CLINICAL CLUES TO SUSPECT A PATIENT HAS MALIGNANT FEVER

In patients with malignant fever, the onset of fever may sometimes precede other clinical manifestations and may be the first clue that patient has an underlying cancer.  There is usually no specific fever pattern seen in patients with malignant fever.

One exception is the classic fever pattern seen in Hodgkin lymphoma albeit uncommon, called the Pel-Epstein fever. This type of fever occurs continuously for several days followed by a period of afebrile episodes of similar duration.  Unlike fever caused by infections, malignant fevers are generally not associated with chills, rigors, tachycardia or hypotension. In addition, the fever is not relieved by paracetamol (Panadol).

In the majority of cases, it is more likely that patients present with other clinical manifestations together with fever. For example, B symptoms which is a triad of persistent fever, drenching night sweats and unintentional weight loss of more than 10% of baseline weight over 6 months, are typically a manifestation of lymphoma. There are several types of lymphoma such as Diffuse large B-cell lymphoma, Hodgkin lymphoma, Peripheral T-cell lymphoma and NK T-cell lymphoma. The presence of any of the B symptoms denotes a worse prognosis and is often associated with extra-nodal disease ie. involving the liver, bone etc. A dull achiness or fullness in the left upper abdomen may indicate splenomegaly or an enlarged spleen due to chronic myeloid leukemia.

Fever with productive cough and hemoptysis maybe due to post-obstructive pneumonia from lung cancer (eg . non-small cell lung cancer or small cell lung cancer) or bulky mediastinal lymphadenopathy from lymphoma. Fever in the context of sudden leg swelling or sudden breathlessness may be due to venous thromboembolic disease (DVT) in cancer patients. These few examples underpin the importance of a detailed history and physical examination in order to make an accurate diagnosis.

At OncoCare Cancer Centre, we do have patients occasionally presenting with malignant fever. Early evaluation is important, for example, patients with suspicion of lymphoma and lymph nodes in the chest and abdomen may not be immediately obvious if a CT scan or PET CT scan is not arranged in a timely manner.

MANAGEMENT OF MALIGNANT FEVER

​Once the diagnosis of cancer is made, the definitive treatment of malignant fever is to address the underlying cancer, either by administering chemotherapy or surgical removal of the tumor.  However, at times the cause of fever can remain elusive despite evaluation. For this group of patients, sometimes the strategy of using a non-steroidal anti-inflammatory (NSAID) challenge is employed.

​This approach has been validated by several clinical trials which demonstrated the effectiveness of NSAIDs such as naproxen and ibuprofen, in suppressing malignant fever. Therefore, empiric treatment with NSAID is not only useful in alleviating symptoms, it may also aid in identifying patients with possible malignant fever.

CONCLUSION

Malignant fever is an important consideration in patients with fever of unknown origin. Other causes such as infections must be thoroughly excluded before making the diagnosis. Hence, a thorough history-taking and physical examination is of utmost importance in making an accurate diagnosis.  A good rule of thumb is to consider the diagnosis of malignant fever in patients with prolonged febrile illness and no evidence of underlying infections. The main management of malignant fever is to address the underlying cancer. However, the use of NSAIDs in malignant fever may provide both symptomatic relief as well as diagnostic utility.

“Expert knowledge means better care for cancer”

Written by:

Dr Kevin Tay
MBBS (Singapore)
ABIM Int. Med (USA)
ABIM Med Onc(USA)
FAMS (Medical Oncology)