Intralesional corticosteroid injection

INTRODUCTION — Intralesional injection (ie, 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 drugs primarily used for intralesional injections are corticosteroids, but bleomycin, fluorouracil, methotrexate, chloroquine, rituximab, and interferons have also been dispensed in this manner [3-8]. 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".)

●(See "Pharmacologic use of glucocorticoids".)

●(See "Major adverse effects of systemic glucocorticoids".)

RATIONALE — 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 certain period of time, resulting in prolonged therapy while avoiding or minimizing the adverse effects of systemic therapy.

CORTICOSTEROID FORMULATIONS — Triamcinolone acetonide is the corticosteroid most widely used for intralesional injection, although dexamethasone, betamethasone, or methylprednisolone acetate are used by some clinicians. Triamcinolone preparations 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 with gentle mixing [9]. 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 corticosteroid crystals 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 [3].

INDICATIONS — Indications for intralesional corticosteroid therapy include acute and chronic, inflammatory processes [10]; hyperplastic and hypertrophic skin disorders; and conditions that typically have a favorable response to systemic and topical corticosteroids (table 1). Examples of chronic, inflammatory dermatoses that are particularly amenable to this type of extended action include thick psoriasis plaques, hypertrophic discoid lupus erythematosus, lichen simplex chronicus, and prurigo nodularis. Other conditions effectively treated with intralesional corticosteroids include alopecia areata, cutaneous sarcoidosis, granuloma annulare, and hypertrophic scars and keloids.

CONTRAINDICATIONS — Intralesional corticosteroid injections may not be indicated in the following situations:

●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. Both topical and intralesional corticosteroids can increase blood glucose levels, typically related to the potency and quantity of the agent used [11,12]. Caution should be used and appropriate monitoring performed when treating a person with diabetes with corticosteroids of any type.

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). Injection of keloids or sensitive body sites (eg, perioral area, palm of the hand) is also associated with considerable pain.

Methods employed to reduce injection pain in settings where pain is problematic (eg, treatment of keloids, treating children) include [13-19]:

●Combination of corticosteroid with local anesthetic – 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 [20]. Another study found that pain scores were actually higher for injections containing lidocaine-epinephrine versus saline [21].

●Prior local anesthesia – Local anesthesia can be administered prior to the injection on the periphery of the treatment site.

●Topical anesthetics – Topical anesthetics, such as eutectic mixture of local anesthetics (EMLA) cream or lidocaine-impregnated tape, can be applied to the injection site prior to the injection. Though they significantly reduce pain, the drawback to topical EMLA cream and lidocaine patches is that they require application of 60 to 120 minutes prior to injections.

●Cooling – Cooling the area with light liquid nitrogen application, cold packs, or cold air device.

●Vibration anesthesia – A vibrating device is applied to the skin adjacent to the injection site for the duration of the injection.

EQUIPMENT — Most intralesional therapy is administered via needle, although a few clinicians prefer jet injection devices. 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.

Typically, 30- or 27-gauge needles are generally used, although 25-gauge needles may be preferable when injecting lesions with dense or thickened tissue, such as scars and keloids. 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 the drug. 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.

Saline is an excellent diluent for all corticosteroids, but some clinicians prefer to dilute with the local anesthetic lidocaine. (See 'Reducing injection pain' above.)

Other standard equipment for injection includes nonsterile gloves, an alcohol swab, 4x4 gauze, adhesive bandage, and protective eyewear.

MIXING THE SOLUTION — Triamcinolone acetonide is available in 10, 40, 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 just be sufficient to treat the lesion and low enough to avoid local or systemic side effects.

To dilute a single dose of a 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 2).

●To obtain a 2 mg/mL concentration, draw up 0.4 mL of saline for each 0.1 mL of 10 mg/mL of triamcinolone acetonide.

●To obtain a 20 mg/mL dilution, draw up 0.5 mL of 1% lidocaine for each 0.5 mL of 40 mg/mL triamcinolone acetonide.

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. It has been shown that waiting longer than five minutes between mixing and injecting can result in the formation of large and potentially harmful aggregates [22]. (See 'Pitfalls' below.)

DOSING — Examples of corticosteroid doses for select conditions amenable to treatment with intralesional corticosteroids are illustrated in the table (table 3).

In general, acute, inflammatory lesions (eg, acne cysts) and lesions in thin-skinned areas (eg, the face and central chest) require lower corticosteroid concentrations and smaller drug quantities than more chronic lesions (eg, psoriasis, lichen simplex chronicus, keloids) and lesions in thick-skinned areas (eg, the scalp and back) [10]. However, there is considerable variation among experts regarding matching the concentration and volume of the corticosteroid injected to the type of lesion being treated.

Patients should be advised that the first treatment may not be completely effective, and more than one injection may be necessary.

INJECTION TECHNIQUE

General principles

●Because most pathologic changes in inflammatory skin lesions occur in the dermis, it is in this layer of skin that corticosteroids should be deposited.

●Caution should be exerted when treating facial and periocular areas to avoid accidental intravascular injection (see 'Pitfalls' below). Details on anatomic sites at increased risk of vascular complications are discussed elsewhere. (See "Anatomic danger zones for facial injection of soft tissue fillers".)

●The clinician should first prepare the skin with alcohol, then insert the needle at a 45 to 90 degree angle into the lesion to the level of mid-dermis, then slowly inject the drug (picture 1 and picture 2). When deposited correctly into the mid-dermis, the skin rises slightly and blanches (picture 3).

●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 on awareness of the different thicknesses of the epidermis and dermis in different body sites, at various ages, and in specific diseases.

●Having completed the injection, gauze is held lightly over the site to stop any bleeding. Occasionally, an adhesive bandage is placed if bleeding continues.

●Hand hygiene is required before and after all patient encounters, even if gloves are worn. Care must be exercised to prevent accidental self-injury, such as not attempting to recap the needle, use of self-sheathing needles, and proper disposal in an approved puncture-resistant container (see "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers", section on 'Minimizing risk'). Because high injection pressures are sometimes required to inject into keloids and other thick dermal plaques, appropriate protective eyewear is essential to avoid splash injury.

Special situations

●Cysts – 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 eyewear 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 – Keloids and hypertrophic scars are directly injected with corticosteroids. However, thick and long-standing 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 (picture 4). (See "Keloids and hypertrophic scars", section on 'Corticosteroid injection, tape/plaster, and ointment'.)

Keloids often need multiple treatments three to four weeks apart until there is adequate flattening of the lesion. It is not unusual to use triamcinolone in strengths of up to 40 mg/mL. However, most dermatologists recommend beginning treatment with triamcinolone 5 to 10 mg/mL to avoid excessive, and sometimes permanent, atrophy and hypopigmentation.

ADVERSE EFFECTS AND PITFALLS

Local adverse effects — The most common adverse effects of intralesional corticosteroid injections are local. These include atrophy (picture 5), hypopigmentation, and rarely, sterile abscess formation. Atrophy and pigment changes usually resolve over several weeks but occasionally persist longer and are sometimes permanent.

●Atrophy – Atrophy can occur in the following situations:

•The drug is deposited too deeply into the skin (eg, fat).

•The dose of the corticosteroid is higher than needed to treat the condition; the risk is higher when using a triamcinolone acetonide concentration higher than 5 mg/mL. However, even with appropriate dosing, atrophy may occur because the particles release the corticosteroid over weeks, and atrophy may not appear immediately.

•Steroid particles have not been well suspended prior to injection.

•Repeated treatments are administered in the same site.

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. (See "Injectable soft tissue fillers: Overview of clinical use".)

●Hypopigmentation – Hypopigmentation and depigmentation can occur with corticosteroid injections. It is most noticeable in individuals with darkly pigmented 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 darkly pigmented skin, should be cautioned about this potential complication [23].

●Sterile abscess – 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. 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 adverse effects — 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 hyperglycemia, Cushing syndrome, and adrenal suppression following intralesional administration of corticosteroids [11,24-26]. 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.

Pitfalls — Frequent pitfalls related to intralesional injections include:

●Using too much of or too concentrated corticosteroid – It is preferable to inject corticosteroids in small amounts and low concentrations and repeat the injection in three to four weeks.

●Placing the corticosteroid incorrectly 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.

●Accidental intravascular injection – Triamcinolone is composed of microcrystal particles that may form aggregates. Serious adverse effects may occur from inadvertent intravascular injection, especially when triamcinolone is administered in combination with lidocaine, which results in formation of large particle aggregates (up to 500 micron) and risk of arterial embolism [27].

Thus, in-depth knowledge of the facial anatomy and vasculature is required when injecting the face or periorbital areas to avoid accidental intravascular injection that may result in retinal artery occlusion and blindness [28-31]. In a 2021 systematic review of 49 patients with steroid-induced vision loss, occlusion occurred in the ophthalmic or central retinal occlusion in most cases, triamcinolone was most frequently used, and injection was performed in the nasal and periocular areas in most cases [32].

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 5^th to 6^th 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 10^th to 12^th 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)")

SUMMARY

●Definition – 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' above.)

●Equipment – A one milliliter Luer lock syringe with 30- or 27-gauge needles, rather than a larger syringe, is typically used, as it allows for better control of the quantity injected. A 25-gauge needle is preferred when injecting lesions with dense or thickened tissue, such as scars. (See 'Equipment' above.)

●Mixing the solution – Triamcinolone acetonide is the corticosteroid most frequently used for intralesional injections and is available as a micronized suspension. Dilution with normal saline or lidocaine may be required to achieve the desired dose (table 2). 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.)

●Injection technique – The dermis is typically targeted during intralesional corticosteroid injections. The needle should be inserted at a 45 to 90 degree angle into the lesion (picture 1). The injection technique and the corticosteroid concentration may vary according to lesion type and site. (See 'Injection technique' above.)

●Adverse effects – Potential side effects of intralesional corticosteroid injection include cutaneous atrophy (picture 5), 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 'Adverse effects and pitfalls' above.)