“Doctor, I’m so tired!” Refining your work-up for chronic fatigue

To address this distinction, take a sleep history, assessing both the quality and quantity of the patient’s sleep to determine how it affects symptoms.²⁷ Consider using a questionnaire designed to help distinguish between sleepiness—and a primary sleep disorder—and fatigue,²⁸ such as the Fatigue Severity Scale of Sleep Disorders (http://www.healthywomen.org/sites/default/files/FatigueSeverityScale.pdf).

What to rule out. In addition to a medical history, the physical examination should be oriented toward ruling out secondary causes of fatigue. In addition to a system-by-system approach to the differential diagnosis, carefully observe the patient’s general appearance, with attention to his or her level of alertness, grooming, and psychomotor agitation or retardation as possible signs of a psychiatric disorder. To rule out neurologic causes, evaluate muscle bulk, tone, and strength; deep tendon reflexes; and sensory and cranial nerves, as well.²⁹

Lab tests to consider. In most cases of ME/CFS, basic studies—complete blood count with differential, erythrocyte sedimentation rate, blood chemistry, and thyroid-stimulating hormone (TSH) levels—are sufficient. When no medical or psychiatric cause has been found, additional tests may be ordered on a case-by-case basis, although laboratory analysis affects the management of fatigue in less than 5% of such patients.³⁰ Tests to consider include:

• Creatine kinase (for patients who report pain or muscle weakness)
• pregnancy test (for women of childbearing age)
• ferritin testing (for young women who might benefit from iron supplementation for levels <50 ng/mL even if anemia is not present)³¹
• hepatitis C screening (recommended by the US Preventive Services Task Force for those born between 1945 and 1965)³²
• human immunodeficiency virus screening and the purified protein derivative test for tuberculosis (based on patient history).

Forego routine testing for other infections

Routine testing for infectious diseases and conditions associated with fatigue, such as Epstein-Barr virus or Lyme disease, immune deficiency, and inflammatory disease, is unlikely to be helpful. Routine testing for infectious diseases and conditions associated with fatigue, such as EBV or Lyme disease, immune deficiency (eg, immunoglobulins), inflammatory disease (eg, antinuclear antibodies, rheumatoid factor), celiac disease, vitamin D deficiency, vitamin B₁₂ deficiency, or heavy metal toxicity, is unlikely to be helpful.²⁹ Additional testing simply to reassure a worried patient usually does not accomplish that objective.³³

Additional studies, referrals to consider. If you suspect that a patient has a sleep disorder, a referral to a sleep clinic to rule out idiopathic sleep disorders, obstructive sleep apnea, or movement disorders that interfere with sleep may be in order. Spirometry and echocardiography may be helpful for some patients. If you suspect peripheral muscle fatigue, a referral for neuromuscular testing is indicated.

CASE › Ms. C’s medical history reveals that she also suffers from irritable bowel syndrome, which she manages with diet and over-the-counter medication, as needed, for constipation or diarrhea. She denies having any other chronic conditions. Her only other symptoms, she reports, are mild upper back pain after spending long hours at the computer, and arthralgias in her left knee and both hands. She admits to being “somewhat depressed” in the last few months, but denies the presence of anhedonia.

The patient’s physical examination is normal, and her depression screen does not meet the criteria for MDD. Her metabolic chemistry panel, complete blood count, TSH, and sedimentation rate are all normal, as well.

Symptom management and coping strategies

When no specific cause of chronic fatigue is found, the focus shifts from diagnosis to symptom management and coping strategies.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.This requires engagement with the patient. It is important to acknowledge the existence of his or her symptoms and to reassure the patient that further investigation may be warranted later, should new symptoms emerge. Advise the patient, too, that periods of remission and relapse are likely.

Strategies designed to motivate patient self-management, as well as the formulation of patient-centered treatment plans, have been shown to reduce symptom scores.³⁴ Participation in a support group, as well as frequent follow-up visits with a primary care physician, a behavioral therapist, or both, may help to provide needed psychological support.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.³⁵ Exercise should be low intensity, such as walking or cycling for 30 minutes 3 times a week, with a gradual increase in duration and frequency over a period of weeks to months. Patients with cancer-related fatigue may benefit from yoga, group therapy, and stress management.³⁶

Associated mood and pain symptoms should be treated, as well. Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.