Evidence supports the use of corticosteroid injection, as its anti-inflammatory properties can provide patients with pain relief, with the aim of improving function. The therapeutic effects of corticosteroids are, however, often temporary, with some studies suggesting no long-term difference between corticosteroids and placebo. Regarding the type of steroid used, there is apparently arbitrary use of particulate (Kenalog and Depo-Medrone) and non-particulate (dexamethasone) steroids.
Mechanism of action of cortisone include synovial blood flow reduction, synovial fluid composition alteration, gene suppression of leukocytes, protease and cytokine production, and altered collagen synthesis. These effects are more potent in corticosteroids with branched esterification and larger particulates, as they are less soluble.
There are known adverse effects of cortisone that need to be discussed with the patient prior to undertaking an injection.
Steroid induced arthropathy: Radiographic follow-up of patients post-joint injection has shown worsening and progression of joint arthropathy. Initial reports suggested this might be steroid induced secondary to repeated IA injections. Studies hypothesised that the proteolytic enzymes in the exudate of corticosteroid-induced synovitis had a chondrotoxic effect and repeated steroids injections in animal models demonstrate deleterious effects on cartilage. In addition, a recent higher-level study has shown that repeated cortisone injection into the knee joint compared to placebo sterile water leads to an increase in MRI-detected articular cartilage wear compared but with no significant clinical improvement compared to placebo. In summary, cortisone injections are not protective for joints and may be harmful in repeated injections.
Septic arthritis can be a catastrophic but rare complication following IA injections. Frequencies of joint infection after IA injection range from 1 in 3000 to 1 in 100,000. It is best practice to adhere to a sterile technique. As corticosteroids can cause immunosuppression, steroid injection should be avoided if patients are on antibiotic treatment or have bacteraemia. Joint injection should not be carried out in the presence of active infection in or near joints.
Systemic effects: Facial flushing has been reported with an incidence of less than 1% seen more frequently with triamcinolone acenotide. Symptoms can last from several minutes to days. A Fainting episode (or vasovagal) can occur due to systemic absorption of the steroid or patient anxiety to the procedure itself with incidences reported between 0%-20%. Joint doses up to 80 mg can be given without undue adverse systemic effects, although doses greater than 50 mg triamcinolone acenotide have been shown to decrease serum cortisol. Systemic effects can be minimised by limiting the number and dose and increasing the interval between joint injections and ensuring intravascular needle placement or injection is avoided. One must be aware of steroid induced hyperglycaemia and consent diabetic patients appropriately. Hyperglycaemia can last for up to 3 weeks. In summary, we should be cautious of the dose and frequency of cortisone in elderly and diabetic patients.
Cutaneous effects: Corticosteroids may cause dermal/subcutaneous tissue atrophy, hypopigmentation, and fat necrosis, with a reported incidence of less than 1%. The mechanism is unknown, but it is thought that presence of corticosteroid crystals can lead to the disintegration of the cellular elements and physiochemical changes in connective tissue. The resultant dermal and/or subdermal changes may form depressions in the skin at the injection site. These changes may be reversible but can months or years to settle. The effects of steroids can leave the skin fragile, susceptible to minor trauma and infection, easy bruising, and increased risk of wound breakdown after surgery. Triamcinolone has a greater risk for dermal changes compared to methylprednisolone due to its increased crystal size.
Tendon rupture: The incidence of tendon rupture is less than 1%, although I suspect the number of reported cases is under-reported. The exact cause for steroid-mediated tendon rupture is unknown. Excessive exertion, degenerative, and inflammatory tendinous attrition can lead to tendon rupture. Steroids may exert a deleterious effect on tendon strength, repair and reduce tensile strength. A recent systematic review revealed a toxic effect on tenocytes and a short term reduction in the mechanical properties of tendons are treatment with local corticosteroid.
Steroid flare A post-injection: self-limited synovitis can occur in approximately 1%-10% of cases following IA injection. Symptoms of joint pain and swelling can be observed several hours post injection and generally subsides within 48 hours. Perceived "worsening of symptoms" can also be seen once the local anaesthetic wears off, and it is important to adequately consent and counsel patients to warn them of this.
Miscellaneous effects: There have been rare reports of drug hypersensitivity to additives or the local anaesthetic within the injectate. Severe joint destruction with osteonecrosis may occur with prolonged repeated IA injections. Corticosteroid use should be carefully considered during pregnancy, and as with all medication, fully informed consent with risks and benefits to the mother and child should be discussed and documented. Although corticosteroids are excreted in small amounts into breast milk, the small dose used intra-articularly, with even smaller systemic absorption, will mean a relatively insignificant amount in breast milk. Furthermore, there is negligible gut absorption from the baby, and so there is no significant risk of hypothalamus-pituitary-adrenal axis suppression. There are, however, documented cases of lactation suppression secondary to triamcinolone injection. Corticosteroids are a substrate of the enzyme CYP3A4, which is targeted and blocked by many anti-retrovirals (ritonavir), anti-fungals, calcium-channel blockers (diltiazem), and the oral contraceptive pill, to name a few. Caution is advised when using corticosteroids with such drugs, as it can result in excess systemic steroid levels and lead to Cushing's syndrome and adrenal suppression. No such interaction has been reported with a reduced dose of methylprednisolone and should be used as an alternative to triamcinolone. Also, corticosteroids may induce the metabolism of HIV-protease inhibitors resulting in reduced plasma concentrations. An under-reported side effect is persistent hiccoughs following corticosteroid injection. The onset of hiccoughs typical occurs hours after steroid injection and has been reported to last up to 2 weeks. The incidence is unknown and a number of mechanisms have been postulated, including cerebrospinal fluid volume imbalance following epidural injections, mixture with bupivacaine, sympathetic pathway blockade, steroid activation of the hiccough reflex arc, and alteration in neurotransmitters in the brainstem.
When and Why
Because of transient and temporary benefit, steroid injections may need to be repeated. Repeat injections should not be given within short intervals to minimise the risks described earlier, though these are relatively insignificant and infrequent. Approximate duration of action of steroids are between 1-2 weeks depending on the type of steroid preparation. A 2- to 3- week interval is suggested if a second corticosteroid injection is required, and a minimum of a 6-week interval if a repeat injection into the same location is performed. The National Institute for Health and Care Excellence recommends the same joint is not injected more than 3 times a year. Weight- bearing joints and tendons subject to sudden strain (eg, Achilles tendon, ankle tendons) should be rested and post injection with avoidance of excessive use. Therapeutic management should be reconsidered after 3 steroid injections into a single site. This, of course, is dependent on the clinical situation, and other management options such as surgery may not possible, leaving steroid injections the only clinically viable therapy.