Severe Epstein-Barr virus-associated hemophagocytic syndrome in six adult patients.

BACKGROUND: EBV associated hemophagocytic syndrome (HPS) is an aggressive and potentially life-threatening condition. So far, most EBV associated HPS has been characterized mainly in infants and children in Asian countries. RESULTS: Here, we report six cases of EBV associated HPS occurring in previously healthy adults in a non-endemic area within a short period of 3 years. All patients presented with fever, hepatosplenomegaly and pancytopenia as well as disturbed liver function tests and coagulopathy. Half were diagnosed as having lymphoma. While EBV-specific serological assays were non-diagnostic in four of the six patients, the presence of EBV DNA in plasma allowed the diagnosis of EBV associated HPS in all patients. CONCLUSION: EBV associated HPS may be more prevalent in non-Japanese adults than was previously considered. Screening for hemophagocytic syndrome, in adults as well as in children, should include real-time PCR for EBV.     

Epstein-Barr virus-associated post-transplant primary smooth muscle tumor of the liver: Report of an autopsy case

Epstein-Barr (EB) virus-associated primary smooth muscle tumors have been reported in immunosuppressed young patients with acquired immunodeficiency syndrome (AIDS) and young people who have undergone liver transplantation. An autopsy case of EB virus-associated smooth muscle cell tumor in a 21 year old female who received immunosuppres-sive therapy following renal transplantation Is repotted. Multiple tumor nodules were present in the liver, but no primary lesion was found in any other organ. Histologically, the nodules were composed of spindle cells, positive for α-smooth muscle action, which were arranged in fascicles and closely associated with vascular channels, thereby suggesting a vascular smooth muscle cell origin. EB virus infection of the tumor cells was clearly demonstrated by in situ hybridization with an EB virus-encoded RNA 1 (EBER-1) probe. The present case illustrates that EB virus infection may play some role in the development of smooth muscle tumors not only in immunocompromised young patients with liver allo-grafts, but also in those with renal allografts.     

Epstein-Barr virus-associated smooth muscle tumors in ataxia-telangiectasia: a case report and review

Chromosomal breakage syndromes, including ataxia-telangiectasia (AT), are autosomal recessive disorders in which DNA repair mechanisms are defective resulting in chromosomal instability. Affected individuals are at high risk for developing malignancy because of the widespread resulting cellular effects. One such effect, severe immunosuppression, can permit virally mediated neoplasms to manifest, similar to those seen in acquired immunodeficiency syndrome (AIDS), congenital immune deficiency syndromes, and posttransplant populations. Epstein-Barr virus (EBV) is a common viral agent known to be associated with lymphoid, epithelial, and smooth muscle malignancies in such patients. Although smooth muscle tumors have been reported in patients with AT, their association with EBV has not been evaluated. We present a case of EBV-associated laryngeal leiomyosarcoma and jejunal cellular leiomyoma in a child with AT. This case suggests that the development of neoplasia in patients with chromosomal breakage syndromes may be related to the immunosuppressive consequences of these diseases, and searching for infectious causes (such as EBV) is important.     

Autopsy findings in patients with acquired immunodeficiency syndrome

We have evaluated the autopsies of 11 patients with HTLV III/LAV-infection. The clinical diagnosis was AIDS in 10 cases and AIDS related complex (ARC) in one case. The most common infectious disease was pneumocystis carinii pneumonia, occurring in 5 cases. 3 patients showed evidence of mycobacterial infections and another three showed cytomegalovirus infections. Kaposi's sarcoma was found in 4 and other malignancies in 3 cases. Our results are in agreement with the findings of other authors.     

Skin aging in patients with acquired immunodeficiency syndrome

To evaluate the histomorphometric skin changes over aging patients with autopsied acquired immunodeficiency syndrome (AIDS). In 29 skin fragments of autopsied elderly (older than 50 years) and nonelderly patients with AIDS, epidermal thickness, the number of layers, the diameter of cells, the percentage of collagen and elastic fibers in the dermis, and the number and morphology of Langerhans cells were assessed. Statistical analysis was performed by SigmaStat 2.03 program. The thickness of the epidermis (92.55 × 158.94 μm), the number of layers (7 × 9 layers), and the diameter of the cells (13.27 × 17.6 μm) were statistically lower among the elderly. The quantity of collagen fibers (9.68 × 14.11%) and elastic fibers (11.89 × 15.31%) was also significantly lower in the elderly. There was a decrease in total (10.61 × 12.38 cel/mm²) and an increase in immature Langerhans cells (6.31 × 4.98 cel/mm²) in elderly patients with AIDS. The aging of the skin of patients with AIDS is amended in different histomorphometric aspects, the epidermis constituents suffer less pronounced changes in normal aging, and the dermis has more intense changes in elastic fibers and collagen.     

Epstein-Barr virus-associated smooth muscle tumour: a distinctive mesenchymal tumour of immunocompromised individuals

immunosuppressed patients are predisposed to the development of smooth muscle tumours which show near consistent association with Epstein-Barr virus (EBV). This report describes a 37-year-old patient with acquired immunodeficiency syndrome who initially presented with two masses in the liver. Image-guided core biopsy revealed a spindle cell tumour with histological and immunological features of smooth muscle neoplasm which was shown by in situ hybridisation for EBV early RNAs to be EBV-associated. The literature on this uncommon entity is critically reviewed and the differential diagnosis is also discussed.     

Laboratory diagnosis of pulmonary toxoplasmosis in patients with acquired immunodeficiency syndrome.

In four cases of pulmonary toxoplasmosis occurring in patients with acquired immunodeficiency syndrome, Toxoplasma sp. was discovered in bronchoalveolar-lavage fluid (three cases) and in lung biopsy specimen (one case) by using the following methods: direct examination of smears stained with eosine-methylene blue fast stain, indirect immunofluorescence assay, and inoculation of MRC5 fibroblast cell line in tissue culture.     

Laboratory diagnosis of mycobacterial infections in patients with acquired immunodeficiency syndrome.

Disseminated mycobacterial infections are commonly seen in acquired immunodeficiency syndrome (AIDS) patients, and laboratory culture is the best method for diagnosing these infections. In addition to conventional agar media, we used BACTEC 12A (Johnston Laboratories, Inc., Towson, Md.) broth medium for culture. More isolates of Mycobacterium avium complex and Mycobacterium tuberculosis were recovered from 12A broth than from Lowenstein-Jensen or Middlebrook 7H11 agar. Also, the average detection time of these mycobacteria was the earliest with 12A broth. Stool examination has been helpful in diagnosing mycobacterial disease in AIDS patients, and in this study both acid-fast stain and culture of fecal material was necessary for efficient detection of mycobacteria. Another sensitive and practical method for detecting mycobacterial infections in patients with AIDS is the Isolator lysis-centrifugation system (Du Pont Co., Wilmington, Del.) which offers the advantage of quantitating the degree of mycobacteremia. Laboratories should be alerted to the possibility of mixed mycobacterial infection in patients with AIDS, and positive cultures should be repeatedly examined to detect coinfection with a slower-growing mycobacterium such as M. tuberculosis as well as M. avium complex.     

Defective regulation of Epstein-Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders

Patients with the acquired immunodeficiency syndrome (AIDS) acquire undifferentiated B-cell lymphomas that are similar to African Burkitt's lymphoma and contain Epstein-Barr virus (EBV). Using an in vitro assay system that measures a complex of cellular responses to EBV-infected lymphocytes, we found that B cells from 7 patients with AIDS and from 10 patients with AIDS-related disorders produced abnormally low numbers of immunoglobulin-secreting cells (P less than 0.001 as compared with normal controls) and that T-cell suppression, which was greater than 80 percent in EBV-seropositive normal controls, was absent. Instead, the patients' T cells markedly increased immunoglobulin production induced by EBV. In further studies, we determined that the mean frequency of circulating EBV-infected B cells capable of spontaneous outgrowth in vitro was 13 per 10(6) B cells in 7 patients with AIDS and 21 per 10(6) B cells in 10 patients with AIDS-related disorders--figures that were significantly higher than the mean in normal controls (P less than 0.001). Thus, patients with AIDS or AIDS-related disorders may be predisposed to the development of EBV-containing lymphomas, because they have a profound defect of T-cell immunity to EBV and abnormally high numbers of EBV-infected B cells in the circulation.     

Alga associated with diarrhea in patients with acquired immunodeficiency syndrome and in travelers.

Spherical bodies resembling coccidian oocysts and measuring 8.0 to 9.0 microns in diameter were seen in the stools of eight persons with explosive, watery diarrhea. Seven had recently traveled to tropical countries, mostly in the Caribbean, and four had acquired immunodeficiency syndrome. The structures were easily discernible in wet mounts by light microscopy and contained variable numbers of granular inclusions, but were refractory to, or stained partially with, 12 commonly used laboratory stains. Electron microscopy revealed an outer fibrillar coat, a thin cell wall, granules, and organelles which were not surrounded by membranes. One type of organelle was similar to the thylakoid photosynthesizing organelles of blue-green algae (cyanobacteria). These findings indicate that the bodies may be a species of blue-green algae.     

Impairment of polymorphonuclear leucocyte function in patients with acquired immunodeficiency syndrome and with lymphadenopathy syndrome.

Granulocyte functions were studied in 20 patients with acquired immunodeficiency syndrome (AIDS), 20 subjects with lymphadenopathy syndrome (LAS) and 15 symptom-free drug addicts (SFDA). Polymorphonuclear leucocyte (PMNL) phagocytosis and killing of C. albicans appeared normal in homosexual men with AIDS, while drug addicts with AIDS or LAS and SFDA showed a significant defect of these functions as compared to healthy controls. Migration of PMNL in response to a chemoattractant was normal in SFDA, but markedly defective both in LAS and in AIDS patients. In the AIDS group no significant differences were evident between homosexual men and drug addicts. We conclude that defective PMNL phagocytosis and killing, unlike defective migration, are somehow related to drug abuse rather than to infection with the causative agent of the immunodeficiency.     

Management of drug allergy in patients with acquired immunodeficiency syndrome

Management of patients with acquired immunodeficiency syndrome (AIDS) is complicated by a high frequency of adverse drug reactions to trimethoprim-sulfamethoxazole and pentamidine. Because of the lack of suitable alternative antiparasitic drugs, some patients who have experienced previous allergic-type reactions to antimicrobial agents may require readministration with incriminated drugs. We report the outcome of seven drug-allergic patients with AIDS evaluated from 1982 to 85. Readministration of pentamidine was carried out without repeated reactions in three patients, and sulfadiazine and sulfamethoxazole-trimethoprim were readministered after very cautious test dosing in two other patients. A generalized maculopapular rash developed after 10 days of sulfadiazine therapy for Toxoplasma chorioretinitis but has been managed with prednisone, 20 to 30 mg/day for 3 months, and sulfadiazine has been continued. The administration of prednisone, 100 to 200 mg daily for treatment of severe cutaneous vasculitis from azulfidine in another patient, did not result in suprainfection. The complexities and potential legal risk of readministration of drugs in the drug-allergic patient with AIDS are emphasized in that coincidental deaths occurred in two patients 48 and 96 hours after readministration of pentamidine.     

Diffuse hyperpigmentation associated with acquired immunodeficiency syndrome.

This article reports a case of diffuse hyperpigmentation in a 56-year-old Latino male after he was diagnosed with acquired immunodeficiency syndrome (AIDS). The possible causes of this hyperpigmentation are discussed.     

Histoplasmosis in patients with acquired immunodeficiency syndrome. Hematologic and bone marrow manifestations

In areas where Histoplasma capsulatum infections are endemic in the United States, there is an increasing frequency of progressive disseminated histoplasmosis (PDH) as an opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). The bone marrow and peripheral blood (PB) specimens in 13 patients with AIDS and PDH were reviewed. Anemia, leukopenia, and thrombocytopenia were found in 12, 10, and 7 patients, respectively. Circulating organisms were detected in the blood smears or buffy coat preparations from five patients and were associated with PB nRBCs and severe absolute monocytopenia. Morphologically, the marrow specimens showed one of four patterns: (1) no morphologic evidence of infection (two patients, one with a positive marrow culture); (2) discrete granulomas (two patients, both with positive marrow cultures); (3) lymphohistiocytic aggregates (six patients, four with positive marrow cultures); and (4) diffuse macrophage infiltrates (three patients, all with positive marrow cultures). Morphologic examination of the bone marrow combined with cultures is useful in diagnosing disseminated histoplasmosis in patients with AIDS. However, the morphologic findings in the bone marrow may be different in patients with AIDS compared with non-AIDS patients, and seemingly nondiagnostic morphologic features must be approached with a high degree of suspicion in diagnosing infections with H. capsulatum in this population.     

Pancreatic pathology in pentamidine-induced diabetes in acquired immunodeficiency syndrome patients.

An acquired immunodeficiency syndrome patient who was treated with pentamidine for a pneumocystis infection developed hypoglycemia followed by diabetes mellitus. The pathologic findings in the pancreas consisted of a significant decrease in the number of insulin-positive cells as measured by immunoperoxidase techniques when compared with comparable tissue from an age- and sex-matched control. There was also a decrease in the staining intensity of the insulin-positive cells, an absolute increase in the glucagon-positive cells, and no significant change in the number of somatostatin-positive cells. Routinely stained histologic sections showed morphologic changes in the islets with features different from those described in insulin-dependent diabetes mellitus or those caused by the toxin Vacor. The islets had increased vascular spaces, no islet cell necrosis, no fibrosis, and no lymphocytic infiltrates when compared with an age-matched control.     

Infection-associated vascular lesions in acquired immunodeficiency syndrome patients

Several reports have recently appeared in the literature describing "unique" non-neoplastic vascular lesions in patients with the acquired immunodeficiency syndrome (AIDS). These lesions may be mistaken clinically and histologically for Kaposi's sarcoma. The terms epithelioid angiomatosis, epithelioid or histiocytoid hemangioma, and pyogenic granuloma have all been used to describe a similar entity in which cat scratch disease bacillus (CSDB) was subsequently identified. Lesions closely resembling this entity occur in patients with bartonellosis. We report a case of a cutaneous vascular lesion on the hand of an AIDS patient in which cytomegalovirus (CMV) and organisms consistent with CSDB were both found. Simultaneous infections with CMV and CSDB have not been previously described. The presence of these organisms in and around endothelial cells may provide the common stimulus for the formation of these reactive vascular proliferations.