Hyaluronic Acid Injection in the Treatment of Small Joint Arthritis in the Hand
Published date : 18 February 2015
Article date : 18 February 2015
Article submitted by: Mr Antonios Mitsakos, SpR in Plastics and Hand Surgery, Chelsea and Westminster Hospital & Mr Maxim Horwitz, Consultant Hand Surgeon, Chelsea and Westminster Hospital
No conflict declared.
Osteoarthritis (OA) is the most common joint disease worldwide. According to the American College of Rheumatology, approximately 70 % of people over the age of 70 have radiographic evidence of osteoarthritis, though only half develop symptoms(1). OA can be defined as a degenerative disorder caused by the biochemical breakdown of joint cartilage. However, OA affects not only cartilage but also the entire joint, including subchondral bone and synovium. OA mostly affects weight bearing joints (knees, hips, spine and feet), but can also involve the small joints of the hand such as the distal interphalangeal (DIPJ), proximal interphalangeal (PIPJ) and carpometacarpal joints (CMCJ) of the thumb in particular. Both abnormal mechanics and inflammation have important roles in the development of OA. The diagnosis of OA is based on clinical findings with confirmation from radiographic studies rather than laboratory abnormalities.
In early OA there is swelling of the articular cartilage with subsequent attempted chondrocyte repair. This stage can last for many years, and leads to hypertrophic repair of the cartilage. This progresses to softening and loss of elasticity of cartilage. In due course, loss of the cartilage leads to loss of the joint space and exposure of underlying bone.
OA is treated with physical therapy and splintage, lifestyle adaptation, analgesia and/or surgery. Surgical approaches to the small joints of the hand include excision arthroplasty, arthrodesis or joint replacement. Drugs for OA can be administered orally or by intra-articular injection. Although corticosteroids are often given as intra-articular injections, there is evidence that injections with hyaluronic acid (HA)(2) are as effective as steroids and can be repeated more often(3). Synovial fluid is essential for the normal function of the joint: it acts both as a lubricant during slow movement and as an elastic shock absorber when movement is rapid. It also delivers nutrition, and transmits cellular signals to the articular cartilage(4).
HA is produced by synoviocytes, fibroblasts and chondrocytes(5) and is the major chemical component of synovial fluid. HA is a natural polysaccharide of high molecular weight, composed of a linear chain of disaccharide units made by sodium glucuronate and N-acetylglucosamine and is widely distributed in body tissues. Natural hyaluronic acid has a molecular weight of 4 – 10 million Daltons, and its concentration in the articular fluid is about 0.35g /100 ml(6). Its high viscosity gives it viscoelastic properties, and it also protects articular cartilage and soft tissue joint surfaces(7).
Beneficial effects of HA include(8),(9),(10),(11),(12):
-Inhibition of the lymphocyte transformation that promotes phagocytic activity of macrophages and leukocytes.
-Reduction of adenosine triphosphate and matrix metalloproteinase levels, thereby slowing joint destruction.
-Promotion of prostaglandin release and the normalisation of native HA synthesis(13)
-Acceleration of proteoglycan synthesis by chondrocytes and tissue inhibitor MMP-1 and the collection of free radicals.
-Modification of the structure of cartilage with effects on chondrocytes and cartilage explants, interleukin 1 and oxygen-derived free radicals.
There is some debate about whether high molecular weight HA is more effective than low molecular weight HA. The greater biological activity of high molecular weight HA preparations have only been shown in vitro and not confirmed in clinical trials. Some authors prefer high molecular weight HA preparations because they have a longer half-life and therefore the number of treatments needed is reduced.
Injection Technique
The intra–articular injection of HA must be performed in a clean environment to minimize the risk of infection.
The use of image guidance is recommended: when injection is performed blindly into the tight small joints of the hand, the failure rate is high and the drug may be infiltrated into the periarticular spaces. This can lead to pain and swelling as well as ineffective treatment.
Ultrasound is a fast, fairly simple, safe and economical technique with advantages over fluoroscopy: it is suitable for patients with sensitivity or intolerance to radiographic contrast media, and no ionizing radiation is involved.
The following products can be used for the injection of the small joints of the hand. Note that the volume needed for a joint is usually no more than 1ml.
GO-ON®
A syringe of GO-ON® contains: 2.5 ml of 1% sodium hyaluronate solution, sodium chloride, sodium monohydrogen phosphate, sodium dihydrogen phosphate and water for injection. It is indicated for use as a viscoelastic supplementation for synovial fluid in joints. The product acts as a lubricant and also provides mechanical support , making it suitable for treatment of the symptoms of OA.
Interactions with Other Agents: There are no reports of incompatibilities of GO-ON® with other solutions for intra-articular administration. The patient may benefit from oral analgesic or anti-inflammatory agents during treatment.
Side effects: Some patients develop a skin rash. In such cases, it is advised to discontinue administration and treat the reaction. Pain (mainly transient pain after administration), swelling and effusion, as well as infection, at the injection site have rarely been reported. A few patients have complained of erythema, heat sensation and heaviness at the injection site.
Hyalgan®
Hyalgan® was the first viscosupplement approved by the FDA in 1997. It contains a high molecular weight fraction of purified natural sodium hyaluronate, extracted from rooster combs. It comes in a 5-injection regimen given weekly providing pain relief for up to 6 months. Some patients benefit from the first three injections given at weekly intervals.
The preparation has not been found to interfere with any other medication for osteoarthritis or any other medical condition. It has also been proven safe for repeat treatment if needed.
It is contraindicated in patients with hypersensitivity to hyaluronic acid preparations. Intra-articular injections are contraindicated in cases of already infected skin or in presence of skin disease at the injection site to reduce the potential for developing septic arthritis. Patients are encouraged to avoid any strenuous or prolonged activities involving their hands for the first 48 hours after the intra-articular injection.
SYNVISC®
Synvisc® is an elastoviscous fluid of high molecular weight, containing hylan A and hylan B polymers produced from chicken combs. Hylan A and B are derivatives of hyaluronic acid. It is indicated for the relief from pain in osteoarthritis (OA) in patients who have not responded satisfactorily to conservative non-pharmacologic therapy.
Synvisc® comes in two different formulations, SYNVISC® and SYNVISC-One®. SYNVISC-One® is a single dose treatment, compared with the three injections required with SYNVISC.
As with other preparations, it should not be administered to patients with infected joints, with active skin disease or with any skin infection around the area where the injection will be given. Reported side effects include (<2% each): pain, swelling, heat, redness, and/or oedema around the joint.
ORTHOVISC®
Orthovisc® is a high molecular weight hyaluronic acid preparation, from bacterial cells, which makes it safe for patients suffering from avian allergies such as to birds, eggs and/or feathers. Orthovisc® is available as a three or four dose injection.
SUPARTZ®
Supatrz® is a sterile mixture containing purified sodium hyaluronate, from chicken combs. In animal models, Supartz® increased the integrity of the cartilage, reduced the cell death rate and improved the overall joint morphology. It also reduced synovitis, stimulated the production of endogenous HA and penetrated to the damaged cartilage promoting repair. In a large-animal model Supartz® significantly increased the production of endogenous hyaluronic acid in synovial tissue. Finally it has also been proven to reduce levels of pro-inflammatory cytokines and the production of cartilage-degrading enzymes in cultured cells.
Reported side effects include pain, oedema, erythema, warmth or bruising at the site, and headache, temperature and tingling skin. Seriousallergic reaction to SUPARTZ® has been described but is rare.
EUFLEXXA
Euflexxa™ is a prescription-only injection therapy administered in a course of 3 injections, usually as one injection a week for three weeks, although some authors recommend 5 injections. Pain relief for six months is described.
The most common side effects include pain at the injection site, skin irritation, swelling, and tenderness around the joint. Other side effects include back pain, mild bruising, erythema at the injection site, mild stiffness, increased temperature and muscle pain.
Conclusion:
Viscosupplementation therapy with HA can be safe and effective in the management of osteoarthritis that does not respond to conventional therapies. HA is mainly recommended when NSAIDS are contraindicated, not tolerated or ineffective (14), (15).
The treatment significantly reduces pain within the first three months and the effect can last for approximately 12 to 18 months.
For small joints (MCPJ, PIPJ, DIPJ) there is a definite advantage in using preparations available in smaller syringes. This can reduce costs and waste given the remarkably small dose accommodated in a small joint space.
References:
1 Zhang, Y. & Jordan, JM. (2010). Epidemiology of osteoarthritis. Clin Geriatr Med, Aug, Vol.26, No.3, pp. 355-369
2 Tang T, Muneta T, Ju Y-J, et al. Serum keratin sulfate transiently increases in the early stage of osteoarthritis during strenuous running of rats: protective effect of intraarticular hyaluronan injection. Arthritis Res Ther. 2008;10:R13. DOI:10.1186/ar2363.
3 Guarda-Nardini, L., Ferronato, G., Favero, L. & Manfredini, D.(2011). Predictive factors of hyaluronic acid injections short-term effectiveness for TMJ degenerative joint disease. J Oral Rehabil, Vol.38, No.5, pp. 315-320
4 Takahashi K, Hashimoto S, Kubo T, et al. Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in experimentally induced osteoarthritis. J Rheumatol. 2000;27(7):1713-1720.
5 O'Regan, M., Martini, I., Crescenzi, F., De Luca, C. & Lansing, M. (1994). Molecular mechanisms and genetics of hyaluronan biosynthesis. Int J Biol Macromol, Vol.16, No.6, pp. 283-286
6 Asari A, Miyauchi S, Matsuzaka S, et al. Molecular weight-dependent effects of hyaluronate on the arthritic synovium. Arch Histol Cytol. 1998;61(2):125-135.
7 Fukuda K, Hidekazu D, Masafumi T, et al. Hyaluronic acid increases proteoglycan synthesis in bovine articular cartilage in the presence of interleukin-1. J Pharm Exp Ther. 1996;277(3):1672-1675.
8 Mitsui Y, Gotoh M, Nakama K, et al. Hyaluronic acid inhibits mRNA expression of proinflammatory cytokines and cyclooxygenase-2/prostaglandin E2 production via CD44 in interleukin-1-stimulated subacromial synovial fibroblasts from patients with rotator cuff disease. J Orthop Res. 2008;26:1032-1037.
9 Wang C-T, Lin Y-T, Chiang B-L, Lin Y-H, Hou S-M. High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. Osteoarthr Cartilage. 2006;14:1237-1247.
10 Waddell DD, Kolomytkin OV, Dunn S, Marino AA. Hyaluronan suppresses IL-1β-induced metalloproteinase activity from synovial tissue. Clin Orthop Relat Res. 2007;465:241-248.
11 Julovi SM, Yasuda T, Shimizu M, Hiramitsu T, Nakamura T. Inhibition of interleukin-1β-stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage. Arthritis Rheum. 2004;50(2):516-525.
12 Julovi, SM., Ito, H., Nishitani, K., Jackson, CJ. & Nakamura, T. (2011). Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res, Vol.29, No.2, pp. 258-264
13 A., Giovannangeli, F., Granata, M. & Lagana?, B. (2010). Hylan g-f 20: review of its safety and efficacy in the management of joint pain in osteoarthritis. Clin Med Insights Arthritis Musculoskelet Disord, Vol.20, No.3, pp. 55-68
14 Stahl S, Karsh-Zafrir I, Ratzon N, Rosenberg N. Comparison of intraarticular injection of depot corticosteroid and hyaluronic acid for treatment of degenerative degenerative trapeziometacarpal joints. J Clin Rheumatol 2005;11:299-302.trapeziometacarpal joints. J Clin Rheumatol 2005;11:299-302
