False negative serological tests may lead to misdiagnosis and mismanagement in osteoarticular brucellosis

Introduction

Osteoarticular involvement is the most common complication of brucellosis – it is estimated that it occurs in 10–85% of patients. ¹ Peripheral arthritis, especially presenting as monoarthritis, has been reported in some brucellosis series, and large joints, such as hip, knee and ankle, are the most frequently affected and may mimic other causes of arthritis. ^2–4 The spinal column is one of the most frequently affected sites (2–54%) in osteoarticular brucellosis with clinical manifestation of spondylitis, discitis, spondylodiscitis, epidural abscess, paraspinal abscess and vertebral collapse. ^5,6

Surgical intervention is reported to be indicated in 1.2–12% of brucellosis cases with osteoarticular complication. ⁴ The intervention may be required in order to drain pyogenic joint effusions or because of arthritis accompanied with adjacent bone osteomyelitis. Mehmet Faruk Geyik et al., from Turkey, reported on two females with arthritis of the hip who had osteomylitis of the adjacent proximal end of the femur; in decompression, debridement and drainage of the hip joint were necessary. ⁷

Diagnostic or curative surgery can be performed in spinal brucellosis. ⁸ Surgical intervention may be necessary for patients with spinal brucellosis who have severe neurological deficits and incapacitating back pains in order to stabilize the spine and relieve the neurological compression. ^5,9 Emine Alp et al. reported that eight (25.8%) of his 31 patients who had spinal brucellosis underwent surgical intervention. ¹⁰

Clinical presentations and para-clinical findings in osteoarticular brucellosis can be non-specific and may mimic many other diseases and other causes of arthritis. ^2–4 There is, therefore, a possibility of misdiagnosis and mismanagement in such cases. The purpose of this study was to determine the amount of misdiagnosis and inappropriate surgical interventions in osteoarticular brucellosis due to seronegative test for brucellosis in our three hospitals.

Patients and methods

The records of 232 patients with brucellosis with osteoarticular involvement who had attended the three teaching hospitals (Shahid Beheshti, Shahid Yahyanejad and Amirkola Children's Hospitals) of the Babol Medical Sciences University between April 2001 to September 2006 were evaluated. These hospitals serve a population of more than two million people living in the province of Mazandaran in the north of Iran.

The diagnosis of brucellosis was established by demonstrating a brucella titre of ≥1:320 in a standard tube agglutination test (STAT) and a titre of 1:160 in 2- mercaptoethanol (2-ME) for patients with clinical signs and symptoms compatible with brucellosis. Peripheral arthritis was diagnosed by the finding of tenderness, swelling, effusion and restriction of motion in any peripheral joint or by unrelieved pain at rest together with serologic findings compatible with brucellosis. Spondylitis was diagnosed with the presence of back pain and characteristic findings on X-ray (epiphysitis of anterosuperior angle of the vertebra, narrowing of the disc space, erosion, sclerosis, vertebral collapse and osteomylitis), magnetic resonance imaging (MRI) and serologic findings compatible with brucellosis. Sacroiliitis was established clinically through either the Faber test or by direct pelvic compression and by using X-ray in the prone position with regard to characteristic changes (poorly defined subchondral osseous line, narrowing or widening of the interosseous line and narrowing or widening of interosseous space) and confirmed with serologic findings compatible with brucellosis.

Among the investigated subjects, there were cases of hip arthritis with: negative serological tests for brucellosis in initial evaluation; negative blood culture for brucellosis; hyperleucocytosis; and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). These cases with a diagnosis of septic arthritis were operated upon. Because of the failure of surgery, serological re-evaluation for brucellosis was performed and a diagnosis of brucellosis was confirmed. There was also one case with severe back pain and a seronegative test for brucellosis in the initial evaluation and clinical and MRI findings consistent with intervertebral disk herniation. This case underwent surgery. With continuing clinical symptoms and signs, in this case serological tests for brucellosis were repeated and the presence of brucellosis was established. All of these misdiagnosed and inappropriately operated upon cases were treated medically and cured uneventfully.

Results

Of 232 cases, 138 (59%) were male with the mean age of 32.7 ± 15 years and 94 (41%) were female with the mean age of 35.2 ± 16 years. The frequency of distribution and patterns of treatment of patients are detailed in Table 1. Polyarthritis, monoarthritis, sacroiliitis and spondylitis were seen in 91 (39%), 60 (26%), 38 (16.5%) and 43 (18.5%) cases, respectively. Of the cases with poly-arthritis and sacroiliitis, 58 (96.7%) cases of monoarthritis and 42(97.7%) of spondylitis were treated medically and recovered (98.7%). Two cases of monoarthritis (hip joint) and one case of spondylitis (1.3%) were misdiagnosed due to a false negative serologic test in the initial evaluation and underwent inappropriate surgery.

Discussion

We report misdiagnosis and inappropriate surgical intervention in osteoarticular brucellosis due to false negative serologic tests for brucellosis in an endemic region of brucellosis. Brucellosis may be overlooked and misdiagnosed because of the difficulty of diagnosis and an absence or lack of experience with laboratory testing. ¹¹ Clinical presentations of brucellar arthritis may be non-specific and may mimic other causes of arthritis. ^2–4 In spondylitis the similarity between a clinical manifestation of disc disorder and brucellar involvement of spine may be considered as the cause of misdiagnosis. Tur et al. and Kilik et al. found spinal brucellosis may mimic intervertebral disk herniation. ^12–14 Misdiagnosis of spinal brucellosis as disk herniation due to non-specific and variable clinical, radiological, computerized tomography (CT) and MRI findings were also reported. ^15–18

A seronegative test for brucellosis in the presence of brucellosis has been previously reported. ^19,20 A case with brucellar spondylodiscitis was reported that had a negative Rose-Bengal test for brucellosis in the initial evaluation and returned as a positive later. ¹⁶ Seronegative tests for brucellosis occur when there is an excess of the titre of antibody (prozone). It was also been reported that blood cultures do not always yield a positive result for brucellosis. ^21,22

In the present study, misdiagnosis and inappropriate surgical intervention occurred in cases with negative blood cultures and seronegative tests for brucellosis with clinical and paraclinical findings compatible with septic arthritis and intervertebral disc herniation. In monoarthritis cases, misdiagnosis and mismanagement involved the hip joint. The hip is a deep joint and open arthrotomy is recommended as an initial approach in septic arthritis of this joint because delay in decompression and drainage may cause dangerous complications. ^23–25

In conclusion, misdiagnosis and mismanagement may happen in osteoarticular brucellosis due to non-specific clinical, radiological, CT and MRI findings, negative blood culture and false seronegative tests for brucellosis. In the current study we present misdiagnoses and inappropriate surgical interventions in osteoarticular brucellosis due to false negative serologic tests for brucellosis in a brucellosis endemic region.