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MKSAP Quiz: 1-year history of fatigue, headaches, sore throat

A 36-year-old man is evaluated for a 1-year history of fatigue, intermittent headaches, sore throat, and joint and muscle pain. He reports no difficulties falling asleep and gets 10 hours of uninterrupted but nonrestorative sleep each night. HIV testing and risk factors are negative. On physical examination, the patient appears anxious. Vital signs and the remainder of the physical examination are normal. The patient's evaluation for sleep disorders is normal. A screening test for depression is negative. What is the most appropriate diagnostic test to perform next?


A 36-year-old man is evaluated for a 1-year history of fatigue, intermittent headaches, sore throat, and joint and muscle pain. He reports no difficulties falling asleep and gets 10 hours of uninterrupted but nonrestorative sleep each night. He has seen several physicians over the past year. Evaluation has included a complete blood count with differential, thyroid-stimulating hormone level, and plasma glucose level that were normal at the time of initial presentation and again 2 months ago. HIV testing performed 4 months ago was negative. He is in a monogamous heterosexual relationship, and there is no history of blood transfusions or injection drug use. Medical history is otherwise unremarkable. Family history is significant for depression and type 2 diabetes mellitus. He takes no medications.

On physical examination, the patient appears anxious. Vital signs and the remainder of the physical examination are normal. The patient's evaluation for sleep disorders is normal. A screening test for depression is negative.

Which of the following is the most appropriate diagnostic test to perform next?

A. Epstein-Barr virus titer
B. Lyme disease titer
C. Repeat HIV testing
D. No further testing

Reveal the Answer

MKSAP Answer and Critique

The correct answer is D. No further testing. This item is available to MKSAP 17 subscribers as item 157 in the General Internal Medicine section. More information is available online.

No further testing is indicated in this patient who meets the clinical criteria for systemic exertion intolerance disease (SEID), previously termed chronic fatigue syndrome. He has fatigue that has persisted for more than 6 months that is not due to exertion and is not relieved by adequate sleep. He also experiences unrefreshing sleep, muscle pain, joint pain without synovitis, headaches, and recurring sore throat.

There is no specific objective laboratory test to diagnose SEID, and since the presenting symptoms are nonspecific, it remains a diagnosis of exclusion. Recommended value-based screening tests include complete blood count, glucose levels, and thyroid function tests. If indicated by the history and physical examination, electrolytes, calcium level, serum creatinine level, hepatic enzyme levels, liver chemistry tests, and antinuclear antibody test may be performed. This patient has undergone evaluation for underlying medical conditions in which fatigue is a common symptom, and all test results were normal. At present, no further testing is indicated, and attention should be directed to management with either graded exercise or cognitive-behavioral therapy.

Although Lyme disease and Epstein-Barr virus have been implicated in the development of SEID, no single infectious cause has been definitively linked. An Epstein-Barr virus titer would not be indicated, as this test is nondiagnostic and not value based. Additionally, antiviral treatment has been shown to be ineffective. Lyme disease testing is also unwarranted because this patient's nonspecific symptoms are not consistent with Lyme disease. Additionally, the pretest probability of Lyme disease is low, and testing for Lyme antibodies is not recommended by the American College of Rheumatology.

Repeat HIV testing in this patient would be low value care. He had a recent negative HIV test and has not had high-risk exposure since that time.

Key Point

  • There is no specific objective laboratory test to diagnose systemic exertion intolerance disease (formerly known as chronic fatigue syndrome); recommended value-based tests to rule out this disease include complete blood count, glucose level, and thyroid function tests.