An unusual presentation of Legionella pneumonia in a returning traveller.

A male patient in his mid-60s presented with a severe pneumonia following return to the UK after travel to Crete. He was diagnosed with Legionnaire's disease (caused by an uncommon serogroup of Legionella pneumophila). He was pancytopenic on admission, and during a long stay on critical care he was diagnosed with a disseminated Aspergillus infection. Bone marrow aspiration revealed an underlying hairy cell leukaemia that undoubtedly contributed to his acute presentation and subsequent invasive fungal infection.

Disseminated sporotrichosis in a patient with hairy cell leukemia treated with amphotericin B and posaconazole.

We describe a case of disseminated Sporothrix schenckii infection in a man with underlying hairy cell leukemia. The immunological defects associated with this malignancy, as well as the management of refractory sporotrichosis are reviewed.

Incidence, risk of infection and survival of hairy cell leukaemia in Denmark.

INTRODUCTION: Few population-based studies exist on incidence, risk of infection and mortality in hairy cell leukaemia (HCL). MATERIAL AND METHODS: We used population-based medical databases to identify 209 patients who were diagnosed with HCL in the period from January 1997 to August 2007 in Denmark. An age- and sex-matched comparison cohort of 2,090 persons was selected from the general population. We computed the incidence of HCL using demographic data. Hospitalizations with pneumonia and bacteraemia were determined from the Danish National Patient Registry. Cox regression analysis was used to estimate the relative risk (RR) of infection and mortality ratios (MRR) adjusting for age, sex and comorbidity. RESULTS: The HCL incidence rates were 1.97 (95% confidence interval 1.51-2.53) and 5.37 (4.57-6.28) per million person-years for women and men, respectively. During a median follow-up of 4.5 years, 48 HCL patients were hospitalized with pneumonia or bacteraemia. The adjusted RR of infection was 8.04 (4.99-12.95) the first year after diagnosis and 1.17 (0.71-1.94) for the remaining follow-up period. The adjusted MRRs were 4.26 (2.61-6.96) and 1.12 (0.75-1.65) the first year after diagnosis and the remaining follow-up period, respectively. CONCLUSION: In the second and subsequent years after HCL diagnosis, the risk of infection and mortality was similar to that of the general population.

[Atypical mycobacteria. Disseminated infection in patients with hematologic diseases]. / Atypiske mykobakterier. Dissemineret infektion hos hoematologiske patienter.

During the last decade interest in atypical mycobacteria (AM), especially Mycobacterium avium complex (MAC) has been intense, as a large number of AIDS patients develop disseminated infection with MAC. Disseminated infection has also been reported in other immunocompromised patients, but in much fewer cases. Among haematological diseases hairy cell leukemia (HCL) and chronic myelogenous leukemia (CML) seem to predispose to disseminated AM infection. We review 53 cases of disseminated AM infection in haematological patients reported in the literature, 39 with HCL, ten CML, and four other haematological diseases, and a review of possible treatment is given. The prognosis seems to depend on the course of the underlying haematological disease, and we conclude that early diagnosis and treatment of the infection is of great importance. Blood and bone marrow should therefore be cultivated for mycobacteria in such patients with persistent fever of unknown cause, and in cases with negative cultures and elevated serum values of alkaline phosphatase liver biopsy should be considered.

[Disseminated Mycobacterium avium infection in three patients with hematologic diseases]. / Dissemineret Mycobacterium avium-infektion hos tre haematologiske patienter.

We report three cases of disseminated Mycobacterium avium complex infection in immunocompromised haematological patients. We conclude that in haematological patients with longlasting fever of unknown cause Mycobacterium avium complex infection should be considered and the relevant cultures from blood and bone marrow should be done.

Detection of Campylobacter upsaliensis from a blood culture by using the BacT/Alert system.

Campylobacter upsaliensis was isolated from the blood of a 60-year-old female with hairy cell leukemia. This spiral-shaped organism was detected in the aerobic BacT/Alert bottle (Organon Teknika, Durham, N.C.) by acridine orange staining and was recovered only on chocolate agar in a microaerophilic atmosphere at 35 degrees C.

Hairy cell transformation of human peripheral blood lymphocytes by Coxiella burnetii.

Hairy cell (HC) transformation of human peripheral blood lymphocytes (PBL) by Coxiella burnetii was studied to clarify the significance of persistency of C. burnetii in a hairy cell line (designated "TOL"). TOL cells which exhibited HC characteristics in hairy cell leukemia (HCL) were persistently infected with C. burnetii. Two strains of C. burnetii, our isolate from TOL cells and the original isolate in 1935, the Nine Mile strain from American Type Culture Collection (ATCC, U.S.A), were inoculated to PBL cultures. HC transformation not only by our isolates (87%) but also by Nine Mile strain (100%) was demonstrated in an average of 20 days. The original observation that Coxiella induced HC transformation in vitro was also confirmed in experiments with PBL exposed to C. burnetii in vivo. Spontaneous development of HC were observed in cultures of PBL only from coxiellemic cases (12/24) but not from C. burnetii negative cases (0/57). All HC cell lines (34) as determined by their morphology and cytochemical markers of HC in HCL remained infected with C. burnetii invariably.

Lack of evidence of Epstein-Barr virus in hairy cell leukemia and monocytoid B-cell lymphoma.

An association between the Epstein-Barr virus (EBV) and hairy cell leukemia (HCL) has been reported. Due to the similarities between HCL and monocytoid B-cell lymphoma (MBCL), an association between EBV and MBCL has been postulated. To address these issues we studied 27 spleens from cases with HCL and 13 tissue specimens from cases with MBCL from various sites for evidence of EBV DNA and RNA by in situ hybridization. Using a genomic EBV internal repeat probe and an oligonucleotide probe directed against the EBER1 gene, we were unable to identify EBV DNA or RNA, respectively, in the tumor cells of any of the cases. The results of our study suggest that EBV may not be strongly linked with either HCL or MBCL.

Hairy cell transformation of human peripheral blood lymphocytes by Coxiella burnetii

Hairy cell (HC) transformation of human peripheral blood lymphocytes (PBL) by Coxiella burnetii was studied to clarify the significance of persistency of C. burnetii in a hairy cell line (designated "TOL"). TOL cells which exhibited HC characteristics in hairy cell leukemia (HCL) were persistently infected with C. burnetii. Two strains of C. burnetii, our isolate from TOL cells and the original isolate in 1935, the Nine Mile strain from American Type Culture Collection (ATCC, U.S.A), were inoculated to PBL cultures. HC transformation not only by our isolates (87%) but also by Nine Mile strain (100%) was demonstrated in an average of 20 days. The original observation that Coxiella induced HC transformation in vitro was also confirmed in experiments with PBL exposed to C. burnetii in vivo. Spontaneous development of HC were observed in cultures of PBL only from coxiellemic cases (12/24) but not from C. burnetii negative cases (0/57). All HC cell lines (34) as determined by their morphology and cytochemical markers of HC in HCL remained infected with C. burnetii invariably.

[Hairy cell leukemia and Mycobacterium malmoense infection]. / Hårcelleleukemi og infeksjon med Mycobacterium malmoense.

We describe a patient with hairy cell leukemia and protracted fever. The patient's condition deteriorated during treatment with alfa Interferon 2b, and his fever persisted. A slight widening of the upper mediastinum appeared after 2.5 months. Mediastinoscopy with lymph node biopsy revealed granulomatous infiltrates with acid-fast bacilli. Cultures of the lymph node material later showed growth of Mycobacterium malmoense. The patient was treated with rifampicin, doxycycline, etambutol and cycloserin for sixteen months and remains afebrile and is gaining weight. His general condition is still improving. An aggressive diagnostic approach is necessary in febrile patients with hairy cell leukemia.

The detection of Epstein-Barr virus in hairy cell leukemia cells by in situ hybridization.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several B-cell lymphoid proliferations. Because patients with hairy cell leukemia (HCL) have a high incidence of seropositivity for EBV antigens, we studied the cells of HCL for evidence of EBV infection using in situ hybridization techniques. EBV mRNA was detected in the tumor cells in four of six cases using a radiolabeled RNA probe. Confirmatory serologic data were available in three cases in which the viral DNA was detected and in one negative case. Our results suggest that EBV infection may have a pathogenetic role in this disorder.

Human retroviruses: a common virology.

There are five known human retroviruses: human T-lymphotropic virus-I (HTLV-I), HTLV-II, HTLV-V, human immunodeficiency virus-1 (HIV-1), and HIV-2. These are related to animal lentiviruses. The simian retroviruses, simian T-lymphotropic virus-I (STLV-I) and STLV-III are related closely to HTLV-I and HIV-2 respectively. HTLV-I and HTLV-II and, possibly, HTLV-V are transforming agents that immortalize the CD4 cell. In contrast, HIV-1 and HIV-2 cause this cell to lyse, resulting in immunodeficiency (ID). HIV-1 and HIV-2 cause severe ID resulting in acquired immunodeficiency syndrome (AIDS). In HTLV-I and HTLV-II, ID is less severe and rarely progressive. Both of these retroviruses induce proliferation of CD4 cells. In HTLV-I, this results in acute T cell leukemia and mycosis fungoides (MF) with hypercalcemia. HTLV-V produces a less severe form of MF without hypercalcemia. Associated lymphomas (AL) occur with HTLV-I. HIV-1 and HIV-2 produce AL as well as Kaposi's sarcoma. Both also cause subcortical dementia because they are neurotropic. All human retroviruses appear to be transmitted sexually and by blood. Transfusional AIDS may be almost entirely eliminated by serologic testing of the blood supply, and transfusional lymphoma can be almost entirely eliminated by universal testing for HTLV-I.

Mycobacterium avium-intracellulare infection associated with hairy-cell leukemia.

A 66-year-old man with hairy-cell leukemia was treated successfully with interferon alfa, with normalization of his hematologic parameters. After 2.5 months he became ill again and, following extensive investigation, Mycobacterium avium-intracellulare grew from a bone marrow specimen. Although initiation of quadruple antituberculous chemotherapy resulted in an improvement of his general condition, after two months he started to develop widespread cutaneous and subcutaneous nodules, biopsy of which showed appearances compatible with mycobacterial infection. Over the next two months the skin lesions progressed slowly so erythromycin, to which in vitro testing showed the organism to be sensitive, was added to his therapy. This resulted in a marked improvement of all skin lesions. This case is the first to be reported of disseminated atypical mycobacterial infection in a patient receiving interferon treatment for hairy-cell leukemia.

HTLV-II and human lymphoproliferative disorders.

HTLV-II is a rarely encountered human retrovirus that has been linked to atypical presentations of hairy-cell leukemia, as well as a variety of T-cell malignancies. Recently, HTLV-II prevalence has increased in the United States, particularly in populations of intravenous drug abusers. Comparative study of HTLV-I and HTLV-II has allowed for important insights into the mechanisms of retroviral replication and T-cell transformation.

Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders.

We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II.

Transformation of hairy cell leukemia to EBV genome-containing aggressive B cell lymphoma.

Hairy cell leukemia is a preplasmacytic B cell leukemia which is not EBV associated, although elevated titers of Epstein-Barr virus (EBV) antibodies have been seen in this leukemia and chronic lymphocytic leukemia. Hairy cells are not readily susceptible to EBV infection in vitro, even though they are EBV receptor-positive B cells. We have observed a 59-year-old patient who after 9 years of hairy cell leukemia developed a well-differentiated IgG-kappa monoclonal B cell lymphoma without further evidence of hairy cell leukemia. Pathologically, the lymphoma showed plasmacytic differentiation, and in the patient's serum, a 2 g/dl monoclonal IgG-kappa component was present. DNA extracted from the lymphomatous lymph node hybridized with DNA fragments of a reiterated sequence of EBV, IR1. The transformation, with no chemotherapy involved, from a preplasmacytic leukemia into a lymphoplasmacytic lymphoma with monoclonal gammopathy may be related to the entry of EBV into these cells. Studies at the molecular level may help understand mechanisms of malignant transformation or interconversion in lymphoproliferative disorders of the B cell type.