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Corresponding author: Collier S. Pace, MD, Division of Plastic and Reconstructive Surgery, VCU Medical Center, West Hospital, 16th Floor North Wing, 1200 E Broad St., Richmond, VA, 23298.
Corticosteroid injections (CIs) are frequently used by hand surgeons to treat a wide range of pathology including de Quervain tenosynovitis and lateral epicondylitis. Although generally viewed as a benign modality, and a way to potentially avoid or postpone surgical intervention, common complications from CI should be considered and discussed with patients before the procedure. One such complication is local soft tissue atrophy and hypopigmentation after injection. We discuss the incidence of soft tissue–related adverse effects from CI, the pathophysiology and influence of different steroid preparations on soft tissues, and potential treatment options once atrophy has occurred.
Corticosteroid injections (CIs) are utilized by hand surgeons to alleviate symptoms related to a wide range of upper extremity pathology, but tenosynovitis and lateral epicondylitis are 2 of the more common disease processes for which this treatment modality is applied. Unfortunately, the underlying etiology and pathophysiology of these conditions have yet to be completely clarified. Tenosynovitis, whether in the form of de Quervain or trigger finger, was commonly thought to be an inflammatory condition. However, that concept has been challenged by the absence of histological inflammatory changes seen in the first dorsal compartment and A1 pulley.
Interestingly, regardless of the pathophysiology of the disease process, many patients with these conditions show an improvement in symptoms with CI.
The decision to inject corticosteroids or operate is surgeon, disease process, and patient dependent. Although successful surgical therapies are available, most patients prefer that nonsurgical modalities be exhausted first. Corticosteroid injections may alleviate symptoms and, in some cases, provide permanent relief. In addition, they can be administered in the clinic, and patients can return to their daily activities with very little recovery required. However, the risk associated with these injections can be underappreciated. For extra-articular injections, the reported incidence of major and minor adverse events ranges from 0% to 5.8%, and 0% to 81%, respectively. Major complications include osteomyelitis, necrotizing fasciitis, tendon ruptures, severe soft tissue atrophy, and hypopigmentation. Minor adverse events include less severe soft tissue changes, steroid flare, skin rash, flushing, and menstrual changes.
In a recent systematic review of 87 studies examining extra-articular CIs, only 5 studies reported the frequency of soft tissue atrophy (1.5%–40%), and 6 studies reported the frequency of skin hypopigmentation (1.3%–4%).
However, of the 8 papers reporting use of CI for lateral epicondylitis, all but 2 of them discuss some form of soft tissue complication occurring in their study. Similarly, 2 of the 3 papers reporting CI use for de Quervain tenosynovitis show soft tissue complications. This suggests that CIs for de Quervain tenosynovitis and lateral epicondylitis are particularly susceptible to soft tissue atrophy and skin hypopigmentation. In fact, the incidence of soft tissue complications related to CI is reported to be as high as 31% for de Quervain tenosynovitis and up to 40% for lateral epicondylitis.
Microscopic changes in atrophied or hypopigmented soft tissue can offer some insight into the pathophysiology of this condition. Subcutaneous tissue samples from sites of CI-induced atrophy reveal a decrease in the number and size of adipocytes, potentially related to the infiltration of “lipophage-like” macrophages (demonstrated via electron microscopy). Other inflammatory cells and tissue necrosis have not been identified.
Post-injection involutional lipoatrophy: ultrastructural evidence for an activated macrophage phenotype and macrophage related involution of adipocytes.
Skin punch biopsies taken from affected areas reveal epidermal and dermal atrophy, flattening of rete ridges, reduced melanin-containing cells, and homogenization of collagen fibers.
Further histopathological analysis has shown a normal number of intact melanocytes along the dermal-epidermal border; however, their function was significantly impaired.
Along with macrophage-induced adipose tissue breakdown and melanocyte dysfunction, glucocorticoids have been shown to independently decrease the synthesis of both type 1 and type 3 collagen in human skin.
The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo.
The natural history of soft tissue atrophy and skin hypopigmentation related to CIs is reasonably consistent in most cases. In general, these side effects tend to manifest between 2 and 4 months after injection, but delays of up to 10 months have been reported.
Post-injection involutional lipoatrophy: ultrastructural evidence for an activated macrophage phenotype and macrophage related involution of adipocytes.
Soft tissue atrophy and hypopigmentation can regress spontaneously, and often do so by 9 to 12 months after the initial injection. However, occasionally, these soft tissue changes can be permanent. Interestingly, soft tissue atrophy from steroid injection appears to be more common in females, although the reason for this is not clear.
Subcutaneous atrophy is usually fairly uniform and centered in the area of injection. Skin hypopigmentation can either be confined to the area of injection or progress in a linear fashion, which is likely due to spread along lymphatic channels or superficial veins.
Patients with darker complexions are at higher risk for noticeable hypopigmentation. Other soft tissue–related changes that can be seen are telangiectasias, alopecia, skin hyperpigmentation, and hypersensitivity.
Hypersensitivity can be particularly bothersome for patients, particularly with injections within the distribution of the superficial radial nerve. In the acute postinjection phase, this can be attributed to a flare reaction or an increase in pain compared with preinjection levels. Although flare reactions were initially described as a steroid crystal–induced synovitis related to intra-articular CIs, extra-articular injections can cause a similar phenomenon.
In addition, if a peripheral nerve happens to be injected directly, hydrocortisone and triamcinolone preparations have been shown to be neurotoxic, causing axonal and myelin degeneration, which could manifest as neuropathic pain.
Whereas the initial descriptions of steroid flare from intra-articular CIs attributed this reaction to rapid intracellular ingestions of steroid crystals, a fundamental explanation for flare related to extra-articular injections has not been elucidated.
Choice of Corticosteroid Agent
The choice of corticosteroid to be used, along with the volume, potency, and diluent, varies substantially amongst practitioners. Kegel et al,
in an American Society for Surgery of the Hand member survey, found that for trigger finger injections, 31.4% prefer triamcinolone acetonide plus lidocaine, 27.1% use betamethasone plus lidocaine, and 15.3% use methylprednisolone plus lidocaine. The remaining 26.2% use 1 of 27 other individual preparations. The total volume injected for specific upper extremity disease processes varied as much as 32-fold, and the potency-adjusted steroid dose varied as much as 356-fold. Surgeons who used betamethasone and dexamethasone injected a significantly higher potency-adjusted dose than those who used methylprednisolone or triamcinolone preparations, which likely demonstrates a lack of understanding of the potency equivalence. Of those surveyed, 91% listed fellowship training, colleague recommendations, or no specific rationale as the reasoning behind their CI practice.
The most common corticosteroids used for injection today are triamcinolone, betamethasone, methylprednisolone, and dexamethasone. Triamcinolone and methylprednisolone preparations contain ester compounds, which make them highly insoluble in water and leads to the formation of microcrystalline suspensions. Betamethasone preparations are generally considered to be more soluble compared with triamcinolone and methylprednisolone. However, some formulations contain a betamethasone ester and a betamethasone salt, with the ester having similar solubility properties to the preparations that form microcrystals.
Dexamethasone is freely soluble in water and does not form microcrystals. The solubility of the various compounds is inversely related to the duration of effect, with triamcinolone acetonide being the least soluble injectable steroid preparation and having the longest-lasting effect. Dexamethasone, therefore, has a shorter duration of effect. Another difference between these compounds has to do with their potency. Dexamethasone and betamethasone are 5 times as potent as triamcinolone and methylprednisolone, with 1 mg of betamethasone being equivalent to approximately 5 mg of methylprednisolone.
The less soluble (longer-acting) preparations have a more detrimental effect on surrounding soft tissues compared with shorter-acting compounds. Animal soft tissues injected with triamcinolone demonstrate significant atrophy. Necrosis of the soft tissue membrane was also visualized, which is in contrast to studies that examine human specimens.
Intra-articular steroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch.
Clinical studies have shown a higher severity and incidence of soft tissue atrophy and skin hypopigmentation with triamcinolone acetonide preparations.
Depth of injection and concentration of the preparation have also been shown to influence soft tissue changes, with superficial and more concentrated injections having a greater adverse effect.
Detailed review of the literature on CI for de Quervain tenosynovitis also suggests that there is a relationship between the type of steroid preparation and its effect on surrounding soft tissues. The reported incidence of soft tissue complications related to CI for de Quervain tenosynovitis varies between 0% and 31%. The study with the highest incidence of soft tissue complications used a relatively high dose of a long-acting corticosteroid (40 mg methylprednisolone), and some patients were injected multiple times.
All of the studies we reviewed that reported adverse effects to the soft tissues after treatment of de Quervain tenosynovitis utilized a long-acting, relatively less soluble, steroid preparation (triamcinolone acetonide or methylprednisolone), whereas the studies that used more soluble preparations (hydrocortisone and betamethasone) had no soft tissue complications.
Nonetheless, some studies utilized long-acting steroid preparations with no reported detrimental effects on the soft tissue, suggesting choice of steroid preparation is not the only factor that influences atrophy and hypopigmentation.
Studies reporting outcomes of CI treatment for lateral epicondylitis also suggest that long-acting, less soluble, preparations result in a higher incidence of soft tissue complications. Price et al
compared injection with 25 mg of hydrocortisone with 10 mg of triamcinolone hexacetonide. They found that patients injected with the triamcinolone preparation had a 40% incidence of skin atrophy, which was double the incidence for hydrocortisone. In a separate cohort, 20 mg of triamcinolone hexacetonide had a higher incidence of skin atrophy than 10 mg of the same solution, but this difference did not reach statistical significance.
Ultimately, the selection of a particular steroid preparation depends on multiple factors. Many surgeons prefer the less soluble options of triamcinolone and methylprednisolone owing to their long-lasting efficacy. However, the same properties that increase the duration of effect of these medications appear to cause harm to the soft tissues. Furthermore, the more soluble preparations are taken up more rapidly by cells and, therefore, have a faster onset. If soft tissue atrophy and skin hypopigmentation are a significant concern, dexamethasone and a soluble betamethasone preparation appear to be more favorable in comparison. Again, it is important to remember the steroid equivalence of the various preparations when determining the injection volume because dexamethasone and betamethasone are more potent.
Technique Recommendations
Although very little evidence-based guidance exists regarding the details of CI techniques, recommendations can be based on our current understanding of corticosteroid physiological mechanisms and soft tissue interactions. When injecting corticosteroids, efforts should focus on precise delivery to the target tissues and minimizing spread to the surrounding soft tissue envelope. A large-gauge needle (18 gauge) creates a track through the soft tissues potentially allowing the steroid preparation to leak into the vulnerable subcutaneous plane. Very small needles (30 gauge), conversely, may make “aiming” the injection difficult, may not be long enough to reach the target area, or may clog during the injection process. Therefore, choosing a moderate/smaller size needle (23–27 gauge) is preferable. In addition, making multiple passes for injection, or injecting while withdrawing, will disperse the preparation unfavorably.
The volume of solution injected will influence the accuracy of steroid delivery. A small amount of solution (1 mL) will be able to be delivered more precisely than the same dose of corticosteroid diluted in 5 to 10 mL of solution. When treating most common upper extremity conditions, such as de Quervain tenosynovitis, lateral epicondylitis, and trigger finger, 0.5 to 2 mL of solution should be sufficient to deliver the chosen corticosteroid accurately, without causing undesirable distribution to the surrounding soft tissues.
Selecting an evidence-based dose of the chosen steroid preparation can be challenging because few high-level studies have been done. The relevant literature reports a wide range of dosages for each compound. Ten milligrams of triamcinolone hexacetonide appears effective for lateral epicondylitis, de Quervain tenosynovitis, and trigger fingers.
Whichever preparation is utilized, the smallest effective dose will be empirically the safest.
Treatment
Most patients should initially be counseled and reassured that treatment of CI-induced soft tissue atrophy and skin hypopigmentation is often unnecessary because these issues will usually resolve within a year.
(Figure 1, Figure 2). Fat grafting not only fills the soft tissue defect but also seems to improve the soft tissue quality through an unknown mechanism that may involve stem cells or growth factor–induced angiogenesis.
Autologous fat grafting has been described as a treatment option for a wide range of disease processes of the upper extremity. As an aesthetic rejuvenation for age-related changes on the dorsum of the hand, good long-term results have been reported.
In addition, fat grafting has been shown to improve range of motion, scar appearance, and satisfaction in patients with unfavorable scarring related to burn reconstruction.
Early experience with fat grafting as an adjunct for secondary burn reconstruction in the hand: technique, hand function assessment, and aesthetic outcomes.
These studies demonstrate a favorable safety profile for the use of fat grafting in the upper extremity, with no major adverse events.
The techniques of fat harvest, processing, and injection vary significantly in the literature, but can typically be performed without the need for general anesthesia. The donor site, usually the abdomen or thighs, is infiltrated with tumescent solution and fat is harvested with a suction cannula. The fat is then usually processed and reinjected into the recipient site. Processing can be done through a variety of methods including straining or with the use of a centrifuge, but no single processing technique has been shown to be superior.
As with any tissue graft, fat graft survival is optimized by maximizing contact of the grafted fat with surrounding vascularized tissues. If a large bolus of fat is injected subcutaneously, the central portion of the fat, which is not in contact with vascularized tissue, may become necrotic and form an inflammatory cyst.
a recognized pioneer in the use of fat grafting, advocates injecting one-tenth of a milliliter with each withdrawal of the infiltration cannula. In addition, injecting the fat slowly appears to reduce the shear force applied to the adipocytes and improves viability.
Soft tissue atrophy and skin hypopigmentation are rare but potentially distressing complications of CIs. These changes usually manifest within several months of the steroid injection and will often resolve within 1 year. Atrophy is related to a decrease in the number and size of adipocytes, along with decreased collagen production, that causes thinning of the dermis and epidermis. Hypopigmentation appears to be related primarily to melanocyte dysfunction. Less soluble (longer-acting) steroid preparations will have a more detrimental effect on surrounding soft tissues. For patients who continue to have bothersome soft tissue atrophy, fat grafting has been shown to be a safe and effective treatment modality.
References
Read H.S.
Hooper G.
Davie R.
Histological appearance in postpartum de Quervain’s disease.
Post-injection involutional lipoatrophy: ultrastructural evidence for an activated macrophage phenotype and macrophage related involution of adipocytes.
The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo.
Intra-articular steroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch.
Early experience with fat grafting as an adjunct for secondary burn reconstruction in the hand: technique, hand function assessment, and aesthetic outcomes.
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