Brucella Osteomyelitis of the Proximal Tibia

Abstract

Brucellosis is a disease of domestic and wild animals that is transmittable to humans. Although endemic in some parts of the world, brucellosis is an uncommon human pathogen in the United States. The clinical presentation of brucellosis is nonspecific, and brucella osteomyelitis can produce lytic lesions on radiographs that resemble neoplasm. Diagnosis can therefore be difficult unless a high index of suspicion is maintained. We present a case of brucella osteomyelitis of the proximal tibia that demonstrates these features.

CASE REPORT

A 79-year-old livestock farmer presented to the Veterans' Administration Medial Center orthopaedic clinic with a chief complaint of right knee pain. The pain had begun several months prior to the clinic visit and was described as a constant, dull ache made worse with weightbearing. The patient denied any history of trauma, constitutional symptoms, or other arthralgias. His health was otherwise poor, suffering from unstable angina, congestive heart failure, insulin-dependent diabetes mellitus, and chronic renal insufficiency.

Examination revealed a normal appearing knee with no effusion, no joint line tenderness, and full range of motion without instability. The proximal tibia was tender to palpation circumferentially. Radiographs and computed tomography scanning revealed an expansile, well corticated, lytic lesion in the metaphysis of the proximal tibia and mild tricompartimental degenerative changes in the knee (Figures 1a-c). Additional work-up revealed a microcytic anemia with a normal white blood cell count and a normal urine-protein analysis. A chest radiograph was negative for focal lesions. Open biopsy of the proximal tibia was planned for definitive diagnosis.

Figure 1a-c.

A, B: AP and lateral views of the right knee show an expansile, lytic lesion in the proximal tibial metaphysis. C: An axial CT image of the proximal tibia demonstrates no fractures or cortical defects.

Figure 1A.

Figure 1B.

Figure 1C.

Soon after his presentation in clinic however, the patient suffered a myocardial infarction and his health rapidly declined, disallowing any surgical intervention. The ensuing 18 months were punctuated by numerous hospital admissions for cardiopulmonary disease and transient ischemic attacks. The internal medicine and cardiology services felt that the patient was too unstable to undergo any surgical procedure. Meanwhile, the knee pain progressed, rendering the patient unable to ambulate. Even at rest, the pain could not be controlled with narcotic pain medication. Repeat radiographs revealed enlargement of the lesion but no fractures. The patient stated that he was contemplating suicide because of the incapacitating pain. After intense discussion with the patient and his family, the high risk of surgical intervention was accepted and excision and curettage of the lesion was scheduled.

Under a regional anesthetic, an incision was made on the anteromedial leg 3 cm distal to the joint line. Upon penetration of the deep fascia, copious amounts of thick, yellow fluid were encountered flowing through a 2 cm by 2 cm defect in the anterior cortex of the tibia. The fluid filled the entire proximal metaphysis. Tissue samples were obtained and sent to the microbiology and pathology labs for analysis. All necrotic and friable tissue was removed, and the wound was irrigated with several liters of saline. The cavity was then filled with tobramycin-impregnated methylmethacralate.

Staining revealed small Gram-negative rods that were urease-positive (Figure 2), and cultures grew Brucella suis. Histopathology was remarkable only for necrotic bone without evidence of neoplasm. The patient's knee pain was nearly completely gone immediately post-operatively and he recovered without any medical complications. Consultation with the infectious disease service was obtained, and the patient was treated with a 3-month course of oral doxycycline and rifampin.

Figure 2.

Gram-negative rods seen on a plate smear from sheep blood agar after 72 hours of incubation, computer-photographed at 1000X.

DISCUSSION

Brucellae are small, gram-negative coccobacilli that can be found worldwide.¹ At least six species have been identified, four of which can cause human disease.² In animals, brucellosis is a chronic infection that causes abortion and sterility; common carriers include cows, sheep, pigs, and dogs. Brucellosis in humans is thought to always derive from exposure to infected animals through ingestion of unpasteurized dairy products, inhalation of aerosolized bacteria, or from direct contact with contaminated animals through contaminated skin or conjunctiva. Upon entry into the body, the pathogens enter the lymphatic system and replicate in regional lymph nodes. Brucellae are facultative intracellular pathogens that have the capacity to survive within the phagocytic cells of the host. Hematogenous dissemination is often followed by bacteria taking residence in organs rich in cells of the reticuloendothelial system, such as the liver, spleen, and bone marrow.¹

The clinical features of brucellosis infection vary and are nonspecific. Constitutional symptoms including fevers, sweats, weight loss, and anorexia may be acute or insidious in onset. More focal symptoms and physical exam findings reflect which organ or organ systems are affected. Gastrointestinal and hepatobiliary involvement is commonly noted, afflicting up to 70% of patients with brucellosis. Endocarditis occurs in less than 2% of cases, but accounts for the majority of brucellosis-related deaths.¹ In a series of 21 children affected with brucellosis, fever (91%), arthralgias or arthritis (83%), and hepato-and/or splenomegaly (63%) were the most common clinical manifestations.³ Skeletal complications are reported in the majority of cases and include arthritis, spondlylitis, osteomyelitis, tenosynovitis, and bursitis.¹ Brucellosis may affect the joints of the appendicular skeleton as either an infective monoarticular arthritis where the pathogen is isolated from the synovial fluid, or as a reactive arthritis with polyarticular involvement where no organism is isolated.⁴ Overall, the sacroiliac articulation is the most commonly reported site of involvement.^2,5

As the history and physical are nonspecific, diagnosis is usually difficult. Laboratory tests often reveal only subtle abnormalities such as mild elevation in inflammatory markers. Liver enzymes may be elevated.³ Radiographic changes are also nonspecific, with findings often mimicking slow growing neoplasms such as giant cell tumor or multiple myeloma. The presence of high or rising specific antibodies can support a presumptive diagnosis, but definitive diagnosis is made only when the pathogen is isolated from tissue.¹ Treatment is generally at least 6 weeks of dual agent antibiotic therapy.^1–3 Relapses are not uncommon, and chronic infection can result from persisting suppurative lesions in the bones, liver, spleen or kidneys.^1,3

A number of cases of human brucellosis have been reported in the literature, most from countries other than the United States. The axial skeleton is most commonly affected^6–11; other reported sites include the carpus¹², pubis¹³, femur^14,15, and the calcaneus¹⁶. Multifocal brucella osteomyelitis involving both tibias and a humerus has also been reported.¹⁷ Most patients were diagnosed only after months or years of symptoms, suggesting insufficient awareness of the disease.

Although uncommon, brucellosis should be regarded as a potential cause of musculoskeletal disease in a patient with exposure to animals.