Fig. 32.1. A The gross specimen of part of the thoracolumbar spine of a patient with advanced brucellosis: there is widespread involvement of the vertebral bodies and the adjacent disc spaces. The granulomatous inflammatory reaction in the bone marrow extends through the cartilage and invades the intervertebral disc. There are focal areas of necrosis within the granulation tissue in several vertebrae. Later in the disease there is reactive bone repair and hypertrophic spur formation and eventually partial ankylosis may occur. B A different section showing similar central granulomas, early compression of several vertebrae, disc space involvement, and some focal areas of necrosis. AFIP 54-16439.

 

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The histological findings can vary with each Brucella organism and with the site of infection. Generally, dense inflammatory cells, including epitheloid cells and histiocytes, form granulomas, which are usually well circumscribed and may have a caseating center. Very rarely, and after many years, calcification may develop: differentiation from sarcoidosis can be difficult. Small granulomas occur in the bone marrow in up to 75% of patients. In the spleen there are granulomas and nodular lymphoid hyperplasia; in the gut there may be small mucosal ulcerations, bordered by granulation tissue. Renal involvement is uncommon, but immune-complex glomerulonephritis occurs. 20% of men with brucellosis will have orchitis, causing atrophy of the seminiferous tubules. There may be non-caseating granulomas in the liver, particularly early in the infection. Cirrhosis is unlikely, but Br. suis leads to foci of hepatic necrosis, in which calcium may be deposited. Abscesses occur, particularly in the lymph nodes and spine.

It is characteristic of brucellosis that, in the spine, the intervertebral discs are involved rapidly by granulomatous tissue starting from the bone marrow, extending through the trabeculae and cartilage, and invading the disc (Fig. 32.1). Bone repair occurs rapidly and the osteophytes which are seen radiologically are evidence of this. Brucellosis characteristically also involves the intradural nerves and nerve sheaths by hematogenous spread or through the meninges. The result can be adhesive arachnoiditis, not always demonstrable on myelography, but seen by computed tomography (CT) or magnetic resonance imaging (MRI). In the brain there may be vasculitis and neuronal necrosis, as well as meningitis and noncaseating granulomas.

Laboratory Diagnosis

The laboratory should be warned when specimens are sent with a suspected diagnosis of brucellosis to avoid accidental infection of the laboratory personnel.
It is not easy to culture any of the brucella: they are slow growing. Blood culture is useful, but needs 6 weeks' incubation; clot, and especially marrow culture, are also frequently used.

It takes 5 to 7 days for hypersensitivity to Brucella antigen to develop; the skin test thus becomes positive at the end of 7 to 10 days and may remain positive indefinitely. This is a highly specific test denoting exposure and infection with Brucella, but not necessarily indicating active disease; the exposure may have been in the past. False-positive results also occur. It is possible for some patients to have a negative skin test, particularly those who are critically ill, whereas in others there may be no immediate reaction to the intradermal injection, but induration may eventually appear 6 months or even longer afterwards.

In many parts of the world, brucellosis is common and, in such populations, the serum titers are usually below 1:100, whereas those with an active infection show a much higher titer, in excess of 1:300. Some laboratories consider any titer over 1:160 as indicative of an active state. After infection and cure, the level declines gradually and may fall below 1:100 after a year or more. Therapy with antibiotics does not interfere with the production of agglutinins nor does it alter the serum titers. Brucella agglutination is the most dependable single test for the diagnosis of brucellosis. Oomen and Waghela (1974) have described a simple, reliable variation - the rose-bengal plate test (RBPT) - utilizing stained and concentrated antigen acidified to inhibit nonspecific agglutinins. It detects IgG-1 antibodies and thus correlates with the activity of the infection. An ELISA is available, but needs special equipment.

The sedimentation rate is usually raised, but is nonspecific. The hemoglobin and red cell count remain normal; the total leukocyte count is either normal or reduced, and there is often a relative lymphocytosis. C-reactive protein is often present, but is only helpful as an indication of active disease. There may be a mild proteinuria.

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