Viral reactivation as a cause of unexplained fever in patients with progressive metastatic breast cancer

Abstract

Patients suffering from metastatic breast cancer and recurrent fever were investigated for viral reactivation or new viral infection as a possible cause of these febrile episodes. Three groups of patients were included in the study: (a) patients under adjuvant chemotherapy with cyclophosphamide, methotrexate and fluoruracil, (b) patients with stable metastatic disease treated with cyclophosphamide, fluoruracil and Adriamycin or mitoxantrone and (c) patients with progressive metastatic disease who also received the latter treatment. During the time of observation, patients under adjuvant chemotherapy did not present with fever or asymptomatic viral reactivation or bacterial infections at all. Out of 7 patients with stable disease, 2 had bacterial infections that coincided with the leukocyte nadir, and 1 presented with asymptomatic reactivation of cytomegalovirus. In contrast, fever in 9 of 11 patients with progressive disease was associated with a reactivation of herpes simplex virus (HSV) and in 3 of them with a consecutive reactivation of varicella zoster virus (VZV). The increase in complement-fixing anti-HSV or anti-VZV antibodies occurred in close association with a rise of the respective preexisting antibodies of the IgG class. In addition, HSV-infected cells were recovered from the urine of 7 patients with progressive disease further corroborating the serological data. Incidentally, natural killer cell activity, which has been postulated to be connected with the defense against viral infections, was found to be significantly lower in the group of patients with progressive disease, as compared to the group of patients under adjuvant chemotherapy (P less than 0.05) or to the group of patients with stable disease (P less than 0.05). We conclude that unexplained fever in patients with progressive metastatic breast cancer may result from viral reactivation.

Neurological Disease Produced by Varicella Zoster Virus Reactivation Without Rash

“…Only 2 of the 19 patients with VZV reactivation had signs: one experienced transient fever, and the other developed hepatitis simultaneously with increasing VZV titers. Serologic analysis has also indicated VZV as the cause of unexplained fever in three of nine metastatic breast cancer patients (Rasoul-Rockenschaub et al 1990). In addition, VZV reactivates subclinically (without pain or rash) in astronauts (Mehta et al 2004), including shedding of infectious virus (Cohrs et al 2008), most likely reflecting transient stress-induced depression of cell-mediated immunity to VZV (Taylor and Janney 1992).…”

The Role of Oral Mucositis on the Systemic Inflammation Parameter IL-8 in Febrile Neutropenic Cancer Patients

“…A possible relationship has been described between the development of mucositis and herpes simplex infection (HSV) as well as the contribution of HSV reactivation to unexplained fever in neutropenic cancer patients (11)(12)(13).…”

Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Prostaglandin E 2 Production through Cyclooxygenase 1, Which Is Dependent on the ERK1/2-p-C/EBP-β Pathway

“…Fever is the host's initial acute response to pathogen infection and plays a critical role in antiviral responses against viral infections, such as influenza virus, chickenpox virus, and respiratory syncytial virus infections (8)(9)(10)(11)(12). Prostaglandin E 2 (PGE 2 ) is an autocrine factor derived from arachidonic acid (AA) through the activation of cyclooxygenase (13)(14)(15).…”