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The role of T-lymphocytes in the reactivation of presumed ocular histoplasmosis scars.

The surprising finding of viable lymphocytes in clinically inactive scars gives more credence to the immunological theory regarding reactivation of histoplasmosis scars. We feel that the T-lymphocyte theory can explain the mechanism by which an inactive scar becomes active upon reintroduction of the antigen. The clinical course of the disease as well as the response to corticosteroid therapy and photocoagulation are also consistent with this hypothesis.

Adrenal Cortex Hormones↗

Comparison of xenon arc and argon laser photocoagulation in ocular histoplasmosis.

Argon laser and xenon arc photocoagulation can be utilized to obliterate choroidal neovascularization in selected cases of macular histoplasmosis. Central vision can be preserved in many instances if criteria for patient selection, treatment techniques, and method of follow-up, as described in this chapter, are adhered to rigidly. Of 40 patients treated with argon laser photocoagulation, 75 percent maintained or improved central vision an average of one year following treatment. Nonetheless, there is a definite need for a prospective controlled study to document the efficacy of this mode of treatment on a long-term basis.

Adult↗

Gastrointestinal histoplasmosis.

Histoplasma capsulatum involves some part of the gastrointestinal tract in 75% of patients with disseminated disease, but clinically obvious gastrointestinal involvement is infrequent. Symptoms include crampy abdominal pain, diarrhea, nasopharyngeal ulcers, and rectal ulcers. Granulomatous constrictive lesions may simulate either carcinoma anywhere in the gut or less commonly Crohn's disease. We describe a patient and discuss gastrointestinal histoplasmosis.

Colonic Diseases↗

Chronic pulmonary histoplasmosis.

Chronic pulmonary histoplasmosis is best regarded as an opportunist or saprophytic infection of abnormal pulmonary spaces by a fungus of very low human pathogenicity. Tissue disease results from host immune response to dispersions of soluble antigen from these focal sources. There are two distinct types of clinical and radiological response. One is an acute or subacute illness manifested by often large segmental pneumonic lesions which tend to heal and are designated as early lesions. The other, usually developing as a complication of the first, is a chronic disease marked by persistent cavitation, low gard chronic illness, and a tendency to promote pulmonary fibrosis and often progressive pulmonary insufficiency. The early lesion is a segmental interstitial pneumonitis with central areas of infarct-like necrosis often adjacent to bullous disease and often outlining prominent emphysematous spaces which appear as radiolucencies. These radiological findings are further characterized by early clearing of the interstitial components, infarct-like contraction of the necrotic zones, obliteration of much of the contained emphysematous and bullous spaces, and healing attended by considerable loss of lung volume. Symptoms are variable but tend to be mild. Malaise, fatigability, low-grade fever, aching chest pain and mild cough lasting a few days to a few weeks are usual. Symptoms are ameliorated by rest. Rest and diminished activity are recommended as treatment. Under these circumstances, 80% of early lesions heal completely and probably most of these would heal spontaneously. Any subsequent course of the disease depends on whether or nor large air spaces, adjacent to or contained within the area of pneumonitis, become infected and persist as cavities. This occurs in 20% of early lesions. Once established, an infected cavity tends to persist and to be attended by symptoms of chronic bronchitis with chronic cough and sputum, fatigability, anorexia, and weight loss. Persisting thickwalled cavities often induce gradual development of pulmonary fibrosis, particulary in the lung bases, apparently from aspiration of antigenic material. This and the accelerated obstructive bronchopulmonary disease often lead to progressive pulmonary insufficiency. The use of amphotericin B is recommended for all persistent thick-walled cavities and in some circumstances surgical resection may be indicated.

Adolescent↗

Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks.

Clinical and laboratory features have been reviewed in 66 episodes of disseminated histoplasmosis that occurred during two large urban outbreaks in Indianapolis. Immunosuppression, age greater than 54 years, and presence of other serious underlying illnesses predisposed to the disseminated form of the disease; only 21% of patients lacked one of these risk factors. Central nervous system findings, splenomegaly, hepatomegaly, and lymphopenia suggested disseminated disease but were present in only about one-third of patients. Miliary or diffuse pulmonary infiltrates also suggested dissemination and were noted in about one-third of patients, while mediastinal lymphadenopathy was present in only 17%. Histoplasmal serologic tests, positive in 90% of patients, provided useful diagnostic clues. The diagnosis could be confirmed by culture in 88% of patients, and special stains were positive in about two-thirds. Although 10% of patients recovered without treatment, 11 patients (17%) died because of failure to suspect the diagnosis and initiate therapy promptly. Amphotericin B was effective in all patients receiving at least 500 mg, but relapse occurred if the total dose was less than 30 mg/kg. Ketoconazole appeared effective in non-immunosuppressed patients but not in those with underlying immunosuppression; however, a controlled trial comparing ketoconazole and amphotericin B is required to establish the role of this new fungistatic oral agent.

Adolescent↗

Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature.

Histoplasmosis is a serious opportunistic infection in patients with AIDS, often representing the first manifestation of the syndrome. Most infections occurring within the endemic region are caused by exogenous exposure, while those occurring in nonendemic areas may represent endogenous reactivation of latent foci of infection or exogenous exposure to microfoci located within those nonendemic regions. However, prospective investigations are needed to prove the mode of acquisition. The infection usually begins in the lungs even though the chest roentgenogram may be normal. Clinical findings are nonspecific; most patients present with symptoms of fever and weight loss of at least 1 month's duration. When untreated, many cases eventually develop severe clinical manifestations resembling septicemia. Chest roentgenograms, when abnormal, show interstitial or reticulonodular infiltrates. Many cases have been initially misdiagnosed as disseminated mycobacterial infection or Pneumocystis carinii pneumonia. Patients are often concurrently infected with other opportunistic pathogens, supporting the need for a careful search for co-infections. Useful diagnostic tests include serologic tests for anti-H. capsulatum antibodies and HPA, silver stains of tissue sections or body fluids, and cultures using fungal media from blood, bone marrow, bronchoalveolar lavage fluid, and other tissues or body fluids suspected to be infected on clinical grounds. Treatment with amphotericin B is highly effective, reversing the clinical manifestations of infection in at least 80% of cases. However, nearly all patients relapse within 1 year after completing courses of amphotericin B of 35 mg/kg or more, supporting the use of maintenance treatment to prevent recurrence. Relapse rates are lower (9 to 19%) in patients receiving maintenance therapy with amphotericin B given at doses of about 50 mg weekly or biweekly than with ketoconazole (50-60%), but controlled trials comparing different maintenance regimens have not been conducted. Until results of such trials become available, our current approach is to administer an induction phase of 15 mg/kg of amphotericin B given over 4 to 6 weeks, followed by maintenance therapy with 50 to 100 mg of amphotericin B given once or twice weekly, or biweekly. If results of a prospective National Institutes of Allergy and Infectious Disease study of itraconazole maintenance therapy document its effectiveness, alternatives to amphotericin B may be reasonable.

Acquired Immunodeficiency Syndrome↗

Polyarthritis and humeral epiphysial separation in an infant with acute disseminated histoplasmosis.

The case of an immunocompetent infant with disseminated histoplasmosis is described. The case is unusual in its clinical presentation in that it is dominated, apart from respiratory infection, by the presence of polyarthritis and complicated by epiphysial separation of both humeri. There was only little involvement of reticuloendothelial tissues. Treatment consisted of surgical correction and itraconazole.

Antifungal Agents↗

Ocular photodynamic therapy with verteporfin for choroidal neovascularization secondary to ocular histoplasmosis syndrome.

PURPOSE: To evaluate the use of ocular photodynamic therapy (OPT) with verteporfin in patients with choroidal neovascularization (CNV) from ocular histoplasmosis syndrome (OHS) and to compare these results with those for a natural history group. METHODS: A retrospective chart review was performed to identify cases of CNV secondary to OHS treated with OPT. Complete data were available for 38 of 41 eligible eyes. Data regarding the following variables were abstracted from the patient charts: demographic characteristics, previous surgery, angiographic features, number and timing of treatments with OPT, follow-up time, and visual acuity. The visual acuity results of eyes receiving photodynamic therapy were compared with those for a natural history cohort. RESULTS: On average, OHS patients who received treatment developed 0.88 line of visual improvement. Visual acuity improved or stayed the same in 69% (22 of 32) of eyes, improved by > or = 2 lines in 44% (14 of 32), and improved by > or = 4 lines in 22% (7 of 32). Patients who received OPT were 2.07 times more likely to have improved or constant vision than were those in the natural history group as described in one retrospective series (odds ratio = 2.07; 95% confidence interval, 0.78-5.56; P = 0.162). Thirty-eight percent (12 of 32) of eyes had undergone submacular surgery for CNV before any OPT. CONCLUSIONS: Ocular photodynamic therapy with verteporfin may be beneficial in patients with CNV secondary to OHS, even in the setting of previous submacular surgery.

Adolescent↗

Photodynamic therapy of subfoveal and juxtafoveal choroidal neovascularization in ocular histoplasmosis syndrome: a retrospective case series.

PURPOSE: To evaluate the safety and effect on visual acuity of photodynamic therapy (PDT) with verteporfin in patients with subfoveal and juxtafoveal choroidal neovascular membranes from ocular histoplasmosis syndrome (OHS). METHODS: Retrospective case series. The visual outcome of 11 patients with subfoveal (n = 6) and juxtafoveal (n = 5) choroidal neovascularization treated with PDT was reviewed. At 1 to 3 months of follow-up, retreatment with PDT was performed if angiography showed leakage. RESULTS: Within the subfoveal group, 3 patients (50%) had improved vision (two or more lines better than initial vision), 2 patients (33.3%) had no change in vision (within 1 line), and 1 (16.7%) lost four lines of vision. At last follow-up, 3 patients (50%) had vision between 20/20 and 20/40 compared with only 1 patient (16.6%) at the initial visit. Mean follow-up was 13.7 months. Within the juxtafoveal group, 3 patients (60%) had improved vision, 1 patient (20%) had no change in vision, and 1 patient (20%) lost nine lines of vision. At last follow-up, 3 of 5 patients (60%) had vision between 20/20 and 20/40 compared with 2 patients (40%) at the initial visit. Mean follow-up was 10.2 months. No significant adverse effects were reported. CONCLUSION: PDT is a safe and promising option for patients with OHS with choroidal neovascularization that is subfoveal or juxtafoveal.

Adolescent↗

Photodynamic therapy for juxtafoveal choroidal neovascularization due to ocular histoplasmosis syndrome.

PURPOSE: To report the use of photodynamic therapy with verteporfin in patients with juxtafoveal choroidal neovascularization (CNV) for ocular histoplasmosis syndrome (OHS). METHODS: Retrospective review. Data regarding the following variables were extracted from patient charts: demographic characteristics, previous surgeries, angiographic features, number and time of treatments, follow-up time, and change in visual acuity. RESULTS: This study sample consisted of 23 eyes of 23 consecutive patients who were treated with photodynamic therapy for the management of juxtafoveal CNV. When post-treatment visual acuity (mean logMAR acuity=0.321) was compared to baseline acuity (mean logMAR visual acuity=3.89) vision improved by more than three Snellen lines in 30% of eyes, remained the same (+/-2 Snellen lines) in 52% of eyes, and worsened (greater than a two-line loss in visual acuity) in 18% of eyes. Although this series was uncontrolled, the patients had a trend toward a therapeutic benefit when compared to published natural history of similar cases (OR=0.292, P value=0.071 when compared to data from the Macular Photocoagulation Study for treatment of juxtafoveal lesions). CONCLUSION: Photodynamic therapy with verteporfin may be beneficial in patients with juxtafoveal CNV secondary to OHS in terms of both visual stabilization and improvement.

Adult↗

Pulmonary function studies in acute pulmonary histoplasmosis.

We performed follow-up pulmonary function studies on three patients with acute pulmonary histoplasmosis over a period of several months, and found that the disease is benign and usually responds well to treatment or is self-limiting. There are four major changes in lung function, namely a restrictive defect, an impairment of diffusing capacity, stiff lung, and obstruction in small airways. These changes usually lead to disturbance of ventilation-perfusion ratios and impaired gas transport across alveolar capillary membranes, resulting in arterial hypoxemia. There is also hypocapnia from alveolar hyperventilation commonly found in restrictive and stiff lung syndrome.

Adult↗

Perianal ulcer in disseminated histoplasmosis.

A 65-year-old man with stage I testicular seminoma, treated with surgery and radiation, had fever of unknown origin, adrenal insufficiency, and an isolated perianal ulcer. Tissue diagnosis of disseminated histoplasmosis was established by biopsy of the perianal ulcer, an unusual cutaneous manifestation of the disease. Treatment with amphotericin B resulted in rapid clinical improvement and complete healing of the perianal ulcer.

Aged↗

Cellular immune response in HIV-infected patients with histoplasmosis.

The relationship of immunity to Histoplasma capsulatum and CD4 count in HIV-1-infected patients is unknown. Samples of blood from people with HIV infection and from HIV-negative volunteers were assessed for immune responsiveness to the histoplasmin antigen using proliferation and interferon-gamma production as indicators of immunity. Results of histoplasmin skin tests, lymphoproliferative responses (LPR), and interferon-gamma production were positive in 9 of 20 (45%) HIV-negative controls, and in vitro measurements agreed highly with skin test reactivity. Among HIV-1-infected patients with recent histoplasmosis, skin test results were positive in none, LPR results were positive in 14%, and interferon-gamma production in 18%. Among HIV-1-infected patients with CD4 counts between 200 and 500 cells/mm(3), LPR was positive in 8% and interferon-gamma production in 33%, and among those with CD4 counts >500 cells/mm(3), LPR was positive in 31% and interferon-gamma production in 46%. In conclusion, immune responsiveness to H. capsulatum was depressed in HIV-1-infected persons with CD4 counts between 200 and 500 cells/mm(3), but approached normal in those with CD4 counts >500 cells/mm(3).

CD4 Lymphocyte Count↗

Histoplasmosis in two human immunodeficiency virus-positive immigrants to Italy: clinical features and management in the highly active antiretroviral therapy era.

We report two cases of histoplasmosis occurring in human immunodeficiency virus-positive patients who immigrated to Italy, and focus our attention on the clinical features and therapeutic aspects, with particular emphasis on secondary prophylaxis. The patients had comparable human immunodeficiency virus baseline parameters, but had a completely different compliance over therapeutic regimens. The two patients were followed in two different city hospitals of our region, Padua and Verona, and the diagnosis was made on the basis of instrumental, histologic, and microbiologic findings. One of them was treated with corticosteroids because of nephrotic syndrome.

AIDS-Related Opportunistic Infections↗

ELISA for early diagnosis of histoplasmosis.

An ELISA was developed and evaluated as a method for detecting antibodies against glycosylated and deglycosylated histoplasmin (HMIN). Sera from patients with histoplasmosis, paracoccidioidomycosis, sporotrichosis, coccidioidomycosis, aspergillosis, cryptococcosis and healthy donors were tested by ELISA against purified, deglycosylated histoplasmin (ptHMIN) and compared with purified, native (i.e. glycosylated) histoplasmin (pHMIN). Although cross-reactivity was not abolished when ptHMIN was used in the test, it was reduced (pHMIN ELISA 93 % versus ptHMIN ELISA 96 %). However, there were statistically significant differences between the sensitivities of these two methods for the detection of antibodies (pHMIN ELISA 57 % versus ptHMIN ELISA 92 %; P < 0.001) and between the efficiency of the methods (pHMIN ELISA 83 % versus ptHMIN ELISA 95 %; P < 0.001). These parameters compare better than previously published data relating to the use of treated HMIN in diagnostic ELISAs. Some of the reactivities of serum samples were compared by immunoblotting using deglycosylated HMIN and by immunodiffusion using the crude antigen. The results demonstrated that cross-reactions with heterologous sera in both ELISAs could also be observed in immunoblotting and arose from shared protein epitopes. These data suggest that ELISA using deglycosylated HMIN is a very sensitive diagnostic method and, by using commercially available antigen, it can be easily standardized and performed faster than previous Western blot-based tests using the same antigen. It provides a useful adjunct to existing methods of diagnosis that could be applied even in situations where laboratory facilities were relatively limited.

Antibodies, Fungal↗

Primary cutaneous histoplasmosis in papuloerythroderma (Ofuji).

We report the first Japanese patient with primary cutaneous histoplasmosis who was infected inside Japan. He was not an immunocompromised host but his cutaneous lesions developed on preexisting papuloerythroderma (Ofuji). The long-term topical corticosteroid treatment for papuloerythroderma, which could have suppressed the local immunological defence system of the skin, might have been responsible for the histoplasma infection in the present case.

Aged↗

A case of primary cutaneous histoplasmosis in a patient with diabetes and multi-infarct dementia.

We report a case of primary cutaneous histoplasmosis in a fifty-year-old African-American woman with diabetes and multi-infarct dementia. The patient developed fever and crusted, nodulo-ulcerative lesions of the skin after accidental superficial trauma to the forehead. The biopsy revealed suppurative granulomatous inflammation with intracellular and extracellular yeast-like cells with associated clear halo measuring 3-4 mm in size. Systemic involvement was not found. The lesions cleared after treatment with itraconazole 200 mg twice a day for 3 weeks. The medication was continued for a total period of 3 months, with no signs of recurrence after one-year of follow-up.

Biopsy, Needle↗