Internal Medicine/Fatigue

Introduction
Fatigue, a pervasive and complex symptom, is encountered frequently in clinical medicine. It is a subjective experience characterized by a profound sense of physical and mental weariness, sluggishness, low energy, and exhaustion. In the realm of clinical practice, fatigue is often defined as the difficulty in initiating or sustaining voluntary mental or physical activities. While fatigue is a nearly universal symptom experienced by individuals during self-limited infections or temporary illnesses, its significance becomes apparent when it persists without a clear underlying cause or when its severity exceeds what would be reasonably expected based on the precipitating factors.

Epidemiology and Global Considerations
Assessing the prevalence and impact of fatigue on a global scale is a challenging endeavor, primarily due to the diverse definitions and survey instruments employed in various studies. In an extensive survey conducted by the National Institute of Mental Health in the United States, the point prevalence of fatigue was found to be approximately 6.7%, with a lifetime prevalence of 25% in the general population. Primary care clinics in both Europe and the United States have reported that between 10% and 25% of patients endorse symptoms of prolonged fatigue (lasting for more than one month) or chronic fatigue (persisting for over six months). Notably, fatigue is rarely the primary reason for individuals seeking medical attention, often emerging as a secondary concern.

Differential Diagnosis
Fatigue poses a multifaceted challenge for clinicians, demanding the distinction from conditions such as muscle weakness, somnolence (excessive sleepiness), and dyspnea (shortness of breath) on exertion. When a patient presents with fatigue, the clinician's primary objective is to pinpoint the underlying cause and establish a therapeutic alliance with the patient. This alliance aims to avoid costly and potentially fruitless diagnostic workups while guiding patients toward effective therapeutic interventions.

The etiology of fatigue is remarkably diverse, encompassing psychiatric, neurologic, and systemic conditions. Psychiatric diseases, including depression, anxiety, and somatoform disorders, frequently manifest with fatigue as a common somatic symptom. Neurologic diseases may give rise to feelings of weakness, although objective muscle weakness is seldom evident upon clinical examination. An array of sleep disorders, such as obstructive sleep apnea, can contribute significantly to fatigue and warrant thorough investigation. Endocrine disorders, liver and kidney diseases, obesity, physical inactivity, and malnutrition can each serve as contributors to fatigue. Infections, medications, cardiovascular and pulmonary disorders, malignancies, hematologic disorders, immune-mediated diseases, pregnancy, and poorly defined conditions like chronic fatigue syndrome and fibromyalgia further underscore the complexity of potential causes.

Approach to the Patient
Effectively navigating the complex terrain of fatigue necessitates a meticulous patient history. This history should delve into the quality, pattern, time course, associated symptoms, and factors that exacerbate or alleviate fatigue. Differentiating between acute and chronic fatigue, understanding whether the impairment is primarily mental or physical, and assessing its impact on daily functioning are critical components of the evaluation process. Additionally, a comprehensive review of the patient's medical history, medication use, and social circumstances can provide invaluable insights.

Laboratory testing plays a pivotal role in identifying the cause of chronic fatigue but is expected to yield a diagnosis in only approximately 5% of cases. As such, an approach rooted in selectivity is advisable. Standard screening tests include a complete blood count with differential to assess for anemia, infection, and malignancy. Electrolytes, glucose, renal and liver function, thyroid function, HIV status, and adrenal function may all be subjects of evaluation. While nonspecific tests like erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA) may be considered, they are unlikely to provide definitive insights in isolation. Extensive, unfocused studies and whole-body imaging scans are typically not recommended due to their inconvenience, potential risks, and propensity to yield unrelated findings that complicate diagnostic clarity.

Treatment
Prioritizing the management of underlying causes of fatigue constitutes the primary objective of treatment, as this approach can lead to complete resolution in certain contexts and symptom amelioration in others. However, in many instances, fatigue remains refractory to traditional disease-modifying therapies, emphasizing the importance of evaluating additional contributors. Antidepressants may prove beneficial, particularly when fatigue is accompanied by symptoms of depression, although their continued use should be reassessed if no discernible improvement is observed. Cognitive-behavioral therapy and graded exercise therapy have demonstrated efficacy in conditions like chronic fatigue syndrome and cancer-associated fatigue. Psychostimulants, such as amphetamines and modafinil, can enhance alertness and concentration in specific clinical contexts, potentially alleviating fatigue in a subset of patients. Additionally, addressing specific deficiencies, such as low vitamin D levels, may lead to improvements in fatigue.

Prognosis
The prognosis associated with fatigue varies significantly based on its duration and the underlying causes. Acute fatigue, which prompts medical evaluation, is more likely to have an identifiable medical, neurologic, or psychiatric cause compared to unexplained chronic fatigue. In cases of unexplained chronic fatigue, psychiatric conditions or a lack of a definitive diagnosis often emerge as the predominant outcomes. Identifying a previously undiagnosed serious or life-threatening cause is rare, even with extended follow-up. Complete resolution of fatigue is infrequent, especially in the short term. However, multidisciplinary treatment approaches can lead to symptomatic improvements that significantly enhance the patient's quality of life.