Extrapulmonary, Chronic Septic Arthritis From Mycobacterium tuberculosis in the Ankle and Subtalar Joints

Abstract

In the United States, rates of Mycobacterium tuberculosis infection have been declining for decades. Osteoarticular tuberculosis of the ankle is rarely observed. We present the case of a 65-year-old man who immigrated to the United States from India 24 years before the onset of symptoms. The patient initially reported atraumatic swelling and pain of the left ankle and foot and was treated for venous insufficiency. Later, the patient was referred to a nonsurgical orthopaedic clinic for additional workup and was found to have elevated inflammatory markers. MRI showed septic arthritis and osteomyelitis of the talus, distal tibia, and calcaneus. Joint aspiration revealed elevated white blood cell counts with predominately PMNs. The patient was then referred to an orthopaedic foot and ankle surgeon and underwent extensive irrigation and débridement. The patient was discharged on empiric antibiotics. Culture results from the original joint aspirate returned 14 days after surgery as positive for acid-fast bacillus, later identified as M tuberculosis by sequencing. Empiric antibiotics were discontinued, and the patient was started on appropriate antituberculotic therapy. This case report illustrates the challenge in the diagnosis of skeletal tuberculosis and the importance of including this condition on the differential for patients with atypical foot and ankle presentations.

The incidence of M tuberculosis infection in the United States has decreased over the past 60 years from nearly 30 cases per 100,000 people in the early 1960s to 2.4 cases per 100,000 in 2021.¹ The lungs are the most common site of infection, being implicated in approximately 80% of cases.^2,3 Extrapulmonary infection most often affects the lymphatics, pleura, bone or joint, and peritoneum—in a descending order of incidence .^4-6 Between 2010 and 2021, skeletal Mycobacterium tuberculosis (MTB) cases comprised 10.2% of all cases of extrapulmonary tuberculosis (EPTB) in the United States.⁴ Infection can occur in any bone or joint of the body with approximately half of cases affecting the vertebral column.^5,7 Large weight-bearing joints such as the hip and knee are the next most common sites of infection.^5,7,8 Rarely, infection occurs in small peripheral bones and joints of the extremities.^4,6,9 Tuberculous arthritis of the ankle is estimated to occur in only 1 to 8 percent of all cases of skeletal MTB.^3,8,10,14 Diagnosis is often delayed because of the rarity, indolent course, and nonspecific symptoms characteristic of skeletal MTB and the lengthy time required for identification of acid-fast bacilli.^{5,7,9,10,13,14}

Case Report

tA 65-year-old man with a history of idiopathic pericarditis, hypothyroidism, right hip osteoarthritis, elevated alkaline phosphatase, and microcytic anemia presented to the emergency department with a 1-week history of left lower extremity swelling and ankle pain. He could not recall any inciting event, but reported difficulty spending long periods of time on his feet at his job as a machine operator. The patient moved to the United States from Northern India 24 years ago. He was referred to the emergency department from an urgent care facility to be evaluated for possible deep vein thrombosis of the left lower extremity. After a negative duplex ultrasonography, the patient was diagnosed with venous insufficiency and was instructed to elevate his leg and wear compression stockings. In the following weeks, workup by endocrinology and hematology for evaluation of the patient's elevated alkaline phosphatase and anemia were normal, except for complete blood count results and iron studies, which suggested an inflammatory etiology as the underlying cause of the patient's anemia.

Five months after initial presentation to the urgent care, the patient was seen at a nonsurgical orthopaedic clinic with worsening left ankle pain and continued swelling. He was no longer able to work because of ankle pain and presented to clinic in a wheelchair. On examination of the left lower extremity, the patient was found to have notable edema from the mid-tibia through the foot, palpable fluctuance posteromedial and posterolateral to the ankle joint, and notable skin changes, but no open wound. His C-reactive protein and erythrocyte sedimentation rate were elevated to 11.9 mg/dL and 98 mm/hr, respectively (institution reference ranges are 0.0 to 0.8 mg/dL for C-reactive protein and 0 to 10 mm/hr for erythrocyte sedimentation rate). Radiographs demonstrated a lateral talar osteochondral lesion and significant posterior tibiotalar effusion (Figure 1). Left ankle MRI revealed findings consistent with tibiotalar and subtalar septic arthritis and osteomyelitis of the talus, distal tibia, fibula, and calcaneus (Figure 2). Ultrasound-guided arthrocentesis of the ankle joint produced a thick aspirate with 87,350 white blood cell counts/µL, 150,000 red blood cell count/µL, 92% PMNs, and a negative initial Gram stain with acid-fast bacillus (AFB) culture and stain pending. The patient was then referred to an orthopaedic foot and ankle surgeon and was subsequently scheduled for surgical irrigation and débridement of the left ankle and subtalar joints 2 days after being seen in the surgical clinic (and 6 days after the initial joint aspiration). On the morning of the operation, the patient noticed spontaneous, serous, semipurulent drainage from the posteromedial ankle. The washout was done without incident. Multiple tissue and bone specimens were collected for culture. Multiple bone specimens were also obtained for pathology. Postoperatively, the patient was administered empiric antibiotics per the direction of infectious disease and was discharged from the hospital in a stable condition after 4 days of negative culture results.

Figure 1.

Ankle radiographs including mortise (A) and lateral (B) views demonstrating a lateral talar osteochondral lesion and posterior tibiotalar effusion.

Figure 2.

MRI scan including sagittal T1 (A) and Short Tau Inversion Recovery (B and C) slices showing bony changes of the talus, tibia, and calcaneus with large posterior fluid collection.

Eight days after the procedure (and 14 days after initial presentation to the nonsurgical orthopaedic clinic), the culture from the initial ankle joint aspirate produced an AFB that was identified 6 days later as M tuberculosis by DNA sequencing and polymerase chain reaction. The patient was instructed to discontinue current antibiotics and was started on direct observed therapy with rifampin, isoniazid, pyrazinamide, ethambutol and concurrent pyridoxine in coordination with infectious disease and the local health department. Ethambutol was discontinued when susceptibility results showed a pansusceptible strain of M tuberculosis. Within 4 weeks of surgery, all the bone specimens and three of the tissue specimens sent for culture grew M tuberculosis (identified with Matrix-assisted laser desorption ionization–time-of-flight mass spectrometry). The bone specimens sent to pathology demonstrated chronic inflammation, foreign-body giant cell reaction, and necrosis. With immunohistochemical staining specific for MTB, acid-fast bacilli were also identified in the pathology specimens, consistent with tuberculous osteomyelitis (Figure 3). Chest, abdominal, and pelvic CT scans and a transthoracic echocardiogram showed no evidence of active MTB infection or constrictive pericarditis.

Figure 3.

Image showing hematoxylin and eosin stain demonstrating rare mycobacterial organisms staining positive with Mycobacterium tuberculosis immunohistochemistry (A) and with images captured with a 60 × objective (B).

Postoperative recovery was complicated by delayed wound healing along the posteromedial ankle at the site of preoperative spontaneous drainage. The patient received wound care treatment including the placement of a wound vacuum-assisted closure. Six months after the operation, the wound had healed, and there was no pain elicited with weight-bearing or with active or passive motion of the ankle and subtalar joints. Pyrazinamide was discontinued after 2 months, and isoniazid and rifampin were continued for an additional 10 months (and then stopped after 1 year of treatment).

Of note, the patient provided consent for publication of this case and associated images.

Discussion

Primary infection with M tuberculosis occurs in peripheral respiratory alveoli of the lungs after inhalation of aerosolized droplets containing tubercle bacilli.¹⁵ Osteoarticular sites may be seeded by hematogenous spread even if the primary infection resolves without becoming clinically evident.^16,17 In such cases, the only evidence of disease may be the rare reactivation at the site of extrapulmonary seeding years after the initial infection.¹⁷

Extrapulmonary tuberculosis involving the musculoskeletal system is an uncommon manifestation of MTB.^4,16 In nonendemic countries such as the United States, most skeletal MTB cases occur in patients of advanced age and in those who have immigrated from endemic regions of the world.^3,5,7,14,18 In addition, immune suppression, crowded living conditions (eg, correctional and long-term care facilities, homeless shelters), and HIV are well-reported risk factors of EPTB infection; patients at greatest risk may also be less likely to receive screening for latent infection.^6,15,18,19 Several previous case reports and series have suggested that past skeletal trauma may also increase the likelihood of subsequent skeletal MTB infection.^18,20,21 The 65-year-old patient discussed in this report had no known history of HIV, immune suppression, or acute ankle trauma, although his employment required > 50 hours of work per week on his feet. He immigrated to the United States from the Punjab region of northwestern India, an MTB-endemic location,¹⁴ 24 years before the onset of symptoms. Before surgery, our patient denied any international travel. After MTB diagnosis was made, the patient recalled travelling to India 3 years before symptom onset. Tuberculosis exposure in an endemic country is, therefore, the presumed event that ultimately led to active articular infection in this patient.

In this report, the patient's presenting symptoms were pain, swelling, and reduced mobility of the left lower extremity. There was a draining sinus of the posteromedial ankle, which first developed coincidentally on the morning of surgery, approximately 6 months after symptom onset. He was also found to be mildly anemic for at least a year before surgery. This presentation is like other cases reported in the literature.^{5,10,12,13,16,21,22} Between 1995 and 2005, Choi et al¹² analyzed 15 cases of osteoarticular tuberculosis of the foot and ankle at their institution in South Korea, finding pain and swelling as the most common symptoms with a draining sinus present in one-third of cases. Dhillon and Nagi identified anemia in 26% of patients with foot and ankle MTB treated over an 11.5-year period in India.²¹

The time between initial presentation to urgent care and identification of M tuberculosis in our patient was 29 weeks 2 days. This extended interim between initial presentation and definitive diagnosis is characteristic of arthritic tuberculosis and illustrative of the diagnostic challenges and transmission risks associated with this condition.^{7,8,10,12,14,15,20,23} In a case series from India of 108 patients with extraspinal osteoarticular tuberculosis, Samuel et al¹⁰ reported that the average time between symptom onset and diagnosis was 12 months. A review of 31 cases of bone and joint MTB in the United Kingdom reported an average interim of 9 months between symptom onset and initiation of treatment.¹⁴ There are several factors that contribute to delayed diagnosis. In nonendemic countries such as the United States, extraspinal osteoarticular tuberculosis of the ankle is exceedingly rare and may not always be considered in the differential diagnosis.^7,14,16,22 Disease onset is typically indolent and produces nonspecific symptoms with a broad differential diagnosis—including pyogenic or fungal arthritis, gout, pigmented villonodular synovitis, rheumatoid arthritis, brucellosis, and (in this case) venous insufficiency—often resulting in misdiagnoses and treatment delays.^7,9,10,12,20 Furthermore, the infection site is often paucibacillary,^16,24 and culture of M tuberculosis requires 2 to 8 weeks.²⁵ In the case presented here, M tuberculosis was first identified 20 days after joint aspiration (14 days after surgery). Of the nine intraoperative specimens sent for AFB stain and culture, six became culture positive after an average delay of 26 days. The bone pathology specimens (obtained from the tibia, talus, and calcaneus) exhibited chronic inflammation, focal necrosis, and foreign-body giant cell reaction. With special staining, acid-fast bacilli were identified in specimens from the talus and calcaneus. Mycobacterial culture is considered the benchmark for the diagnosis of skeletal M tuberculosis infection and allows for growth-based drug susceptibility testing.^{14,15,22,24,25} AFB smear, histologic examination, and nucleic acid amplification tests are additional tools that aid in diagnosis. AFB smear and culture should be ordered for patients with suspicious signs/symptoms and MTB-associated risk factors (travel/immigration from MTB endemic country, advanced age, HIV, immune suppression, and crowded living). The time to diagnosis in this case was on the lower end of the spectrum reported in the literature.^10,14

The risk of transmission of M tuberculosis from a patient with exclusively extrapulmonary disease is typically low—except for cases of laryngeal/oral cavity MTB or cases involving an open abscess with a high concentration of infectious organism—because a sufficient inoculum of aerosolized bacilli must be inhaled to produce infection.^15,17 There may be an increased risk of transmission during surgical operations involving EPTB, especially when the presence of MTB infection has not yet been elucidated or the operation involves aerosol-producing activities including suctioning and open abscess irrigation.^15,23,26 Appropriate environmental and respiratory protection measures reduce the risk of transmission in healthcare settings.^15,23 Because the causative organism was unknown at the time of surgery in this case, the surgical team and operating room staff used only routine surgical personal protective equipment. Postexposure testing included QuantiFERON interferon-gamma release assay after exposure and again after 8 to 12 weeks, and returned with no positive results.

This report presents the case of a 65-year-old man who immigrated from India 24 years ago and was found to have chronic septic arthritis and osteomyelitis of the left ankle and subtalar joints due to infection by M tuberculosis. This case illustrates the importance of including M tuberculosis on the differential diagnosis for patients presenting with signs/symptoms consistent with chronic septic arthritis with concomitant risk factors of MTB. In surgical treatment of undiagnosed EPTB, the risk of transmission to HCWs is reduced when appropriate environmental and respiratory controls are in place.^15,23 Although tuberculous arthritis of the ankle is exceedingly rare, prompt diagnosis is essential to prevent destructive sequelae.^9,14,15