Ultrasound-guided platelet-rich-plasma injections for reducing sacroiliac joint pain: A paradigmatic case report and literature review

1. Introduction

Sacro-iliac joint (SIJ) is a diarthrodial joint that is functionally responsible for the transfer of loads from the spine to the legs [1, 2]. It has been estimated that up to 30% of cases of atypical low back pain (LBP) might be related to SIJ pain, with a consequent noteworthy functional impairment [3, 4, 5].

In this context, sacroiliac joint pain is often not specifically treated due to the lack of precise diagnosis and concomitant other neuromuscular conditions [5, 6, 7], with crucial implications in terms of disability and psychosocial burden [3, 8, 9].

Several conservative treatments have been proposed to reduce pain and functional impairment in these patients, including rehabilitation (i.e., core and pelvic muscle training, muscle strengthening), oxygen-ozone therapy, oral medications, and corticosteroid injection [10, 11, 12, 13]. This latter is the most used therapy among the therapeutical approaches for SIJ pain currently available in the clinical practice [12]; however, the results are frequently short-lived and the pharmacological approach might be related to potential side effects in particular cases [14].

As described hereafter in this paradigmatic case, mitochondrial dysfunction represents a heterogeneous group of disorders characterized by a wide variability of clinical symptoms that might affect the musculoskeletal system causing muscle weakness, exercise intolerance, and fatigue [15, 16].

More in detail, fluoroquinolone-induced mitochondrial dysfunction is a disease leading to increased oxidative stress, with crucial implications regarding corticosteroid treatments [17]. Indeed, these drugs are widely used for SIJ pain management and seem to exacerbate mitochondrial dysfunction and oxidative damage worsening skeletal muscle cell metabolism with detrimental effects on patients’ functioning and disability [17].

In this context, in case of fluoroquinolone-induced mitochondrial dysfunction, other therapeutic interventions like Platelet-Rich-Plasma (PRP), a high concentration of autologous grow factors, might be performed as anti-nociceptive and reparative intervention for SIJ pain [12, 13, 18, 19, 20].

However, there is still little evidence supporting the use of PRP to treat sacroiliac joint pain [12, 13, 18, 19, 20] and, to date, its use in subjects affected by mitochondrial disorders has never been investigated yet.

Therefore, by the present paradigmatic case report, we sought to assess the role of PRP ultrasound-guided injection in reducing sacroiliac joint pain in a patient affected by mitochondrial dysfunction not responsive to other conservative approaches.

2. Case report

A 52-year-old Caucasian male was referred to an outpatient physical medicine and rehabilitation department in June 2020. He presented with bilateral pain in the sacroiliac region, described as a low back pain exacerbated by position changing. He had a non-relevant medical history, except for a previous diagnosis (more than 10 years before) of a fluoroquinolone-related mitochondrial dysfunction, confirmed by high blood levels of lactates and pyruvates and histological analysis on skeletal muscle biopsy.

At the baseline physical evaluation, the patient had the following vital signs: blood pressure = 130/80 mmHg; pulse = 75 bpm; temperature = 36.3 ∘ C. Range of Movement (ROM) limitations were assessed at the lumbar tract of the spine, especially in rotation movements while pain was exacerbated when lying down on the examination couch. Furthermore, provocative tests for SIJ pain were performed. More in detail, Gaenslen maneuver, the distraction test, the sacral thrust test and the Faber test were all positive, supporting the clinical diagnosis of sacroiliac joint pain. Hip joint ROM was in the normal range of value for age and sex regarding all movement planes. The patient described pain at rest (NPRS = 8), not evoked by femoral head palpation and alleviated by walking. Moreover, no discomfort was caused by paravertebral muscle mass nor spinous processes palpation; both spine flexion-extension movements were conserved and Lasègue and Wasserman tests were negative, such as the Valleix points palpation. Thus, the patient received a diagnosis of pain related to sacroiliac joint dysfunction and the pelvis and hip X-rays and lumbar spine magnetic resonance imaging (MRI) did not reveal any other conditions potentially responsible for clinical presentation.

Non-steroidal anti-inflammatory drugs, physical therapy and rehabilitation have been proposed without a self-reported improvement of sacroiliac joint pain. Therefore, a mini-invasive intervention has been considered; however, corticosteroids injections were contraindicated due to the concomitant diagnosis of mitochondrial dysfunction, and thus the risk of causing oxidative stress; therefore, despite being an effective intervention for sacroiliac joint pain, this treatment option was ruled out.

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Thus, we proposed a PRP ultrasound-guided injection. The patient was explained the rationale of the proposed therapy, and consented to the treatment, and to this case report presentation. This study was approved by the Institutional Review Board and was performed in accordance with the Declaration of Helsinki.

The PRP preparation was performed by the Transfusion Medicine and Immunohematology Unit of the University Hospital. More in detail, the autologous predeposit technique was used, taking an average of 200–280 ml of whole blood in single or multiple bags. The portion of the plasma fraction having platelet concentration higher than the baseline levels was divided from the other blood fractions with usual processing methods, by double centrifugation with a Haereus TM Cryofuge TM 6000i centrifuge (the 1 st one at 1700 rpm and the 2 nd one at 3500 rpm), obtaining a rich platelet concentrate, that was split into three units of about 10 ml to be used for intraarticular infiltration.

Thus, on June 17 th , 2020, the first PRP ultrasound-guided injection for sacroiliac joint was performed (T0) following sterile conditions. Alpinion (Ecube 8, Alpinion Medical Systems, Seoul, Korea) ultrasound machine with a low-frequency curvilinear transducer was used as a guide to inject 3 ml of leukocytes-free PRP bilaterally in the upper part of the sacroiliac joint with a 22-Gauge cutting-edge spinal needle under real-time ultrasound guidance using an “in-plane” approach (see Fig. 1). A second PRP ultrasound-guided injection was performed on July 1 st , 2020 (T1).

We assessed the patient at baseline prior to the first PRP injection (T0), prior to the second PRP injection (T1), at 1 month (T2) and at 6-month after the first injection (T3). A further long-term follow-up assessment was carried out after 1 year from the treatment (T4).

The following outcome measures were assessed: NPRS, Brief Pain Inventory (BPI) [21], Oswestry Disability Index (ODI) [22], EQ-5D-3L, and EQ-VAS [23]. No adverse events occurred. At T1, the patient reported a considerable reduction of pain (NPRS = 8 vs 5 post treatment), lower low back disability (ODI = 92% vs 56%), and an improved HRQoL (EQ-VAS: 4 vs 6) (see Table 1 for further details). At the 6-month follow-up evaluation, the patient reported absence of pain (NPRS = 0), a minimal low back disability (8%) and a high HRQoL (EQ-VAS = 9). On the other hand, a small worsening of pain (NPRS = 1) was reported after 1 year from the treatment.

Sacroiliac joint pain is a common painful condition related to a considerable burden in terms of loss of functioning, increased disability and reduced HRQoL [3]. Therapeutic options for SIJ pain might include corticosteroids [10], oxygen-ozone therapy [11], extracorporeal shock wave therapy [24], and PRP [12, 13, 19]. However, considering the consistent pharmacological restrictions together with the patient clinical features, we decided to treat the patient with autologous PRP injections at SIJ level, reporting that the therapy was well tolerated by the patient, without any adverse reaction.

Mitochondrial dysfunction is a challenging diagnosis for clinicians and requires complex and personalized management [25]. Parikh et al. [25] recently published a consensus statement aimed to review the literature available, giving prompt and effective recommendations for mitochondrial disorder diagnosis and management. They found out that in most cases the diagnosis relies on biomarkers as lactate and pyruvate determination in blood, urine and cerebrospinal fluid followed by a pathology and biochemical test on muscle tissue biopsy. Therefore, given the little used in routine clinical practice of these complex diagnostic tests, fluoroquinolone-induced mitochondrial dysfunction might be frequently underdiagnosed and underestimated [25].

In this scenario, considering the consistent pharmacological restrictions together with the patient clinical features, we decided to treat the patient with autologous PRP injections at SIJ level, according to previous studies [13, 19].

Growing evidence has supported the positive effects PRP injections in different tissues and several pathological conditions; these positive effects are mainly linked to the secretome of the platelets, including growth factors triggering tissue growth, tropism, and vascularization [26, 27, 28].

However, to date, few low-quality studies supported the effectiveness of ultrasound-guided PRP injections in the SIJ despite promising results were reported in terms of pain reduction and functional improvement, with sustained disability and pain reduction at 6 months, and after 1 year and 4 years of treatment [13, 19, 29]. The results of the present case report are in accordance with the few studies currently available in the literature [13, 19, 20, 29].

Similarly, a recent RCT [20] compared ultrasound-guided PRP injection for SIJ pain with corticosteroid injection. The authors reported significant differences between groups in terms of pain relief after 3 months from the treatment ( p = 0.0002), suggesting that PRP injection might provide better long-term effects [20]. On the other hand, a similar RCT performed by Chen et al. reports that both groups improved pain at 1, 3 and 6 months, however subjects who received steroid injections reported lower pain scores than subjects who received platelet rich plasma, observing significantly more responders (defined as pain scores that improved by 50% or more from baseline) at 1 and 3 months in the corticosteroid group [30]. However, the recent systematic review by Burnham et al. [31] underlined the lack of randomized placebo-/sham-controlled trials on the efficacy of PRP injections at the SIJ level, concluding that the literature supporting this technique is very low quality.

Moreover, the literature data showed a positive effect of corticosteroids injections in 27–67% of patients suffering from SIJ pain [32, 33], although the long-term efficacy of corticosteroids injections in SIJ pain is still debated in the literature [34].

Hence, after the above-mentioned the literature review and considering the findings of this case report, we could hypothesize that PRP injection might be an effective and safe therapeutic option in young patients affected by genetic diseases. We also reported that the treatment was well tolerated by the patient, without any adverse reaction, considering that PRP injections might represent the most suitable opportunity to optimize pain management and minimize complications [35, 36].

Beside PRP injections, another potential intervention to avoid medications and induce pain relief in patients suffering from sacroiliac joint pain might be the radiofrequency neurotomy [36]. This technique allows performing selective denervation of the sacroiliac joint, with evidence supporting a positive role on pain relief and functional improvement [37, 38].

However, given the young age and the patient’s characteristics, we decided to avoid procedures performing anatomical damages and to enhance natural healing linked to PRP [26, 27, 28].

To the best of our knowledge, this is the first report assessing safety and tolerability of this novel treatment to reduce sacroiliac joint pain in a patient affected by mitochondrial dysfunction. Moreover, the patient reported pain relief and a significant decrease in disability with a consequent increase in HRQoL at any evaluation; these positive results lasted for 6 months. Future evaluations will allow us to better understand the clinical impact of PRP injections on sacroiliac joint pain in this patient.

We are aware that this case report is not free from limitations: first, the rarity of the pathological condition described leads to poor reproducibility of this study; second, the absence of a long-term follow-up; third, the study design could not allow reporting strong conclusions.

4. Conclusions

This study suggested that PRP injection could be considered a safe and effective therapeutic option to reducing pain in patients affected by sacroiliac joint pain and a concomitant mitochondrial dysfunction. However, further studies are needed to provide more consistent results to improve the use of this technique in sacroiliac joint pain.