Comparison of sequential cytomegalovirus isolates in a patient with lymphoma and failing antiviral therapy

BACKGROUND: Long-term anti-cytomegalovirus (CMV) treatments in immunocompromised patients are hampered by resistance to antiviral drugs. Longitudinal changes in the resistance genotype may depend on changes in selective pressure and the complexity of CMV isolates. OBJECTIVE: To evaluate longitudinal changes in the CMV resistance genotype and phenotype along with strain-specific variability in a patient with non-Hodgkin\u27s lymphoma in whom successive anti-CMV treatments failed. STUDY DESIGN: The resistance phenotype and genotype of seven CMV isolates collected from one patient during a 2-year follow-up period were retrospectively analysed. In parallel, we used glycoprotein B (gB) genotyping, and a- and UL10-13-sequence analysis to study CMV interstrain variability. RESULTS: The patient was infected by at least three CMV strains plus variants of the parental strains. Resistance to ganciclovir, cidofovir and foscarnet was successively detected during the follow-up period. UL97 protein kinase changes responsible for resistance to ganciclovir were initially detected at residues 591 and 592, and then at position 594. Decreased sensitivity to foscarnet coincided with the appearance of amino acid substitution N495K in DNA polymerase, whereas cross-resistance to ganciclovir and cidofovir was due to the L501I substitution. CONCLUSIONS: The CMV isolates obtained from our patient were complex mixtures of strains. Changes in resistance genotypes depended on resistance selective pressure and were not linked to interstrain variation

Unusual manifestations of type II cryoglobulinaemia associated with Waldenström's macroglobulinaemia

Cryoglobulinaemia in association with Waldenström's macroglobulinaemia is relatively common, ranging from 8% to 18% of cases; however, < 5% have symptoms or complications. We describe a patient with a history of cutaneous, peritoneal, and fallopian tube vasculitis related to type II cryoglobulinaemia associated with Waldenström's macroglobulinaemia. Cytotoxic treatment was initiated (cyclophosphamide, vincristine, and prednisone) and had a good initial response. However, after the third course of chemotherapy, the patient presented with septic shock and died. Even though cryoglobulinaemia is a model of systemic vasculitis, peritoneal and fallopian tube vasculitis associated with type II cryoglobulinemia has not been described previously. Key Words: cryoglobulinaemia • Waldenström's macroglobulinaemia • peritoneum • fallopian tub