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The syndrome of presumed ocular histoplasmosis in Mexico: a preliminary study.

A study to screen for the syndrome of presumed ocular histoplasmosis (SPOH) among native populations from three Mexican states was performed. Two of these states, Guerrero and Querétaro, were selected as histoplasmosis is endemic there, whereas Tlaxcala was considered a control, due to the absence of reported cases. A total of 253 individuals were submitted to ocular fundus examination to obtain evidence of SPOH. A high percentage of positive reactors to histoplasmin skin test (ST) was observed in Guerrero (83%) and Querétaro (53%), whereas in Tlaxcala positive ST were almost absent (2.04%). Only five individuals had retinal lesions, although these lesions were not characteristic of the syndrome. Stimulation of these individual's cells showed different patterns in the histoplasmin-induced lymphocyte transformation response, and two out of five individuals with retinal lesions presented a stimulated response, as well as three controls without lesions. Histocompatibility antigens (HLA) were determined in a sample of each population and no particular allele, including HLA-B7, was found to be related to SPOH as reported in the USA; however, HLA-B22 was found in three individuals who developed pulmonary histoplasmosis. Results do not provide clinical evidence or data on specific HLA risk factors, for the presence of SPOH in the population studied.

Alleles↗

Oral histoplasmosis in India: a case report and an overview of cases reported during 1968-92.

Oral histoplasmosis in a 30-year-old male with no history of travel outside India is described. An ulcerating lesion was located on the hard palate. A chest X-ray was normal. Based on physical examination, regional lymph nodes, liver and spleen were not involved. The diagnosis was established by demonstrating yeast-like budding cells in a biopsy of the lesion and by isolating Histoplasma capsulatum in pure culture. The identity of the isolate was confirmed by a chemiluminescent DNA-probe assay and the exoantigen test. A review of the Indian literature from 1968 to 1992 revealed the occurrence of 25 authentic cases of histoplasmosis in India. In 19 cases, lesions were confined to the oral cavity confirming prior observation that histoplasmosis in Indian patients tends to occur primarily in extrapulmonary sites, particularly the oral cavity.

Adult↗

Therapy of systemic histoplasmosis in immunosuppressed mice with the triazole D0870.

Because histoplasmosis is a life-threatening disease in AIDS and other compromised patients, we examined the efficacy of D0870 (Zeneca) in immunosuppressed mice against systemic histoplasmosis. Oral therapy with fluconazole given once daily (QD) was ineffective in prolonging survival, whereas itraconazole given once or twice daily (BID), fluconazole given BID or D0870 given QD or given every other day (QOD) were efficacious (P < 0.001). Burdens of Histoplasma capsulatum in the liver and spleen of survivors showed that D0870 given QD or QOD and itraconazole given BID caused dose-responsive reduction of infectious burden. Infection was cleared more readily from the liver than from the spleen. Overall, D0870 was > or = 20-fold more efficacious than fluconazole or itraconazole and itraconazole was > ten-fold better than fluconazole for the treatment of systemic histoplasmosis in the immunosuppressed model.

Animals↗

Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy.

We performed a prospective observational study to assess the safety of stopping maintenance therapy for disseminated histoplasmosis among human immunodeficiency virus infected patients after response to antiretroviral therapy. All subjects received at least 12 months of antifungal therapy and 6 months of antiretroviral therapy before entry. Negative results of fungal blood cultures, urine and serum Histoplasma antigen level of <4.1 units, and CD4+ T cell count of >150 cells/mm3 were required for eligibility. Thirty-two subjects were enrolled; the median CD4+ T cell count at study entry was 289 cells/mm3. No relapses of histoplasmosis occurred after a median duration of follow-up of 24 months. This corresponded to an observed relapse rate of 0 cases per 65 person-years. The median CD4+ T cell count at final study visit was 338 cells/mm3. Discontinuation of antifungal maintenance therapy appears to be safe for patients with acquired immunodeficiency syndrome with previously treated disseminated histoplasmosis and sustained immunologic improvement in response to antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

Modulation of immune responses in murine pulmonary histoplasmosis.

The influence of endogenous interleukin (IL)-12 on the course of pulmonary histoplasmosis was examined in naive and immune mice. All naive animals pretreated with anti-IL-12 monoclonal antibody (MAb) died by day 14. All mice died when anti-IL-12 MAb was initiated as late as postinfection day 3. Unlike those of controls, lungs of naive mice given anti-IL-12 MAb had depressed levels of interferon (IFN)-gamma and increased tumor necrosis factor (TNF)-alpha. The 2 groups had similar IL-4 levels. Administration of anti-IL-4 MAb rescued mice from the inimical effects of anti-IL-12 MAb. Survival of mice given both anti-IL-12 and anti-IL-4 MAb was associated with a blunted TNF-alpha response. In reinfection histoplasmosis, treatment with anti-IL-12 MAb did not alter survival. Fungus burden in lungs, livers, and spleens differed at week 2, but not at week 1, of infection. Thus, endogenous IL-12 is critical for optimal generation of a protective immune response in pulmonary histoplasmosis.

Animals↗

Histoplasmosis in AIDS: advances in management.

Histoplasmosis is one of the most common opportunistic infections in HIV-infected patients who reside in endemic areas, and "imported infections" also occur elsewhere. A recent decline in the incidence of histoplasmosis appears to correlate with advances in antiretroviral therapy. Histoplasmosis occurs due to either dissemination of newly acquired infection or reactivation of latent foci of infection. Major risk factors include a CD4 count < or = 150/microL, positive complement fixation serology for the Histoplasma capsulatum mycelial antigen, and a history of exposure to chicken coops; in addition, suboptimal antiretroviral therapy seems likely to be a risk factor. Although there are a variety of clinical manifestations, most patients present with a several-week history of fever, chills, weakness, and weight loss. Diagnosis is based on positive cultures of blood, bone marrow, or other sites; detection of antigen in serum or urine; or characteristic histopathologic findings in biopsy specimens. Induction therapy consists of amphotericin B for acutely ill patients or itraconazole for patients with mild to moderately severe disease. Subsequent lifelong maintenance therapy with itraconazole is recommended. In patients with CD4 counts of < or = 150/microL, itraconazole is effective primary prophylaxis.

AIDS-Related Opportunistic Infections↗

Corticosteroids as an antiangiogenic agent for histoplasmosis-related subfoveal choroidal neovascularization.

The purpose of this study was to evaluate the role of corticosteroids in managing subfoveal choroidal neovascularization (CNV) secondary to the presumed ocular histoplasmosis syndrome. The cases of eighteen patients with histoplasmosis-related subfoveal CNV treated with corticosteroids were reviewed. Ten patients received oral prednisone for 4 to 6 weeks, and eight received a single sub-Tenon's injection of triamcinalone. Visual acuity outcomes were analyzed along with side effect profiles. At two-week follow-up, the prednisone group showed a median improvement in Snellen visual acuity of +2.0 lines, while the triamcinalone group remained essentially stable with a 0.5 line median loss. At treatment end (4 to 6 weeks), both groups showed no significant change in median acuity at 0.0 and -1.0 lines, respectively. Median final vision at 3 months also remained essentially stable at -0.5 lines for each group. Three patients reported anxiety, all of whom were taking prednisone 80 mg daily. Two patients reported increased appetite and weight gain on regimens of prednisone 80 and 100 mg daily. There were no adverse effects reported in the other patients receiving oral prednisone or in any patient receiving sub-Tenon's triamcinalone. The results suggest a beneficial effect of corticosteroids in stabilizing subfoveal CNV secondary to ocular histoplasmosis. In this small series, oral prednisone resulted in a short-term improvement in visual acuity, which stabilized over longer follow-up. The sub-Tenon's triamcinalone group achieved similar final stabilization without the initial improvement. Corticosteroids may be particularly valuable in managing neovascularization in patients who are awaiting interventions currently under development, in preventing recurrence after subfoveal surgery, or in treating non-surgical candidates. Further study is warranted to define the precise role of corticosteroids in this condition.

Administration, Oral↗

Disseminated histoplasmosis complicating bone marrow transplantation.

A patient receiving allogeneic bone marrow transplant for treatment of acute myelomonocytic leukemia died on the 78th post-transplant day with clinically unrecognized disseminated histoplasmosis. Granulomas and Histoplasma organisms were found in the histologic sections of the marrow aspirate. Patients from endemic areas referred to transplant centers may be at high risk for disseminated histoplasmosis when treated with long-term prednisone for graft-versus-host disease. Aspiration of bone marrow with use of clot sections is a minimally invasive, sensitive, and rapid means of detecting granulomatous infection in such febrile immunosuppressed hosts. Disseminated histoplasmosis has not been described previously as a complication of bone marrow transplantation.

Adult↗

Recurrent urban histoplasmosis, Indianapolis, Indiana, 1980-1981.

In January 1981, informal surveillance of acute histoplasmosis in Indianapolis, Indiana, revealed a marked increase in disease activity for the last quarter of 1980. Fifty-one patients with onset of acute histoplasmosis during this period were identified through review of hospital admissions, emergency room visits, and serologic records at Indianapolis hospitals and the Indiana State Board of Health. In a retrospective case-control study, the authors found a significant association between developing acute histoplasmosis during this period and working or attending classes in a 2 sq mi (5.2 sq km) area encompassing the Indiana University-Purdue University campus (p = 0.015, Fisher's exact test). A review of construction activities on or near the campus during the epidemic period suggested that the probable source of infection was excavation activity for a large new indoor swimming complex (natatorium). Skin tests and serosurveys of students on campus by a newly developed radioimmunoassay for histoplasmal immunoglobulin M antibodies supported the association of infection with exposure to this site (p less than 0.05).

Disease Outbreaks↗

Disseminated histoplasmosis in a patient with sarcoidosis: a controversial relationship and a diagnostic dilemma.

The diagnosis of sarcoidosis in patients with disseminated histoplasmosis remains controversial. It has been suggested that the immune abnormalities in sarcoidosis predispose one to disseminated histoplasmosis. Two cases have been reported that indicate a possible relationship between the two diseases. This is a case of sarcoidosis complicated with disseminated histoplasmosis in which the controversial relationship between the two diseases is emphasized and the available medical literature is reviewed.

Diagnosis, Differential↗

Cutaneous manifestations of histoplasmosis in the acquired immune deficiency syndrome.

The clinical and histologic features of cutaneous histoplasmosis in three patients with acquired immunodeficiency syndrome (AIDS) are described. The patients presented with multiple discrete papules on the extremities, trunk, and face, some of which were follicular. Histologically, the skin biopsies were characterized by a sparse perivascular infiltrate with polymorphonuclear leukocytes, lymphocytes, and occasional histiocytes. Prominent leukocytoclasia and associated dermal necrosis were seen around the superficial blood vessels of the dermis. The Histoplasma capsulatum organisms were for the most part extracellular and difficult to visualize on the hematoxylin and eosin-stained sections. A diagnosis of atypical leukocytoclastic vasculitis was considered. Histoplasmosis is a relatively common mycosis among AIDS patients, and it is sometimes the first manifestation of the syndrome. The clinical and histologic findings described herein may be relatively common among AIDS patients and are quite different from those of classic disseminated histoplasmosis.

AIDS-Related Opportunistic Infections↗

Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature.

Histoplasmosis remains a common infection in endemic regions of North America and Latin America, causing a broad spectrum of clinical findings. Experience during recurrent outbreaks in Indianapolis has shown the importance of immunosuppressive conditions including the acquired immunodeficiency syndrome (AIDS) as a risk factor for disseminated disease and expanded our knowledge of the common clinical manifestations. Pericarditis, rheumatologic manifestations, esophageal compression, and sarcoidlike manifestations were found to be relatively common findings in histoplasmosis. These studies have established the useful role of serologic testing and have led to the discovery of antigen testing for diagnosis of histoplasmosis. This experience also has offered the opportunity to examine the outcome of treatment in persons with AIDS, contributing to studies that have found itraconazole to be an excellent alternative to amphotericin B in persons with mild or moderately severe infection.

AIDS-Related Opportunistic Infections↗

Oropharyngeal histoplasmosis.

Histoplasmosis, though usually a silent pulmonary infection, may progress to a severe, sometimes fatal disseminated infection. In the chronic form of disseminated histoplasmosis, granulomatous lesions of the upper aerodigestive tract are common. These lesions can be mistaken for carcinoma on initial presentation, as in the case we have presented here. The clinical course of patients with acute, subacute, or chronic disseminated forms of this disease correlates well with the histopathologic findings. Diagnosis is best made by culture or biopsy of a characteristic lesion. Although amphotericin B remains the standard treatment of disseminated histoplasmosis, the imidazole compounds such as ketoconazole, either alone or in combination with amphotericin B, have also been shown to be effective.

Adult↗

Disseminated histoplasmosis in patients with AIDS.

Disseminated histoplasmosis was diagnosed in 36 (4%) of 980 patients with AIDS seen at Parkland Memorial Hospital in Dallas, Texas before September 30, 1989. Diagnostic sensitivity of blood culture plus examination of peripheral smear was 88%; sensitivity of bone marrow aspiration and blood culture was 80%. Median CD4 lymphocyte count at diagnosis was 33/cu mm. Median actuarial survival from the date histoplasmosis was diagnosed was 188 days. Thirteen (36%) of the 36 patients died before adequate antifungal therapy could be administered, while 13 survived long enough to receive 1,500 mg of amphotericin B; actuarial survival of the latter group from the date 1,500 mg of amphotericin B had been infused was 47% at 1 year. The substantial early mortality of AIDS-associated disseminated histoplasmosis and the modestly encouraging survival of those who were diagnosed in time to receive adequate therapy raise the issues of surveillance, prophylaxis, and empiric therapy for this infection in selected HIV-positive patients.

Acquired Immunodeficiency Syndrome↗

Diagnosis of systemic histoplasmosis in patients with AIDS.

To compare various laboratory methods for diagnosis of systemic histoplasmosis, we retrospectively reviewed the charts of 165 patients with AIDS (acquired immunodeficiency syndrome). In eight of those patients, systemic histoplasmosis was confirmed by laboratory techniques. The laboratory methods used were histomorphology and microbiology. Tissues and fluids used for fungal cultures and histochemical stains included blood, bone marrow, lung, skin, pleura, esophagus and colon biopsy specimens, sputum, cerebrospinal fluid, bronchial washing/brushing, and pleural and peritoneal fluids. Results were positive in 83% of blood cultures and 71% of bone marrow cultures, making these tissues the best sources of Histoplasma organisms for microbiologic study. Similarly, Histoplasma sp could be demonstrated by fungal stains in 75% of bone marrow biopsy specimens as the main source for morphologic documentation of systemic histoplasmosis. The other tissues and fluids were only occasionally positive either microbiologically or morphologically. There was cross-positivity between morphologic and microbiologic methods in 80% of confirmed cases, making both methods equally reliable. However, the results were obtained within 48 hours by histomorphology, allowing prompt initiation of antifungal therapy. Although more specific results were produced by microbiologic methods, it took 18 to 35 days to grow the organism.

AIDS-Related Opportunistic Infections↗

Disseminated histoplasmosis and Wegener's granulomatosis.

Disseminated histoplasmosis is an unusual complication in endemic areas and has been reported in patients with an immunodeficient state, either from human immunodeficiency virus (HIV) infection or transplantation. In the non-HIV population, rare cases of disseminated histoplasmosis have been reported in patients with leukemia and Hodgkin's disease and patients receiving steroid therapy for various diseases. We report a case of disseminated histoplasmosis in a patient with Wegener's granulomatosis.

Adult↗

Chest pain resulting from histoplasmosis pericarditis: a brief report and review of the literature.

Histoplasmosis is an endemic disease in many regions of the United States. Physicians must be aware of the clinical syndromes and take advantage of epidemiologic clues when diagnosing histoplasmosis pericarditis. Clinicians must also be familiar with the uses and limitations of a battery of serologic and mycologic tests. Finally, further clinical trials are needed to study the role of antifungal therapy in the treatment of histoplasmosis pericarditis.

Adult↗

New and classic insights into presumed ocular histoplasmosis syndrome and its treatment.

PURPOSE OF REVIEW: Presumed ocular histoplasmosis syndrome classically presents with atrophic choroidal scars, which are thought to progress into choroidal neovascularization in a small proportion of patients. The pathophysiology of the disease, including its underlying etiology, continues to be controversial and subject to ongoing research. Even more important is the controversy that surrounds the optimal treatment for choroidal neovascularization in patients with presumed ocular histoplasmosis, in particular that of subfoveal localization. RECENT DEVELOPMENTS: Intense efforts oriented toward defining the most beneficial therapeutic modality have resulted in some well-designed, large studies that evaluated submacular surgery, photodynamic therapies, and anti-angiogenic therapies, as well as small pilot studies exploring new therapeutic approaches for choroidal neovascularization. SUMMARY: Important results obtained by these studies were recently made public, and the conclusions that may be drawn from them, as well as an update on findings concerning presumed ocular histoplasmosis etiology, epidemiology, and pathophysiology are presented in this report.

Choroidal Neovascularization↗