Pneumocystis Pneumonia in Patients Treated With Rituximab

Abstract

Original Research P neumocystis pneumonia (PcP) remains a serious threat to immune-compromised patients. Host defenses against PcP have largely been attributed to CD4 1 lymphocytes, which are defective in most diseases associated with PcP. 1 However, animal stud ies have also indicated a role for B lymphocytes and antibody defenses in this infection. 2 In addition, recent stud ies have suggested that the novel anti-B-lymphocyte agent rituximab may be associated with the development of PcP. [3][4][5][6][7][8][9][10][11] Rituximab is a monoclonal antibody that binds to the CD20 antigen on B lymphocytes. It has been used for both hematologic malignancies such as chronic lymphocytic leukemia and for non-Hodgkin's lymphoma. More recently, this agent has been used in infl ammatory conditions and has been approved for the treatment of patients with rheumatoid arthritis and antineutrophil cytoplasmic antibodies-associated Abbreviations: G-CSF 5 granulocyte-colony stimulating factor; GPA 5 granulomatosis with polyangiitis (Wegener); PcP 5 Pneumocystis pneumonia; PCR 5 polymerase chain reaction; R-CHOP 5 rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone; TMP-SMX 5 trimethoprim-sulfamethoxazole

Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones’s Locker?

“…Recent clinical observations suggest this association with PCP is related to RTX based treatment regimens [3]. The incidence of PCP is increased in patients receiving biweekly RTX, cyclophosphamide, adriamycin, vincrisitine and prednisolone (R-CHOP-14) therapy compared to standard R-CHOP every 21 days [21], from 2% with standard R-CHOP [22] to 6-11% with R-CHOP-14 [21].…”

“…A retrospective study from a single centre -Mayo Clinic Rochester between 1998 and 2011-identifies 30 patients that developed PCP after RTX treatment: 90% have haematological malignancies and 10% are only treated with RTX [3]. The patients are mostly older male -73% male with a median age of 70 years -and 27% have chronic renal disease [3].…”

“…The patients are mostly older male -73% male with a median age of 70 years -and 27% have chronic renal disease [3]. PCP occurs after a median of 4 RTX cycles and a mean of 77 days after its last administration [3].…”

“…The patients are mostly older male -73% male with a median age of 70 years -and 27% have chronic renal disease [3]. PCP occurs after a median of 4 RTX cycles and a mean of 77 days after its last administration [3]. Patients have low lymphocytes (0.38x10^9/L), CD4 (0.25x10^9/L ) and CD8 (0.77x10^9/L) counts at PCP onset with undetectable B cells count [3].…”

“…PCP usually has an acute onset (fever, dry cough and respiratory failure) and can be life-threatening with a mortality rate exceeding 30% [2,3]. Treatment with methotrexate [4], high-dose prednisolone [4] and cyclophosphamide [5] in association with lymphopenia increases the risk for PCP in GPA patients.…”