What is the pathophysiological mechanism underlying the development of fever in patients with lymphoma?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

Fever in lymphoma occurs primarily due to the release of cytokines by cancer cells or the immune system's response to the cancer, and it is often accompanied by other B symptoms including night sweats and unexplained weight loss, which are important diagnostic indicators. When lymphoma develops, the cancerous lymphocytes can produce inflammatory chemicals like interleukin-1, interleukin-6, and tumor necrosis factor, which act on the hypothalamus in the brain to raise the body's temperature setpoint 1. Additionally, as cancer cells die, they release substances that trigger an immune response, further contributing to fever. In some cases, particularly with Hodgkin lymphoma, patients may experience cyclical fevers known as Pel-Ebstein fevers, where high temperatures alternate with periods of normal temperature.

The presence of fever and other B symptoms typically suggests more advanced disease and may influence treatment decisions. According to the most recent guidelines, fever is a common symptom in patients with lymphoma, especially those with Hodgkin lymphoma, and it is often associated with a poor performance status 1. The NCCN panel recommends that patients with lymphoma should be treated with appropriate chemotherapy, immunotherapy, or radiation therapy, and that modifications to cancer treatment should not be made solely on the basis of HIV status 1.

Some key points to consider in the management of fever in lymphoma include:

  • Fever is a common symptom in patients with lymphoma, especially those with Hodgkin lymphoma 1
  • The presence of fever and other B symptoms typically suggests more advanced disease and may influence treatment decisions 1
  • Fever generally resolves when the underlying lymphoma is effectively treated with appropriate chemotherapy, immunotherapy, or radiation therapy 1
  • Patients with lymphoma may experience cyclical fevers known as Pel-Ebstein fevers, where high temperatures alternate with periods of normal temperature 1
  • The NCCN panel recommends that patients with lymphoma should be treated with appropriate chemotherapy, immunotherapy, or radiation therapy, and that modifications to cancer treatment should not be made solely on the basis of HIV status 1.

It is also important to note that patients with lymphoma may be at increased risk for infectious complications, particularly those with advanced or refractory disease, and that prophylactic antibiotics and dose reduction in early cycles can be considered in patients with low CD4+ T-cell counts 1. Overall, the management of fever in lymphoma requires a comprehensive approach that takes into account the underlying disease, the patient's performance status, and the potential risks and benefits of different treatment options.

From the Research

Fever in Lymphoma

  • Fever is a common symptom in patients with lymphoma, particularly in those with advanced stages of the disease 2.
  • Lymphoma patients presenting with fever of unknown origin (FUO) often have aggressive lymphomas, poor performance status, and advanced disease stage 3, 4.
  • The subtypes of lymphoma that commonly present with FUO are B cell non-Hodgkin's lymphoma (B-NHL) and T cell non-Hodgkin's lymphoma (T-NHL) 3, 4.

Clinical Characteristics

  • Patients with lymphoma and FUO often have systemic symptoms such as night sweats, unexplained weight loss, and elevated serum ferritin levels 3, 4.
  • They may also have pancytopenia, hypohepatia, and elevated lactate dehydrogenase (LDH) levels 4.
  • The detection of ferritin levels during hospital stay may help predict the long-term survival rate in patients with FUO 3.

Diagnosis and Misdiagnosis

  • Lymphoma patients with FUO can be misdiagnosed with connective tissue diseases (CTD) due to similar clinical features such as skin rashes and autoantibody positivity 5.
  • Misdiagnosis can lead to delayed diagnosis and treatment, highlighting the importance of close follow-up and repeated histopathological examination 5.
  • Positron Emission Tomography/Computed Tomography (PET/CT) scans can provide complementary information for an etiological diagnosis of FUO and help establish an early diagnosis 4.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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