Brief Communications
Intra-arterial Infusion of Temporary Embolic Agent as a New Treatment in a Patient With Osteoarthritis of the Fingers
Sheng-Chun Kung1 , Meng-Yi Chou2 , Kai-Wen Yang2 , Yung Hsu2

1Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, Taiwan

2Department of Radiology, Miaoli General Hospital, Ministry of Health and Welfare, Miaoli, Taiwan

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Outline

Osteoarthritis (OA) of the hand is highly prevalent with women over the age of 50, and the distal interphalangeal (DIP) joint is the most common site. The initial treatment of DIP-OA is usually conservative.
Non-steroidal anti-infl ammatory drugs (NSAIDs) and intra-articular steroid injections only provide temporary relief of symptoms. Arterial embolization is an emergent minimally invasive procedure in treatment of knee and trapeziometacarpal OA with safety and durable effi cacy. Herein, we present a case with symptomatic DIPOA successfully treated by intra-arterial infusion of temporary embolic agent. A 67-year-old woman with osteoporosis presented to our out-patient department with a 2-year history of fi ngers pain of the right hand. She suffered with pain, swelling and stiffness in multiple DIP joints, with the worst pain at the DIP joint of the 3rd finger. Her fi nger pain is still annoying despite receiving conservative treatments and taking oral NSAIDs. On a 10-cm visual analog scale (VAS), the pain score was 8 cm at the fi rst visit. The plain radiography of her right hand revealed DIP joint space narrowing of the 2nd–5th fi ngers, with joint space loss, osteophytes formation and subchondral sclerosis at the 3rd fi nger. An intra-arterial infusion of imipenem/cilastatin sodium (IPM/CS) under both ultrasound and fluoroscopy was performed. After local anesthesia, the radial artery (RA) in the distal forearm was antegradely punctured using a 21-gauge needle under ultrasound. Then, diluted IPM/CS was injected into distal RA directly, and the embolic agent moving to the target DIP joints was confi rmed under fluoroscopy. The VAS score decreased to a 2 cm immediately after arterial embolization and kept decreasing to 0 cm in 1 month. Her swelling and stiffness were also partially improved. Her pain score was 0 cm in 6 months without taking any analgesic. Intra-arterial infusion of IPM/CS directly into RA is a minimally invasive procedure in treatment of DIP-OA of the hand with durable effi cacy. Intra-arterial infusion of IPM/CS can be performed with or without fl uoroscopy. It is a feasible treatment option for patients with refractory DIP-OA of the hand.


Introduction

Osteoarthritis (OA) of the hand is highly prevalent with women over the age of 50 [1]. The distal interphalangeal (DIP) joint is the most common site, followed by the trapeziometacarpal (TM) joint and the proximal interphalangeal joint of the hand [2]. The prevalence of hand radiographs ranges from 27% to 80% although many of these may be asymptomatic [3,4]. The prevalence rates of symptomatic hand OA increased in older age groups and are greater in women, which could be up to 26% [5]. Patients with symp-tomatic OA suffered with pain, swelling, and stiffness of joints, which led to impaired hand function and diffi culty with daily activities. The initial treatment was usually conservative. Non-steroidal anti-infl ammatory drugs (NSAIDs) and intra-articular steroid injections may be used to provide temporary relief of symptoms. Arthrodesis, very rarely the fi rst option, is preserved for patient with debilitating pain and deformity of DIP-OA because it can result in reduced range of motion [6,7].

OA is accompanied with low-grade inflammation of the synovial joints [8,9]. Abnormal angiogenesis allows accumulation of inflammatory cells and enables the growth of sensory nerves in OA [10,11]. Hence, occluding these abnormal vessels in OA by means of intra-articular infusion of embolic agents might decrease the inflammation and pain. Intra-arterial infusion of imipenem/cilastatin sodium (IPM/ CS) directly through an indwelling needle into the posterior tibial artery had been reported as minimally invasive embolic treatment option for plantar fasciitis [12]. Recently, Inui et al. [13] has demonstrated the effi cacy and safety of intra-arterial infusion of IPM/ CS with/without radiographic monitoring in treatment of TM-OA by retrograde puncture of radial artery (RA) under ultrasound. Herein, we report a case of refractory painful DIP-OA successfully treated by intra-arterial infusion of IPM/CS directly into RA after antegrade puncture of RA under ultrasound.

Case Presentation

A 67-year-old woman presented to our out-patient department with a 2-year history of fi ngers pain of the right hand. She had medical history of osteoporosis and received denosumab injection once every 6 months. She suffered with pain, swelling, and stiffness in multiple DIP joints, with the worst pain at the DIP joint of the 3rd fi nger. On a 10-cm visual analog scale (VAS), the pain score was 8 cm at the fi rst visit. The morning stiffness of her fi ngers lasted no longer than 10 minutes. The plain radiograph of her right hand revealed DIP joint space narrowing of the 2nd– 5th fingers, particularly narrowing at the 3rd finger with osteophytes formation and subchondral sclerosis (Figure 1). Her laboratory tests, including complete blood count, anti-nuclear antibody, rheumatoid factor and erythrocyte sedimentation rate, prothrombin time/ activated partial thromboplastin time, and serum creatinine, are within normal limit. Her fi nger pain is still annoying despite receiving conservative treatments and taking oral NSAIDs. After we discussed with the patient and explained the potential risks of arterial embolization with the off-label use of IPM/CS, she wrote informed consent and decided to receive the treatment.

The intra-arterial treatment was performed under both ultrasound and fluoroscopy in the angiography room. After the patient received local anesthesia, the RA in the distal forearm was antegradely punctured under ultrasound with a 21-gauge needle. A 2.9-French introducer (Cook Micropuncture Access Sets; Cook Medical, Bloomington, IN, USA) is then placed over the 0.018-inch guidewire into the artery. After removing the guidewire, we performed angiogram of right hand by manual injection of iodinated contrast media (Figure 2) and checked the evoking pain at the target joints induced by contrast media. The embolic agent was prepared by mixing a suspension of 500 mg of IPM/CS in 10 mL iodinated contrast media. Totally 3.5 mL of diluted IPM/CS (175 mg IPM/CS) was then slowly infused via the RA, and the embolic agent moving to the target DIP joints was confirmed under fluoroscopy (Figure 3). Pain of the target DIP joints was also evoked while embolization. We ended the procedure after we confi rmed that the target fingers turned pale because of the effect of embolization. Following the removal of the introducer and achieved hemostasis, the skin color turned mild erythema because of reperfusion. The VAS score decreased to a 2 cm immediately after arterial embolization. She then went back home 2 hours after the treatment and was followed in our out-patient department. Her pain score decreased to 1 cm in 2 days and was 0 cm in 1 month. Her swelling and stiffness were also partially improved. Her pain score was 0 cm in 6 months without taking any analgesic. There was no skin ulceration, peripheral paresthesia, or muscle weakness developed during the follow-up period.

Figure 1. Plain Radiograph Poster-Anterior View of the Right Hand The radiographic image revealed distal interphalangeal (DIP) joint space narrowing of the hand. The DIP joint of the 3rd fi nger (red circle) revealed joint space loss with osteophytes formation, which is compatible with hand osteoarthritis.

Figure 2. Angiogram by Manual Injection of Contrast Media via Distal Radial Artery (RA) The RA in the distal forearm was antegradely punctured under ultrasound with a 21-gauge needle. The arterial access was created by using a 2.9-French dilator. The angiogram via distal RA showed contrast media in radial and palmar arteries.

Figure 3. Angiogram by Manual Injection of Embolic Agent via Distal Radial Artery Under fl uoroscopy, we saw embolic agent (a suspension of 500 mg of imipenem/cilastatin sodium in 10 mL iodinated contrast media) reach the distal interphalangeal joint of the 3rd fi nger (red triangles).

Discussion

Transcatheter arterial embolization (TAE), a general procedure in management of neoplasms and vascular problems, is now an emerging option for treatment in chronic musculoskeletal pain. Okuno et al. [14,15] first introduced TAE as a method of treatment in chronic musculoskeletal pain using IMP/ CS. Previous studies have noted abnormal vessel developments around the affected knee in patients with knee OA [16,17]. These abnormal vessels are associated with newly formed perivascular nonmyelinated sensory nerves and pain related to OA [11]. Therefore, we thought that the mechanism of pain relief is related to embolization of the abnormal vessels in pain generators, which results in the reduction of excessive angiogenesis, infl ammatory process, and new unmyelinated sensory nerve. Inui et al. [13] have revealed the effi cacy of intra-arterial infusion of IPM/ CS in treatment of TM-OA with symptoms relief lasted as long as 2 years. It is notable that the therapeutic effects of arterial embolization may be inferior in patient with advanced stage of OA [13,18,19]. In cases of advanced OA with structural damage, the infl ammatory response may be diffi cult to terminate. Early intervention for OA can reduce infl ammation, which may postpone the progression of OA [20].

Ischemic complications might be the major concern of this kind of treatment. Previous studies have reported prolonged skin color change and sensory paresthesia using permanent embolic material [21,22]. However, IPM/CS is a temporary embolic agent with particle size ranging from 10 μm to 130 μm in iodinated contrast media [23]. When being intravenously administered, IPM has a half-life of approximately 1 hour [24]. Prior study has shown partial to complete recanalization within 48 hours after IPM/CS embolization of rat renal arteries and suggests that the degradation of the IPM/CS embolic complex occurs within hours to days [25]. The date, IPM/CS as a temporary embolic, without serious ischemic complications have been reported and has fewer nontarget adverse events than permanent embolic agents [26]. Because of this, we can perform TAE simply via distal RA for DIPOA without much concern about the complications of nontarget embolization in normal fingers. The case reported in this article also did not have any adverse event after the patient received arterial embolization using IPM/CS, except for transient skin color change. The skin would turn pale and white after the arterial infusion of IPM/CS and return to the normal color after approximately 30 minutes after reperfusion [13]. In the study of Inui et al. [13], 31 patients received intra-arterial infusions of IPM/CS by retrograde puncture of RA under ultrasound. The total number of treatment was 1 for 11 patients (35.5%), 2 for 12 patients (38.7%), 3 for 6 patients (19.4%), and 4 for 2 patients (6.4%) within 24 months. There were also no ischemic complications or arterial injury [13]. Nevertheless, there are still some potential complications regarding RA access, including access site hematomas, artery spasm, occlusion, perforation, pseudoaneurysm, or arterio-venous fistula formation. Allen test and more recently the Barbeau test can be performed to assure adequate collateral circulation via the ulnar artery and patency of the palmar arch. In patient with type D response of Barbeau test, transtradial procedures have higher risk of ischemia in event of RA complications. The complication rates can be reduced by using smaller sheath and reducing the number of attempts at artery cannulation [27,28].

There are still issues regarding this technique which will be able to be studied in the future. For the case of this article, IPM/CS is infused into the distal RA under fluoroscopy because fluoroscopy is useful to confirm how exactly the embolic agent moves. However, Inui et al. [13] also performed intra-arterial infusion of IPM/CS for TM-OA without under fluoroscopy. The distribution of embolic agent was judged based on the patients’ complaints of evoked pain and transient cutaneous color change of the infused area [13]. Hence, the best endpoint of embolization with or without fluoroscopy is still not well evaluated. Second, the IPM/CS particle size is adjustable by changing the concentration, which demonstrated a downward shift in the size distribution when we used a higher volume of contrast media [23]. Third, there are other temporary embolic agents which may be candidates for transarterial embolization, but the feasibility and safety in direct infra-arterial infusion with possibility of nontarget embolization still need to be investigated [26].

In conclusion, intra-arterial infusion of IPM/CS was performed for DIP-OA refractory to conservative treatment. The patient’s pain greatly improved immediately after arterial embolization and progressively improved in the following 1 month. Her pain score was 0 cm in 6 months after the treatment. Intra-arterial infusion of IPM/CS is a minimally invasive procedure and could be performed in an outpatient setting with or without fluoroscopy. It is a feasible treatment option for patients with DIP-OA of the hand with durable outcome.

Acknowledgment

We are grateful to Dr. Keng-Wei Liang (Department of Medical Imaging, Chung Shan Medical University Hospital) for demonstration of the procedures of TAE in treatment of chronic musculoskeletal pain.

Conflict of Interest

None.


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References
1

Kalichman L, Hernández-Molina G.

Hand osteoarthritis: an epidemiological perspective.

Semin Arthritis Rheum. 2010;39(6):465-476. doi:10.1016/j.semarthrit.2009.03.001

Article CrossRef Scopus

2

Wilder FV, Barrett JP, Farina EJ.

Joint-specific prevalence of osteoarthritis of the hand.

Osteoarthritis Cartilage. 2006;14(9):953-957. doi:10.1016/j.joca.2006.04.013

Article CrossRef

3

Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT.

Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly: the Framingham study.

Am J Epidemiol. 2002;156(11):1021- 1027. doi:10.1093/aje/kwf141

Article CrossRef Scopus

4

Lawrence RC, Felson DT, Helmick CG, et al; National Arthritis Data Workgroup.

Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.

Arthritis Rheum. 2008;58(1):26-35. doi: 10.1002/art.23176

Article CrossRef Scopus

5

Litwic A, Edwards MH, Dennison EM, Cooper C.

Epidemiology and burden of osteoarthritis.

Br Med Bull. 2013;105:185-199. doi:10.1093/bmb/lds038

Article CrossRef

6

Vitale MA, Fruth KM, Rizzo M, Moran SL, Kakar S.

Prosthetic arthroplasty versus arthrodesis for osteoarthritis and posttraumatic arthritis of the index finger proximal interphalangeal joint.

J Hand Surg Am. 2015;40(10):1937- 1948. doi:10.1016/j.jhsa.2015.05.021

Article CrossRef Scopus

7

Rongières M.

Surgical treatment of degenerative osteo- arthritis of the fingers.

Chir Main. 2013;32(4):193-198. doi:10.1016/j.main.2013.03.006

Article CrossRef

8

Ikeda K, Nakagomi D, Sanayama Y, et al.

Correlation of radiographic progression with the cumulative activity of synovitis estimated by power Doppler ultrasound in rheumatoid arthritis: difference between patients treat- ed with methotrexate and those treated with biological agents.

J Rheumatol. 2013;40(12):1967-1976. doi:10.3899/ jrheum.130556

Article CrossRef

9

Berenbaum F.

Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!).

Osteoarthritis Car- tilage. 2013;21(1):16-21. doi:10.1016/j.joca.2012.11.012

Article CrossRef

10

Ashraf S, Mapp PI, Walsh DA.

Contributions of angio- genesis to inflammation, joint damage, and pain in a rat model of osteoarthritis.

Arthritis Rheum. 2011;63(9):2700- 2710. doi:10.1002/art.30422

Article CrossRef

11

Mapp PI, Walsh DA.

Mechanisms and targets of angio- genesis and nerve growth in osteoarthritis.

Nat Rev Rheu- matol. 2012;8(7):390-398. doi:10.1038/nrrheum.2012.80

Article CrossRef

12

Shibuya M, Sugihara E, Miyazaki K, Fujiwara K, Sakuga- wa T, Okuno Y.

Intra-arterial infusion of temporary embolic material in a patient with plantar fasciitis: a case report.

Cardiovasc Intervent Radiol. 2021;44(11):1823- 1826. doi:10.1007/s00270-021-02908-z

Article CrossRef

13

Inui S, Yoshizawa S, Shintaku T, Kaneko T, Ikegami H, Okuno Y.

Intra-arterial infusion of imipenem/cilastatin sodium through a needle inserted into the radial artery as a new treatment for refractory trapeziometacarpal os- teoarthritis.

J Vasc Interv Radiol. 2021;32(9):1341-1347. doi:10.1016/j.jvir.2021.06.024

Article CrossRef

14

Okuno Y, Matsumura N, Oguro S.

Transcatheter arterial embolization using imipenem/cilastatin sodium for ten- dinopathy and enthesopathy refractory to nonsurgical management.

J Vasc Interv Radiol. 2013;24(6):787-792. doi:10.1016/j.jvir.2013.02.033

Article CrossRef

15

Okuno Y, Oguro S, Iwamoto W, Miyamoto T, Ikegami H, Matsumura N.

Short-term results of transcatheter arterial embolization for abnormal neovessels in patients with adhesive capsulitis: a pilot study.

J Shoulder Elbow Surg. 2014;23(9):e199-e206. doi:10.1016/j.jse.2013.12.014

Article CrossRef

16

Lee SH, Hwang JH, Kim DH, et al.

Clinical outcomes of transcatheter arterial embolisation for chronic knee pain: mild-to-moderate versus severe knee osteoarthritis.

Cardiovasc Intervent Radiol. 2019;42(11):1530-1536. doi:10.1007/s00270-019-02289-4

Article CrossRef Scopus

17

Bagla S, Rholl KS, van Breda A, Sterling KM, van Breda A.

Geniculate artery embolization in the management of spontaneous recurrent hemarthrosis of the knee: case series.

J Vasc Interv Radiol. 2013;24(3):439-442. doi:10.1016/j.jvir.2012.11.011

Article CrossRef Scopus

18

Okuno Y, Korchi AM, Shinjo T, Kato S, Kaneko T.

Midterm clinical outcomes and MR imaging changes after transcatheter arterial embolization as a treatment for mild to moderate radiographic knee osteoarthritis re- sistant to conservative treatment.

J Vasc Interv Radiol. 2017;28(7):995-1002. doi:10.1016/j.jvir.2017.02.033

Article CrossRef

19

van Zadelhoff TA, Okuno Y, Bos PK, et al.

Association be- tween baseline osteoarthritic features on MR imaging and clinical outcome after genicular artery embolization for knee osteoarthritis.

J Vasc Interv Radiol. 2021;32(4):497- 503. doi:10.1016/j.jvir.2020.12.008

Article CrossRef

20

Taguchi H, Tanaka T, Nishiofuku H, et al.

A rat model of frozen shoulder demonstrating the effect of transcatheter arterial embolization on angiography, histopathology, and physical activity.

J Vasc Interv Radiol. 2021;32(3):376- 383. doi:10.1016/j.jvir.2020.10.017

Article CrossRef Scopus

21

Hwang JH, Park SW, Kim KH, et al.

Early results of transcatheter arterial embolization for relief of chronic shoulder or elbow pain associated with tendinopathy re- fractory to conservative treatment.

J Vasc Interv Radiol. 2018;29(4):510-517. doi:10.1016/j.jvir.2017.11.013

Article CrossRef

22

Bagla S, Piechowiak R, Hartman T, Orlando J, Del Gaizo D, Isaacson A.

Genicular artery embolization for the treatment of knee pain secondary to osteoarthritis.

J Vasc Interv Radiol. 2020;31(7):1096-1102. doi:10.1016/ j.jvir.2019.09.018

Article CrossRef

23

Aihara T.

A basic study of super-selective transcatheter arterial chemotherapy and chemoembolization (1)— establishment of an animal model for superselective transcatheter arterial chemotherapy and preparation for appropriate suspension of microembolization.

Kawasaki Med J. 1999;25(1):47-54. doi:10.11482/ KMJ-J25(1)047-054.1999.pdf

Article

24

Choudhury SR, Babes L, Rahn JJ, et al.

Dipeptidase-1 is an adhesion receptor for neutrophil recruitment in lungs and liver.

Cell. 2019;178(5):1205-1221.e17. doi:10.1016/ j.cell.2019.07.017

Article CrossRef

25

Yamada K, Jahangiri Y, Li J, et al.

Embolic characteristics of imipenem-cilastatin particles in vitro and in vivo: im- plications for transarterial embolization in joint arthrop- athies.

J Vasc Interv Radiol. 2021;32(7):1031-1039.e2. doi:10.1016/j.jvir.2021.02.006

Article CrossRef

26

Koucheki R, Dowling KI, Patel NR, Matsuura N, Mafeld S.

Characteristics of imipenem/cilastatin: considerations for musculoskeletal embolotherapy.

J Vasc Interv Radiol. 2021;32(7):1040-1043.e1. doi:10.1016/j.jvir.2021.04.006

Article CrossRef Scopus

27

Shroff A, Siddiqui S, Burg A, Singla I.

Identification and management of complications of transradial procedures.

Curr Cardiol Rep. 2013;15(4):350. doi:10.1007/s11886- 013-0350-x

Article CrossRef Scopus

28

Raelson C, Ahmed B.

Prevention and management of ra- dial access complications.

Curr Treat Options Cardiovasc Med. 2020;22:9. doi:10.1007/s11936-020-0808-2

Article CrossRef