Synovial tuberculosis in wrist diagnosed based on metagenomic next-generation sequencing: A case report

Abstract

Synovial tuberculosis in the wrist is a rare disease that is usually misdiagnosed at the early stage. In this case, we presented a 67-year-old male with wrist joint tuberculosis who presented repeated left wrist joint edema for more than 2 years. The patient received surgery twice. During the second surgery, the combination of metagenomic next-generation sequencing (mNGS) and pathological analysis contributed to the detection of Mycobacterium tuberculosis in lesion tissues. Conventional anti-tubercular therapy confirmed the diagnosis of synovial tuberculosis in the wrist joint. In conclusion, mNGS contributed to the rapid and accurate detection of tubercle bacillus.

Introduction

Synovial tuberculosis in the wrist is a rare disease with an incidence of less than 1% among the pulmonary tuberculosis. ¹ This infection condition is rare and the onset is slow with no specific manifestations for the onset and lesion sites, which usually led to misdiagnosis and treatment delay. ² The clinical diagnosis of osteoarticular tuberculosis is mainly relied on the acid-fast staining, microbial culture, and histopathologic examination. However, the sensitivity of these tests was relatively low, for example, that for the acid-fast bacillus to the ZiehlNeelsen staining was merely 20%. ³ In recent years, the application of metagenomic next-generation sequencing (mNGS) greatly enhances the diagnostic rate of tubercle bacillus, which is helpful to the rapid diagnosis of joint tuberculosis. ⁴

Case presentation

Written informed consent was obtained from the patient. The study protocols were approved by the Ethics Committee of our Hospital (No.: 2021192).

A 67-year-old male presented to Department of Hand Surgery of our hospital due to left wrist joint swelling, which required re-surgery because of no definite pathological diagnosis and failure of first surgery. Recurrence was noticed 3 months after surgery, and gradual numbness was noticed in position near the little finger, with occasional finger numbness in the night. The imaging findings of left wrist were shown in Figures 1 and 2. Erythrocyte sedimentation rate showed slight increase, and the other inflammatory index was normal. Left wrist magnetic resonance findings were indicated in Figure 3. After excluding the surgical contraindications, the patient received removal of lesions in the left wrist, wrist joint debridement, tendon brisement, and plaster immobilization in order to relieve the compression as soon as possible. During the surgery, rice body-like substances were observed in a jasmine color in lesions (Figure 4(a)–(c)), and the samples were submitted for bacterial culture, pathological analysis, and mNGS.

Figure 1.

The wrist and finger motion were limited to some extent.

Figure 2.

X-ray imaging for the left wrist indicated osseous damages in the distal part of left ulna combined with soft tissue edema. In addition, the ulnar and radialis space beneath the wrist showed widening. The density of the wrist joint surface showed elevation.

Figure 3.

Multiple nodule shadows around the joint and bone resorption at the distal end of ulna and radius.

Figure 4.

Rice bod-ylike substances observed in lesion during the surgery.

Postoperative mNGS performed by BGI (https://en.genomics.cn/) indicated presence of a composite group of Mycobacterium tuberculosis and 23 DNA sequences, with a sequencing depth of 100 M and a sensitivity of 10 copies/ml. The drug resistance test performed by BGI for rifampicin and isoniazid were all negative. On day 5, there was no bacteria after culture, and the results were still negative on day 28. Histopathological analysis showed presence of Langhans giant cells, epithelioid granuloma, and central necrosis (Figure 5). On this basis, tuberculosis in left wrist was highly suspected, and isoniazid, rifampicin, pyrazinamide, and ethambutol were given for the treatment. The wound healing was good. Two months later, the patient received administration of isoniazid and rifampicin for 4 months, and was followed up for 12 months. There was no recurrence of swelling in the wrist.

Figure 5.

Pathological findings indicated tuberculosis.

Discussion

In clinical settings, it is hard to find the osteoarticular tuberculosis as it is usually confounded with other joint diseases such as chronic or subacute pyogenic arthritis. ⁵ Some of the lesions could be misdiagnosed as chronic osteomyelitis since there might be osseous damages. ⁶ In addition, its diagnosis is still a challenge due to lacking typical clinical manifestation and low sensitivity of the techniques for the testing of tubercle bacillus. ⁷ The diagnosis of extra-pulmonary tuberculosis is mainly based on the pathogen examination. The examination methods include acid-fast staining, microbial culture, and histopathological examination; however, the sensitivity of these techniques is not high. Single surgery may induce infection and bone injury, which may lead to treatment failure. ⁸ As a newly developed method, the mNGS has been commonly utilized in the diagnosis of pathogens as it shows high efficiency, no shifting, and broad spectrum.^9,10 Besides, it has been recommended by many experts.^11–14 In this study, 23 M. tuberculosis sequences were detected in the tissues obtained after surgery. The samples showed an extremely low possibility of M. tuberculosis pollution, and the release of nucleic acid from the M. tuberculosis was relatively low. These bring in great significance even the sequence number is not too much. Combining with the pathological findings featured by typical rice body signs, we concluded that the patient was diagnosed with M. tuberculosis infection.

Conclusion

In summary, for the infection with unknown causes in the wrist, the application of mNGS contributed to the compensation of conventional microbial culture for the screening of pathogens, which improved the diagnostic rate of pathogen and resulted in the rapid diagnosis of joint tuberculosis. In addition, it may provide helpful information for the cases that were not typical in symptoms and the establishment of treatment regimens by the clinical physicians.