Fever of Unknown Origin (No Reason) and Causes of FUO

Fever of unknown origin or FUO is a chronic fever for which no cause can be conclusively identified. There are three criteria that define FUO and this includes :

  1. A persistent or recurrent body temperature of 38.3C (101F) or more,
  2. A fever continuing for more than 3 weeks,
  3. No conclusive diagnosis of the cause of the fever despite 3 days of inpatient care or 2 outpatient visits.

Pyrexia with No or Few Symptoms

Non-specific Fever Tests

A diagnosis of a specific medical condition is made upon the clinical presentation, which are the signs evident to the doctor and symptoms reported by the patient, along with a medical history. Investigations confirm the diagnosis and allows a doctor to assess the severity of the condition.

The presence of a fever with no other symptoms or vague and transient symptoms is referred to as a non-specific fever. In this instance, a diagnosis is difficult to make without further investigation. Some of the investigations that would be considered in the event of a non-specific fever include:

  • White blood cell (WBC) count and/or complete blood count (CBC)
  • Sputum test
  • Throat culture
  • Urinalysis
  • Stool test
  • Lumbar puncture
  • Chest x-ray

Other tests may be considered based on the patient’s medical, travel, occupational, sexual and family history. Recreational habits, drug usage (prescription/narcotic), lifestyle and nutrition as well as vector exposure (animal/insect contact, bites and stings). If no conclusive diagnosis can be reached after the clinical evaluation and investigations, the fever may be referred to as a fever of unknown origin (FUO). A factitious fever is where a patient manipulates the body temperature readings to record higher levels than is actually present and this has to be excluded as a possible cause of a fever of unknown origin.

Causes of a Fever of Unknown Origin

Infectious Causes of a Fever of Unknown Origin

An infection is caused by pathogenic microorganisms. These are the more common cause of a fever of unknown origin.

  • Abscess
    • Especially abdominal, pelvis and dental abscesses.
    • Consider if there is a history of trauma, gynecological procedures, peritonitis, diverticulosis.
  • Cytomegalovirus (CMV)
    • Consider if there is a history of blood transfusion or if HIV-positive.
  • Epstein-Barr virus (EBV)
  • Human Immunodeficiency Virus (HIV)
    • Consider if there is a history of  risky behavior like multiple sexual partners, unprotected sex, IV drug use.
    • Refer to Stages of HIV/AIDS.
  • Endocarditis
    • Inflammation of the inner lining of the heart and heart valves. In an FUO, this is usually due to an infection and is referred to as infective endocarditis.
  • Travel-Related Fevers
    • Consider if there is a history of recent travel.
    • Refer to Traveler’s Fever for a list of causes of a non-specific fever after travel.
  • Osteomyelitis
    • Inflammation of the bone due to an infection.
  • Sinusitis
    • Inflammation of the paransal sinuses due to an infection.
  • Tuberculosis (TB) – especially extrapulmonary TB.
  • Other
    • Fungal infections
    • Parasitic infections

Rheumatological / Autoimmune Diseases

This include inflammatory conditions caused by the body’s immune activity against its own tissues.

  • Adult Still’s disease
  • Giant cell arteritis (temporal arteritis)
  • Inflammatory bowel disease
  • Polyarteritis nodosa
  • Polymyalgia rheumatica
  • Reactive arthritis
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE)

Neoplastic / Malignancy

This includes malignant tumors.

  • Colon cancer
  • Liver cancer (hepatoma)
  • Leukemia and myeloma
  • Lymphoma
  • Renal cell carcinoma
  • Stomach cancer
  • Cancer of the pancreas
  • Metastatic cancer

Miscellaneous (Other Causes)

  • Alcoholic cirrhosis
  • Drug fever
  • Factitious fever – high body temperature due to manipulation by the patient.
  • Deep vein thrombosis (DVT)
  • Pancreatitis (inflamed pancreas)
  • Inflammatory bowel disease
  • Familial Mediterranean Fever (refer to periodic fever syndrome in Chronic Fever)
  • Thyrotoxicosis (hyperthyroidism) and thyroiditis
  • Sarcoidosis

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