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PubMed1991

Disseminated histoplasmosis in AIDS patients in Maryland.

These patients demonstrate the difficulty in arriving at the diagnosis of disseminated histoplasmosis. The diagnosis in two of the three patients also served as the initial AIDS case-defining opportunistic infection. In each of these patients, the clinical presentations were atypical and in only one patient was a positive exposure history elicited. Recurrent bowel obstruction was the presenting complaint in the first patient and the diagnosis was made only on pathologic exam of the resected small bowel. The second patient's diagnosis was made on biopsy of the colon via colonoscopy. The third patient's diagnosis also eluded an extensive FUO workup; he was diagnosed by bone marrow culture and silver stain of a mediastinal lymph node biopsy, despite serial negative serologic tests for histoplasmosis. The first two patients had significant gastrointestinal disease which is a relatively unusual manifestation for disseminated histoplasmosis. The third patient illustrates the limited diagnostic usefulness of serologic testing in AIDS patients and the continued usefulness of bone marrow analysis in an FUO evaluation. In conclusion, these case presentations demonstrate that disseminated histoplasmosis in patients with HIV infection can present with unusual manifestations, outside of the typical endemic arca, without a positive exposure history or positive serologic test, and may be the initial AIDS case-defining opportunistic infection in these patients. Consequently, a disseminated histoplasmosis should be considered in all AIDS patients with perplexing clinical presentations.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Histoplasmosis: update 1989.

Histoplasmosis is a relatively mature disease that was first described 85 years ago. Histoplasmosis was long thought to be a rare and uniformly fatal illness. However, widespread use of skin testing in the 1940s proved that it was a common infection, especially in the central United States, and almost invariably benign. Primary histoplasmosis often presents as a self-limited, nonspecific respiratory infection, and thus, it was realized that a huge iceberg of subclinical and mildly symptomatic cases had been missed for years, since only the highly symptomatic and progressive infections had been diagnosed. Once the disease was recognized as a common one, many new clinical forms of the illness were recognized, including diffuse infiltrates due to heavy exposure, chronic cavitary disease resembling tuberculosis, and complications of primary infection, including mediastinal granuloma and the superior vena caval syndrome. Despite the mature state of histoplasmosis, it is still a disease capable of producing surprises. In this article, the history of histoplasmosis is reviewed, as well as current major concepts about the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of this infection. Newer developments are then highlighted using the same outline.

Chronic Disease↗

PubMed1989

Sarcoidlike manifestations of histoplasmosis.

We have evaluated 11 patients with sarcoidosis accompanied by laboratory evidence for histoplasmosis. Clinical findings were typical of those described in sarcoidosis. Eight patients were treated with corticosteroids and responded promptly without progression of histoplasmosis. One patient received a 35 mg/kg course of amphotericin B without clinical improvement, but responded appropriately to corticosteroid therapy. Another patient had positive sputum cultures for Histoplasma capsulatum 5 years after initial diagnosis of sarcoidosis, but showed no improvement in the pulmonary infiltrate after treatment with amphotericin B. Although histoplasmosis and sarcoidosis may be interrelated in several ways, we postulate that H capsulatum may have triggered a chronic inflammatory disease recognized as sarcoidosis in some of these patients, a hypothesis yet to be tested. Alternative explanations for the association of histoplasmosis and sarcoidosis include the coincidental occurrence of two separate illnesses in a "hyperendemic" area for histoplasmosis and false-positive serologic test results caused by the heightened humoral immune response observed in sarcoidosis.

Adult↗

PubMed1985

Treatment of blastomycosis and histoplasmosis with ketoconazole. Results of a prospective randomized clinical trial. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

In a multicenter prospective randomized trial, the efficacy and toxicity of low-dose (400 mg/d) and high-dose (800 mg/d) oral ketoconazole were compared in 80 patients with blastomycosis and in 54 with histoplasmosis. Among 65 patients with blastomycosis treated for 6 months or more, high-dose treatment was more effective (100% success rate compared with 79%; p = 0.001). Among 19 patients with chronic cavitary histoplasmosis treated for 6 months or more, both regimens were equally effective (overall success rate, 84%). In 20 patients with localized or disseminated histoplasmosis treated for 6 months or more, low-dose treatment was more effective (100% success rate compared with 57%; p = 0.03). The success rate for all patients with histoplasmosis treated for 6 months or more was 85%. Adverse effects occurred in 81 of 134 patients (60%) and were commoner with the high-dose regimen. Ketoconazole is effective for immunocompetent patients with non-life-threatening, nonmeningeal forms of blastomycosis and histoplasmosis. Because of the higher frequency of side effects associated with the high dose, ketoconazole therapy should be initiated with the low dose.

Adult↗

PubMed1986

Progressive disseminated histoplasmosis in patients with the acquired immune deficiency syndrome: a report of 12 cases and a literature review.

Progressive disseminated histoplasmosis is an increasingly common cause of infection in patients with acquired immune deficiency syndrome (AIDS) from areas endemic for histoplasmosis. We report 12 cases of progressive disseminated histoplasmosis associated with AIDS and review 20 previously reported cases. The clinical presentation of progressive disseminated histoplasmosis is nonspecific with persistent fever, weight loss, and splenomegaly. Frequently progressive disseminated histoplasmosis was the initial clue to the presence of AIDS. Bone marrow culture is the best method for establishing a diagnosis. Relapses were common both with ketoconazole and after a 2.0 to 2.5 g course of amphotericin B. This suggests a 2.0 to 2.5 g course of amphotericin B followed by long term ketoconazole suppression may be the best therapeutic regimen in these patients.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Digestive disorders in histoplasmosis. Report of a case of ulcerous enterocolitis caused by Histoplasma capsulatum (author's transl)].

Report of a new American histoplasmosis caused by Histoplasma capsulatum in a young adult Haitian, and review of the digestive disorders as reported in the previous medical papers. In the present case, the first localization detected was a granulomatous hepatitis which lead to the disclosure of an ulcerous entercolitis. Tuberculosis and Crohn disease were first suspected, but their treatment induced a worse turn of the patient's condition and compelled to a laparotomy, which shown ulcerous entercolitis with associated lymph-nodes. Per operative pathological examination gave evidence of Histoplasma capsulatum yeasts. Treatment, first with miconazole and later on with amphotericin B could not prevent the death of the patient affected by a deficiency of cell mediated immunity. Disseminated histoplasmosis is rare: 1 out of 5,000 cases of American histoplasmosis-digestive disorders are generally detected by surgery or post-mortem examination. They occur in 20 p. 100 of the cases envolving the whole digestive tract from mouth to anus, giving mucous ulcerations, difficult to detect by X ray. Endoscopic control with biopsies has therefore a great value. In Histoplasma duboisii, histoplasmosis digestive disorders are very unusual and localized to intestine. They may be detected by surgery, or by endoscopies. In the reported case, in spite of the geographical origin of the patient, the diagnosis of American histoplasmosis was not retained because of the negativity of the immunological tests and of the biopsies performed before surgery. An afterward checking of these biopsy specimens gave evidence of a few yeasts. Special dyeing technique may have made the diagnosis somewhat earlier; this is important because new non toxic imidazole drugs seem to be active against these yeasts.

Adult↗

PubMed1994

[Bone and joint sites of African histoplasmosis (Histoplasma duboisii). Apropos of a case and review of the literature].

The authors report a case of disseminated African histoplasmosis with bone and joint involvement in a black 28-year-old citizen of the Central African Republic who presented with a 17-month history of multiple osteoarticular lesions (sternoclavicular joints, humerus, ribs), cutaneous lesions (face, scalp, thorax), and lymphadenopathy. Clinical manifestations resolved rapidly under treatment with ketoconazole (600 mg/d for 10 days then 400 mg/day for nine months). Persistent yeast cells were then found upon examination of a lymph node biopsy specimen. The characteristics and diagnosis of osteoarticular lesions due to African histoplasmosis are discussed on the basis of a review of the literature. Bone and joint lesions due to African histoplasmosis have not yet been reported in patients with the acquired immunodeficiency syndrome. However, the expanding epidemic of human immunodeficiency virus infection in Africa can be expected to result in an increase in the incidence of African histoplasmosis. Imidazole derivatives are easier to use on a long-term basis than amphotericin B and have significantly improved our ability to treat African histoplasmosis.

AIDS-Related Opportunistic Infections↗

PubMed1993

Resistance mechanisms in murine experimental histoplasmosis.

The study by use of immunocytochemical methods shows that the spleen of mouse infected intravenously by Histoplasma capsulatum is heavily infiltrated by macrophages. The CD4+ and CD8+ T cells are diffused and sparsely distributed throughout the spleen. It appears that experimental histoplasmosis in animals presents as a disease of the mononuclear phagocyte systems. Macrophages are important cells in controlling replication of intracellular H. capsulatum. Factors that affect the infiltration and activation of macrophages are, thus, important in host defense against histoplasmosis. Depletions of endogenous TNF-alpha in animals infected with sublethal dose of H. capsulatum results in death of these animals. The fungus burden in these animals is high and macrophages are not capable of restricting proliferations of the fungus. However, the role of TNF-alpha in histoplasmosis is not a direct activation of macrophages and is still yet to be defined. IFN-gamma has been shown to fully activate mouse peritoneal macrophages and partially activate splenic macrophages for anti-histoplasma activity. The importance of IFN-gamma in host defense against histoplasmosis is studied by use of resistant A/J and susceptible C57BL/6 mouse strains. There is a good correlation of early production of IFN-gamma by spleen cells of infected mice with the ability of the animals to clear the infection. Spleen cells of resistant A/J mice are more efficient than susceptible C57BL/6 mice in production of IFN-gamma. Recombinant inbred progeny of A/J and C57BL/6 mice are used to locate the genes that control resistance to histoplasmosis. Preliminary studies show that the resistance phenotype is controlled not by a single gene but by multiple genes.

Animals↗

PubMed1996

Small bowel obstruction from gastrointestinal histoplasmosis in acquired immune deficiency syndrome.

Disseminated histoplasmosis is a rare condition that is associated with an underlying immune disorder in approximately 25 per cent of patients. It often leads to GI histoplasmosis, but when the disease predominantly affects the GI tract few, if any, pulmonary symptoms appear. Although histoplasmosis of the gastrointestinal system has been described, it rarely causes a small bowel obstruction. In fact, a recent review of the English literature revealed 77 cases of gastrointestinal histoplasmosis, with only none having clinical presentation solely involving of the jejunum and ileum in acquired immune deficiency syndrome (AIDS) patients. At the time of urgent abdominal exploration, both patients had several areas of bowel strictures with subjacent mesenteric adenopathy. They required resection of small bowel segments. Pathology examination established the diagnosis of histoplasmosis, and both patients were discharged home after antifungal therapy.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Disseminated histoplasmosis in AIDS patients. A study of 2 cases and review of the Spanish literature].

The characteristics of two cases of histoplasmosis in AIDS patients in our institution are presented together with a review of the 11 cases published in Spain since 1988 in addition to the current knowledge on histoplasmosis in patients with human immunodeficiency virus infection (HIV). In all except 2 of the 13 patients there was epidemiologic history of a stay in a country in which histoplasmosis is endemic. The 12 cases described in which this information is available had CD4 counts under 100/microL. The clinical manifestations of presentation were fever (92.3%) associated or not with other unspecific symptoms (asthenia, anorexia, cough, diarrhea) with a subacute course of two or three months. Physical examination demonstrated hepatosplenomegaly in 76.9% of the cases and 61.5% of the patients presented cutaneous lesions. Thoracic radiography was abnormal in 55% (61.5% had respiratory symptoms). Diagnosis was achieved by isolation of the fungus in the cutaneous biopsies in all the patients with dermatologic involvement and in 7 cases identification was performed in the bone marrow. In all the cases induction treatment was with anphotericin B and in those who reached the maintenance phase itraconazol was used in 7 cases and ketoconazol in one case. None of the patients treated with itraconazol, including the two in our center, presented recurrence at the time of completion of follow up. In conclusion, histoplasmosis is frequently presented as a prolonged febrile syndrome with unspecific characteristics, thus emphasizing the importance of including travel history to other countries in the anamnesis. The increase in journeys to endemic countries and immigration from these areas had led to an increase in the number of cases of histoplasmosis in patients with HIV infection in Spain.

AIDS-Related Opportunistic Infections↗

PubMed1998

Reactivation of inflammatory lesions in ocular histoplasmosis.

BACKGROUND: Active inflammation has not been traditionally associated with the ocular histoplasmosis syndrome. OBJECTIVE: To investigate the occurrence of presumed inflammatory chorioretinal lesions in patients with the ocular histoplasmosis syndrome. METHODS: Patients seen with acute symptoms and a clinical picture of ocular histoplasmosis were observed prospectively between August 13, 1993, and December 2, 1997. Symptoms, visual acuity, and fluorescein sodium angiography were used to document changes in inflammatory loci. RESULTS: Twelve patients were seen with active inflammatory lesions. Eleven had resolution of the loci with lessening of symptoms and improvement in acuity and angiographic findings. A typical subretinal neovascular membrane developed in 1 patient 8 months after the onset of symptoms. CONCLUSIONS: Inflammatory chorioretinal lesions can reactivate in the ocular histoplasmosis syndrome. In most of these patients, neovascularization did not develop and visual acuity was preserved.

Acute Disease↗

PubMed1995

Mediastinal histoplasmosis presenting with esophageal involvement and dysphagia: case study.

Esophageal involvement with histoplasmosis is uncommon, but has been recognized in two clinical settings. Most commonly, the esophagus becomes involved as a result of contiguous mediastinal lymphadenopathy. Such patients usually present with dysphagia secondary to midesophageal compression or stricture. The esophagus can also be involved in cases of disseminated histoplasmosis. Esophageal ulcers or nodular lesions are the usual clinical manifestations in this setting. We report a case of mediastinal histoplasmosis with esophageal narrowing and mucosal ulceration that presented with dysphagia. The diagnosis was established at thoracotomy by the histologic finding of necrotizing granulomas and a positive fungal stain. The case was successfully treated with amphotericin B. The literature on esophageal and gastrointestinal histoplasmosis is reviewed.

Adult↗

PubMed1983

Histoplasmosis in Veterans Administration hospitals in middle America.

A series of clinical studies of histoplasmosis based on demonstrations of etiology led to descriptions of chronic pulmonary histoplasmosis, the principal type in adults, and amphotericin B as an effective therapy. A participant recreates the atmosphere of discovery during the contributions of a team comprising a mycologist, a surgeon and two physicians using cultures of excised lung and sputum to clearly identify cases of chronic pulmonary histoplasmosis. Subsequently cooperating physicians in several V.A. Hospitals carried out randomized studies of treatment, dosage, and side effects that established Amphotericin B as the sole curative therapy for chronic pulmonary histoplasmosis for 20 years.

Amphotericin B↗

PubMed1990

Gonarthritis as only manifestation of chronic disseminated histoplasmosis.

A native from Surinam (South America), known to have a chronic gonarthritis for 20 years, died from an acute disseminated histoplasmosis. His gonarthritis was retrospectively shown to have been due to histoplasmosis. Although histoplasmosis rarely presents as a monarthritis, unacquaintance with this entity may result in fatal acute dissemination of the histoplasmosis.

Arthritis, Infectious↗

PubMed2005

High 18F-fluorodeoxyglocose uptake in adrenal histoplasmosis; a case report.

Adrenal histoplasmosis is one of the most common adrenal granulomatous infections in endemic areas. Although CT or MRI findings of adrenal histoplasmosis have been documented, there are no reports regarding 18F-fluorodeoxyglocose (FDG) positron emission tomography (PET) findings. We report a case of bilateral adrenal histoplasmosis showing a significantly high uptake of 18F-fluorodeoxyglocose on PET study. Adrenal histoplasmosis should be considered as one of the differential diagnoses in cases of adrenal tumors with intense FDG uptake, even in non-endemic areas.

Adrenal Gland Diseases↗

PubMed1979

Bat-associated histoplasmosis in Maryland bridge workers.

An epidemic of acute prolonged febrile respiratory disease affecting nine of 19 workers on a Maryland State bridge maintenance crew was diagnosed as histoplasmosis by serologic testing in all and by isolation of the organism in one. In our investigation, it was revealed that work on a particular bridge was associated with disease. Culture of bat guano from the site two months later revealed H. capsulatum. Four previously uninfected epidemiologic investigators also became ill with histoplasmosis following collection of soil and bat guano. This outbreak reveals that bats and bat guano are a source of histoplasmosis, suggests that only brief exposure is necessary for acute infection and reemphasizes that histoplasmosis is not confined to the midwestern states.

Animals↗

PubMed1980

Chronic pulmonary histoplasmosis following the excavation of a bird roost.

The clinical and epidemiologic characteristics of chronic pulmonary histoplasmosis, as compared with the more familiar acute pulmonary histoplasmosis, are relatively unknown. Opinions vary as to the pathogenesis, and only the severe forms of the disease are readily recognized. Over a 22 month period following the excavation of blackbird roost, an unusual outbreak of chronic pulmonary histoplasmosis occurred in a town in southern Kentucky. Thirteen of the cases developed over a span of only four months. An associated outbreak of acute pulmonary histoplasmosis did not occur. During the course of the ensuing investigation, the residential addresses of the affected persons were noted to be clustered about the previously excavated blackbird roost. A case-control study was initiated; the median distance of the residential addresses of the affected persons was found to be 1.0 miles from the roost, compared with 3.2 miles for the control subjects (P less than 0.001). It was concluded that (1) the excavated blackbird roost had served as the common source of the epidemic; (2) the inhalation of exogenous spores accounted for the infections; (3) the spectrum of clinical illness ranged from asymptomatic and mild illness to cavitary disease with considerable morbidity; and (4) following excavation, blackbird roosts may remain an infection hazard for an indefinite period of time.

Animals↗

PubMed1983

Treatment of disseminated and progressive cavitary histoplasmosis with ketoconazole.

Ten patients with disseminated histoplasmosis and seven with progressive cavitary histoplasmosis were treated with ketoconazole, an imidazole derivative that is well absorbed orally and relatively nontoxic. Seven of seven noncompromised hosts with disseminated disease tolerated therapy well and achieved clinical and mycologic cures. Although well tolerated in all three compromised hosts with disseminated disease, none achieved clinical and bacteriologic cures. All patients with progressive cavitary disease tolerated therapy well and six of seven achieved clinical and radiographic cures. Therefore ketoconazole appears safe and effective in the treatment of disseminated or progressive cavitary histoplasmosis in the noncompromised host. In the compromised host with disseminated histoplasmosis, ketoconazole does not appear to be effective and more conventional therapy appears warranted.

Adult↗