Great imitator: an unusual presentation of osteoarticular tuberculosis of the knee with gram-negative bacterial arthritis

Abstract

A 33-year-old man presented with a 2-year history of right knee swelling with fungating masses and white-yellow discharge. Severe pain, limited movement and signs of sepsis were absent. Debridement, partial synovectomy and arthrotomy were done for the multiple sinuses that developed over the knee. Synovial tissue analysis yielded a positive acid-fast bacillus smear and Mycobacterium tuberculosis PCR test, while aerobic culture studies grew Pseudomonas aeruginosa and Acinetobacter baumannii. Chronic granulomatous inflammation was seen on histopathology. Alongside antibiotic therapy, multiple debridements of the right knee were required to eradicate the infection and allow wound repair. A flap coverage with split-thickness skin graft was performed after the bacterial infection resolved, and the patient was discharged ambulatory with minimal pain. Such atypical presentations of monarthritis require immediate workup and a prompt referral to a multidisciplinary team to establish the diagnosis and initiate appropriate management before irreversible joint destruction and disability ensues.

Background

Osteoarticular tuberculosis (TB) is rare worldwide, accounting for 1%–4.3% of all cases of TB and 5%–15% of extrapulmonary TB cases.^1–3 In low-income and middle-income countries, it commonly occurs between the second and third decades of life, with a male-to-female ratio of 1.3:1. Peripheral arthritis accounts for 30% of the osteoarticular TB syndromes, with most patients presenting with a mild, insidious monarthritis.^4–6 The knee is involved in around 10%–20% of peripheral osteoarticular TB.^{5 7 8} Monarthritis of the knee is rare at 0.1%–0.3%. Its slowly progressive nature leads to a delay in diagnosis due to patients not seeking medical help immediately or clinicians failing to recognise the disease in its early stages.⁹ Concomitant tuberculous and bacterial septic arthritis is uncommon in the literature. There have been at least four case reports of glenohumeral TB arthritis with a bacterial infection—one with $\beta$-haemolytic Streptococcus, and three with Staphylococcus aureus, but coinfection of TB and bacteria, especially gram-negative ones, is a rare occurrence overall.^10–14 Here, we present a case of osteoarticular TB and bacterial arthritis of the knee developing complications that may mimic numerous conditions causing monarthritis.

Case presentation

A 33-year-old man presented with a 2-year history of swelling of the right knee, developing fungating masses and sinuses with white, nonfoul-smelling discharge on the anterior knee 1 month before the consultation. There was associated intermittent low-grade fever, undocumented weight loss and difficulty in ambulation. Persistence of the knee swelling and the enlarging wounds prompted him to consult at a local hospital where he was given methylprednisolone 16 mg daily for 5 days and amoxicillin-clavulanic acid and clindamycin for 10 days. However, his knee did not improve and he continued to have fever and chills. He had non-disabling left knee swelling with a sinus in the left popliteal area draining chalky white discharge 4 years prior to the current consult, but no workup was done. This left knee arthritis coincided with a diagnosis of pulmonary TB, for which he received antitubercular medications for 6 months. There was complete resolution of the left knee arthritis and sinus tract on the third month of therapy. The rest of his medical history was unremarkable. He denied using illicit drugs and having sexual intercourse outside his marriage. He had an insignificant travel history. He worked as a farmer, but claimed to never have had any knee injury.

He was haemodynamically stable and afebrile on admission. Physical examination revealed an erythematous, warm right leg with fungating masses measuring around 2×2 cm each, which eventually ruptured and formed multiple enlarged sinuses in a semicircumferential arrangement on the anterior right knee, with white-yellow caseous discharge and tenderness on palpation (figure 1). There was pain on active and passive movement of the knee and slight limitation in flexion and extension, causing difficulty in weight-bearing and ambulation. Other joints were normal. Inguinal lymphadenopathy was present. The rest of his physical examination was unremarkable.

Figure 1.

Anteroposterior (A) and medial (B) views of the right knee with multiple sinuses, caseous discharge and surrounding cellulitis.

Investigations

Diagnostic tests revealed normocytic and normochromic anaemia, with normal leucocyte and platelet counts (haemoglobin 102 g/L, leucocytes 8.6 x 10⁹/L, platelets 279 x 10⁹/L). Fasting blood sugar, serum electrolytes, liver function tests and kidney function tests were normal (sodium level 134 mmol/L, potassium level 3.8 mmol/L, calcium level 2.33 mmol/L, aspartate aminotransferase 32 U/L, alanine aminotransferase 30 IU/L, creatinine 0.72 mg/dL). Serum albumin was low at 2 g/dL. Right knee X-rays showed juxta-articular osteopenia, lytic changes with overhanging edges in the medial and lateral condyles of the tibia, narrowing of the medial and lateral femorotibial joint spaces and lateral displacement of the patella (figure 2), suggestive of an inflammatory arthritis with concomitant cellulitis. CT scan or MRI of the knee was not done due to financial limitations. HIV serology by ELISA was negative.

Figure 2.

Anteroposterior (A) and lateral (B) X-ray views of the right knee taken after the first debridement revealing osteopenia, lytic changes and narrowing of the medial and lateral femorotibial joint spaces consistent with Phemister’s triad. Overlying staple wires and gauze markers are seen.

Debridement and arthrotomy of the right knee was done. Intraoperative tissue specimen yielded an acid-fast bacillus (AFB) smear count of 3+ and a positive test on Mycobacterium tuberculosis PCR (MTB-PCR) showing rifampicin sensitivity, which we opted to do in lieu of TB synovial fluid culture due to the urgency of confirming the diagnosis. Moderate heavy growth of Pseudomonas aeruginosa was seen on synovial aerobic culture studies, with repeat cultures showing coinfection with light growth of Acinetobacter baumannii. Blood cultures were negative. The final histopathological diagnosis was chronic granulomatous inflammation suggestive of tuberculous aetiology (figure 3). The chest X-ray did not show any findings suggestive of TB.

Figure 3.

A histological section of knee tissue stained with H&E shows the following: (A) vast areas of necrosis (×40, bottom half of image), (B) granuloma formation, with ill-defined aggregates of epithelioid histiocytes and surrounding chronic inflammation (×100), (C) nodular granuloma (×100, centre).

Differential diagnosis

True to its reputation as ‘The Great Masquerader’, TB can mimic other insidious arthritides. Histopathological diagnosis is key in differentiating it from certain conditions such as pigmented villonodular synovitis and malignancy.^15–18 Of note, simultaneous occurrence of two or more of these conditions in a single joint is not impossible. In our patient, the histopathological findings and positive AFB smear and MTB-PCR confirmed the diagnosis. Fungal infection could not be ruled out because cultures were not done, but this was unlikely with the patient’s improvement with antibacterial and antitubercular medications.

Treatment

The patient was initially given ceftriaxone for the cellulitis. He was later shifted to piperacillin-tazobactam (4.5 g intravenously every 8 hours) and vancomycin (1 g intravenously every 12 hours) as empiric therapy for bacterial septic arthritis. Vancomycin was removed with culture guidance. Gentamicin (200 mg intravenously every 24 hours) was added to cover for A. baumannii. These were given for a total of 4 weeks. Daily therapy with isoniazid (H; 225 mg), rifampicin (R; 450 mg), pyrazinamide (Z; 1200 mg) and ethambutol (E; 825 mg) was started along with intramuscular streptomycin (750 mg daily).

The initial debridement and arthrotomy revealed caseous discharge in the joint space, seropurulent discharge on the suprapatellar pouch, friable meniscus and generalised synovitis, but with an intact patellar tendon and maintenance of the articulating surfaces of the patella, femur and tibia (figure 4A–C). Partial synovectomy was also done, removing nonviable and infected tissue. Due to the severe infection and the large soft tissue defect, the patient underwent four more sessions of debridement and arthrotomy, with the goal of eradicating the source of infection and removing necrotic tissue to provide a healthy bed of granulation tissue, allowing coverage of the joint and wound.

Figure 4.

(A) Predebridement view of the right knee showing sinuses that directly communicate with the joint. (B, C) Intraoperative picture of the same knee with caseous and seropurulent discharge, friable meniscus and generalised synovitis. (D) Postfinal debridement showing absence of pus and caseation, as well as formation of granulation tissue.

Outcome and follow-up

With the repeat procedures, the seropurulent discharge gradually decreased, the caseous discharge disappeared and granulation tissue started to form (figure 4D). Coverage with a rotation muscle flap using the medial gastrocnemius was performed after the fourth debridement. The flap was covered with a split-thickness skin graft. After 1 week, at graft site inspection, there was >90% skin graft incorporation and resolution of the infection. The patient was discharged improved after starting range-of-motion exercises and physical therapy.

Using the classification criteria of TB arthritis by Tuli et al, our patient was in the stage of early arthritis (stage II) based on marginal joint erosions and joint space diminution but with maintenance of the contour of the articulating surfaces.¹⁹ In such cases, it is expected that 50%–70% of the function of the joint will be regained with a combination of rest, range-of-motion exercises, splinting, synovectomy and antitubercular therapy. The patient took TB medications for a total of 1 year (2 months of HRZE and 10 months of HR). Complete wound healing was noted 4 months postoperatively. The patient was then lost to follow-up in the subsequent years and discontinued his streptomycin, but was contacted again 3 years after the operation (figure 5). He reports limited flexion of the right knee and occasional activity-related knee pain, but states that these do not interfere with his current work as a fisherman.

Figure 5.

Right knee 3 years postsurgery. (A) Anterior view of the knee showing healed wounds, mature scar and quiescent graft and donor site. (B) Medial view of the knee.

Discussion

A history of pulmonary and possible left knee TB and residence in an endemic country may have predisposed our patient to osteoarticular TB. As in most cases, involvement of the knee likely came from seeding of the bone marrow via haematogenous spread of a primary infection, with the lungs as the primary site in up to 30% of cases.^{20 21}

In the setting of an insidious monoarticular arthritis, a high index of suspicion and a good history are key in clinically diagnosing TB arthritis. A delay of 2 months to 10 years in diagnosis is observed due to the indolent course, mild and non-specific symptoms especially in the early stages, absence of active TB in other sites, and the low specificity of radiographic and laboratory findings.9 11 22 23 This finding is corroborated by a local study of 65 patients with TB arthritis, where the mean duration from the onset of symptoms to consult was 21 months, ranging from 3 months to 15 years. Similarly, fever, weight loss and malaise were uncommon at 22%, 15% and 6%, respectively. As such, a correct diagnosis of TB arthritis at the onset was made only in 10% of patients.²⁴ For diagnosis, the positivity of synovial fluid AFB smears may be as low as 27%, while synovial fluid culture may yield positive results in up to 80%.²⁵ Synovial biopsy may be positive in 90%–95% of cases and remains the gold standard.^{26 27} PCR has also proven to be a useful test for osteoarticular TB, with a sensitivity of 60%–70% and a specificity of above 90%.^{28 29}

A review of case reports on TB arthritis shows that, following diagnosis, treatment duration ranged from 3 to 12 months, with a mean of 10 months.¹ The optimal duration of medical therapy for musculoskeletal TB is unclear. While some studies show that rifampicin for 6-9 months may be sufficient,³⁰ local TB guidelines recommend treatment of new cases for 1 year with HRZE for 2 months and HR for 10 months. TB reactivation after a 6-month treatment for pulmonary TB may support the observation that higher relapse rates may occur among those treated with shorter courses.³¹ For confirmed rifampicin-sensitive TB in patients who received 1 month or more of antitubercular drugs, retreatment with 2 months of HRZE and streptomycin, 1 month of HRZE and 9 months of HRE are recommended.³² Despite being lost to follow-up and taking only 1 year of treatment with the regimen used for new cases, our patient’s knee significantly improved. His course is consistent with current literature citing clinical improvement or cure with optimal antitubercular therapy in 90%.^33–35 However, some patients may proceed to have persistent destructive changes despite a relatively short delay in diagnosis and 1 year of treatment.³⁶ Sequelae may vary from simple synovial inflammation to extensive bone erosions, crippled ligaments, rupture of the joint capsule and severe articular destruction requiring total knee arthroplasty. While the role of surgery in the general treatment of non-spinal musculoskeletal TB remains unclear, surgery may be necessary in severe and refractory cases, uncertain diagnoses and/or joint deformity.^{7 32} Surgical procedures may include incision and drainage of abscesses, synovectomy, arthrodesis, corrective osteotomy and arthroplasty.⁷ Due to the risk of TB reactivation and prosthesis rejection with total arthroplasty in a joint with active TB, a disease-free interval of 10 years between chemotherapy and arthroplasty is suggested.^{7 37 38} A case series of 16 patients with knee TB showed reduced rates of reactivation with preoperative chemotherapy of at least 2 months, continued postoperatively.³⁸

TB arthritis accompanied by bacterial arthritis in a single joint is seldom reported.^{11 13 14} Two cases describe unilateral swelling and warmth of the knee with draining sinuses, with one describing a straw-coloured discharge from the sinus.^{11 13} Most cases of superinfection with pyogenic bacteria is a complication of a draining sinus, which was present in our patient.¹² Locally, 26% of patients with TB arthritis present with a draining sinus or abscess, and coinfection with bacterial arthritis is seen in 10 of 65 patients.²⁴ Our patient’s knee, with its masses and multiple sinuses, could be mistaken for a malignant growth with superimposed bacterial infection or even vegetative pyoderma gangrenosum.

This case illustrates one of several sequelae of delayed diagnosis and management of osteoarticular TB. Concomitant infection of the joint with TB and other bacterial pathogens, although rare, may occur and must be considered. Immediate workup and a multidisciplinary approach are vital in ruling out mimics and providing prompt management, which can entail multiple procedures, longer hospital stays, higher costs and greater structural damage to the joint.

Patient’s perspective.

‘My knee problem had a great impact on my work as a farmer. I was having difficulty working, and noticed that my knee wasn’t getting any better. Despite my worries, I was confident that the doctors at the hospital would be able to fix my knee; but whenever I look back at what happened, I remember that this is something I wouldn’t want to experience again. I recognize that the recurrence of my knee problem was due to the fact that I took the anti-TB medications for only 6 months the first time. My ordeal in the hospital taught me to be more mindful of my health, and to seek help immediately when I feel something’s wrong so it won’t go awry again. Overall, I was thankful that the doctors were able to fix my knee. It gets painful once in a while when I overwork myself, but the surgery and tablets allowed me to return to my work and help my family again.’

Learning points.

• Because of its insidious course and often non-specific presentation, osteoarticular tuberculosis (TB) is often diagnosed late. Lack of awareness among patients and failure of clinicians to recognise the disease may both contribute to the delay.

• Osteoarticular TB may mimic other chronic arthritides and lead to differing opinions on the management approach at the onset.

• Increased clinical awareness of osteoarticular TB, including its atypical presentations, can facilitate immediate workup and a prompt referral to a multidisciplinary team to establish the diagnosis and initiate appropriate management in a timely manner.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s)