Paracoccidioidomycosis and infection by the human immunodeficiency virus

We present two cases of paracoccidioidomycosis, one occurring in an AIDS patient and the other in an HIV infected man. This is the first report of such association. The first patient, which was already followed for HIV infection (group IV-A) presented with high fever and hepatosplenomegaly. Plain X-ray, ultrasound and CT-scan of the abdomen showed solid nodules in the spleen, some of them with calcification. Both the direct smear and the culture of a bone marrow aspiration revealed Paracoccidioides brasiliensis. The patient died of acute disseminated Paracoccidioidomycosis. The second patient, a man anti-HIV seropositive presented with a mass on the right lower abdomen and inguinal region. A biopsy of the mass showed the association of Hodgkin's disease of the mixed cellularity type and paracoccidioidomycosis. With the expanding AIDS epidemic we believe this report emphasizes the need to consider Paracoccidioidomycosis in HIV infected persons in countries where this mycosis is endemic. We also suggest the inclusion of Paracoccidioidomycosis as a potential opportunistic infection in these areas.     

Gastrointestinal paracoccidioidomycosis: an overview

Paracoccidioidomycosis is the most prevalent mycosis in Latin America. Although the lungs are the primary site of infection, physicians often see patients because of disseminated disease. Imported paracoccidioidomycosis has been described in different regions of the world in patients who lived in endemic areas. Gastrointestinal disease owing to P. brasiliensis is rarely recognized in life because of nonspecific clinical manifestations. Gastrointestinal disease can present as part of progressive dissemination of infection or as a result of local complications from a silent healing process. This review will summarize the salient features of gastrointestinal paracoccidioidomycosis.     

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.     

Disseminated paracoccidioidomycosis (South American blastomycosis) in the United States

Paracoccidioidomycosis or South American blastomycosis (SAB) is a systemic mycosis endemic to South America but rarely recognized in North America. Visceral dissemination has not been described in the eight cases previously reported from the United States. The patient we describe represents the first case of visceral disseminated SAB, with testicular, adrenal and probable hepatic involvement, diagnosed in the United States. The pathogenesis, clinicopathologic manifestations and therapy of SAB, with particular attention to disseminated paracoccidioidomycosis with adrenal insufficiency, is reviewed.     

Progressive disseminated histoplasmosis in patients with the acquired immune deficiency syndrome: a report of 12 cases and a literature review

Progressive disseminated histoplasmosis is an increasingly common cause of infection in patients with acquired immune deficiency syndrome (AIDS) from areas endemic for histoplasmosis. We report 12 cases of progressive disseminated histoplasmosis associated with AIDS and review 20 previously reported cases. The clinical presentation of progressive disseminated histoplasmosis is nonspecific with persistent fever, weight loss, and splenomegaly. Frequently progressive disseminated histoplasmosis was the initial clue to the presence of AIDS. Bone marrow culture is the best method for establishing a diagnosis. Relapses were common both with ketoconazole and after a 2.0 to 2.5 g course of amphotericin B. This suggests a 2.0 to 2.5 g course of amphotericin B followed by long term ketoconazole suppression may be the best therapeutic regimen in these patients.     

Opportunistic tropical infections in immunosuppressed patients

Autoimmune and autoinflammatory diseases are associated with severe morbidity, and represent an impactful health and economic burden worldwide. The treatment of these diseases can include a course with detrimental side effects. Immunosuppression increases the risk of opportunistic infections, but in some cases, the abrupt discontinuation of these medications can result in immune reconstitution inflammatory syndrome. Special attention must be directed to endemic tropical infections, such as leishmaniasis, Chagas disease, malaria, arbovirosis, yellow fever, leprosy, paracoccidioidomycosis, disseminated strongyloidiasis, and ectoparasitosis. These endemic diseases of developing countries can be considered as possible emerging diseases in developed regions partially because of environmental factors and migration. In the present article, we aim to review the evidence-based aspects of the most important opportunistic tropical infections in immunosuppressed patients. We also aim to review the important aspects of vaccination, chemical prophylaxis, and treatment for these infections in people with medication-induced immunosuppression.     

Disseminated histoplasmosis in the acquired immunodeficiency syndrome. Report of five cases from a nonendemic area

Disseminated histoplasmosis is predominantly a disease of the immunocompromised. However, it has been reported infrequently in patients with the acquired immunodeficiency syndrome (AIDS), and then almost exclusively from patients residing in endemic areas. We report five cases of disseminated histoplasmosis in patients with AIDS in a nonendemic area. The initial diagnosis was made by fiberoptic bronchoscopy in three patients and by bone marrow and liver biopsy specimens in one patient each. All patients had fungemia, septic shock, and multiple organ involvement. Three patients had a fulminant course and died within four weeks. Two patients had more prolonged courses, with one survival period of ten months. We conclude that patients with AIDS are at high risk to contract disseminated histoplasmosis with an extremely high morbidity and mortality. This risk is not limited to residents of endemic areas.     

Epidemiología actual y diagnóstico de laboratorio de las micosis endémicas en España

Histoplasmosis and paracoccidioidomycosis are emerging infections in Spain associated with immigration and travelling. In last three decades a total of 128 cases of histoplasmosis have been reported in Spain, 59 in travellers, 63 in immigrants, three associated to drug abuse, two in laboratory workers, and one in a solid organ transplant receptor. In 1969 the first Spanish case of paracoccidioidomycosis was published and a total of 21 cases have been reported so far. Those patients suffered from the chronic form of the disease with period of latency as long as 50 years. Other endemic mycoses such as blastomycosis, coccidioidomycosis, lobomycosis, pythiosis and sporotrichosis have not increased in frequency. Microbiological cultures of endemic fungi must be handled in facilities which comply with international biosafety regulations and must also be taken into account for cultures from patients with suspected endemic mycosis.     

Histoplasmosis in the acquired immune deficiency syndrome

This report describes the experience with disseminated histoplasmosis in seven of 15 patients with the acquired immune deficiency syndrome (AIDS) diagnosed in Indianapolis since 1981. Three were homosexual, two were intravenous drug addicts, one was the spouse of another patient with AIDS and disseminated histoplasmosis, and the seventh was a hemophiliac. Six had associated infections: candidiasis in three, Pneumocystis carinii pneumonia, recurrent mucocutaneous herpes simplex infection, and disseminated Mycobacterium avium infection in two each, and disseminated infection with an unidentified mycobacterium in one. Clinical diseases suggested sepsis in four. Histoplasma fungemia occurred in five, but the diagnosis was established first by visualization of organisms in blood or bone marrow in three. Results of Histoplasma serologic tests were positive in each. Three died before receiving 50 mg of amphotericin B, three had prompt improvement with amphotericin B, and one was treated with ketoconazole to prevent dissemination. However, two of the three patients treated with amphotericin B had relapses after a 35 mg/kg course, and the third died within a month following therapy. Disseminated histoplasmosis is a major opportunistic infection in patients with AIDS from endemic areas. AIDS should be strongly considered in otherwise healthy persons with disseminated histoplasmosis, especially if risk factors for AIDS are present. Amphotericin B is not curative in these patients.     

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.     

Progressive disseminated histoplasmosis in the acquired immunodeficiency syndrome: a model for disseminated disease

Progressive disseminated histoplasmosis (PDH) is a relatively common infectious illness in human immunodeficiency virus (HIV)-infected patients. In Houston, Texas, (which is moderately endemic for histoplasmosis) the frequency of PDH is 5% among patients with acquired immunodeficiency syndrome (AIDS), almost as high as that of those with cryptoccal disease. In highly endemic areas, the frequency of PDH in AIDS is even greater, up to 75% in some areas. It is likely that as the HIV epidemic continues to penetrate to more remote, highly endemic areas, more and more cases of PDH will occur. It is also clear that PDH may develop in HIV-infected patients who presently live in nonendemic areas, but who previously resided in endemic areas. It is important that all physicians who care for HIV-infected patients become thoroughly familiar with the clinical manifestation of this illness. Timely diagnosis depends on a high degree of diagnostic suspicion since the illness seldom presents with primary respiratory symptoms. It is prudent to consider PDH in the differential diagnosis of any systemic, wasting, febrile illness in HIV-infected individuals, especially if currently or in the past they have resided in areas endemic for the fungus. Similarly, whenever PDH is diagnosed in any patient who is in a high-risk group for HIV infection, prompt testing for HIV should be performed.     

Gastrointestinal histoplasmosis in patients with AIDS: case report and review.

Histoplasmosis is the most common endemic mycosis in individuals with AIDS, occurring in 2%-5% of this population. Infection is more likely to be disseminated than in immunocompetent individuals and generally presents insidiously with nonspecific symptoms. The gastrointestinal tract is involved in 70%-90% of cases of disseminated histoplasmosis, yet gastrointestinal histoplasmosis per se is infrequently encountered in patients with AIDS. The diagnosis of gastrointestinal histoplasmosis is often not suspected, particularly in areas of nonendemicity, and a delay in diagnosis may lead to increased morbidity and risk of death. Since antifungal therapy improves outcome for >80% of AIDS patients with histoplasmosis, it is essential that caregivers be aware of the varied presentations of gastrointestinal histoplasmosis in order to diagnose and to treat this potentially life-threatening infection effectively.     

Rupioid histoplasmosis: first case reported in an AIDS patient in Argentina

Disseminated histoplasmosis is a relatively common AIDS-defining illness, occurring in almost 4% of patients living in endemic areas and it may be the first clinical expression of the HIV infection. A broad spectrum of clinical skin lesions associated with Histoplasma capsulatum infection have been described in AIDS patients, such as erythematous macules, papules, nodules, and pustules. Herpetic, acneiform, erythema multiforme-like, molluscum contagiosum-like, vasculitic, and exfoliative forms have also been reported. To our knowledge, this is the first case of disseminated histoplasmosis in an AIDS patient presented as a rupioid eruption.     

Biliary Paracoccidioidomycosis: An Unusual Infection Simulating Malignant Neoplasm

Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis and is restricted to Latin America. It normally affects lungs, skin and lymph nodes. Abdominal organs are usually not involved. In rare cases paracoccidioidomycosis may simulate neoplasm. Herein we describe our experience with four cases of paracoccidioidomycosis mimicking cholangiocarcinoma. To the best of our knowledge, this is the largest case series on this subject produced in English. Paracoccidioidomycosis must be considered as a differential diagnosis of cholangiocarcinoma, especially in individuals who come from endemic areas.     

Paracoccidioidomycosis and AIDS: report of the first two Colombian cases.

The records of the first two Colombian patients with AIDS and paracoccidioidomycosis are presented. Both patients were males and had no known risk factors for HIV although in the past they had worked in the field where they could have been infected with the fungus. They exhibited the juvenile type of disease with multiple organ system involvement and symptoms of short duration. They were deeply immunodepressed as indicated by less than 100 CD4 T lymphocytes per mL; however, serologic tests revealed circulating anti-Paracoccidioides brasiliensis antibodies and in one patient the first diagnostic clue came from such tests. In one case, the mycosis preceded the AIDS diagnosis while in the other, both pathologies were discovered simultaneously. Antimycotic therapy with itraconazole was administered for over 10 months, with an initial dose of 200 mg/day followed by 100 mg/day; marked improvement of the mycotic signs and symptoms was soon noticed an there have been no signs of relapse. The patients improvement was also due to the combined retroviral treatment that was instituted. In spite of the rarity of the AIDS-paracoccidioidomycosis association, physicians practicing in endemic areas should consider the presence of the mycosis in immunosuppressed patients, since a prompt diagnosis and institution of combined antimycotic-anti-retroviral treatments would result in patient improvement and survival. It appears possible that the longer survival time of today's AIDS patients would give the quiescent fungus the opportunity to revive, multiply and cause overt disease.     

Histoplasmosis due to Histoplasma capsulatum capsulatum and HIV infection

PURPOSE: Histoplasmosis due to Histoplasma capsulatum is a granulomatous fungic infection which appears opportunistic and disseminated in immunocompromised patients, especially among HIV patients in whom it can lead to death. Histoplasmosis is endemic in numerous areas worldwide, but in Europe most of the cases reported are imported. We describe the clinical features and the available diagnosis methods issued from our experience in French Guyana. METHODS: Contamination occurs by inhalation of spores contained in dust. Most endemic areas are located on the American continent, including the French West Indies, where the incidence of histoplasmosis among HIV patients in French Guyana varies from 1.2 to 2.2% per year. In non-immunocompromised patients, histoplasmosis is asymptomatic most of the time. In HIV patients, the disseminated form is common and may occur many years after exposure to the fungus. RESULTS: Non-specific symptoms, similar to those of either tuberculosis or other opportunistic infections, may reveal disseminated histoplasmosis in patients with AIDS. Early treatment (amphotericin B or itraconazole) is effective; however, it should be followed by a lifelong antifungic treatment (itraconazole) to prevent relapse. CONCLUSION: The infection should be suspected in any febrile HIV-infected patient with CD4 blood cell count < 200/mm3, if he/she ever travelled in an endemic zone. Direct examination of smear relating to clinical symptoms help guide diagnosis, while culture will confirm it after at least 4 weeks. Efficient serologic techniques for HIV-infected patients are not available in Europe.     

Histoplasmosis: a study of 158 cases in Venezuela, 2000-2005

Histoplasmosis, a granulomatous disease caused by Histoplasma capsulatum, is endemic in Venezuela. We conducted the current study to appraise retrospectively the demographic data, clinical features, diagnostic methods, and treatment of patients with histoplasmosis from January 2000 to December 2005.We reviewed the medical records of outpatient cases with a diagnosis of histoplasmosis and considered clinical samples processed at our laboratory. We collected demographic, epidemiologic, and clinical data from each case as available, including results of any mycologic examinations performed. Treatment and outcome data were available for some patients.We assessed 158 cases of histoplasmosis: 103 (65.2%) patients came from the Caracas metropolitan area; 53 were associated with acquired immunodeficiency syndrome (AIDS), 14 with tuberculosis, and 8 with paracoccidioidomycosis. Six pediatric patients were malnourished. Epidemiologic data suggested histoplasmosis in most cases. Patients received treatment with itraconazole and/or amphotericin B.Our results may reflect changes in the epidemiology occurring in Venezuela, perhaps due to environmental changes and the presence of AIDS. Several mycologic exams are necessary to ensure a proper diagnosis. More reliable data and statistics on this infection are necessary to monitor outbreaks closely and to establish if there is an epidemic pattern.     

LIMITED ADRENAL RESERVE IN PARACOCCIDIOIDOMYCOSIS: CORTISOL AND ALDOSTERONE RESPONSES TO 1–24 ACTH

Adrenal function in twenty-three patients with paracoccidioidomycosis (South American Blastomycosis) has been assessed by measuring the response to adrenocortical stimulation with 1-24 ACTH. Two patients with overt Addison's disease showed very low basal levels and the complete absence of an increase in either cortisol or aldosterone secretion. Six patients showed probable diminished adrenal reserve in terms of cortisol and three patients showed diminished reserve in terms of aldosterone function. These findings indicate an incidence of significant hypoadrenalism in 44% of hospitalized patients with disseminated paracoccidioidomycosis.     

Cutaneous Manifestations of Endemic Mycoses

All of the endemic mycoses have cutaneous and mucocutaneous manifestations that are most commonly seen when patients have disseminated infection. Biopsy of skin lesions is simple and safe and can assist in making a timely diagnosis of disseminated infection. Primary cutaneous inoculation infection has been reported with all of the endemic mycoses, but is rare. In this situation, a nodule or ulcer occurs at the inoculation site, is often accompanied by lymphangitis and regional lymphadenopathy, and systemic symptoms and signs as almost always absent. Mucosal lesions are common with disseminated histoplasmosis, but also have been described in patients who have disseminated blastomycosis and coccidioidomycosis. Biopsy is essential to rule out cancer and allows a rapid diagnosis of the endemic fungal infection.     

Bone marrow involvement and eosinophilia in paracoccidioidomycosis]

The authors described three acute paracoccidioidomycosis patients with bone marrow involvement. P. brasiliensis yeast forms were observed in bone marrow smears of all them, and in one case, culture also revealed fungus growth. The mononuclear phagocytic system involvement, the blood eosinophilia and the negative skin hypersensibility responses were emphasized in all of them, as well as the severity of the disease in one case, with disseminated bone lesions and 20.260 eosinophils/mm3 in peripheral blood. The authors discuss the possible role of eosinophil in the host-parasite interaction in paracoccidioidomycosis, suggesting that TH 2 subpopulation activation and increased IL 5 and GM-CSF secretions may be responsible by eosinophilia in the most severe case.