Last updated: November 6, 2014

Synonyms: Undulant fever, Malta fever.

ICD-9 Code: 023;
ICD-10 Code: A23

Definition: Systemic infection with Brucella is uncommon and may cause fever, peripheral arthritis, sacroiliitis, or spondylitis.

Etiopathogenesis: Humans may acquire Brucella by ingesting infected unpasteurized dairy products (e.g., cheese), exposure to aerosolized bacteria, or contact with broken skin or conjunctiva. Brucella is a gram-negative coccobacillus. Brucella arthritis is usually caused by direct seeding of the synovium. Some cases appear to be “reactive” (i.e., not caused by direct infection). Brucella septic arthritis is usually monarticular or axial, is persistent, and requires antibiotic therapy. The reactive arthritis is usually intermittent, self-limited, sterile, nondestructive, and polyarticular.

Demographics: Brucella has a worldwide distribution. Most cases are reported from South America. Brucella spp include Brucella abortus (zoonotic source, cow), Brucella melitensis (goat), and Brucella suis (pig). Although B. abortus is most common in the United States, B. melitensis is most common worldwide. Infection occurs at all ages and in both genders. Those at risk include veterinarians, farm and slaughterhouse workers, and persons ingesting unpasteurized milk or cheese.

Cardinal Findings: Acute infection is associated with bacteremia and may show fever (101°–104°F), arthralgias, headache, or malaise. Fever, diaphoresis, and weight loss may be undulant. Hepatosplenomegaly and uveitis are common. In the subacute form, fever is less common. Acute peripheral arthritis of the lower extremities (e.g., hip or knee) is common. Arthralgias and myalgias are seen in more than half of patients. Sacroiliitis is usually unilateral and nondestructive. Spondylitis commonly affects the lumbar spine.

Uncommon Findings: Lymphadenopathy, pulmonary symptoms, orchitis, tendinitis, bursitis, and epicondylitis.

Complications: Local microabscesses (i.e., paraspinal abscess often manifesting as antibiotic resistance), endocarditis, thrombophlebitis, hepatitis, and CNS infection may occur.

Diagnostic Tests: Routine laboratory testing may show leukopenia, relative lymphocytosis, thrombocytopenia, or abnormal hepatic enzymes. Culture of organism from joint fluid is slow (3–4 weeks) and is positive in <50% of samples. Bone marrow culture may improve culture yield or show granulomas. Serologic tests (ELISA or agglutination reaction) for IgM or IgG (chronic) anti- Brucella antibody are usually positive.

Imaging: Sacroiliitis appears as blurring of articular margins of the sacroiliac joints, seldom with erosions. Spondylitis appears as intervertebral erosions, disc narrowing, and reactive osteophytes with a “parrot-beak” appearance. Scintigraphy may be useful in identifying spondylitis or sacroiliitis.

Keys to Diagnosis: Bacteriologic or serologic evidence of infection signals the diagnosis, which requires a high index of suspicion, especially in the at-risk population.

Differential Diagnosis: Spondyloarthropathies, septic arthritis, psittacosis, tuberculosis, human immunodeficiency virus (HIV), and rickettsial infections must be considered.

Therapy: At least 4 to 6 weeks of combination antibiotic therapy with tetracycline (doxycycline) plus a second agent (rifampin, streptomycin, or trimethoprim) is effective in most.

Monitoring: Clinical response and serum antibody levels should be monitored for a year after treatment.

Prognosis: Most patients do very well. The relapse rate is 5%. Mortality is rare and usually owing to endocarditis.

Colmenero J, Reguera JM, Fernandez-Nebro A, et al. Osteoarticular complications of brucellosis. Ann Rheum Dis 1991;50:23–26. PMID:1994863
Zaks N, Sukenik S, Alkan M, et al. Musculoskeletal manifestations of brucellosis: a study of 90 cases in Israel. Semin Arthritis Rheum 1995;25:97–102. PMID:8578316

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