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Mycobacterium tuberculosis infection of a presumed Charcot joint.

Abstract: A 65-year-old male with peripheral neuropathy and small lymphocytic lymphoma presented with erythema and edema of the left foot. A Charcot midfoot was diagnosed and treated with a total contact cast and restricted weight bearing. However, subsequent analysis of bone and synovial fluid months later revealed Mycobacterium tuberculosis infection.

Key Words: Charcot, mycobacterium tuberculosis, neuropathic arthropathy, osteomyelitis


Mycobacterium tuberculosis (MTB) infection involving the foot is rare in developed countries, accounting for approximately 0.1 to 0.3% of all patients with extrapulmonary tuberculosis (TB). (4) The atypical site, lack of clinical suspicion, and ability of MTB to mimic other conditions leads to diagnostic and therapeutic delays. We describe a case of MTB infection of the foot in a patient initially diagnosed with Charcot joint.

Case Report

A 65-year-old male with stage IV small lymphocytic lymphoma presented with febrile neutropenia, cough, and 1 month of left lower extremity edema associated with 2 days of mild erythema. Two months prior, he completed fludarabine-based chemotherapy followed by high-dose prednisone. Other medical history included type 2 diabetes, severe peripheral neuropathy, and chronic pancytopenia. Examination revealed a febrile patient (38.4[degrees]C) with clear lungs and an unremarkable cardiac examination. The left foot demonstrated intact skin without ulceration, however, edema and mild erythema were noted over the medial aspect of the midfoot. The extremity was warm with brisk pulses and decreased sensation to light touch. Foot and ankle films showed no evidence of fracture or bony destruction. A left lower lobe infiltrate was present on chest radiography, prompting empiric therapy with levofloxacin for community-acquired pneumonia. Foot and ankle magnetic resonance imaging (MRI) showed marrow edema in the midfoot bones with soft tissue fluid collections. Infectious pathologies were considered; however, the clinical scenario was consistent with Charcot joint. The fever and neutropenia resolved, and he was discharged with a total contact cast and levofloxacin for community-acquired pneumonia. Two weeks later, the left lower extremity erythema had resolved, and the total contact cast was continued for presumed neuropathic joint with bimonthly evaluations.

At 4 months, a medial ulceration developed over the midfoot bony prominence that was followed clinically and did not appear infected. The following month, the patient reported increasing pain; examination showed subcutaneous fluid from the ulceration superior to the medial hindfoot and ankle. Aspiration revealed cloudy fluid. Irrigation, debridement, and external fixation were then performed. Synovial fluid demonstrated monosodiumurate crystals, and rhodamine-auramine stain showed acid-fast bacilli. Synovial fluid and bone cultures yielded MTB. Therapy was initiated with isoniazid, rifampin, pyrazinamide, and ethambutol. The patient reporteda distant history of a positive purified protein derivative, but never received latent TB treatment. Chest radiography was normal; however, chest computed tomography was consistent with miliary TB. Although sputum smears were negative, cultures grew MTB.


Bone and joint TB accounts for approximately 1% of all cases of TB in the United States. (3) Infection of the foot is rare, usually resulting from a granulomatous focus with insidious spread to adjacent joints. This can be disastrous in the midfoot because of the interconnection of multiple joints and may result in severe bony destruction and malformation. (4)

Bone and joint TB symptoms are often insidious, with an average time to diagnosis of 19 months. (1) The earliest symptom reported by patients is local pain. (3,9) Swelling and limitation of joint movement ensue but often precede systemic symptoms or radiographic changes by months. (9,11) Our patient did not have pain until 5 months after presentation, the acuity of which probably represented a gout attack rather than MTB infection.

Acute neuropathic arthropathy (ie, Charcot joint) presents with erythema, edema, and pain that mimics bone and joint MTB. Initially described in patients with tabes dorsalis, 92% of today's neuropathic joints are related to lower extremity diabetic neuropathy. (6) Sixty-five percent occur in the midfoot and frequently lead to ulceration and deformity. (6) With no specific confirmatory test and the necessity to eliminate infectious causes, neuropathic arthropathy is a clinical diagnosis of exclusion.

Radiographic characteristics of bone and joint TB are nonspecific. Severe osteoporosis is a hallmark during active disease, involving bones adjacent to the tuberculous focus. Joint space narrowing, subchondral cysts, and erosions may be seen after many months. Involvement of the entire midfoot may lead to collapse of the arch, similar to Charcot joint (Fig. 1). (4) MRI shows marrow edema in the predestructive phase, as early as six to twelve weeks after the onset of infection. (4) Computed tomography and MRI may also show cortical breaks, soft tissue collections, and cavitations can be seen at an early stage before they are evident on radiographs.


The diagnosis of bone and joint TB in developed countries can prove difficult because of its rarity and the absence of certain clinical indicators traditionally used to diagnose TB. For example, up to half of the cases of bone and joint TB have a negative chest radiograph. (1,3,7,9) Purified protein derivative testing is positive in up to 90% of patients; however, the incidence of bone and joint TB is higher in patients with advanced age, and there may be more frequent false-negative tests. (3,5,9) The definitive diagnosis of bone and joint TB involves isolation of the organism. Acid-fast bacilli stains and cultures of synovial fluid are positive in 20 and 80% of cases, respectively. (3) However, the gold standard remains synovial or bone biopsy, with a diagnostic yield of 90%. (1,3)

Diagnosis of MTB can be facilitated by precipitation of a gout attack. Although the coexistence of bone and joint TB and gout has been reported, the association between the two conditions is difficult to discern. Infection is a known precipitant of gout, causing local pH changes and cytokine release, which leads to deposition of microcrystals in the joint. (5) Alternatively, joints damaged by gout may be more prone to infection during hematogenous spread. (7)

An important risk factor in developing bone and joint MTB is an immune-compromised state, as evidenced by the recent resurgence of MTB in association with human immunodeficiency virus infection. (3) The patient in our case was immune-compromised from fludarabine chemotherapy followed by high-dose prednisone therapy. Fludarabine is a purine analog commonly used for chronic lymphocytic leukemia and other hematogenous tumors. A significant side effect is the development of opportunistic infections (OIs) caused by myelosuppression and lymphocytopenia, specifically CD4+ lymphocytes. (2,8,10) Byrd et al found 3.2% of patients had OIs during or after treatment with fludarabine. Of the 73 OIs. 3 were caused by MTB. (2) In addition, the risk of OI is increased when fludarabine therapy is combined with corticosteroids. (2,8,10) Although considerable improvement in CD4 count occurs within 3 months after discontinuation of therapy, quantitative abnormalities may persist for 1 to 2 years. (8)

Treatment of bone and joint TB involves multidrug therapy with the antituberculosis medications. The optimal treatment duration is unknown, but a prolonged course of therapy for a minimum of 12 to 18 months is generally recommended. (12) Acutely, MTB joints should be rested and immobilized followed by early and active mobilization. (3,11) Early diagnosis and vigorous treatment can accomplish healing without residual joint deformity. Surgery is reserved for correction of deformities and improvement of function in diseased joints. (3,11)


Bone and joint TB is uncommon in developed countries. However, the frequency may increase with the ongoing human immunodeficiency virus epidemic and the increasing use of drugs that alter cell-mediated immunity. Diagnosis usually requires culture of synovium or bone due to the low yield from synovial fluid. Importantly, the diagnosis is often delayed due to mimicry of other syndromes such as Charcot joint. As a result, a high index of suspicion is necessary to establish the diagnosis.


1. Boulware DW, Lopez M, Gum OB. Tuberculous podagra. JRheumatol 1985;12:1022-1024.

2. Byrd JC, Hargis JB, Kester KE, et al. Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis. Am J Hematol 1995;49:135-142.

3. Davidson PT, Quoc Le H. Musculoskeletal tuberculosis. In Schlossberg D (ed). Tuberculosis and Nontuberculosis Mycobacterial Infections. 4th edition. Philadelphia: WB Saunders Co, 1999, pp 204-220.

4. Dhillon MS, Nagi ON. Tuberculosis of the foot and ankle. Clin Orthop 2002;398:107-113.

5. Houdaille L, Prevot G, Ripault H, et al. Miliary tuberculosis with crystal deposition disease leading to a diagnosis of tuberculous arthritis. Joint Bone Spine 2002;69:338-340.

6. Krause JO, Brodsky JW. The natural history of type 1 midfoot neuropathic feet. Foot Ankle Clin 1997;2:1-22.

7. Lorenzo JP, Csuka ME, Derfus BA, et al. Concurrent gout and Mycobacterium tuberculosis arthritis. J Rheumatol 1997;24:184-186.

8. Morrison VA. The infectious complications of chronic lymphocytic leukemia. Semin Oncol 1998;25:98-106.

9. Muradali D, Gold WL, Vellend H, et al. Multifocal osteoarticular tuberculosis: report of four cases and review of management. Clin Infect Dis 1993;17:204-209.

10. Schriever F, Huhn D. New directions in the diagnosis and treatment of chronic lymphocytic leukaemia. Drugs 2003;63:953-969.

11. Tuli SM. General principles of osteoarticular tuberculosis. Clin Orthop 2002;398:11-19.

12. Watts HG, Lifeso RM. Tuberculosis of bones and joints. J Bone Joint Surg Am 1996;78:288-298.

Jason F. Okulicz, MD, Bradley A. Lloyd, MD, John O. Krause, MD, and Nicholas G. Conger, MD

From the Department of Internal Medicine, Department of Infectious Diseases, and Department of Orthopedics, Wilford Hall Medical Center, Lackland Air Force Base, Texas.

The views expressed herein are those of the authors and do not reflect the official policy of the Department of Defense, the United States Air Force, or other departments of the US government.

Reprint requests to Dr. Jason F. Okulicz, 2200 Bergquist Drive, Suite 1, Attn: MMIMR, Lackland AFB, TX 78236. Email:

Accepted April 1, 2005.


* Bone and joint tuberculosis is uncommon in the United States; however, the human immunodeficiency virus epidemic and the increasing use of drugs that alter cell-mediated immunity may lead to increased incidence.

* The diagnosis of bone and joint tuberculosis is often delayed because of the mimicry of other syndromes (such as Charcot joint) and may be facilitated by the precipitation of an acute gout attack.

* Early diagnosis is aided by a high degree of clinical suspicion, and prolonged medical treatment is necessary to prevent joint deformity.
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Title Annotation:Case Report
Author:Conger, Nicholas G.
Publication:Southern Medical Journal
Date:Sep 1, 2005
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