Evidence for the presence of synovial sheaths surrounding the extensor tendons at the metacarpophalangeal joints: a microscopy study
Arthritis Research & Therapy volume 24, Article number: 154 (2022)
MRI-detected inflammation around the extensor tendons of metacarpophalangeal (MCP-) joints is prevalent in RA and poses a markedly increased risk of RA development when present in arthralgia patients. Such inflammation is called ‘peritendinitis’ since anatomy literature reports no presence of a tenosynovial sheath at these tendons. However, the presence or absence of tenosynovium at these extensor tendons has never been studied. Therefore, an anatomical and histological study of extensor tendons at the MCP-joints of three embalmed human hands was performed. Immunohistochemical staining showed the presence of markers for synovial macrophages and fibroblast-like synoviocytes bordering a natural dorsal space next to the extensor tendon, suggesting the presence of a synovial lining. This implies that contrast-enhancement on MRI around extensor tendons at MCP-joints observed in early RA and pre-RA likely represents tenosynovitis and that inflammation of this synovial tissue is an early feature of RA.
Human anatomy is one of the oldest cornerstones of medical education. It may seem surprising that advances in this field are still made. However, modern imaging techniques, such as MRI, visualize the human body in increasingly finer detail, posing new questions how to anatomically interpret what is seen . For rheumatoid arthritis (RA), this applies to tenosynovitis of the hand and foot, i.e. inflammation of the synovial sheaths that surround tendons, which was recently reported to be characteristic for RA .
In feet of RA-patients, MRI-detected inflammation surrounding metatarsophalangeal (MTP)-tendons occurs frequently. Surprisingly, anatomical literature left it undetermined whether these tendons are surrounded by synovial sheaths. A recent anatomical study revealed that these tendons do possess synovial sheaths, both at flexor and extensor sides, implying that MRI-detected inflammation surrounding MTP-tendons in RA represents tenosynovitis .
Also in the hands of RA-patients, at the flexor and extensor tendons of metacarpophalangeal (MCP-) joints, MRI-detected tenosynovitis is prevalent. Moreover, in patients with arthralgia, contrast-enhancement around MCP-extensor tendons poses a high risk of RA-development . According to anatomical atlases, the MCP-extensor tendons lack a synovial sheath; therefore, inflammation around extensor tendons is termed ‘peritendinitis’. The source of these anatomical images is unclear; to the best of our knowledge, the presence or absence of a synovial sheath at these extensor tendons was never studied. We hypothesized that the tissue surrounding the MCP-extensor tendons is not different from MTP-joints and thus that a tenosynovial sheath is present. Therefore, to reconsider the current anatomical information, and with the ultimate aim to improve our understanding of tissues inflamed in early RA, we performed a microscopy study of the extensor tendons at the MCP joint and performed immunohistochemical staining for markers of synovial tissue (fibroblast-like synoviocytes and macrophages).
Three embalmed human hands obtained from bodies donated for research and education were dissected. The materials studied belonged to persons (77- and 90-year-old males and a 92-year-old female) without morphological signs or known history of RA. From the first two hands, a block containing the cutis, subcutis, extensor digitorum tendon, surrounding connective tissue and underlying bone was removed at the MCP-joints, on which routine histology was performed with haematoxylin–eosin (HE) staining. From a third hand, a block of tissue was removed at the third MCP-joint without the bony element. On this specimen, next to HE, immunohistochemical staining was performed using anti-CD68 (14–0688-82, ThermoFisher, USA, 0.5 μg/ml; detection of macrophages), anti-CD55 (PA5-78,991, ThermoFisher, USA, 0.5 μg/ml; detection of fibrobrast-like synoviocytes) and anti-cadherin-11 (AF1790, R&D Systems, USA, 0.2 μg/ml; detection of fibroblast-like synoviocytes) antibodies. Methods and results are presented in more detail supplementary (S1).
Upon microscopy of the HE-stained transverse sections, we observed a thin space at the dorsal side of the extensor digitorum tendon (Fig. 1A–C). At the palmar side of the tendon, condensed connective tissue mainly consisting of collagen was present. The results of the extensor tendons at the third MCP-joint are presented, the other MCP-joints revealed a similar image. Immunohistochemical staining was performed to further characterize the connective tissue surrounding the extensor tendon (Fig. 1D). This showed expression of CD68, CD55 and cadherin-11, consistent with the presence of macrophages and fibroblast-like synoviocytes. Especially at the dorsal side of the tendon (lane 1), a thin layer positive for CD55 and cadherin-11 was detected bordering the natural space. Also CD68-positive macrophages were present in this layer. The tissue at the palmar aspect of the tendon (lane 2) has no cadherin-11 expression while CD55 was widely expressed, consistent with scattered fibroblasts. In addition, some scattered macrophages were detected.
The results from microscopy provided evidence for presence of synovial tissue near the extensor tendons of MCP-joints, suggesting that contrast-enhancement around these tendons observed in RA represents tenosynovitis and thus inflammation of synovial tissue. An anatomical and histological study of extensor tendons from patients with active RA and controls would be the ultimate proof. Possibly, as synovial inflammation is known to involve hyperplasia and synovial thickening , the expression of markers used may be higher in case of active inflammation around the tendon. However, such materials are challenging to obtain. To the best of our knowledge, only a single histopathology study of tenosynovium from patients with longstanding active RA has ever been performed, which examined extensor tendons at the level of the wrist . Histopathological studies on tenosynovitis, at any location, from RA or even pre-RA stages are lacking. This is a subject for future studies.
Interestingly, MRI-detected contrast-enhancement around MCP-extensor-tendons is mostly observed at the dorsal side of the tendon (Fig. 2), which is consistent with increased expression of synovial tissue markers most distinctively dorsal to the tendon. At the palmar part of the tendon the synovial lining was unclear. This might be explained by the thinness and fragility of this uninflamed tissue in healthy individuals. Additionally, the fibrous bands that interconnect the extensor-tendons to prevent subluxation whilst flexing fingers may also play a role; a dense connection may prevent the presence of an epithelium-lined space at the palmar side as observed at the flexor tendons. Remarkably, the contrast-enhancement on MRI is more flattened than around flexor tendons (Fig. 2). Presumably, this may be partly explained by the aforementioned fibrous bands causing pressure on the tendon-sheaths (Fig. 3, Supplementary Table S2 and S3). Extensor tendons are also anatomically smaller than flexor tendons and become flattened at the level of the MCP joints where they merge with the dorsal expansion of lumbrical and interosseous muscles into the extensor hood [6, 7]. Further studies with larger numbers of specimen are warranted to study anatomic variants. Nonetheless, our data suggest that contrast-enhancement around extensortendons in RA represents tenosynovitis, which may warrant modification of the classic anatomic pictures of the hand as proposed in Fig. 4. Thus, advanced imaging led to multidisciplinary research that challenged previous assumptions and revisited anatomic knowledge, resulting in a better understanding of tissues involved in RA-development. Ultimately this knowledge contributes to unravelling RA-pathophysiology.
Availability of data and materials
Data can be requested from the corresponding author.
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This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Starting grant, agreement No 714312), and the Dutch Arthritis Society.
Ethics approval and consent to participate
All anatomical specimens were obtained from human bodies that were donated according to the Dutch Burial and Cremation Act to the department of Anatomy and Embryology at the Leiden University Medical Center for use in scientific research and medical education. Since the bodies had been donated for medical research under this act, no additional local ethics approval was needed for this specific research. During life, all the donors have signed an informed consent form to state that their body can be used for any kind of medical research, which was approved by the mayor of the city.
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Supplementary methods (S1). Table S2. Patterns of extensor tendons on the dorsum of the hand according to the literature. Table S3. Frequency of intermetacarpal fibrous bands according to the literature.
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Dakkak, Y.J., van Dijk, B.T., Jansen, F.P. et al. Evidence for the presence of synovial sheaths surrounding the extensor tendons at the metacarpophalangeal joints: a microscopy study. Arthritis Res Ther 24, 154 (2022). https://doi.org/10.1186/s13075-022-02841-7
- Tendon sheath
- Rheumatoid arthritis