A 41-year-old active duty U.S. Air Force enlisted man with a 3-week history of fevers, arthralgias, and myalgias

Military Medicine, Jan 2003 by Gilliland, William R

Case Management Study

Walter Reed Army Medical Center

A 41-year-old active duty male was transferred to Walter Reed Army Medical Center in Washington, DC, for further evaluation of fever, rash, myalgias, arthralgias, and respiratory failure. An extensive evaluation with input from numerous subspecialties of medicine was performed. The patient was eventually diagnosed with adult Still's disease, which is a diagnosis of exclusion. This case illustrates the importance of having a broad differential diagnosis when evaluating a patient with fever of unknown origin, with emphasis on the approach to young, active duty military personnel.

Introduction

A 41-year-old white male, active duty, U.S. Air Force E-5, stationed at McGuire Air Force Base, New Jersey, presented to the outpatient clinic with a 4-week illness that began with sore throat. After initially being treated with amoxicillin and ibuprofen for presumed bacterial pharyngitis, he presented again for care with the additional complaints of fever to 103deg.F, fatigue, arthralgias, and myalgias. He also noted a maculopapular rash on his chest, arms, and legs that began several days after amoxicillin was begun. He returned to the clinic 1 week later with continued symptoms as well as a new maculopapular rash. Evaluation with a monospot test and antistreptolysin 0 (ASO) titer was negative. One week later, he reported continued symptoms. Repeat testing with a monospot and ASO titer was again normal. His erythrocyte sedimentation rate (ESR) and C-reactive protein level were both elevated at 85 mm/hour (0-15 mm/hour) and 27.84 mg/dL (0.02-5.00 mg/dL), respectively.

1. Which of the following statements is true?

a. An elevated ESR indicates an underlying autoimmune connective tissue disease.

b. A negative monospot test rules out infection with Epstein-Barr virus.

c. A positive ASO titer would indicate the diagnosis of acute rheumatic fever.

d. Taking a good travel history is important in this patient.

e. This patient's high fevers indicate an infectious process.

The ESR often indicates the presence of an inflammatory process; however, it is a very nonspecific test. Extremely high levels can be seen in malignancies, infections, and collagenvascular disease. Additionally, as an individual ages, the ESR increases. A good rule-of-thumb for correcting an ESR for age is as follows: for men, the normal ESR is approximately age divided by 2; for women, the normal ESR is (age plus 10) divided by 2. In comparison, C-reactive protein levels are elevated very early (within 4-6 hours) in inflammatory processes and are more specific than the ESR because it is not affected by anemia, polycythemia, and macrocytosis. The monospot test and heterophil antibody tests are the most common screening tests used to detect infection with Epstein-Barr virus. They are negative in approximately 10% of adult patients who have infectious mononucleosis. Antibodies to various Epstein-Barr virus proteins, including viral capsid antigen, early antigen, and Epstein-Barr nuclear antigen are present in 100% of patients with mononucleosis. These additional antibody tests are ordered in patients who are heterophile antibody or monospot negative but in whom there is a strong clinical suspicion for infection with EpsteinBarr virus.I An increased ASO titer indicates a group A streptococcal infection within the past 2 months. The diagnosis of rheumatic fever requires objective proof of a preceding group A streptococcal infection (i.e., with either a positive throat culture or an elevated or rising ASO titer) in the setting of certain clinical manifestations. These clinical findings, known as the major Jones criteria, include carditis, polyarthritis, chorea, and erythema marginatum. Thus, the diagnosis cannot be made with a positive ASO titer alone. In this case, a normal ASO titer on two occasions makes a preceding group A streptococcal infection (and therefore acute rheumatic fever) unlikely.

A thorough travel history is important in any patient presenting with fever. In the active duty military population, this is essential as they are more likely to have traveled to uncommon geographic areas where atypical diseases are prevalent. Additionally, living and working in close quarters makes the spread of disease more likely. In this case, the patient had recently returned from Turkey, but none of his travel companions became ill. High fevers are not specific for infections. Many connective tissue diseases are associated with fevers, such as rheumatoid arthritis, systemic lupus erythematosus, vasculitis, and adult Still's disease.

Additional laboratory tests were also drawn and were unrevealing, including tests for viral illnesses (cytomegalovirus, parvovirus, and human immunodeficiency virus), tuberculosis, and connective tissue disease serologies (antinuclear antibody, antineutrophil cytoplasmic antibodies, and rheumatoid factor). The patient's condition was unchanged after a 3-day empiric course of azithromycin and he re-presented to a civilian emergency department with a fever of 104deg.F, an elevated white blood cell count of 27,000/mm3 (4,800-10,800/ mm3), and hypotension (systolic blood pressure, 90 mm Hg). Additional laboratory tests showed elevated liver-associated enzymes and a hematocrit of 22% (42-52%). Joint swelling was apparent in his wrists and elbows. He was admitted to the Intensive Care Unit with a diagnosis of sepsis, etiology unknown.