Cold anesthesia for pain reduction during intralesional steroid injection for nodulocystic acne

In any dermatologic procedure, patient acceptance of treatment is heavily influenced by intraprocedural pain. Intralesional triamcinolone injections are very important in keloid scar and nodulocystic acne treatment. However, the main problem of needle‐stick procedures is pain. Cryoanesthesia is ideally intended to cool only the epidermis during treatment and has advantage which did not require application time.

Thus, topical anesthetic creams have the problem of requiring application time.
Other anesthetic methods include iontophoresis, cold anesthesia, and vibration anesthesia; however, each method has its own limitations. 2Iontophoresis of lidocaine for dermatological use is 80%-100% effective in providing anesthesia to intact skin before injections, incisions, abrasions, laser surgery, and cautery. 3ntophoresis also requires a typical application time of 10 min. 4yoanesthesia is ideally intended to cool only the epidermis during treatment and has advantage which did not require application time. 5However, existing cold anesthesia method lacks ability to control the temperature.Excessive cooling has led to frostbite and other side effects in some cases.CryoVIVE® (RecensMedical), which was recently introduced to the market, is a device that can perform precision cooling by dropping the skin temperature using CO 2 gas.This device also has thermo-sensor-enabled real-time temperature and duration monitoring.However, no clinical studies have evaluated the efficacy and safety of CryoVIVE® for anesthesia during needle-stick procedures.This study aimed to investigate the pain-reducing effect and safety of CryoVIVE® during intralesional triamcinolone acetonide (TA) injections for nodulocystic acne lesions in actual clinical settings.

| MATERIAL S AND ME THODS
The study was approved by the institutional review board of Chung-Ang University Hospital (IRB No. 2205-026-508).

| Stage 1
To determine the safety and efficacy of the device, 34 subjects underwent a non-randomized controlled pilot trial.The subjects received TA injections in acne lesions accompanied with cryoanesthesia.

| Stage 2
The effectiveness and safety of cryotherapy were evaluated using split-face comparison.This prospective study evaluated the effect of cold anesthesia with intralesional TA injections on patient comfort.Thirty adults (age > 18 years) who were scheduled to undergo intralesional TA injections for at least two acne lesions (each on their split-face) were enrolled.
The exclusion criteria for this study were the following: (1) pregnancy or breastfeeding, and (2) any other medical skin condition that could increase the risk of infection.All patients were given written informed consent regarding publication of their details and images.

| Procedure
Initially, the treatment area was thoroughly cleansed with a gentle skin cleanser.Patients did not receive any other pretreatment for pain management.Patients received 2.5 mg/mL of TA injections using a 30-gauge needle with cold anesthesia using a portable cryotherapy device CryoVIVE®, with the temperature setting within 0-3°C, allowing for slow cooling on the one site.Patients received only TA injection without cryoanesthesia on the other side.The device is ergonomically designed to allow the physician to inject with one hand while holding the device with the other (Figure 1).Contact tip of CryoVIVE® was disinfected with benzalkonium chloride cleaner before and after use to prevent contamination.

| Evaluation
Pain intensity was evaluated using the Visual Analogue Scale (VAS) (0 = absence of pain, 10 = most severe pain) during both treatments with and without cold anesthesia.Pain assessments were performed immediately after the procedure.Overall patient satisfaction scores (scale, 0-10) were also obtained after the treatment.Any adverse events, such as dyspigmentation, pain, erythema, blistering, and edema, were observed and reported by both subjects and physicians during the laser treatment and at each visit.

| Statistical analysis
In Stage 2, the paired t-test was used to compare the score between lesions treated with and without forced cold anesthesia with SPSS 26.0 (SPSS Inc.) program.p-values <0.05 were considered statistically significant.

F I G U R E 1
Photograph showing intralesional injection of triamcinolone with cryoanesthesia using Cryovive®.

| Stage 1
In total, 34 patients were treated with TA injections.The mean VAS score for during TA injection with the cold anesthesia device was 2.80 ± 0.79.Side effects, such as erythema, edema, and crusting, were not observed.Since there were no safety issues, Stage 2 was proceeded.

| Stage 2
In total, 60 acne lesions in 30 patients were treated with TA injections.The mean VAS score during treatment without cold anesthesia was 5.933 ± 2.03.In contrast, the mean VAS score for the same patients during TA injection with the cold anesthesia device was 3.667 ± 2.23, which was significantly lower (p < 0.05) (Figure 2).The mean subjective satisfaction scores on the lesion with and without cold anesthesia were 3.867 and 2.5, respectively (p = 0.0004).No side effects including discoloration or scarring were observed.

| DISCUSS ION
7][8] In acne treatment, intralesional corticosteroid injections effectively reduce inflammation of individual acne lesions. 6Despite common use, severe intraprocedural pain reduces patient satisfaction and compliance.There are few available anesthetic options for painful injection procedures; however, the ideal method remains unknown.The ideal anesthetic should provide painless, effective analgesia with rapid onset, prolonged duration, and minimal side effects. 4 the field of dermatology, topical EMLA® cream is the most commonly used anesthetic. 9However, EMLA® cream is timeconsuming because of its slow onset of analgesic effect and it can also induce tingling, burning, and pulling sensations.Meanwhile, for the last two decades, cryoanesthesia has gained interest as a convenient and relatively noninvasive pain-control modality in dermatology. 10Cryotherapy decreases the temperature of the skin and underlying tissues 2-4 cm deep, decreasing the activation threshold of tissue nociceptors and the conduction velocity of pain nerve signals, thereby eliciting a local anesthetic effect. 11One advantage of cryoanesthesia is that it does not require application time; instead, it induces an anesthetic effect nearly immediately after application.
The vasoconstriction caused by cooling also helps reduce the risk of post-procedure edema and bruising. 12eviously introduced to the market, Ethyl Chloride® (Gebauer Company) delivered through a propellant spray is one cryoanesthesia medium.Upon contact with skin, it vaporizes, causing a transient drop in local temperature to between −10 and −20°C, and inducing immediate anesthesia on the affected skin through nerve receptor desensitization. 4Liquid nitrogen has also been used as a cryoanesthesia medium.However, the most important disadvantage of cryoanesthesia is the possibility of frostbite.Prolonged freezing can lead to dyspigmentation or atrophic scarring. 10 contrast, CryoVIVE® has a relatively low possibility of side effects such as frostbite or dyspigmentation through monitoring and maintaining the skin temperature via real-time thermo-sensor.
Unlike hyperthermic exposure, the cold temperature itself does not cause cell damage, and ice formation inside or outside the cell causes cell damage. 13When cells are cooled below the freezing point, reaching −10 to −18°C, ice formation occurs, causing lethal cell and tissue damage.Therefore, real-time temperature monitoring can reduce the risk of frostbite.With this method, the danger of frostbite is significantly less than that with traditional cryoanesthetic methods.Some refrigerants have harmful effects associated with the ozone layer, whereas CO 2 gas is usually safe.Moreover, rapid evaporation prevents intense and prolonged skin contact, consequently reducing contact sensitization.Another advantage is that the device is small and light enough to be held in one hand, allowing for one-handed cooling and one-handed injection.This anesthetic method provides tolerable treatment for patients through an excellent safety profile, high level of patient acceptance, and ease of use. 5 Our study shows that the cryoanesthesia reduces pain without any observed adverse events.Moreover, CryoVIVE® improves pain sensation with intralesional corticosteroid injections.Some reports have suggested local anesthetic methods for reducing pain followed by steroid injections.Wang et al.
10 compared pain induced by TA with and without prior application of the cryotip to treat keloid scars.Average F I G U R E 2 Patients' self-assessed pain score during intralesional triamcinolone injection by Visual Analogue Scale (VAS) score with and without cryoanesthesia.The pain score significantly decreased after applying cryoanesthesia (***p < 0.001).