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Disseminated histoplasmosis in systemic lupus erythematosus: case report and review of the literature.

OBJECTIVES: To report a patient who developed both central nervous system systemic lupus erythematosus (SLE) and disseminated histoplasmosis and to review the literature regarding histoplasma infection in patients with SLE. METHODS: MEDLINE review of the medical literature published in English. RESULTS: Disseminated histoplasmosis occurs rarely in patients with SLE. The main risk factor is treatment with corticosteroids at doses of 20 mg/d or greater. Fever, dyspnea, pleurisy, and weight loss are typical presenting symptoms. The most commonly involved tissues are lung, liver, and bone marrow. In our patient, both SLE flare and disseminated histoplasmosis were present simultaneously. CONCLUSIONS: Opportunistic infection is an important complication of SLE and may be difficult to diagnose. Symptoms of infection may mimic those of a lupus flare, or conversely, symptoms may be masked by the use of corticosteroids. Fever, unexplained tissue involvement, atypical clinical patterns, and poor response to immunosuppressive therapy should alert the clinician to aggressively pursue evaluation of possible infection in patients with SLE.

Female↗

[Disseminated histoplasmosis: an atypical ulcerous form in an HIV-infected patient].

INTRODUCTION: Histoplasma capsulatum var capsulatum is a dimorphic fungi predominating on the American continent. It is responsible for disseminated histoplasmosis associated with AIDS. The presentation in the form of cutaneous ulceration is uncommon and misleading. OBSERVATION: A 25 year-old man presented with 3 ulcerations, of 2 to 4 cm in diameter, localized on the lower lip and knees. The patient exhibited fever, alteration in his general status of health and a pulmonary interstitial syndrome. He was seropositive for the human immunodeficiency syndrome (HIV). His lymphocyte CD4+ level was of 1/mm3. Diagnosis of histoplasmosis was established by direct examination and culture of the cutaneous ulcerations and bronchoalveolar washing fluid. DISCUSSION: The clinical aspect of cutaneous localizations of disseminated histoplasmosis is usually multiple, disseminated, papular or nodular-type lesions. Ulcerations represent less than 20% of the cases described. In our patient, the aspect of the lesions at first evoked cutaneous leishmaniosis. Direct mycological examination followed by culture confirmed the final diagnosis.

Adult↗

Disseminated histoplasmosis presenting as urinary tract obstruction in a renal transplant recipient.

Disseminated histoplasmosis occasionally involves the kidney, but the infection usually does not cause either urinary symptoms or a decrease in renal function. We present a case of disseminated histoplasmosis in a renal transplant recipient who presented with urinary obstruction in the allograft from a sloughed renal papilla infected with the fungus. At the same time the patient had chronic meningitis from Histoplasma capsulatum. The literature on renal involvement with histoplasmosis is reviewed.

Constriction, Pathologic↗

Diagnosis of histoplasmosis by detection of the internal transcribed spacer region of fungal rRNA gene from a paraffin-embedded skin sample from a dog in Japan.

The lesions of histoplasmosis in dogs in Japan differ from those in dogs in North America. Affected dogs in Japan have had multiple granulomatous or ulcerated foci in skin or gingiva and have not had pulmonary or gastrointestinal lesions. The present report introduces a polymerase chain reaction (PCR) diagnosis of canine histoplasmosis and the characteristic of disease in Japan. The surgically removed skin ulcerate samples from a 5-years-old female Shiba-inu native to Japan without traveling out of the country were evaluated. Tissue samples had many yeast-like organisms in the macrophages. DNA was extracted from paraffin-embedded tissue samples. A nested PCR technique was applied. The detected sequence of the internal transcribed spacer of ribosomal RNA gene had 99.7% in homology with Ajellomyces capsulatus (the teleomorph of Histoplasma capsulatum). Clinical manifestations, historical background of equine epizootic lymphangitis in Japan, and a human autochthonous case of histoplasmosis farciminosi indicated that this dog might have been infected with H. capsulatum var. farciminosum as a heteroecism.

Animals↗

Histoplasmosis.

The diagnosis of histoplasmosis depends on recognition of the different clinical manifestations of infection, accompanied by knowledge of the accuracy and limitations of tests used for diagnosis of fungal infections. Although most infections are asymptomatic, histoplasmosis can be severe, or even fatal, in patients who have experienced a heavy exposure, have underlying immune defects, or develop progressive disease that is not recognized and treated. This article provides an up-to-date clinical review of histoplasmosis, focusing on recognition, diagnosis, and management.

AIDS-Related Opportunistic Infections↗

Oral histoplasmosis in HIV-infected patients. A report of two cases.

Histoplasmosis is a fungal infection caused by the organism Histoplasma capsulatum. Disseminated disease usually occurs in immunosuppressed patients or in patients with chronic illnesses. Although relatively uncommon, histoplasmosis has been reported in patients with AIDS, and oral lesions have been noted on multiple sites and in various clinical presentations. We present two HIV-positive cases with oral lesions as the initial signs of histoplasmosis. Both patients responded well to IV amphotericin B but later suffered recurrences despite being maintained on systemic antifungal therapy.

AIDS-Related Opportunistic Infections↗

Review of oral histoplasmosis in Malaysians.

We reviewed biopsy records for 37 cases of oral histoplasmosis for patient characteristics, clinical features, and histopathologic findings. These represented cases diagnosed in the Division of Stomatology, Institute for Medical Research, Kuala Lumpur between July 1967 and October 1994. All were male patients who ranged in age from 11 to 79 years (mean age, 56.7 years). There were 40.6% Malays, 37.8% Chinese, 18.9% Indians, and 2.7% other races. Five patients with mouth lesions as the initial presenting lesions were proven to be cases of disseminated histoplasmosis. In the remaining cases apart from the biopsy-proven oral histoplasmosis lesions, the extent of the disease elsewhere was unknown. The majority of these lesions involved the gingiva, tongue, and palate in decreasing order of frequency. The most frequent presenting symptom was oral mucosal ulceration. Squamous cell carcinoma and tuberculosis were the two most common clinical differential diagnoses. Our present findings compare favorably with published reports from other regions.

Adolescent↗

Oral histoplasmosis as an indicator of HIV infection.

Histoplasmosis as a serious opportunistic infection in association with AIDS has assumed considerable importance. We have gathered 20 case reports from the literature of oral histoplasmosis in HIV-infected patients. In some cases, oral lesions appear to be the primary or only manifestation of disease. We report one such case of oral histoplasmosis in a bisexual man who was seen with ulcerations on the palate and proved to be infected by HIV.

AIDS-Related Opportunistic Infections↗

Histoplasmosis in a Brazilian center: clinical forms and laboratory tests.

Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic in many regions of the Americas, Asia and Africa. It has a wide spectrum of clinical manifestations, from asymptomatic infection to severe disseminated disease. A retrospective study was carried out to describe the clinical forms and assess the clinical significance of the laboratory diagnostic tests of patients with histoplasmosis during the period of July 1987 to December 2003 at Instituto de Pesquisa Clínica Evandro Chagas/ FIOCRUZ, RJ, Brazil. Seventy-four patients were included. Forty-nine percent of the cases (n = 36) occurred in HIV positive patients who presented with disseminated disease. The remaining 38 cases were classified in different clinical forms. Histoplasma capsulatum was isolated from 69.5% of the clinical specimens sent to culture. Immunodiffusion and immunoblot were positive in 72.6% and 100% of the performed tests, respectively. Histopathologic findings suggestive of H. capsulatum were found in 63.2% of the performed exams. Serology had a lower proportion of positivity amongst AIDS patients, when compared with HIV negative patients (X2 = 6.65; p lower than 0.008). Statistical differences between AIDS and non-AIDS patients were not observed with culture and histopathology. The specific role of each test varies according to the clinical form. Physicians need to know the value and limitations of the available diagnostic tests, but before that, they have to think about histoplasmosis and consider this clinical entity in their differential diagnosis.

AIDS-Related Opportunistic Infections↗

Efficacy of interferon-gamma and amphotericin B for the treatment of systemic murine histoplasmosis.

The number of cases of systemic histoplasmosis has increased substantially in recent years, and improved therapy is needed. We examined the efficacy of immunomodulation with interferon (IFN)-gamma alone or in combination with a suboptimal regimen of amphotericin B for the treatment of primary systemic murine histoplasmosis. In the first study, BALB/c mice were infected with Histoplasma capsulatum G217B and treated with 10(5) U of IFN given every other day either preinfection and postinfection or only postinfection, alone or in combination with amphotericin B. IFN alone given subcutaneously (s.c.) postinfection prolonged survival over untreated controls (P < 0.01), whereas intravenous (i.v.) administration was ineffective. All combination regimens and amphotericin B alone significantly prolonged survival (P < 0.0001). The combination regimens of amphotericin B and IFN i.v. (pre- and postinfection) or IFN s.c. (postinfection) reduced the fungal burden in the liver and spleen; the latter regimen had superior efficacy in the spleen (P < 0.05) to either amphotericin B or IFN alone. After infection with a low-challenge inoculum, IFN given s.c. (pre- and postinfection) alone caused a significant reduction in fungal burden in the spleen (P < 0.001). In an acutely lethal model, combination regimens of IFN s.c. or i.v. and amphotericin B again prolonged survival (P < 0.01-0.001), with amphotericin B plus IFN given s.c. (pre- and postinfection) superior to all regimens (P < 0.05-0.01). This regimen also showed enhanced efficacy in causing the reduction of fungal burden in the spleen (P < 0.05). These results indicate that IFN in combination with AmB shows enhanced efficacy in the treatment of systemic histoplasmosis and support the potential utility of IFN as an adjunctive therapy.

Administration, Cutaneous↗

Chronic pulmonary histoplasmosis in the State of Rio de Janeiro, Brazil.

Three cases of chronic pulmonary histoplasmosis affecting aged patients with chronic obstructive pulmonary disease are reported. They had a history of recurrent episodes of respiratory infection and presented radiological lung lesions inducing a misdiagnosis of chronic pulmonary tuberculosis of the adults. The diagnosis of histoplasmosis, suggested by the immunodiffusion test and the detection of yeastlike cells in smeared and stained sputum, was confirmed by the isolation and identification of Histoplasma capsulatum var. capsulatum in selective media. The treatment was carried out with amphothericin B and ketoconazole or itraconazole. Clinical, radiologic, mycologic and serologic improvement was obtained in all the patients. However, relapses occurred within a period of 1 to 18 months after the interruption of the treatment. Mycological diagnosis and the difficulties observed in the treatment were discussed. In addition data on the epidemiology of histoplasmosis in the state of Rio de Janeiro, Brazil, were presented.

Aged↗

Disseminated histoplasmosis with atypical cutaneous lesions in an Italian HIV-infected patient: another autochtonous case.

Disseminated histoplasmosis is recognized as a common AIDS-defining opportunistic disease in endemic areas (Americas, Africa, East Asia), while it is rarely described in Europe, usually in individuals returning from endemic regions, or following endogenous reactivation of a latent infection imported long before from overseas countries. However, reports of autochtonous cases in Europe suggest the possible, endemic presence of Histoplasma capsulatum in some European regions, such as the South of France or the Po valley in Italy. A case of disseminated histoplasmosis with atypical, papular and ulcerate skin lesions in an Italian HIV-infected patient, without history of travels outside his native region, is described. Our patient represents the fifth autochtonous case of AIDS-associated histoplasmosis described in Italy.

AIDS-Related Opportunistic Infections↗

Histoplasmosis in dogs and cats.

Histoplasma capsulatum is endemic throughout most of the United States with a high prevalence of infections in the Midwest and South. Histoplasmosis is the second most common systemic fungal disease in cats that may be more susceptible than dogs. Infection occurs by inhalation of conidia from the mycelial phase, which subsequently convert to the yeast form. Histoplasma capsulatum is phagocytized and harbored by cells of the mononuclear phagocyte system. Infection may be subclinical or cause clinical pulmonary granulomatous disease or dissemination. Disseminated disease predominantly affects the liver, spleen, gastrointestinal tract, bone and bone marrow, integument, and eyes. Primary gastrointestinal histoplasmosis also occurs. Clinical signs of histoplasmosis often are nonspecific, including chronic wasting, fever, anorexia, respiratory signs, and lameness. Gastrointestinal signs (eg, diarrhea with hematochezia or melena) are common in dogs. The definitive diagnosis is made by identification of the yeast in tissue samples. Itraconazole is the treatment of choice.

Animals↗

The epidemiology of histoplasmosis: a review.

Histoplasmosis is the most common endemic mycosis in the United States and has recently emerged as an important opportunistic infection among human immunodeficiency virus (HIV)-infected persons living in areas where it is endemic. In this article, we describe the epidemiologic and ecologic features of histoplasmosis, highlighting the implications for prevention. Surveillance and education of the public and health care providers are needed to determine the disease burden of histoplasmosis. Development of better diagnostic tests for detection of disease in humans and of the organism in the environment will help in designing better prevention strategies.

AIDS-Related Opportunistic Infections↗

[The so-called "ocular histoplasmosis syndrome"].

The authors describe seven patients presenting with ophthalmoscopic findings typical of "presumed ocular histoplasmosis syndrome." However, no humoral antibodies could be demonstrated. Moreover, the results of skin tests were all negative even after "boostering." Hence, the diagnosis of ocular histoplasmosis had to be ruled out. Tests for listeriosis, lues, leptospirosis, ornithosis, Toxocara canis, toxoplasmosis, Larva migrans, and Candida albicans were also negative. There are evidently other, so far unknown, agents which lead to an ophthalmoscopic picture that mimics ocular histoplasmosis with its typical "punched-out lesions" and central hemorrhagic chorioretinopathy. One of these agents may be Epstein-Barr virus, because two of six patients had increased antibody levels of Epstein-Barr nuclear antigen and early antigen, indicating an active or persistent state of viral infection.

Adult↗

Disseminated histoplasmosis with embolic endovascular complications: a case report.

A 57-year-old man had subacute embolic ischemia of his right foot and subsequent acute embolic ischemia of his left foot after angiography. Thrombus removed at the time of the left femoral thromboembolectomy grew Histoplasma capsulatum confirming the diagnosis of disseminated histoplasmosis. Surgical revascularization of the right leg and parenteral amphotericin B was followed by chronic ketoconazole therapy for 16 months. The patient has remained asymptomatic at 30 months after operation. Effective treatment of endovascular infection with ischemic complications of Histoplasmosis requires surgical revascularization and intensive chemotherapeutic intervention. Histoplasmosis is a ubiquitous infection in endemic areas that often has an asymptomatic subclinical course. Involvement of the cardiovascular system is rarely reported. Previous case reports have described infected cardiac valves and aortic aneurysms. This report describes the uncommon presentation of disseminated Histoplasma capsulatum infection as a peripheral embolic event and the successful management with revascularization combined with systemic amphotericin B followed by ketoconazole therapy.

Histoplasmosis↗

Imported and autochthonous histoplasmosis in Bergamo province, Northern Italy.

This paper reviews the Italian literature and illustrates the results of a survey on Histoplasma capsulatum var. capsulatum infection carried out in the Bergamo area of Italy over the last 10 y. During the period January 1989-July 1999, 7 patients were diagnosed as being affected by the H. capsulatum var. capsulatum infection. Until 1999 41 cases have been described in the Italian literature (9 before the 1980s, 6 in the 1980s and 26 in the 1990s). The epidemiological profile of histoplasmosis is well-defined: risk factors are activities such as visiting caves or building sites, travelling and immigration, and it affects both immunocompetent and patients with AIDS. However, in the past, the Italian soil was considered as a low-endemic pabulum for H. capsulatum var. capsulatum and only a few autochthonous cases of histoplasmosis have been reported in Italy, specifically in the Po valley. In the present series, the identification of new cases in the Po valley in Lombardy suggests the possible autochthonous presence of histoplasmosis in Italy.

Adult↗

Isolated central nervous system histoplasmosis in immunocompetent hosts: a series of 11 cases.

Histoplasmosis of the central nervous system occurs in a significant percentage of patients with Histoplasma capsulatum infection, but has usually been described in association with immunosuppression and/or disseminated histoplasmosis. We aim to review the clinical and laboratory features of isolated histoplasmosis of the central nervous system in the immunocompetent host by presenting a series of 11 cases with this condition. Most of these patients presented with headache, meningeal irritation signs and mental status changes, comprising a somewhat different picture from that described in immunosuppressed patients. Moreover, almost all patients had signs of ventricular dilatation in neuroimaging studies, and 8 of the 11 patients had a ventriculoperitoneal shunt at the time of diagnosis, suggesting hydrocephalus to be an important feature of this condition and/or the possibility of shunt infection by the fungus. Immunodiffusion analysis of the cerebrospinal fluid appeared to be the most efficient way to reach the diagnosis and should be considered in immunocompetent patients with chronic lymphocytic meningitis, especially in those who have ventricular shunt or live in endemic areas of Histoplasma capsulatum.

Adolescent↗