| April 1, 2006 | CONTACT AUTHOR
Please address all correspondence to: Victoria Bengualid, MD Department of Medicine 7th floor St. Barnabas Hospital 183rd Street and 3rd Avenue Bronx, NY 10457 vbengualid@pol.net
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Victoria Bengualid, MD and Judith Berger, MD
Keywords: osteoarticular tuberculosis, paradoxical reaction
A 25-year-old man, HIV negative, from Ecuador presents with a history of two months of fever, weight loss, pain and swelling of his right knee, left wrist, left elbow and right finger. A wrist biopsy was done which showed necrotizing granulomas, AFB positive. Cultures grew M. tuberculosis. The patient was started on treatment with four tuberculosis medications.
Despite four weeks of treatment, his symptoms worsened with new lesions developing in the right clavicle and rib. A total body gallium scan showed uptake not only in the lesions that were symptomatic (right knee, left wrist, right finger, left elbow, right clavicle and rib) but in multiple other areas; in the right and left ribs, right neck, left shoulder, right hilum and mediastinum, mid thoracic spine and lumber spine, periorbital areas, both ankles and proximal feet and right wrist, and lower tibia (figure 1).
Figure 1


His right finger developed a draining sinus tract, x-ray revealed a dislocation of the 2nd metacarpal phalangeal joint, a destructive lesion in the head of the 2nd and 5th metacarpal (figure 2). Because of complaints of headaches, a head CT and LP were done. The LP was negative, but an 8 mm lesion was noted in the posterior right temporal lobe.
Figure 2

Because of progression of his symptoms despite six weeks of therapy, he had a biopsy of the clavicular lesion. The biopsy revealed non-caseating granulomatus osteomyelitits. AFB smear and cultures were negative. Sensitivities on his initial isolate showed a pan-sensitive Mycobacteria. Two weeks after the sternal biopsy his symptoms improved. A repeat gallium scan showed decreased or resolution of activity in multiples lesions. One year later he was clinically and radiographically cured.
Osteoarticular involvement is a rare complication of disseminated tuberculosis. Many patients have evidence of pulmonary involvement1. This patient’s chest x-ray showed bilateral pleural thickening. Multifocal involvement (2 or more sites) is even less frequent, ranging from 0-1% of patients with osteoarticular involvement2-6. Presence of more than 15 lesions (as in this case) is extremely unusual.
Response to antituberculus therapy is excellent in these patients. Therefore this patient’s initial lack of response and progression of lesions was felt to be due to a “paradoxical response” to treatment. This has been described in patients with intracranial lesions or meningitis, or lymph node involvement7-10. Other cases have been reported in a patient with an abdominal lesion11-12, and a patient with pulmonary lesions13. It has also been described in HIV positive patients at the time of initiation of HAART therapy14-16.
The paradoxical response is defined as patients who have worsening of their symptoms on appropriate antitubercular medications. In a study by Cheng et al17, they determined that the median time to develop the paradoxical response after initiation of treatment is 56 days. In addition, patients with disseminated symptoms were more likely to develop this response (62.5% vs 17.0%). Both of these findings were present in our patient. Other studies have shown that the paradoxical reaction occurs more commonly in HIV positive than HIV negative patients (36% vs2%)16. This often correlates with the initiation of highly active anti-retroviral therapy as opposed to the initiation of TB therapy16.