07/12/2024
Spectrum of Rotator Cuff Disease 💡
▶️ Rotator cuff (RC) tears represent a spectrum of disease, from tendinopathy, to partial-thickness tears and to full-thickness tears of varying sizes (s. figure, modified after Bedi et al. 2024, https://pubmed.ncbi.nlm.nih.gov/38332156/)
⬛ RC tendinopathy
▶️ The proposed mechanisms of RC tendinopathy include intrinsic, extrinsic, or combined mechanisms (https://pubmed.ncbi.nlm.nih.gov/18801774/, https://pubmed.ncbi.nlm.nih.gov/20846766/, https://pubmed.ncbi.nlm.nih.gov/26390274/)
1️⃣ External mechanisms are characterized by inflammation of the bursa above the rotator cuff and bursal-sided RC tendon compression due to altered shoulder kinematics. When the larger muscles (deltoid) over-compensate due to rotator cuff dysfunction, the rotator cuff cannot function as an effective force couple, resulting in the humeral head elevating rather than depressing during shoulder motion (https://pubmed.ncbi.nlm.nih.gov/6825348/). This abnormal motion exacerbates bursal inflammation, causing pain during motion, overhead activities, and sleep (https://pubmed.ncbi.nlm.nih.gov/38332156/). But for years, the theory of external shoulder impingement has been strongly questioned scientifically (https://www.tandfonline.com/doi/abs/10.1179/1743288X11Y.0000000027, https://pubmed.ncbi.nlm.nih.gov/33244115/, https://pubmed.ncbi.nlm.nih.gov/30707445/).
A unique subset of RC tendinopathy with an extrinsic mechanism is internal impingement. Patients with internal impingement tend to present with pain located in the posterior and superior aspects of the shoulder typically while the arm is in abduction and external rotation of the late cocking phase of throwing (https://pubmed.ncbi.nlm.nih.gov/8534293/, https://pubmed.ncbi.nlm.nih.gov/8504590/). In this position, the articular aspect of the RC tendons becomes mechanically impinged between the posterior superior glenoid rim and the humeral head (https://pubmed.ncbi.nlm.nih.gov/20846766/).
2️⃣ There is a growing body of evidence to support an intrinsic mechanism. Intrinsic mechanisms relate to factors that directly influence tendon health and quality, including aging, (https://pubmed.ncbi.nlm.nih.gov/10471998/) genetics, (https://pubmed.ncbi.nlm.nih.gov/19411462/) vascular changes, (https://pubmed.ncbi.nlm.nih.gov/19293165/) and altered loading (https://pubmed.ncbi.nlm.nih.gov/19364757/).
▶️ Tendinopathy as a potential precursor to tears, exhibits disorganized collagen, increased inflammatory cells, and reduced vascularity. However, symptoms do not consistently correlate with the histopathological severity of tendinopathy or the extent of rotator cuff tears. The prevalence of asymptomatic partial-thickness and full-thickness RCTs has been reported to range from 8% to 40% and from 0% to 46%, respectively (https://pmc.ncbi.nlm.nih.gov/articles/PMC7026731/). This disconnect underscores the complex interplay between structural degeneration, inflammation, and pain perception, which may be influenced by central nervous system mechanisms (https://pubmed.ncbi.nlm.nih.gov/38332156/).
⬛ Progression of the disease
The progression from tendinopathy to partial- and full-thickness tears is not fully understood but is thought to begin with a failed healing response to microtrauma and the role of inflammation in these conditions has been re-evaluated and is thought to be an important contributor (https://pubmed.ncbi.nlm.nih.gov/15634833/, https://pubmed.ncbi.nlm.nih.gov/28596062/). This involves increased inflammation mediated by tenocytes and immune cells releasing pro-inflammatory cytokines such as TNF, IL-6, and IL-1β. IL-17A, in particular, is notable for its role in promoting inflammation and apoptosis in rotator cuff tendons (https://pubmed.ncbi.nlm.nih.gov/27263531/).
⬛ Pain and the neuroimmune system
An upregulation of the glutamatergic system has been observed in patients with rotator cuff tendinopathy. Glutamate localizes to tenocytes and is detected on macrophage glutamate receptors, suggesting its role in pain modulation (https://pubmed.ncbi.nlm.nih.gov/24872365/).
▶️ In summary, rotator cuff disease evolves from biomechanical dysfunction and inflammatory responses to chronic structural degeneration, with pain perception influenced by neuroimmune changes. The bursa and inflammatory pathways, particularly IL-17A, represent key areas for understanding disease mechanisms and potential therapeutic interventions.
▶️ A review by Lo and colleagues in 2023 found biochemical changes such as inflammatory molecules in the subacromial bursa, levels of IL‐1 β and IL‐6 in the synovial fluid of the glenohumeral joint and serum levels of VEGF to demonstrate moderate to strong correlations (r = 0.66–0.75) with rotator cuff related shoulder pain.
📸 Figure modified after Bedi et al. (https://pubmed.ncbi.nlm.nih.gov/38332156): Representative pathology and functional differences in rotator cuff pathology. RC-tendinopathy, partial-thickness and small full-thickness tears present with similar symptoms, with pain on overhead activity, pain at night and variable findings on clinical examination. Patients with larger and massive tears will have lost their force couple and have difficulty elevating their arm, and are more likely to have a positive external rotation lag test than patients with small tears.
