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Immunoglobulin M and G histoplasmal antibody response in histoplasmosis.

Radioimmunoassays for IgM and IgG histoplasmal antibodies were developed and proved to be specific for their respective immunoglobulin classes, sensitive, and reproducible. Elevated IgM antibodies were detected in 59.8% of patients with histoplasmosis and 7.9% of control subjects. Elevated IgG antibodies occurred in 80.4% of patients with histoplasmosis but in only 12.9% of control subjects. Radioimmunoassay was nearly twice as sensitive as complement fixation for identifying patients with mild, presumably asymptomatic, infection. Of 13 patients with serologic follow-up at least 1 yr later, elevated IgM antibodies cleared, whereas IgG antibodies persisted in 7. In an epidemiologic investigation of a recurrent histoplasmosis outbreak, only the radioimmunoassay was able to prove the hypothesis that construction for a swimming complex was the source of exposure. These assays promise to be useful for clinical and epidemiologic investigations.

Antibodies, Fungal↗

Histoplasmosis of the larynx.

Granulomatous diseases caused by infectious agents are being seen more frequently than before. Infection with Histoplasma capsulatum is one such granulomatous disease. This condition may have protean manifestations, with involvement of the larynx of particular interest to the Otolaryngologist. Histoplasmosis of the larynx may present difficult diagnostic problems and may closely mimic carcinoma. A case of histoplasmosis of the larynx treated at the University of Cincinnati Medical Center is presented and used to highlight the mode of presentation and the management of this particular disease. The clinical presentation of histoplasmosis is discussed with emphasis on involvement of the upper aerodigestive tract. The diagnostic tests of practical value are outlined. Amphotericin B is the treatment for this disease entity.

Aged↗

Histoplasmosis: the otolaryngologist's perspective.

Within the upper aerodigestive tract, histoplasmosis often mimics carcinoma, making prompt and accurate diagnosis imperative. More severe and potentially lethal infections with Histoplasma capsulatum are now being seen as the numbers of patients at the extremes of age, as well as those with compromised immune systems, increase. We reviewed the cases of 115 hospitalized patients with disseminated histoplasmosis. Of these, 9 patients were identified with otolaryngologic manifestations: 4 were infected with human immunodeficiency virus (HIV), 1 was diabetic, and 3 were renal transplant patients. Sites of involvement included the larynx (in 2 cases) and the oral cavity and oral pharynx (in 7 cases). Eight of the 9 patients had a positive biopsy result; the other, a positive culture. Treatment with amphotericin B was generally effective, while the use of newer azole anti-fungal agents were less effective. As the number of immunocompromised patients continues to increase in modern clinical practice, histoplasmosis will undoubtedly be encountered more frequently in the head and neck area.

Amphotericin B↗

The pathologic spectrum of gastrointestinal and hepatic histoplasmosis.

We characterized the pathologic spectrum of lesions in gastrointestinal and hepatic histoplasmosis by studying cases of disseminated disease in immunocompromised and immunocompetent patients from endemic and nonendemic areas. We evaluated 56 specimens from 52 patients with H&E and silver stains. Of these patients, 43% presented with gastrointestinal rather than pulmonary symptoms. Thirty-one percent had gastrointestinal lesions, 10% had liver lesions, and 43% had both. Gross gastrointestinal features included ulcers (49% of patients), nodules (21%), hemorrhage (13%), obstructive masses (6%) and normal mucosa (23%). Microscopic gastrointestinal findings included diffuse lymphohistiocytic infiltration (83%), ulceration (45%), lymphohistiocytic nodules (25%), or minimal inflammatory reaction (15%) but only rare well-formed granulomas (8.5%). The most common hepatic finding was portal lymphohistiocytic inflammation; discrete hepatic granulomas were seen in less than 20% of involved livers. The pathologist must be aware of the broad range of gastrointestinal and hepatic lesions produced by histoplasmosis and, in particular, that well-formed granulomas are rare. Given the appropriate clinical context, histoplasmosis should be considered in both immunocompetent and immunocompromised patients, regardless of pulmonary symptoms, in nonendemic as well as endemic areas.

Adolescent↗

Acute histoplasmosis. Description of an outbreak in northern Louisiana.

An outbreak of acute histoplasmosis occurred in northern Louisiana in September 1977. All six men who cleared a field of bamboo cane known to be a blackbird roosting site were affected. All had clinical and roentgenographic findings of acute pulmonary histoplasmosis, and all recovered. Seroconversion or fourfold rise in antibody to Histoplasma capsulatum yeast--or mycelial-form antigens were demonstrated in five. Immunodiffusion testing showed that all six patients developed H capsulatum M bands, and two developed H bands specific for active infection. The H capsulatum was isolated from the soil in the cane field. This is the first report of an outbreak of histoplasmosis in Louisiana and the first known isolation of H capsulatum from Louisiana soil.

Adult↗

Pulmonary histoplasmosis. A possible risk in people who cut decayed wood.

We report three unrelated outbreaks of acute pulmonary histoplasmosis associated with cutting and gathering firewood in Minnesota. Clinical symptoms and laboratory findings from nine patients are reported. All recovered without treatment. This report emphasizes that physicians must consider cutting and gathering wood, especially decayed wood, as a potential risk for acute pulmonary histoplasmosis even in areas of the country where histoplasmosis is not considered prevalent.

Adolescent↗

Treatment of histoplasmosis and blastomycosis.

Prior to the development of ketoconazole, the treatment of systemic histoplasmosis and blastomycosis was limited to AMB. The convenience of oral dosing, combined with avoidance of the significant toxicities associated with AMB, make ketoconazole an attractive alternative for the treatment of selected forms of histoplasmosis and blastomycosis. Although high-dose (800 mg/day) ketoconazole is generally more effective than low-dose (400 mg/day), therapy should be initiated at the lower dose due to significantly more adverse effects at higher doses; the daily dose should be increased in patients with progressive disease. Caution should be exercised when ketoconazole is used to treat patients with GU tract disease and in patients with naturally occurring or pharmacologically induced achlorhydria. Thus, AMB remains the drug of choice for difficult to treat cases of histoplasmosis and blastomycosis; however, recent studies have established ketoconazole as the drug of choice in immunocompetent patients with non-life-threatening, non-meningeal H capsulatum and B dermatitidis disease.

Amphotericin B↗

Acute disseminated histoplasmosis and endocarditis.

Acute disseminated histoplasmosis is a frequent condition in HIV carriers. Thirty-five cases of endocarditis caused by Histoplasma capsulatum have been reported in international literature, and all these descriptions correspond to a context of subacute disseminated histoplasmosis. This paper presents the case of a HIV-positive patient with fever, dyspnea, weight loss, vomiting and polyadenopathies to whom histoplasmosis was diagnosed following blood-cultures and isolation of the agent responsible for cutaneous lesions, and in whom aortic-valve vegetations were found during an echocardiogram. The patient was treated with amphotericin B and had a good outcome; subsequent echocardiograms showed no vegetations. Literature on the subject is reviewed, with special emphasis on diagnosis and treatment of previously described cases.

Acquired Immunodeficiency Syndrome↗

Mediastinal histoplasmosis: report of the first two Brazilian cases of mediastinal granuloma.

This report documents the first two Brazilian cases of mediastinal granuloma due to histoplasmosis, presenting selected aspects on the diagnosis. Tissue samples revealing histoplasmosis were obtained from each of the patients by mediastinoscopy and thoracotomy. In the second patient, a subcarinal calcified mass eroded into the bronchial tree, leading to secondary bilateral aspiration pneumonitis one week after thoracotomy. Although rare, histoplasmosis should be included in the differential diagnosis of mediastinal granuloma, specially if there are calcifications greater than 10 mm in dimension.

Adult↗

Imported histoplasmosis in Spain.

Histoplasma capsulatum is a dimorphic fungus endemic in the American continent but not in Europe, where cases are usually imported. Its favorite habitat is in warm humid soils. Guano from birds and bats enhance the sporulation of the mycelial phase.1 Man acquires H. capsulatum through inhalation of spores. Most people infected by this fungi remain asymptomatic, but around 10-50% can start an illness ranging from acute pulmonary histoplasmosis to chronic histoplasmosis. In both, there is close clinical resemblance to pulmonary tuberculosis. Immunodepressed patients undergo a more severe form of the disease, usually presenting in the acute disseminated form. We present seven immunocompetent patients with histoplasmosis acquired after traveling to several American countries.

Histoplasmosis↗

Central nervous system histoplasmosis mimicking a brain tumor: difficulties in diagnosis and treatment.

Neurologic involvement occurs in 10% to 20% of patients with disseminated histoplasmosis. We describe a 20-year-old woman who had headache and diplopia but no evidence of systemic infection. Magnetic resonance imaging showed an enhancing mass in the thalamomesencephalic and third ventricular region. After subtotal resection of what was presumed to be a glioma, the patient had symptoms and signs of meningitis. Subsequent pathological review demonstrated noncaseating granulomas, and serologic tests and cultures confirmed the diagnosis of histoplasmosis. Initiation of antifungal therapy and removal of an infected shunt system resulted in clinical improvement. Clinicians should maintain a high index of suspicion in patients who are from any area endemic for histoplasmosis.

Adult↗

Disseminated histoplasmosis with unusual cutaneous lesions in a patient from the Philippines.

The incidence and prevalence of histoplasmosis in Southeast Asia has not been extensively described. The first microbiologically documented case of disseminated histoplasmosis with cutaneous papulonodules in a 56-year-old woman from the Philippines is reported. She presented with fever and generalized papulonodular lesions in various stages, which evolved into vesicles with central necrosis that resembled molluscum contagiosum with an indurated erythematous halo. Biopsies revealed a granulomatous mass of lymphohistiocytic and epithelioid cells with intracellular budding yeast cells and dark nuclei. Cultures were positive for Histoplasma capsulatum. The patient was treated with amphotericin B (3 g) and 5-fluorocytosine (50 mg/kg/day), followed by ketoconazole (400 mg/day). Her clinical course was complicated by intractable hemolytic anemia that was initially treated with corticosteroids. A splenectomy was subsequently performed. Pneumonia and a brain abscess caused by Nocardia asteroides were secondary complications. Nine months after her admission, repeat testing was diagnostic for systemic lupus erythematosus. This patient serves to re-emphasize that cutaneous lesions in an immunocompromised patient must be evaluated by biopsy and culture analysis. Disseminated histoplasmosis in the immunocompromised host may present with unusual cutaneous lesions, and must be considered even in a nonendemic area.

Amphotericin B↗

Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS.

BACKGROUND: In patients with moderate to severe histoplasmosis associated with AIDS, the preferred treatment has been the deoxycholate formulation of amphotericin B. However, serious side effects are associated with use of amphotericin B. OBJECTIVE: To compare amphotericin B with liposomal amphotericin B for induction therapy of moderate to severe disseminated histoplasmosis in patients with AIDS. DESIGN: Randomized, double-blind, multicenter clinical trial. SETTING: 21 sites of the U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group. PATIENTS: 81 patients with AIDS and moderate to severe disseminated histoplasmosis. MEASUREMENTS: Clinical success, conversion of baseline blood cultures to negative, and acute toxicities that necessitated discontinuation of treatment. RESULTS: Clinical success was achieved in 14 of 22 patients (64%) treated with amphotericin B compared with 45 of 51 patients (88%) receiving liposomal amphotericin B (difference, 24 percentage points [95% CI, 1 to 52 percentage points]). Culture conversion rates were similar. Three patients treated with amphotericin B and one treated with liposomal amphotericin B died during induction (P = 0.04). Infusion-related side effects were greater with amphotericin B (63%) than with liposomal amphotericin B (25%) (P = 0.002). Nephrotoxicity occurred in 37% of patients treated with amphotericin B and 9% of patients treated with liposomal amphotericin B (P = 0.003). CONCLUSION: Liposomal amphotericin B seems to be a less toxic alternative to amphotericin B and is associated with improved survival.

AIDS-Related Opportunistic Infections↗

Risk factors for disseminated or fatal histoplasmosis. Analysis of a large urban outbreak.

An outbreak of histoplasmosis in Indianapolis involving 488 clinically recognized cases including 60 patients with disseminated or fatal infection permitted statistical analysis of risk factors. Being male, white, under 5 years of age, having chronic obstructive lung disease, and living near the presumed source of the outbreak were not risk factors for fatal or disseminated histoplasmosis. Age greater than 54 years and immunosuppression were the only risk factors for disseminated or fatal infection. Dissemination should be excluded in patients with histoplasmosis who are immunosuppressed or older than 54 years. Specific antifungal treatment is more likely to be required in those two groups rather than in patients without risk factors.

Adolescent↗

[Cutaneous histoplasmosis in nine patients with AIDS].

UNLABELLED: In AIDS patients the diagnosis of systemic mycosis is a clinical challenge. When cutaneous affection occurs, the diagnosis is difficult because of the non-specific clinical findings. We describe nine patients with AIDS and cutaneous histoplasmosis as the initial clinical manifestation. These patients were diagnosed from 1987 to 1998. In all the diagnosis of histoplasmosis was done by skin biopsy and fungal isolation. The main skin lesions were papules combined with pustules or nodules in 6 of 9 patients, ulcers (1/9), erythematous plaques (1/9) and nodules (1/9). Head and trunk were the main anatomical locations of the lesions. All had fever, 7/9 had liver and spleen enlargement and 5/9 had weight loss. At the time of diagnosis all patients had a low CD4+ lymphocyte counts with a mean of 47 cells/microL. Amphotericin B was the initial treatment followed by itraconazole. Five patients died, one day after diagnosis and four after 5, 8, 11 and 12 months. Four are alive at 3, 3, 19 and 26 months of follow-up. CONCLUSIONS: In AIDS patients the skin involvement by histoplasmosis should always be included among the differential diagnoses specially in patients with face and trunk papules and fever and hepatosplenomegaly. Skin and bone marrow cultures were the most reliable diagnostic methods, but skin biopsy was the fastest procedure.

AIDS-Related Opportunistic Infections↗

Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei; current status and future trends.

Effective serodiagnosis of systemic fungal infections is of increasing importance, particularly with regard to the identification of infection with Histoplasma capsulatum, Paracoccidioides brasiliensis and Penicillium marneffei. Methodology has been based either around antibody or antigen detection, although there is clear overlap between the two. Antibody-based detection systems for the diagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei have now begun to incorporate a range of highly purified and well-characterized antigens, in contrast to the situation of a few years ago when relatively crude preparations derived from either whole cells or culture filtrate were used. The application of such antigens offers improvements in reproducibility and specificity, although the detection of meaningful antibody responses in immunosuppressed individuals remains a problem. Partly as a consequence of this a great deal of attention has focused on the development of antigen detection assays, and such methods have proved particularly successful, as for instance in the serodiagnosis of histoplasmosis in AIDS patients. The recent utilization of monoclonal antibodies in the development of antigen detection methods for the diagnosis of histoplasmosis and paracoccidioidomycosis offers further scope for improvement in this area.

AIDS-Related Opportunistic Infections↗

Use of corticosteroids for treating dogs with airway obstruction secondary to hilar lymphadenopathy caused by chronic histoplasmosis: 16 cases (1979-1997).

OBJECTIVE: To examine use of corticosteroids in treating dogs with airway obstruction secondary to hilar lymphadenopathy caused by chronic histoplasmosis. DESIGN: Retrospective study. ANIMALS: 16 dogs. PROCEDURE: Records for dogs with airway obstruction examined from January 1979 through December 1997 were reviewed. Dogs were included in the study if they had hilar lymphadenopathy documented radiographically and bronchoscopically, had serum antibodies against Histoplasma capsulatum, and did not have organisms in any cytologic or histologic samples. Dogs were assigned to groups on the basis of treatment given (5 dogs, corticosteroids only; 5 dogs, corticosteroids and antifungal medication; 6 dogs, antifungal medication only). RESULTS: Clinical signs resolved in < 1 week in dogs treated only with corticosteroids. In dogs treated with corticosteroids and an antifungal medication, improvement was evident in a mean of 2.6 weeks. In 5 of 6 dogs treated with only an antifungal medication, clinical signs resolved in a mean of 8.8 weeks. Dogs receiving corticosteroids did not develop active or disseminated histoplasmosis. CLINICAL IMPLICATIONS: Corticosteroids can be used successfully in the treatment of dogs with hilar lymphadenopathy secondary to histoplasmosis. Affected dogs must be carefully evaluated for active infection. Specimens obtained by means of bronchoalveolar lavage, tracheal washing, or other methods should be examined to exclude the possibility of an active infection, which could result in corticosteroid-induced dissemination of disease.

Adrenal Cortex Hormones↗

African oral histoplasmosis mimicking lip carcinoma: case report.

A case of localised African histoplasmosis with an unusual presentation in a 56 year old Nigerian farmer is reported. The lesion presented as an ulcer clinically mimicking squamous cell carcinoma of the lower lip. An incisional biopsy and culture studies confirmed African histoplasmosis and the ulcer healed spontaneously without treatment. This case is reported to highlight the unusual location and clinical course of African histoplasmosis.

Biopsy↗