Injection Therapy and Biologics

CHAPTER 17

Injection Therapy and Biologics

Amir Mahajer, DO, FAOCPMR, FAAPMR, and Julia Louisa Iafrate, DO, CAQSM, FAAPMR

Any athlete may experience an injury that does not improve with time or conservative medical care. Identifying the pain generator and the biomechanical trigger(s) is crucial to developing a comprehensive treatment plan and return-to-play protocol for the athlete. Sports treatment plans require collaboration between the allied health care team and coaching staff. Injury type, severity of pain, and functional decline may all necessitate early physician referral and intervention such as injection therapy or operative management. This chapter introduces the topic of injection therapy as one possible intervention that can help an athlete return to play safely and in less time in some cases.

Sports injuries can be categorized as acute, subacute, or chronic. An early injury is acute prior to four weeks; between four weeks and three months an injury is described as subacute; and after three months it is generally described as chronic. The majority of nonemergent musculoskeletal injuries will improve with conservative measures within the first four to six weeks. There are notable exceptions to this, which should be addressed early by a physician, such as significant or progressive pain, moderate to severe disability, and neurologic compromise. In general, more invasive procedures such as percutaneous needle tenotomy or ultrasonic tenotomy are reserved for chronic conditions. Typically, athletic trainers and therapists assess and reassess the athlete at regular intervals and should be able to identify individuals who are failing to improve. The coaching staff should be informed of progress throughout the recovery and rehabilitation period. Interdisciplinary treatment greatly improves outcome regardless of intervention. Interventions may include rehabilitation and bracing, medications, manual manipulation, medical massage, physical and occupational therapy, injections, regenerative medicine, or surgery or some combination of these. The main indication for injection therapy is to decrease local pain and inflammation, identify pathology, or confirm the pain generator. For example, medical staff might collect joint fluid to evaluate for crystals, blood, infection, or inflammatory fluids. The most common therapeutic substances injected are a combination of corticosteroids (steroids) and anesthetics. In addition, viscosupplementation and autologous (collected from oneself) blood or tissue injection may be used, mainly concentrated plasma or cell injectates or both.

Joint Aspiration

Joint aspiration, also known as arthrocentesis, may be therapeutic or diagnostic. Arthrocentesis (the removal of joint fluid) may be all that is required to relieve intraarticular pressure on the joint capsule, which is highly innervated by nerves. Removing excess fluid from a joint typically reduces pain and improves joint mobility. Trauma, repetitive stress injury, or intraarticular pathology may lead to acute swelling that may benefit from aspiration alone.

Additionally, once collected, the fluid can be analyzed for crystal diseases, blood, infection, and inflammatory fluid. Gross analysis of synovial fluid includes volume, viscosity, color, and clarity. A physician may order the following tests for synovial fluid analysis: Wright’s stain for cell count and differential, gram stain and culture, polarized light microscopy, and blood work including complete blood count with differential, acute phase reactants, and uric acid. In complicated cases, a synovial tissue biopsy may be required and sampled during surgical arthroscopy. It is important to note that dual pathologies may exist, such as gouty and septic arthritis.

Risk of Joint Infections

A joint may become infected if sterility is compromised during a joint aspiration or injection, and is one of the most severe adverse events. A joint infection (septic arthritis) is considered an emergency, because it leads to rapid destruction of the joint, which may lead to significant long-term consequences for the athlete. The pathogen differs in different populations. Bacteria, fungi, and viruses can all lead to joint infection. The most common pathogens are bacteria and, in adults, primarily staphylococcus aureus followed by streptococci. Haemophilus influenza predominates in young children. In sexually active young adults, Neisseria gonorrhoeae infections may also spread and cause joint infections. The main joint affected in adults is the knee, and in children the hip. Along with severe joint pain, the athlete may complain of redness, swelling, warmth, limited range of motion, and fever. Careful counseling of athletes is crucial when they are signing a consent. The athlete must be made aware and express clear understanding of the signs of joint infection after aspiration or injection.

Corticosteroids

Injectable medications may include anesthetic, corticosteroids, viscosupplementation, nonsteroidal anti-inflammatory drugs, and autologous plasma and cells. Corticosteroid injections combined with anesthetics are used for the majority of injections. Several studies have found that the use of nonsteroidal anti-inflammatory drugs in place of steroids in cases such as shoulder impingement syndrome with subacromial-subdeltoid bursa injections and joint injections to be equally efficacious. There are many other substances used off-label (not for their approved indicated use) for injections such as dextrose, phenol, or ethyl alcohol in prolotherapy when targeting soft tissue structures or to produce neurolysis or hydrodissection when targeting nerves.

When discussing risks and benefits and alternatives to injection therapy especially with steroids, it is important to state the common adverse effects as well as the potential serious adverse effects, such as the following:

Permanent skin discoloration

Local fat loss, atrophy

Elevated blood sugar

Elevated blood pressure

Hormonal suppression

Injury to nerves or arteries

Tendon or ligament rupture

Infection

Increased pain

Avascular necrosis and osteoporosis

Also, we can subdivide steroids into two groups: particulate and nonparticulate. It is important to note that the size of the particles in particulate steroids has been found to block blood vessels and cause significant harm. It is recommended that nonparticulate steroids be used when injecting near vulnerable vascular targets.

Intraarticular steroid injection therapy has been extensively studied, and its use is currently recommended by multiple medical societies. While some studies find no severe adverse effects with steroid injections, others comparing saline versus steroid injections or anesthetic alone into joints found that repeat steroid injections, or use of certain anesthetics, may lead to long-term cartilage damage and may worsen osteoarthritis of the joint. It is also well known that when injecting steroids in or around tendons and ligaments, there is an increased risk of tendon or ligament rupture. For this reason, the use of steroid injections around these soft tissue structures is strongly discouraged for in-season athletes. It is recommended that injections with anesthetics and steroids be limited in number and with special attention to anesthetic choice and concentration based on the subspecialized physician’s judgment and clinical circumstances with regard to moderate to severe pain and disability.

Viscosupplementation

In painful osteoarthritis, the joint’s natural fluid chemistry is compromised. Hyaluronic acid injections may provide short- and long-term relief. A common therapy includes viscosupplementation—a high-molecular-weight fluid injection of hyaluronic acid—that provides joint lubrication and protection. It reportedly provides anti-inflammatory effects and increases a joint’s natural hyaluronic acid production. Multiple studies have found viscosupplementation to decrease joint pain and increase function. New evidence suggests repeat viscosupplementation for safe and effective long-term treatment in osteoarthritis of the knee.

Sympathetic Blocks

Complex regional pain syndrome (CRPS) usually affects the arms or legs four to six weeks after an injury or a medical procedure. Though rare, the majority of CRPS cases are associated with a fracture, followed by soft tissue injuries in blunt trauma or sprains or strains, as seen commonly in contact sports. A small subset of individuals may develop CRPS after surgery such as carpal tunnel release. Complex regional pain syndrome is categorized as I and II, without and with known peripheral nerve injury, respectively. The medical team must have a good understanding of the condition, because it may manifest as pain out of proportion to the original injury and present with additional neurovascular changes such as abnormal sensation, weakness, or warm swelling followed by a cold fibrotic limb. This is a severe and debilitating condition that requires prompt medical attention. Because the sympathetic autonomic nervous system is believed to play a role in the abnormal rewiring of the pain signal, sympathetic blocks (injections) may be performed in an attempt to diagnose and improve sympathetic-mediated CRPS. Sympathetic blocks are thought to improve the sympathetic nervous response and decrease pain and related symptoms.

Botulinum Toxin

For athletes, particularly those in the performance arts, spasticity and dystonia can lead to significant disability. Both spasticity and dystonia are movement disorders that hamper performance and can decrease the ability of an individual to perform activities of daily living. It is recommended that these athletes be referred to a specialist in movement disorders, usually a neurologist or physical medicine and rehabilitation physician. Once a diagnosis is established and if more conservative approaches fail, the use of botulinum toxin may be a reasonable intervention. The most common adverse effect of botulinum toxin is weakness locally, or possible spread of toxin that causes weakness at a distant site. This weakness can cause difficulty swallowing or speaking if it affects the muscles involved in these functions. It must be administered by a skilled clinician, and the athlete must be fully aware of these possible adverse effects.

Platelet-Rich Plasma

Advances in regenerative treatments include cell-based and plasma-based therapies. The idea of regenerative medicine therapies includes injecting live cells originating from bone marrow or adipose (fat) tissue directly at the site of injury or pathology. These cell lines were thought to have “stem cells” that may proliferate into different tissue types, such as cartilage or tendon in musculoskeletal injuries. This has been found not to be the case. Instead, it’s believed that these injections create “intercellular communication” that leads to decreased inflammation, improved function, and even tissue healing (see figure 17.1). Platelet-rich plasma (PRP) is one of these types of therapies that holds promise for healing.

FIGURE 17.1 Ultrasound guided platelet-rich plasma (PRP) injection for rotator cuff tendinopathy and shoulder impingement syndrome.

© Amir Mahajer, DO

Platelet-rich plasma is a growing therapeutic modality in treating musculoskeletal disorders and particularly for sports injuries. Multiple studies have demonstrated safety and efficacy for athletes with pain and functional decline. Platelets are known to be an important component of clot formation (i.e., after a cut, the bleeding stops due to the presence of platelets). Over the past years, research has identified other possible actions of platelets. Parts of platelets known as growth factors seem to promote tissue healing.

Accurate and Safe Injection Methods

If an injection procedure is planned, simply knowing which structure is involved and selecting the appropriate substance is not enough. The medication(s) then must be injected accurately and safely to the target site. For many years, physicians have used their knowledge of the body’s structure to estimate the safe and accurate placement of the needle tip. This is crucial in avoiding vulnerable structures such as the lungs, blood vessels, nerves, and tendons. In recent decades, advances in technology and guidance methods have improved, allowing for statistically significant improvements in accuracy.

The most common imaging systems used for targeting musculoskeletal and neuromuscular structures are fluoroscopic or X-ray (XR), ultrasound (US), peripheral nerve stimulation (PNS), and electromyography (EMG) guidance. These systems require special equipment and training. X-ray guidance is best used to view bony landmarks and joint spaces. However, it does raise the risk of ionizing radiation, and care must be taken to use the lowest possible dose. Preprocedure planning, reviewing past images, low-dose settings, proper patient positioning, radiation shielding, and collimation are among the most common ways to reduce the total ionizing radiation exposure. Ultrasound guidance is the modality of choice when targeting superficial soft tissue structures such as joints, nerves, tendons, and ligaments. Point-of-care US is often available for first diagnosis and, if needed, to guide the needle tip safely and accurately to the target site. Peripheral nerve stimulation guidance uses electrical field stimulation to approximate needle placement near nerve plexuses or peripheral nerves. In cases of spasticity or dystonia, EMG guidance can be utilized to find the affected target muscle(s). At times, XR or EMG guidance can be combined with US guidance to help identify the target structure(s) by directly visualizing the soft tissue structures, allowing for direct needle placement to reduce ionizing radiation exposure and additional tissue trauma if multiple needle passes may have been required.

A fairly new US-guided minimally invasive technique exists for treatment of recalcitrant tendinopathy from chronic tendon damage. Chronic tendon injuries are problematic for athletes. They cause diminished productivity and disability. Following injury, which consists of hemorrhage and clot formation with platelet degranulation, tendons go through three stages of healing. These involve acute inflammation and breakdown of damaged tissue; cell migration and proliferation at the injury site, and laying down of weak collagen type III; and remodeling of tissue and synthesis of strong collagen type I. If the tissue does not appropriately follow these stages, it ends up as chronically damaged tendon tissue, which can be detrimental to an athlete’s ability to compete.

FIGURE 17.2 Percutaneous ultrasonic tenotomy of the left common extensor tendon of the elbow: MicroTip cutting device and placement over lateral epicondyle (a) and ultrasound image showing MicroTip within tendon tissue at lateral epicondyle (b).

Known as percutaneous ultrasonic tenotomy, this minimally invasive procedure involves the removal of damaged tissue under US guidance. It is often recommended in patients with symptoms ongoing for greater than three months who have failed at least one conservative treatment. Under local anesthesia, a small incision is made at the skin surface and the microtip of the device is directed toward the damaged tendon tissue. It then delivers optimized ultrasonic energy to precisely cut diseased tendon tissue while sparing healthy tissue (see figure 17.2). The procedure takes less than 30 minutes and is extremely safe. Postprocedure care may involve limited weight bearing for a week, physical therapy, and follow-up diagnostic US to ensure healing. Players can usually be back in sports within 6 to 12 weeks.

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