INTRODUCTION — Intralesional injection, the direct delivery of medication percutaneously into skin lesions, has been an important part of dermatologic therapy since it was first introduced in 1961 [1,2]. Intralesional injections are effective for a wide range of indications, are easily performed, and are relatively safe.
The rationale for intralesional therapy is simple: to deliver a medication directly into a specific skin lesion to treat local tissues with minimal systemic effects. The skin also serves as a reservoir, allowing medication deposited in the dermis to be delivered over a period of time, resulting in prolonged therapy while avoiding or minimizing the adverse effects of systemic therapy.
The drugs primarily used for intralesional injections are corticosteroids, but bleomycin, fluorouracil, methotrexate, chloroquine, rituximab, and interferons have also been dispensed in this manner [3-6]. This topic will review the indications, techniques, and adverse effects of intralesional injection of corticosteroids. The use and adverse effects of topical and systemic corticosteroids are discussed separately. (See "Topical corticosteroids: Use and adverse effects" and "Pharmacologic use of glucocorticoids" and "Major side effects of systemic glucocorticoids".)
CORTICOSTEROID FORMULATIONS — Triamcinolone acetonide and triamcinolone diacetate are the most widely used intralesional corticosteroids, although dexamethasone, betamethasone, or methylprednisolone acetate are used by some clinicians. Triamcinolone agents are available as micronized suspensions. Characteristics associated with micronized suspensions that make them desirable for intralesional administration are the small size of the corticosteroid particles, stability at room temperature, and ease of resuspension of corticosteroid particles with gentle mixing . Small corticosteroid crystals are more efficiently delivered to the treatment site, thereby decreasing the total administered dose of the drug and reducing the risk of systemic side effects and skin atrophy. In addition, because micronized crystals of corticosteroid are in a depot form, the active ingredients are stored in the tissues and released over a period of weeks, making this type of corticosteroid delivery system well suited for the treatment of chronic inflammatory dermatoses . Examples of chronic inflammatory dermatoses that are particularly amenable to this type of extended action include psoriasis, lichen simplex chronicus, cutaneous lupus erythematosus, and prurigo nodularis.
INDICATIONS AND CONTRAINDICATIONS — Indications for intralesional corticosteroid therapy are acute and chronic, inflammatory processes ; hyperplastic and hypertrophic skin disorders; and conditions that typically have a favorable response to systemic and topical corticosteroids. In addition to anti-inflammatory properties, the atrophogenic effect of corticosteroids can also be used advantageously when treating hypertrophic lesions, such as thick psoriasis plaques, cutaneous sarcoidosis (ie, lupus pernio), lichen simplex chronicus, hypertrophic discoid lupus erythematosus, hypertrophic scars, and keloids.
Intralesional injections are not advised when the possibility of infection is present, either as the etiology of the lesion or as a secondary sequela. Diabetes is not an absolute contraindication to intralesional corticosteroid therapy; in fact, judicious use of intralesional injections can result in lower blood glucose levels as compared with repeated applications of a potent topical corticosteroid. Regardless, caution should be used and appropriate monitoring performed when treating diabetic patients with corticosteroids of any type.
EQUIPMENT — Most intralesional therapy is administered via needle, although a few clinicians prefer jet injection devices. Typically, 30- or 27-gauge needles are used, although 25-gauge needles may be preferable when injecting lesions with dense or thickened tissue, such as scars. The needles are placed on 1 or 3 mL Luer lock syringes to prevent the needle separating from the syringe under the pressure of injection. One milliliter syringes are most frequently used because the quantity of medication delivered is usually in the tenths or even hundredths of a milliliter, and the smaller syringe allows for greater quantitative accuracy.
A larger bore needle (21 or 22 gauge) is used to draw up the solution and to dilute the corticosteroid with saline or lidocaine, then it is removed and replaced with the small injecting needle. Thirty-gauge needles are the most desirable and widely used by dermatologists because they produce less discomfort when penetrating the skin and prevent rapid injection, which is associated with increased pain. Smaller-gauge needles also allow greater precision in injecting the desired quantity of drug.
Other standard equipment for injection includes nonsterile gloves, an alcohol swab, 4x4 gauze, and protective eye wear.
MIXING THE SOLUTION — Triamcinolone acetonide is available in 10 mg/mL, 40 mg/mL, and 80 mg/mL multidose vials. When using corticosteroids from multidose vials, it is advised that dilution of the corticosteroid be done in the syringe immediately prior to injection. The final concentration should be just sufficient to treat the lesion and low enough to avoid local or systemic side effects.
To dilute a single dose of corticosteroid, it is necessary to gently shake the corticosteroid bottle to resuspend the particles. Sterile saline for injection or 0.5% or 1% lidocaine without epinephrine may be used as the diluent, especially when using high corticosteroid concentrations or injecting more than 1 mL into a single site (table 1):
Immediately before injecting a lesion, gently shake or roll the syringe to ensure even suspension of the drug in the diluent, and consequently, even delivery into the tissue.
REDUCING INJECTION PAIN — While pain is rarely associated with low concentrations of corticosteroids, patients may experience pain during, and for a short time after, injection of higher concentrations (eg, 20 to 40 mg/mL); with certain conditions, such as keloids; and in sensitive body sites, such as the perioral area and palm of the hand.
Some clinicians use 1% lidocaine as diluent for corticosteroids to reduce pain. However, a study comparing saline and unbuffered lidocaine as diluents found no significant difference in discomfort between the two . Other methods have been employed to reduce injection pain in settings where pain is problematic, such as in the treatment of keloids or when treating children. These include prior local anesthesia administered on the periphery of the treatment site; topical anesthetics, such as eutectic mixture of local anesthetics (EMLA) cream or lidocaine-impregnated tape; by cooling the area with light liquid nitrogen application or cold packs; and by vibration during injections [10,11]. Though they significantly reduce pain, the drawback to topical EMLA cream and lidocaine patches is that they require application up to 120 minutes prior to injections . One study demonstrated modest pain relief by cooling tissues prior to injection with cold air .
INJECTION TECHNIQUES — Most pathology in inflammatory skin lesions is in the dermis, and it is in this layer of skin that corticosteroids should be deposited. The clinician should first prepare the skin with alcohol, then insert the needle at a 45 degree to 90 degree angle into the lesion to the level of mid-dermis, then slowly inject the drug (picture 1). When deposited correctly into the mid-dermis, the skin rises slightly and blanches (picture 2).
Enough material is injected to just slightly raise the skin surface; often this is only tenths of a milliliter. For large lesions, the needle should be withdrawn partially and redirected to cover additional areas, or the needle can be removed and reinserted in another site. Caution is needed to avoid injecting into subcutaneous tissue; this is easy to recognize because the injected solution flows easily into subcutaneous fat, while resistance is felt when correctly injecting into dermis. Correct injection technique depends upon knowledge of skin anatomy and particularly an awareness of the different thicknesses of epidermis and dermis in different body sites, at various ages, and in specific diseases.
When injecting inflamed acne cysts or cysts and sinuses of hidradenitis suppurativa, the tissue immediately surrounding the cyst or sinus but still well within the zone of inflammation is the target area. Protective eye wear is strongly advised, especially when dealing with cystic lesions, to prevent material discharged from the injection or the cyst from splashing into the eyes. (See "Hidradenitis suppurativa: Management", section on 'Intralesional corticosteroids'.)
Keloids and hypertrophic scars are directly injected with corticosteroids; however, thick and longstanding keloids are often so tough that they must be softened by pretreatment for 5 to 20 seconds with liquid nitrogen. Alternatively, an injection can be performed immediately peripheral to the affected tissue, directing the needle toward the keloid. Keloids often need multiple treatments three to four weeks apart until there is adequate flattening of the lesion (picture 3). It is not unusual to use triamcinolone in strengths of up to 40 mg/mL; however, most dermatologists recommend beginning treatment with triamcinolone, 10 mg/mL, and increasing the concentration as needed to avoid excessive and sometimes permanent atrophy and hypopigmentation. (See "Keloids and hypertrophic scars".)
Having completed the injection, gauze is held lightly over the site to stop any bleeding. Occasionally an adhesive bandage is placed if bleeding continues.
Data on intralesional corticosteroid therapy for many of the disorders treated with this modality are limited, and there is quite a bit of variation among the experts regarding matching the concentration and volume of corticosteroid injected to the type of lesion being treated. In general, acute inflammatory lesions (eg, acne cysts) and lesions in thin skinned areas such as the face and central chest necessitate lower corticosteroid concentrations and smaller drug quantities than more chronic conditions (eg, psoriasis, lichen simplex chronicus, keloids) and lesions in thick-skinned areas like the scalp and back (table 2) .
SIDE EFFECTS, COMPLICATIONS, AND PITFALLS — The most common side effects of intralesional corticosteroid injections are local. These include atrophy, hypopigmentation, and rarely, sterile abscess formation. Atrophy and pigment changes usually resolve over several weeks but occasionally persist longer and are sometimes permanent (picture 4):
●Atrophy can occur when a drug is deposited too deeply into the skin (eg, fat), when the dose of a corticosteroid is higher than needed to treat the condition (there is a higher risk using >5 mg/mL triamcinolone acetonide), when steroid particles have not been well suspended prior to injection, and when there are repeated treatments in the same site. At times, even with appropriate dosing, atrophy may occur. Because the particles release corticosteroid over weeks, atrophy may not appear immediately.
In most cases of atrophy, no treatment is needed, as there is resolution with time. However, some atrophic lesions may be persistent. Dermal fillers, such as poly-L-lactic acid, hyaluronic acid, and calcium hydroxylapatite, are used for a variety of cutaneous atrophies due to other causes, but there are no published data specific to steroid-induced atrophy.
●Hypopigmentation and depigmentation can occur with corticosteroid injections. It is most noticeable in individuals with darker skin (skin phototypes IV to VI) and is thought to be due to a direct cytotoxic effect of the corticosteroids on melanocytes. Greater amounts and concentrations of corticosteroids (such as those used in the treatment of keloids) increase the risk for loss of pigment. Pigment changes may last up to a year. Patients, especially those with darker skin, should be cautioned about this potential complication .
●Although uncommon, sterile abscesses can occur after corticosteroid injections. A sterile abscess is one due to inflammation around foreign material in the skin rather than an infectious agent, and the steroid microparticles may be the cause of this reaction. A sterile abscess can appear as an asymptomatic or slightly painful, pink or skin-colored nodule, papule, or pustule at the injection site, or it may be a firm nodule in the skin. If pustular, the abscess can be drained by stabbing the pustule with a number 11 blade and draining the contents. Systemic antibiotics are not necessary.
Complications related to intralesional injections typically can be avoided by using the lowest concentration and smallest quantity of drug needed to achieve the desired results. It is preferable to inject corticosteroids in small amounts and low concentrations and have to repeat the injection in three to four weeks than to overestimate the corticosteroid dose and suffer a complication. Patients should be advised that the first treatment may not be completely effective and more than one injection may be necessary.
In addition to using too much of or too concentrated a corticosteroid, another pitfall is incorrect placement of the corticosteroid into the skin. When deposited in the subcutaneous layer, the atrophic effect may be exaggerated and the therapeutic anti-inflammatory effect minimized. Likewise, injecting too high in the skin, in the upper dermis and epidermis, may cause sloughing of the skin. Additionally, placement close to the epidermis may increase the risk for loss of pigment.
Systemic adverse effects of intralesional corticosteroids due to systemic absorption are infrequent, especially when corticosteroids are used in low doses and at three- to four-week intervals as generally recommended for the treatment of cutaneous lesions. However, there are reports of Cushing syndrome and adrenal suppression following intralesional administration of corticosteroids [15-17]. Repeated, frequent injections producing a high cumulative dose of a corticosteroid (more than 40 mg per month) may result in systemic adverse effects, especially in children.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Keloids (The Basics)")
●Intralesional injection is a technique used to administer medication directly into the skin. The anti-inflammatory and atrophogenic effects of injected corticosteroids are useful for the treatment of a variety of skin disorders. (See 'Indications and contraindications' above.)
●The use of a one milliliter syringe, rather than a larger syringe, allows for better control of the quantity injected. A small diameter needle, such as a 30-gauge needle, will decrease patient discomfort. (See 'Equipment' above.)
●Triamcinolone acetonide is the most frequently used medication for intralesional corticosteroid injections and is available as a micronized suspension. Dilution with normal saline or lidocaine may be required to achieve the desired dose (table 1). The syringe should be shaken or rolled immediately prior to injection to ensure even suspension of the drug during delivery. (See 'Mixing the solution' above.)
●The dermis is typically targeted during intralesional corticosteroid injections. The concentration of corticosteroid and the injection technique vary according to lesion type and site. (See 'Injection techniques' above.)
●Potential side effects of intralesional corticosteroid injection include cutaneous atrophy (picture 4), hypopigmentation, and abscess formation. The lowest dose required to achieve the desired effect should be utilized to minimize this risk. Systemic side effects may occur in patients receiving frequent high doses of corticosteroids. (See 'Side effects, complications, and pitfalls' above.)