Acne Nodules and Cysts

Patients with tender large nodulocystic lesions can expect to get symptomatic relief within 24 hours of an intralesional injection. The lesion will flatten within 2 to 3 days with an effective injection.¹ Although this should not be the primary treatment of acne, it can provide short-term relief while employing more long-term treatment regimens.

One small study evaluated the effectiveness of intralesional injections of steroids in the therapy of nodulocystic acne.¹ They found that 0.63 mg/mL of triamcinolone was as effective as 2.5 mg/mL.¹ Betamethasone injections were no better than saline controls.¹ One review article states that concentrations of 3.3 and 5 mg/mL of triamcinolone are standard dilutions for intralesional acne injections.²

We recommend using 1 to 3.3 mg/mL of triamcinolone for nodulocystic acne depending on the location of the lesions and the experience of the clinician and patient. Triamcinolone can be injected with minimal pain using a 30-gauge needle on a 1-mL syringe at a 45- to 90-degree angle with the skin (Figure 16-3).

FIGURE 16-3 Nodulocystic acne being injected with dilute triamcinolone.

(Copyright Richard P. Usatine, MD.)

For acne cysts on the face, it is safer to use 1 to 2 mg/mL to make sure that atrophy does not occur. On the trunk consider using 2 to 3.3 mg/mL of triamcinolone. Enough suspension should be injected to see and feel the cyst become distended, but no more than 0.1 mL is needed for any one cyst. One injection site per acne cyst should be adequate. If the cyst is large and soft, do not inject more volume because that can lead to atrophy. If there is a lot of purulent material inside the cyst, a quick incision and drainage (with lidocaine and a No. 11 scalpel) before injecting the steroid may be helpful.

Acne Keloidalis Nuchae

Acne keloidalis (Figure 16-4) occurs on the posterior neck most commonly in men with highly pigmented skin. It is an inflammatory condition that is exacerbated by shaving the back of the neck. It has features of acne and folliculitis. Over time keloidal-type scars occur and can become very large. Treatment and prevention include not cutting the hair too short and using topical steroids and topical retinoids. Tender and painful keloidal nodules can be injected with triamcinolone for some relief. Concentrations of 5 to 10 mg/mL can be used. The heavier the fibrosis and scarring, the larger the needle needed to inject the lesion.

FIGURE 16-4 Acne keloidalis nuchae being treated with intralesional steroids.

(Copyright Richard P. Usatine, MD.)

Alopecia Areata (Figure 16-5)

Although a recent Cochrane review on the treatment of alopecia areata (Figure 16-5) found no RCTs on the use of intralesional steroids (and many other treatments), they did acknowledge that this is a commonly used treatment for alopecia areata.³ Considering the possibility of spontaneous remission in the early stages of the disease, it is reasonable to reassure the patient and recommend tincture of time. However, many patients are seeking an active treatment. Intralesional steroid for alopecia areata is a well-accepted standard treatment and often gives patients hope that they will regain their hair. Recommended concentrations of triamcinolone range from 5 to 10 mg/mL for the scalp, but the higher concentrations often cause scalp atrophy. Therefore we recommend using 5 mg/mL of triamcinolone for the scalp. Alopecia areata can affect the eyebrows and the beard. For those regions it is safer to stick with a lower concentration of triamcinolone such as 3.3 mg/mL. A long 27-gauge needle (1.25 to 1.5 inches) will allow for treatment of larger areas with fewer injections per site.

FIGURE 16-5 (A) Alopecia areata being injected with triamcinolone. (B) Regrowth of hair at a site of alopecia areata that had been previously injected with triamcinolone. Note how the new hair is white. This is not a side effect of the triamcinolone injection but a common characteristic of hair regrowth at the site of alopecia areata.

(Copyright Richard P. Usatine, MD.)

Cutaneous Lupus

Intralesional steroids have been used for decades to treat patients with all types of localized cutaneous lupus (Figure 16-6).^4,5 Widespread cutaneous lupus is best treated with topical steroids and systemic agents when indicated. For specific local lesions that are not responding well, discuss the option of intralesional steroids with the patient. Our recommendation is to use from 2.5 to 5 mg/mL depending on the site. Special care should be taken when treating lupus on the face in a darkly pigmented individual because hypopigmentation can be a particularly unacceptable adverse effect.

FIGURE 16-6 Discoid lupus. This patient had biopsy proven lupus paniculitis at that site and had relief of her pain after the intralesional steroid injection.

(Copyright Richard P. Usatine, MD.)

Hidradenitis Suppurativa

Injecting painful acute hidradenitis suppurativa cysts (Figure 16-7) is similar to injecting acne cysts, but a higher concentration of triamcinolone (3.3 to 5 mg/mL) is acceptable because these lesions are usually in the axilla, chest, or groin and less prone to atrophy. Also a little skin atrophy is generally more acceptable in these locations than the face. It may be best to use the lower end of this range when injecting hidradenitis around the breasts because this area is of more cosmetic concern. Because the cysts are often larger than acne, a 3-mL syringe may be needed to provide more volume for injection. Large, purulent cysts can be drained with a No. 11 scalpel first before injecting the steroid.

FIGURE 16-7 Chronic and acute hidradenitis suppurativa prior to steroid injections.

(Copyright Richard P. Usatine, MD.)

Granuloma Annulare

Granuloma annulare (Figure 16-8) is an idiopathic granulomatous disease that typically appears in ringlike formations. Treatments for localized disease include high-potency topical steroids and injections of triamcinolone. We recommend using 5 mg/mL of triamcinolone and a 27-gauge needle. Four injection sites are usually needed to cover one annular lesion, so a syringe larger than 1 mL is often needed. We prefer not to inject more than 4 mL total. Inject into the granulomatous lesion and not below the lesion. Our experience has shown steroid injections to be more effective than topical steroids. If the condition is disseminated, there are other treatments to consider.

FIGURE 16-8 Granuloma annulare being injected with triamcinolone.

(Copyright Richard P. Usatine, MD.)

Hypertrophic Scars and Keloids

A hypertrophic scar (Figure 16-9) is one in which the scar tissue is raised and prominent over the area that was cut, burned, or traumatized. It may show prominent suture marks and can be redder or differently pigmented compared with the surrounding tissue. Hypertrophic scars frequently regress over a few years. A keloid is similar to a hypertrophic scar but it grows beyond the limits of the original surgery. Keloids tend to become quite raised and enlarged. There are histologic differences between hypertrophic scars and keloids. For the purpose of intralesional injection, however, they are treated identically.

FIGURE 16-9 (A) Acne keloid being injected with triamcinolone. (B) Hypertrophic scar after a knife wound being injected with triamcinolone.

(Copyright Richard P. Usatine, MD.)

Persons with darker skin are at higher risk than light-skinned persons of developing keloids. Keloids most commonly occur on the chest, shoulders, and other areas of increased skin tension but can occur anywhere on the skin. They tend to be more common after a traumatic lesion. Keloids frequently occur after ear piercing and acne scarring. Table 16-1 provides a list of possible treatments for keloids. Surgical excision frequently induces more scarring exacerbating the original problem. If excision is deemed necessary, scarring can be limited by including dilute steroids in the anesthetic, injecting steroids into the surgical site after surgery, using minimal tissue pressure techniques, and postoperative occlusion with silicone sheets for several months.

Initially start with 10 mg/mL of triamcinolone for the first treatment of a keloid or hypertrophic scar. The needle should be introduced into the body of the keloid at a 20- to 30-degree angle with the skin. It is important that the tip of the needle is within the keloid and not below it. Proper needle position should result in significant pressure while injecting and a blanching of the keloid as the suspension is injected into the area. If the solution flows in easily, the needle is most probably too deep. If the needle is too deep, reposition it and restart the injection. Inject firmly while advancing the needle and observing the keloid blanch.

If the MadaJet is being used, activate it by cocking the lever, place the tip lightly on the tissue and release the unit by pushing the button with the thumb. A whitening change will be seen. Apply the next “shot” right next to the original one and progress until the entire lesion is treated.

Large keloids may need multiple injections at one time to adequately infiltrate the lesion. Sometimes the needle can be pulled back and reoriented for the next injection from the same puncture site. The quantity injected should be just enough to blanch the entire keloid white. Hypertrophic scars are injected using the same technique. A 3-mL Luer-Lok syringe facilitates the injection into these firm structures. Without the Luer-Lok it is easy for the needle to come off and spray the clinician in the eyes. Even with a Luer-Lok syringe it is important to wear eye protection when injecting lesions under pressure.

Keloids can be treated with cryosurgery alone or in combination with intralesional steroids. In one small controlled study, ten patients with keloids were treated with intralesional steroid and cryosurgery vs. intralesional steroid or cryosurgery alone.⁶ Patients were treated at least three times 4 weeks apart. In terms of keloid thickness, the keloids responded significantly better to combined cryosurgery and triamcinolone vs. triamcinolone alone or cryotherapy alone. Pain intensity was significantly lowered with all treatment modalities. Pruritus was lowered only with the combined treatment and intralesional corticosteroid alone.⁶

In another study 20 patients with hypertrophic and keloidal scars received two 15-second cycles (total 30 seconds) of cryosurgery treatments once monthly for 12 months with intralesional injections of 10 to 40 mg/mL triamcinolone once monthly for 3 months.⁷ Topical application of silicone gel was added three times daily for 12 months. The control group included 10 patients who received treatment with silicone sheeting only. After 1 year, improvement was seen in all parameters, especially in terms of symptoms, cosmetic appearance, and associated signs compared to baseline and compared to the control group.⁷

Layton et al. reported that the intralesional injection of a steroid is helpful but cryotherapy is more effective (85% improvement in terms of flattening) for recent acne keloids located on the back.⁸ Treatment with intralesional triamcinolone was beneficial, but the response to cryosurgery was significantly better in early, vascular lesions.⁸

If the keloid is older and/or firmer, it may not respond to injection therapy as well as softer and newer lesions. In such cases, it may help to pretreat the keloid with cryotherapy. It is not necessary to freeze a margin of normal tissue. After liquid nitrogen or another freezing modality is applied to the keloid, it is allowed to thaw and develop edema. This generally takes 1 to 2 minutes, which allows for easier introduction of intralesional steroids into the lesions.

In one double-blind clinical trial, 40 patients were randomized to receive intralesional triamcinolone (TAC) or a combination of TAC and 5-fluorouracil (5-FU).⁹ Both groups received injections at weekly intervals for 8 weeks and lesions were assessed for erythema, pruritus, pliability, height, length, and width. Both groups showed an acceptable improvement in nearly all parameters, but these were more significant improvement in the TAC + 5-FU group (P < 0.05 for all except pruritus and percentage of itch reduction). Good to excellent improvement were reported by 20% of the patients receiving TAC alone and 55% of the patients in the group receiving TAC and 5-FU.⁹

Earlobe keloids may be excised with a shave excision and injection of the base with steroid (Figure 16-10). It is hard to get much volume of steroid into the base of these keloids, so 40 mg/mL triamcinolone is preferred as the concentration for injection. Another option is to use the radio-frequency electrosurgery technique with a pure cutting setting and a steroid in the anesthetic.

FIGURE 16-10 A keloid was shaved from the ear lobe and the bleeding stopped using electrocoagulation. The base is being injected with 40 mg/mL triamcinolone to prevent regrowth.

(Copyright Richard P. Usatine, MD.)

According to one article, simple excision of earlobe keloids can result in recurrence rates approaching 80%.¹⁰ A randomized prospective trial comparing steroid injections versus radiation therapy found that 2 of 16 keloids (12.5%) recurred after surgery and radiation therapy, whereas 4 of 12 (33%) recurred after surgery and steroid injections. These results did not produce a statistically significant difference. No alteration of skin pigmentation, wound dehiscence, or chronic dermatitis was observed in any patient in either group.¹⁰ While radiation therapy was considered easy to obtain in this study, it is reasonable to use steroid injections in office practice.

Localized Dermatitis (Lichen Simplex Chronicus, Prurigo Nodularis)

In a recent review paper, no studies were found on the use of intralesional steroids for psoriasis or localized dermatitis since the 1960s.¹¹ The authors describe their personal experience as excellent using 2.5 mg/mL triamcinolone for localized dermatitis (such as lichen simplex chronicus, prurigo nodularis, and nonspecific eczema).¹¹ We recommend using 2.5 to 5.0 mg/mL triamcinolone with a 27-gauge needle for the treatment of localized dermatitis. Because prurigo nodularis (Figure 16-11) can be particularly difficult to treat, the higher concentration may be needed.

FIGURE 16-11 Prurigo nodularis is being injected with triamcinolone.

(Copyright Richard P. Usatine, MD.)

Psoriasis

In the same review paper, no good clinical studies were found on the use of intralesional steroids for psoriasis (Figure 16-12).¹¹ The authors describe their personal experience as virtually 100% effective using 2.5 mg/mL triamcinolone for small plaques of psoriasis on the trunk and limbs.¹¹ In one small series, five patients with chronic intermittent palmoplantar pustulosis were treated with intralesional injections of 3.3 to 5.0 mg/mL of triamcinolone acetonide.¹² Prompt clearing of symptoms and lesions occurred and lasted 3 to 6 months. Despite the discomfort experienced from the injections, patients preferred this treatment modality over others available in 1984. Side effects included hypopigmentation, cutaneous atrophy, and, in one patient, exacerbation of a latent dermatophyte infection.¹² Despite the lack of evidence for the use of intralesional steroid injections for localized psoriasis, it is an accepted treatment option. We recommend using from 2.5 to 5.0 mg/mL with a 27-gauge needle for injection.

FIGURE 16-12 (A) Plaque psoriasis on the leg being injected with triamcinolone. (B) Plaque psoriasis over the MCP joints being injected with triamcinolone.

(Copyright Richard P. Usatine, MD.)

Sarcoidosis

Cutaneous sarcoidosis (Figure 16-13) may respond to intralesional steroids in a similar manner as other granulomatous diseases such as granuloma annulare. Cutaneous sarcoidosis is often found on the face of black women so the concentration of steroid must take the risks of atrophy and hypopigmentation into account. Concentrations of 2.5 mg/mL on the face and 5 mg/mL on the body should provide some relief from cutaneous sarcoidosis.

FIGURE 16-13 Sarcoidosis on the face of a black woman. One option for treatment is the use of intralesional triamcinolone.

(Copyright Richard P. Usatine, MD.)

Tattoo Reactions

Occasionally someone will react with painful swelling and edema around the dye of a new tattoo. Most often it is the red dye (Figure 16-15). When that occurs, one treatment option is to inject the areas of inflammation with triamcinolone.

Candida Antigen

Steroids are not the only injectables that can be used for dermatologic conditions. Verrucae (warts) can be treated with intralesional Candida antigen or bleomycin sulfate. Verrucae can and often do resolve spontaneously on their own. However, they can persist for years, multiply, or cause pain as well as cosmetic concerns. Treatment is often attempted with over-the-counter remedies (topical acids, occlusive techniques, and most recently with cryorefrigerants) and can be successful. When this fails, more aggressive treatments are often tried in a physician’s office including cryotherapy, debridement with application of stronger acids, curettement with or without cautery, laser, and more. Each of these is generally accompanied by pain and various levels of disability as well as an open wound. Failures and recurrences even with aggressive treatment are common. Add to this the clinical scenarios where patients present with hundreds of warts, huge mosaic warts, and extensive periungual warts and one can understand the frustration patients and their caregivers often feel when treating this common problem.

Faced with the difficulty of treating warts, a new approach was taken in 1992. The idea was to somehow focus the immune system on the area where the wart existed. Candida antigen causes an immune response of erythema and occasionally pruritus in the majority of immune-competent individuals. The thought was that if the Candida were injected into the warts the immune response would eliminate the wart due to the increased immunologic activity in the area.

The first study of more than 100 patients who were treated with intralesional Candida was published in 2000. It reported that 85% of patients were completely cleared after three injections at 1-month intervals.¹³ The advantages to this method of treatment are that if the patient’s immune system recognizes the verrucous protein as foreign, then all lesions disappear, recurrences are rare, and there are no open wounds to deal with after treatment.

Candida antigen is an excellent method of treating most common warts, considering the results, cost, ease of administration, lack of scarring, and virtually no lasting side effects (after nearly 20 years of use).

This technique has not been tried on condyloma but can be used for virtually all other warts.

Candida antigen has been used for tuberculosis testing for 50 years or more but does not have FDA approval for the treatment of warts. Because it is approved for human use, malpractice policies will cover its administration should any unforeseen problems arise.

The Pfenninger Candida Protocol: Steps and Principles13,14

1. Obtain the Candida antigen (generic 1 : 1000 or proprietary Candin 1 : 500). Use caution if using allergy extracts to be sure the concentration is not too high.

2. For Candin, dilute 1 : 1 with 2% lidocaine without epinephrine. For generic, mix 1 : 4. This is counterintuitive but the generic seems to produce more of a reaction. See Table 16-4 for specific dilutions. Concentrations can be increased slowly if no immunologic response (e.g., redness, pain) is observed after the initial treatment.

3. Apply a topical anesthetic at least 15 minutes prior or use a cryorefrigerant to ease the pain of injection. The majority of warts occur on the fingers, toes, and feet, which are all very sensitive areas.

4. Inject 0.1 mL (maximum of 0.3 mL depending on the size of the lesion) of solution intralesionally or intradermally. Several points need to be made:

• The injection should take some force. If it goes in too easily, the needle is subdermal and the needed response will not occur. Inject as if you were trying to obtain a wheal although it will not happen due to the fibrous nature of the wart tissue (Figure 16-16).

• Wear protective face shield since the solution often “squirts out” of the wart.

• Use a Luer-Lok syringe since the needle frequently pops off with the pressure applied unless it is locked in place. A 30-gauge needle limits the pain of injection.

5. The total amount injected per visit is limited to 1 mL. Very little material is needed to incite an immune response. If there are 20 warts, try for 0.05 mL per lesion. Obviously, if there are 40 or 50 warts, it will be impossible to treat them all. However, all warts may disappear with treatment of less than the entirety due to the immune response. Some have suggested just pricking the needle into the warts if there is extensive disease. Again, this is just one of many possibilities that have not been studied.

6. Establish a return visit for 1 month. Should the warts resolve, the visit can be cancelled. If the warts persist, another treatment can be given using the same parameters. A third visit should be set up after the second if needed.

7. If after three injections at monthly intervals the warts persist, there are several options.

• If the verrucae are smaller, continue with the Candida antigen if so desired.

• Other traditional physical treatments can be tried. Often the warts are at least diminished in size, which now makes this a more tolerable option.

• Bleomycin injections can be used. In the case of hundreds of lesions, bleomycin can be used on some of the lesions while Candida is used on others (see below).

8. In the absence of immunocompromised conditions (including smoking), expect 65% to 75% of lesions to resolve after the first visit. Younger patients and lesions present less than a year appear to respond best. With each succeeding treatment, approximately 50% of patients will respond.

9. Expect tenderness for a few days, erythema, peeling, and occasionally some pruritus (Figure 16-16B). Occasionally there can be a vigorous immune response with erythema and tenderness (as also occurs with too concentrated or too much volume of solution). There will be no scarring, hypo- or hyperpigmentation, or open wounds.

10. Patients may resume normal activities including bathing and group sports immediately after injection being limited by pain only. See Appendix A for a patient information handout titled Wart Therapy.

 

TABLE 16-4 Candida Dilutions

Creating 1.0 mL for Injection	Candida Antigen (mL)	2% Lidocaine (no Epinephrine) (mL)
Generic 1 : 1000	0.25	0.75
Candin 1 : 500	0.5	0.5

FIGURE 16-16 (A) Candida antigen injection of periungual warts. (B) It is not unusual for erythema to develop around warts injected with Candida antigen. These warts on the leg were injected the day before this photo was taken.

(A: Courtesy of John L. Pfenninger, MD; B: Copyright Richard P. Usatine, MD.)

There is no J-code (a number assigned to each medication for billing) for Candida antigen treatment, therefore the cost of the antigen cannot be billed to insurance. It is quite expensive, especially if the proprietary type is used. Generally, it works out best if the antigen is supplied by the physician for the first visit. The patient is then given a prescription to be filled at the pharmacy to bring with them to the next visit. Make sure that patient knows that the Candida antigen must be refrigerated while storing it at home.

Your prescription should say “Candin antigen (or generic Candida antigen), 1 vial for therapeutic use to treat warts.”

The remainder of the antigen in the leftover vial will build up a supply for the clinician to use for future patients for their “first visit.” Reimbursement for either the lesion injection codes or lesion destruction codes alone is inadequate to cover the costs of antigen so patients should be made aware that they will need to pay for that in addition to the injection fee. Some insurance plans will pay the pharmacist (even though they will not reimburse the physician).

Bleomycin

Bleomycin sulfate is a chemotherapeutic agent. Like Candida antigen, it too has not been approved by the FDA for the treatment of verrucae but it has been well studied and used for more than 20 years.^15,16 Its efficacy is similar to that of Candida antigen but reactions are often more robust. It has not been used for the treatment of condyloma but can be used in all other areas where warts develop.