Frozen Shoulder
a form of arthrofibrosis
Shoulder arthrofibrosis is called “frozen shoulder” and “adhesive capsulitis” [1]-[3]. In fact, arthrofibrosis is known by many names [4], an unfortunate situation that allows misunderstandings to persist and making access to treatments more difficult. The main difference between the joint pathologies is that knee arthrofibrosis is usually the result of trauma, while shoulder arthrofibrosis is typically idiopathic (has no obvious cause), but may arise from a series of small insults that are not noticed, or damaged structures that place stress on the joint [4].
Arthrofibrosis is a pathological wound healing response that can occur in any joint and is characterised by joint contractures, adhesions of tissues and pain. In all joints, including shoulders, these processes manifest as chronic pain and debilitating restriction of joint movement [1]. Pain can disturb sleep, and the loss of motion of the shoulder can make daily living activities extremely difficult [5]. Pain diminishes as inflammation resolves, and the condition can become “residual arthrofibrosis” for a time [4], which is sometimes referred to as the “thawing” phase. Diagnosis relies on symptoms and the exclusion of other problems such as dislocation, infection and fractures [3]. MRI and ultrasound imaging can assist the diagnosis.
Shoulder arthrofibrosis is a common problem worldwide, afflicting around 8 % of men, and 10 % of women of working age [5], which probably makes it the most common form of arthrofibrosis. A study of twins reported a genetic predisposition for shoulder arthrofibrosis in some people [4] and it’s more common when other conditions increase inflammation. For example, shoulder arthrofibrosis can affect up to 38 % of people with thyroid problems and 76 % of people with diabetes over their lifetime [6]. However, other conditions are not always present. Fibrosis commonly affects the rotator cuff interval, which is formed by the major tendons that attach to the joint [6], and the subcoracoid fat pad and pouch [2].
The pathology of shoulder arthrofibrosis is the same as for other joints [4]. Arthrofibrosis occurs after trauma (including surgery), prolonged immobilisation of the joint and infection [1]. An insult begins a cascade of inflammation, proliferation of myofibroblasts (the cells that cause fibrosis), scar tissue production and joint capsule thickening [3]. Myofibroblasts grow large numbers of adhesion molecules on their surface that stick to surrounding tissues and create adhesions and contractions.
It’s a common assumption that shoulder arthrofibrosis completely resolves over time, but recent studies indicate that this is not accurate [6] and around 40 % of people still have symptoms after 4 years [5]. Increased pain in the affected shoulder is associated with an increase in the density of nerves in the joint [2][6], (see Pain blog), and this may explain why resolution can be difficult. It’s therefore important to understand what helps and what may be harmful, and to get early and gentle treatment.
Unfortunately, it’s not yet clear which treatments for shoulder arthrofibrosis are the most effective; however, injections of corticosteroids and physical therapy, including passive stretching in the pain-free zone, are currently the primary treatments. A recent analysis concluded that physiotherapy, surgical release of adhesions in the capsule and manipulation under anaesthesia helped, but the difference in outcomes was unlikely to be clinically important [5]. It is worth noting that manipulation under anaesthesia (that tears adhesions apart) and surgery can potentially have serious side effects [3][5], and may worsen symptoms by re-injuring the tissues [1][6]. Pain management and reducing inflammation can help people recover with fewer associated risks. Corticosteroids are frequently injected into the joint and can greatly reduce inflammation, but can also have toxic effects on cartilage when repeated. Collagenase injections in the shoulder have shown promise and appear to be safe [3][4]. Non-operative, next generation therapies that target inflammation and fibrosis are currently being sought [3].
Although “frozen shoulder” is easy to say, calling it “shoulder arthrofibrosis”, or simply “arthrofibrosis” instead will help the community and clinicians understand and access better care in the future.
Interview
with
Dr Millar
Dr. Kayley Usher interviews Prof. Dr. Neal Millar about frozen shoulder (shoulder arthrofibrosis). Professor Neal Millar is an Academic Consultant Orthopaedic Surgeon specialising in shoulder surgery, having completed shoulder fellowships in Sydney and New York. Past work has highlighted the role of inflammation and cytokines in tendon disease and is currently focused on understanding the role of microRNA in the post transcriptional regulation of collagen synthesis and immediate tissue repair processes implicated in tendinopathy. Dr Millar is first author of the review article "Frozen Shoulder", published in Nature Reviews - Disease Primers, in 2022.
"Patients will come saying that they've got significant pain at night and and day and there's nothing they can do about it. Another symptom that's associated with shoulder arthrofibrosis obviously is stiffness, but the stiffness can be a gradual onset."
"One of the first things you'll lose with a frozen shoulder range of movement is the loss of external rotation. It can even be subtle."
"A plane shoulder X-ray will help you differentiate between osteoarthritis and frozen shoulder which are the main two diagnoses."
"Frozen shoulder affects about 8% of men and about 10% of females, most common in the 50s and 60s, and the peak age is around the mid-50s."
"There's no difference in the pathology… if you biopsy an ankle- or knee arthrofibrosis and compare it to frozen shoulder, it's very, very, very similar diseases."
"It's important to check for systemic metabolic issues, diabetes., hyperlipidemia (high cholesterol) and even hypoadrenalism."
"Inflammation has certainly come to the fore as one of the main drivers of the disease."
"It's all those cytokines, immune cells and things that disrupt the fibroblast. It all affects the structure and that's why you get stiffness. That's ultimately why you can't move your shoulder or it's irritable to move."
"In all diseases when you have inflammation, you get associated neuro-inflammation. In other words, the nervous system is irritated and starts and produces a range of factors that cause pain."
"About 40% of the patients never really make a full recovery."
"Physiotherapy should really be patient orientated, so if your patient has very high pain levels, you're not going to do very much with them. Those weeks are to get their pain under control. The important thing is the right treatment intensities for that patient. All we have to do is passive stretch."
"I've moved away from using surgery as much. Now, I use surgery as a last resort."
"I think it’s rare, but yes, surgeries can certainly make things worse. They can get a pain response from that and they can become more stiff."
"After surgery we get you moving straight away, and then it's really a case of seeing the physio immediately after this in the first few days and starting a stretching and range of movement protocol."
"Overall from a capsular release, you're looking at about three month recovery period until you're getting good functionality back in your arm, and that sort of time frame is what to expect."
"Surgery should not be done aggressively and early because there's plenty of evidence to show physio and other things work."
"I think what you'll see over the next number of years is research into the immune system. It has a massive role to play in this disease, and therapies will be targeted towards that."
References
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Blessing, W. A., Williamson, A. K., Kirsch, J. R. & Grinstaff, M. W. The Prognosis of Arthrofibroses: Prevalence, Clinical Shortcomings, and Future Prospects. Trends Pharmacol Sci, doi:10.1016/j.tips.2021.02.007 (2021).
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Fields, B. K. K. et al. Adhesive capsulitis: review of imaging findings, pathophysiology, clinical presentation, and treatment options. Skeletal Radiol 48, 1171-1184, doi:10.1007/s00256-018-3139-6 (2019).
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Le, H. V., Lee, S. J., Nazarian, A. & Rodriguez, E. K. Adhesive capsulitis of the shoulder: review of pathophysiology and current clinical treatments. Shoulder Elbow 9, 75-84, doi:10.1177/1758573216676786 (2017).
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Usher, K. M. et al. Pathological mechanisms and therapeutic outlooks for arthrofibrosis. Bone Research 7, doi:10.1038/s41413-019-0047-x (2019).
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Rangan, A. et al. Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial. The Lancet 396, 977-989, doi:10.1016/s0140-6736(20)31965-6 (2020).
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de la Serna, D., Navarro-Ledesma, S., Alayón, F., López, E. & Pruimboom, L. A Comprehensive View of Frozen Shoulder: A Mystery Syndrome. Frontiers in Medicine 8, doi:10.3389/fmed.2021.663703 (2021).
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