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Malabsorption syndrome occurring in the course of disseminated histoplasmosis: case report and review of gastrointestinal histoplasmosis.

Histoplasmosis is caused by the dimorphic fungus, Histoplasma capsulatum. The disease spectrum varies from a mild respiratory infection to a lethal, disseminated form. Involvement of any part of the gastrointestinal tract may occur with the disseminated form, and symptoms reflect that portion involved. A case of malabsorption syndrome occurring during the course of disseminated histoplasmosis is reported, and the literature of gastrointestinal histoplasmosis is reviewed.

Biopsy

Histoplasmosis in children: emerging insights and evolving guidelines.

PURPOSE OF REVIEW: This review provides an update on the epidemiology, risk factors, clinical presentation, diagnosis, and management recommendations incorporating recommendations from recent publications including the Infectious Disease Society of America guidelines for the management of pulmonary and disseminated histoplasmosis. RECENT FINDINGS: Updates to the epidemiology of histoplasmosis indicate a broader geographic range than historically defined. Updated guidelines do not recommend routine treatment for asymptomatic, mild and moderate pulmonary histoplasmosis although itraconazole can be offered for immunocompromised children or for prolonged or worsening symptoms. Liposomal amphotericin B is recommended as initial treatment for severe histoplasmosis syndromes (severe pulmonary and disseminated histoplasmosis). Fibrosing mediastinitis, a late complication of histoplasmosis is treated with stenting of vessels and bronchi. Recent studies demonstrate that rituximab (anti-CD20 monoclonal antibody) may stop progression or lead to regression of progressive fibrosis. SUMMARY: Histoplasmosis has manifold manifestations, many of which are self-limited and do not require treatment. Severe histoplasmosis and its complications should be treated with liposomal amphotericin B followed by itraconazole. Clinical trials are needed to assess the efficacy of rituximab for the treatment of fibrosing mediastinitis.

Humans

The value of the skin test and complement fixation test in the diagnosis of chronic pulmonary histoplasmosis.

Histoplasmin skin test results in patients with chronic pulmonary histoplasmosis from Missouri and Texas were compared to results in a previous study of U.S. Navy recruits. When consideration was given to geographic areas from which persons from each group were admitted to the study, it was found that the recruits were as likely to have a positive skin test as were those with the disease. In a similar manner, the Texas histoplasmosis patients were compared to groups of patients from that state with chronic obstructive pulmonary disease and with pulmonary tuberculosis. Again, no significant differences were found. It was concluded that the histoplasmin skin test is not of value in the diagnosis of chronic pulmonary histoplasmosis. Histoplasmosis complement fixation test data from the chronic pulmonary histoplasmosis group were compared to data from the chronic obstructive pulmonary disease and pulmonary tuberculosis groups. The usefulness of the complement fixation test in chronic pulmonary histoplasmosis is limited, as with any test, by false-positive and false-negative reactions. A decision theory method was used to define the limits of usefulness.

Chronic Disease

Isolated nodular cutaneous histoplasmosis. The initial manifestation of recurrent disseminated disease.

Cutaneous manifestations of histoplasmosis may be divided into primary and secondary lesions. Primary cutaneous histoplasmosis is rare; to our knowledge, there are only three reported cases in the literature. Secondary cutaneous histoplasmosis develops during the course of disseminated disease. An isolated nodule of the hand was the initially appearing sign of recurrent disseminated disease in our patient. Because of the extreme rarity of primary cutaneous histoplasmosis, cutaneous lesions that are proven to be due to histoplasmosis should alert the physician to the presence of disseminated disease.

Adult

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

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

Immunodiagnosis of histoplasmosis in a compromised host.

Three serological tests for the diagnosis of histoplasmosis were compared for sensitivity and specificity in serum from blood bank donors, patients with histoplasmosis, and infected or noninfected immunosuppressed patients. The histoplasmin latex agglutination test was positive in 9% of the normal patients, 33% of the histoplasmosis patients, and 61% of the noninfected immunosuppressed patients. Since the test is prone to many false-positive results in patients with inflammatory diseases or non-Histoplasma infections, it has limited potential as a screening test among compromised patients. Immunodiffusion and counterimmunoelectrophoresis using a mycelial antigen were found to be more sensitive than either test using a combined yeast and mycelial antigen or a pure yeast phase antigen. Counterimmunoelectrophoresis at pH 7.2 proved to be the test of choice for serodiagnosis of histoplasmosis, resolving 85% of the immunocompetent infected patients and 100% of the infected immunosuppressed patients. Results indicated that counterimmunoelectrophoresis in conjunction with immunodiffusion could be used as a screening protocol to determine infection in incoming patients in a cancer hospital.

Antibodies, Fungal

Disseminated histoplasmosis in renal transplant recipients.

Five cases of disseminated histoplasmosis complicating renal transplantation are reported. Nine previously reported cases from the literature are reviewed. In this setting disseminated histoplasmosis usually presents as a nonspecific systemic febrile illness that may be fulminant or more subacute. Five of 14 patients presented with skin lesions; only one patient presented with primary pulmonary symptoms of cough and dyspnea. Three of our patients and three others previously reported on survived the infection and maintained good function in the transplanted kidney despite prolonged therapy with amphotericin B. Immunosuppression was the only predisposing factor that could be identified with certainty in the five patients reported on herein. However, in two of the five patients the onset of disseminated histoplasmosis coincided with a well documented cytomegalovirus infection; the viral infection may have been a factor predisposing to infection in these two cases.

Adult

Histoplasmosis of skin and lymph nodes and chronic lymphocytic leukemia.

Nodular skin and cervical lymph node lesions of histoplasmosis, unassociated with systemic symptoms of the infection, developed in a 63-year-old man with untreated chronic lymphocytic leukemia. The histologic patterns in both the skin and lymph node were those of a lymphoproliferative disorder, but Histoplasma organisms were found within a few scattered histiocytes after a careful search. The subtle clinical and pathologic presentation might lead one to overlook the organisms and to believe that the leukemic process had progressed, resulting in potentially dangerous systemic involvement of histoplasmosis and unnecessary chemotherapy for his leukemic process. Complete remission of histoplasmosis was obtained with amphotericin B therapy.

Dermatomycoses

Histoplasmosis in the Cape Province. A report of the second known outbreak.

Histoplasmosis is a rare disease in the Cape Province. The diagnosis of acute disseminated histoplasmosis in a patient who presented at Groote Schuur Hospital 3 weeks after a caving expedition, led to the identification of acute benign pulmonary histoplasmosis in 9 other people who had explored the same cave. Possible explanations for this outbreak are discussed.

Aged

African histoplasmosis of the jejunum. Report of a case.

A case of histoplasmosis of the jejunum is presented. This is apparently the first reported case of African histoplasmosis primarily affecting the jejunum. Grossly, there was stricture formation together with tubercles scattered over the surface of the bowel and adjoining mesentery. Also the mesenteric lymphnodes were enlarged. It is therefore difficult to distinguish jejunal histoplasmosis from tuberculosis, carcinoma and lymphoma of the jejunum and diagnosis can only be based on the demonstration of the characteristic yeast cells from the specimen.

Adult

Comparison of immunodiffusion and complement fixation tests in the diagnosis of histoplasmosis.

The immunodiffusion and complement fixation tests for histoplasmosis were compared on 2,090 initial sera from 70 proven cases of histoplasmosis, 177 routine chest hospital patients, and 1,843 coal miners from outside the major endemic area for histoplasmosis. The complement fixation test using histoplasmin as antigen detected antibodies in the sera of 72.8% of the 70 proven cases, while the complement fixation test using yeast antigen detected antibodies in 94.3% of the case sera, and the immunodiffusion test using histoplasmin antigen detected antibodies in 90% of the sera. The tests were also compared for sensitivity, specificity, and ease of performance.

Antibodies, Fungal

Histoplasmosis mimicking childhood non-Hodgkin lymphoma.

Cell surface markers are becoming increasingly important in the diagnosis of malignant lymphoid diseases. We present a case of pulmonary histoplasmosis with a pleural effusion. The differential diagnosis included non-Hodgkin lymphoma because the pleural fluid cells were cytologically identical to convoluted lymphoblasts; the cells also formed rosettes with sheep erythrocytes at 37 degrees C, suggesting that they were malignant thymus-derived lymphoblasts. Since cultures of pleural fluid were negative for bacteria and fungi, the correct diagnosis of histoplasmosis was made only after conventional histology identified Histoplasma capsulatum organisms in pleural nodules. Thus, until we have a better understanding of the significance of cell surface markers, we should continue to rely on conventional histology for the diagnosis of lymphomas.

Child

Pulmonary alveolar proteinosis and histoplasmosis: report of three cases.

Pulmonary alveolar proteinosis (PAP), in addition to acute generalized histoplasmosis, was found at autopsy of three adult males, 23, 51, and 52 years of age. All three patients became ill in the same region of Venezuela, south of Lake Maracaibo, an area considered highly endemic for histoplasmosis. The PAP may be due to an environmental factor.

Adrenal Cortex

Trephine biopsy of the bone marrow in disseminated histoplasmosis.

Twenty-two patients had bone marrow aspirates for culture and marrow trephine biopsies for histologic examination during the evaluation of an illness eventually proved to be disseminated histoplasmosis. These procedures provided evidence of involvement of the bone marrow with Histoplasma capsulatum in 19 cases. Fungi were demonstrated in trephine biopsy sections in 15 of the patients, permitting a rapid specific diagnosis. Three patterns of bone marrow morphology were observed; each reflected a variation of macrophage proliferation. In two of the patterns, diffuse macrophage proliferation and loose aggregates of macrophages, typical 2 to 4 microns intracellular hisoplasma organisms were numerous and obvious in hematoxylin and eosin-stained sections, were infrequent and were often relatively large (6 to 12 microns). There were four patients from whom H. capsulatum was cultured when organisms could not be demonstrated in either hematoxylin and eosin- or silver-stained sections. The patients with diffuse proliferation of macrophages in the marrow comprised a distinct clinical group associated with immunosuppression, a fulminant course and a fatal outcome despite therapy. Patients in the other two morphologic groups responded well to therapy even though the immune responses on many were also suppressed. Bone marrow examination is an excellent diagnostic procedure in disseminated histoplasmosis. Trephine biopsies permit a rapid diagnosis in most cases and may be of prognostic significance.

Adolescent

Histoplasma capsulatum in the presumed ocular histoplasmosis syndrome.

I demonstrated Histoplasma capsulatum organisms in disciform macular lesions, as well as a peripapillary lesion and peripheral atrophic scars in both eyes and in the lung of a patient with no history of active histoplasmosis. Autopsy findings were compatible with those of the presumed ocular histoplasmosis syndrome.

Aged

Lymphocyte stimulation by yeast phase Histoplasma capsulatum in presumed ocular histoplasmosis syndrome.

We measured skin reactions serum antibody, and lymphocyte stimulation to Histoplasma antigens in a series of patients with presumed ocular histoplasmosis syndrome and in controls. The most sensitive test, lymphocyte stimulation to H. capsulatum sonicate, also correlated with severity of the disease. Lymphocyte stimulation to Histoplasma may be a useful adjunct to the monitoring of presumed ocular histoplasmosis syndrome.

Antibodies, Fungal