Isolated tuberculous osteomyelitis of the wrist: A case report

Abstract

Extrapulmonary tuberculosis is an infection by Mycobacterium tuberculosis (MTB) involving any organ besides the lungs. Rarely, tuberculosis (TB) can infect the bones and joints, which accounts for only 1%-5% of total TB cases in Europe and the United States. In this case report, we present a 29-year-old man with history of gout who presented with chronic left wrist pain. Imaging demonstrated synovitis and erosive arthritis of the distal radius, ulna, and carpal bones. An initial synovial biopsy showed granulomatous inflammation but mycobacteria were not detected by microscopic examination or broad-spectrum polymerase chain reaction (PCR). Seven months later, a repeat bone biopsy showed TB osteomyelitis. The patient was then treated with anti-tuberculous therapy. Notably, imaging findings included the “penumbra sign,” a highly specific feature seen on magnetic resonance imaging for subacute osteomyelitis. This case illustrates the challenges in diagnosing extrapulmonary TB osteomyelitis.

Introduction

Extrapulmonary tuberculosis (EPTB) is an uncommon manifestation of Mycobacterium tuberculosis (MTB) infection. In 2023, there were 8.2 million new cases of tuberculosis (TB) globally, of which 6.9 million were pulmonary and 1.3 million extrapulmonary [1]. Bone and joint TB is an even rarer manifestation of EPTB, comprising only 1%-5% of total TB cases in developed countries and 10%-15% of EPTB cases [2,3].

The diagnosis of EPTB is challenging due to the paucibacillary nature of the organism and limited diagnostic accessibility, which can make sampling for diagnostic tests challenging [4]. TB can be diagnosed bacteriologically by polymerase chain reaction (PCR) tests such as GeneXpert MTB/RIF—which detects both TB as well as bacterial resistance to rifampin (RIF)—culture, or histopathology. According to the World Health Organization, diagnosis can also be made clinically in the setting of characteristic symptoms and radiologic findings without a positive bacteriologic result [1].

Sensitivities for many of the diagnostic tests for TB are reduced in EPTB due to low bacillary load compared to pulmonary TB, leading to frequent misdiagnosis or delayed diagnosis. This is particularly true for bone and joint TB, which often presents with nonspecific clinical presentation and increased false negative test results. The wide range of symptoms and ability for TB to affect any organ system has earned TB the title of the “great mimicker” [2,5]. Additionally, imaging modalities such as radiographs or magnetic resonance (MR) often reveal nonspecific findings, such as osteopenia and ill-defined lytic lesions, further contributing to the difficulty in diagnosis [5].

Delayed diagnosis of bone and joint TB can result in permanent deformity, severe osteoarticular destruction, and increased mortality risk, especially in elderly patients [3,6]. Studies have shown that chronic osteomyelitis can result in a chronic inflammatory reaction, increasing the risk for cardiovascular disease, stroke, renal disease, and depression, all of which can contribute to mortality [6]. Early diagnosis and treatment of TB are critical for improved outcome and resolution without the need for surgical intervention.

We hereby present the case of a 29-year-old man diagnosed with TB osteomyelitis of the left wrist over a year after his first presentation, whose biopsy was initially negative for TB by PCR and histopathology. The case illustrates the challenges in the diagnosis of EPTB and highlights the importance of repeat testing and maintaining a high clinical suspicion for TB.

Case Presentation

A 29-year-old man with a history of gout presented with chronic left wrist pain, swelling, and decreased range of motion. The patient’s clinical symptoms had insidiously begun at least 5 years ago but worsened in the past 8 months, which prompted a referral to our institution. The patient’s gout was well-controlled with diet with no recent flares. The patient was born in the Philippines and received the Bacille Calmette–Guérin vaccine at birth. He immigrated to the United States 12 years ago and had traveled extensively in the Philippines and Indonesia 6 years prior, the year before his wrist symptoms first began. The examination of the patient’s wrist and hand was significant for swelling at the medial wrist, decreased range of motion, and normal pulses and sensation. Rheumatologic workup—erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), rheumatoid factor (RF), cyclic citrullinated peptides (CCP), and anti-nuclear antibody (ANA)—was negative. The patient reported a history of 2 previous aspirations of the wrist swelling, which were unrevealing and negative for gout crystals.

A prior radiograph of the left wrist obtained at an outside institution showed osseous erosions of the carpal bones, distal radius, and ulna (Fig. 1). Initial outside MRI of the left wrist showed extensive synovitis of the distal radioulnar joint and osseous marginal and central erosions of the distal radius, ulna, and carpal bones (Fig. 2). Repeat wrist radiograph 5 months later showed worsening erosions, particularly at the distal ulna (Fig. 3). Given the negative CT gout study of the wrist (Fig. 4) and negative aspirations for crystals, gouty arthropathy was deemed unlikely. The patient was nevertheless started on colchicine due to elevated uric acid levels. The differential diagnosis at this point included atypical septic arthritis, osteomyelitis, and non-infectious inflammatory arthritis. Surgical biopsy was recommended for definitive diagnosis.

Fig. 1.

Wrist radiograph: AP radiograph of left wrist shows numerous erosions at the distal radius (short arrow), distal ulna (long arrow), scaphoid (arrowhead), and second through fifth carpometacarpal joints.

Fig. 2.

Wrist MRI: (A) Coronal T1-weighted MR image shows erosions of distal radius, ulna, scaphoid, lunate, triquetrum, capitate, hamate, and base of 2nd through 5th metacarpals. There is extensive synovitis at the distal radioulnar joint and radiocarpal joint. (B) Axial T2 FS MR image shows erosions of distal radius, ulna, and synovitis at the distal radioulnar joint.

Fig. 3.

Wrist radiograph: AP radiograph of left wrist 5 months later shows worsening of the osseous erosions, especially at the distal ulna (black arrow). There are numerous osteolytic lesions of the carpal bones, metacarpal bone bases, and the distal radius/ulna.

Fig. 4.

Dual energy gout CT: Gout CT of left wrist shows numerous osseous erosions. No monosodium urate crystal was detected to support a diagnosis of gout (no green pixels).

The patient underwent open synovial biopsy and resection of the soft tissue mass at the distal ulna. Pathology revealed non-necrotizing granulomatous inflammation, with negative bacterial and fungal cultures, negative acid-fast bacillus (AFB) smear, as well as negative broad-range PCR (Fig. 5). Due to negative infectious workup, no antimicrobial therapy was initiated.

Fig. 5.

Synovial biopsy: Photomicrograph of nodular proliferation of non-necrotizing granulomatous inflammation (H&E, x100).

Over the next several months, the patient experienced persistent wrist pain and decreased range of motion, with gradual recurrence of the wrist mass. Repeat wrist MRI was obtained at our hospital, and demonstrated worsening osseous lesions, and new visualization of the “penumbra sign” which was identified retrospectively (Fig. 6). The penumbra sign is a characteristic MR sign of subacute osteomyelitis, representing a thin granulation tissue layer around an abscess cavity with higher signal intensity than the main abscess on T1-weighted images [7].

Fig. 6.

Wrist MR: (A) Coronal T1 weighted image shows worsened osseous erosions. There is a cortical break at the ulnar diametaphysis suggestive of infectious process (black arrowhead). The image also demonstrates the “penumbra sign” (two black arrows). (B) Axial T1 weighted image shows “penumbra sign” as well (two black arrows) at the distal ulnar erosion, suggestive of subacute osteomyelitis. (C) Axial T1 FS post-gadolinium image shows extensive synovitis of the distal radioulnar joint. There is peripheral rim enhancement of the osseous erosions, corresponding to granulation tissue (“penumbra sign,” two white arrows).

Prompted by the worsening lesions and negative workup to date, repeat biopsy was recommended of the left wrist soft tissue mass as well as radius and ulna bony lesions, which was performed 7 months after the initial biopsy. Pathology of the bone biopsies showed necrotizing granulomas and mycobacteria on an AFB special stain (Fig. 7). Culture and GeneXpert MTB/RIF of the specimens were positive for TB, confirming the diagnosis of TB osteomyelitis of the wrist.

Fig. 7.

Bone biopsy: (A) Photomicrograph of necrotizing granulomatous inflammation (H&E, x200). (B) AFB stain showing focal acid-fast positive rods (arrow).

The patient was started on standard rifampin, isoniazid, ethambutol, and pyrazinamide (HRZE) therapy for the first 2 months, followed by rifampin and isoniazid for the continuation phase. There was no evidence of pulmonary TB, with negative sputum AFB smears, negative chest radiograph, and no pulmonary symptoms. On a 4 month follow up visit, the patient had notable improvement in both pain and range of motion of his left wrist, though still with limitations compared with the contralateral side. Imaging at this time demonstrated persistent lytic lesions throughout the radius, ulna, and carpal bones. Fig. 8

Fig. 8.

Wrist radiograph (4 months after treatment initiation): AP radiograph of the left wrist showing lytic lesions of the radius, ulna, and carpal bones.

Discussion

TB osteomyelitis is a rare manifestation of extrapulmonary TB, accounting for only 1%-5% of TB cases in developed countries [2,3]. Bone and joint TB typically consists of a bimodal age distribution in developed countries, affecting primarily natives above age 55 or immigrants between age 20 to 35. Most TB osteomyelitis involves the spine. Wrist and hand involvement account for only 4%-11% of TB osteomyelitis [3]. Cases of isolated unilateral wrist osteomyelitis without pulmonary involvement and negative open biopsy, as seen in this case, are a rare presentation of TB.

TB osteomyelitis presents diagnostic difficulties due to its paucibacillary nature, which decreases the sensitivity of many standard diagnostic tests. Ziehl–Neelsen staining and AFB culture of fine needle aspiration from bone/synovial tissue have reported sensitivities of 0.30-0.36 and 0.37-0.97 respectively [8]. The nonuniform distribution of TB, combined with the challenges of obtaining tissue from relatively inaccessible sites, contributes to the variable sensitivities and frequent false negatives for different diagnostic tests [2,9]. In our case, the initial biopsy resulted in negative AFB stain and negative broad-range PCR, obscuring the diagnosis of TB and prolonging the duration of untreated osteomyelitis.

GeneXpert MTB/RIF (a PCR technique) was developed to detect pulmonary TB and rifampin resistance, with high sensitivity and specificity in pulmonary specimens and quicker turnaround time relative to culture. However, its sensitivity and specificity are less well established in EPTB though it remains widely used. PCR is useful in the diagnosis of paucibacillary TB, as fewer bacilli are needed for positive results compared to culture or AFB staining, though low bacterial load can still result in false negative PCR results. One meta-analysis found the sensitivity and specificity of GeneXpert MTB/RIF for bone and joint TB to be 81% and 99% respectively [10], though the sensitivity has been shown to decrease in the setting of smear negative EPTB, possibly due to a low bacillary count or insufficient sampling [4,[11], [12]]. These findings highlight the variable diagnostic utility of PCR in musculoskeletal TB, which may be enhanced when used alongside culture, clinical assessment, and imaging [13]. PCR remains an important test for rapid diagnosis of EPTB, but awareness that a negative result does not exclude TB is crucial to avoid diagnostic delays.

Bone and joint TB is associated with significant diagnostic delays, ranging from 3 to 25 months from initial presentation [14]. The patient discussed in this case report had ongoing symptoms for several years, but was not diagnosed with TB osteomyelitis until a year after his initial presentation to our institution. The diagnosis of TB osteomyelitis is complicated by nonspecific clinical symptoms such as pain, arthritis, and soft tissue swelling that result in broad differential diagnoses including gout, rheumatoid arthritis, calcium pyrophosphate deposition (CPPD), septic arthritis, sarcoidosis, and multicentric reticulohistiocytosis [3,5]. In the United States, only 6.9% of people with bone and joint TB also had pulmonary TB, making the diagnosis of TB more difficult in the absence of characteristic pulmonary symptoms and with negative chest radiographs [3]. In this case, diagnosis was further complicated due to the patient’s chronic and progressive symptoms isolated to his wrist and unclear TB history. Delays in diagnosis and treatment can cause irreversible bone and joint destruction and deformities requiring surgical intervention, such as arthrodesis or joint replacement, whereas early diagnosis and treatment often result in complete resolution [3]. Lange et al. reported a case of osteoarticular tuberculosis with ulcer of the knee with multiple negative cultures, which led to a several month diagnostic delay and severe joint destruction and necrosis, ultimately requiring above the knee amputation [15]. In endemic regions, empiric treatment of TB with HRZE is often initiated based on clinical and radiological findings instead of relying on laboratory confirmation, which can reduce morbidity and joint destruction but may lead to drug resistance and underdiagnosis of TB mimickers [14].

Imaging findings for TB osteomyelitis can be a useful tool for clinical diagnoses. Radiograph findings of bone and joint TB include soft tissue swelling initially, with later stages often showing osteopenia and periarticular bone destruction [3]. Characteristic MR findings of wrist TB include synovial thickening of the flexor and extensor tendons with fluid collections of the tendon sheath that have low signal intensity on T1-weighted images [16]. Other common MR findings include joint space narrowing, bone marrow edema, or abscess formation [17]. The “penumbra sign” is a relatively obscure sign that has a positive predictive value, negative predictive value, and specificity all greater than 90% in detecting subacute osteomyelitis on MRI. In our case, the patient had a positive penumbra sign identified retrospectively on his second MRI. Earlier recognition of the penumbra sign could have facilitated prompt diagnosis and initiation of anti-tuberculoid therapy, potentially precluding the need for invasive diagnostic procedures like a bone biopsy. Knowledge of common imaging findings of TB osteomyelitis, including the penumbra sign, is diagnostically important, particularly in cases of TB osteomyelitis where false-negative laboratory results are common [7].

Conclusion

This case report demonstrates the diagnostic challenges associated with extrapulmonary TB, particularly TB osteomyelitis. TB osteomyelitis is a rare manifestation of TB that is difficult to diagnose due to the paucibacillary nature of the disease, which can lead to false negative test results and a nonspecific, indolent clinical presentation. Key radiologic findings such as the penumbra sign can be useful in increasing suspicion for TB osteomyelitis. Repeat testing and maintaining a high index of suspicion for TB, especially in immigrants from endemic regions, are important diagnostic considerations for early diagnosis and treatment.

Patient consent

The patient provided written informed consent and has given their approval for the publication of this case report.