Introduction:
Fever of unknown origin (FUO) in neutropenic patients occurs in individuals having weak or compromised immune systems. The most common cause of weak immunity is chemotherapy which is used in the treatment of cancer. Weak immunity increases the risk of getting infections and diseases. FUO in neutropenic patients is suspected if the diagnosis remains unclear even after three days of proper examination and evaluation in addition to getting a negative blood cultures report after 48 hours.
What Is Neutropenia?
Neutropenia is a condition that occurs due to an abnormally low count of neutrophils. Neutrophils are the white blood cells that help in fighting against infections. White blood cells are made up of four cell types which are neutrophils, lymphocytes, monocytes, and macrophages. Each of them is essential for the body's defense against pathogens. Neutrophils usually make up the majority of the white blood cells and are the key infection fighters of the body’s immune system. In addition, neutropenia is a typical side effect of chemotherapy that raises the risk of infection.
What Is Fever of Unknown Origin (FUO)?
Fever of unknown origin is characterized by a temperature of more than 100.9 degrees Fahrenheit or 38.3 degrees Celcius that lasts for more than three weeks with no apparent cause despite one week of proper investigation. The distinctive characteristic of FUO is the absence of a clear cause of fever. In FUO, the cause of the fever is not identified even after the appropriate examinations and investigations with blood tests. Therefore, it becomes very difficult to make a diagnosis.
What Are the Types of FUO?
Fever of unknown origin is of four types. The types have been listed below:
1. Classic: This type exhibits a temperature of more than 38.3°C or 100.9°F that lasts more than three weeks. The causes of classic FUO include infection, malignancy, and collagen vascular disease.
2. Nosocomial: Nosocomial FUO is identified as a persistent fever in a patient who has been hospitalized for a minimum of 24 hours without showing any symptoms of an illness, infection, or disease that might have been present before admission. Evaluation of a minimum of three days is required without establishing the source of the fever. Septic thrombophlebitis (an infection-caused blood clot and vein inflammation), pulmonary embolism (blockage of a lung artery by a blood clot), Clostridium difficile enterocolitis (inflammation of the intestines due to a bacterial infection), and drug-induced fever are among the common causes that might result in nosocomial FUO. Sinusitis may also be a factor in people who have nasogastric or nasotracheal tubes.
3. Neutropenic FUO: Neutipenic FUO is also known as immune-deficient FUO. Neutropenic FUO is described as a recurring fever in a patient with a neutrophil count of 500 cells/mm3 or less who has undergone evaluation for three days without identifying the cause of the fever.
The normal absolute neutrophil count (ANC) ranges between 2500 and 6,000. When the absolute neutrophil count is reduced to less than 1,000, this condition is called neutropenia Therefore, this type of FUO is called neutropenic FUO. In addition, the risk of infection rises when ANC drops below 500.
The majority of the cases of neutropenic FUO are caused by opportunistic bacterial infections. Its treatment is usually done by broad-spectrum antibiotics. Apart from bacterial infections, infections caused by the herpes simplex virus and infections caused by fungi like hepatosplenic candidiasis and aspergillosis are responsible for causing this type of FUO.
4. Human Immunodeficiency Virus (HIV) Associated FUO: HIV-associated FUO is identified as a recurrent fever that lasts for more than four weeks in an outpatient or lasts three days in a hospitalized patient having an HIV infection. The primary cause of this type of FUO is acute HIV infection. This virus makes the patients more prone to opportunistic infections. The most common causes include cytomegalovirus, mycobacterium avium intracellulare complex, pneumocystis carinii pneumonia, drug-induced fever, Kaposi's sarcoma, and lymphoma.
How Is FUO Diagnosed?
The diagnosis of FUO includes the following:
-
A detailed history of the patient (medicine history, dietary exposure) is taken and a thorough physical examination is done including skin, joints, and lymph nodes.
-
The fever is checked and a history of fever should be confirmed. During taking a history of FUO, recent travel (travel to tuberculosis or malaria-infected areas), pet exposure or other animals, and recent contact with individuals having the same symptoms should be included. This is particularly important because it helps in establishing the diagnosis of FUO.
-
Family history helps in identifying inherited causes of fever like Mediterranean fever. Apart from this, medical history should be taken to reveal any past history of lymphoma, rheumatic fever, or inflammatory bowel disease. In addition, patients who are taking medicines are examined for drug-induced fever.
-
Various diagnostic tests and imaging are done to confirm the diagnosis of FUO. The most common investigations include complete blood count (CBC), liver function test (LFT), erythrocyte sedimentation rate (ESR), urinalysis (routine urine test), and basic culture tests.
-
Apart from these tests, X-rays, sonography, magnetic resonance imaging (MRI), computed tomography (CT), and nuclear medicine scanning are done.
-
Sonography and CT scan are done to find out the cause of FUO in case of cancer such as lymphoma, or abscess.
-
X- rays can be done in cases of tuberculosis, cancers, and pneumocystis carinii pneumonia.
-
Echocardiography like transthoracic or transesophageal is done in cases of bacterial endocarditis.
-
A venous Doppler study is done in the case of venous thrombosis.
What Is the Treatment of FUO?
Treatment of FUO is based on the underlying disorder causing the FUO. The fever is treated with antipyretics considering the duration of the fever. In addition, nonsteroidal anti-inflammatory drugs (NSAIDs) and antihistamines are also used for the treatment of FUOs in those individuals who show no trace of underlying causes.
Broad-spectrum antibiotics are used in FUO in neutropenic patients. HIV- associated FUO are treated with antiviral medicines.
Conclusion:
Fever of unknown origin (FUO) in neutropenic patients is a type of FUO that occurs in immunocompromised patients most common in cancer patients. The diagnostic feature includes low neutrophil counts with recurrent fever persistent for three days without any usual cause. The cause of this type of FUO includes bacterial, viral, and fungal infections due to a weakened immune system. The treatment includes broad-spectrum antibiotics and antipyretics for controlling fever.
