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February 2019, Volume 69, Issue 1

Special Communication

Inflammatory arthritis and Mycobacterium Tuberculosis infection: a diagnostic and management challenge for Knee arthroplasty in endemic areas

Authors: Obada Hasan  ( Department of Surgery, Section of Orthopaedics, The Aga Khan University, Karachi Pakistan )
Riaz Lakdawala  ( Department of Surgery, Section of Orthopaedics, The Aga Khan University, Karachi Pakistan. )
Vickash Kumar  ( South City Hospital Karachi )
Faisal Mahmood  ( Infectious Disease, Department of medicine, The Aga Khan University, Karachi Pakistan )
Shahryar Noordin  ( Department of Surgery, Section of Orthopaedics, The Aga Khan University, Karachi Pakistan )


Tuberculosis continues to be one of the most challenging health problems more prevalent in developing countries. Pakistan ranks 5th in tuberculosis prevalence among the high-burden countries. Prosthetic joint infection of the knee by acid fast bacilli is a rare and distressing complication, occurring in nearly 1% of primary joint
arthroplasties requiring prolonged medical treatment and multiple surgeries. A recent publication extensively reviewed English literature from 1952 to 2016, and
repor ted only 64 prosthetic joint infec tion with tuberculosis, of which 27 cases involved the knee. Tuberculosis is a global health problem adding to the
challenges that arthroplasty surgeons face in our resource-constrained setting. Furthermore, it presents as other inflammatory arthritis with almost same laboratory and radiological findings. The current paper was planned to highlight the preoperative and postoperative challenges that the arthroplasty surgeon may have in diagnosis and management of this rare infection. We included studies from 1996 to date which reported knee tuberculosis prosthetic joint infection that were managed by medication alone or with surgical intervention in patients who had undergone arthroplasty.
Keywords: Knee arthroplasty, TB prosthetic joint infection, Endemic, Inflammatory arthritis.


Tuberculosis ( TB) continues to be one of the most challenging health problems and is more prevalent in developing countries. Pakistan ranks fifth in TB prevalence amongst the high-burden countries.1 In this day and age joint replacement surgeries have become popular in developing countries where TB also has high prevalence. Prosthetic joint infection (PJI) of the knee by acid fast bacilli (AFB) is a rare and distressing complication occurring in nearly 1% of primary joint arthroplasties2,3 requiring prolonged medical treatment and multiplesurgeries. Patients can present with a palpable mass  (cold abscess), draining sinus/fistula, and painful erythema. Therefore high clinical suspicion is mandatory for diagnosis of PJI by mycobacterium. Adding to this challenge is inflammatory arthritis affecting the knee joint present with almost identical features on clinical
examination, laboratory tests and radiographic findings. Laboratory tests include tuberculin skin test (TST ), erythrocytes sedimentation rate (ESR) and cultures of synovial fluid, cytology and histology with different rates of accuracy. In endemic areas with mycobacterium TB (MTB), the low threshold of suspicious is indeed helpful for early diagnosis and management of this catastrophic infection. Factors contributing to delayed diagnosis include its low incidence, varied clinical manifestations, co-infection with pyogenic bacteria accounting for 37% cases, and
low index of suspicion.4 First case of peri-PJI with MTB was reported in 1977(5). A recently 2018 publication extensively reviewed Englishlanguage literature from 1952 to 2016, and reported only 64 PJI with TB, of which 27 cases involved the knee.6


Pathology: Three pathogenic mechanisms have been reported: active TB arthritis present at the time of surgery but not known to clinician; TB spread by haematogenous route from foci elsewhere; and surgical trauma to old granulomas resulting in recurrence of TB arthritis.5-8 Recent studie shave highligh ted human immunodeficiency virus (HIV) as an important risk factor for re-activation of TB in previously infected joints.9,10 Estimated risk of re-activation has been reported between 0% and 31%, with total knee arthroplasty (TKA)
more at risk than total hip arthroplasty (THA) (27% and 6%).11 Staphylococcus is the most common organism for prosthetic infections followed by gram-negative and streptococcus species, while atypical infections are rare.18,12MTB has limited biofilm-formation capacity which, if formed, is very thin and has a lesser tendency to adhere to implants compared to the biofilmforming staphylococci which have ample biofilm-forming capacity and stronger ability to multiply and adhere on surface of all types of implants.13-15Because of these factors, MTB is more susceptible to anti-TB agents and, if implant is stable, removal of hardware is not needed.13 , 16 Nevertheless, emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has complicated its management.16
Clinical presentation: PJI of knee with MTB has a varied clinical presentation. Constitutional symptoms, including fever, weight loss and night sweats, are not seen in all cases and a previous history of pulmonary Koch\'s is often absent.17,18 Patients can present with a palpable mass (cold abscess), draining sinus/fistula, and painful erythema. Therefore high clinical suspicion is mandatory for diagnosis of PJI by mycobacterium. Onset of symptoms within 2 month after ar throplasty is considered "early presentation" whereas onset of
symptoms after 2 months is labelled as "delayed presentation".7,19
Role of lab investigation: The ESR level may be elevated, but has a low specificity. ESR levels remain elevated for about 90 days or more than a year after arthroplasty,
 making it a less valuable test at least during this timeframe.14,20 TST is sensitive, but has a reduced positive predictive value (PPV) in populations with a low infection rate. It may report false negative results in patients who are immune-compromised, malnourished or HIVpositive. 3 It is also not able to differentiate between active and latent TB. Clinical utility of different tests in diagnosing extra-pulmonar y TB also need to be considered (Table 1).

Role of radiological investigation: Plain radiographs either of knee or chest are not specific. Radiological findings may show subchondral cysts, subchondral erosions or implant loosening, but these findings may also be present with pyogenic infection, aseptic loosening and will be absent in early presentation where the implant is stable.21,22 Magnetic resonance imaging (MRI) has low sensitivity due to artefacts caused by the implant. MRI findings reveal large intra-articular effusions, peri-articular osteo porosis, and gross thickening of the remainingsynovial membrane which are not clinically relevant in isolation after arthroplasty.8 Nuclear medicine is the most valuable diagnostic procedure to detect the prosthesis involvement and loosening,23 but literature review has reported their use to be limited. Bone scans findings with technecium-99m or indium-111 are non-specific because findings mimic pyogenic infection, metastatic disease and non-specific inflammation.5
Grams staining / histological diagnosis:
Aspiration of synovial fluid is another modality, but yield is low, with reported sensitivity of 80%. Literature reports synovial biopsy as gold standard in diagnosing PJI of knees.24-26 It has sensitivity of about 90%, but should always be added with cultures to get information about antibiotic resistance.27,28 Culture specimens taken from draining sinuses are usually contaminated.3,6 Staining and visualisation of mycobacterium with Ziehl-nelson is time-saving and cost-effective, but yield of positive test is less than  culture 17Polymerase chain reaction (PCR), though one of the recent diagnostic modalities, has significant specificity, but is less sensitive at 60%. There are limited studies mentioning its use in the diagnosis of PJI.29-32 Treatment: Since PJI of knee with mycobacterium is rare, ith varied presentation and delayed diagnoses; therere no specific guidelines for its management. Several different treatment plans have been advised for PJI of knee by AFB. Management varies from case to case. Literature reports treatment options that range from chemotherapy alone to arthrodesis or revision in addition to chemotherapy.
Conservative management: Early onset PJI of knee has been managed by retention of the implant with prolonged chemotherapy. There is great controversy regarding treatment duration of chemotherapy and combination of drugs in the literature. Cases of PJI with  MTB managed with medications alone are worth taking
a look at (Table 2).

Surgical management: Surgical treatment options include debridement alone, single-stage or two-stage implant exchange or removal of prosthesis and arthrodesis. Chemotherapy alone or with surgical debridement has been used in early onset PJI. In late onset PJI, implant usually gets loose, and removal of implant is often required.33 Wolfgang shared his
experience of late onset PJI in knee, managed with removal of implant, extensive debridement and twostage revisions with adjuvant chemotherapy and good
results at 1-year follow-up.32 A successful case of staged procedure in TB arthritis is also known.

Figure 1 and 2 summarize a case of 55 years old lady presented with
right knee pain, stiffness and difficulty walking not responding to conservative measures. Right knee was swollen, warm and tender with moderate effusion. Active
range of motion 0-110 degrees. No varus/valgus or AP instability was seen on clinical examination. Blood tests were normal except for ESR and CRP, 75mm/hr and
2.14mg/dL, respectively. These features suggested erosive arthritis, which could be inflammatory. However TB should be considered high up in the differentials par ticularly in endemic areas with MTB. Patient underwent debridement and open biopsy at first stage, which confirmed the diagnosis of TB. Multidisciplinary approach including the surgeon, infectious disease team and microbiologist was followed. Following ATT for 10 months, patient had a successful TKA with an excellent outcome. This strengthens the concept that not every erosive arthritis is a systemic inflammatory rheumatoid type, particularly so in our endemic areas of TB. Patient had no varus/valgus or AnteroPosterior (AP) instability on clinical examination. Blood tests were normal except for raised ESR and CRP. Pre-operative knee X-ray showed juxta-articular osteopenia, peripheral osseous erosions  and narrowing of joint space. These features suggested erosive arthritis, which could be inflammatory. However, TB should be considered high up in the differentials, par ticularly in endemic areas with MTB. Patient underwent debridement and open biopsy at first stage, which confirmed the diagnosis of TB. In endemic areas, one, therefore, has to make sure that TB is considered in the differential diagnosis of inflammatory arthritis as the radiological features alone are not enough to differentiate between these conditions. Indeed, these two different pathologies of arthritis present with same laboratory and radiological findings include elevated ESR and CRP, as well as erosive arthritis without formation of osteophytes and with mono-articular involvement.Cases of TB-PJI managed surgically by debridement and retention of implant, debridement and explant, staged procedure (debridement followed by TKA) or arthrodesis have been known (Table 3).

Surgical treatment depends on the status of implant fixation. Implant may be retained if it is stable and only debridement followed by chemotherapy may be required. This strategy has been reported successfully in multiple cases and studies.19,29,35,36 In case of implant loosening or co-infection with pyogenic organism, removal of loose implant and staged revision have been reported.37,38 In recurrent infection cases in severely sick patients, arthrodesis, if bone stock is available, or above-knee amputation, in cases with significant bone loss and destruction, can be potential options to improve patients\' quality of life.

Figure 3 and 4 showing a 68 year old lady with multiple comorbids. Right TKA done for reported advanced OA outside our institution. Presented with pain and swelling of right knee within 11 months postoperatively. Patient u nder went d ebridement and implant removal. Peroperative cultures grew MTB. Planned for revision TKA once free from disease or arthrodesis. Patient was kept on ATT but was not compliant and had multiple hospital admissions due to heart failure, asthma, electrolyte imbalance and drowsiness. This unfortunate sick lady had recurrent TB infection with significant bone loss and ultimately underwent above knee amputation.


Obtaining synovial specimens and specifically requesting TB culture and histology are the most pertinent investigations. Early diagnosis and treatment may prevent prosthetic loosening and avoid revision surgery with significant benefit to the patient and optimising outcomes and resources. Adding to this challenge is inflammatory arthritis affecting the knee joint present with almost identical features on clinical examination, laboratory tests and radiographical findings. TB should always be amongst differential diagnosis in cases of erosive inflammatory arthritis in endemic areas. Needless to say that this issue should be dealt with in multi-disciplinary setting including experienced surgeon, infection disease control consultant, histopathologist and public health workers to improve the outcome of these patients in a developing country.

We declare that this paper was not previously
presented or published anywhere. This was not part of any other projects.
Conflict of Interest: No conflicts of interest to disclose.
Sources of Funding: No funding from any source for this


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