Fever often signals the body’s response to illness, indicating that the immune system is actively fighting off an infection or other ailment. However, there are instances when a fever persists without an obvious cause, presenting a complex medical challenge. This situation, often termed “unexplained fever,” requires a systematic approach to uncover the underlying reason for the elevated body temperature.
Understanding Unexplained Fever
An “unexplained fever,” formally known as Fever of Unknown Origin (FUO), is characterized by specific criteria. A person is considered to have FUO if their oral temperature consistently reaches 101°F (38.3°C) or higher on multiple occasions. This elevated temperature must persist for at least three weeks, or after three days of inpatient investigation, without a clear diagnosis being established despite initial routine medical assessments.
The challenge in diagnosing FUO stems from the vast array of potential causes. While most persistent fevers are diagnosed within a week of hospital evaluation or three outpatient visits, those that extend beyond this period often defy immediate explanation. This diagnostic puzzle necessitates a thorough and often prolonged investigation to identify the root cause.
Categories of Potential Causes
Unexplained fevers can arise from a broad spectrum of conditions, typically categorized into infectious, inflammatory/autoimmune, malignant, and miscellaneous causes.
Infectious causes remain a significant category, accounting for 25% to 50% of FUO cases in adults. These often involve persistent or unusual infections. Examples include tuberculosis, various types of abscesses such as abdominal or pelvic abscesses, and certain viral infections like Epstein-Barr virus (EBV) and cytomegalovirus (CMV).
Inflammatory or autoimmune conditions represent another substantial category, contributing to 10% to 30% of FUO cases. These are chronic diseases where the immune system mistakenly attacks the body’s own tissues, leading to widespread inflammation and fever. Examples include adult-onset Still’s disease, systemic lupus erythematosus (SLE), rheumatoid arthritis, vasculitides, and granulomatous disorders.
Malignancies, or cancers, are responsible for 2% to 30% of FUO cases. Certain cancers are known to cause fever. Lymphomas, including both Hodgkin and non-Hodgkin types, are frequently implicated. Other cancers that can present with unexplained fever include leukemias and renal cell carcinoma.
Miscellaneous causes encompass a diverse range of less common conditions. Drug-induced fever, where certain medications trigger an elevated temperature, is a notable example. Other causes include pulmonary emboli, thyroiditis, and factitious fever.
Investigating the Cause
Diagnosing an unexplained fever involves a systematic process to pinpoint the underlying cause. The initial approach begins with a comprehensive medical history and a thorough physical examination.
Initial broad tests are typically performed to screen for common issues. These usually include a complete blood count (CBC), inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which indicate inflammation in the body, and urinalysis. Blood and urine cultures are also routinely collected to identify bacterial infections.
Subsequent targeted investigations are guided by initial findings and any specific symptoms the patient presents. Advanced imaging techniques, such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans, may be employed. Specialized blood tests, such as autoimmune markers or specific infectious disease serologies, may be ordered. If suspicious areas are found, biopsies of tissues like bone marrow, lymph nodes, or liver may be performed for microscopic examination. The diagnostic process often benefits from a multidisciplinary approach, involving specialists from various fields who collaborate to determine the most appropriate next steps.
What to Do When Fever Persists
If you are experiencing a persistent fever without a clear explanation, seeking medical attention is a prudent step. It is advisable to consult a doctor if a fever is high, continues for an unusual length of time, or is accompanied by other concerning symptoms, even if it does not yet meet the formal criteria for Fever of Unknown Origin. Symptoms such as severe thirst, dark urine, lightheadedness, weakness, new severe muscle cramps, or worsening existing symptoms warrant medical evaluation.
Preparing for your doctor’s visit can greatly assist in the diagnostic process. It is helpful to compile a detailed medical history, including any recent travel, current and past medications, potential exposures to illnesses, and a precise timeline of your symptoms, noting when the fever started and any patterns it follows. This comprehensive information provides valuable clues that can guide the medical team’s investigation.
Diagnosing an unexplained fever can be a lengthy and intricate process, requiring patience from both the individual and the healthcare providers. It is important to maintain open and clear communication with your healthcare team throughout this journey, asking questions and sharing any new developments in your symptoms. While some cases of FUO may never receive a definitive diagnosis, many resolve spontaneously, and the long-term outlook is generally favorable even without an identified cause.