Pneumocystis jirovecii-induced chronic interstitial lung disease in Waldenström's macroglobulinemia.

Infections with Pneumocystis jirovecii can result in asymptomatic colonization or induce life threatening clinical symptoms. However, there appears to be a 'gray area' between colonization and severe pneumonia that remains underestimated so far. We describe a case with chronic interstitial lung disease and chronic cough that was attributed to P. jirovecii. The patient's history of chronic cough, although very likely being fostered by the underlying Waldenström's macroglobulinemia and interstitial lung disease, was most likely caused by P. jirovecii infection. This gives raise to the hypothesis that P. jirovecii infections do not necessarily induce life threatening pneumonia. Consequently, serial testing is required in eligible patients with positive PCR results in order to discriminate between colonization, 'gray zone' infection, and beginning pneumonia.

Community-acquired infections associated with increased risk of lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia.

Emerging evidence supports the role of immune stimulation in the development of lymphoplasmacytic lymphoma/Waldenström Macroglobulinaemia (LPL/WM). Using the population-based Surveillance, Epidemiology End Results-Medicare database we investigated the exposure to 14 common community-acquired infections and subsequent risk of LPL/WM in 693 LPL/WM cases and 200 000 controls. Respiratory tract infections, bronchitis [odds ratio (OR) 1·56], pharyngitis (OR 1·43), pneumonia (OR 1·42) and sinusitis (OR 1·33) and skin infection, herpes zoster (OR 1·51) were all significantly associated with subsequent increased risk of LPL/WM. For each of these infections, the findings remained significantly elevated following the exclusion of more than 6 years of Medicare claims data prior to LPL/WM diagnosis. Our findings may support a role for infections in the development of LPL/WM or could reflect an underlying immune disturbance that is present several years prior to diagnosis and thereby part of the natural history of disease progression.

Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers.

Natural antibodies (NAbs) are present in circulation even before the exposure to antigen and they exert various biological functions. They are polyreactive and mainly represented by immunoglobulin M (IgM), which is the first antibody produced in an ongoing immune response to infection and/or immunization. IgM is always secreted as a polymer with predominant pentameric structure, although other polymeric forms such as hexamer can be also formed. The biological functions of hexameric IgM are still not known and it is proposed that its existence as a NAb could be deleterious. However, the nature of IgM hexamers has not been investigated yet. In this paper, we have tested the expression of natural idiotope and antigenic specificities of pentameric and hexameric IgM polymers originating from sera of patients with Waldenström's macroglobulinemia, as well as patients suffering from recurrent urinary bacterial infections. We demonstrate that although pentameric IgM polymers can exist as natural and immune antibodies, IgM hexamers are exclusively immune and do not exist as NAbs.

Candida tropicalis and Penicillium marneffei mixed fungaemia in a patient with Waldenström's macroglobulinaemia.

A patient with Waldenstrom's macroglobulinaemia who had previously been treated with cladribine presented with septic arthritis caused by Escherichia coli. The patient's condition subsequently deteriorated, and he succumbed to pneumonia and mixed fungaemia due to Candida tropicalis and Penicillium marneffei. Profound lymphopenia coexisted with fungaemia. This is the first reported case of mixed Penicillium marneffei and Candida fungaemia and penicilliosis marneffei in a patient with Waldenstrom's macroglobulinaemia. Penicilliosis marneffei should be considered as a potential complication in patients with markedly impaired cell-mediated immunity who have travelled to or resided in endemic areas. Patients who have undergone therapy with purine nucleoside analogues such as fludarabine and cladribine are also at risk.

[Pseudolymphoma and ventricular maltoma in patients with chronic gastritis, ulcer and Helicobacter pylori infection]. / Pseudolymfom og ventrikelmaltom hos patienter med kronisk gastritis, ulcus og Helicobacter pylori-infektion.

Among 128 patients with malignant B-lymphoproliferative disorders, 19 patients had long lasting dyspepsia and gastroscopy showed chronic active gastritis or gastric ulcer. PCR analysis for TCR and IgH clonality in biopsies showed local involvement of the malignant lymphocyte clone in four patients out of eight indicating presence of these cells in the inflammatory infiltrate. Weak B-cell clonality was found in four patients. A close relationship was seen between lymphocytic clonality and immune response to H. pylori Cag A, and all patients had parietal cell antibodies. Thus, the malignant clone may participate in the local inflammatory reaction, and continued local stimulation by H. pylori as well as parietal cell antigens may lead both to autoimmunity as well as a clonal development of lymphocytes.

Potentially pathogenic microorganisms in the oral cavity during febrile episodes in immunocompromised patients with haematologic malignancies.

The purpose of the study was to describe the occurrence of potentially pathogenic microorganisms during febrile episodes in haematologic patients, who had been treated with anti-neoplastic drugs within the previous 4 weeks. During a 9-month period 78 consecutive febrile episodes occurred in 46 patients who were examined daily. On day 1, before antibiotic treatment was started, members of the normal flora were found in 83%, Candida spp. in 72%, Enterobacteriaceae in 29%, Pseudomonas aeruginosa in 8%, Staphylococcus aureus in 14%, coagulase-negative staphylococci in 26% and enterococci in 17% of the febrile episodes. During the subsequent antibiotic treatment, the prevalence of members of the normal oral flora was markedly reduced from day 1 (83%) to day 7 (6%), and the normal flora was replaced by potentially pathogenic microorganisms. A rise was found in the prevalences of Candida spp. (from 72 to 92%) and coagulase-negative staphylococci (from 26 to 49%) from day 1 to day 4. The prevalences of Enterobacteriaceae and P. aeruginosa showed no day-to-day changes, and were not different in patients hospitalized for more or less than 24 h prior to inclusion into the study, suggesting that their detection was not due to acquisition during hospitalization or antibiotic treatment. The oral occurrence of species of microorganisms regularly found in septicaemia, suggests that the oral cavity may play a role as a port of entry of septicaemia in patients with haematologic malignancies.

Staphylococcus aureus bacteremia in patients with hematological malignancies and/or agranulocytosis.

A total of 6,253 cases of Staphylococcus aureus bacteremia, including 274 (4.4%) endocarditis cases, were registered in Denmark in the period 1975-1984. Patients with hematological malignancies and/or agranulocytosis accounted for 479 of the bacteremia cases. The incidence of endocarditis in this group of patients was only 0.4% as compared to 4.7% in other patients with staphylococcal bacteremia (p less than 0.01). The lower incidence of endocarditis complicating bacteremia in these patients may justify a shorter course of therapy than usually recommended for suspected endocarditis. Patients with hematological malignancies and other patients with agranulocytosis had a higher mortality (49 and 46%, respectively) than other patients with S. aureus bacteremia (33%). The highest mortality was found in patients with multiple myeloma (71%, p less than 0.01), the lowest in patients with acute lymphocytic leukemia (28%, p less than 0.01). The higher mortality in these patients may indicate that empiric antibiotic regimens in granulocytopenic patients should include a specific anti-staphylococcal agent.