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Imaging Quiz Answer: Fever of Undetermined Origin in a Soldier

Carlos E. Jiménez, MD; Inku Hwang, MD



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Gallium scans (figure 2) demonstrated abnormally increased radiotracer uptake in the lacrimal, parotid, and submandibular glands. Also noted is abnormal bilateral uptake in the axillary and hilar lymph nodes. Finally, there was persistent abnormal uptake in the kidneys at 72 hours. Bilateral increased gallium 67 citrate uptake in the hilar lymph nodes and salivary glands represents a distinct pattern highly specific for the diagnosis of sarcoidosis.


A biopsy of the kidneys to evaluate the etiology of the patient's renal insufficiency confirmed the diagnosis of sarcoidosis with the presence of characteristic noncaseating granulomas.

Evaluating for FUO

Fever of undetermined origin (FUO) has been defined by Larson et al(1) as "febrile illness lasting more than 3 weeks with temperatures higher than 101°F (38.2°C), and with no source of fever found after 1 week of inpatient workup." In today's managed care environments, an intensive patient workup is usually done on an outpatient basis but would also span a 1-week period.

The evaluation of FUO is challenging for the physician because of the extensive differential diagnosis involving multiple tests. Frequent causes include chronic infections, neoplasms, connective tissue disorders, drug reactions, and granulomatous diseases. Review of the literature indicates that infections and neoplasms account for as much as two thirds of all cases of FUO. Among young adult, nonimmunocompromised patients who do not have significant travel or surgical histories, the most likely causes of FUO are mycobacterium infections, viral infections (including cytomegalovirus and Epstein-Barr virus), lymphoma, and sarcoidosis.

Identifying Sarcoidosis

Sarcoidosis is a systemic disease of unknown etiology characterized by noncaseating granulomas. It can involve many organs including the lungs, eyes, salivary glands, lymph nodes, skin, joints, liver, central nervous system, and kidneys. Most of the dysfunction associated with sarcoidosis is a result of granulomatous infiltration of the affected organs and the resulting inflammatory response. The disease occurs most frequently in adults aged 20 to 40, and is more common and severe in the black population.

Presenting symptoms of sarcoidosis vary considerably. Approximately a third of patients who are eventually diagnosed with sarcoidosis present with the complaints of dyspnea and nonproductive cough. Systemic symptoms such as fatigue, fever, and malaise are found in another third of the patients, and the remainder of patients are asymptomatic on initial presentation. In the asymptomatic patients, the condition is discovered because of an incidental finding on an imaging study (2).

A biopsy is generally performed on the most accessible abnormal organ. Noncaseating granulomas in the tissues of a patient who has clinical and/or radiologic findings consistent with sarcoidosis will help to confirm the diagnosis. As sarcoidosis is a diagnosis of exclusion, other causes of granulomas such as neoplastic, fungal, and mycobacterial diseases should be ruled out (3). On rare occasions, these other granulomatous diseases can mimic sarcoidosis when a biopsy alone, without further studies, is obtained.

Using Gallium Imaging

Gallium imaging is regarded by many experts as the most sensitive test in the evaluation of FUO, since it can reveal tumors as well as chronic granulomatous and indolent infections. Gallium 67 citrate is a radioactive iron analogue that localizes at sites of inflammation or infection by binding to serum lactoferrin, an iron-binding protein released in large amounts by the active chemotactic neutrophils that localize in areas of inflammation. Gallium is also known to bind to certain tumor cell surfaces that exhibit iron-binding protein receptors, such as lymphomas, hepatomas, and sarcomas.

For optimal tissue-to-background ratio, gallium imaging is usually performed 72 hours after injection. Normal sites of tracer biodistribution include the liver, spleen, and bone marrow. Mild salivary gland uptake can also be seen. In sarcoidosis, characteristic scintigraphic gallium findings are often detected long before they can be seen in other radiologic studies. Abnormal uptake is most often seen in the hilar lymph nodes or pulmonary parenchyma or both. Paratracheal and hilar lymph node uptake (figure 2) in a pattern resembling the Greek letter lambda (not shown) is referred to as the "lambda sign." Prominent gallium uptake is also frequently observed in the parotid, salivary, and lacrimal glands, and is called the "panda sign" because of its resemblance to the face of the panda bear. The simultaneous presence of the lambda and panda signs on gallium imaging is highly specific for sarcoidosis (4).

There are three main clinical uses for gallium imaging in sarcoidosis: It can be used to distinguish between active sarcoidosis and fibrotic changes in post-therapy patients; it is ideal for whole-body evaluation and can localize nonpulmonary sites of disease activity; and, although a gallium scan is not needed in classic presentations of sarcoidosis, it can be an important diag Inostic tool in atypical cases in which the diagnosis is uncertain. It can be especially helpful in asymptomatic patients, as well as in patients who present with nonspecific systemic symptoms. In this patient, a gallium scan was ordered because of the lack of radiographic findings.


Corticosteroids are the main treatment for sarcoidosis, but treatment is usually reserved for patients who have progressive pulmonary disease or clinically significant extrapulmonary involvement. In the absence of severe incapacitating disease, the majority of patients may be monitored without pharmacotherapy, as spontaneous remission is common. Relapses following spontaneous remissions are uncommon (2).

Because of worsening renal insufficiency, the patient was treated with 40 mg of prednisone daily for the first few weeks, with a dramatic improvement in both his symptoms and his renal function. Over the next few months, corticosteroid dosage was tapered off, and the patient has remained in remission since that time.


  1. Larson EB, Featherstone HJ, Petersdorf RG: Fever of undetermined origin: diagnosis and follow-up of 105 cases. Medicine (Baltimore) 1982;61(5):269-292
  2. Bascom R, Johns CJ: The natural history and management of sarcoidosis. Adv Intern Med 1986;31:213-220
  3. Crystal RG: Sarcoidosis, in Wilson JD et al (eds): Harrison's Principles of Internal Medicine, ed 12. New York City, McGraw-Hill, Inc, 1991, pp 1463-1469
  4. Sulavik SB, Spencer RP, Weed DA, et al: Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis. J Nucl Med 1990;31(12):1909-1914

The opinions or assertions presented here are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or Department of Defense.

Dr Jiménez is a staff physician and Dr Hwang is a first-year fellow in the nuclear medicine service in the department of radiology at Walter Reed Army Medical Center in Washington, DC. They are members of the Society of Nuclear Medicine. Address correspondence to Carlos E. Jiménez, MD, Nuclear Medicine Service, Dept of Radiology, Walter Reed Army Medical Center, 6825 16th St NW, Washington, DC 20307-5001; e-mail to [email protected], or link to e-mail via the nuclear medicine service website at



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