MKSAP Quiz: Periodic fever over the past 3 months

A 43-year-old man is seen in follow-up for fever up to 38.3 °C (101 °F) occurring periodically over the past 3 months. He has no associated symptoms other than fatigue. Following a physical exam, lab studies, and other tests, what is the most appropriate diagnostic test to perform next?


A 43-year-old man is seen in follow-up for fever up to 38.3 °C (101 °F) occurring periodically over the past 3 months. He has no associated symptoms other than fatigue. He reports no recent travel, animal exposures, or tick or insect bites. He does not eat raw meats, raw seafood, or unpasteurized dairy products. He returns for further evaluation after initial testing. Family history is negative for undiagnosed fevers. He takes no medications.

On physical examination, temperature is 37.8 °C (100.1 °F), blood pressure is 114/72 mm Hg, pulse rate is 88/min, and respiration rate is 14/min. A complete physical examination is unremarkable.

Laboratory studies:

Erythrocyte sedimentation rate 10 mm/h
Hematocrit 44%
Leukocyte count 4200/µL (4.2 × 109/L) with a normal differential
Platelet count 320,000/µL (320 × 109/L)
Alkaline phosphatase Normal
Lactate dehydrogenase Normal
Kidney and liver chemistry tests Normal
Urinalysis Normal

HIV testing is negative. An interferon-γ release assay for tuberculosis is negative. Three sets of blood cultures are negative.

A chest radiograph is normal.

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

A. Bone marrow biopsy
B. CT of the abdomen and pelvis
C. Liver biopsy
D. Lumbar puncture


MKSAP Answer and Critique

The correct answer is B. CT of the abdomen and pelvis. This content is available to MKSAP 18 subscribers as Question 5 in the Infectious Disease section. More information about MKSAP is available online.

The most appropriate diagnostic test in this patient is CT of the abdomen and pelvis. He meets the criteria for classic fever of unknown origin, which is defined by fever of 38.3 °C (100.9 °F) or greater for 3 or more weeks that remains undiagnosed after two visits in the ambulatory setting. Taking a careful, detailed history is the starting point in evaluating a patient with fever of unknown cause. The history may need to be repeated on subsequent visits because subtle clues may be revealed only later. All symptoms should be considered relevant. A history of comorbid conditions and a surgical, obstetric or gynecologic (in women), medication, travel, and social history should be elicited followed by a careful physical examination that includes full neurologic, musculoskeletal, ear-nose-throat, eye or funduscopic, skin, lymphatic, and urogenital examinations. The results of basic laboratory and imaging studies along with the history and physical examination findings are used to guide further evaluation. In this patient, the initial evaluation for infectious causes (tuberculosis, endocarditis, urinary tract infection), neoplasms (lymphoma, leukemia), and connective tissue disease is unrevealing. Therefore, the patient should undergo CT of the abdomen and pelvis (with and without contrast) to evaluate for abscess, neoplasm (hepatoma, renal cell carcinoma), splenomegaly, and lymphadenopathy. The prognosis is good for adults who remain undiagnosed after extensive evaluation.

Bone marrow biopsy is generally considered when the complete blood count is abnormal and a process involving the bone marrow (such as tuberculosis, histoplasmosis, or malignancy) is evident.

Liver biopsy is considered in the setting of abnormal liver chemistry tests and a suggested abnormality on imaging. It would not be appropriate at this time.

If signs or symptoms referable to the central nervous system are evident, imaging of the head and lumbar puncture should be considered. However, this patient has no central nervous system findings.

Key Point

  • Initial studies for fever of unknown origin in most patients typically include a complete blood count with differential, complete metabolic profile with kidney and liver studies, at least three blood culture sets and cultures of other bodily fluids (such as urine or from other sources based on clinical suspicion), an erythrocyte sedimentation rate, tuberculosis testing, and serology for HIV; it is reasonable to perform chest imaging (radiography or CT) as initial diagnostic imaging.