Case 10

Brendan O’Reilly

Patient Background Left-handed female presented to the ultrasound department with continued left swelling following a fall 5 months previously, resulting in a tender, swollen, bruised left forearm with reduced movement. X-ray at the time of her emergency visit reported a ‘subtle displaced transverse fracture to the distal radius’ (Figure 1). The patient was placed in a below the elbow cast until a review in the local hospital Virtual Fracture Clinic (VFC). Upon review, the cast was removed, and the patient was given a physiotherapist wrist information exercise sheet to follow. Nevertheless, the patient remained symptomatic and on examination in the Orthopaedic Clinic 2 months after the accident, the patient presented with pain on extension and abduction with a positive Finkelstein test (Goubau et al., 2014) - (Appendix 1) and pain on resisted abduction of the thumb, felt along the course of the first dorsal department. An ultrasound request was organised by the Orthopaedic Surgeon who suspected de Quervain’s disease. The purpose of the ultrasound examination was to confirm clinical findings with a view to an ultrasound guided corticosteroid injection if clinically appropriate Figure 1. Anterior –posterior X-ray of the left wrist with discrete, non-displaced, transverse fracture (white arrow) of the distal radius.

The patient presented to the ultrasound department with swelling to the radial aspect of the left wrist, the clinical prior to ultrasound imaging was of the first carpal-metacarpal (CMC) joint, ganglia, infectious tendosynovitis, Wartenberg’s syndrome and intersection syndrome (Shiraj et al., 2013, Rowland et al., 2015)

Ultrasound Examination & Findings In accordance with the Society of Radiographers (SoR) and British Medical Ultrasound Society (BMUS), Guidelines for Professional Ultrasound Practice, verbal patient consent prior to the ultrasound examination was obtained. The patient sat opposite the operator with forearm placed upon the couch. Using a high frequency (7-18MHz) GE Logiq hockey stick ultrasound linear probe in an ergonomic setting, the wrist was moved into lateral, pronation and supination positions to visualise extensor and flexor wrist , nerves, bony contours and synovial structures. These structures were assessed in transverse and longitudinal sections. Emphasis was placed upon assessment of the extensor tendons of compartment I, abductor pollicis longus and extensor pollicis brevis tendons. During assessment of the wrist in the lateral position and thumb facing upwards, ultrasound in transverse section demonstrated thickening of the extensor tendons of compartment I in B- mode with synovial thickening (Figure 2) and increased vascularity with power Doppler (Figure 3) , sonographically in keeping with de Quervain’s . No other extensor or flexor wrist , synovial thickening, neuropathy or bony erosions evident. In view of the preliminary ultrasound findings, the benefits and risks and side effects of an intra- articular corticosteroid injection therapy under ultrasound guidance were discussed. Figure 2.

Thickened left extensor compartment 1 (white arrow) with thickened synovium (arrowhead) in Brightness-mode.

Figure 3. Thickened extensor compartment I on the left with increased power Doppler signal on the right.

While studies and clinical experience have proven ultrasound guided steroid intra-articular injections with their anti-inflammatory properties are relatively safe, provide pain relief and give greater function (Stephens et al., 2008; MacMahon et al., 2009; NICE Osteoarthritis, 2020) , the side effects of this type of therapy relevant to the patient case were explained and are summarised in Appendix 2 with references. Side effects of corticosteroid therapy not relevant to the patient history include diabetic hyperglycaemia, which can persist for 5 to 21days, requiring glycaemic post procedure monitoring (Wang & Hutchinson, 2006; Younes et al., 2007) and bleeding, particularly in patients on anti-coagulation therapy however, studies have shown that stopping anti- coagulation is not required before joint injection provided the INR is within the therapeutic range and less than 4.5 (Conway et al., 2013). Locally the decision to administer corticosteroid for joint injections for those patients on anti-coagulation therapy is clinically dependent. In the setting of the patient case study, who had not been prescribed anti- coagulation therapy, the risk of bleeding remained a side effect for this procedure, of which the patient was informed.

Considering Covid 19, information sharing between clinician and patient is advised by studies from Little et al., 2020 and Morgan & Dattani, 2020. This is regarding the benefits of the intra-articular steroid injection procedure but also the increased immunosuppressive risks to the patient of acquiring Covid 19 following corticosteroid injection therapy. Little et al., 2020 (page 4) goes on to explain ‘where a patient has significant disease activity and there are no effective alternatives, corticosteroid injection should be considered following a shared risk assessment with the patient as part of ‘Montgomery guided’ consent processes’. The patient was made aware that if they contacted the disease following consenting to the procedure then the outcome could be much worse. The patient had already exhausted more conservative treatments for their condition which had been ineffective. While was also an option, involving release of the first dorsal compartment of the wrist and dividing or excising a strip of the with a 97.5 % success rate, this is associated with a high cost, surgical complications (Garcon et al., 2018) and higher waiting times particularly in light of the impact of Covid 19 pandemic on National Health Service. The patient was also given the option not to proceed with treatment or to wait until the Covid 19 pandemic had passed and proceed with the treatment only then. After deliberation, the patient opted to proceed with the injection in view of her persistent symptoms, loss of function and waiting time which she felt outweighed the risks and side effects of injection. A World Health Organisation Surgical safety checklist for Radiological Interventions (Clinical Radiology, 2019, page 12 - Appendix 2) was completed.

Intra-articular Injection Procedure under Ultrasound Guidance Traditionally, intra-articular injection procedures involving the prescribing and administer of medicines was performed between clinician and patient until the publication of the Department of Health final Crown report review on prescribing, supply and administration of medicines (Crown Report, Department of Health 1999). Following the report, ‘legal frameworks were developed that allowed services to be re-designed and for healthcare professionals to work more flexibly for the benefits of patients’ (SCoR & BMUS 2019, Guidelines for Professional Ultrasound Practice, page 143). As a result, there are now several legal options for some statutorily registered healthcare professionals for supplying and/or administering medicines including the commonly used Patient Group Directions (PGD)’, (SCoR & BMUS, 2019) which is used by practicing extended scope Radiographers at the local hospital. A PGD operates under the authorisation of trained and competent individuals and is a written instruction for the sale, supply and/or administration of medicines to groups of patients who may not be individually identified before presentation for treatment. It is used in situations where patient care is benefitted usually in cases where there is an immediate effect. Limitations to working under a PGD include cannot deliver unlicensed medication and cannot delegate responsibility. PGD can however use ‘off label’. The option for staff to train to become independent prescribers (IP) and supplementary prescribers (SP) is also available. The prescribing and administration of corticosteroids for this patient was performed under a patient specific direction (PSD) framework whereby the trainee Advance Practitioner Sonographer was guided by the Consultant MSK Radiologist mentor following patient assessment and delegation of supply and/or administration of medicines. The patient intra-articular procedure commenced with sterile technique to minimise infection including wearing sterile gloves, cleaning of the effected site with sterile cleaning solution and the use of a Tegaderm film over the hockey stick probe to maintain sterility with sterile ultrasound gel. Using a 25 gauge 1 inch needle and 5mls syringe, local anaesthetic (2mls of lidocaine hydrochloride), was injected at a 45° angle using ultrasound guidance in-plane technique from a distal to proximal direction (Figure 4) into the skin and into the extensor compartment I tendon sheath. Following this 20mg of Methylprednisolone Acteate (Depo- Medrone) and 1ml of 0.25% bupivacaine was injected into the extensor compartment I tendon sheath at the level of the distal radius with no immediate complication. Confirmation that the needle was correctly sited in the tendon sheath was demonstrated by using the in- plane technique and rising of the tendon sheath with reduced pressure (Figure 5). Rest of the limb was advised following the examination for 2 weeks with repeat second steroid injection offered if symptoms persisted.

Figure 4.

Figure 5. Visualisation of needle (arrow) and lifting of tendon sheath (arrowhead).

De Quervain’s Disease, Treatment Rationale & Discussion De Quervains is defined as the stenosing tenosynovitis of the of the abductor pollcis longus and extensor pollicis brevis (Lee et al., 2014), causing impaired gliding of these tendons in the narrow and constricted fibro-osseous compartment. It is caused by the overuse and repetitive activities of wrist in ulnar deviation, extension and abduction of the thumb (Pooswamy & Muralidharaogpalan, 2019). It affects 0.5% of working men and 1.3% of working women (Walker-Bone et al., 2004). Risk factors include manual work, , early motherhood and post-menopausal status (Vuillemin et al., 2012). Rheumatoid arthritis is also a causative factor (Weiss et al., 1994). The presence of a dividing septum in extensor compartment 1 (Minamikawa et al., 1991) and multiple slips of the extensor abductor pollicis longus have also been associated with de Quervains (Mansur et al., 2010). Histopathological in de Quervain’s examination shows mainly degenerative changes like myoxoid degeneration, fibrocartilaginous metaplasia and deposits of mucpolysaccharide (Clark et al., 1998) however Kuo et al., (2015) demonstrated the presence of inflammatory cells in this condition which increased with disease progression. Non-surgical treatment of de Quervain disease included immobilisation with splinting and therapeutic exercises however these techniques were unsuccessful. This is supported by Richie& Eriner, 2003 who found the above techniques only 14 % successful in the treatment of de Quervain’s. Corticosteroid injection however, under ultrasound guidance has been shown to be effective and a safe method for treatment (Danda et al., 2016 and Pooswamy & Muralidharaogpalan, 2019). The combination of injection and thumb splinting has been demonstrated to show improved functional outcome in comparison to injection alone in one study (Mardami-Kivi et al., 2014). Other non-invasive methods for the treatment of de Quervain’s include (da Silva et al., 2014), ozone oxygen and hyaluronic acid injections (Moretti,2012), ultrasound-guided percutaneous needle tenotomy, platelet-rich plasma (PRP) injection( Peck & Ely, 2013), prolotherapy (Tseng et al., 2012) and ultrasound guided methotrexate injection (Allam et al., 2017). Failing conservative measures, surgery is an option but as discussed earlier, despite high success rates has drawbacks. Intra-articular corticosteroid injection of joints is the main method used at the local site for the treatment of tendinopathy, including de Quervain disease following exhaustion of all other conservative means. Ultrasound advantages for guided corticosteroid injection include real time assessment and guidance with visualisation of the needle throughout the procedure. The needle bevel tip can be accurately positioned to the area of interest for maximum therapeutic effect, thus avoiding important structures such as vessels and nerves and causing unnecessary side effects to subcutaneous tissues. Additionally, in comparison to blind needle positioning, ultrasound guided needle placement provides high accuracy and low complication rate.

It is particularly advantageous at assessing more superficial structures more quickly in comparison to other imaging modalities such as CT and is also beneficial when injecting into extensor compartment I sub-compartments when there is a dividing septum or multiple slips (McDermott et al., 2012). Rousset et al., 2010 has suggested that the presence of an osseous ridge/double ridge on the radial floor sonographically is associated with the presence of an extensor compartment I septum. Observation of this is important as steroid injection can then be directed into both compartments thereby improving outcome (Sawaizumi et al., 2007). Nevertheless, the ability to identify such structures is reliant on the ultrasound skills and experience of the operator. Disadvantage with multiple injections are that there is an increase of procedure side effects. No obvious septum was visualised in the patient case study. Alongside the advantages above, ultrasound also has good resolution, is safe (as it does not use non-ionizing radiation), does not cause patient claustrophobia effects as with MRI, can be used dynamically with fast time duration, cost-effective in comparison to other imaging modalities such as MRI, portable and has the ability to compare an abnormal tissue site to the contralateral normal side and thus support preliminary findings. This is highlight in (Figure 6) of the case study. Ultrasound is also able to identify earlier bony cortical and soft tissue changes such as in Rheumatology patients in comparison to x-ray, thereby providing an earlier diagnosis and therefore earlier treatment with improved patient outcome (Taljanovic et al., 2015). Power Doppler is also used to identify vascular structures and to reflect the degree of to a joint i.e. (Figure 3) - (Taljanovic et al., 2015). Ultrasound disadvantages include operator dependency. The ability to identify and provide an accurate diagnosis using all sonographic technical parameters available relies on the training, competency and clinical experience of the ultrasound operator. Ultrasound operators also need to be alert to the many sonographic artefacts that occur, particularly in musculoskeletal ultrasound such anisotropy which can give the impression of an abnormal hypoechoic tendon/tissue, caused by the ultrasound probe not perpendicular to the area of interest.

Figure 6. Normal extensor compartment I tendons on the left (white arrow) of the image in comparison to thickened hypoechoic tendinopathy with synovial thickening in extensor compartment 1 on the right of the image (white arrowhead).

The purpose of the local anaesthetic used in the case study is immediate pain relief, diagnostically differentiate between local and referred pain (Tallia & Cardone, 2003), add volume to the cortico-steroid enabling spread within the joint space (Stephens et al., 2008) and disruption of any adhesions (Buchbinder & Green, 2004). 2 mls of Lidocaine Hydrochloride and 1 ml of 0.25% bupivacaine were the 2 anaesthetics used for the examination. The former has an onset of 1 to 2 minutes and duration of 1 hour while the latter, an onset of 30 minutes and a duration of 8 hours (Shah et al., 2019). Ropivacaine is also available to use in the department however the choice between ropivacaine and bupivacaine for intra-articular steroid injections is debatable. Burke & Price (2017) have shown that concentrations of less than 0.75% ropivacaine and 0.25% bupivacaine or less have fewer chondrotoxic effects on osteoarthritic cartilage. The article further describes the similar chemical make-up of both drugs but also important differences such as ropivacaine diffuses less readily than bupivacaine into the systemic system and therefore has fewer cardiovascular and central nervous system toxic effects. Bupivacaine is more potent than ropivacaine, which allows it to reach the same therapeutic level as ropivacaine at lower concentrations. A final point is that ropivacaine is more expensive than bupivacaine (Burke & Price (2017).

The choice of corticosteroid is based on clinical experience as well as local and national guidance. Locally the main corticosteroids used are triamcinolone acetonide 20mg/ml (Kenalog) and methylprednisolone acetate 20mg/mL (Depo-Medrone). The clinical effects of these are to reduce blood flow (Caldwell, 1966), lower leukocyte and inflammatory modulator response ( Lavelle et al., 2007) and alter local collagen synthesis (Wei et al., 2006) thereby reducing pain and inflammation (Stephens et al,. 2008). Based on recommendations by the National Institute for Health and Care Excellence (2017) methylprednisolone is the preferred choice for smaller joints due to its smaller particle size (0.5-26 μm) in comparison to triamcinolone acetonide which has particle size of 15-60 μm and therefore used on larger joints such as the hip. Methylprednisolone is also used on larger joints but is suggested for superficial soft tissue injections while triamcinolone is used for deeper sites. Doses of methylprednisolone vary to joint site but locally 40mg are used for larger joints (knee, ankle and shoulder) while 20mg are used for superficial structures such as the hand and foot. Some cases have discussed the toxic effect on articular cartilage by steroid injection however, it was also argued that the accelerate joint damage may also be due to overuse (Douglas, 2012). Further studies with humans and primates have shown no harm with multiple injections to the knee (Philipose et al., 2011) while some studies have also supported the notion that steroid has a chondral-protective effect (Douglas, 2012). Contraindications for intra-articular injection include sepsis, known hypersensitivity to an intra-articular agent, osteochondral and intra-articular fracture, severe joint destruction and unstable coagulopathy (Shabani et al., 2015).

Patient Outcome On presentation, the patient described the severity of her wrist pain as 9 out of 10. Following diagnosis of de Quervain disease sonographically and intra-articular steroid injection the patient’s pain scale had subsided to1 to 2 out of 10. There remained some reduced dorsi- extension and flexion of the wrist but this was non painful. No follow up orthopaedic appointment has been organised. The patient was advised that the therapeutic effect of the injection may be temporary, prevailing for 6 weeks or possible longer. A repeat injection was offered if symptoms did persist however it was discussed that a repeat steroid injection maybe less effective. On assessment of this Oh et al., 2017 argued that 90% of de Quervain’s disease patients did report improvement after a second injection if the initial steroid injection procedure was successful but, this study also suggested that cases of female sex and BMI >30 are associated with increased treatment failure. NICE (2017) current guidelines recommend that the same joint is not injected more than 3 times in one year.

Conclusion: De Quervain disease is a debilitating condition causing inflammation, pain and reduced function to extensor compartment I. It is more prevalent in women and in pregnancy and is associated with and rheumatoid arthritis. Anatomical variations in extensor compartment 1 such as a dividing septum or multiple tendon slips have also been associated with the disease. Intra-articular cortico-steroid injection under ultrasound guidance is a cost-effective, safe and quick method to treat this condition. Efficiency, in comparison to other techniques such as ‘blind’ injection, is optimised by accurate ultrasound guidance of the needle into the tendon sheath, thus avoiding other important structures. There are however procedure side effects and a current increased risk of contracting Covid 19. These adverse effects/risks need to be shared between operator and patient prior to proceeding. Accuracy and effectiveness of this procedure is reliant upon the ultrasound and clinical skills and experience of the operator, who must maintain their competency through reflective practice, training, audit and clinical peer review. Procedure failure can be attributed to poor training and poor injection technique.

References: Allam, AE.Al-Ashkar, DS. Negm, AA, Wu, WT, Chang, KV. (2017). ‘Ultrasound-guided methodrexate injection for De Quervain disease of thew wrist: what lies beyond the horizon?’, JP R, 10, 2299-2302. Buchbinder, R. Green, S. (2004) ‘Effect of arthrography shoulder joint distension with saline and corticosteroid for adhesive capsulitis’, British Journal of Sports Medicine, 38(4), 384- 385. Burke SA, Price LM. (2017). ‘Bupivacaine vs. Ropivacaine: Looking at the chondrotoxic effects of intraarticular anaesthetics in osteoarthritic joints’, MU Scholarly Commons Physician Assistant Capstones. http://commons.lib.jmu.edu/pacapstones/24. Published May 16, 2017. Caldwell, JR. (1996). ‘Guide to selection and indications for use’, Drugs, 52(4), 507-514. Conway, R. O’Shea, FD. Cunnane, G. Doran, MF. (2013). ‘Safety of joint and soft tissue injections in patients on anticoagulation’, Clinical Rheumatology,32 (12), 1811-1814. Clarke, MT, Lyall HA, Grant JW, Matthewson MH. (1998). ‘The histopathology of de Quervain's disease’, J Hand Surg Br; 23:732. Clinical Radiology, the Royal College of Radiologists. (2019). ‘Guidance on implementing Safety checklists for radiological procedures’, www.rcr.ac.uk (Accessed: November 2020). Da Silva, JB. Batig, A. Lia, F. (2014). ‘Acupuncture in De Quervains ? ™ disease: a treatment proposal’, Acupunct. Med, 32(1), 70-72. Department of Health. (1999). ‘Review of prescribing, supply and administration of medicines’. Chair: Dr June. Crown London: DH

Douglas, RJ. (2012). ‘Cortocosteroid injection into the osteoarthritic knee: drug selection dose, and injection frequency’, International Journal of Clinical Practice, 66 (7), 699-704.

Garcon, J. Charruau, B. Marteau, E. Laulan, J. Bacle, G. (2018). ‘Results of surgical treatment of De Quervain’s tenosynovitis: 80 cases with a mean follow-up of 9.5 years’, Orthopaedics & Tarmatology: Surgery & Research, 104, 893-896.

Gaujpoux-Viala, C. Dougados, M. Gossec, L (2009). ‘Efficacy and safety of steroid injections for shoulder and elbow tendonitis: a meta-analysis of randomised controlled trials’, Ann Rheum Dis, 68 (12), 1843-9.

Goubau JF, Goubau L, Van Tongel A, Van Hoonacker P, Kerckhove D, Berghs B.J (2014). ‘The wrist hyperflexion and abduction of the thumb (WHAT) test: a more specific and sensitive test to diagnose de Quervain tenosynovitis than the Eichhoff's Test’.

Hand Surg Eur (3):286-92. Gray, G. Tenenbaum, J. Gottleib, NL. (1981). ‘Local corticosteroid injection treatment in rheumatic disorders’, Semin Arthritis Rheum, 10, 231-254.

Gurses IA, Coskun O, Gayretli O, et al., (2015). ‘The anatomy of the fibrous and osseous components of the first extensor compartment of the wrist: a cadaveric study’, Surg Radiol Anat, 37, 773–7.

Kuo, YL. Hsu, CC. Kuo, LC, Wu, PT. Sho, CJ. Wu, KC. (2015) ‘Inflammation is present in de Quervain’s disease-Correlation study between biochemical and hisptipathological evalulation’, Ann Plast Surg, 74 (Suppl 2), S146-51.

Lavelle, W. Lavelle, ED. Lavelle, L. (2207). ‘Intra-articular injection’, Med Clin North Am, 91(2), 241-50.

Lee, HJ.Kim, PT. Aminata, IW. Hong, HP. Yoon, JP. Jeon, IH. ‘Surgical release of the first extensor compartment for refractort de Quervain’s tenosynovitis: surgical findings and functional evaluation using DASH score’, Clin Orthop Surg,6(4),405-9.

Little, CP. Birks, M. Horwitz, MD, Ng, CY. Warwick, D. (2020). ‘Covid-19: A rethink of corticosteroid injection?’, Bone & Joint Open, 1|(6), 1-6.

MacMahon, P. Eustance, S. Kavanagh, E. (2009). ‘Injectable cortosteroid and local anesthetic preparations: a review for Radiologists’. Radiology, 252, 647-661.

Mansur, DI. Krishnamurthy, A. Nayak SR. (2010). ‘Multiple tendons of abductor pollicis longus extensors’, Int J Anat Var, 3, 25–6.

McDermott, JD. Ilyas, AM. Nazarian, LN. Leinberry, CF. (2012). ‘Ultrasound –guided injections for de Quervain’s tenosynvitis’, Clin Orthop Relat Res’, 470(7), 1925-1931.

Mardani-Kivi, M. Karimi Mobarakeh, M. Bahrami, F. Hashemi_Motlagh, K. Saheb-Ekhtiari, K. Akhoondzadeh, N. (2014). ‘ Corticosteroid injection with and withour thumb spica cast for de cQuervain tenosynovitis’, J Hand Surg Am, 39(1), 37-41.

Minamikawa Y, Peimer CA, Cox WL, et al. (1991). ‘De Quervain's syndrome: surgical and anatomical studies of the fibroosseous canal’. Orthopedics14 (5), 45–9.

Moretti, M. (2012). ‘Effectiveness of oxygen-ozone and hyaluronic acid injections in De Quervian’s syndrome’,Int J Ozone Ther, 11(1), pp. 31-33.

Morgan, C. Dattani, R. (2020). ‘ Should I use steroid injections to treat shoulder pain during the Covid 19 pandemic’, JES International, 1-4.

National Institute for Health and Care Excellence Clinical Knowledge Summaries (2017) Availableat:https://cks.nice.org.uk/topics/osteoarthritis/#!presribinginfosub:2 (Accessed: November 2020).

Nicholas, AW> (2005). ‘Complications associated with the use of corticosteroids in the treatment of athlestic injuries’. Clin J Sports Med, 15 (5), 370—375. Oh, JK. Messing, S. Hyrien, O. Hammert, WC. (2017). ‘Effectiveness of Corticosteroid Injections for Treatment of de Quervain’s Tenosynovitis’, Hand (NY), 12 (4), 357-361.

Peck, E. Ely, E.(2013). ‘Successful treatment of de Quervains tenosynovitis with ultrasound guided percutaneous needle tenotomy and platelet-rich plasma injection: a case presentation’, PMR, 5 (5), pp. 438-441. Doi: 10.1016/j.pmrj.2013.02.006.

Philipose, J. Baker, K. O’Rourke, KS. Deodhar, A. (2011). ‘Joint Aspiration and Injection: A look at the Basics. Tapping into a valuable diagnostic and treatment resource’, The Journal of Musculoskeletal Medicine, 28 (6).

Possswamy, SS. Muralidharagpalan, NR. (2019). ‘Intra sheath corticosteroid for De Quervain’s tenosynovitis’. International Journal of Research in Orthopaedics, 5 (3), 403-407.

Richie, CA. Eriner, WW Jr. (2003). ‘Corticosteroid injection for treatment of de Quervain’s tenosynovitis: a pooled quantitative literature evaluation’ , J Am Board Fam Pract, 16, 102- 6.

Rousett, P. Vuillemin-Bodaghi, V. Laredo, JP. Parlier-Cuau, C. (2010). Anantomic ‘Variations in the First Extensor Compartment of the Wrist: Accuarcy of US’,Radiology, 257 (2), 427-433.

Rowland, P. Phelan, N. Gardiner, S. Linton, Kenneth & Galvin, R. (2015). ‘The Effectiveness of Corticosteroid Injection for De Quervain’s Stenosing Tenosynovitis (DQST): A Systematic Review and Meta-Analysis’. The Open Orthopaedics Journal, 9, 43-444.

Sawaizumi, T. Nanno M. Ito H. (2007). ‘De Quervain’s disease: efficacy of intra-sheath triamcinolone injection’, Int Orthop, 31(2), 265–268 .

Shabani, F. Farrier, R. Krishnaiyan, C. Hunt, C. Uzoigew, CE. Venkatesan, M. (2015) ‘Common intra-indications and interactions of drugs in orthopaedic practice’, 97 (4)

Shah, A. Mak, SD. Davies, M. James, SL. Botchu, R. (2019). ‘Musculoskeletal Corticosteroid Administration: Current Concepts’, Canadian Association of Radiologists Journal’, https://doi.org/10.1016/j.carj.2018.11.002

Shiraj, S. Winalski, C.S. Delzell, P. Sundaram, M. (2013). ‘Radiologic case study. Intersection syndrome of the wrist’, Orthopaedic, 36 (3), 165-,225-227.

Society of Radiographers and British Medical ultrasound Society. (Revision 4, 2019) Available at: https://www.bmus.org/static/uploads/resources/Guidelines_for_Professional_Ultrasound_Pra ctice_v3_OHoz76r.pdf (Accessed: November 2020).

Stephens, MB., Beutler, AI, O’Connor, . (2008). ‘Musculoskeletal injections: a review of the evidence’. Am Fam Physician, 78, 971-976. Taljanovic, MS. Melville, DM. Gimber, LH. (2015). ‘High resolution of rheumatologic disease’, Radiographics, 35 (7), 2026-2048.

Tallia, AF. Cardone, DA, (2003). ‘Diagnostics and therapeutic injection of the sshoulder region’, AM Fam Physician, 67(6), 1271-1278.

Tseng, V. Ibrahim, V Yokel, NR. (2014). ‘Prolotherapy for de Quervain’s tenosynovitis/tendonosis: a case report’, PM R, 4 (10), S275.

Vuillemin, V. Guerini, H. Bard, H. Morvan, G. (2012). ‘Stenosing tenosynovitis’. J Ultrasound 15(1), 20–28.

Walker-Bone, K. Palmer, K. Reading, I. Coggon, D. Cooper, C. (2004). ‘Prevalence and imapact of musculoskeltal disorders of the upper limb in the general population’, Arthritis Rheum, 51(4), 642-651.

Wang, A. Hutchinson, D. (2206). ‘The effect of cortocsteroid injection at the shoulder joint on blodd gluscose levels in diabetic patients’. J Hand Surg (am), 31(6), 979-981.

Wei AS., Callaci, JJ. Juknelis, D. (2006). ‘ The effect of corticosteroid on collagen expressionin injured rotator cuff tendon’, J Bone Joint Surg AM, 88(6), 1331-1338.

Weiss, AP. Akelman, E. Tabatabai, M. (1994). ‘De Quervain’s tenosynovitis in pregnant and post-partum women’, Obstet Gynaecol. 68, 411-894.

Younes, M. Neffati, F. Touzi, M. (2207). ‘Systemic effects of epidural and intra-articular glucocorticoid injections in diabetic and non-diabetic patients’, Joint Bone Spine, 74(5), 472- 476.

Appendix 1

Finkelstein Test– ulnar deviation of wrist while thumb grasped in palm of hand with pain elicited in extensor compartment 1 during ulnar deviation of wrist (bottom picture, arrow).

Appendix 2

Side Effects Prevalence Added note Reference

Steroid flare 1%-10% Symptoms subside <48 hours Gray et al., 1981

Infection 1in 3000 to 1 Best practice septic technique Stephens et al., 2008 ;

in 100,000 advocated to reduce risk Holland et al,. 2012

Gray et al., 1981; Facial flushing <1% 24 to 72 hours Brinks et al., 2010)

Skin hypopigmentation <1% to 4% More prevalent in dark skinned Gaujoux-Viala et al., populations and in superficial 2009; Nicholas, 2005 injections

Fat atrophy 2.4% May take 2 years to resolve Nicholas, 2005

Tendon rupture <1% Avoid injecting weight bearing Stephens et al., 2008 tendons

Appendix 3

Case 11

Catherine Williams

A Critical Evaluation of the Role of Ultrasound in the Diagnosis and Treatment of Morton’s Neuroma: A Case Study

Introduction Morton’s neuroma (MN) was first described by Thomas Morton in 1876 and is a benign thickening of a plantar interdigital nerve between the metatarsal heads (McNally, 2014) (see Appendix 1). It is also known as “Morton’s , Morton’s entrapment, interdigital neuroma, intermetatarsal neuroma and interdigital nerve compression syndrome” (National Institute for Health and Care Excellence (NICE), 2016, para. 1). It is not a true neuroma however, as it is a degenerative rather than proliferative process, thought to occur due to compression from biomechanical overloading, deformity and/or calf muscle tightness (Gougoulias, Lampridis and Sakellariou, 2019; Santos, Morrison and Coda, 2018). This causes perineural fibrosis and axonal degeneration, with the third webspace most commonly affected (Bianchi and Martinoli, 2015). It is 4-15 times more prevalent in women and this is likely related to wearing high heels which increase pressure in the forefoot (NICE, 2016, para. 3). Patients typically present with burning pain and paraesthesia in the affected webspace and may describe the sensation of walking on a pebble (Pomeroy, Wilton and Anthony, 2015). Conservative treatments such as activity and footwear modification, nonsteroidal anti-inflammatory medications and plantar orthoses are recommended initially and if unsuccessful orthopaedic referral advised (NICE, 2016, para. 5). This case study provides an example, and critical evaluation, of the role of diagnostic ultrasound and ultrasound guided corticosteroid injections (USG-CSI) in a patient with MN who was referred to orthopaedic outpatients (OOPD) with symptom relapse following conservative treatment and a landmark guided (blind) corticosteroid injection (CSI) in the community.

Clinical Presentation A 35 year old female (Patient A) was referred by Podiatry to the OOPD at XXX National Health Service (NHS) Trust in January 2020 for assessment of persistent right metatarsalgia. The referral detailed a 3 year history of a burning sensation in the right forefoot on weight bearing (WB) with toe numbness. Tight footwear and driving exacerbated her symptoms. Patient A works as a cleaner, is a non-smoker, is not overweight and has no pre-existing health conditions. In March 2019, an ultrasound scan of her right foot was performed elsewhere which reported intermetatarsal in the third webspace. Following, orthoses and footwear advice, a blind CSI into the third webspace was performed by a Podiatrist in April 2019, with symptomatic relief for 4-5 months. However, her symptoms had since reoccurred resulting in the onward referral.

The Orthopaedic Surgeon conducted a of Patient A’s feet and reported symmetrical appearances, with irritable second and third right webspaces on the webspace tenderness test (pain elicited when examiners thumb is pushed into the webspace). A positive Mulders click was also noted in the third webspace (a painful, palpable click on lateral compression of the forefoot). WB plain film radiographs (x-rays) were unremarkable (see Appendix 2, Figures 1, 2 and 3) and in view of the symptoms, clinical findings and previous ultrasound, a repeat ultrasound was requested, along with an USG-CSI, to clarify the diagnosis as a MN was suspected.

The Role of Diagnostic Imaging in the Diagnosis of MN Due to the wide range of differential diagnoses for metatarsalgia, x-rays are recommended as a first line investigation to assess bony anatomy and exclude pathologies such as stress fracture or as a cause (Di Caprio et al. 2018; Gougoulias, Lampridis and Sakellariou, 2019). Evaluation should include foot and ankle views, performed WB where possible to provide biomechanical information (Ho, Lui and Tam, 2015). However, whilst these are inexpensive, ultrasound is superior for assessing soft tissues and is advised if no x- ray abnormality is detected and/or clinical findings are equivocal, as with Patient A. Whilst, her presenting symptoms and clinical examination were highly suggestive of MN, ultrasound was necessary to confirm the diagnosis due to the history and fact multiple webspaces were symptomatic (Gougoulias, Lampridis and Sakellariou 2019; Santiago et al. 2018).

A Canon Aplio i800 ultrasound machine and 4-14MHz linear array probe demonstrated MN in the second and third webspaces of the right foot with associated intermetatarsal bursae. In longitudinal section MN appear as a fusiform, elongated hypoechoic lesion, situated in the webspace just proximal to the metatarsal heads (See Appendix 3, Figures 1 and 2). In transverse section they appear as a round hypoechoic lesion in the webspace just proximal to the metatarsal heads. Visualisation of the MN’s was improved with lateral compression of the forefoot using the free hand, resulting in plantar displacement of the MN’s between the metatarsal heads (sonographic Mulder’s sign) (Bianchi and Martinoli) (See Appendix 2 Figures 3 and 4). In addition, the lesions were partially compressible, aiding differentiation from intermetatarsal bursitis alone, which usually efface completely.

MN is a common cause of metatarsalgia and should always be in the differential diagnosis (Adams, 2010). Clinical examination is highly accurate for MN (as with Patient A), with research demonstrating a 96% sensitivity for the webspace tenderness test and 61-98% sensitivity for Mulder’s click (Di Caprio et al. 2018; Mahadevan et al. 2015). However, ultrasound is useful to confirm the diagnosis, determine the site and size of MN, detect MN and exclude other causes of symptoms. Therefore, it can prevent patients from unnecessary invasive treatments for an incorrect diagnosis (Lee et al. 2007). Furthermore, ultrasound is cost effective, quick, radiation free, readily available, portable, dynamic, can guide treatments and has no known contraindications. Nevertheless, despite its excellent visualisation of soft tissues, detection of small MN’s is challenging and extremely operator dependent with a long learning curve (Ata, Onat and Ozcakar, 2016).

The alternative, Magnetic Resonance Imaging (MRI), has superior soft tissue contrast and can examine larger areas. However, it is not routinely performed for suspected MN at our NHS Trust due to its cost, contraindications, long acquisition times and lack of availability. In addition, a metanalysis by Xu et al. (2015) comparing sensitivity and specificity of Ultrasound and MRI for MN, with surgery as a reference standard, found similar sensitivity values for both modalities (Ultrasound 0.90, MRI 0.93) and a higher specificity for ultrasound (0.88 versus 0.68 for MRI) indicating better overall diagnostic accuracy for ultrasound. Conversely, in a similar metanalysis by Bignotti et al. (2015), whilst similar results were noted for sensitivity (Ultrasound 0.90, MRI 0.9), MRI was more specific (1.00 versus 0.854) resulting in the opposite conclusion. This suggests that the most accurate modality remains unclear with multiple factors that make comparison difficult; accuracy of ultrasound depends on operator experience, size of studied MN may impact on detection rates and false positive/true negative rates could not be calculated as not all patients went on to surgery. In the context of the existing evidence and its limitations, ultrasound has thus far prevailed as the preferable examination due to its previously detailed inherent advantages. Nevertheless, MRI does have a limited role for atypical cases or those with a markedly restricted webspace preventing adequate ultrasound assessment (Bianchi & Martinoli, 2015). Regardless of which is utilised though, findings must be interpreted in conjunction with clinical assessment as detection of asymptomatic MN’s is common (Di Caprio et al. 2018).

The Role of Ultrasound in the Treatment of MN Following diagnostic ultrasound Patient A was verbally consented through a process of shared decision making (SDM) for an USG-CSI with local anaethesthic (LA). SDM “involves healthcare professionals and patients working together to make choices about medicines based on clinical evidence and the patients informed preferences about what they hope to gain from the treatment” (NICE, 2019, p. 1). This is a legal requirement which ensures patients understand the risks of the proposed treatment and alternatives (NICE, 2019). Consequently, information was provided to Patient A on the risks of the procedure including: allergic reaction, infection, steroid flare, skin changes, depigmentation and poor therapeutic response (Netto et al. 2018). No cautions or contraindications were identified during discussion. In view of the current novel coronavirus (2019-nCoV) pandemic, information was also given on the potential risks of receiving corticosteroids if incubating the virus. Currently, the impact of corticosteroids in this situation remains unknown, with limited research available. Previously, corticosteroids have been associated with adverse effects such as delayed viral clearance when used on patients with Middle East Respiratory Syndrome coronavirus and severe acute respiratory syndrome coronavirus (Russell, Miller and Baillie, 2020). Likewise a small study of 2019-nCoV reported that corticosteroids increased the severity of the virus (Zha et al. 2020). However, these studies were not undertaken in the context of the low doses used for musculoskeletal injections and consequently a risk/benefit approach is advised for these on an individual basis (British Society for Rheumatology (BSR) et al. 2020). During the initial wave of the pandemic all non-urgent surgery was cancelled at our NHS Trust with only limited lists operating now. Currently, it’s unknown when full operating capacity will resume. Given Patient A’s symptoms, failed conservative treatment, previous relief with CSI, the waiting times and risks of surgery, an USGI-CSI was deemed appropriate and patient A agreed. In addition, in accordance with local protocol (see Appendix 4), patient A was not deemed vulnerable to 2019-nCoV so no shielding or test was needed prior to proceeding.

USG-CSI Technique Patient A was positioned supine on the ultrasound couch with her legs extended. The operator wore personal protective equipment in accordance with local 2019nCoV infection control policies and England guidance (2020) and aseptic technique was used. The 4-14 MHz linear array ultrasound probe was placed in long axis on the plantar aspect of the second and third webspaces whilst 0.5ml 1% lidocaine (LA) was injected subcutaneously, and around, each MN in turn. Two 25 gauge orange needles were used (one for each webspace) and inserted using a dorsal in-plane approach (see Appendix 5). Once LA injection was complete and the needles abutted the MN’s, 20mg (0.5ml) of Methylprednisolone (CSI) was injected around each MN (see Appendix 6). There were no complications and Patient A reported an immediate absence of her usual pain. A pain diary was issued to document injection response and she was advised to rest for 48 hours and use ice and analgesia to manage any post injection flare symptoms. At time of writing, the pain diary had not been returned so no information on longer term outcomes is currently available.

A dorsal needle approach was chosen as the skin is thinner in this area resulting in improved disinfection, patient tolerance, and a reduced risk of plantar fat pad atrophy (Netto et al. 2018). Skin changes such as subcutaneous fat atrophy are a risk of CSI and can cause pain and affect gait. Methylprednisolone was administered rather than Triamcinolone Acetonide (TA) as the risk of this is lower with this corticosteroid, despite its similar potency (McNally, 2014). Lidocaine was used as a LA as it has a faster onset than bupivacaine, providing immediate pain relief and diagnostic information on if the MN is the pain generator. In addition, 1% strength was used as higher strengths are associated with chondrocyte toxicity (Murakami, 2015). Use of LA prior to CSI enabled the needle positions to be confirmed as visualisation was challenging due to the thin needle used chosen to minimise discomfort. Total volume of fluid administered to each webspace was limited to 1ml to reduce the risk of extravasation complications (Netto et al. 2018).

The Role of Injection Therapy LA and CSI is the most commonly used interventional non-operative treatment for MN (Gougoulias, Lampridis and Sakellariou, 2019). Whilst LA alone provides diagnostic information, addition of corticosteroid is thought to provide longer symptomatic relief by reducing the surrounding inflammatory response (Bianchi and Martinoli, 2015). Compared with orthoses, CSI produced better outcomes for MN with patient satisfaction significantly better (p<0.01) at 1, 6 and 12 months (Saygi et al. 2005). This study was subject to bias though as patients could not be blinded to their treatment and the sample was small (n=82) limiting external validity. However, a further study also found significantly improved outcomes (p=0.02) at 3 months following LA and CSI, when compared with LA alone, further indicating CSI can improve MN symptoms (Thomson et al. 2013). Furthermore, this was a methodologically superior randomised controlled trial (RCT) with enough power to generalise results. Unfortunately though this study could not maintain blinding beyond 3 months and consequently the long term efficacy of CSI remains unestablished. Nevertheless, LA and CSI can confirm the diagnosis, improve symptoms, guide further treatment, and delay or avoid surgery (Di Caprio et al. 2018; Netto et al. 2018). For example, in a study evaluating a staged treatment programme of conservative measures followed by LA and CSI, followed by surgery, 79% (n = 91) of patients avoided surgical treatment (Bennett et al. 1995). This has clear patient benefits given that risks of surgery for MN include abscess, haematoma, stump neuroma, hammertoe and keloid scar formation (Masala et al. 2017).

Evidence for USG-CSI Therapy USG-CSI for Patient A enabled the administration of the LA and corticosteroid to be visualised in real time ensuring it reached the MN’s. As discussed earlier, accurate LA injection is a valuable part of the diagnostic pathway (particularly in the context of a limited response to blind injection), as surgical decisions may depend on response (McNally. 2014). USG-CSI is also thought to reduce procedural and post procedural pain as trauma to the area is minimised as a result of being able to see the needle (Murakami, 2015). However, whilst there is no doubt that ultrasound guidance improves injection accuracy, with acromioclavicular joint injections demonstrating 100% accuracy for USG-CSI versus 40% accuracy for blind injections (no study on injection accuracy specific to MN could be identified), the impact on efficacy remains unclear given the systemic effect of CSI (Peck et al, 2010 in Malanga, Axtman and Mautner, 2014). A double blinded RCT comparing USG- CSI with blind injections for 36 patients with MN found that whilst both patient groups mean visual analogue scores (VAS) improved significantly, there was no statistical differences between them at any review point, indicating no increased efficacy with USG-CSI (Mahadevan et al. 2016). However, improvement in Manchester Oxford Foot Questionnaire Index and patient satisfaction information favoured USG-CSI in the short term (3 months) almost reaching statistical significance (p = 0.059 and p=0.066), a result which may have been different with a larger sample size. In comparison, a similar study by Santiago et al. (2018), with a larger sample of 56 patients, demonstrated improved VAS and Manchester Foot Pain and Disability Scores in both groups, but the USG-CSI group showed significantly better improvements at follow up intervals of 45 days, 2 months and 3 months. Both groups were randomly assigned with no differences in mean age or neuroma size. Consequently, these results suggest USG-CSI does improve efficacy with further advantages noted of fewer cases of skin depigmentation (one versus 5 in the blind group) and significantly fewer repeat injections (2.1 ± 0.1 versus 2.7 ± 0.2, p = 0.01). However, given that in both studies the blind injection groups still showed symptomatic improvement, it could be argued the additional cost of USG-CSI is unjustified. However, at our NHS trust, many patients receive USG-CSI as an adjunct to diagnostic ultrasound limiting additional costs. In addition, improved accuracy arguably has the potential to reduce long term costs through improved patient outcomes. Alternative Treatments to USG-CSI Therapy Currently alternative treatments to USG-CSI for MN in the United Kingdom consist of ultrasound guided alcohol injections or surgery (neurectomy or nerve decompression) (NICE, 2016). Alcohol injections are a form of chemical neurolysis which cause dehydration and necrosis of the MN, however this is associated with pain, bruising, numbness and soft tissue necrosis (Netto et al. 2018). In addition, it requires multiple sessions (up to 6) making it more time consuming and expensive than USG-CSI (Goldin & Shiple, 2014). Nevertheless, a systematic review of 11 studies investigating this treatment found it is relatively safe (with only some reports of short term adverse effects) and demonstrated evidence of symptomatic improvement (Santos, Morrison and Coda, 2018). However, all 11 studies lacked methodological rigour with no RCT identified, only case series, providing low level evidence at high risk of bias. Comparison between studies was difficult due to differences in injection methodology, with variations in numbers of injections given, alcohol concentrations used, injection intervals, follow up intervals and outcome measures. Consequently, further higher quality research is needed to establish conclusions on this treatment and as a result it is not offered at our NHS Trust.

Another treatment with potential is ultrasound guided radiofrequency ablation (RFA) which currently can only be used if specific clinical governance arrangements exist (NICE, 2015). This is a minimally invasive, percutaneous alternative to surgery which uses a radiofrequency probe attached to a generator to deliver pulses of thermal energy into the webspace causing thermal ablation of the MN (NICE, 2015). This demonstrated promising results in a study of 22 MN with significant improvements in VAS at 8 weeks (p=<0.001) and 8 months (p=<0.008) and no significant adverse effects (Shah et al. 2019). Similarly, 3 studies identified in a review by Matthews et al. (2019) also demonstrated favourable results after a mean follow up of 7 months. However, again all of these studies were low quality (uncontrolled pre/post study designs) with RCT’s needed to establish conclusions. This is also true of a study by Climent et al. (2013) of botox injections for MN which demonstrated symptomatic improvement in 70.6% patients at 3 months after a single injection, and two studies on cryoneurolysis (freezing the nerve using an ultrasound or MRI guided probe) which was successful after a mean review period of 11.4 months (Cazzato et al. 2016; Friedman, Richman and Adler, 2013). Whilst these treatments show promise, the low number of studies and lack of high quality evidence means they are not currently offered within the NHS.

Surgery is offered at our NHS Trust as a last resort following the use of an USGI- CSI with LA. This is because the success rate for neurectomy rarely exceeds 80% and there is a high rate of complications; 25% for neurectomy and 7% for neurolysis (Masala et al, 2017, Santiago et al. 2018). Consequently, confirming the diagnosis and webspace with USG-CSI prior to operating is crucial for ensuring the highest chance of success. Given that the LA resulted in an immediate resolution of Patient A’s symptoms she may be offered surgery in the future should her symptoms persist post USG-CSI.

Conclusion MN is a common cause of metatarsalgia which has a marked female predilection, as was the case with Patient A (NICE, 2016). Although clinical examination is highly sensitive for MN, x-rays and ultrasound help exclude other causes of pain, with MRI reserved for difficult/ atypical cases (Di Caprio et al, 2018; Mahadevan et al. 2015). Injection of LA and corticosteroid improves symptoms when compared with orthoses and LA alone and can delay/ avoid the need for surgery (Bennett et al. 1995; Saygi et al. 2005; Thomson et al. 2013). The use of USG-CSI improves accuracy of the procedure, with potential advantages including less procedural and post-procedural pain, fewer adverse effects and fewer repeat injections; although effect on efficacy remains unclear (Mahadevan et al. 2016; Murakami, 2015; Santiago et al. 2018). In addition, CSI is the only non-surgical invasive treatment that has shown efficacy in a RCT (Thomson et al. 2013). Whilst alternative non-surgical invasive treatments show promise, further higher quality research is needed to establish conclusions on their efficacy. It is possible however, that ultrasound may have a wider role in future treatment as a means of guiding these procedures. Most importantly though, no treatment should be undertaken without informed consent and shared decision making, a discussion which requires additional risk/benefit analysis due to the 2019-nCoV pandemic. However, this is only one of many safety considerations with careful thought also given to medication used, needle approach and risk of adverse effects.

REFERENCES Adams, W.R. (2010) ‘Morton’s Neuroma’, Clinics in Podiatric Medicine and Surgery, 27, pp. 535-545. doi:10.1016/j.cpm.2010.06.004

Ata, A.M., Onat, S.S. and Ozcakar, L. (2016) ‘Ultrasound Guided Diagnosis and Treatment of Morton’s Neuroma’, Pain Physician, 19, pp. e355-e357. Available at: https://www.painphysicianjournal.com/current/pdf?article=MjUzMA%3D%3D&journal=94 (Accessed 5 November 2020).

Bianchi, S. and Martinoli, C. (2015) Ultrasound of the Musculoskeletal System. New Delhi: Springer India.

Bignotti, B., Signori, S., Sormani, S.P., Molfetti, L., Martinoli, C. and Tagliafico, A. (2015) ‘Ultrasound versus Magnetic Resonance Imaging for Morton Neuroma: A Systematic Review and Meta-Analysis’, European Radiology, 25, pp. 2254-2262. doi:10.1007/s00330-015-3633- 3

British Society for Rheumatology et al. (2020) Management of patients with musculoskeletal and rheumatic conditions who: are on corticosteroids; require initiation of oral/IV corticosteroids; require a corticosteroid injection. Available at: https://www.rheumatology.org.uk/Portals/0/Documents/COVID- 19/MSK_rheumatology_corticosteroid_guidance.pdf (Accessed 5 November 2020).

Cazzato, R.L, Garnon, J., Ramamurthy, N., Tsoumakidou, G., Caudrelier, J., Thenint, M.A., Rao, P., Koch, G. and Gangi, A. (2016) ‘Percutaneous MR-guided Cryoablation of Morton’s neuroma: rationale and technical details after the first 20 patients’, Cardiovascular and Interventional Radiology, 39(10), pp. 1491–8. doi:10.1007/s00270-016-1365-7

Climent, J.M., Mondejar-Gomez, F., Rodriquez-Ruiz, C., Diaz-Llopis, I., Gomez-Gallego, D. and Martin-Medina, P. (2013) ‘Treatment of Morton Neuroma with Botulinum Toxin A: A Pilot Study’, Clinical Drug Investigation, 33, 497-503. doi:10.1007/s40261-013-0090-0

Di Caprio, F., Meringolo, R., Eddine, M.S. and Ponziani, L. (2018) ‘Morton’s Interdigital Neuroma of the Foot’, Foot and Ankle Surgery, 24, pp. 92-98. doi:10.1016/j.fas.2017.01.007

Friedman, T., Richman, D. and Adler R. (2012) ‘Sonographically guided cryoneurolysis: preliminary experience and clinical outcomes’, Journal of Ultrasound in Medicine, 31(12), pp. 2025–34. doi:10.7863/jum.2012.31.12.2025

Goldin, M. and Shiple, B. J. (2014) ‘Morton’s Neuroma Injection’, in in Malanga, G. and Mautner, K. (ed.) Atlas of Ultrasound-Guided Musculoskeletal injections. New York: McGraw-Hill Education, pp. 413-418.

Gougoulias, N., Lampridis, V. and Sakellariou, A. (2019) ‘Morton’s Interdigital Neuroma: Instructional Review’, European Federation of National Association of Orthopaedics and Traumatology Open Reviews, 4, pp. 14-24. doi:10.1302/2058-5241.4.180025

Ho, S.C., Lui, T.H. and Tam, K.F. (2015) ‘Radiological Approach to Forefoot Pain’, Journal of Orthopaedics, Trauma and Rehabilitation, 19(1), pp. 7-14. doi:10.1016/j.jotr.2014..07.001

Lee, M., Kim, S., Huh, Y., Song, H., Lee, S., Lee, J. and Suh, J. (2007) ‘Morton Neuroma: Evaluated with Ultrasonography and MR Imaging’, Korean Journal of Radiology, 8(2), pp. 148-155. doi:10.3348/kjr.2007.8.2.148

Mahadevan, D., Attwal, M., Bhatt, R. and Bhatia, M. (2016) ‘Corticosteroid injection for Morton’s Neuroma with or without ultrasound guidance: a randomised controlled trial’, The Bone & Joint Journal, 98(4), pp. 498-503. doi:10.1302/0301-620X.98B4.36880

Mahadevan, D., Venkatesan, M., Bhatt, R. and Bhatia, M. (2015) ‘Diagnostic Accuracy of Clinical Tests for Morton’s Neuroma Compared with Ultrasonography’, The Journal of Foot and Ankle Surgery, 54(4), pp. 549-553. doi:10.1053/j.jfas.2014.09.021

Malanga, G.A., Axtman, M. and Mautner, K. R. (2014) ‘The Rational and Evidence for Performing Ultrasound-Guided injections’, in Malanga, G. and Mautner, K. (ed.) Atlas of Ultrasound-Guided Musculoskeletal injections. New York: McGraw-Hill Education, pp. 18- 22.

Masala, S., Cuzzolino, A., Morini, M., Raguso, M. and Fiori, R. (2017) ‘Ultrasound-Guided Percutaneous Radiofrequency for the Treatment of Morton’s Neuroma’, Cardiovascular and Interventional Radiology, 41, 137-144. doi:10.1007/s00270-017-1786-y

Matthews, B.G. (2019) ‘The effectiveness of non-surgical interventions for common plantar digital compressive neuropathy (Morton’s Neuroma): a systematic review and meta-analysis’, Journal of Foot and Ankle Research, 12. doi:10.1186/s13047-019-0320-7

McNally, E. (2014) Practical Musculoskeletal Ultrasound. Rev. edn. London: Churchill Livingstone. Murakami, A. M. (2015) ‘Ultrasound-Guided Injections: A Technical Review’, Aspetar Sports Medicine Journal. Available at: https://www.aspetar.com/journal/viewarticle.aspx?id=255#.X6Pk50dxfIU (Accessed 5 November 2020).

National Institute for Health and Care Excellence (NICE). (2015) Radiofrequency Ablation for symptomatic interdigital (Morton’s) neuroma. Available at: https://www.nice.org.uk/guidance/ipg539 (Accessed 5 November 2020). National Institute for Health and Care Excellence (NICE). (2016) Morton’s Neuroma. Available at: https://cks.nice.org.uk/topics/mortons-neuroma/ (Accessed 5 November 2020).

National Institute for Health and Care Excellence (NICE). (2019) Shared Decision Making. Available at: https://www.nice.org.uk/advice/ktt23/resources/shared-decision-making-pdf- 58758011521477 (Accessed 5 November 2020).

Netto, C.D.C., Fonseca, L.F.D., Nascimento, F.S., O’Daley, A.E., Tan, E.W., Dein, E.J., Godoy-Santos, A.L. and Schon, L.C. (2018) ‘Diagnostic and Therapeutic Injections of the Foot and Ankle – An Overview’, Foot and Ankle Surgery, 24, pp. 99-106. doi:10.1016/j.fas.2017.02.001

Pomeroy, G., Wilton, J. and Anthony, S. (2015) ‘Entrapment Neuropathy About the Foot and Ankle: An Update’, Journal of the American Academy of Orthopaedic Surgeons, 23(1), pp. 58-66. doi:10.5435/JAAOS-23-01-58

Public Health England. (2020) COVID-19: Personal protective equipment use for non- aerosol generative procedures. Available at https://www.gov.uk/government/publications/covid-19-personal-protective-equipment-use- for-non-aerosol-generating-procedures (Accessed 5 November 2020).

Russell, C.D., Millar, J.E. and Baillie, J. K. (2020) ‘Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury’, The Lancet, 395(10223), pp. 473-475. doi:10.1016/S0140-6736(20)30317-2

Santiago, F.R., Munoz, P.T., Pryest, P., Martinez, A.M. and Olleta, N.P. (2018) ‘Role of Imaging Methods in Diagnosis and Treatment of Morton’s Neuroma’, World Journal of Radiology, 10(9), pp. 91-99. doi:10.4329/wjr.v10.i9.91 Santos, D., Morrison, G. and Coda, A. (2018) ‘Sclerosing Alcohol Injections for the Management of Intermetatarsal Neuroma’s: A Systematic Review’, The Foot, 35, pp. 36-47. doi:10.1016/j.foot.2017.12.003

Saygi, B., Yildirim, Y., Saygi, E.K., Kara, H. and Esemenli, T. (2005) ‘Morton Neuroma: Comparative Results of Two Conservative Methods’, Foot & Ankle International, 26(7), pp. 556-559. doi:10.1177/107110070502600711

Shah, R., Ahmed, M., Hanu-Cernat, D. and Choudhary, S. (2019) ‘Ultrasound-guided radiofrequency ablation for treatment of Morton’s Neuroma: initial experience’, Clinical Radiology, 74(10), pp. 815.e9-815-e13. doi:10.1016/j.crad.2019.07.002

Thomson, C.E., Beggs, I., Martin, D., McMillan, D., Tudor Edwards, R., Russell, D., Yeo, S.T., Russel, I.T., Gibson, J.N.A. (2013) ‘Methylprednisolone Injections for the Treatment of Morton Neuroma: A Patient Blinded Randomised Trial’, The Journal of Bone & Joint Surgery, 95(9), pp. 790-798. doi:10.2106/JBJS.I.01780

Xu, Z., Duan, X., Yu, X., Wang, H., Dong, X. and Xiang, Z. (2015) ‘The Accuracy of Ultrasonography and Magnetic Resonance Imaging for the Diagnosis of Morton’s Neuroma: A Systematic Review’, Clinical Radiology, 70(4), pp. 351-358. doi:10.1016./j.crad.2014.10.017

Zha, L., Li, S., Pan, L., Tefsen, B., Li, Y., French, N., Chen, L.,Yang, G. and Villaneuva, E. V. (2020) ‘Corticosteroid Treatment of Patients with Coronavirus Disease 2019 (COVID-19), The Medical Journal of Australia, 212(9), pp. 416-420. doi:10.5694/mja2.50577

Bibliography Nuttall, D. and Rutt-Howard, J. (ed.) (2020) The Textbook of Non-Medical Prescribing. 3rd edn. Oxford: Wiley Blackwell.

Park, Y.H., Lee, J.W., Choi, G.W. and Kim, H.J. (2017) ‘Risk factors and the associated cutoff values for failure of corticosteroid injection in treatment of Morton’s neuroma’, International Orthopaedics, 42, 323-329. doi:10.1007/s00264-017-3707-8

Resteghini, P. (2017) Diagnostic Musculoskeletal Ultrasound and Guided Injection: A Practical Guide. New York: Thieme.

Spinner, D.A., Kirschner, J.S. and Herrera, J.E. (ed.) (2014) Atlas of Ultrasound Guided Musculoskeletal Injections. New York: Springer.

Valero, J., Gallart, J., Gonzalez, D., Deus, J. and Lahoz, M. (2015) ‘Multiple Interdigital Neuromas: A Retrospective Analysis of 279 Feet with 462 Neuromas’, The Journal of Foot and Ankle Surgery, 54(3), pp. 320-322. doi:10.1053/j.jfas.2014.05.011

Appendix 1 –Anatomical Illustration of MN

Figure 1: Illustration demonstrating location of a MN, between the metatarsophalangeal joints, in this case the 3rd and 4th (3rd webspace), as this is the most commonly affected (Goldin and Shiple, 2014, p. 413, fig. 102-1.

Appendix 2 – Plain Film Radiographs of Patient A’s Right Foot F

Figure 1: WB Dorsoplantar Projection Figure 2: Dorsoplantar Oblique Projection

Figure 3: WB Lateral Ankle Projection

Appendix 3 – Diagnostic Ultrasound Images of Patient A’s Right Forefoot

* *

Figure 1: Longitudinal section of the 2nd webspace demonstrating a MN and associated intermetatarsal bursa. Image obtained with the transducer in a sagittal plane on the plantar aspect of the foot, parallel to the metatarsal heads. * indicates MN, * indicates associated intermetatarsal bursa. * *

Figure 2: Longitudinal section of the 3rd webspace demonstrating a MN and associated intermetatarsal bursa. Image obtained with the transducer in a sagittal plane on the plantar aspect of the foot, parallel to the metatarsal heads. * indicates MN, * indicates associated intermetatarsal bursa.

Figure 3: Transverse section of the MN in the 2nd webspace with callipers indicating outline and size. Image obtained with the transducer positioned on the plantar aspect of the foot, axial to the metatarsal heads, with lateral compression of the forefoot applied using the free hand to improve visualisation.

Figure 4: Transverse section of the MN in the 3rd webspace with callipers indicating outline and size. Image obtained with the transducer positioned on the plantar aspect of the foot, axial to the metatarsal heads, with lateral compression of the forefoot applied using the free hand to improve visualisation. Appendix 4 – Local Protocol for CSI during 2019nCoV Pandemic Current or deferred referral for Ultrasound (USS) +/- CSI

Patient invited for diagnostic USS Patient defers, e.g. shielding Appropriate IF:- there is active synovitis, OR If CSI not appropriate. severe symptoms and no remaining STOP options ( had trial of conservative managementCSI and appropriate continuing ) OR Therapeutic arthrogram referral OR USG-CSI without prior diagnostic

OR 14 days self-isolation

Therapeutic arthrogram/ USG-CSI (same Radiologist as Diagnostic appt, vulnerable patients at start of list)

Normal post injection advice Post injection 5-10 days self-isolation suggested for vulnerable

Appendix 5 - USG-CSI Technique

Figure 1: Example of dorsal, in-plane approach used for USG-CSI of both the 2nd and 3rd webspaces. The ultrasound probe was positioned in long axis on the plantar aspect of the right forefoot, in the appropriate webspace, at the level of the metatarsophalangeal joint. The 25 gauge orange needles were inserted through the dorsal aspect of the 2nd and 3rd webspaces in turn, a distal to proximal direction, towards the MN’s, keeping the needle as close to parallel with the probe as possible (“in-plane”) (Goldin and Shiple, 2014, p. 416, fig. 102-80).

Appendix 6 - Post USG-CSI Ultrasound Image

Figure 1: Post USG-CSI ultrasound image of 3rd webspace demonstrating the injectate fluid surrounding the MN. Red arrow indicates approximate needle approach (same approach used for the 2nd webspace).

Case 12 David Howell

Posterior Tibial Tendinopathy and Hyaluronic Acid Injections

A 58 year old lady initially presented in June 2019 with worsening posterior medial ankle pain. There had been no history of trauma. Her job involved mainly standing and usually she would walk 30 minutes to work, which she was now unable to do. She had tried resting, including time off work, icing and elevating and anti-inflammatories, but was still symptomatic.

Past medical history included hypertension, hypothyroidism and previous obesity. Over the preceding year, through sensible eating and exercise, she had lost over 5 stone in weight, and now had a healthy BMI of 23. She took an angiotensin receptor blocker for her blood pressure, levothyroxine for her hypothyroidism and had no known allergies.

Examination findings showed a normal range of motion through her ankle joint. She did overpronate, more so on her symptomatic side. She had a slight lateral deviation of her heel, a flattened arch and ‘too many toes’ sign.

Image from https://orthoinfo.aaos.org/en/diseases-- conditions/adult-acquired-flatfoot/ (2/11/2020 at 1045)

She had weakness on single leg heel raise (could manage 2) and was tender along the course of the posterior tibial tendon (PTT). There was some soft tissue swelling, but no redness or warmth. On heel raise she could produce a longitudinal arch (Hubscher manoeuvre), indicating a flexible flatfoot.

The Achilles tendon was non-tender through its course to insertion.

With a history of (PMR) and hypothyroidism, bloods were checked, which showed normal inflammatory markers and also normal thyroid function. She also had no other symptoms of PMR.

X-rays showed no evidence of arthritis in either her tibiotalar or subtalar joint.

A clinical diagnosis of posterior tibial tendinopathy dysfunction was made.

We initially tried conservative management, including initial rest with a boot when weight- bearing for 2 weeks, then a progressive loading programme through the local physiotherapy department. She also started to use an orthotic, with a medial arch support.

She initially improved and returned to work however, a holiday involving a lot of walking caused a recurrence of her symptoms. She was seen by the lower limb orthopaedic surgeon, who suggested a prolonged 6 week period when weight bearing in a boot, followed by a repeated loading programme. Again, her symptoms settled to a degree, but she still was symptomatic after long periods at work on her feet. She walked with a slow, antalgic gait, and her pain was 4/10 on the visual analogue scale. COVID-19 did hamper her access to appropriate heath care professionals and further discussions regarding treatment options. She was very keen to avoid surgical intervention.

Review in October 2020 continued to show the above clinical signs. Ultrasound examination showed a normal anterior joint, with no effusion. Her extensor tendons were all normal. Lateral ankle examination was also normal. The Achilles tendon (AT) showed a normal fibrillar pattern, and no activity with power doppler (PD). There was slight cortical irregularity at its insertion, but no tenderness on sonopalpation, and no activity with PD. The medial ankle ligament complex was all normal, including on dynamic testing.

The PTT did show some loss of its normal fibrillar pattern along its course posterior to the medial malleolus, along with thickening (7mm versus 5mm on the asymptomatic side). There was surrounding fluid, greater than on the asymptomatic side, with slight activity on PD. Flexor digitorum longus, and flexor hallucis longus were normal.

The diagnosis was stage 2 disease.

Background

‘Flatfeet’ is the common term used for either ‘adult acquired flatfoot deformity’ (AAFD) or ‘posterior tibial tendon insufficiency’ (PTTI). It can affect 5-15% of the population and can be either congenital or acquired. 7-15% can be symptomatic and present to a health care professional. (Ling and Lui, 2013)

It has a wide clinical spectrum, which can progress from a tendinosis of the PTT through to a complete tear (PTTI). AAFD is caused by both PTTI (a dynamic stabiliser) and failure of the static stabilisers (bone and ligaments). The spring ligament complex (calcaneal-navicular ligament) is the most commonly compromised static stabiliser. (Vulcano et al, 2013)

This causes the ‘flatfoot’ with: ‘plantar sag and forefoot adduction through the talonavicular and subtalar joints, which leads to plantar and medial migration of the talar head causing the arch to flatten and the foot to displace under the talus. Involvement and failure of the interosseous ligament between the calcaneus and talus can cause the heel valgus.’ (Vulcano et al, 2013)

The condition is associated with a pre-existing flat foot, female sex, diabetes, high impact sports, raised BMI and hypertension. (Vulcano et al, 2013) There are also associations with previous trauma and inflammatory and tendon rupture with local steroid injections. (Geideman and Johnson, 2000)

There are four recognised stages ranging from solely tendon involvement, through to bony involvement with degeneration of the tibio-talar joint. The initial classification system was devised by Jonson and Strom, who recognised three stages. A fourth stage was suggested by Myerson. (Myerson, 1997) Although several others have been developed, it is still widely recognised. (Ross et al, 2017) and (Abousayed et al, 2016)

Image from Chhabra et al, (2011)

Alrnolder et al, (2015) showed ultrasound to be ‘slightly’ more accurate than MR to identify tendinosis, complete and partial tears. Its use as a cost effective modality was recommended as a first line investigation. The spring ligament complex can also be visualised on ultrasound, including abnormalities such as thickening, loss of normal echogenicity and increased vascularity. (Mansour et al, 2008) Hsu et al, (1997) suggested a tendon width of >6mm could be diagnostic of a tenosynovitis, and diagnostic confidence increased if combined with the ‘target sign’(fluid around the tendon within the sheath). Ultrasound can also visualise the tendon and may show hypoechoic thickening, loss of normal fascicular pattern and synovial thickening. Neovascularisation can also be demonstrated with power doppler. (Drakonakiet et al, 2016) Fluid alone around the tendon can be a common finding, (Lee et al, 2019) so must be interpreted along with other ultrasound and clinical findings.

It therefore seems reasonable, when reviewing the above table and evidence, that ultrasound +/- x-ray along with clinical examination can be used for diagnosis, especially in stages 1 and 2.

Conservative treatment has been shown to be successful for stage 1 and 2 disease (Alverez et al, 2016). Treatments include NSAIDs, orthotics, bracing and strengthening exercises. Vulcano et al, (2017) also suggested initial conservative management, regardless of disease stage.

Anatomy and Aetiology

Image taken from https://brookbushinstitute.com/article/role-tibialis-posterior-fatigue-foot- kinematics-during-walking 2/11/20 @ 1150

The PTT originates from the proximal posterior tibia and fibula and interosseous membrane. Its distal tendinous part inserts into mainly the navicular tuberosity, but also the base of the medial, intermediate and lateral cuneiforms, and 2nd, 3rd and 4th metatarsals. The direction of muscle force changes from vertical to horizontal as it passes posteriorly the inferiorly around the medial malleolus. The PTT is at risk of poorer blood supply compared to other tendons due to its incomplete central mesotenon, in particular between the well vascularised musculotendinous junction and its insertion. It is in this area of hypo vascularity that pathology to the tendon is mostly seen, increasing in degrees of tendinopathy through to failure. Petersen et al, (1997) showed by immunohistochemical investigation that there was no laminin (reflecting vascularization) where the PTT glides round the bone, and this area therefore had no blood supply. This area was instead replaced by fibrocartilage. If the dynamic stability is lost, then it can affect the static stabilisers as described above, and lead to advancing pathology, including bony/joint involvement. (Ling and Lui, 2013)

Discussion

Review of the evidence using the University of East London’s online library shows no specific evidence for the use of hyaluronic acid (HA) and PTT.

However, the patient had tried the majority of all other evidence based conservative approaches and was still symptomatic and very keen to try and avoid surgery. In our local area, currently all surgery is very delayed with COVID 19 and emergencies are being prioritised. The use of HA had been recommended as a treatment option by the orthopaedic consultant she had also seen, who had had successful experiences in its use with similar cases, when injected under ultrasound guidance. As part of my training, I had also seen HA used for the same condition by the MSK Consultant Radiologist, along with HA for other . Other Sports Medicine Consultants and Specialist Physiotherapists I have worked with also had used this as a treatment modality.

Local steroid injection is an option, but must be used with extreme caution around a weight bearing tendon, due to the risk of rupture. Ikpeze et al, (2019) actually go a step further, and say local steroid is contraindicated, although the paper was written for management of elderly patients (although did include a study on over 40s).

Oloff and Lam, (2017) reviewed the evidence for plasma rich protein (PRP) and posterior tibial tendinopathy. They noted limited evidence with small study sizes, and could not recommend either way its use. Potential use was discussed with the patient, who felt it could be a future treatment option. Reviewing its benefits on other tendinopathy, Chen et al, (2017) showed a benefit with PRP and improvements in pain with lateral epicondylitis and rotator cuff injuries. Cruciani et al, (2019) did an ‘umbrella review’ of PRP and soft tissue injuries – they did fine the studies to be of low quality with risk bias, but with some evidence of benefit.

Other locally available treatments include topical glyceryl trinitrate. Several studies have shown its benefit in tendinopathy, both short and long-term, but none specifically for posterior tibial tendinopathy. (Paoloni et al, 2017)

Shockwave therapy is another treatment option again with limited evidence. However, recently Robinson et al, (2020) did show statistically significant improvements in a small study (10 patients) treated with radial shockwave and importantly with no adverse outcomes. Lynen et al, (2017) compared 2 HA injections, given a week apart to focal shockwave treatment (3 treatments). They showed better outcomes in the HA group and also found it was better tolerated.

Unfortunately, in our area, there is no state funding for this treatment so the patient felt it wasn’t an option for her and had confidence in the treatment suggested by the Orthopaedic Consultant.

Hyaluronic Acid

HA is present in synovial fluid of both joints and tendon sheaths. Studies have shown its use can improve tendon gliding resistance. (Taguchi et al, 2009) Osti et al, (2015) showed HA may ‘improve tendon viability and proliferation.’ There is an increase collagen type 1 (which is the predominant collagen in tendons, providing the main structural support). They also showed that HA didn’t cause an increase in collagen type 3, which is seen in tendinopathy, so hypothesised this also maybe protective to tendons. Tuncay et al, (2002) also showed in animal studies on rats’ tendons that there was a likely anti-inflammatory effect caused by HA, ‘by inhibiting leucocyte function’.

Ultrasound guidance can ensure safe delivery of HA within the sheath, but not into the tendon. Wu et al, (2016) did show that intra-tendinous injection could cause tendon damage, with ongoing inflammation seen up to day 42.

Evidence for HA and tendinopathy is sparse, but growing. A Cochrane review suggested that currently there was not enough evidence to recommend its use in either Achilles or patellar tendinopathy. (Kearney et al, 2015) However, ISAKOS 2015 showed a significant benefit of HA in patellar tendinopathy. This was compared to local steroid injection – this study arm was actually stopped early, as there was no benefit. They suggested the use of HA, after conservative measures had failed, and as an alternative prior to surgery.

OARSI 2016 compared steroid to HA alone or HA plus Botox for patella tendinopathy – again the HA and HA plus Botox showed favourable results, and also a safe treatment option.

Gorelick et al, (2015) showed using HA alone, or in combination with steroid was superior to steroid alone, especially from 6-12 months in lateral epicondylitis. In a separate paper, Gorelick et al, (2015) also showed benefit of HA in Achilles tendinopathy when compared to steroid or conservative measures with both function and pain. Orlandi et al, (2015) looked at the addition of HA to steroid for de quervains tenosynovitis and showed benefit in terms of outcome and recurrence. Fogli et al, (2017) also showed HAs benefit for US guided peritendinous injections, including reducing tendon thickness and neovascularisation and described it as a ‘safe’ procedure. Fogli et al, (2017) also found that HA had the same effect on all tendinopathies in the study (Achilles, patella and lateral elbow).

Number of injections

Flores et al, (2017) in their prospective randomised trial comparing HA and physical therapy to physical therapy alone, showed significant benefit, and gave 2 injections a week apart. Of note, they also emphasised the importance of physical therapy, and it still being the ‘gold standard treatment.’ Kumai et al, (2014) used just a single injection of HA and found this to be of benefit in tendinopathy, and safe at a volume of 2.5ml. Frizziero et al, (2019) found 3 HA injections, given a week apart, showed benefit at 90 days for Achilles and mid portion patella tendinopathy. There aren’t any large RCTs comparing optimal dose or frequency of injections.

Local Anaesthetic (LA)

Honda et al, (2016) showed in both in vitro and in vivo the negative effects of LA (lidocaine) on tendons, including weakening and cell death of tenocytes. Also, from past experience of peritendinous injections (for example, de quervains tenosynovitis) the space is small for the injectate, so it seems pragmatic not to dilute the HA with LA, to ensure the full dose can be given.

Post Procedure Boot

The local orthopaedic consultant did recommend a boot to off-load the tendon after injection. This suggestion seems to be following previous experience of injections involving steroid around the tendon, (with increased risk of rupture) rather than HA. Frizziero et al, (2019) allowed patients in their study to weight bear, but avoid strenuous activity post procedure, with no adverse outcomes. However, I followed the advice of the Consultant.

Informed consent

The patient was requesting an HA injection, and that was her expectation. We had an initial consultation to discuss the procedure, and gain informed consent, after explaining the risks and limited evidence. She was aware of the risks of using steroid, and why we were avoiding its use. However, it was also important that I felt it was a reasonable treatment option, and I could confidently justify the procedure. Evidence was based on HAs positive effects on other tendinopathies outlined above, with no published data specifically for posterior tibial tendinopathy. Folgi et al, (2017) stated the beneficial effect of HA was the same on the three tendons in their study.

I felt it was reasonable to use, given the request by a Consultant Orthopaedic colleague, and positive results from other MSK colleagues. She had failed conservative approaches, and was keen to avoid surgery. Side effects are very rare, and I felt the main side effect would be it didn’t work, and would be unlikely to worsen her condition. The prolonged period in a boot would help off-load her, followed by a structured loading program. She had had a treatment failure when using a boot then loading program previously, so if she did have benefit this time, one could hypothesise the addition of HA helped. Ostenil tendon specifies it’s use if for tendinopathy, and the patient clearly had evidence of this, clinically and on ultrasound images. Its delivery was under ultrasound guidance, so the risk of it being placed into the tendon was low. It was given in the dose of 40mg in 2ml. Product literature suggests 2 doses a week apart, which I followed.

All of the above was explained, highlighting the limitation of evidence, and we were doing this based on evidence of HA in other tendinopathies. I specifically informed her that there was no evidence currently in the literature for treatment of posterior tibial tendinopathy. I also explained the small risk of infection, possible pain, and the rationale of not using LA. Although I cannot find any reported cases, there potentially is a chance of allergic reaction, and possible tendon rupture, which I explained, along with ostenil tendon being a medical device. She was also aware of how to use the boot post procedure, and had planned follow up with a physiotherapist, for a structured loading program. She was also given post procedure advice, and who and how to contact if any problems.

It is important to use a validated tool, before the procedure and to monitor response to treatment. This needs to be easy and quick to do in a clinical setting, and reproducible. It could provide a basis to publish a number of cases, either with positive or negative results. Budiman-Mak et al, (2013) showed the ‘foot function index – revised’ to be valid for PTT and easy to use. Ross et al, (2018) also showed a number of clinical tests that were reliable to assess function, including heal raise (maximum number). This again is easy to perform in a clinic. There are numerous other tests that could be used to assess outcomes, especially if one was designing a RCT.

Procedure

The patient was asked to lie comfortably in a supine position, with her knee flexed at 90 degrees. A pillow was placed under her ankle for support. Our standard clinical procedures were followed regarding infection control with both skin and probe preparation. The posterior tibial tendon was identified, along with the location of the neurovascular bundle. With the tendon in a transverse view, an in plane approach from the posterior side was used, and ostenil tendon delivered with clear needle visualisation. The procedure was repeated after a week. She wore the boot when weight bearing, from the 1st injection, and for 1 week after the 2nd injection.

All of the above, including what was discussed, was documented in her notes.

Conclusion

It is clear that there is a huge lack of evidence specially for HA in posterior tibial tendinopathy and only limited evidence for its use in other tendinopathies. Although there is supporting clinical evidence for other tendinopathies, they are separate clinical entities, and we must be mindful of this. But, potentially it maybe a successful treatment and halt the need for surgical intervention in some cases. It does otherwise seem a large leap from conservative treatment to operation, with its own associated risks. Many studies are also at risk of bias, with funding from the producing drug companies. Large, unbiased RCTs need to be carried out, on individual tendinopathies (both mid portion and insertional), with validated outcome measures. One needs to account for the different stages of tendinopathy we are treating and the effect on outcomes this may have. Any comparison arms would also need to be standardised, such as loading programs or orthotics used, for example. Assessing optimal dose and number and frequency of injections needs to be assessed, along with longer term outcomes. The need for off-loading post procedure with HA for lower limb peri-tendinous injections also needs further studies. Tendinopathy and tendon health is far from simple and often there will be ongoing factors at play – BMI, cholesterol, and genetics, which need to be accounted for. Ideally, comparing it to a sham treatment would be of benefit, but this may not gain ethical approval. Comparing it to steroid, especially in a weight bearing tendon again would likely not be ethical, due to risk of harm. It could also be compared to other emerging treatments, such as PRP and again with shockwave (Lynen et al, 2017) (both focal and radial) but with perhaps 5 or 6 treatments, which often in clinical practice we use.

A simple and practical suggestion would be to develop an online national tool to record data, to help understanding of procedures and outcomes. If successful, this could be expanded on an international scale. An online anonymised proforma could be quick to complete (with patient consent), for example in this case: PTT Age Risk factors (e.g. BMI) Foot function index – revised score pre-procedure US findings – hypoechoic thickening/loss of normal fascicular pattern/synovial Thickening/neovascularisation Injection given and frequency Loading program yes/no Follow up foot function index – revised score

The British Society of Urogynaecology have an online Audit database to do exactly this – record surgical data to help understanding for future studies and maintain best practice. It is information we should be recording in the notes and could be easily transferable, and encouraged and set up by either The Faculty of Sport and Exercise Medicine or the British Association of Sport and Exercise Medicine. With patient consent, email follow up could monitor longer term benefits.

My initial background is in General Practice, where my treatment has predominately always been evidence-based. Published, high quality evidence is lacking and clearly need to be put in to place, to keep up with the rapidly growing world of sports and musculoskeletal medicine, which seems to be more experimental and hearsay. We want to ensure we are doing best by are patients, and above all ensure we are doing no harm.

References: Abousayed MM, Tartaglione JP, Rosenbaum AJ, Dipreta JA. Classifications in Brief: Johnson and Strom Classification of Adult-acquired Flatfoot Deformity. Clinical Orthopaedics ad Related Research. 2016

Alvarez RG, Marini A, Schmitt C, Saltzman CL. Stage I and II posterior tibial tendon dysfunction treated by a structured nonoperative management protocol: an orthosis and exercise program. Foot Ankle International 2006

Arnoldner MA, Gruber M, Syré S, Kristen KH, Trnka HJ, Kainberger F, Bodner G. Imaging of posterior tibial tendon dysfunction Comparison of high-resolution ultrasound and 3T MRI. European Journal of Radiology. 2015

Budiman-Mak, E., Conrad, K.J., Mazza, J. et al. A review of the foot function index and the foot function index – revised. Journal of foot and ankle research 2013

Canata GL, Casale V ISAKOS 2015: Hyaluronic acid effective vs corticosteroid in patellar tendinopathy Accessed from myorthoevidence.com/AceReports 3/11/2020

Chen X, Jones IA, Park C, Vangsness CT. The Efficacy of Platelet-Rich Plasma on Tendon and Ligament Healing: A Systematic Review and Meta-analysis With Bias Assessment. The American Journal of Sports Medicine. 2018

Chhabra A, Soldatos T, Chalian M, Faridian-Aragh N, Fritz J, Fayad LM, Carrino JA, Schon L. 3-Tesla magnetic resonance imaging evaluation of posterior tibial tendon dysfunction with relevance to clinical staging. Journal of Foot Ankle Surgery 2011

Cruciani M, Franchini M, Mengoli C, et al. Platelet-rich plasma for sports-related muscle, tendon and ligament injuries: an umbrella review. Blood Transfusion. 2019

Flores C, Balius R, Álvarez G, et al. Efficacy and Tolerability of Peritendinous Hyaluronic Acid in Patients with Supraspinatus Tendinopathy: a Multicenter, Randomized, Controlled Trial. Sports Med Open. 2017

Fogli M, Giordan N, Mazzoni G. Efficacy and safety of hyaluronic acid (500-730kDa) Ultrasound-guided injections on painful tendinopathies: a prospective, open label, clinical study. Muscles Ligaments Tendons Journal 2017

Frizziero A, Vittadini F, Oliva F, Vetrano M, Vulpiani MC, Giordan N, Masiero S, Maffulli N. THU0492 efficacy of us-guided hyaluronic acid injections in Achilles and Patellar mid- portion tendinopathies: a prospective multicentric clinical trial Annals of the Rheumatic Diseases 2019

Geideman W and Johnson J Posterior tibial tendon dysfunction Journal of Orthopaedic & Sports Physical Therapy 2000

Gorelick L, Gorelick AR, Saab A, Ram E, Robinson D Lateral Epicondylitis Injection Therapy: A Safety and Efficacy Analysis of Hyaluronate versus Corticosteroid Injections Advance Techniques in Biology and Medicine 2015

Gorelick L, Rozano-Gorelick A, Saab A, Ram E Single Hyaluronate Injection in the Management of Insertional Achilles Tendinopathy in Comparison to Corticosteroid Injections and Non-invasive Conservative Treatments Scholars Bulletin 2015

Honda H, Gotoh M, Kanazawa T, Nakamura H, Ohta K, Nakamura K, Shiba N. Effects of lidocaine on torn rotator cuff tendons. Journal of Orthopaedic Research. 2016

Hsu TC, Wang CL, Wang TG, Chiang IP, Hsieh FJ. Ultrasonographic examination of the posterior tibial tendon. Foot Ankle International. 1997

Ikpeze TC, Brodell JD Jr, Chen RE, Oh I. Evaluation and Treatment of Posterior Tibialis Tendon Insufficiency in the Elderly Patients. Geriatric Orthopaedic Surgical Rehabilitation. 2019

Kearney RS, Parsons N, Metcalfe D, Costa ML. Injection therapies for Achilles tendinopathy. Cochrane Database of Systematic Reviews 2015

Kumai T, Muneta T, Tsuchiya A, Shiraishi M, Ishizaki Y, Sugimoto K, Samoto N, Isomoto S, Tanaka Y, Takakura Y The short-term effect after a single injection of high-molecular-weight hyaluronic acid in patients with enthesopathies (lateral epicondylitis, patellar tendinopathy, insertional Achilles tendinopathy, and plantar ): a preliminary study, Journal of Orthopaedic Science, 2014

Lee S, Oliveira I, Li Y, Welck M, Saifuddin A. Fluid around the distal tibialis posterior tendon on ankle MRI: prevalence and clinical relevance. British Journal of Radiology. 2019

Ling SK, Lui TH. Posterior Tibial Tendon Dysfunction: An Overview. Open Orthopaedic Journal. 2017

Lynen N, De Vroey T, Spiegel I, Van Ongeval F, Hendrickx NJ, Stassijns G. Comparison of Peritendinous Hyaluronan Injections Versus Extracorporeal Shock Wave Therapy in the Treatment of Painful Achilles' Tendinopathy: A Randomized Clinical Efficacy and Safety Study. Archives of Physical Medicine and Rehabilitation. 2017

Mansour R, Teh J, Sharp RJ, Ostlere S. Ultrasound assessment of the spring ligament complex. European Radiology 2008

Myerson MS. Adult acquired flatfoot deformity: treatment of dysfunction of the posterior tibial tendon. Instructional Course Lectures. 1997

Oloff L, Lam J Does PRP Have Promise for Advanced Posterior Tibial Tendinopathy in Athletes? Podiatry Today 2017

Orlandi D, Corazza A, Fabbro E, Ferrero G, Sabino G, Serafini G, Silvestri E, Sconfienza LM. Ultrasound-guided percutaneous injection to treat de Quervain's disease using three different techniques: a randomized controlled trial. European Radiology. 2015

Osti L, Berardocco M, di Giacomo V, Di Bernardo G, Oliva F, Berardi AC. Hyaluronic acid increases tendon derived cell viability and collagen type I expression in vitro: Comparative study of four different Hyaluronic acid preparations by molecular weight BMC Musculoskeletal Disorders. 2015

Paoloni JA, Murrell GA. Three-year follow-up study of topical glyceryl trinitrate treatment of chronic non-insertional Achilles tendinopathy. Foot and Ankle International. 2007

Petersen W, Hohmann G, Stein V, Tillmann B. The blood supply of the posterior tibial tendon. Journal of Bone and Joint Surgery 2002

Petrella, RJ, Petrella AF, Decaria J OARSI 2016: Efficacy and safety of hyaluronan with/without Botox for patella tendinopathy Accessed from myorthoevidence.com/AceReports 3/11/2020

Robinson D, Mitchkash, M, Wasserman, L Tenforde, A Nonsurgical Approach in Management of Tibialis Posterior Tendinopathy with Combined Radial Shockwave and Foot Core Exercises: A Case Series The Journal of Foot and Ankle Surgery 2020

Ross MH, Smith MD, Vicenzino B. Reported selection criteria for adult acquired flatfoot deformity and posterior tibial tendon dysfunction: Are they one and the same? A systematic review. PLoS One. 2017

Ross MH, Smith M, Plinsinga ML, Vicenzino B. Self-reported social and activity restrictions accompany local impairments in posterior tibial tendon dysfunction: a systematic review. Journal of Foot and Ankle Research. 2018

Taguchi M, Zhao C, Sun YL, Jay GD, An KN, Amadio PC. The effect of surface treatment using hyaluronic acid and lubricin on the gliding resistance of human extra synovial tendons in vitro. Journal of Hand Surgery America. 2009

Tuncay I, Ozbek H, Atik B, Ozen S, Akpinar F. Effects of hyaluronic acid on postoperative adhesion of tendo-calcaneus surgery: an experimental study in rats. Journal of Foot and Ankle Surgery. 2002

Vulcano E, Deland JT, Ellis SJ. Approach and treatment of the adult acquired flatfoot deformity. Current reviews in musculoskeletal medicine 2013

Wu PT, Jou IM, Kuo LC, Su FC Intratendinous Injection of Hyaluronate Induces acute Inflammation: A Possible Detrimental Effect) Intratendinous Injection of Hyaluronate Induces Acute Inflammation: A Possible Detrimental Effect. PLOS ONE 2016

Case 13

Michael McMahon

Ultrasound Guided injection case study- Greater Trochanteric pain syndrome

Introduction:

Mrs A was a 55-year-old housewife referred to the musculoskeletal (MSK) physiotherapy clinic by her general practitioner (GP) with a 2-year history of gradual onset of right hip pain. She reported right lateral hip with some buttock pain with some referred lateral thigh pain spreading to ½ way down leg, nil to knee. She also reported some longstanding mild intermittent lower back pain, but denies any pain radiating down past the knee or paraesthesia. Her hip pain was rated as VAS 7/10 and was aggravated by right side lying, plonged walking, sitting to standing, getting in and out of a car and climbing stairs. She denied any morning stiffness in her hip and there was no locking, giving way or clicking reported. No issues with turning over in bed. She did report disturbed sleep and could be woken at night if she lies on the affected side. Her PMH included hypertension and hypercholesteremia for which she took medications and she was otherwise systemically well.

Following a course of physiotherapy, she was then referred into a MSK specialist review clinic for a second opinion as she had no improvement to date with her treatment. She has had 6 sessions of physiotherapy aimed at lumbar and hip mobility, with some general strengthening exercises prescribed for the lower back and hip regions. Due to her high levels of pain and night pain she was struggling to adhere to the prescribed exercise regime. The clinical question was to establish a diagnosis and indicate whether further physiotherapy or further imaging and intervention was required.

The purpose of the MSK review appointment was that she would be seen by an advanced practice physiotherapist with access to imaging to help guide further management. This second opinion clinic was established on the assumption that effective treatment is dependent upon accurate differential diagnosis, and in Mrs A’s case there was no specific diagnosis, she was undergoing general rehabilitation with limited improvement to date.

Examination and Differential Diagnosis:

The differential diagnosis was between lumbar spine referred pain, hip osteoarthritis

(OA) and localised greater trochanteric pain syndrome (GTPS). There was a low index of suspicion of specific red flags that can be associated with hip presentations such as a stress fracture, AVN or metastatic disease given her and routine PMH. GTPS is a very common but often unrecognized or misdiagnosed condition. Accurate diagnosis and differentiation of GTPS from lumbar spine pathologies are essential in avoiding potential unnecessary spinal treatments- in one study over 50% of patients who presented to an orthopaedic spine clinic had GTPS

(Lee et al, 2018). Generally, anterior hip and groin pain comes from intra-articular hip disorders while lateral hip pain is more likely from extra-articular disorders (Grumet et al., 2010).

On questioning Mrs A’s symptoms were more centred on her lateral hip, with milder back and buttock pain. On physical assessment Lumbar active of range movements reproduced local spinal pain only, nil hip pain. There was no capsular restriction of hip movements usually seen in osteoarthritic presentations (Cibulka et al., 2009.)

She had localised tenderness on palpation over the greater trochanter which reproduced her pain. Her pain was also reproduced after single standing on the affected side for 15 seconds. There was also pain with resisted hip abduction and the resisted external derotation test. Her lateral hip pain was also reproduced with the FABER test which has been suggested as clinically diagnostic in a study by

Fearan et al., (2012). The 30‐second single‐leg stance and resisted external derotation tests had very good sensitivity and specificity for the diagnosis of tendinous lesion and bursitis in patients with MRI‐documented refractory GTPS

(Lequesne et al., 2008). Grimaldi et al., (2016) from a small sample study found that a patient who reports lateral hip pain within 30 seconds of single-leg-standing is very likely to have GTPS. They also found that patients with lateral hip pain who are not palpably tender over the greater trochanter are unlikely to have MRI-detected GTPS.

Greater Trochanteric Pain syndrome (GTPS)

Greater Trochanteric Pain syndrome (GTPS) is a debilitating condition causing lateral hip pain (Grimaldi and Fearon, 2015). It affects up to 23.5% of women and 8% of men between 50 and 75 years old (Segal et al., 2007). Patients with GTPS report difficulty sleeping and moderate to severe pain and disability (Fearon et al., 2013).

Sufferers report comparable quality of life and functional performance, to people with advanced osteoarthritis of the hip (Fearon et al., 2014). On top of this many cases are recalcitrant, with a high proportion of patients still experiencing symptoms twelve months from onset (Rompe et al., 2009). Because of the functional connection between the lumbopelvic and hip region a concurrent or past history of low back pain was found in 20-62% of patients with GTPS (Mulligan et al., 2015). GTPS is a described as a syndrome with a wide spectrum of aetiologies reflecting the anatomy of the structures outside the hip joint capsule. There are five muscle tendons that insert on to the greater trochanter and three bursae in the region of the greater trochanter. The term GTPS includes tendinopathies, tendinous tears, bursal inflammation and effusion.

Originally considered an inflammatory condition of the trochanteric bursa; recent imaging, surgical and histology studies have suggested it to be, most commonly, a condition associated with tendinopathy of the gluteus medius and gluteus minimus tendons at the site of their insertion onto the greater tuberosity of the femur (Fearon et al., 2010; Long. et al., 2013). One study found MRI evidence in a group of 24 subjects that nearly all had gluteus medius abnormalities but bursitis was only present in 8% of the subjects (Del Buono et al, 2012). However, as an associated array of pathologies are witnessed on imaging (including tendinopathy, partial and full thickness tendon tears, bursitis and iliotibial band abnormalities) and imaging of asymptomatic individuals reveals many false positives (Ganderton et al., 2017;

Ramirez et al., 2014), the term greater trochanteric pain syndrome (GTPS) is now used clinically to describe the uncertainty surrounding the definitive pain source from these associated pathologies

Consequently, imaging findings should be used to support or confirm the diagnosis in the context of a thorough clinical examination as opposed to the sole criteria for the identification of GTPS. The high prevalence of this pathology in combination with its effect on quality of life issues speaks to the urgency for effective and efficient intervention strategies.

Imaging:

The diagnosis of GTPS is assisted with imaging studies. MRI showed good accuracy for the diagnosis of tears of the gluteus medius and gluteus minimus tendons. The identification of an area of hyperintensity superior to the greater trochanter on a T2- weighted image had the highest sensitivity and specificity for tears at 73% and 95%, respectively (Cvitanic et al., 2004). However, Blankenbaker et al, (2008) found a high prevalence (50%) of peritrochanteric T2 imaging abnormalities in patients without trochanteric pain. In a small study, ultrasound was shown to have a high positive predictive value for gluteal tendon tears (positive predictive value = 1.0) (Fearon et al, 2013).

Docking et al., (2019) compared US and MRI imaging to identify the presence of a pathological gluteus medius tendon in comparison to surgical and histological findings. Ultrasound identified 17 out of the 19 pathological gluteus medius tendons correctly. However, 5 of the 6 normal tendons were incorrectly identified as exhibiting pathology on ultrasound. MR rated 11 out of 17 pathological tendons as abnormal, with 4 out of 6 normal tendons identified correctly. Both imaging modalities were poor at identifying and differentiating between tendinosis and partial-thickness tears

(Docking et al., 2019).

Although not as common as previously thought, the presence of a trochanteric bursa is still proposed to be a contributor in pain in GTPS. Fearon et al., (2014) in a histological study of tendon and bursa tissue biopsies found there was a significantly greater presence of Substance P in the bursa but not in the tendon of subjects with

GTPS compared to controls. They extrapolated that an increased presence of

Substance P in the trochanteric bursa may be related to the pain associated with

GTPS. With Mrs A. a hip x-ray was ordered which minimal degenerative joint changes which again lessened suspicion that hip osteoarthritis was a significant cause of her symptoms. An office-based US scan was undertaken in clinic to assess the greater trochanter region. Ultrasound appears to be clinically useful modality in the diagnosis of greater trochanteric pain syndrome (Fearon et al, 2014). A GE Logiq E9 machine with a high frequency linear array transducer (6-15MHz) was used to perform the scan. Mrs A. was positioned in left side-lying with the uppermost hip and knee flexed.

Images were obtained with the probe placed in the coronal plane so that it lay longitudinally over the greater trochanter initially to visualise the gluteus medius and minimus tendons at their insertion onto the greater trochanter (Resteghini, 2017).

The probe was then turned through 90 degrees to lie in the transverse plane over the greater trochanter to visualise the gluteus minimus attachment on the anterior facet and gluteus medius insertion onto the lateral facet (Resteghini, 2017). On viewing the images there was a thickened, hypoechoic gluteus medius tendon with loss of the normal fibrillar pattern. There was mild enthesopathic changes with irregularity over the lateral facet of the greater trochanter present. There was an area of anechoic fluid collection in the location of the greater trochanteric bursa. These US findings of gluteus medius tendinopathy with associated trochanteric bursa further support the diagnosis of GTPS when combined with clinical assessment.

Management:

The diagnosis and management options were discussed with Mrs A. She had completed 6 sessions of physiotherapy, but her high pain levels were still limiting her functionally. Injection therapy was proposed as a treatment option to help alleviate her pain and allow her to further engage in her rehabilitation. Mrs A was provided with an information leaflet on corticosteroid injections (CSI) outlining the rational for

CSI, proposed benefits and possible side effects. This was discussed alongside the theoretical risk of the steroid affecting her immune response in light of the Covid pandemic. The BSR/CSP/BOA/RCGP updated clinical guide during the Covid-19 pandemic for the management of MSK conditions from November 2020 state that a

CSI can be considered in lateral hip pain presentations where a patient has failed first line measures, has high levels of pain and disability and a continuation of symptoms will have a significant negative effect on their health and wellbeing. Mrs A met these criteria and was considered low risk as she has no significant past medical history that would put her in a high-risk category. Following this shared decision- making discussion Mrs A was then able to reach an informed decision to proceed with the CSI. A consent form was completed and signed by the patient

Mrs A was again placed in contralateral side lying with the uppermost hip and knee flexed. I was stood behind the patient and the ultrasound machine was placed in front of the patient. This allowed me a direct line of sight to both patient and machine and allowed me to accurately and safely insert the needle. A green 21G 40mm needle was chosen to deliver the medicine after reviewing the depth of the target on ultrasound imaging. The injection site and probe were cleaned using “Chloraprep”, a chlorhexidine and isopropylr alcohol solution. Sterile gel was applied to the target area and sterile gloves were donned. Using a longitudinal in plane with a superior to inferior approach 40mg of “Depo-Medrone”/ Methylprednisolone in 1ml solution and

3ml 1% Lidocaine was injected as a bolus using a no-touch 2-syringe technique into the trochanteric bursa overlying the gluteus medius tendon. The step by step injection procedure to minimise infection was followed as described by Saunders and

Longworth (2012). The injection was performed under our trust Patient Group Directive, which is a supply and administration framework for the provision of medication widely used within the NHS. The CSP (2016) recommends that physiotherapists who are not independent prescribers work within the limits of a PGD to allow them to administer medications. A 2-syringe technique was used as mixing two licensed medicines such as a local anaesthetic and a corticosteroid constitutes, under the terms of the Human Medicines Regulations, the manufacture of a new unlicensed product which therefore cannot be administered under a PGD (CSP,

2016).

Mrs A sat in the waiting room for 15 minutes afterwards to monitor for any post injection adverse effects. She was advised on relative rest for one week and was booked for further physiotherapy input to target the gluteal muscles with a progressive loading programme. A telephone follow-up call was undertaken 6 weeks after the injection. Mrs A reported a 90% improvement in her pain levels, with no pain at night now and VAS 1/10 with certain activities. She had restarted her rehabilitation and was overall very satisfied with the outcome.

Role of Injection therapy:

The NICE guidelines on GTPS (2016) state that over 90% of people with greater trochanteric pain syndrome recover fully with conservative treatment such as rest, pain relief, physiotherapy, and corticosteroid injection. They advise if initial conservative treatment does not provide adequate symptom relief, a peri- trochanteric corticosteroid injection and referral to physiotherapy should be offered.

Corticosteroid injection is an established second-line treatment for GTPS that has been shown to be efficacious but not necessarily in the long term (Brinks et al.,

2009). They compared corticosteroid injections (40 mg of triamcinolone acetate combined with 1% or 2% lidocaine) versus usual care and showed a clinically relevant effect for CSI at 3-month follow-up for pain at rest and with activity. At a 12- month follow-up visit, there was no difference in outcomes (Brinks et al, 2009). This short term effect finding has been supported by systematic reviews of GTPS management (Del Buona et al., 2012, Chowdhury et al., 2014). However a recent randomised controlled trial found the most significant improvements in short term pain relief occurred in the education and exercise group, rather than the injection group (Mellor et al., 2018).

In this case in line with the trust PGD, Depo-Medrone (Metylprednisolone), a synthetic gluco-corticoid, was used to reduce inflammation and pain. It depresses formation, release and activity of endogenous mediators of inflammation.

Glucocorticoids stabilise phospholipid membrane by inhibiting phospholipase A2, and therefore decrease formation of arachidonic acid and further inflammatory mediators from prostaglandin and leukotriene pathways (Shah et al, 2019).

From my literature search there does not appear to be many studies comparing landmark versus ultrasound guided injections for GTPS. Mitchell et al., (2017) in a study comparing US-guided and anatomic landmark injection of the trochanteric bursa found similar 2-week and 6-month outcomes; and as a result advocated landmark procedures. They advised that US guidance should be reserved for extreme obesity or injection failure. A systematic review of conservative management of GTPs showed fluoroscopy-guided injections failed to show additional benefit to landmark guided (Barratt et al., 2017).

McEvoy et al., (2013) compared ultrasound-guided corticosteroid injections into the greater trochanter bursa versus subgluteus medius bursa for treatment of GTPS.

They found from a sample of sixty-five injections that there was a statistically significant difference in pain reduction between greater trochanteric bursa and subgluteus medius bursa injections with a median pain reduction of 3 as opposed to

0 (p < 0.01). They concluded that CSI into the greater trochanteric bursa may be more effective than injections into the subgluteus medius bursa for treatment of

GTPS. It is worth noting there was no statistically significant association between pain relief and ultrasound findings.

Park et al., (2016) undertook a retrospective study of factors associated with success of USGI in GTPS. They found there was no statistically significant association between effective treatment and the ultrasound findings of tendinosis, bursitis, partial or full-thickness tear, and enthesopathic changes. This study suggests rather than

US findings that knee osteoarthritis and lower back pain might be associated with a poor outcome of ultrasound-guided trochanteric bursa injection for GTPS.

Regarding other injection alternatives to corticosteroid in GTPS there is limited evidence available. There is one trial currently recruiting that may provide an interesting option when published. Platelet-rich plasma (PRP) is an autologous blood product, which has a higher concentration of growth factors postulated to provide enhanced healing and anti-inflammatory properties. The Hip Injections PRP Vs

Placebo (HIPPO) trial aims to assess the ability of PRP to improve symptoms and function in patients with GTPS. HIPPO is a single-centre, double-blind randomized placebo-controlled study in patients with a radiologically confirmed diagnosis of gluteus medius or minimus tendinopathy with swelling within the tendon insertion with or without bursitis. Participants will receive one ultrasound (US) guided

PRP/placebo injection into the trochanteric bursa and surrounding gluteus medius/minimus tendons (Oderuth et al., 2018). A recent systematic review in 2020 compared PRP and surgery for GTPS. It was based on only 5 low quality studies for each intervention with very small patient numbers but concluded both PRP and surgical intervention for the treatment of recalcitrant GTPS showed statistically and clinically significant improvements (Walker-Santiago et al., 2020).

Conclusion/Reflection:

Mrs A case was chosen in part as she had a trochanteric bursa as part of her GTPS presentation. The 2 previous US guided injections on GTPS patients I had undertaken prior to Mrs A only had features of Gluteus medius tendinopathy with no bursitis present. I have had some feedback from my mentor that I can apply to much probe pressure and this may compress a small sized bursa and, in this instance, I maintained light pressure when undertaking the US scan. The presence of the bursitis made this an easier injection as there was a specific target to aim for, whereas previously with just tendinopathic features only around G. Med tendon I was somewhat uncertain where exactly the injection target should be aimed at. As a result, I feel I had better needle visualisation during the procedure. Using the 2- syringe technique method makes USGI more complicated as you have to re-site the needle after changing syringes, but again the presence of the anechoic fluid helped with accurate placement. As I was alone with Mrs A and had the US machine on the opposite side of the bed, I was unable to take any images during this procedure. I will have to adapt my set up in the future as understand that there should be a record of the procedure for medicolegal reasons. I have undertaken a lot of landmark GPTS injections in the past and am interested to see does the addition of USGI improve clinical outcomes. There is considerable technical skill to undertake a guided injection and it is an area I will need to invest considerable time and practice in order to become proficient References:

Barratt, P.A., Brookes, N., Newson, A., (2017). Conservative treatments for greater trochanteric pain syndrome: a systematic review. British Journal of Sports

Medicine ;51(4),97-104.

Blankenbaker, D., Ulrick, S., Davis, K., De Smet, A., Haaland, B. and Fine, JP.

(2008). Correlation of MRI findings with clinical findings of trochanteric pain syndrome. Skeletal Radiology. 37(7), 903-09

Brinks, A., van Rijn, R.M., Willemsen, S.P. (2011). Corticosteroid injections for greater trochanteric pain syndrome: a randomized controlled trial in primary care.

Annals of Family Medicine. 9(3),226–34.

Chowdhury, R., Naaseri, S. and Lee, J. (2014). Imaging and management of greater trochanteric pain syndrome. Postgraduate Medical Journal. 90(2), 576–81

Cibulka, M., White, D., Woehrle, J., Harris-Hayes, M., Enseki, K., Fagerson, T.,

Slover, J. and Godges, J. (2009). Hip Pain and Mobility Deficits – Hip Osteoarthritis:

Clinical Practice Guidelines Linked to the International Classification of Functioning,

Disability, and Health from the Orthopaedic Section of the American Physical

Therapy Association. Journal of Orthopaedic Sports Physical Therapy. 39(4), A1-

A25.

Cvitanic, O., Henzie, G., Skezas, N., Lyons, J. and Minter J. (2004) MRI diagnosis of tears of the hip abductor tendons (gluteus medius and gluteus minimus). American

Journal of Roentgenology. 182(1),137-43

CSP 2016. The use of medicines with injection-therapy in physiotherapy services. 5 th Edition. https://www.csp.org.uk/system/files/documents/2019-

04/pd003_medicines_injection_therapy_5th_edition_oct_2016_1.pdf Del Buono, A., Papalia, R., Khanduja, V., (2012) Management of the greater trochanteric pain syndrome: a systematic review. British Medical Bulletin.102(10),

115–31.

Docking, S., Cook, J., Chen, S., Scarvell, J., Cormick, W., Smith, P. and Fearon, A.

(2019). Identification and differentiation of gluteus medius tendon pathology using ultrasound and magnetic resonance imaging. Musculoskeletal Science and Practice.

6 (41),1-5

Fearon, A.M., Twin, J., Dahlstrom, J.E. (2014). Increased substance P expression in the trochanteric bursa of patients with greater trochanteric pain syndrome. Rheumatology International. 34(7), 1441–1448

Fearon, A., Scarvell, J., Cook, J. and Smith P. (2010). Does ultrasound correlate with surgical or histologic findings in greater trochanteric pain syndrome? A pilot study.

Clinical Orthopaedic Related Research. 468(7):1838-44

Ganderton, C., Semciw, A., Cook, J. and Pizzari, T. (2017). Demystifying the Clinical

Diagnosis of Greater Trochanteric Pain Syndrome in Women. Journal of Womens

Health. 26(6), 633-643.

Grimaldi, A. and Fearon, A. (2015). Gluteal Tendinopathy: Integrating

Pathomechanics and Clinical Features in Its Management. Journal of Orthopaedic

Sports Physical Therapy. 45(11), 910-22

Grimaldi, A., Mellor, R., Nicolson, P., Hodges, P., Bennell, K. and Vicenzino, B.

(2017). Utility of clinical tests to diagnose MRI-confirmed gluteal tendinopathy in patients presenting with lateral hip pain. British Journal of Sports Medicine. 51(6),

519-524. Grumet, R,. Frank, R., Slabuagh, M., Virkus, W., Bush-Joseph, C., Nho, S. (2010).

Lateral hip pain in an athletic population: differential diagnosis and treatment options.

Sports Health. 2(3):191-6.

Lequesne, M., Mathieu, P., Vuillemin-Bodaghi, V., Bard, H. and Djian, P. (2008)

Gluteal tendinopathy in refractory greater trochanter pain syndrome: diagnostic value of two clinical tests. Arthritis & Rheumatology. 59(2), 241-6.

Long, S., Surrey, D. and Nazarian, L. (2013). Sonography of greater trochanteric pain syndrome and the rarity of primary bursitis. American Journal of Roentgenology.

201(5),1083-6.

Mellor, R., Bennell, K., Grimaldi, A., Nicolson, P., Kasza, J., Hodges, P., Wajswelner,

H., and Vicenzino, B. (2018). Education plus exercise versus corticosteroid injection use versus a wait and see approach on global outcome and pain from gluteal tendinopathy: prospective, single blinded, randomised clinical trial. BMJ. 2(5), 361-66

Mitchell, W.G., Kettwich, S.C., Sibbitt, W.L. et al (2018). Outcomes and cost- effectiveness of ultrasound-guided injection of the trochanteric bursa. Rheumatology

International. 38 (9), 393–401

McEvoy, J., Lee, K., Blankenbaker, D., del Rio A. and Keene, J. (2013). Ultrasound- guided corticosteroid injections for treatment of greater trochanteric pain syndrome: greater trochanter bursa versus subgluteus medius bursa. American Journal of

Roentgenology. 201(2), 313-7

Mulligan, E., Middleton, E., and Brunette, M. (2015). Evaluation and management of greater trochanter pain syndrome. Physical Therapy and Sport.16(3),205-14. NICE Guidelines on Greater trochanteric pain syndrome (trochanteric bursitis).

(2016). https://cks.nice.org.uk/topics/greater-trochanteric-pain-syndrome- trochanteric-bursitis/

Oderuth, E., Ali, M., Atchia, I. and Malviya, A. (2018). A double-blind randomised control trial investigating the efficacy of platelet rich plasma versus placebo for the treatment of greater trochanteric pain syndrome (the HIPPO trial): a protocol for a randomised clinical trial. Trials. 21(1):517

Park, K., Lee, W. and Lee, J., (2016). Factors Associated with the Outcome of

Ultrasound-Guided Trochanteric Bursa Injection in Greater Trochanteric Pain

Syndrome: A Retrospective Cohort Study. Pain Physician. 19(4), 547-57.

Ramírez, J., Pomés, I., Sobrino-Guijarro, B., Pomés, J., Sanmartí, R., Cañete, J.

(2014). Ultrasound evaluation of greater trochanter pain syndrome in patients with spondyloarthritis: are there any specific features? Rheumatology

International.34(7):947-52

Resteghini, P. (2017). Diagnostic musculoskeletal ultrasound and guided injection: A practical guide. Thieme.

British society of Rheumatology and other health organisations statement: November

2020 Management of patients with musculoskeletal and rheumatic conditions who: - are on corticosteroids - require initiation of oral/IV corticosteroids - require a corticosteroid injection. https://www.rheumatology.org.uk/practice-quality/covid-19- guidance

Rompe, J., Segal, N., Cacchio, A., Furia, J., Morral, A., and Maffulli, N. (2009) Home training, local corticosteroid injection, or radial shock wave therapy for greater trochanter pain syndrome. American Journal of Sports Medicine. 37(10),1981-90 Saunders, S & Longworth, S. (2012). Injection techniques in musculoskeletal medicine: A practical manual for clinicians in primary and secondary care. 4th ed.

Churchill Livingstone

Segal, N., Felson, D., Torner, J., Zhu, Y., Curtis, J., Niu, J. and Nevitt, M. (2007).

Multicenter Osteoarthritis Study Group. Greater trochanteric pain syndrome: epidemiology and associated factors. Archives of Physical Medicine and

Rehabilation.88(8), 988-92.

Shah, A., Mak, D., Davies, A., James, S. and Botchu, R. (2019). Musculoskeletal

Corticosteroid Administration: Current Concepts. Canadian Association of Radiology

Journal. 70(1),29-36.

Stephens, G., O'Neill, S., French, H., Fearon. A., Grimaldi, A., O'Connor, L.,

Woodley, S. and Littlewood, C. (2018). A survey of physiotherapy practice in the

United Kingdom for patients with greater trochanteric pain syndrome.

Musculoskeletal Science and Practice. 40(9), 0-20.

Tan, L., Benkli, B., Tuchman, A., Li, J, Desai, N., Bottiglieri, T., Pavel, J., Lenke, L.,

Lehman, R., (2018). High prevalence of greater trochanteric pain syndrome among patients presenting to spine clinic for evaluation of degenerative lumbar pathologies.

Journal of Clinical Neuroscience, 53(5) 89-91

Walker-Santiago, R., Wojnowski, N., Lall, A., Maldonado, D. Rabe, S. and Domb, B.

(2020). Platelet-Rich Plasma Versus Surgery for the Management of Recalcitrant

Greater Trochanteric Pain Syndrome: A Systematic Review. Arthroscopy. 36(3),

875-888.

Case 14

Stephen Bramson

Ultrasound Guided Aspiration & Injection of the Gleno-Humeral Joint (GHJ) Presentation 83-year-old female with recurrent pain and gross swelling of the left shoulder with significant reduction in range of movement. Relevant Medical History Hypertension Arthritis Eczema Hypercalcemia Hypercholesterolaemia Osteoporosis Multiple previous fractures (recent T10, old T6 & T8, left wrist and ankle)

Current Medication Amlodipine Bendroflumethiazide Prednisolone Adcal D3 Not tolerating oral bisphosphonates.

The patient has a weekly cleaner but remains active running her own business, drives, lives alone, independent of ADLs, mobile with walking stick and furniture walks at home. Mobility is limited by pain in the neck and left shoulder for which she takes analgesia. The patient was on long term prednisolone for her eczema (currently 5mg) with no other obvious secondary osteoporosis risk factors. High risk for major osteoporotic fractures with a FRAX Score of 64%. Lowering the risk of further significant fracture with associated morbidity by increasing mobility, reducing pain, and risk of falls are the goals of intervention.

Investigations Initial x-rays (images A and B) demonstrated moderate OA changes to the GHJ with osteophytic lipping of the glenoid and humeral head with mild narrowing of the subacromial space in keeping with possible rotator cuff injury type pattern.

Image A: X-ray; AP view Image B: X-Ray; Y view

Subsequent diagnostic ultrasound scan of the left shoulder (images C and D) in Summer 2018 demonstrated a large effusion in the anterior, lateral, and posterior aspects of the glenohumeral joint with internal synovial hypertrophy and hyperaemia on the outer joint capsule. Very few fibres of the Long Head of Biceps (LHB) tendon were demonstrated in keeping with a rupture. There was a complete tear of the subscapularis and supraspinatus. The AC joint was degenerative. Very irregular bone contour was evident in the head or humerus.

Image C: Image D: Diagnostic ultrasound; subscapularis Diagnostic ultrasound; supraspinatus

Previous Management 80 ml of inflammatory viscous joint fluid was previously aspirated under ultrasound guidance (September 2018) by a consultant rheumatologist. As potential differential diagnosis included septic arthritis, gout or pseudogout, aspirated synovial fluid was sent for analysis; microscopy, culture and sensitivity (MC&S), cell count, gram stain, crystallography, and TB culturing (all negative). Subsequently, a repeat aspiration of 100 ml of inflammatory joint fluid was performed under ultrasound guidance (November 2018) by the consultant rheumatologist, followed by injection of 80mg methylprednisolone with 2ml 2% lidocaine.

Referral (June 2019) Referred by the consultant rheumatologist for further repeat ultrasound guided aspiration and cortico-steroid injection to the left GHJ.

Ultrasound Guided Aspiration and Corticosteroid Injection (CSI) to the left GHJ (July 2019) Patient information leaflet on injection therapy, including associated risks had been sent to the patient in the post prior to appointment, allowing the patient time to process the information to facilitate appropriate informed consent. Pre-procedural scan (image E) confirmed a current large effusion distending the glenohumeral joint / sub acromial bursa of the left shoulder consistent with previous imaging.

Image E: Pre-procedure ultrasound image

Following appropriate informed verbal consent including risk of infection, skin depigmentation, fat atrophy, post injection flare and recurrence, and no recent infections, 5ml of 1% lidocaine was infiltrated to the GHJ under ultrasound guidance with 121ml of blood stained fluid aspirated (image F). As infection was not suspected from the clinical presentation and previous negative synovial fluid analysis, 40mg in 1ml of the corticosteroid methylprednisolone was injected to the GHJ with the procedure being well tolerated with no immediate adverse effects.

Image F Critical reflection: improved preparation with adequate stock of larger syringes (20/50ml) would have led to improved technical efficiency of aspiration procedure. Discussion As a non-prescriber within the NHS, the above procedure was performed under the direction of a Patient Group Directive (PGD) which prohibits the mixing of two licensed medicines together, creating a new unlicensed product, before administration (CSP 2016). Therefore, the above procedure was performed using an aseptic technique with the same needle in situ (green 21G 40mm), with change of syringe performed following initial infiltration of local anaesthetic, to multiple syringe changes for aspiration and finally, injection of corticosteroid. Compared to previous procedures, a lower dose of 40mg methylprednisolone was used in alignment with maximum dose permitted under the PGD.

Following a massive growth in the literature over the last decade, a position statement (Finnoff 2015) by the American Medical Society for Sports Medicine (AMSSM) highlights there is now strong evidence that Ultrasound Guided Injections (USGI) are more accurate than Land Mark Guided Injections (LMGI), moderate evidence that they are more efficacious and preliminary evidence that they are more cost-effective.

An interesting original study on 12 cadaver specimens by Gofeld (2019), confirmed continuity of the GHJ capsule and the biceps tendon sheath through injection of blue dye into the biceps groove, validating this anterior approach as a simple alternative to accessing the glenohumeral joint. A study of 100 patients by Rutten (2009) concluded that compared to fluoroscopically guided techniques, US-guided injections to the shoulder and especially the anterior approach are significantly less time consuming, more successful on the first attempt, cause less patient discomfort and eradicate the need for radiation and iodine contrast. However, Chen (2015) stated the posterior GHJ approach is preferred in glenohumeral joint injection as less extravasation will occur as compared with the anterior rotator interval approach and avoids the axillary neurovascular structures. As outlined by Smith (2009) advanced planning of the procedure is important for successful intervention including review of regional anatomy (with power doppler), selecting shortest possible route skin to target tissue while minimising the neovascular risk and optimising needle visualisation. The procedure was performed with portable GE Logiq E with patient comfortable in supported long sitting on with left shoulder slightly adducted and in internal rotation. With screen, patient and line of needle all in view and with the high frequency 12MHz linear transducer probe positioned in a longitudinal position, the needle was advanced, from posterior- lateral position, in plane and parallel to the probe for optimum visualisation, into the distended posterior joint capsule. This procedure was performed from a posterior lateral approach due to personal clinical preference and experience that this tends to be a non-sensitive technique with the additional benefit that the patient is not directly visualising the needle. Ultrasound guidance also provided real time monitoring, allowing optimisation of the volume of fluid aspirated.

Long-acting, usually insoluble steroid formulations are frequently used as intra- articular or intramuscular injections in rheumatic diseases, due to their effect on reducing pain and inflammation. For large joints (e.g. shoulder) both triamcinolone and methylprednisolone have been recommended and for smaller joints (e.g. finger), hydrocortisone or methylprednisolone. Both triamcinolone and methylprednisolone have approximately 5 times the potency of hydrocortisone. Triamcinolone has duration of action of 2-3 weeks compared to Methylprednisolone of 3-4 weeks (Stephens 2008). For musculoskeletal injections, lidocaine hydrochloride is the most frequently used local anaesthetic, with a rapid onset and duration of action ranging from 80 to 120 minutes, making it ideal for both subcutaneous and intra-articular anaesthesia. Only 1% lidocaine concentration should be used, as doses greater than 1% concentration have been associated with chondrocyte toxicity (Murakami 2015). Complications of intra-articular injection include post injection flare of pain (2-10%), skin atrophy (1 %), fat atrophy (1 %), and facial flushing (<1-12%). Less commonly reported side effects include iatrogenic infection (risk of 1 in 1,000) (Stephens 2008).

The recent COVID-19 pandemic is caused by a newly identified coronavirus infection (SARS-CoV-2) in humans which in severe cases can lead to the formation of a ‘inflammatory cytokine storm’ which can cause respiratory distress, multi-system organ failure and death (Amani 2020). Several governing bodies from leading health professions in the UK subsequently produced joint guidance (BSR et al 2020) around the concern that due to their immunosuppressive effects’, steroids can increase the risk from SARS-CoV-2. This guidance was initially widely interpreted on a national basis as steroid injections being contraindicated during COVID-19 (Little 2020) and their subsequent temporary cessation of their use for MSK pathology. Little (2020) discusses how some observational studies have found corticosteroid use conferred a dose-related increased risk of infection in rheumatic patients, who are already at double the population baseline risk of developing infections, however it’s important to recognise the comparatively very small doses used in most musculoskeletal corticosteroid injections (CSI).

There is a genuine risk that suspending the legitimate use of a CSI that could alleviate pain, improve quality of life and delay, if not remove, the need for surgery may expose individuals to higher risks than the so far unproven risk from a relatively low dose of steroid, is in itself unethical (Amani 2020, Little 2020). The original guidance summarises that an individual risk analysis should take place on a case- by-case basis and a steroid injection should only be considered at the minimum appropriate dose if a patient has significant disease activity and/or intrusive and persisting symptoms, has failed first-line measures including simple analgesia, activity modification, splinting and exercise and there are no appropriate alternatives.

In line with Montgomery (2015), the judgement to proceed must follow an informed shared decision-making process including risks and implications of CSI versus alternative management strategies with the patient having the mental capacity (Mental Capacity Act 2005) and appropriate time to reflect their decision with the process recorded in their medical notes. The aspiration and injection discussed in this case study was performed prior to the COVID 19 pandemic. The additional increased risk associated with the medical history of hypertension and the patients age (83) balanced against the acknowledgement of the high risk of osteoporotic fractures and the reliance on shoulder function to maintain the patient’s mobility and independence would form the focus of any future individual risks analysis for this patient.

Alternative management Dean (2013) discusses how as the body of evidence in the literature has gradually questioned the validity of common clinical diagnostic tests of the shoulder, there has been a shift towards increased utilisation of radiological imaging modalities such as ultrasound and MRI. Glenohumeral joint osteoarthritis can mimic frozen shoulder which is why all stiff shoulders should be X-rayed to assist diagnosis (Sinha 2017). However, careful interpretation of investigation findings is required prior to any intervention including guided injections as the cause of shoulder pain can be multifactorial even in the presence of confirmed pathology as demonstrated by Templehof (1999) who showed from a prospective study of 411 volunteers that asymptomatic rotator cuff tears increase with age, with up to 51% in those greater than 80 years of age.

Levy (2008) acknowledges that the management of massive rotator cuff tears in medically unfit, elderly patients can be difficult and concludes that anterior deltoid rehabilitation programmes are suitable for this population to improve pain and function. The patient has not previously benefited from physiotherapy to the shoulder. The surgical option with a clinical presentation of a massive with GHJ arthritis would include a reverse shoulder replacement (Petrillo 2017), however the patient is not considered a surgical candidate due to her comorbidities. Ultrasound guided intervention remains an appropriate option. One alternative to using corticosteroid includes performing the aspiration in isolation to improve pain and function, thus removing the concern over the additional use of corticosteroids during the COVID pandemic.

Over the past decade there has been a rapid rise in the clinical use of platelet-rich plasma (PRP) injections in the management of orthopaedic conditions including mild- moderate OA. The platelets contain growth factors which are believed to stimulate chondrocyte proliferation, leading to cartilage repair. A randomised controlled trial of 30 participants by Smith (2016) concluded intra-articular autologous conditioned plasma injections provide safe quantifiable benefits for pain relief and functional improvement in knee OA. Schnieder (2018) discusses how recent literature has shown equivocal to minor benefit of PRP use for shoulder pain, function, and healing. Overall, the body of literature is currently inconclusive regarding the clinical benefit and cost-effectiveness of PRP in the treatment of shoulder pathology. However few complications have been reported from PRP, therefore it may be a viable treatment method in specific populations, such as patients for whom corticosteroid use is a concern. Despite the expanding plethora of PRP-related citations, there remains a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded demonstrating efficacy. Consequently, PRP procedures should only be performed with special arrangements for clinical governance, consent, and audit or research (Smith 2016 & NICE 2019).

Viscosupplementation with hyaluronic acid is a well-tolerated treatment for joint OA and has been proven to be effective treatment for mild-moderate knee OA (Henrotin 2015). Messina (2016) reviews the literature and discusses how hyaluronic acid injections are indicated for cuff arthropathy and degenerative arthritis without articular effusion of the shoulder to aid conservative management due to evidence of improved pain and mobility scores. However, in 2014 the National Institute for Health and Care Excellence (NICE) advised against offering hyaluronic acid injections within the NHS due to inconsistent evidence demonstrating statistically significant effects with the benefits not considered clinically important. Mesenchymal Stem Cells (MSC) offer another promising and emerging alternative intervention. A systematic review of 61 articles and 2390 patients by Jevotoysky (2018) concluded stem cell therapy appears to alleviate the symptoms of osteo- arthritis and potentially halt cartilage damage. However, to date there remains limited high-quality evidence and long term follow up, and like PRP, is associated with lack of consistency and diversity of MSC preparations, with subsequent dearth of reproducibility.

Summary

The patient was reviewed by the consultant rheumatologist 2 months post procedure with the shoulder no longer a source of complaint. No further shoulder intervention has been requested or performed in the 14 months following the aspiration and injection focussed on during this case report, performed in July 2019.

The repeat ultrasound guided aspiration and corticosteroid injection described in this case study proved to have been a safe, appropriate, timely and effective intervention. Recurrence of symptoms during the current COVID-19 pandemic would lead to a review of the risk-benefit analysis of using corticosteroid in this individual with appropriate consideration given to alternative options.

Reference list Amani, L., Warraich, R., Lee, J. and Tahir, H. (2020). Steroid Injections & COVID-19: Are Specialists Justified in Defying the Guidelines? Int. J. Clin. Rheumatol, 15(4), pp.129-130.

British Society for Rheumatology (BSR), British Orthopaedic Association, British Association of Spine Surgeons, Faculty of Pain Medicine of the Royal College of Anaesthetists, Royal College of General Practitioners, The British Pain Society, Charted Society of Physiotherapy (16th June 2020) Management of patients with musculoskeletal and rheumatic conditions who: Are on corticosteroids, Require initiation of oral / IV corticosteroids, Require a corticosteroid injection

Chartered Society of Physiotherapy (CSP). (2016). The use of medicines with injection-therapy in physiotherapy services. 5th Edition, PD003. Chen, C.P., Lew, H.L. and Hsu, C.C. (2015). Ultrasound-guided glenohumeral joint injection using the posterior approach. American journal of physical medicine & rehabilitation, 94(12), p.e117. Dean, B.J.F., Gwilym, S.E. and Carr, A.J., (2013). Why does my shoulder hurt? A review of the neuroanatomical and biochemical basis of shoulder pain. British journal of sports medicine, 47(17), pp.1095-1104. Finnoff, J.T., Hall, M.M., Adams, E., Berkoff, D., Concoff, A.L., Dexter, W. and Smith, J. (2015). American Medical Society for Sports Medicine (AMSSM) position statement: interventional musculoskeletal ultrasound in sports medicine. PM&R, 7(2), pp.151-168. Gofeld, M., Hurdle, M.F. and Agur, A. (2019). Biceps tendon sheath injection: an anatomical conundrum. Pain Medicine, 20(1), pp.138-142. Henrotin, Y., Raman, R., Richette, P., Bard, H., Jerosch, J., Conrozier, T., Chevalier, X. and Migliore, A., (2015). Consensus statement on viscosupplementation with hyaluronic acid for the management of osteoarthritis. In Seminars in arthritis and (Vol. 45, No. 2, pp. 140-149). Jevotovsky, D.S., Alfonso, A.R., Einhorn, T.A. and Chiu, E.S., (2018). Osteoarthritis and stem cell therapy in humans: a systematic review. Osteoarthritis and cartilage, 26(6), pp.711-729. Levy, O., Mullett, H., Roberts, S. and Copeland, S., (2008). The role of anterior deltoid reeducation in patients with massive irreparable degenerative rotator cuff tears. Journal of shoulder and elbow surgery, 17(6), pp.863-870. Little, C.P., Birks, M.E., Horwitz, M.D., Ng, C.Y. and Warwick, D. (2020). COVID-19: A rethink of corticosteroid injection? Bone & Joint Open, 1(6), pp.253-256. Messina, C., Banfi, G., Orlandi, D., Lacelli, F., Serafini, G., Mauri, G., Secchi, F., Silvestri, E. and Sconfienza, L.M., (2016). Ultrasound-guided interventional procedures around the shoulder. The British journal of radiology, 89(1057), p.20150372. Murakami, A. (2015) Ultrasound Guided Injections A Technical Review. ASPETAR Sports Medicine Journal. Vol 4. Petrillo, S., Longo, U.G., Papalia, R. and Denaro, V. (2017). Reverse shoulder arthroplasty for massive irreparable rotator cuff tears and cuff tear arthropathy: a systematic review. Musculoskeletal surgery, 101(2), pp.105-112. Rutten, M.J., Collins, J.M., Maresch, B.J., Smeets, J.H., Janssen, C.M., Kiemeney, L.A. and Jager, G.J. (2009). Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MR arthrography. European radiology, 19(3), pp.722-730. Schneider, A., Burr, R., Garbis, N. and Salazar, D., (2018). Platelet-rich plasma and the shoulder: clinical indications and outcomes. Current reviews in musculoskeletal medicine, 11(4), pp.593-597. Silverstein, E., Leger, R. and Shea, K.P., (2007). The use of intra-articular hylan GF 20 in the treatment of symptomatic osteoarthritis of the shoulder: a preliminary study. The American journal of sports medicine, 35(6), pp.979-985. Sinha, R., Patel, P., Rose, N., Tuckett, J., Banerjee, A.N., Williams, J., Aldridge, S. and Stuart, P., (2017). Analysis of hydrodilatation as part of a combined service for stiff shoulder. Shoulder & elbow, 9(3), pp.169-177. Smith, J. and Finnoff, J.T. (2009). Diagnostic and interventional musculoskeletal ultrasound: part 2. Clinical applications. PM&R, 1(2), pp.162-177. Smith, P.A. (2016). Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. The American journal of sports medicine, 44(4), pp.884-891. Stephens, M.B., Beutler, A. and O'Connor, F.G., (2008). Musculoskeletal injections: a review of the evidence. American family physician, 78(8), pp.971-976. Tempelhof, S., Rupp, S. and Seil, R., (1999). Age-related prevalence of rotator cuff tears in asymptomatic shoulders. Journal of shoulder and elbow surgery, 8(4), pp.296-299.

Web references

FRAX Assessment Tool https://www.sheffield.ac.uk/FRAX/ Centre for Metabolic Bone Diseases, University of Sheffield, UK

Mental Capacity Act (2005) https://www.legislation.gov.uk/ukpga/2005/9/contents Montgomery v Lanarkshire Health Board [2015] SC 11 [2015] 1 AC 1430 https://www.bailii.org/uk/cases/UKSC/2015/11.html

Osteoarthritis: care and management (2014) NICE https://www.nice.org.uk/guidance/cg177

Platelet-rich plasma injections for knee osteoarthritis (2019) NICE https://www.nice.org.uk/guidance/ipg637