September 30, 2018
complications of corticosteroids cover

Frequency, Cartilage Loss and Common Complications of Corticosteroid Injections

After introduction and comparison of corticosteroid agents, we are now going to move into reviewing the complications common with corticosteroid injections.  As mentioned previously, corticosteroid injections were first documented in the 1950s and have become a staple of office based orthopedic management.  

Many orthopedic practices in the United States will perform injections in 3-month intervals or more spaced out if possible. The main reasoning behind the limitation of injections is preservation of cartilage and avoidance of side effects. There is contrasting evidence regarding repeated corticosteroid joint injections and cartilage damage. Two studies in the 1960s and 1970s concluded that repeated steroid injections do not lead to rapid cartilage destruction or advanced joint space narrowing [1, 2]. A study in 1986 showed a decrease in proteoglycan content in synovial fluid and questioned these studies. Proteoglycan content are molecules that are degraded and released from synovial fluid during osteoarthritis of synovial fluid [3]. There are multiple studies in animal models (mice, rats and rabbits) that suggest intra-articular corticosteroids do lead to cartilage damage and the term hydrocortisone arthropathy emerged in the 1960s and 70s [4, 5, 6, 7.]

Studies in humans have been inconclusive and the frequency used today is based on professional opinion.  Throughout the 1990s and 2000s, the ranges recommended repeat injection from 6 weeks to 6 months but many suggested 8-12 weeks with weight-bearing joints [8, 9, 10, 11].  A 2002 study by Renauld et al., which measured joint space by fluoroscopy guided radiographs, concluded there was no long-term deleterious effects with triamcinolone injections every 3 months for two years [12].  A more recent study in 2017 by McAlindon showed that patients receiving triamcinolone injections every 3 months for 2 years had greater cartilage loss on MRI compared to those injected with saline in 140 patients with knee OA [13]. This has led some providers to question the current standards [22].

Up to five percent of injections will have a postinjection flare, or a localized inflammatory response that typically arises within 24 hours and resolves around 48 hours to 72 hours. Some have proposed this to be chemical synovitis in response to insoluble steroid crystals [15]. Symptoms can range from small joint effusion to disabling pain. Immediate symptoms <2 hours have been reported, but are rare [14]. Analgesic therapy and conservative management are usually sufficient to treat these flares. If symptoms last greater than 24 hours, some providers will perform a joint aspiration to rule out infection.

example of corticosteroid injection of the knee

Image 1. Clinical example of corticosteroid injection in the knee (courtesy of springloaded)

Facial flushing can happen in up to 15 percent of patients and is more common in females [16]. There has been a wide range reported from less than one percent to more than twenty percent in some studies regarding epidural injections [17].  This typically occurs within a few hours of the injection and can last for 3-4 days.  An uncomfortable sensation along with flushing has been described and the flushing can turn into a rash that affects the face and upper trunk region.  Conservative management and antihistamines have been encouraged for management, although this is unlikely a true allergy. Using antihistamines before subsequent injections in patients with a history of flushing or rash has also been utilized.

Skin changes are also not uncommon and tend to occur more often when superficial structures are injected such as ganglion cysts.  This will typically present as an asymptomatic circular hypopigmented area. Fat pad atrophy or lipodystrophy has a more delayed onset and is typically reported a few weeks to a few months after the injection.  Clinically, this presents as a dimple in the skin at the site of the injection and can be accompanied by hypopigmentation [18]. These are rare with orthopedic injections and are more common with intramuscular steroid injections.  

hypopigmentation from cortisone injection

Image 2. Hypopigmentation following a corticosteroid injection (courtesy of davidlnelson.md).

The most concerning complication is joint sepsis, although this is exceedingly rare and current estimates are 1 in 50,000 [19].  A review in 2017 showed a rate of 0.08% during more than 22,000 corticosteroid injections or aspirations [20].  Most clinicians use either alcohol, chlorhexidine or betadine.  There is a wide range of precautions taken before injections and no standard set of precautions exists, likely because of low incidence.

Other common complications that are typically transient include an increase in blood sugars for up to one week and suppression of the hypothalmic-pituitary axis [21].  An increase in hepatic glucose synthesis and antagonization of insulin effects can worsen glucose intolerance, thus raising blood sugars.  Clinicians should warn patients about this and patients that are currently taking insulin may need to increase their dosage following injections.  Some providers will limit doing multiple corticosteroid injections if the patient’s Hemoglobin A1C has been uncontrolled, although there are no guidelines regarding this.  

Intra-articular corticosteroid injections have been shown to decrease cortisol levels by up to 22% but almost all returned to normal in 72 hours.  Another study measured labs including cortisol and levels returned to normal in 1-2 weeks in twenty-five patients [21, 22, 23].  This could put patients at higher risk for adrenal crisis if subject to trauma, infection or surgery.  Proper counseling to avoid high risk activities or extreme heat, cold or dehydration for the following two weeks. It may also be prudent to avoid a corticosteroid injection in the weeks following major trauma, an infection or surgery.

In summary, the frequency of injections is based more on professional opinion than it is on scientific evidence. Injectable corticosteroids remain standard practice in many orthopedic offices, although some providers are starting to decrease their usage of scheduled 3 month injections due to a recent study showing greater cartilage loss with 8 injections in a 2 year period when compared to saline. Most of the side effects are transient in nature and easily managed.

References

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2. Balch HW, Gibson JM, El‐Ghobarey AFet al. Repeated corticosteroid injections into knee joints. Rheumatol Rehabil 1977; 16: 137–40
3. Saxne T, Heinegard D, Wollheim FA.Therapeutic effects on cartilage metabolism in arthritis as measured by release of proteoglycan structures into the synovial fluid. Ann Rheum Dis 1986; 45: 491–7
4. Mankin HJ, Conger KA. The acute effects of intra‐articular hydrocortisone on articular cartilage in rabbits. J Bone Joint Surg Am 1966; 48: 1383–8
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13. Mcalindon, T., Lavalley, M., Harvey, W., Price, L., Driban, J., Zhang, M., & Ward, R. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA 2017, 317(19), 1967-1975
14. Young, P., & Homlar, K. Extreme Postinjection Flare in Response to Intra-Articular Triamcinolone Acetonide (Kenalog). American Journal of Orthopedics 2016 (Belle Mead, N.J.), 45(3), E108-11.
15. Kahn CB, Hollander JL, Schumacher HR: Corticosteroid crystals in synovial fluid. JAMA 1970;211:807-809
16. Pattrick, M., & Doherty. Facial flushing after intra-articular injection of steroid. British Medical Journal (Clinical Research Ed. 1987; 295(6610), 1380.
17. DeSio, J., Kahn, C., & Warfield, C. Facial Flushing and/or Generalized Erythema After Epidural Steroid Injection. Anesthesia & Analgesia 1995, 80(3), 617-619.
18. Cole, B. J., & Schumacher, R. H. Injectable Corticosteroids in Modern Practice. Journal of the American Academy of Orthopaedic Surgeons 2005, 13(1), 37-46.
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20. Petersen, S., Andreasen, R., & Hansen, I. SAT0565 The frequency of septic arthritis after arthrocentesis and intra articular glucocorticoid injection is low. Annals of the Rheumatic Diseases 2017, 76(S2), 990-990
21. Mader, R., Lavi, I., & Luboshitzky,R. Evaluation of the pituitary–adrenal axis function following single intraarticular injection of methylprednisolone. Arthritis & Rheumatism 2005, 52(3), 924-928’
22. Price, EJ. Corticosteroid Injections Ineffective for Knee Osteoarthritis. Am Fam Physician. 2017 Sep 15;96(6):406
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