Dermatologic/Mucosal Conditions, Corticosteroids, Intravenous Antibiotics Impact Febrile Neutropenia Risk

Dermatologic or mucosal conditions that might affect barrier integrity, use of corticosteroids, and intravenous antibiotics prior to chemotherapy may increase the risk of febrile neutropenia and should be considered in prophylaxis use and febrile neutropenia prediction modeling, according to a new study.

Risk of febrile neutropenia varies based not only on chemotherapy regimens, but also on patient and disease-related characteristics, including chronic obstructive pulmonary disease, congestive heart failure, thyroid disease, and osteoarthritis. While previous research has found that these conditions alter the risk of febrile neutropenia, the underlying mechanisms of why are less understood.

“We hypothesized that the increased febrile neutropenia risk associated with these comorbidities may be mediated at least in part through the following biological mechanisms: bone marrow suppression, impaired neutrophil and other immune cell function, disturbances of barrier function/increased availability of pathogenic microbes, and impaired bacterial flora,” explained the authors of the study.

They added, “…we further hypothesize that other clinical conditions that potentially lead to one or more of these pathogenic states may also increase risk of febrile neutropenia during chemotherapy.”

The authors hypothesized that surgery, radiation, use of corticosteroids and antibiotics, and certain dermatologic/mucosal conditions, in particular, increase the risk of febrile neutropenia.

To assess the hypothesis, the authors studied 15,971 patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who were treated with myelosuppressive chemotherapy between 2000 and 2009 at Kaiser Permanente Southern California.

During the study period, 4.3% of patients developed febrile neutropenia during the first chemotherapy cycle. The authors observed that certain dermatologic/mucosal conditions were marginally associated with febrile neutropenia (adjusted hazard ratio [aHR], 1.40; 95% CI, 0.98-1.93) and corticosteroid use overall was associated with a statistically significant increase in febrile neutropenia risk (aHR, 1.53; 95% CI, 1.17-1.98). As the duration of corticosteroid use increased, so did the risk of febrile neutropenia, with the aHR increasing from 1.78 for use of less than 15 days to 2.86 for use of 45 to 90 days.

While there was no association observed with oral antibiotic use, intravenous antibiotic use was marginally associated with increased risk (aHR, 1.35; 95% CI, 0.97-1.87). No other potential risk factors examined were linked to risk of febrile neutropenia.

The authors noted that there is biological plausibility to support these associations, including that corticosteroid use suppresses immune cell function, and thus increases susceptibility to pathogenic microbes. “In hematologic malignancies such as non-Hodgkin lymphoma, corticosteroids are often used in high doses, increasing the risk of infection with a broad spectrum of pathogens,” they wrote.

Additionally, skin and mucosal injuries that break down barrier integrity lead to a point of entry for microorganisms that cause blood stream infections and directly contribute to fever. Because there was no febrile neutropenia risk associated with oral antibiotic use but there was with intravenous use, the authors suggest that intravenous antibiotics may have a more profound impact on the balance of bacterial flora and other immune functions, which increase febrile neutropenia risk.

Reference

Family L, Li Y, Chen LH, Page JH, Klippel ZK, Chao C. A study of novel febrile neutropenia risk factors related to bone marrow or immune suppression, barrier function, and bacteria flora. J Natl Compr Canc Netw. 2018;16(10):1201-1208. doi: 10.6004/jnccn.2018.7051.