Three patients died before treatment was commenced. Two patients died within the first two days of induction of therapy. Nine patients demonstrated dramatic healing of the cutaneous lesions. CONCLUSIONS: Despite the clinicopathological spectrum of DCH and the attendant host immunocompromise, timely and appropriate treatment of DCH may be lifesaving and allows rapid healing of skin lesions. A high index of clinical suspicion and skin biopsies and culture are crucial for accurate diagnosis.

Adult↗
PubMed2001

Treatment of histoplasmosis.

Histoplasmosis is an endemic mycosis, which is most prevalent in the Ohio and Mississippi valleys of North America. The causative organism is a dimorphic fungus, Histoplasma capsulatum. Histoplasmosis can present as a self-limited disease or cause life-threatening diseases resulting in considerable morbidity and mortality. Treatment is appropriate in patients with diffuse acute pulmonary infection, chronic pulmonary infection, mediastinal granuloma causing obstruction of important structures, or disseminated infection. Other chronic forms of disease such as fibrosing mediastinitis and broncholithiasis are unresponsive to pharmacologic treatment. Options for therapy include amphotericin B or one of its lipid formulations, and ketoconazole, itraconazole, or fluconazole. Recently, newer antifungal agents have been evaluated in animals models of histoplasmosis. Of these, a new triazole, posaconazole (SCH56592) appears most promising. Generally, amphotericin B or one of the lipid formulations is recommended as initial treatment in patients with more extensive diseases, felt to be ill enough to require hospitalization, and itraconazole for those who have milder illness, or to complete treatment after patients respond to amphotericin B. The role of intravenous formulation of itraconazole for severe histoplasmosis is unknown because studies comparing it with amphotericin B have not been conducted.

Amphotericin B↗
PubMed2002

[Histoplasmosis group disease in bat researchers returning from Cuba].

CASE HISTORY: Four males (age 25 to 40 years) and one female (age 25) were admitted to our hospital almost simultaneously with symptoms of fever up to 38 degrees C, dry cough, thoracodynia, dyspnoea, myalgia and arthralgia. All patients belonged to a team of eight German bat researchers who had returned from Cuba 10 days before, where they had investigated bats in caves. Another member of the team had only mild histoplasmosis and was followed in our outpatient clinic. Two scientists who wore their breathing masks continuously during their work in the caves did not fall ill. EXAMINATIONS: Chest X-rays of all in-patients showed pulmonary infiltrates correlating with the severity of their illness. In all patients specific IgG antibodies against Histoplasma capsulatum-antigen were found in the Western Blot assay, confirming the diagnosis of histoplasmosis. TREATMENT: Treatment with oral itraconazole 200 mg b.d was given to four inpatients for 6 weeks, in the fifth patient itraconazole was discontinued because of an increase of liver transaminases. CONCLUSION: Antimycotic treatment of advancing histoplasmosis seems appropriate also in immunocompetent patients. The high number of patients within this group suggests high numbers of Histoplasma capsulatum in the caves. Wearing breathing masks throughout the work in the caves may prevent histoplasmosis even in case of high infectious doses. Pre-travel recommendations for cave researchers have to emphasize the continuous use of breathing masks and vaccination against tetanus and rabies.

Adult↗
PubMed2002

Oral histoplasmosis in Brazil.

OBJECTIVE: We report 10 cases of histoplasmosis with oral manifestations seen in a teaching hospital in Brazil. STUDY DESIGN: This is a retrospective study of the sociodemographic, clinicopathologic, and treatment data of these cases. RESULTS: Overall, 8 of 10 cases were seropositive for human immunodeficiency virus (HIV), whereas 2 were negative. The predominant oral manifestations found in HIV-seropositive patients were ulcers, oral pain, and odynophagia; both of the HIV-seronegative patients were symptom-free. HIV infection was suspected in 7 cases because of the presence of oral lesions of histoplasmosis. Asthenia, fever, weight loss, lymphadenopathy, and hepatosplenomegaly were found only in HIV-seropositive patients. Radiographs in 3 out of 10 patients suggested pulmonary involvement. Amphotericin B was the antifungal therapy chosen, and clinical remission of oral lesions occurred in an average of 30 days (accumulated doses: 500-1500 mg). Itraconazole was very effective as a follow-up treatment in terms of prevention of recurrence. CONCLUSION: Histoplasmosis only rarely affects HIV-seronegative patients; however, the possibility of hidden immunodepression should be considered when oral manifestations of histoplasmosis are present.

AIDS-Related Opportunistic Infections↗
PubMed1987

Canine histoplasmosis in Rio de Janeiro: natural and experimental infections.

Seven of 73 mongrel dogs in Rio de Janeiro gave positive results in skin tests with a polysaccharide mycelial antigen from Histoplasma capsulatum. Five of the positive reactors were necropsied and four of them had disseminated histoplasmosis proved by histopathology and culture. Four healthy puppies exposed for 10 min to soil at the site of a known outbreak of histoplasmosis developed symptoms and died 7-14 days after exposure with fulminant histoplasmosis. These experiments show the value of dogs as epidemiological indicator of histoplasmosis and as experimental models for the disease.

Animals↗