Need for anti-tuberculosis treatment in patients with latent tuberculosis infection who undergo arthroplasty: a case report

Introduction

Tuberculosis (TB) is one of the leading causes of death globally (1). In 2018, there was an estimated 10 million new TB cases globally, and 1.2 million [human immunodeficiency virus (HIV) negative] TB deaths and 251,000 (HIV positive) TB deaths (1). Mycobacterium TB infections affect about 1/3 of the world’s population (2). The number of TB cases in China accounts for 9% of the world’s total, and with 1,300,000 new cases every year, China is 1 of 30 countries with a high TB burden (2). Based on the state of the disease, TB is divided into latent tuberculosis infection (LTBI), active TB, and non-active TB. About a 1/4 of the global population is infected with latent TB (3). LTBI refers to a special state in which the host has sustained an immune response with mycobacterium TB antigens after infection with mycobacterium TB, but there is no evidence of clinically active TB. LTBI can progress to active TB.

About 90% of those infected with mycobacterium TB have asymptomatic latent infections (2). It has been reported that 85–90% of newly diagnosed active TB cases evolve from patients with LTBI (4). The ɣ-interferon release assay (IGRA), which detects ɣ-interferon production in T lymphocytes stimulated by specific antigens of mycobacterium TB, has many advantages. A study suggest that IGRA has high specificity, good reproducibility, and is not affected by swelling and allergic reactions in the diagnosis of mycobacterium TB infection (5). IGRA is recommended by the World Health Organization (WHO) for the detection of LTBI (2). T-SPOT.TB is a test for IGRA that directly counts the T cells that release ɣ-interferon. T-SPOT.TB is the 4th IGRA approved by the Food Drug Administration. At present, a diagnosis of LTBI does not depend on the pathogen and clinical manifestations of mycobacterium TB, but on the cellular immune response status of specific antigens of mycobacterium TB (6). The diagnosis of LTBI is based on positive IGRA results.

Artificial arthroplasty has achieved great success in the 20th century. With improvements in living standards and economic conditions, the number of artificial arthroplasty procedures performed is also increasing. It is estimated that as many as 1 million hip arthroplasties are performed worldwide each year, and that this number is increasing (7,8). In the United States (US), 700,000 knee arthroplasties are performed annually, and this number is increasing worldwide (9). The vast majority of people undergoing arthroplasty are aged 60 years and older (10,11). In the United Kingdom, the average age of patients undergoing hip arthroplasty is 69 years, and 68% of hip arthroplasty patients are older than 65 years (10,11). In Australia, 64% of patients undergoing hip arthroplasty are older than 65 years, and the median age of knee arthroplasty patients is 60 years (12,13).

Arthroplasty patients represent a special population. Arthroplasty patients are hospitalized for a long time, may be unable to adapt to the hospital environment, and are subject to mental and surgical stress, all of which can lead to significant increases in the incidence of TB infection (14). At the same time, aging and surgical trauma can reduce the ability of the body to fight infection, which can also promote the recurrence of old or dormant TB infections (14).

At present, reports on the diagnosis and treatment of patients with LTBI who undergo arthroplasty and the clinical effects of anti-TB treatments are rare. This article reviews the clinical results of the diagnosis, treatment, management, and anti-TB treatment of 1 patient with LTBI who underwent artificial arthroplasty at the Department of Joint Surgery of Shandong Second Provincial General Hospital. We present the following case in accordance with the CARE reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5830/rc).

Case presentation

This article reports the case of a female patient, who was born in 1946, and who had continued to reside in her place of birth. In 2018, at the age of 71 years, the patient had experienced right knee pain for >10 years and responded poorly to non-surgical treatment. The patient had no history of medical disease, and no history of, or exposure to, TB. Additionally, the patient had no cough or sputum, no hypothermia or night sweats, and no other general conditions, such as abnormal wasting.

On examination of the right knee joint, no erythema and no sinus tracts or scarring were observed. However, the patient had pressure pain in the joint space, and joint mobility with 5 degrees of extension and 100 degrees of flexion. The results of the other physical examinations were negative. The Hospital for Special Surgery (HSS) score for the knee joint was 52.

Imaging showed a 20-degree valgus deformity of the right lower extremity, the narrowing of the lateral joint space, and osteoarthritic changes in the 3 interventricular spaces (Figure 1). Computed tomography (CT) of the chest showed no calcification, fibrous scar, or pleural effusion.

Figure 1 Pre-operative anteroposterior and lateral radiographs showing tricompartmental osteoarthritis with valgus deformity. R, right.

The patient underwent a positive T-SPOT test and was diagnosed with LTBI and osteoarthritis of the right knee (Kellgren-Lawrence, IV) based on the patient’s symptoms, signs and ancillary examinations; however, the patient had no clinical signs of active TB. After discussion and gaining the patient’s consent, a posterior stabilized cemented artificial total knee arthroplasty was performed in May 2018 (P.F.C; DePuy Orthopedics, Warsaw). Intraoperatively, the joint fluid was clear, with mild synovial hyperplasia and synovial edema. The patient’s post-operative synovial pathology results showed non-specific inflammatory changes. The imaging findings showed a good prosthesis position and force line (Figure 2). The patient took rifampicin (450 mg) once a day on an empty stomach and isoniazid (300 mg) once a day on an empty stomach 2 weeks after the operation for 3 months. The patient recovered satisfactorily and returned to normal life 3 months after the surgery. ‘I am very satisfied with the results of this procedure,’ the patient said 3 months after surgery.

Figure 2 Immediate post-operative anteroposterior and lateral radiographs showing the implant after knee arthroplasty. R, right.

During the follow-up period, attention was paid to the clinical manifestations of the patient (e.g., whether there was pain or swelling, the range of motion, and the HHS score). The post-operative follow-up continued to October 2022, 53 months after the surgery (Figure 3). At which time, the patient was pain-free, with a mobility of 5 degrees of extension and 120 degrees of flexion, a HSS score of 94, and no restriction in her daily activities.

Figure 3 Timeline of interventions and outcomes. LTBI, latent tuberculosis infection.

The work was approved by the ethics committee of Shandong Second Provincial General Hospital (No. XYK20211002). All procedures performed in this study were in accordance with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Globally, LTBI occurs in about 1/4 of the world’s population. In approximately 5–10% of patients, LTBI progresses to active TB during their lifetime; the progression to active TB is related to the immune status of the host (15). One of the mechanisms of TB is the blood-borne transmission of LTBI through unidentified focal sites, in which infected monocytes migrate from the granuloma to inflammatory sites (16). The WHO recommends the preventive treatment of LTBI for people who are likely to progress to active TB and for those who would benefit from preventive treatment (2).

In 2020, the National Association of TB Control and the United States Centers for Disease Control and Prevention established treatment guidelines for LTBI. The guidelines contain 3 versions of a preferred scheme and 2 alternative treatment options that are suitable for LTBI patients sensitive to isoniazid and rifampicin (17). The drugs in the preferred regimen have good tolerability and efficacy, require a short treatment time, and have high treatment completion rates. The preferred protocols are as follows: (I) isoniazid and rifapentine once a week for 3 months. The potential disadvantages of this regimen are that the drugs are relatively expensive and may require multiple medications associated with systemic drug reactions or influenza-like syndromes; (II) Rifampicin once a day for 4 months; and (III) Rifampicin and isoniazid once a day for 3 months.

There is an alternative for patients with LTBI who cannot receive the preferred regimen, such as patients with drug intolerance or drug interactions; that is, isoniazid once daily for 6 or 9 months. In the selection of treatment regimens, shorter treatment regimens are preferred, which have good tolerability, high treatment completion rates, and are effective in the treatment of patients with LTBI. The WHO recommends: isoniazid once daily for 6 or 9 months, rifapentine plus isoniazid once a week for 3 months, isoniazid rifampicin daily for 3–4 months, or rifampicin daily for 3–4 months (2). From the safety point of view, 3–4 months of rifampicin and 3 months of rifapentine plus isoniazid had lower hepatotoxicity and higher completion rates.

TB has been reported to reoccur in LTBI patients after arthroplasty who do not receive anti-TB treatment. Hattrup et al. reported the case of a 78-year-old patient who underwent shoulder arthroplasty for humeral head necrosis and developed a post-operative TB infection of shoulder (18). The patient’s father and sister had developed TB as children, and the patient tested positive for tuberculin at that time but had no history, or clinical or imaging findings indicating TB. Reyes et al. reported the case of a patient with LTBI complicated by systemic lupus erythematosus and Sjogren’s syndrome who underwent right total hip arthroplasty without anti-TB treatment (19). During the operation, TB was found in the hip joint, and the patient was diagnosed with a TB infection. McCullough et al. reported a case of TB infection after a right total hip arthroplasty in a LTBI patient who had not received anti-TB therapy (20).

Harwin et al. reported the case of a 60-year-old patient with LTBI who underwent total knee arthroplasty (21). The patient had come into contact with a TB patient some 25 years ago and received anti-TB treatment for 1 year despite having no positive TB test results and no clinical manifestations of active TB at that time; however, a TB infection occurred after the artificial knee arthroplasty. This patient developed TB infection after anti-TB treatment and the TB infection was thought to be related to the patient’s rheumatoid arthritis.

Due to the lack of diagnosis and treatment guidelines for artificial arthroplasty in patients with LTBI, this patient was given anti-TB drugs for 2 weeks after the operation. The follow-up period was 53 months, the clinical effect was good, and the patient returned to self-care. No prosthesis loosening, osteolysis, or TB recurrence was observed.

This study had its limitations. First, it was a retrospective study with a short follow-up period. Since a diagnosis of LTBI cannot be used to determine whether the TB disease is active, LTBI needs to be combined with clinical manifestations, such as a low fever, night sweats, wasting, and weakness, and imaging tests, such as a chest X-ray or chest CT, to exclude active TB disease. However, a literature search revealed that reports on patients with LTBI who had to undergo arthroplasty were rare. To date, this is the first report of a patient with LTBI who had to undergo arthroplasty.

Anti-TB treatment should be administered to patients with LTBI who have to undergo artificial arthroplasty.

Conclusions

Patients with LTBI who undergo artificial arthroplasty require anti-TB treatment to reduce the risk of TB recurrence.

Acknowledgments

We would like to thank Michael Strickland (Department of Anthropology, University of California, Los Angeles, USA) for his assistance in writing this article.

Funding: This work was supported by the Projects of Medical and Health Technology Development Program in Shandong Province (grant No. 202104070644).

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-22-5830/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5830/coif). All authors report that this work was supported by the Projects of Medical and Health Technology Development Program in Shandong Province (grant No. 202104070644). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The work was approved by the ethics committee of Shandong Second Provincial General Hospital (No. XYK20211002). All procedures performed in this study were in accordance with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Global tuberculosis report 2019. 2019, Geneva: World Health Organization Licence: CCBY-NC-SA3.0I GO.
2. Guidelines on the management of latent tuberculosis infection. 2019, World Health Organization: WHO/HTM/TB/2015.01. Geneva: World Health Organization; 2019.
3. Houben RM, Dodd PJ. The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling. PLoS Med 2016;13:e1002152. [Crossref] [PubMed]
4. Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004;350:2060-7. [Crossref] [PubMed]
5. Lee SH, Lew WJ, Kim HJ, et al. Serial interferon-gamma release assays after rifampicin prophylaxis in a tuberculosis outbreak. Respir Med 2010;104:448-53. [Crossref] [PubMed]
6. Mack U, Migliori GB, Sester M, et al. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J 2009;33:956-73. [Crossref] [PubMed]
7. Organisation for Economic Co-operation and Development. OECD health data. 2017. Available online: http://dx.doi.org/10.1787/health-data-en
8. Ferguson RJ, Palmer AJ, Taylor A, et al. Hip replacement. Lancet 2018;392:1662-71. [Crossref] [PubMed]
9. Weinstein AM, Rome BN, Reichmann WM, et al. Estimating the burden of total knee replacement in the United States. J Bone Joint Surg Am 2013;95:385-92. [Crossref] [PubMed]
10. Inacio MCS, Paxton EW, Graves SE, et al. Projected increase in total knee arthroplasty in the United States - an alternative projection model. Osteoarthritis Cartilage 2017;25:1797-803. [Crossref] [PubMed]
11. National Joint Registry for England, Wales, Northern Ireland and the Isle of Man: 15th annual report. National Joint Registry. 2018. Available online: http://www.njrreports.org.uk/
12. Australian National Joint Replacement Registry annual report 2018. Australian Orthopaedic Association. 2018. Available online: https://aoanjrr.sahmri.com/annual-reports-2018
13. Pabinger C, Lothaller H, Geissler A. Utilization rates of knee-arthroplasty in OECD countries. Osteoarthritis Cartilage 2015;23:1664-73. [Crossref] [PubMed]
14. Kim SJ, Kim JH. Late onset Mycobacterium tuberculosis infection after total knee arthroplasty: a systematic review and pooled analysis. Scand J Infect Dis 2013;45:907-14. [Crossref] [PubMed]
15. Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974;99:131-8. [Crossref] [PubMed]
16. Barr DA, Whittington AM, White B, et al. Extra-pulmonary tuberculosis developing at sites of previous trauma. J Infect 2013;66:313-9. [Crossref] [PubMed]
17. Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep 2020;69:1-11. [Crossref] [PubMed]
18. Hattrup SJ, Bhagia UT. Shoulder arthroplasty complicated by mycobacterium tuberculosis infection: a case report. J Shoulder Elbow Surg 2008;17:e5-7. [Crossref] [PubMed]
19. Reyes HA, Ruiz MA, Sy AM, et al. Multifocal Osteoarticular Tuberculosis in a Lupus With Sjogren Syndrome Patient. Am J Ther 2017;24:e498-9. [Crossref] [PubMed]
20. McCullough CJ. Tuberculosis as a late complication of total hip replacement. Acta Orthop Scand 1977;48:508-10. [Crossref] [PubMed]
21. Harwin SF, Banerjee S, Issa K, et al. Tubercular prosthetic knee joint infection. Orthopedics 2013;36:e1464-9. [Crossref] [PubMed]