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Histoplasmosis of the gingiva. Report of a case.

A 71-year-old white man presented with a large ulcerated lesion which extended to the facial and palatal aspects of the maxillary left first and second bicuspids. A biopsy was made because the lesion appeared to be carcinomatous. It proved to be benign but it was positive for histoplasmosis. Although the patient had a 9 month history of weight loss, fatigue, frequent nausea, night sweats, respiratory symptoms, and other symptoms compatible with a diagnosis of histoplasmosis, skin tests and complement fixation tests had been consistently negative. After the diagnosis was made and the organism was cultured from the oral lesion, therapy (amphotericin B) was initiated and the patient responded favorably. Within 12 months, the symptoms regressed, the oral lesions healed, and the patient regained 25 lb.

Aged↗

[Three cases of imported histoplasmosis in our hospital].

Since 1999 we have observed three cases of imported histoplasmosis in our hospital. One was an immunocompetent individual and two further patients were immunosuppressed (renal transplantation and HIV infection C3). Two patients were born in endemic areas (Equatorial Guinea and Ecuador) and a third patient had a history of previous travel to the Peruvian Amazonia. The different clinical presentations and diagnostic tools of histoplasmosis are discussed.

English Abstract↗

African histoplasmosis: a review.

African histoplasmosis caused by Histoplasma capsulatum var. duboisii is an important deep mycosis endemic in Central and West Africa and in the island of Madagascar. The disease is characterized by presence of granulomatous lesions in the skin, subcutaneous tissues and bones. Lungs and other internal organs are rarely involved. The natural reservoir of the etiological agent has only been recently discovered in a bat cave in Nigeria. The status of asymptomatic infection is not certain. Investigations on skin and serum reactivity have suggested frequent prevalence of asymptomatic infections due to H. capsulatum var. duboisii among the residents in the vicinity of the cave microfocus of the fungus. The exact portal of entry into the body is not known, but inhalation into the lungs and direct inoculation in the skin have been incriminated. Laboratory diagnosis is confirmed by in vitro conversion into large yeast forms (8-15 mum in diameter) and by the demonstration of these forms within giant cells of tissues of experimentally infected animals There are no major clean-cut physiological differences between the two varieties, viz. capsulatum and duboisii. The cell wall of H. capsulatum var duboisii contains a glucan with beta 1-4 linkages in addition to a galactomannan shared with H. capsulatum var. capsulatum. Like the var. capsulatum var. duboisii has marked proteinase and collagenase activities in both mycelial and yeast forms, suggesting a possible pathogenic role for these enzymes. Both varieties have a common exoantigen. The yeast form of H. capsulatum var. duboisii contains the antigen found in the serotype 1,4 of var. capsulatum. A monoclonal antibody test has been developed that can recognize some epitopes in H. capsulatum var. capsulatum but not in the var. duboisii. There is need to develop specific serological diagnosis for the disease. Also there should be greater international awareness about African histoplasmosis. Amphotericin B and several antimycotic azoles like ketoconazole, itraconazole and fluconazole have been successfully employed for treatment.

Journal Article↗

Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: one-year results of an uncontrolled, prospective case series.

OBJECTIVE: To evaluate the safety and effect on visual acuity of photodynamic therapy with verteporfin (Visudyne, Novartis AG) in patients with subfoveal choroidal neovascularization (CNV) secondary to the ocular histoplasmosis syndrome (OHS). DESIGN: Open-label, three-center, noncomparative prospective case series. PARTICIPANTS: OHS patients with subfoveal CNV lesions no larger than 5400 micro m in greatest linear dimension (GLD) with classic or occult CNV extending under the geometric center of the foveal avascular zone and best-corrected visual acuity letter score of 73 to 34 (approximate Snellen equivalent 20/40-20/200). METHODS: Twenty-six patients received verteporfin (6 mg/m(2)) infused IV over 10 minutes. Fifteen minutes after the start of infusion, a laser light at 689 nm delivered 50 J/cm(2) at an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 micro m larger than the GLD of the lesion. At 3-month follow-up examinations, retreatment with the same regimen was applied if angiography showed fluorescein leakage. Safety assessments were also made. MAIN OUTCOME MEASURES: Visual function measurements were the changes from baseline in visual acuity and contrast sensitivity scores and the proportion of patients who, based on best-corrected visual acuity scores, (1) gained 7 or more letters, (2) lost 8 or more letters, and (3) lost 15 or more letters. RESULTS: One patient was omitted from the study at the month 3 examination for not meeting the visual acuity eligibility requirements at baseline. By the month 12 examination, but excluding any retreatment at that visit, patients had received an average of 2.9 treatments of a maximum of 4 possible treatments. The month 12 median improvement from baseline in visual acuity of the remaining 25 patients was 7 letters, and median contrast sensitivity improved by 2 letters. Median visual acuity improvement was also 7 letters when three patients, who failed to meet all photographic eligibility requirements at baseline, were excluded. At the month 12 examination, 14 (56%) patients gained 7 or more letters of visual acuity from baseline, whereas 4 (16%) patients lost 8 or more letters, of which 2 (8%) lost 15 or more letters. No serious systemic or ocular adverse events were reported. CONCLUSIONS: Median visual acuity improved after verteporfin therapy for at least 1 year in a small uncontrolled prospective case series of patients with subfoveal CNV caused by OHS. Verteporfin therapy seemed to be safe and well tolerated in these patients. Two-year data from this study will provide important, additional information on the safety and effect of verteporfin therapy for the treatment of subfoveal CNV secondary to OHS.

Adult↗

OCULAR HISTOPLASMOSIS.

Case reports of three residents of Ontario with clinical histoplasmic chorioretinitis are presented. The diagnosis was made on the basis of the clinical appearance, the presence of calcified lesions in the chest, a negative skin test to tuberculin, and a positive skin test to toxoplasmin. All patients were treated with intravenous amphotericin B. Except for transitory elevation of blood urea nitrogen, there were no serious complications from the drug and in all cases the lesions in the eyes were improved. Histologic or cultural proof of the presence of fungus in the eye is not available, but clinical and laboratory findings can combine to point to the diagnosis of histoplasmosis. In such cases, since vision is at stake, treatment with amphotericin B should be considered.

Amphotericin B↗

Histoplasmosis. Association with circulating immune complexes, eosinophilia, and mesangiopathic glomerulonephritis.

A patient with disseminated histoplasmosis, eosinophilia, and transient mesangiopathic glomerulonephritis stimulated a search for the presence of circulating immune complexes. Serum samples obtained on the fifth and 11th hospital days were strongly positive for ciculating immune complexes by both the Raji cell radioassay and the C1q solid phase assay. During the course of complete clinical recovery without therapy, both assays were weakly positive for circulating immune complexes on day 33. On day 56 they were negative. Using this case as a prototype, possible mechanisms for the renal immunopathology and the eosinophilic response are discussed with reference to the immunological perturbations thay may be observed in systemic mycotic infection.

Adult↗

Histoplasmosis in pregnancy: case series and report of transplacental transmission.

Although a healthy pregnancy seems to confer an increased susceptibility to systemic fungal infections, to our knowledge, no known association exists in the case of Histoplasma capsulatum. In addition, to our knowledge, transplacental transmission of H capsulatum has not been previously described. We describe a series of patients treated at our institutions between 1997 and 2000 with evidence of transplacental transmission of H capsulatum. Mechanisms of increased risk of histoplasmosis during pregnancy are proposed, although this risk has yet to be proved.

Adult↗

Surgical removal vs observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic: I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9.

OBJECTIVE: To present visual acuity findings and related outcomes from eyes of patients enrolled in a randomized trial conducted by the Submacular Surgery Trials (SST) Research Group (SST Group H Trial) to compare surgical removal vs observation of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis. METHODS: Eligible patients 18 years or older had subfoveal choroidal neovascularization (new or recurrent) that included a classic component on fluorescein angiography and best-corrected visual acuity of 20/50 to 20/800 in 1 eye ("study eye"). Patients were examined 3, 6, 12, and 24 months after enrollment to assess study outcomes and adverse events. Best-corrected visual acuity was measured by a masked examiner at the 24-month examination. A successful outcome was defined a priori as 24-month visual acuity better or no more than 1 line (7 letters) worse than at baseline. RESULTS: Among 225 patients enrolled (median visual acuity 20/100), 113 study eyes were assigned to observation and 112 to surgery. Forty-six percent of the eyes in the observation arm and 55% in the surgery arm had a successful outcome (success ratio, 1.18; 95% confidence interval, 0.89-1.56). Median visual acuity at the 24-month examination was 20/250 among eyes in the observation arm and 20/160 for eyes in the surgery arm. The prespecified subgroup of eyes with visual acuity worse than 20/100 at baseline (n = 92) had more successes with surgery; 31 (76%) of 41 eyes in the surgery arm vs 20 (50%) of 40 eyes in the observation arm examined at 24 months (success ratio, 1.53; 95% confidence interval, 1.08-2.16). Five (4%) of 111 eyes in the surgery arm subsequently had a rhegmatogenous retinal detachment. Twenty-seven (24%) of 112 initially phakic eyes in the surgery arm (none in the observation arm) had cataract surgery during follow-up, all among patients older than 50 years. Recurrent choroidal neovascularization developed by the 24-month examination in 58% of surgically treated eyes. CONCLUSIONS: Overall, findings supported no benefit or a smaller benefit to surgery than the trial was designed to detect. Findings support consideration of surgery for eyes with subfoveal choroidal neovascularization and best-corrected visual acuity worse than 20/100 that meet other eligibility criteria for the SST Group H Trial. Other factors that may influence the treatment decision include the risks of retinal detachment, cataract among older patients, and recurrent choroidal neovascularization and the possibility that additional treatment will be required after submacular surgery.

Adult↗

Surgical removal vs observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic: II. Quality-of-life findings from a randomized clinical trial: SST Group H Trial: SST Report No. 10.

OBJECTIVE: To report findings regarding health-related quality-of-life outcomes by treatment arm, both overall and within subgroups defined by selected baseline characteristics, among patients who participated in the Submacular Surgery Trials (SST) randomized trial of observation vs surgical removal of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis (SST Group H Trial). DESIGN AND METHODS: Eligible patients were 18 years or older and had subfoveal choroidal neovascularization (including a classic component on fluorescein angiography) and visual acuity of 20/50 to 20/800 inclusive in the eye randomly assigned to surgery or observation. Trained interviewers, who were masked to treatment assignment, administered the National Eye Institute Visual Function Questionnaire (NEI-VFQ), the 36-Item Short-Form Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS) by telephone before enrollment and at 6, 12, and 24 months after enrollment; early enrollees also had interviews at 36 and 48 months. Baseline clinical examinations provided data regarding visual acuity, other aspects of vision, and presence of unilateral or bilateral choroidal neovascularization. RESULTS: Of 225 patients interviewed at baseline and enrolled, 201, 190, and 161 patients (respectively, 89%, 85%, and 88% of those eligible to be interviewed) were interviewed 12, 24, and 36 months later. The NEI-VFQ scores in both treatment arms improved from baseline (median score, 75) to the 24-month interview. Patients in the surgery arm had 4-point larger improvements, on average, than patients in the observation arm (95% confidence interval, 1-8 points). The largest differences between treatment arms for mean 24-month improvements from baseline were in the role difficulties subscale (9 points) and dependency subscale (8 points), with larger mean improvements in the surgery arm. Scores on the SF-36 worsened by approximately 1 point on the physical component summary and improved by 2 points or more on the mental component summary in both treatment arms by 24 months in comparison to baseline. The percentage of HADS-defined "definite cases" of both anxiety and depression declined from baseline in each treatment arm. CONCLUSIONS: Vision-targeted quality of life improved more after submacular surgery than with observation, supporting a possible small overall benefit of surgery suggested by the ophthalmic outcomes reported elsewhere. Ophthalmologists and patients similar to those who participated in the SST Group H Trial should be aware of the effects of submacular surgery on specific aspects of vision-targeted quality of life as well as on ophthalmic outcomes when considering this treatment approach.

Adult↗

Health- and vision-related quality of life among patients with ocular histoplasmosis or idiopathic choroidal neovascularization at enrollment in a randomized trial of submacular surgery: Submacular Surgery Trials Report No. 5.

OBJECTIVES: To (1) summarize vision-targeted and general health-related quality-of-life scores at baseline and quantify the effect of the ophthalmic problem, (2) evaluate the strength of relations between visual acuity and interview scores, and (3) compare scores for patients who also had choroidal neovascular lesions in the fellow eye (bilateral cases) with those of patients who had choroidal neovascularization in only the study eye (unilateral cases) at time of enrollment in a randomized trial of surgical removal of subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or of idiopathic origin. DESIGN: Eligible patients had subfoveal choroidal neovascularization (including some classic choroidal neovascularization) and a visual acuity of 20/50 to 20/800 (Snellen equivalent), inclusive, in the eye to be assigned randomly to surgery or observation. Interviews that incorporated the 39-item version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) and 2 other instruments were conducted by telephone by trained interviewers before patients enrolled and were assigned randomly to surgery or observation. Information from baseline clinical examinations and fluorescein angiograms interpreted centrally by masked readers was used to classify patients as unilateral or bilateral cases and to provide potential explanations for variability of interview responses using linear regression models. RESULTS: The median overall NEI-VFQ score was 75 (interquartile range, 60-84). The median scores on individual subscales ranged from 55 (general vision) to 100 (color vision). The visual acuity of the better-seeing eye accounted for much of the variability in scores on most NEI-VFQ subscales; a 3-line difference in visual acuity was associated with a 10-point or greater difference in scores on 5 subscales after adjustment for other characteristics of patients and eyes. Scores on most scales of all 3 instruments differed between unilateral cases (n = 167) and bilateral cases (n = 58). Even after adjustment for visual acuity and reading speed of the better-seeing eye, age, gender, and scores on the other instruments, scores on the NEI-VFQ near and distance activities subscales differed by almost 13 and 10 points, respectively, between unilateral and bilateral cases. Neither age nor gender was an important independent explanatory variable for NEI-VFQ scores. CONCLUSIONS: Unilateral and bilateral cases had vision-targeted health-related quality-of-life scores worse than those published for a reference population without eye disease. Furthermore, despite younger age, better visual acuity, and better short-term visual prognosis, bilateral cases had NEI-VFQ scores at baseline similar to those published for 2 groups of patients with age-related macular degeneration. Unidentified factors, in addition to the visual acuity of the better-seeing eye, affected patients' perceptions of visual function.

Adolescent↗

Presumed ocular histoplasmosis syndrome. The fellow eye.

The fundus photographs of 308 patients with presumed ocular histoplasmosis syndrome (POHS) were examined. Bilateral macular involvement was found in 20% of the cases. The incidence of maculopathy, peripapillary lesions, and peripheral "punched-out" lesions in one fundus and only peeipapillary changes in the fellow eye was 12%. The incidence of these features in one fundus and clinically inactive, atrophic scars in the posterior pole of the fellow eye was 23%. Twenty-five patients with atrophic lesions in the macular area of the fellow eye were followed for an average of 24 months. Six patients (24%) demonstrated activation of eight previously documented atrophic lesions resulting in macular involvement. One patient also demonstrated activation from a pre-existing juxtapapillary lesion. None of the remaining 18 patients exhibited any evidence of serous or hemorrhagic retinal sequelae in the fellow eye.

Adolescent↗

De novo subretinal neovascularization in the histoplasmosis syndrome.

A 22-year-old man was seen with the ocular histoplasmosis syndrome. This case demonstrates that spontaneous or "de novo" neovascularization without prior pigmentary changes can occasionally, although rarely, give rise to the disciform macular disease process and the potential for loss of central vision. The lesion initially responded favorably to treatment with heavy argon laser photocoagulation in the parafoveal area, including the papillomacular area, but subsequent areas of neovascularization proved intractable to laser therapy.

Adult↗

Presumed ocular histoplasmosis syndrome. A clinicopathologic correlation of a treated case.

A patient with bilateral presumed ocular histoplasmosis had been successfully treated in his symptomatic right eye with laser photocoagulation for subretinal neovascularization in two areas of the macula. The left eye also showed neovascularization clinically and histopathologically but was not treated because there was no detectable leakage and the vision was not affected. There was no change in the left eye over a two-year period. Clinicopathologic correlation of the treated and untreated macular lesions and the peripapillary and peripheral lesions is presented.

Eye↗

Linear streaks of the equator in the presumed ocular histoplasmosis syndrome.

A fourth sign of the presumed ocular histoplasmosis syndrome (POHS), peripheral streak lesions, is added to the common triad of disseminated punched-out atrophic spots, peripapillary atrophy, and macular disciform lesions. The streaks are of variable length, width, and pigmentation. They are almost invariably in the equatorial region and oriented parallel to the ora serrata. Streak lesions were found in 5.0% of patients with the POHS.

Adolescent↗

Multifocal choroiditis and panuveitis. A syndrome that mimics ocular histoplasmosis.

A review of 28 cases of multifocal choroiditis with vitreous inflammatory cells demonstrates that these patients have chorioretinal scars similar to those in the presumed ocular histoplasmosis syndrome (POHS), but they have a low incidence of positive histoplasmin skin test reactions and calcified granulomata on chest x-ray films. Anterior chamber inflammation is a frequent finding. The epidemiologic background of these patients is different from those with POHS. The subjects in this study were also different from patients with birdshot or vitiliginous choroiditis and acute posterior multifocal placoid pigment epitheliopathy. However, unilateral cases are difficult to distinguish from cases of diffuse unilateral subacute neuroretinitis. While it is possible that a subretinal nematode may have caused some of the unilateral cases in this review, multiple causative agents are likely, including an unidentified agent that causes cross reactions to histoplasmin skin tests.

Adolescent↗

Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Macular Photocoagulation Study Group.

Persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 144 eyes assigned to krypton red laser photocoagulation in the Ocular Histoplasmosis Study-Krypton Laser were examined to describe persistence and recurrence in these patients. Persistent neovascularization was observed among 23% of treated patients and recurrent neovascularization was observed among an additional 8%. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. Patients with high blood pressure were more than 2.5 times as likely to have persistent neovascularization as patients without high blood pressure (95% confidence interval = 1.5, 4.8). Eyes in which the neovascular component of the complex was within 200 microns of the center of the foveal avascular zone were twice as likely to have persistent neovascularization (95% confidence interval = 1.2, 4.6). Eyes in which the treatment did not cover the neovascularization completely or did not meet the required level of intensity on the foveal side had a persistence rate approximately three times that of eyes in which the neovascularization was covered completely by intense, confluent burns (95% confidence interval = 1.7, 6.5). This last finding is of particular importance for ophthalmologists who treat similar patients.

Adult↗

Five-year follow-up of fellow eyes of individuals with ocular histoplasmosis and unilateral extrafoveal or juxtafoveal choroidal neovascularization. Macular Photocoagulation Study Group.

OBJECTIVES: To document the incidence of choroidal neovascularization (CNV) in unaffected fellow eyes among individuals with ocular histoplasmosis and extrafoveal or juxtafoveal CNV in 1 eye; to determine whether the location and type of "histo spots" in the macula predict the site of future CNV development in second eyes; to describe changes over time in neovascular lesions present in fellow eyes at baseline; and to describe changes in visual acuity of fellow eyes with and without CNV at baseline. DESIGN, PATIENTS, AND SETTING: Five-year prospective follow-up study of fellow eyes of 516 patients enrolled in 2 randomized clinical trials of laser photocoagulation of extrafoveal and juxtafoveal CNV. Best-corrected visual acuity and reading vision were measured, and both maculas were photographed at baseline and at 6-month intervals. MAIN OUTCOME MEASURES: Cumulative incidence of CNV in fellow eyes free of neovascular maculopathy at the time of study enrollment, 5-year change in visual acuity of fellow eyes from baseline, and incidence of legal blindness (visual acuity < or = 20/200 in the better eye). RESULTS: Photographically documented CNV developed in 35 (9%) of 394 eyes initially free of neovascular maculopathy; nevertheless, good visual acuity was maintained in most newly affected eyes until the end of the 5-year follow-up period. Histo spots of any type in the macula at baseline tripled the risk for later development of CNV in comparison to eyes without histo spots in the macula. Although the type of histo spots present in the central macula at baseline did not predict future CNV development, in 32 of 35 second eyes in which CNV developed and in 7 of 9 fellow eyes in which a second area of CNV developed during follow-up, CNV was preceded by an "atypical" histo spot in the same location. Among 122 patients who had bilateral neovascular maculopathy initially, 100 were examined 5 years later; 8 (8%) were legally blind, compared with 3 (1%) of 339 patients examined who had unilateral CNV initially. At the 5-year examination, 355 (81%) of 439 patients examined had a visual acuity of 20/20 or better in at least 1 eye, including 74 (55%) of 134 patients who had bilateral neovascular maculopathy. CONCLUSIONS: Although the incidence of CNV in fellow eyes that initially were unaffected remained low throughout 5 years of follow-up, it persisted at a nearly constant rate. The risk of legal blindness was low, even for patients who had bilateral involvement. Perhaps most important, 81% of all patients followed up for 5 years retained a visual acuity of 20/20 in at least 1 eye, and 20% retained this visual acuity in both eyes. Retrospective review of photographs suggests that the ophthalmologist should pay special attention to areas of the central macula in which new "atypical" histo spots are observed, with the goal of treating CNV that may develop in the same area at a time when the benefits of laser treatment may be greatest.

Adult↗

Mediastinal and cervical histoplasmosis simulating malignancy.

A 12-year-old boy had a purulent mass in the anterior cervical region in association with an anterior mediastinal mass caused by Histoplasma capsulatum. The cervical mass probably represented spread of the disease, perhaps along the same pathways followed in Hodgkin's disease and other conditions that are known to involve the anterior mediastinum and the anterior cervical nodes simultaneously. An infectious disease (histoplasmosis) can cause a constellation of symptoms suggestive of a lymphoma or other malignancy.

Child↗