Objectives: To evaluate the efficacy and safety of ultrasound-guided injection of platelet-rich plasma (PRP) in the treatment of supraspinatus tendonitis after 12 weeks of follow-up. Subjects and methods: A prospetive controlled clinical trial was followed up to 12 weeks in 44 patients with supraspinatus tendonitis.
Journal of military pharmaco-medicine n08-2017 INITIAL EVALUATION OF EFFICACY OF AUTOLOGOUS PLATELET-RICH PLASMA ULTRASOUND-GUIDED INJECTION IN SUPRASPINATUS TENDONITIS TREATMENT Nguyen Duc Phong*; Pham Hoai Thu*; Nguyen Van Hung* SUMMARY Objectives: To evaluate the efficacy and safety of ultrasound-guided injection of platelet-rich plasma (PRP) in the treatment of supraspinatus tendonitis after 12 weeks of follow-up Subjects and methods: A prospetive controlled clinical trial was followed up to 12 weeks in 44 patients with supraspinatus tendonitis, who were divided into two groups: 22 patients (22 supraspinatus tendons) received a single ultrasound-guided injection of PRP into supraspinatus tendon sheath, 22 patients (22 supraspinatus tendons) were given a single ultrasound-guided injection of 0.5 ml methylprednisolone acetate 40 mg/mL (Depo-Medrol) into supraspinatus tendon sheath Results: After 12 weeks of treatment, there were improvement in VAS, abduction angle of shoulder joint and SPADI scores in the studied group: The average VAS and SPADI scores were decreased from 6.5 to 2.5 points and from 57.6 to 27.4 points, respectively The average abduction angle of shoulder joint was increased from 88.40 to 155.10, significantly higher than that in the control group (p < 0.05) Side effects observed the investigated group were: 18.2% of the patients increased pain at the injection site more than 24 hours (compared to 13.6% in the control group) (p > 0.05) and there was no serious complication in both groups Conclusions: A single ultrasound-guided injection of PRP is more effective than a single ultrasound-guided injection of Depo-Medrol in treatment of supraspinatus tendonitis The procedure is a safe theraputic intervention * Keywords: Supraspinatus tendonitis; Autologous platelet-rich plasma; Ultrasound-guided injection INTRODUCTION Peri-shoulder joint soft tissue inflammation is a group of the periarticular soft tissue disorders of shoulder, including ligaments, tendons, bursas it often causes pain and reduces range of motion of the shoulder and affects patients’ quality of life Perishoulder joint soft tissue inflammation is classified into four clinical types: shoulder pain, acute shoulder pain, shoulder pseudo-paralysis and frozen shoulder [2] The most common disorder is shoulder pain, in which supraspinatus and long head of biceps tendons are usually affected [1] Supraspinatus tendon lies in a narrow space under the scapula In the arm abducted and 90o elevated postion, the tendon is squezzed and rubbed between the femoral head and the coraco-acromial ligaments, which reduces the blood flow to the tendon, causes the tendon vulnerable to injury, resulting in inflammation, calcification, * Hanoi Medical University Corresponding author: Nguyen Van Hung (hungnnguyenvn@gmail.com) Date received: 20/08/2017 Date accepted: 28/09/2017 172 Journal of military pharmaco-medicine n08-2017 partial thickness tear or full thickness tear of the tendon [3] Although pain killer, nonsteroidal anti-inflammatory drugs may be effective in treatment of supraspinatus tendonitis, they can cause many complications with long-term use, such as peptic ulcers, gastrointestinal bleeding, hypertension, renal and liver damage, ect Injection of corticosteroids has the rapid effect in improving symptoms but repeated and prolonged usage can result in tendon rupture [7] Autologous platelet-rich plasma (PRP) contains growth factors and antiinflammatory cytokines, is a new therapeutic procedure for treatment of tendinitis with good efficacy and less side effects There have been some studies on the treatment of tendinitis with PRP therapy in the wold, however, there is no systematic study of the application of PRP in treatment of supraspinatus tendonitis in Vietnam In addition, ultrasound-guided procedure is recommeded for the acuracy of the injection into the injured tissue Therefore, we conducted this study with objectives: To evaluate the efficacy and safety of ultrasound-guided injection of PRP in the treatment of supraspinatus tendonitis after 12 weeks of follow-up SUBJECTS AND METHODS Subjects Our study included 44 patients who were diagnosed with supraspinatus tendinitis based on clinical features and ultrasound examination (acrominal pain, restricted movement, positive Jobe test) [7] Subjects were divided into groups: studied group included 22 patients (22 supraspinatus tendinitis) were treated with PRP injection under ultrasound guidance and control group of 22 patients (22 supraspinatus tendinitis) treated with Depo-Medrol injection under ultrasound guidance Patients were treated at Rheumatology Department in Bachmai Hospital from 10 - 2016 to - 2017 Patients agreed to participate in the study The exclusion criteria were patients with another types of peri-shoulder joint soft tissue inflammation, such as acute shoulder pain, shoulder pseudo-paralysis and frozen shoulder, neurological pain, local and systemic infections, haematological disease or anticoagultaion drug use, hemoglobin below 110 g/L, platelet below 150,000/mm3, pregnancy, topical steroid injections within weeks before the study, patients not agree to participate in the study Patients who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) must quit the drug within week prior to the enrolment in the study Methods Controlled clinical trial with intevention, longitudinal follow-up study Patients in the research group were injected with 2.5 mL of PRP produced using Adistem technology under ultrasound guidance, into the supraspinatus tendon sheath, in a single dose The control group was injected with 0.5 mL methylprednisolone acetate 40 mg/mL (Depo-Medrol), a corticosteroid indicated for local treatment of tendosynovitis, in the supraspinatus tendon sheath under ultrasound guidance The procedure was performed by a rheumatologist with assistance 173 Journal of military pharmaco-medicine n08-2017 of medison accuvix v 10.0 ultrasound machine, linear probe - 13 Mhz at the Department of Rheumatology, Bachmai Hospital Assessment of outcomes was based on VAS score, SPADI score and shoulder abduction angle at baseline (T0), week after treatment (T1), weeks after treatment (T4), weeks after treatment (T8) and 12 weeks after treatment (T12) Side effects of therapy were observed and noted at any time of the study Patients in the studied group did not use nonsteroidal anti-inflammatory drugs (NSAIDs) within days after injection, the control group was treated in combination with nonsteroidal anti-inflammatory drugs: mobic 7.5 mg x tablets/day, myonal 50 mg x tablets/day or equivalent doses * Data analysis: Data in the study were analyzed using SPSS statistics 20 software RESULTS Characteristics of patients Table 1: Patients’ characteristics Research group Control group (n = 22 tendons) (n = 22 tendons) Age 61.4 ± 9.4 60.1 ± 8.2 > 0.05 Male 68.2% 63.7% > 0.05 Female 31.8% 36.3% > 0.05 22.1 ± 2.8 21.6 ± 1.3 > 0.05 Right 68.2% 63.7 % >0.05 Left 31.8% 36.3% >0.05 Duration (month) 10.6 ± 8.4 10.1 ± 5.8 > 0.05 VAS (T0) 6.5 ± 1.1 6.5 ± 0.8 > 0.05 Abduction angle (T0) 88.4 ± 7.9 87.9 ± 8.7 > 0.05 SPADI (T0) (%) 57.6 ± 7.4 58.4 ± 4.3 > 0.05 BMI Side of the affected tendon p There was no difference in age, gender, duration of illness, BMI, side of the inflammed tendon, pain intensity, abduction angle, shoulder joint function between the two study groups (p > 0.05) 174 Journal of military pharmaco-medicine n08-2017 Evaluation of the efficacy of supraspinatus tendonitis treatment by autologous PRP therapy * According to VAS score: Figure 1: Evaluate the results of treatment by VAS score (n = 22 tendons) At the time of initial treatment, week and weeks after treatment, there was no difference of the two groups in terms of VAS score improvement (p > 0.05) After and 12 weeks of treatment, the patients treated with PRP improved VAS score better than control group, statistically significant p < 0.05 * According to abduction angle: Table 2: Improvement of abduction angle Research group (n = 22 tendons) X ± SD Control group (n = 22 tendons) X ± SD p T0 (1) 88.4 ± 7.9 87.9 ± 8.7 > 0.05 T1 (2) 108.2 ± 14.8 109.3 ± 10.3 >0.05 T4 (3) 127.7 ± 12.7 131.6 ± 10.4 > 0.05 T8 (4) 143.2 ± 11.1 135.5 ± 11.4 < 0.05 T12 (5) 155.1 ± 13.3 145.2 ± 14.5 < 0.05 ∆ T8 - 54.8 ± 11.0 47.5 ± 15.9 > 0.05 ∆ T12 - 66.8 ± 12.1 57.3 ± 18.2 < 0.05 p < 0.001 p < 0.001 p1,5 Both therapies improved the shoulder abduction angle (p < 0.05) At 12 weeks post-treatment, patients treated with PRP improved better than those treated with Depo-Medrol (p < 0.05) 175 Journal of military pharmaco-medicine n08-2017 * According to improvement of shoulder function: Figure 2: Evaluate the results of treatment by SPADI score (n = 22 tendons) Both groups had improvement in shoulder function compared with pretreatment, p < 0.05 From the fourth week after treatment, the PRP injection group had a better improvement compared to the Depo-Medrol injection group, p < 0.05 Side effects of the therapy Table 3: Side effects of the therapy Position Local Systemic Others Side effects Research group (n = 22 tendons) Control group (n = 22 tendons) Number Percentage (%) Number Percentage (%) Pain increase after 24 hours 18.2 13.6 Infection 0 0 Shock 0 0 Blush, headache dizziness 0 4.6 Hemorrhage 0 0 In the studied group, patients (18.2%) developed pain after injection and in the control group, patients (22.7%) developed pain after injection The difference was not statistically significant In the control group, there was one patient presenting with flushing after injection, but none of the patients had any other serious side effects 176 Journal of military pharmaco-medicine n08-2017 DISCUSSION Evaluation of the efficacy of supraspinatus tendinitis treatment by autologous PRP therapy (PRP is the plasma volume of whole blood that has a platelet concentration higher than the basal level in the original vein blood PRP contains many growth factors and some cytokines that have antiinflammatory and wound healing effects Growth factors such as PDGF, VEGF, EGF, PDEGF, PDAF, ECGF are involved in wound healing process through angiogenesis, cell division, cell differentiation and healing [8] The cytokines produced during platelet activation, such as the interleukin I receptor antagonist (IL-IRA), are powerful anti-inflammatory agents which reduce the intensity and duration of pain, release beta-endorphins which provide analgesic, anti-inflammatory effects IL-4, IL-10, in addition to anti-inflammatory, also play a role in tissue regeneration of tendons, ligaments [9] Since Depo-Medrol is a corticosteroid, it has anti-inflammatory and analgesic effects, however, no studies have documented the role of corticosteroids in wound healing process Therefore, PRP works better than Depo-Medrol due to its effects on lesion regenerative healing The results in our study showed significant improvement in VAS scores in both groups after week and weeks of treatment (p < 0.05) However, there was no difference between the two groups (p > 0.05) This result was similar to that of Nguyen Thi Xuan Huong (2015), VAS score at week and weeks in DepoMerol injection patients under the ultrasound guidance, decreased from 6.2 ± 0.6 to 2.3 ± 1.2 and 0.7 ± 0.9, respectively [5] However, the reduction of VAS score in our study was lesser than in the author's study, probably because the patients in our study group had a longer duration of disease (10.6 ± 8.4 vs 6.4 ± 7.6 years) At weeks and 12 weeks post-treatment, PRP-treated group was associated with better pain relief than Depo-Medroltreated group (p < 0.05) (figure 1), similar to the results of Sengodan et al (2017) in patients with rotator cuffs syndrome, VAS score at weeks and 12 weeks after PRP injection decreased from 5.4 ± 0.9 to 3.2 ± 0.9, and 2.6 ± 0.8 [10] In this study, both treatment groups showed improvement in shoulder range of motion In the research group, the mean shoulder abduction angle after 12 weeks of treatment increased from 88.4 ± 7.9o to 155.2 ± 13.3o, higher than that in the control group Shoulder abduction angle also increased from 87.9 ± 8.7o to 145.2 ± 14.5o, statistically significant (p < 0.05) (table 2) This finding was similar to the results of Serdar et al (2013) in patients with rotator cuffs disease After weeks, weeks and 12 weeks of autologous PRP treatment, shoulder abduction angle was increased from 90o up to 110o, 140o and 160o (p < 0.05), respectively Although there are many scores to evaluate shoulder joint function, the SPADI score was used in this study since it was previously used in most of the studies The results showed that both treatments improved shoulder function and this improvement was statistically significant 177 Journal of military pharmaco-medicine n08-2017 starting from week 4th (p < 0.05) (figure 2) At this time, the studied group had a better SPADI score than the control group After 12 weeks of treatment, SPADI score of the studied group and control group decreased from 57.6 to 27.4 and from 58.4 to 41.8 points (p < 0.05), respectively This result was similar to the results of Serdar et al (2013) SPADI scores in autologous PRP group after 12 weeks of treatment decreased from 77.5 to 27.6 (p < 0.05) Similarly, the study by Dongwook et al (2013) found that SPADI score after 12 weeks of treatment for supraspinatus tendonitis by PRP decreased from 62.3 to 21.1 points, more effective than acupuncture (p < 0.05) [12] The rusults from our study suggested that patients with tendinitis treated with PRP injection under the guidance of ultrasound had better results, longer lasting effects compared to Depo-Medrol injection (p < 0.05) Side effects of the therapy Previous studies had shown that PRP therapy is a safe, less side effect treatment In the investigated group, 22 patients (22 supraspinatus tendons) received PRP, there were patients had shoulder pain increased after the injection (18.2%) However, it was only mild pain There were cases with self-limited pain and cases needed treatment with low dose acetaminophen Similarly, in the DepoMedrol injection group, there were patients with shoulder-joint pain (13.6%), among which patients were treated with low dose acetaminophen In the Depo-Medrol 178 injection group, there was one patient who was flushed after the injection However, the patient had a history of hypertension, so the symptom disappears quickly after 30 minutes of rest when blood pressure returned to normal In addition, both methods had no other serious complications The study by Nguyen Tran Trung [6] on the treatment of lateral epicondylitis with autologous PRP, there were 54.8% of patients suffering pain at the injection site, in which 38.7% lasted for days and 16.1% of patients had pain in week Research by Segodan et al (2017) also showed that the most common side effect after PRP injection was pain, but usually mild and self-limited [10] CONCLUSION Autologous injection of PRP under the giudance of ultrasound for the treatment of supraspinatus tendonitis has improved pain and shoulder joint function better than Depo-Medrol injection The procedure is a promissing and safe therapeutic intervention REFERENCES Trần Ngọc Ân Viêm quanh khớp vai Bệnh thấp khớp Nhà xuất Y học 2002, tr.364-374 Đào Hùng Hạnh Sử dụng siêu âm đeer phát tổn thương viêm quanh khớp vai Luận văn Thạc sỹ Y học Trường Đại học Y Hà Nội 1995, tr.26-57 Tăng Hà Nam Anh, Nguyễn Huy Toàn, Cao Bá Hưởng CS Kết điều trị rách chóp xoay qua nội soi Tạp chí Y Dược TP Hồ Chí Minh 2013, tháng 2, tr.62-66 Journal of military pharmaco-medicine n08-2017 Nguyễn Thị Ngọc Lan Bệnh học xương khớp nội khoa Nhà xuất Giáo dục 2012 Nguyễn Thị Xuân Hương Nghiên cứu hiệu điều trị viêm quanh khớp vai thể viêm gân gai corticosteroid hướng dẫn siêu âm Luận văn Chuyên khoa Cấp II Trường Đại học Y Hà Nội 2015, tr.42-45 Nguyễn Trần Trung Đánh giá kết điều trị liệu pháp huyết tương giàu tiểu cầu tự thân điều trị viêm lồi cầu xương cánh tay Luận văn Thạc sỹ Y học Trường Đại học Y Hà Nội 2015 Speed C.A Fortnightly review: Corticosteroid injections in tendon lesions BMJ 2001, 323 (7309), pp.382-386 Giotis D, Aryaei A, Vasilakakos A et al Effectiveness of biologic factors in shoulder disorders The Open Orthopaedics Journal 2017, 11, pp.163-182 LLiknur Sanli, Barnes Morgan et al Single injection of platelet - rich plasma (PRP) for the treatment of refractory distal biceps tendonitis: long-term results of a prospective multicenter cohort study Knee Surg Sports Traumatol Arthrosc 2016, 24 (7), pp 23082312 10 Sengodan V.C, Kurian S, Ramasamy R Treatment of partial rotator cuff tear with ultrasound-guided platelet-rich plasma Clin Imaging Sci J 2017, pp.7-32 11 Serdar K, Tan A.K, Yilmaz B, Yasar E et al Platelet-rich plasma injections in the treatment of chronic rotator cuff Am J Sports Med 2013, 2609, p.41 12 Dong-wook R, Park G.Y, Yong-Kyun Kim Y.K et al Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: a randomized controlled trial Clin Rehabil J 2013, 113, p.27 179 ... systematic study of the application of PRP in treatment of supraspinatus tendonitis in Vietnam In addition, ultrasound- guided procedure is recommeded for the acuracy of the injection into the injured... evaluate the efficacy and safety of ultrasound- guided injection of PRP in the treatment of supraspinatus tendonitis after 12 weeks of follow-up SUBJECTS AND METHODS Subjects Our study included 44... of military pharmaco-medicine n08-2017 Evaluation of the efficacy of supraspinatus tendonitis treatment by autologous PRP therapy * According to VAS score: Figure 1: Evaluate the results of treatment