FUO

Question 1

Criteria

Answer 1

1. Fever: Body temperature higher than
   38.3°C (101°F) measured on at least one week.
2. Unknown origin: The cause of the fever remains undiagnosed despite one week of inpatient investigation or three outpatient visits.

Question 2

Causes of FUO

Answer 2

1. Infectious diseases:
   Infections are a significant cause of FUO. These can include:

a). Bacterial infections: Such as
endocarditis, tuberculosis, abscesses, or infective osteomyelitis.

b). Viral infections:
Certain viral illnesses, like Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus (HIV), can cause prolonged fever.

c). Parasitic infections: In some regions, parasitic infections like malaria, toxoplasmosis, or visceral leishmaniasis can be considered.

d). Fungal infections: Deep-seated fungal infections, such as histoplasmosis or coccidioidomycosis, may present with prolonged fever.

2. Inflammatory and autoimmune disorders:
   Various inflammatory and autoimmune conditions can cause FUO, including:

a). Autoimmune diseases: Systemic lupus erythematosus (SLE), rheumatoid arthritis, or vasculitis can present with prolonged fever.

b). Inflammatory bowel disease: Conditions like Crohn’s disease or ulcerative colitis may cause prolonged fever.

c). Granulomatous diseases: Disorders such as sarcoidosis or granulomatosis with polyangiitis (formerly Wegener’s
granulomatosis) can present with prolonged fever.

3. Malignancies: Some types of cancers can cause FUO, including:
   a). Lymphomas: Both Hodgkin’s lymphoma and non-Hodgkin’s lymphoma can present with prolonged fever.

b). Leukemias: Acute or chronic leukemias may cause persistent or recurrent fever.

c). Solid tumors: Certain solid tumors, such as renal cell carcinoma or hepatocellular carcinoma, can be associated with prolonged fever.

4-Drug reactions: Fever can be a side effect of certain medications or drug reactions, including hypersensitivity reactions or drug-induced autoimmune syndromes.

a). Antibiotics: Certain antibiotics, such as beta-lactams (e.g., penicillins, cephalosporins) and sulfonamides, can occasionally cause fever as an adverse reaction.

b). Antiepileptic drugs: Some antiepileptic medications, like phenytoin or carbamazepine, have been reported to cause fever in rare cases.

c). Nonsteroidal anti-inflammatory drugs (NSAIDs):
Although uncommon, some individuals may develop fever as a reaction to NSAIDs.

d). Antihypertensive medications: Medications like beta-blockers or angiotensin-converting enzyme (ACE) inhibitors have been implicated in drug-induced fever.

e). Antipsychotic medications: Certain antipsychotic drugs, such as clozapine, may rarely cause fever.

5. Miscellaneous causes: There are various other less common causes of FUO, including:

a). Periodic fever syndromes: Genetic disorders like familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), or hyper-IgD syndrome (HIDS) can cause recurrent episodes of fever.

b). Temporal arteritis: Inflammation of the temporal arteries, known as temporal arteritis or giant cell arteritis, can present with fever of unknown origin.

c). Other rare conditions: Conditions like adult-onset Still’s disease, factitious fever, or drug fevers may also be considered.

Question 3

Classification

Answer 3

1. Classification of FUO: FUO can be further classified into three subtypes based on the duration of fever:

a). Classic FUO: Fever lasting for more than three weeks with no apparent cause after one week of inpatient investigation or three outpatient visits.

b). Nosocomial FUO: Fever that develops in hospitalized patients and persists for more than three days.

c). Neutropenic FUO: Fever in patients with low white blood cell counts (neutropenia) that persists for more than three days.

Question 4

Investigation

Answer 4

When investigating the cause of Fever of Unknown Origin (FUO), a wide range of diagnostic tests may be performed depending on the patient’s clinical presentation, medical history, and physical examination findings. Here are some specific tests that may be done:

1. Blood tests: A variety of blood tests can be conducted to evaluate various aspects, including:a. Complete blood count (CBC): To assess for abnormalities in white blood cells, red blood cells, and platelets.b. Inflammatory markers: Tests such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can indicate the presence and severity of inflammation.c. Blood cultures: To detect bacterial, fungal, or other microbial infections in the bloodstream.d. Serology tests: These tests measure the presence of antibodies specific to certain infections, such as hepatitis, HIV, or Lyme disease.e. Autoimmune markers: Tests may be performed to assess for specific autoantibodies associated with autoimmune diseases, like antinuclear antibodies (ANA) or rheumatoid factor (RF).
2. Imaging studies: Various imaging techniques can help visualize internal structures and detect abnormalities. Common imaging modalities used in the evaluation of FUO include:a. X-rays: To examine the chest, abdomen, or specific bones for signs of infection, inflammation, or tumors.b. Computed tomography (CT) scan: Provides detailed cross-sectional images of the body to identify abnormalities in organs, lymph nodes, or blood vessels.c. Magnetic resonance imaging (MRI): Uses powerful magnets and radio waves to produce detailed images of organs and tissues, helping to detect abnormalities.d. Ultrasound: Uses sound waves to create images of internal organs, aiding in the evaluation of abdominal or pelvic abnormalities.
3. Microbiological tests: Depending on the suspected infection, specific microbiological tests may be performed, such as:a. Cultures: Collecting samples (e.g., blood, urine, sputum) to identify the presence of bacteria, fungi, or other microorganisms.b. Polymerase chain reaction (PCR): A molecular technique used to detect the genetic material of infectious agents like viruses or bacteria.c. Serological tests: These tests evaluate the presence of antibodies against specific infectious agents, such as bacteria, viruses, or parasites.
4. Biopsies: In some cases, a biopsy may be necessary to obtain a tissue sample for further examination under a microscope. Biopsies can be performed on various organs or tissues, depending on the suspected underlying cause.a. Examples include bone marrow biopsy, lymph node biopsy, liver biopsy, or biopsy of affected organs like the lung or kidney.

These are just a few examples of the tests that may be employed during the diagnostic workup for FUO. The specific tests conducted will depend on the patient’s individual clinical scenario and the suspected underlying cause based on the initial evaluation. The healthcare provider overseeing the patient’s care will determine which tests are most appropriate.

Question 5

Treatment

Answer 5

The treatment of fever of unknown origin (FUO) in pediatrics depends on the underlying cause once it is identified. However, in cases where the cause remains unknown, the management primarily focuses on supportive care and symptomatic treatment. Here are some general treatment approaches for pediatric patients with FUO:

1. Supportive care: Providing comfort measures and supportive care is essential. This includes ensuring adequate hydration, maintaining a comfortable ambient temperature, and promoting rest.
2. Fever management: The use of antipyretic medications, such as acetaminophen (paracetamol) or ibuprofen, is commonly employed to reduce fever and alleviate associated symptoms. These medications should be administered according to the appropriate dosage based on the child’s age and weight, following the guidance of a healthcare professional.
3. Monitoring and observation: Regular monitoring of the child’s temperature, vital signs, and overall clinical status is important. Documenting the pattern and duration of fever episodes can provide valuable information for diagnostic evaluation.
4. Symptomatic treatment: Depending on the child’s symptoms, targeted symptomatic treatment may be provided. For example, if the child has pain, analgesics appropriate for their age can be administered. If there are respiratory symptoms, such as cough or congestion, supportive measures like saline nasal drops or humidifiers may be helpful.
5. Infection control measures: If an infectious cause is suspected, appropriate infection control measures should be implemented to prevent the spread of infection, both within the household and in healthcare settings. This includes practicing good hand hygiene, covering the mouth and nose when coughing or sneezing, and avoiding close contact with individuals who are ill.
6. Nutritional support: Ensuring adequate nutrition is important for pediatric patients with FUO. If the child has a decreased appetite, offering small, frequent meals or providing nutritional supplementation may be necessary to maintain proper growth and development.
7. Psychological support: Pediatric patients and their families may experience emotional distress due to the prolonged illness and diagnostic uncertainty. Providing psychological support, addressing concerns, and maintaining clear and open communication with the family can help alleviate anxiety and stress.

It is important to note that the treatment approach for FUO in pediatrics is highly dependent on the underlying cause. Once a diagnosis is established, specific treatments targeting the identified condition will be initiated. Therefore, a thorough diagnostic evaluation and collaboration with pediatric specialists are essential to guide appropriate treatment strategies for pediatric patients with FUO.