Fever of unknown origin

Fever of Unknown Origin (FUO) refers to a condition in which a patient has an elevated temperature (fever) exceeding 38.3°C (101°F) on several occasions over a period of more than three weeks, without an established diagnosis after initial investigation. The concept of FUO was first defined in 1961, aiming to categorize patients who presented a diagnostic challenge to clinicians. Over the years, the criteria have been refined, but the essence remains the exploration of a persistent fever without a clear cause.

Etiology

The causes of FUO can be broadly classified into four main categories: infectious diseases, neoplasms, autoimmune disorders, and miscellaneous causes. Infections account for approximately 25-40% of FUO cases and can include entities like Tuberculosis, Endocarditis, and various viral, bacterial, and fungal infections. Neoplasms, or cancers, are responsible for about 20-30% of cases, with Lymphoma being a common culprit. Autoimmune diseases, such as Rheumatoid arthritis and Systemic lupus erythematosus, account for another 10-20% of cases. The miscellaneous category includes a wide range of conditions, from Thromboembolic disease to factitious fever.

Diagnosis

The diagnostic approach to FUO is systematic and often requires a multidisciplinary team. Initial evaluation includes a detailed patient history, physical examination, and basic laboratory tests. Further investigations are guided by clinical suspicion and may involve advanced imaging techniques like CT scans or MRI, and specialized laboratory tests. In some cases, invasive procedures such as biopsy may be necessary to obtain a definitive diagnosis.

Management

Management of FUO is directed by the underlying cause, once identified. In cases where a specific diagnosis is made, treatment is tailored to the specific condition. For infectious causes, appropriate antibiotics or antiviral medications are prescribed. Neoplasms may require surgery, chemotherapy, or radiation therapy. Autoimmune disorders are often managed with immunosuppressive medications. In a significant number of cases, however, the cause of the fever remains elusive even after extensive investigation, leading to a therapeutic challenge.

Prognosis

The prognosis of FUO varies widely depending on the underlying cause. Infections and autoimmune conditions, when identified and treated appropriately, often have a favorable outcome. Neoplastic causes of FUO may have a more guarded prognosis, depending on the type and stage of cancer. In cases where no cause is identified, the approach is often conservative, with symptomatic treatment and close monitoring.

Epidemiology

The incidence of FUO varies globally, influenced by factors such as geographic location, prevalence of certain infectious diseases, and access to healthcare. Advances in diagnostic techniques have led to a decrease in the proportion of cases that remain undiagnosed, but FUO continues to represent a significant clinical challenge.

History

The term "Fever of Unknown Origin" was coined by Dr. Petersdorf and Beeson in 1961, setting the initial criteria for the condition. Since then, the definition has evolved, reflecting advances in medical diagnostics. The original criteria focused on hospital inpatients, but subsequent revisions have broadened the scope to include outpatients and specific populations such as immunocompromised patients.

See also

• Infectious disease
• Autoimmune disease
• Cancer
• Diagnostic medicine