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Acute Histoplasmosis in Spelunkers Returning from Mato Grosso, Peru.

Background: Histoplasmosis is a fungal disease with a worldwide distribution. Travelers returning from endemic areas with a history of exposure to fungal spores have a high risk of infection. Methods: We report four cases of acute pulmonary disease in Italian spelunkers returning from Mato Grosso, Peru. Results: Symptoms and radiologic findings were consistent with acute pulmonary illness. Laboratory data supported the hypothesis of histoplasmosis. Conclusions: Histoplasmosis should be considered in the differential diagnosis in travelers returning from endemic areas, who report a risk of exposure, and present with respiratory illness. In this setting, seroconversion may be considered diagnostic of pulmonary histoplasmosis.

Journal Article↗

HISTOPLASMOSIS IN MONTREAL DURING THE FALL OF 1963, WITH OBSERVATIONS ON ERYTHEMA MULTIFORME.

Although Montreal is in an endemic area, significant clinical histoplasmosis with systemic manifestations has been, until recently, infrequently diagnosed. However, since the autumn of 1963, 31 cases of clinically significant histoplasmosis have been seen by the authors. These were divided into two groups: (1) patients in whom the diagnosis was established on the basis of histological and/or cultural demonstration of the fungus; (2) patients in whom the diagnosis was based on a positive histoplasmin skin test, a complement fixation antibody titre of 1:32 or greater and compatible clinical and radiological findings. An additional group of 11 patients who presented with erythema multiforme was investigated and a heretofore unrecognized relationship between histoplasmosis and erythema multiforme was established.

Adolescent↗

Submacular surgery for subfoveal choroidal neovascular membranes in patients with presumed ocular histoplasmosis.

OBJECTIVE: To determine the visual results, recurrence rates, and postoperative complications of surgical removal of subfoveal choroidal neovascularization (CNV) in patients with the presumed ocular histoplasmosis syndrome. DESIGN: A consecutive surgical series of 63 eyes of 62 patients with subfoveal CNV and the presumed ocular histoplasmosis syndrome with longer than 6 months of follow-up. SETTING: Tertiary care university medical center. METHODS: Patients underwent surgical removal of subfoveal CNV using vitreoretinal surgical techniques. The anatomical and functional results of surgery were analyzed. RESULTS: The median age of the patients was 42 years (range, 16-68 years), and the median follow-up time was 24 months (range, 6-48 months). Visual acuity improved by 2 or more Snellen lines in 22 (35%) of the 63 eyes, was unchanged in 28 (44%) of the eyes, and worsened in 13 (21%) of the eyes. Eleven (17%) of the 63 eyes improved to a visual acuity of 20/50 or better. Eyes with an initial visual acuity of 20/200 or worse had a better prognosis for improved vision (ie, 26 [41%] of the eyes) than those with an initial visual acuity of 20/100 or better (ie, 5 [8%] of the eyes). Recurrence of the subfoveal CNV occurred in 24 (38%) of the 63 eyes and was more common in those eyes that received preoperative laser photocoagulation (ie, 15 [47%] of the eyes). The median time to recurrence was 5 months after surgery. Post-operative complications included macular striae in 4 (6%) of the 63 eyes, rhegmatogenous retinal detachment in 2 (3%) of the eyes, retinal tear in 1 (1.6%) of the eyes, and progression of cataract in 19 (30%) of the eyes. CONCLUSIONS: Surgical excision of subfoveal CNV may be an effective therapeutic modality in patients with the presumed ocular histoplasmosis syndrome that offers the possibility of improving central vision in many patients. Factors possibly associated with a favorable visual prognosis include younger patient age and the absence of previous laser photocoagulation.

Adolescent↗

Intestinal perforation from gastrointestinal histoplasmosis in acquired immunodeficiency syndrome. Case report and review of the literature.

Gastrointestinal involvement with histoplasmosis in patients with the acquired immunodeficiency syndrome is a rare but documented phenomenon. Most patients present with diarrhea, fever, and abdominal pain. We present a case of a woman who tested positive for the human immunodeficiency virus antibody who developed an intestinal perforation due to Histoplasma capsulatum of the ileum. The patient, whose only risk factor was a blood transfusion 8 years earlier, had been previously diagnosed as having disseminated histoplasmosis with gastrointestinal involvement. While receiving oral antifungal treatment (itraconazole), she developed two separate areas of ileal perforation due to H capsulatum. Complications from gastrointestinal involvement with histoplasmosis, such as perforation, should be considered in patients infected with the human immunodeficiency virus with signs and symptoms suggesting abdominal disease.

Acquired Immunodeficiency Syndrome↗

Disseminated histoplasmosis with reactive hemophagocytosis: aspiration cytology findings in two cases.

Two cases of disseminated histoplasmosis associated with reactive hemophagocytic syndrome are described. The clinical presentation was with prolonged unexplained fever and hepatosplenomegaly. On a strong clinical possibility of tuberculosis, antitubercular treatment was initiated in both patients. Lymph node (case 1), splenic (case 2), and bone marrow aspiration, however, showed sheets of proliferating histiocytes, and intracellular and extracellular histoplasma organisms. Aspiration cytology was thus valuable in establishing the final diagnosis. The patients had a fulminant clinical course and died of hemorrhagic shock within 48 hr of hospital admission before specific therapy could be initiated. Histoplasmosis can mimic tuberculosis clinically. There is a need for an increased awareness of the clinicopathological spectrum of histoplasmosis, especially its rarer manifestations as hemophagocytic syndrome. In suspected cases, aspirations from the lymph node, liver, and spleen can be performed safely and should be utilized for early diagnosis.

Adult↗

Diagnosis of histoplasmosis in urine cytology: reactive urothelial changes, a diagnostic pitfall. Case report and literature review of urinary tract infections.

Histoplasmosis not uncommonly causes systemic infection, particularly in immunocompromised patients. In systemic infection, the urinary tract is often involved, although the diagnosis of histoplasmosis in urine cytologic specimens has never been reported. Urinary tract histoplasmosis may present with gross hematuria, raising clinical suspicion for malignancy. The index case presented with intermittent gross hematuria, suprapubic pain, significant weight loss, hoarse voice, and a painful tongue ulcer. Examination of the patient revealed an ulcerated tongue lesion, an anal ulcer, a polypoid lesion on the vocal cord, and cystoscopic examination of the urinary bladder revealed erythematous patchy areas. Surgical biopsy sections from the vocal cord and tongue lesion were diagnostic of histoplasma infection. Urine cytologic examination showed atypical urothelial cells suspicious for malignancy. However, fungal stains performed on the urine specimen showed histoplasma organisms. We conclude that with a high index of suspicion, and the use of special stains, histoplasma organisms can be identified in urine.

Antifungal Agents↗

Evaluation of an ELISA for the detection of anti-Histoplasma ribosomal and antihistoplasmin antibodies in histoplasmosis.

We have developed an indirect sandwich enzyme-lined immunosorbent assay (ELISA) for the detection of antibodies to Histoplasma ribosomes and histoplasmin; we used this test for demonstration of these antibodies in sera from proven cases of histoplasmosis and other infections. Serum dilutions from five negative controls used in each experiment were normalized against 50 normal sera, and a factor of the mean absorbance was used to establish a positive reaction. Antiribosomal antibodies were detected in 97% of the known histoplasmosis patients with ELISA titers ranging from 1:100 to over 1:12,800. In contrast, antibodies to histoplasmin were detected in only 75% of these sera; titers ranged from 1:100 to 1:12,800. Cross-reactions with sera from other fungal infections (blastomycosis, coccidioidomycosis, paracoccidioidomycosis, cryptococcosis, candidiasis, and aspergillosis) were seen in 46% of the cases with ribosomes and 37% with histoplasmin. Fifty percent of the sera from tuberculosis patients gave positive reactions with ribosomes and 29% with histoplasmin. These results warrant further studies on the significance of antibodies to ribosomes and histoplasmin in immunity to histoplasmosis.

Antibodies, Fungal↗

Clearance of Histoplasma capsulatum variety capsulatum antigen is useful for monitoring treatment of experimental histoplasmosis.

We sought to determine whether measurement of Histoplasma capsulatum var. capsulatum antigen concentration in tissues and blood provided a marker for antifungal effect of itraconazole in a nonlethal murine model of histoplasmosis. Treatment with itraconazole (Sporanox), in cyclodextrin, was evaluated in a pulmonary model of histoplasmosis. Mice infected with 4.0 x 10(7) yeast-phase organisms by endotracheal inoculation were treated with itraconazole, 1.5 mg twice daily by gavage, for 10 consecutive days, beginning on day 4 of infection. All mice were sacrificed on day 15 of infection. Blood, spleen, and lung tissues were removed for culture and quantification of antigen. Numbers of organisms were significantly lower in spleens from the treated group: 20.8 +/- 41.8 vs. 65.8 +/- 39.1 in the control group, P = 0.017. Numbers of organisms in lung were 9.6 +/- 27.3 colony forming units in treated versus 24.2 +/- 36.3 in control animals, P = 0.267. Antigen concentrations in spleen tissue and serum were lower in treated versus control mice: spleen, 1.8 +/- .6 units in treated versus 11.0 +/- 2.3 in controls, P < 0.001; serum, 0.8 +/- 0.2 units in treated versus 2.2 +/- 1.0 units in controls, P < 0.001. Lung antigen concentrations were similar in the two groups, 19.2 +/- 1.4 units in treated compared to 17.9 +/- 3.0 units in control mice, P = 0.142. The cyclodextrin formulation of itraconazole (Sporanox) demonstrated antifungal activity in experimental histoplasmosis. Antigen detection was a useful marker for antifungal effect.

Animals↗

Immunopathology of reactivation of experimental ocular histoplasmosis.

We have established a non-human primate model of experimental ocular histoplasmosis. This model has been shown to result in chronic lesions that resemble typical 'histo spots' or choroidal scars but that contain infiltrates of lymphocytes for as long as 10 yr following intracarotid injection of live Histoplasma capsulatum. Using this model, we attempted to reactive these late choroidal lesions via intracarotid challenge with specific antigen (heat-killed H. capsulatum). No clinical changes suggestive of reactivation of these lesions were observed following this antigenic challenge. However, immunopathologic analysis of choroidal lesions at 1, 3 and 7 days after antigenic challenge revealed significant increases in both the numbers of inflammatory cells and the relative percentages of the helper/inducer lymphocyte and macrophage populations. Our results demonstrate that, following antigenic challenge, a cellular change, consistent with a type IV delayed hypersensitivity, can be observed in previously active, but clinically quiescent, histoplasmosis lesions. In light of the many parallels between our primate experimental model and human ocular histoplasmosis, our findings suggest that, in the human, significant immunopathologic activity may occur subclinically in the choroid of affected individuals. It is possible that repeated bouts of subclinical reactivation may induce or enhance chronic choroiditis and, over many years, ultimately produce slow progressive damage to the Bruch's membrane/retinal pigment epithelium complex, resulting in clinically 'active' macular disease and, in selected cases, subretinal neovascularization.

Animals↗

Changes in immunoregulatory lymphocyte populations in patients with histoplasmosis.

Circulating T-lymphocyte subpopulations were enumerated in 65 patients with histoplasmosis and correlated with the different clinical manifestations of the disease. Acute pulmonary histoplasmosis, rheumatologic, disseminated, and chronic inflammatory manifestations of histoplasmosis were all associated with a significant elevation above normal of OKT8+ (suppressor-cytotoxic) lymphocytes and a significantly lower than normal OKT4+ (helper-inducer)-lymphocyte to OKT8+-lymphocyte ratio. In contrast, cavitary disease was associated with an increase in OKT4+ lymphocytes, a decrease in OKT8+ lymphocytes, and a higher than normal OKT4/OKT8 ratio. Clinical recovery was associated with normalization of these values. Functional activity determined by coculture techniques correlated closely with T-lymphocyte subset measurements. These distinct subset abnormalities may help monitor immunological aspects of disease activity.

Antibodies, Monoclonal↗

Epidemiological study of sporotrichosis and histoplasmosis in captive Latin American wild mammals, São Paulo, Brazil.

Sporotrichosis and histoplasmosis are deep mycosis with a high incidence in human beings in Brazil. In domestic animals histoplasmosis has been described only in dogs, but the occurrence of sporotrichosis among domestic animals in Brazil has been described in dogs, cats, mules and asses. There is also a case of this disease reported in a chimpanzee (Pan troglodites). The purpose of this research was to perform an epidomiological study of these mycoses using delayed hypersensitivity tests (histoplasmin and sporotrichin) in Latin American wild mammals. This research was assayed using 96 healthy animals at Parque Zoológico de São Paulo, Brazil: Primates: 33 Cebus apella--weeping-capuchin and 16 Callithrix jacchus--marmoset; Procyonidae: 37 Nasua nasua--coatimundi and 10 Felidae (Panthera onca--jaguar; Felis pardalis--ocelot Felis wiedii--margay; Felis tigrina--wild cat). For intradermic tests, the following antigens were used: Sporothrix schenkii cell suspension (sporotrichin, histoplasmin-filtrate), Histoplasma capsulatum cell suspension (histoplasmin), and Histoplasma capsulatum (polysaccharide). The positivity to histoplasmin was 44.79% (Cebidae 15.15%; Callithricidae 6.25%; Procyonidae 86.49% and Felidae 50.00%, respectively). With respect to sporotrichin, 30.21% (Cebidae 6.06%, Callithricidae 0.0%; Procyonidae 64.86% and Felidae 30.00% respectively). The pattern of infection is similar to that shown by human beings and this may suggest that these animals could be involved in the epidemiologic chain of sporotrichosis and histoplasmosis, the second most prevalent human deep mycoses in Brazil. It is important to point out the absence of similar studies in Latin American wild animals.

Animals↗

[A case of AIDS-associated histoplasmosis in Germany].

In a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection with Histoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication of H. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.

Acquired Immunodeficiency Syndrome↗

Histoplasmosis in hairy cell leukemia: case report and review of the literature.

Progressive disseminated histoplasmosis (PDH) has been described in only six patients with hairy cell leukemia (HCL). Herein we describe an additional patient with HCL and disseminated histoplasmosis. Additionally, we note that three of seven cases of disseminated histoplasmosis and HCL have occurred in East Texas. PDH is to be suspected in febrile HCL patients in an endemic area who fail to respond to antibacterial therapy. We emphasize that serologic studies are useful in the diagnosis of PDH in HCL patients, and these patients respond well to therapy.

Acquired Immunodeficiency Syndrome↗

Histoplasmosis capsulati and duboisii in Europe: the impact of the HIV pandemic, travel and immigration.

The present report describes a fatal case of imported AIDS-related disseminated histoplasmosis capsulati infection associated with multiple coexisting infections, diagnosed with cultural recovery of Histoplasma capsulatum var. capsulatum with a commercial radiometric Mycobacterium medium. The epidemiological and clinical features of histoplasmosis capsulati and duboisii in Europe are reviewed by examining also 69 documented cases of Histoplasma capsulatum var. capsulatum infection (25 in AIDS patients) and 17 cases of Histoplasma capsulatum var. duboisii infection (3 in HIV-infected patients), described since 1980. This draws special attention to the role played during recent years by the emergence of the HIV pandemic and the progressive intensification of travel and immigration as risk factors for this disease in our continent. AIDS patients, who are prone to multiple concurrent opportunistic infections which may share clinical and laboratory features with each other and with other HIV-associated diseases, represent the most relevant current group at risk for severe disseminated histoplasmosis, which may come to medical attention far from their place of origin.

AIDS-Related Opportunistic Infections↗

Diagnosis and management of histoplasmosis.

Histoplasmosis occurs throughout the world but is more common within the endemic areas of North America, particularly in fertile river valleys. Disease manifestations range from asymptomatic infection in the normal host with low-inoculum exposure to rapidly fatal, disseminated infection in the severely immunocompromised host, emphasizing the importance of cellular immunity in defense against Histoplasma capsulatum. Diagnosis depends on a high index of suspicion, knowledge of the clinical and epidemiologic features of the infection, and a thorough understanding of the uses and limitations of fungal cultural and serological laboratory procedures. Recently, a method has been developed for rapid diagnosis based on detection of a polysaccharide antigen in body fluids of patients with histoplasmosis. Amphotericin B remains the preferred treatment for more severe forms of histoplasmosis, particularly in the immunocompromised host, but oral treatment with ketoconazole or newer imidozoles appears to be effective in less severe infections in non-immunocompromised individuals.

Amphotericin B↗

Pulmonary histoplasmosis in a Japanese male: report of a case.

A case of pulmonary histoplasmosis, which is rare in Japan, is reported herein. A 43-year-old man who had worked in Mexico for 2 years and had come back to Japan 3 months earlier, presented at our hospital because of an abnormal shadow on his chest roentogenogram with no symptoms. His chest roentogenogram as well as chest computed tomograms revealed a 2-cm-diameter nodule in the anterior basal segment of his right lung and an enlargement of the subcarinal lymph node. Although these pictures seemed to indicate an advanced lung cancer, no malignant cells were found based on the brushing cytology findings after bronchoscopy. An exploratory thoracoscopic tumor resection and biopsy of the enlarged lymph node led to a histological diagnosis of an abscess due to histoplasma. The hospital course was uneventful. Postoperatively, amphotericin B was administered for 1 year. This is the eighth case of pulmonary histoplasmosis reported in Japan. A pulmonary nodule together with mediastinal lymphoadenopathy seems to be characteristic in these patients. Histoplasmosis should therefore be considered in the differential diagnosis, since overseas travel has now become common-place for the Japanese.

Adult↗

CT evaluation of active adrenal histoplasmosis.

We describe three patients with puzzling systemic illnesses in whom computed tomography (CT) led to the diagnosis of active adrenal histoplasmosis. CT was performed in two patients because of gastrointestinal symptoms and weight loss and in the third because of fever developing 2 years after an apparent cure of histoplasmosis. All three patients had adrenal enlargement on CT with features of granulomatous adrenal disease in two. Hormone assays performed after CT supported the diagnosis of adrenal insufficiency and fine-needle adrenal aspiration biopsy with special stains of the aspirates showed histoplasma organisms in all three patients. The combination of adrenal enlargement on CT and laboratory findings of adrenal insufficiency should suggest the diagnosis of histoplasmosis, especially in endemic areas.

Adrenal Gland Diseases↗

[Papular exanthema in systemic histoplasmosis and HIV infection].

A 34-year-old HIV-infected African woman developed fever, weight loss and widespread papules on her trunk, arms and face. Skin biopsy and culture revealed histoplasmosis caused by Histoplasma capsulatum varietas capsulatum (American histoplasmosis). Even though antimycotic treatment and intensive care were started immediately the patient died because of the systemic mycosis within a few days. Histoplasmosis is a rare disease in Europe but endemic in some areas of the USA (e.g., Ohio, Mississippi) and of Africa. Additionally histoplasma capsulatum varietas duboisii is endemic in Central and South Africa.

AIDS-Related Opportunistic Infections↗