Nontuberculous mycobacterial infection in the differential diagnosis of chronic cough.

Patients presenting with chronic coughs are seen frequently by allergists/immunologists. When the usual diagnostic and therapeutic maneuvers do not control symptoms, it is worthwhile to consider whether a non-tuberculous mycobacterial (NTM) infection might be playing a role in the pathogenesis of the coughing. Sputum culture should be considered along with a pulmonary computerized axial tomography scan. NTM infection should be added to the differential diagnosis list for patients with chronic coughs unresponsive to conventional therapy.

Monoclonal gammopathy of undetermined significance and Russell body formation in Helicobacter pylori gastritis.

BACKGROUND: Infection by Helicobacter pylori has been linked to monoclonal gammopathy of undetermined significance (MGUS). MGUS is thought to develop due to chronic antigenic stimulation in people with a specific genetic predisposition. METHODS AND RESULTS: We describe a patient presenting with dyspepsia associated with H. pylori-related erosive gastritis. Histopathologic findings revealed infiltration with plasma cells containing accumulated condensed intercisternal immunoglobulins, the so-called 'Russell bodies'. In addition, MGUS was present with total immunoglobulins within the normal range but a significantly decreased serum concentration of IgG subtype 3. Molecular analyses demonstrated IgH formation, T-cell receptor gamma rearrangement, and alterations within the IgHG3 gene sequence. Following H. pylori eradication, gastritis and dyspepsia gradually resolved but MGUS persisted for at least 22 months. CONCLUSIONS: This is the first report to demonstrate that upon infection with H. pylori, an impaired secretory capacity of plasma cells due to specific molecular changes can present as Russell body gastritis. The molecular findings question a pathogenetic link between Russell bodies and H. pylori, but suggest genetic alterations in the immunoglobulin locus as the possible cause for both MGUS and Russell body gastritis.

Transient monoclonal gammopathy in a patient with Bartonella quintana endocarditis.

Monoclonal gammopathy has been reported rarely in association with infectious diseases. Viral infection has been the most frequently reported. We report a case of Bartonella quintana endocarditis in a 45-year-old homeless male associated with a monoclonal IgG kappa gammopathy. The gammopathy disappeared after 8 months of antibiotics while the Bartonella antibody titre was decreasing. This correlation suggests a causative role for B. quintana for the monoclonal gammopathy. To the best of our knowledge, this the first report of monoclonal gammopathy in the course of B. quintana infection.

High prevalence of Helicobacter pylori infection and monoclonal gammopathy of undetermined significance in patients with chronic idiopathic neutropenia.

The prevalence of Helicobacter pylori infection was evaluated in 120 patients with chronic idiopathic neutropenia (CIN), 8 patients with monoclonal gammopathy of undetermined significance (MGUS) associated with CIN, and 74 age- and sex-matched normal volunteers, all derived from the same geographical area. The purpose of the study was to investigate the possible causal relationships of H. pylori infection with the development of MGUS in CIN patients. We found that the prevalence of H. pylori infection was elevated to 69.2% in the group of CIN patients, 100% in the group of patients with CIN-associated MGUS, and 32.4% in the group of control subjects. No statistically significant difference, however, was found in the prevalence of H. pylori infection between CIN patients with concomitant MGUS and CIN patients without MGUS, no resolution of the gammopathy after eradication of the bacterium, no significant rise in the titers of serum anti-H. pylori antibodies, and no formation of an abnormal precipitation line in immunoelectrophoresis using a saline extract of NCTC11367 H. pylori reference strain as antigen. We concluded that there is no evidence that H. pylori infection is the cause of MGUS in CIN patients.

Helicobacter pylori infection and monoclonal gammopathy of undetermined significance.

A recent report found resolution of monoclonal gammopathy of undetermined significance (MGUS) in nearly 30% of patients upon eradication of concomitant Helicobacter pylori (H. pylori) infection. We performed serologicalal testing for H. pylori on 93 MGUS patients and 98 control subjects. Seroprevalence of H. pylori was not significantly different between the two groups, 30% and 32% respectively. A retrospective review of Mayo Clinic records revealed identical diagnosis rates of H. pylori infection (33%) by serology, breath or stool testing between patients with MGUS and those with negative monoclonal protein studies. There was no evidence of resolution of MGUS with H. pylori therapy.

Fatal B-cell lymphoproliferative syndrome in allogeneic marrow graft recipients. A clinical, immunobiological and pathological study.

We have studied four cases of fatal B-cell lymphoproliferative syndrome (LPS) developing among 333 patients (incidence 1.2%) treated with allogeneic bone marrow transplantation (BMT). All four patients had received a T-cell depleted graft. Onset of the first clinical symptoms (palpable lymph node enlargement in three and IgA-lambda paraproteinemia in two patients) occurred between 41 and 188 days post-BMT (median 76 days). The course of the LPS was rapidly progressive in all cases, leading to death in 2-5 weeks. The peripheral blood showed progressive pancytopenia with disproportionally high numbers of activated NK cells, apparently compensating for the T-cell deficiency. Post-mortem histological studies disclosed polymorphic B-cell proliferations, most pronounced in the lymph nodes, spleen, liver, lungs and kidneys. Lymphohemopoietic cells were of donor origin in three patients. In the fourth patient, graft failure suggested a host origin for the proliferating cells. Immunophenotyping and gene rearrangement analysis revealed polyclonal proliferation in one patient, monoclonal proliferation in another patient, and an oligoclonal pattern in the other two patients. The clinical behavior of the LPS was independent of clonality. Immunohistologically, the proliferating cells showed characteristics of relatively mature B-cells in three cases, and pre-B-cell features in one case. Epstein Barr virus (EBV) serology indicated seroconversion (primary infection) in one child, and chronic active EBV infection in both adults. EBV DNA as well as EBV nuclear antigen (EBNA) were detected in infiltrated tissues of all four patients. The labeling pattern on in situ hybridization suggested a replicative EBV infection comparable to that in lymphoblastoid cell lines. We conclude that EBV-associated LPS developing as a result of post-transplant immunodeficiency is a distinct clinicopathologic entity, differing from non-Hodgkin's lymphoma (including Burkitt's lymphoma) and infectious mononucleosis of the immunocompetent host.

Activated T-lymphocytes with polyclonal gammopathy in patients with human T-lymphotropic virus type I--associated myelopathy.

Human T-lymphotropic virus type I (HTLV-I)--associated myelopathy (HAM) has been shown to be closely related to HTLV-I infection. However, the mechanism by which this disease occurs after infection with HTLV-I is still obscure. We found that HAM patients have unusually high proportions of CD4+ HLA-DR+ cells, CD8+HLA-DR+ cells, OKT9+ cells, and CD38(OKT10)+ cells in their peripheral blood, all of which suggest the presence of activated T-lymphocytes. Antibody titer against HTLV-I was much higher in HAM patients than in HTLV-I carriers without evident neurological disease (p less than 0.01). Polyclonal gammopathy was also observed in most HAM patients, and 6 of 10 patients were positive for rheumatoid factor. These observations, coupled with the previous observation that corticosteroid therapy improves clinical symptoms in some patients, make it likely that continuous activation of the immune system, initiated by HTLV-I infection, plays a key role in the pathogenesis of HAM.