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PubMed1986

Serodiagnosis of histoplasmosis.

The standard serologic tests for diagnosis of histoplasmosis include the complement fixation test (CF), which is quite sensitive, and the immunodiffusion test (ID), which is fairly specific. Radioimmunoassay (RIA) is an experimental serological test even more sensitive than CF, but also less specific. Problems with the specificity of serodiagnosis are addressed followed by a discussion of the sensitivity of the three tests in the different forms of histoplasmosis-chronic cavitary histoplasmosis, progressive disseminated histoplasmosis, and acute pulmonary histoplasmosis. Next, serologic results from a large point-source outbreak of acute pulmonary histoplasmosis in Orono, Minn, are presented. These results are used to define the sensitivity of the three tests in acute symptomatic pulmonary histoplasmosis and also to detail the time course of the appearance of antibodies measurable by each test. Finally, a case of sporadic severe acute pulmonary histoplasmosis is presented in which the approach to serodiagnosis was based on lessons learned from the Orono outbreak.

Adult↗
PubMedDate not supplied

Cervical and mediastinal abscess as a manifestation of histoplasmosis.

Histoplasmosis is the most common endemic respiratory mycosis in the United States. Disseminated histoplasmosis generally is initially seen with systemic or respiratory complaints. Presentation of histoplasmosis as a neck mass is rare. Due to this unusual presentation and the diagnostic implications, we present a case of disseminated histoplasmosis that presented as a neck abscess. Unusual presentations of histoplasmosis may occur even in patients who are not immunocompromised. The diagnosis and management of histoplasmosis is reviewed. Histoplasmosis should be considered in the workup of a cervical abscess even in the immunocompetent host.

Abscess↗
PubMed1992

Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group.

OBJECTIVE: To assess the efficacy and toxicity of orally administered itraconazole in the treatment of nonmeningeal, nonlife-threatening forms of blastomycosis and histoplasmosis. DESIGN: Prospective, nonrandomized, open trial. SETTING: Multicenter trial at 14 university referral centers. PATIENTS: Eighty-five patients with culture or histopathologic evidence of blastomycosis (48 patients) or histoplasmosis (37 patients). Patients receiving other systemic antifungal therapy were excluded. INTERVENTIONS: Itraconazole was administered orally at doses of 200 to 400 mg/d. Patients in whom treatment was considered a success were treated for a median duration of 6.2 months (blastomycosis) and 9.0 months (histoplasmosis). Disease activity was assessed at baseline; drug efficacy and toxicity were evaluated at monthly intervals during therapy, and efficacy was evaluated at regular follow-up visits after completion of therapy. The median duration of posttreatment evaluation for successfully treated patients was 11.9 months (blastomycosis) and 12.1 months (histoplasmosis). MEASUREMENTS AND MAIN RESULTS: Among the 48 patients with blastomycosis, success was documented in 43 (90%). The success rate for patients treated for more than 2 months was 95% (38 of 40). Among the 37 patients with histoplasmosis, success was documented in 30 (81%). The success rate for patients treated for more than 2 months was 86% (30 of 35). All patients with histoplasmosis in whom treatment failed had chronic cavitary pulmonary disease. Toxicity was minor; only 25 (29%) patients experienced any side effects, and itraconazole toxicity necessitated stopping therapy in only 1 patient. CONCLUSIONS: Itraconazole is a highly effective therapy for nonmeningeal, nonlife-threatening blastomycosis and histoplasmosis. The drug is associated with minimal toxicity.

Adult↗
PubMed1990

Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients.

Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure.

Adult↗
PubMed1980

Pulmonary, mediastinal, and cardiac presentations of histoplasmosis.

Sixty-one patients with histoplasmosis were identified. They ranged from 14 months to 67 years old. There were 56 male and 5 female patients. Disease presentations were categorized into pulmonary (47), mediastinal (11), pericardial (2), and cardiac (1). Twenty of the patients with pulmonary involvement had histoplasmomas treated by wedge resection (18) or lobectomy (2). Twenty-two of the 27 cavitary lesions were treated by lobectomy and 4 by segmental resection, and 1 required pneumonectomy. The patients with mediastinal granulomas or fibrosis underwent exploration for diagnosis and curative or palliative procedures. Two patients with pericardial histoplasmosis required pericardial windows to relieve acute tamponade. One patient with disseminated histoplasmosis required aortic valve replacement for histoplasmosis valvulitis with severe regurgitation. The 1 operative death was a patient requiring pneumonectomy for mediastinal histoplasmosis. Indications for operative intervention in pulmonary histoplasmosis included resection of a new or enlarging pulmonary nodule to provide a definite pathological diagnosis and resection of persistent thick-walled pulmonary cavities. Mediastinal granuloma with or without fibrosis required exploration for diagnosis, palliation, or cure. Fungal endocarditis necessitated treatment with amphotericin B and valve replacement to stabilize the patient's hemodynamic status and prevent embolization of large fungal vegetations. Pericardial effusion, a rare manifestation of histoplasmosis, was seen as acute tamponade requiring emergency intervention.

Adolescent↗
PubMed1984

Differentiation of lymphoma from histoplasmosis in children with mediastinal masses.

The differentiation of mediastinal masses caused by lymphoma from those caused by histoplasmosis may require thoracotomy. We reviewed the medical records of 37 children undergoing initial evaluation for anterior or middle mediastinal masses. Sixteen had biopsy-proved lymphoma, and 21 had histoplasmosis; seven with histoplasmosis underwent thoracotomy. Age, sex, fever, weight loss, duration of illness, anemia, erythrocyte sedimentation rate, nonspecific reactants, and lung infiltrates and calcifications were similar in both groups. Masses were in the middle mediastinum in all patients with histoplasmosis and in 69% with lymphoma. Masses were in the anterior mediastinum in one of 21 (5%) with histoplasmosis and 13 of 16 (81%) with lymphoma. Among patients with lymphoma, histoplasmal complement fixation antibody titers were less than 1:8 in 14 of 15 (93%); a single patient had a titer of 1:16. The CF titers were greater than or equal to 1:32 in 14 of 21 (67%) with histoplasmosis. In children with middle mediastinal masses, a histoplasmal CF yeast or mycelial titer greater than or equal to 1:32 is strongly suggestive of acute histoplasmosis and biopsy is not required. Children not fulfilling these criteria should undergo diagnostic biopsy.

Adolescent↗
PubMed2002

Acquired immunodeficiency syndrome-related oral and/or cutaneous histoplasmosis: a descriptive and comparative study of 21 cases in French Guiana.

BACKGROUND: Oral or cutaneous acquired immunodeficiency syndrome (AIDS)-related histoplasmosis is a rare presentation of disseminated histoplasmosis. OBJECTIVE: To describe this clinical presentation and to compare it with other forms of AIDS-related disseminated histoplasmosis. METHODS: A cross-sectional study of patients with AIDS-related disseminated histoplasmosis was performed. CD4 counts and survival were compared between patients with oral or cutaneous histoplasmosis and patients with nonmucocutaneous disseminated histoplasmosis. RESULTS: The mean CD4 lymphocyte count was lower in patients with mucocutaneous lesions than in patients with nonmucocutaneous disseminated histoplasmosis (29 vs. 72/mm3, P = 0.002). The proportion of survivors 1 month after diagnosis did not differ significantly between the two groups (13/21 vs. 32/45, P = 0.4). At 6 months, the proportion of survivors was significantly lower for patients with mucocutaneous lesions (6/21 vs. 22/39, P = 0.03). CONCLUSIONS: These results suggest that mucocutaneous lesions occur at a later stage of human immunodeficiency virus infection, but are not, in themselves, associated with a higher level of mortality. The excess mortality at 6 months reflects deaths from other complications of severe immunodepression. This study confirms the polymorphism of mucocutaneous lesions, emphasizing the need for systematic testing for Histoplasma in all cases of mucocutaneous lesions in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Disseminated histoplasmosis in persons infected with human immunodeficiency virus.

Disseminated histoplasmosis is an AIDS-defining illness that occurs in about 5% of AIDS patients residing in histoplasmosis-endemic areas of the United States (the Mississippi and Ohio river valleys). This disease develops as a result of acute infection and perhaps also as the result of reactivation of latent infection: cases reported from areas such as New York City, where histoplasmosis is not endemic, are most likely due to reactivation of an infection acquired earlier in a histoplasmosis-endemic area, while cases in histoplasmosis-endemic areas are most likely due to acute infection, especially in outbreak settings. Disseminated histoplasmosis in HIV-infected patients is usually associated with advanced immunosuppression, with CD4+ lymphocyte counts of < 75/mm3. Currently, histoplasmin skin testing of HIV-infected patients does not seem to be useful in detecting previous exposure and therefore is not helpful in identifying groups of patients who are at risk for dissemination and who should be targeted for preventive efforts. The current public health recommendation for HIV-infected patients is to avoid exposure to sites likely to harbor high levels of Histoplasma capsulatum, such as chicken coops and bird roosts. The role of chemoprophylaxis is not clear, but an ongoing study by the Mycoses Study Group is evaluating the role of prophylactic itraconazole. If strategies for the prevention of disseminated histoplasmosis in HIV-infected patients are to be improved, studies must better define the risk factors for this opportunistic infection, describe its natural history, and develop more reliable tests to predict its development.

AIDS-Related Opportunistic Infections↗
PubMed1996

Fluconazole therapy for histoplasmosis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

We assessed the efficacy of oral fluconazole (200-800 mg daily) in the treatment of non-life-threatening acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, or disseminated histoplasmosis in patients without human immunodeficiency virus infection. Of 27 evaluable patients, two had progressive acute pulmonary histoplasmosis, 11 had chronic pulmonary histoplasmosis, and 14 had disseminated histoplasmosis. Median durations of treatment in each of the three groups were 6 months, 7 months, and 11 months, respectively. Nineteen patients were treated with 400 mg of fluconazole daily (two of these patients received 800 mg daily for a portion of their treatment courses), seven were treated with 200 mg daily, and one was treated with 800 mg daily. Treatment was successful in 17 (63%) of 27 cases. Both of the patients with acute pulmonary infection responded to therapy, as did five (46%) of 11 patients with chronic pulmonary infection and 10 (71%) of 14 patients with disseminated infection. No substantial toxicity was observed. We conclude that fluconazole therapy for histoplasmosis is only moderately effective and should be reserved for patients who cannot take itraconazole.

Female↗
PubMed1984

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

Acute Disease↗
PubMed2004

Epiglottic histoplasmosis presenting in a nonendemic region: a clinical mimic of laryngeal carcinoma.

Histoplasma capsulatum is a dimorphic fungus endemic to North America. Histoplasmosis is primarily an inhalation-acquired mycosis that is encountered rarely outside of endemic regions. In nonendemic regions, histoplasmosis may present a diagnostic challenge and both clinical and laboratory vigilance are required to accurately identify infection. Unusual clinical presentations with limited physical findings may compound the difficulty in diagnosis. We describe a 78-year-old retired soil science professor who presented with an eroded epiglottic mass secondary to disseminated histoplasmosis in a nonendemic region (Alberta). Clinically, this mass was thought to represent a primary laryngeal carcinoma, as no other buccal or oropharyngeal ulcers were identified. Histoplasmosis was confirmed by tissue biopsy and a positive immunodiffusion test for immunoglobulin G. Disseminated histoplasmosis is often associated with laryngeal and oropharyngeal disease; however, isolated epiglottic histoplasmosis is rare. Histoplasmosis should be included in the differential diagnosis of neoplasms and chronic ulcers of the upper aerodigestive tract.

Aged↗
PubMed2003

Diffuse ulcerations due to disseminated histoplasmosis in a patient with HIV.

Disseminated histoplasmosis is a serious disease that affects the skin, lungs, and internal organs. It is one of the diseases that characterize acquired immunodeficiency syndrome (AIDS), and in endemic areas is one of the more commonly observed infections in AIDS patients. The mortality rate in patients with AIDS and histoplasmosis is high if untreated. Disseminated histoplasmosis may have a variety of dermatological manifestations. In this article, we provide the first report of diffuse ulcerations due to disseminated histoplasmosis. These ulcers developed while the patient was on stavudine, lamivudine, and indinavir, and had a CD-4 count of 525 mm3. The patient's histoplasmosis resolved with itraconazole monotherapy. Histoplasmosis is a well-described opportunistic infection that accompanies human-immunodeficiency virus (HIV) infection. We report an unlikely victim of disseminated histoplasmosis who suffered this infection while on antiretroviral therapy and with a CD-4 count of 525/mm3. Notably, he had a normal chest x-ray and disseminated cutaneous ulcers. The diagnosis was made by skin biopsy, and his infection responded promptly to itraconazole therapy. This case serves as a reminder that the immunological derangements and cutaneous alterations wrought by HIV remain unpredictable in nature and extent.

Adult↗
PubMedDate not supplied

Evaluation of enzyme linked immunosorbent-assay and western blot for diagnosis of histoplasmosis.

This study evaluates the use of a enzyme linked immunosorbent assay (ELISA) for the diagnosis of histoplasmosis and it compares it with a complement fixation test. The results showed a sensitivity of 86% in this diagnosis of acute pulmonary histoplasmosis and specificity of 91% using anti-human IgG. For antihuman IgM the sensitivity was 66% and the specificity 100%. There was a good correlation between the titer of complement fixation test and the optical density index by ELISA. Neither ELISA or complement fixation were useful for the diagnosis of disseminated histoplasmosis in immunocompromised patients. Using Western blot we identified antibodies against four different histoplasma antigens (91, 83, 70 and 38 kD) in sera from patients with histoplasmosis. These antigens were identified also in patients with disseminated histoplasmosis. We conclude that ELISA is a useful test for the diagnosis of histoplasmosis, and the Western blot could be useful for the diagnosis of disseminated histoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1997

AIDS-related disseminated histoplasmosis in San Francisco, California.

The published reports of patients with the acquired immunodeficiency syndrome (AIDS) with disseminated histoplasmosis come mostly from institutions located in endemic areas for histoplasmosis, where disease is thought to occur by either primary infection or reactivation. The characteristics of reactivation disease are not well delineated. We describe the clinical features of reactivation disseminated histoplasmosis in 46 residents of San Francisco, California, with AIDS who did not report recent travel to an area endemic for histoplasmosis. Patients presented with illness lasting days to months, manifested most frequently by fever, chills, sweats, cough or dyspnea, gastrointestinal complaints, malaise, and weight loss. Physical examination and imaging studies were notable for hepatosplenomegaly, lymphadenopathy, or abnormal pulmonary findings in more than half of patients. Laboratory studies revealed a high rate of cytopenia, elevated serum lactate dehydrogenase levels, abnormal liver function test values, respiratory alkalosis with hypoxemia, and a median CD4 lymphocyte count of 36 x 10(9) per liter. The clinical presentation of reactivation disseminated histoplasmosis in patients with AIDS living in San Francisco is similar to that of disseminated histoplasmosis reported in patients with AIDS living in endemic areas. Reactivation disseminated histoplasmosis should be considered in any AIDS patient with a low CD4 lymphocyte count, a febrile illness, and a history of travel or residence in an endemic area.

AIDS-Related Opportunistic Infections↗
PubMed1994

Risk of visual impairment attributable to ocular histoplasmosis. Washington County Follow-up Eye Study Group.

PURPOSE: To compare 15-year incidence rates of visual impairment and vision-threatening conditions between cases with ocular histoplasmosis and controls residing in the same endemic community. METHODS: Controls and cases with and without disciform lesions who were between 30 and 69 years of age when selected, interviewed, and examined in 1970 were reinterviewed and reexamined in 1985. RESULTS: Of the 252 cases and controls examined in 1970, 216 were still alive in 1985. Of these, 202 (94%) were interviewed; 197 (91%) underwent visual acuity measurement; and 173 (80%) were examined by a study ophthalmologist. Both in 1970 and in 1985, cases with disciform macular lesions of ocular histoplasmosis had a higher prevalence of both unilateral and bilateral visual impairment and blindness. Although prevalence of visual impairment and blindness in 1985 was similar among controls and cases of ocular histoplasmosis without disciform lesions, this group of cases had about twice the incidence of visual impairment as that of controls. However, the 95% confidence intervals on estimates of relative risks were broad and included unity. No new disciform lesions attributable to ocular histoplasmosis were found in 28 eyes of 18 cases free of them in 1970 or among 148 controls. CONCLUSIONS: The 15-year risk of visual impairment and blindness appears to be somewhat higher among adults aged 30 years and older who have only peripheral atrophic scars characteristic of ocular histoplasmosis than among individuals without such scars who live in the same endemic community. Adults who already have a disciform lesion attributed to ocular histoplasmosis in one eye are at low risk of development of a disciform lesion in the fellow eye later in life.

Adult↗
PubMed2002

Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept.

OBJECTIVE: Two tumor necrosis factor alpha (TNFalpha) antagonists were recently licensed in the US. Infliximab was licensed in 1998 for the treatment of Crohn's disease (CD), and since 1999, it has been licensed in combination with methotrexate for treatment of rheumatoid arthritis (RA). Etanercept was licensed in 1998 for treatment of RA and, more recently, for juvenile RA and psoriatic arthritis. Because of potential immunosuppression related to use of anti-TNFalpha agents, we sought to identify postlicensure cases of opportunistic infection, including histoplasmosis, in patients treated with these products. METHODS: The US Food and Drug Administration's (FDA) passive surveillance database for monitoring postlicensure adverse events was reviewed to identify all reports received through July 2001 of histoplasmosis in patients treated with either infliximab or etanercept. RESULTS: Ten cases of Histoplasma capsulatum (HC) infection were reported: 9 associated with infliximab and 1 associated with etanercept. In patients treated with infliximab, manifestations of histoplasmosis occurred within 1 week to 6 months after the first dose and typically included fever, malaise, cough, dyspnea, and interstitial pneumonitis. Of the 10 patients with histoplasmosis, 9 required treatment in an intensive care unit, and 1 died. All patients had received concomitant immunosuppressive medications in addition to infliximab or etanercept, and all resided in HC-endemic regions. CONCLUSION: Postlicensure surveillance suggests that acute life-threatening histoplasmosis may complicate immunotherapy with TNFalpha antagonists, particularly infliximab. Histoplasmosis should be considered early in the evaluation of patients who reside in HC-endemic areas in whom infectious complications develop during treatment with infliximab or etanercept.

Adult↗
PubMed1991

Colonic histoplasmosis in acquired immunodeficiency syndrome. Report of two cases.

Colonic histoplasmosis is a rare entity. There have been four previous reported cases within the population of patients with human immunodeficiency virus (HIV) infection. Because of the increasing incidence of HIV infection within regions where histoplasmosis is endemic, this condition may become more common. Gastrointestinal histoplasmosis has protean clinical manifestations, and symptoms are often nonspecific. Any patient with HIV infection who has unexplained GI symptoms should undergo evaluation for possible histoplasmosis. Aggressive long-term amphotericin B therapy has been effective in HIV patients with histoplasmosis. Resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group.

PURPOSE: Amphotericin B has been the treatment of choice for disseminated histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). Oral antifungal agents would be welcome alternatives to standard treatment of disseminated histoplasmosis in less severe cases. The purpose of this study was to assess the efficacy and safety of itraconazole therapy in patients with AIDS and disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial conducted in university hospitals of the AIDS Clinical Trial Group. All patients had AIDS and first episodes of disseminated histoplasmosis. Patients with central nervous system involvement or with severe clinical manifestations were excluded. Patients were treated with itraconazole BID by mouth 300 mg for 3 days and then 200 mg BID for 12 weeks. Resolution of clinical findings, clearance of positive cultures, and drug tolerance were the main outcome measurements. A secondary objective was effect of therapy on Histoplasma capsulatum var capsulatum antigen levels. RESULTS: Of 59 evaluable patients, 50 (85%) responded to therapy. Five patients withdrew because of progressive infection, 1 died of a presumed pulmonary embolus within the first week of therapy without improvement, 2 withdrew because of toxicity, and 1 was lost to follow-up after week 2 of therapy. Patients with moderately severe clinical (fever > 39.5 degrees C or Karnofsky score < 60) or laboratory abnormalities (alkaline phosphatase > 5 times normal or albumin < 3 g/dL) at baseline tended to respond more poorly than did other patients. Resolution of complaints of fever and improvement in fatigue occurred after a median of 3 and 6 weeks, respectively, and weight gain after 2 weeks. Fungemia cleared after a median of 1 week. H capsulatum var capsulatum antigen cleared from the urine and serum at rates of 0.2 and 0.3 units per week, respectively. CONCLUSIONS: Itraconazole is safe and effective induction therapy for mild disseminated histoplasmosis in patients with AIDS, offering an alternative to amphotericin B in such cases. Patients with moderately severe or severe histoplasmosis should first be treated with amphotericin B and then may be switched to itraconazole after achieving clinical improvement.

AIDS-Related Opportunistic Infections↗