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Caecal perforation in a renal transplant patient with disseminated histoplasmosis.

A renal transplant patient developed a fatal caecal perforation after Histoplasma capsulatum infection acquired abroad. Disseminated histoplasmosis is an uncommon fungal infection, usually seen in patients with impaired immunity. The diagnosis should be considered in immunosuppressed patients who develop prolonged fever or whose health deteriorates unexpectedly after travelling overseas. The infection is endemic in parts of the United States of America but occurs all over the world. Rapid diagnosis is often possible by histological examination of infected tissues. Treatment if started early may lead to recovery, but if it is not treated it is usually fatal.

Cecal Diseases↗

Histoplasmosis of the central nervous system.

Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed.

Adrenal Glands↗

Disseminated histoplasmosis in an AIDS patient treated with itraconazole.

A patient with AIDS presented with a fever, shortness of breath and a productive cough. A provisional diagnosis of Pneumocystis carinii pneumonia was made; however, blood cultures and bone marrow examination revealed disseminated infection with Histoplasmosis capsulatum. This was treated by itraconazole with initial success, but the patient relapsed while on maintenance therapy.

Acquired Immunodeficiency Syndrome↗

Bronchoscopic findings in a case of bronchopulmonary histoplasmosis.

At bronchoscopic examination extensive areas of fibrinous slough covering bronchial mucosal inflammation and ulceration were seen in a case of progressive diffuse bronchopulmonary histoplasmosis. Rigid bronchoscopy was needed to obtain sufficient biopsy material for specific histological diagnosis.

Amphotericin B↗

Lymphangiographic findings in histoplasmosis.

The lymphangiographic findings of histoplasmosis in an 11-year-old girl are presented and correlated with the histopathology of a mediastinal lymph node. Nonconfluent lymphadenographic defects with discrete margins measuring 2-4 mm in diameter were seen, corresponding to the microscopic demonstration of nodal granulomas of the same size. This is quite different from the lymphadenographic pattern usually present in lymphoma but might be seen in certain stages of other granulomatosis diseases.

Child↗

Fibrous mediastinitis: a late manifestation of mediastinal histoplasmosis.

Fibrosing mediastinitis is an uncommon manifestation of histoplasmosis that occurs primarily in younger patients. Findings include tracheobronchial narrowing, compromise of the main pulmonary artery and veins, and circumferential narrowing of the esophagus. The initial chest radiograph is often diagnostic, although additional studies including tomography and angiography help clarify the extent and severity of the disease process.

Adolescent↗

Mediastinal histoplasmosis granuloma: evaluation with CT.

Mediastinal granuloma secondary to histoplasmosis was described in three patients. Computed tomographic scans in each patient demonstrated a large, low-attenuation mediastinal mass crossed by enhancing septae. Other granulomatous diseases may produce similar abnormalities. The differential diagnosis of such lesions was discussed.

Adult↗

Pulmonary histoplasmosis.

Histoplasmosis is a common infection in the central United States and is acquired through inhalation of airborne spores. The majority of infected persons have an asymptomatic, self-limiting illness. Clinical pneumonia occurs in those with exposure to a large number of infecting spores. Resolution of the pneumonia often leaves calcified pulmonary nodules, calcified mediastinal lymph nodes, or splenic calcifications. Chronic disease, which mimics tuberculosis, may develop in those with underlying emphysema. In patients with deficient cell-mediated immunity, Histoplasma capsulatum may disseminate throughout the body; this often is fatal. Delayed manifestations arise months or years after the primary infection. Broncholithiasis occurs when peribronchial calcific nodes produce bronchial obstruction. Mediastinal granuloma is the continued proliferation of fibrous tissue in draining mediastinal lymph nodes. These granulomas may obstruct adjacent veins, arteries, or airways and lead to various clinical symptoms.

Animals↗

Novel abnormality in subpopulations of circulating lymphocytes. T gamma delta and CD2-, 3+, 4-, 8- lymphocytes in histoplasmosis-associated immunodeficiency.

A patient, who had developed anergy after disseminated histoplasmosis and who had gone on to develop a cardiomyopathy, demonstrated an unusually large proportion of T lymphocytes bearing the gamma and delta chains of the T cell receptor (TCR-gamma/delta). These gamma delta + cells composed over half of the circulating lymphocytes and were clearly divisible into two subgroups based on the level of expression of the gamma and delta chains and their ability to bind one of the monoclonal antibodies reactive with the TCR-delta chain. In addition, the patient showed an abnormally high proportion of circulating lymphocytes having the CD2-, 3+, 4-, 8- phenotype which has been only recently described. The pattern of lymphocyte subpopulations changed over the 9 years that the patient was followed since his original infection and appears to characterize a novel abnormality.

Antibodies, Monoclonal↗

Experimental histoplasmosis in the mouse. Immunoglobulin class response, total immunoglobulin A levels, immune complex formation, and occurrence of antigen in serum and urine.

Biotin-avidin enzyme-linked immunosorbent assays (ELISA) were developed to study the appearance of free antibody of the IgM, G, and A classes of immune complexes (IC) containing those classes and of antigen in the serum and urine of mice with experimentally induced, disseminated histoplasmosis (histo) over a period ranging from 4 to 64 days after infection. Free IgM was detected 4 days after infection, remained at low levels, and disappeared on Day 64, whereas free IgG was first detected on Day 7 and rose to very high levels before declining on Day 64. Free IgA was detected only once, on Day 21. IC containing IgM were seen first on Day 4, remained at low levels, and became undetectable on Day 64. IC containing IgM were detected on Day 7, peaked on Day 14, and declined through Day 64. IC containing IgA wee seen at low levels on Days 7, 14, and 21. Estimation of total IgA levels, done by single radial immunodiffusion, showed a statistically significant decrease on Day 14, followed by a slightly significant increase on Days 21 and 30. Antigen was detected in as much as 80% of serum specimens and 100% of urine samples during the first 2 wk postinfection but rarely afterwards. We conclude that ELISA provides a highly sensitive way to study antibody, IC, and antigen in host body fluids during histo infection and that IgM and antigen detection can be very early indices of infection. Measurements of IC and total IgA seem to be of relatively less importance in detection of infection.

Animals↗

Chronic pulmonary histoplasmosis with declining complement fixation titers and persistence of positive sputum culture. A case report.

A patient with culturally proved chronic pulmonary histoplasmosis was treated with amphotericin B. Complement fixation titers decreased but sputum cultures remained positive for Histoplasma capsulatum 5 months after original therapy. Lobectomy and a subsequent course of amphotericin B were necessary. Exceeding the minimal inhibitory concentrations of amphotericin B did not eradicate the organism and declining complement fixation titers failed to have prognostic significance.

Amphotericin B↗

Immunologic studies of patients with histoplasmosis.

Immunologic responses of patients with active histoplasmosis (Group I) were compared to the responses of healthy persons with positive histoplasmin skin-test reactions (Group II), and to those of healthy persons with negative histoplasmin skin-test reactions (Group III). Cellular immune responses were significantly depressed in patients. Seven (54 per cent) of 13 patients failed to respond to histoplasmin skin testing, and two (15 per cent) failed to respond to skin-test antigens unrelated to Histoplasma capsulatum. Lymphocyte transformation (LT) responses of patients were severely depressed in vitro (p less than 0.001) to Histoplasma antigens when compared to the responses of healthy, histoplasmin-reactive donors. Transformation responses to Candida antigen were not impaired in the patient population. Culturing lymphocytes of patients in serum obtained from healthy donors as opposed to autologous serum resulted in a significant (p less than 0.05) increase in LT responses to H. capsulatum. Responses to Candida antigen and to mitogens were not affected by the serum source. Serum-mediated suppression of LT responses correlated (p less than 0.01) with complement-fixing antibody titers to Histoplasma yeast-phase antigen and suggests that antibody, either alone or complexed with antigen, may suppress T-cell response in vitro in this disease.

Adolescent↗

Iron and host resistance in histoplasmosis.

Factors modulating host resistance to Histoplasma capsulatum are only partially understood. The role of iron-binding proteins in infectious diseases has been an area of recent in-depth investigation. The present study reaffirmed the necessity of iron for growth of H. capsulatum. Transferrin saturation was found to be of importance in withholding iron, and antigen-specific antibody had no added effect. Serums of patients with various clinical classes of histoplasmosis were found to exhibit abnormalities in iron metabolic parameters. However, based on transferrin saturation data, iron withholding by transferrin does not appear to be a significant host defense mechanism in vivo. Further studies presented herein suggest a protective effect of phagocytosis and sequestration by the macrophage-phagocyte system.

Antibodies, Fungal↗

The pathogenesis of experimental pulmonary histoplasmosis. Correlative studies of histopathology, bronchoalveolar lavage, and respiratory function.

A murine model of acute pulmonary histoplasmosis was employed to study the pathogenesis of the disease process by means of histopathology, bronchoalveolar lavage, and respiratory function tests. These studies were performed on C57BL/6 mice from 8 h to 8 wk after intranasal inoculation of 10(5) yeast forms of Histoplasma capsulatum and on age-matched control animals that received saline only. At Week 1, the histopathology was characterized by subacute inflammation consisting of polymorphonuclear leukocytes (PMN), lymphocytes, and macrophages that infiltrated the interstitium around small bronchioles and adjacent alveoli. At Weeks 2 and 4, the infiltrates were comprised predominantly of lymphocytes and macrophages; noncaseating granulomas were present at Week 2. Aggregates of lymphoid cells were prominent along the bronchial tree and in perivascular distribution. Those in close contact with bronchiolar epithelium resembled hyperplastic bronchus associated lymphoid tissue. Quantitative studies of cells in the BAL fluid revealed a large influx of PMN at Week 1 with return to normal range by Week 2. At this time there was a significant (p less than 0.02) increase in lymphocytes that persisted through Week 8, although histopathologic changes were minimal in lung at this time. A significant decrease in the DLCO/TLC at Week 2 in association with a normal vital capacity indicated impairment of respiratory function secondary to the alveolitis induced by H. capsulatum infection rather than a reduction of lung volume. This model offers promise for additional correlative studies of lymphocyte subsets in lung tissue and alveolar spaces as well as of the functions subserved by these respective populations.

Animals↗

Equine histoplasmosis presenting as a tumor in the abdominal cavity.

A 3.5-year-old Thoroughbred mare presented at necropsy with a large mass at the root of the mesentery and multiple smaller mesenteric masses. The mucosa of the small intestine contained numerous raised nodules. Histologic examination revealed severe granulomatous mesenteric lymphadenitis and enteritis. Epithelioid macrophages and multinucleated giant cells frequently contained numerous intracytoplasmic yeast organisms, which were strongly positive on immunohistochemical staining when using a polyclonal antibody against Histoplasma spp. A diagnosis of abdominal histoplasmosis was made based on the gross, microscopic, and immunohistochemical findings.

Animals↗

Pharmacotherapy of disseminated histoplasmosis in patients with AIDS.

OBJECTIVE: To review the pharmacotherapy of disseminated histoplasmosis (DH) in patients with AIDS. The article provides an overview of the pathophysiology, epidemiology, clinical presentation and diagnosis of this disease. Clinical trials reporting intervention with antifungal therapy are reviewed, with an emphasis on efficacy and toxicity of these agents. DATA SOURCES: A MEDLINE search from 1976 to the present was performed to identify pertinent biomedical literature, including reviews. STUDY SELECTION: All available reviews and clinical trials in AIDS patients were evaluated, as were all available case series and interventional clinical trials. DATA SYNTHESIS: DH in patients with HIV infection is an AIDS-defining opportunistic infection caused by Histoplasma capsulatum. It is most frequently observed in HIV-infected patients living in or traveling to endemic regions. The clinical presentation most often includes fever and weight loss, but may be complicated by comorbid illness such as other opportunistic infections. Diagnosis is best established by histologic examination of peripheral blood smear or bone marrow aspirate, or isolation of the organism in cultures of blood, bone marrow, and respiratory secretions. Serologic examinations may provide supportive diagnostic information. Detection of histoplasma polysaccharide antigen (HPA) in serum or urine may prove to be a promising approach for the rapid diagnosis and therapeutic monitoring of DH in AIDS patients. In contrast to immunocompetent hosts, high relapse rates are reported after therapy in AIDS patients. Therefore, initial (induction) therapy is routinely followed by long-term (maintenance) therapy to prevent relapse. Issues regarding the selection, dosage, and duration of therapy, as well as prophylaxis of patients at highest risk, still need to be addressed by controlled clinical trials. CONCLUSIONS: Amphotericin B is presently the drug of choice for induction therapy. Maintenance therapy with either amphotericin B or an oral azole antifungal agent active against H. capsulatum is necessary to prevent relapse. Itraconazole, a triazole antifungal agent, may provide effective alternative therapy for both induction and maintenance treatment of DH.

AIDS-Related Opportunistic Infections↗

Chronic disseminated histoplasmosis in an apparently immuno-competent Belgian patient.

A 77 year-old Belgian man was admitted for weight loss and elevated liver enzymes. He used to live in Central Africa until 1986 and denied any travel outside Belgium during the last decade. Physical examination was unremarkable except for a lip ulceration. Blood tests showed increases of liver enzymes and CEA. In the search of an abdominal cancer, CT showed a normal liver but enlarged surrenal glands, while colonoscopy disclosed multiple mucosal lesions. Colic and lip biopsies identified Histoplasma capsulatum var capsulatum. HIV serology was negative. Lymphocyte count was normal but lymphocyte function was depressed. The patient dramatically improved under oral treatment with Itraconazole 400 mg daily for six months. This case indicates that chronic disseminated Histoplasmosis can reactivate in a healthy and apparently non-immunocompromised person living in Europe.

Aged↗