Rita V. Linkner, MD; Andrew Sohn, BA; Kristina Goldenberg, MD; Mark Lebwohl, MD Mount Sinai School of Medicine, Department of Dermatology, New York, New York
Disclosure: Drs. Linkner, Sohn, and Goldenberg report no relevant conflicts of interest. Dr. Lebwohl is an investigator and consultant for Ranbaxy Laboratories, Ltd. Funding for this study was provided by Ranbaxy Laboratories, Ltd.
Objective: Triamcinolone acetonide spray is a topical corticosteroid indicated for the relief of inflammatory/pruritic manifestations of corticosteroid-responsive dermatoses. There are clinical reports of an antipruritic, cooling sensation appreciated upon application. This study was designed to quantify the cryotherapeutic cooling effect of triamcinolone acetonide spray. Design: Using an infrared video camera, skin surface temperature was evaluated for change upon application of the triamcinolone acetonide and two comparator ingredient components of triamcinolone acetonide:ethanol alcohol in a non-aerosolized spray and triamcinolone acetonide cream. Setting: This was an open-label, single center, comparator study. Participants: This study enrolled 20 subjects with a diagnosis of either an acute or chronic steroid-responsive dermatosis. Ten additional controls were also enrolled. Measurements: Using an infrared video camera, skin surface temperature was evaluated for change upon application of the triamcinolone acetonide and two comparator ingredient components of triamcinolone acetonide:ethanol alcohol in a non-aerosolized spray and triamcinolone acetonide cream. Results: Across every study cohort, the average change in skin surface temperature with triamcinolone acetonide (between 16–18ºC; P<0.001 for all comparisons, Figure 1 and Figure 2) was significantly greater than the change demonstrated by both the non-aerosolized spray (between 5–7ºC) and the triamcinolone acetonide cream (between 5.0–6.5ºC). Conclusion: The transient temperature change of nearly 20ºC with triamcinolone acetonide is most likely attributable to the refrigerant properties of the isobutane propellant of this product. Similar to other common cryotherapy methods, triamcinolone acetonide can achieve very low skin surface temperatures, which may result in localized relief of pruritus. (J Clin Aesthet Dermatol. 2013;6(11):28–31.)
Triamcinolone acetonide spray (Kenalog Spray®, Ranbaxy Laboratories, Ltd., T spray) is a mid-potency, class 4/5 topical corticosteroid indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Unlike more potent steroid products, T spray has no time limitations on its use; therefore, it is commonly prescribed to treat flares of a variety of skin disorders including psoriasis, atopic dermatitis, seborrheic dermatitis, and contact dermatitis.
In contrast to creams or ointments, sprays permit easy coverage of large as well as hard-to-reach areas, such as the scalp or back. Currently, T spray is the only aerosolized, mid-potency corticosteroid spray available (http://medlibrary.org/lib/rx/meds/kenalog/page/2, accessed on June 11, 2013).
An open-label, non-comparator study involving 42 patients with chronic steroid-responsive dermatoses investigated the use of T spray applied up to four times a day for 28 days. Improvement of lesions after one week of treatment was experienced by 85 percent of patients with 95 percent reporting a preference of the spray over previously used creams and ointments. Most importantly, 56 percent of patients reported an antipruritic cooling sensation with application.
The authors designed an open-label, single center, comparator study involving 30 subjects to help elucidate the etiology of T spray’s skin surface temperature (SST) change by using an infrared thermal camera. One of the main components of T spray is the aerosol propellant, isobutane, which has refrigerant properties. T spray also contains dehydrated alcohol. When alcohol evaporates and changes from a liquid to a gaseous state, there is a reduction in SST as heat is removed from the skin’s surface. Using an ethanol alcohol in a nonaerosolized spray (A spray) as a comparator will help to determine the main mechanism of cooling as either the alcohol component (main ingredient in the A spray) versus isobutane refrigerant component (main ingredient in the T spray). Triamcinolone acetonide cream (T cream) served as the nonspray, nonpropellant comparator.
MATERIALS and METHODS
This open-label, single center, comparator study enrolled 20 adult subjects with a clinical diagnosis of either a chronic steroid-responsive dermatosis (i.e., psoriasis, atopic dermatitis, vitiligo) or an acute steroid-responsive dermatosis (i.e., atopic dermatitis, contact dermatitis, psoriasis, first-degree sunburn) with a target lesion that was assessable for severity of inflammation. Ten additional healthy control subjects were also enrolled in this study, which was held in the dermatology department at Mount Sinai School of Medicine, New York, New York, in April 2012. All patients provided written consent to participate after receiving detailed information on the purpose and design of the study. The latter was approved by the Institutional Review Board at the Mount Sinai School of Medicine. Female subjects of childbearing potential were required to have a negative urine pregnancy test result prior to study initiation. Exclusionary requirements for enrollment included subjects who were pregnant and/or nursing, those with a known hypersensitivity to any component of the study product, subjects with any visible signs of steroid over use (striae, telangiectasia, hypopigmentation, etc.), and those using any medication or having a disease that interfered with interpretation of the study. Patients with cold urticaria, cryoglobulinemia, Raynaud’s phenomena, or paroxysmal cold hemoglobulinuria were also excluded.
Of the 30 subjects, 10 were healthy controls, 10 had chronic steroid-responsive dermatoses, and 10 had acute steroid-responsive dermatoses. The 10 healthy controls had target areas that were matched to those in the diseased cohorts. At least two anatomic areas were targeted on each control to provide enough data to permit statistical analysis.
All patients applied T spray as indicated for a two-second interval, either over areas of active disease (for the acute and chronic steroid-responsive groups) or over anatomically matched areas of normal skin in the control cohort. Diseased subjects’ target lesions were required to have at least a mild severity to be included in the study. Using an infrared video camera (FLIR T400, FLIR Systems, Inc.), SST was evaluated for maximum temperature change upon application of the T spray. Subjects were evaluated in a temperature-controlled room with the camera placed a standardized distance of 25cm from the target area. Once the skin returned to its baseline temperature, this procedure was repeated with two-second application of the A spray. Once the skin returned to its baseline temperature again, this procedure was repeated with a two-second application of T cream. Statistical evaluations of the SST differences from baseline to maximum post T spray application were calculated using a two-sample of equal variance, two-tailed t-test.
Total enrollment in this clinical study was 30 patients. Slightly more than half of patients were women (56%). The average age was 40 years with ages ranging from 23 to 70 years old. The majority of patients were Caucasian (67%), followed by Asian (23%), and African American (10%). Sites of dermatoses included scalp, elbows, hands and feet, antecubita, upper and lower back, and inner aspects of the wrists and arms.
Across every study cohort, the average change in SST with T spray (average between 16–18ºC; P<0.001 for all comparisons; Figures 1 and 2) was significantly greater than the change demonstrated by both the A spray (average between 5–7ºC) and the T cream (average between 5.0–6.5ºC). The transient temperature change of nearly 20ºC or 68ºF with T spray is most likely attributable to the refrigerant properties of the isobutane propellant of this product. In the control cohort, the lowest temperature value recorded with T spray application was 7.5ºC, with an average of 12.8ºC. Both A spray and T cream did produce consistent, although non-significant changes in the SST across all groups, therefore, these components may contribute in a limited capacity to the SST changes seen when utilizing T spray.
Itch is perhaps the most prevalent manifestation of allergic and inflammatory skin diseases.[2,3] While the pathophysiology surrounding pruritus remains poorly understood, decreasing the temperature of the skin has been long shown to alleviate or abolish experimentally induced and pathologic itch. In the 1980s, Fruhstorfer et al enrolled 18 patients with atopic dermatitis into a study where each subject rated the intensity of spontaneous itch on the affected forearms before, during, and after immersion in a water bath of initial temperature of either 10ºC or 45ºC. In 40 normal controls, the same methodology was used after itch was elicited with topical histamine applied to the volar forearms. The skin area was heated or cooled by the water at a rate of 0.5ºC/sec while itch intensity was continuously evaluated. Overall, clinical and experimental itch were inhibited significantly more by cooling rather than heating.
From our common experiences, we can appreciate that temperature changes are associated with pain, burning, and itch as well as relief of these symptoms by decreasing the skin’s temperature. These effects are transmitted via primary afferent sensory neurons in the epidermis and dermis which have cells bodies located in the dorsal root ganglia. Upon stimulation, via the spinal cord and contralateral spinothothalamic tract, information is transported to “pruritus” centers, which can trigger defense responses, such as scratching.
Cryotherapy has been defined as the therapeutic cutaneous application of any material which removes heat therefrom, thereby producing a decrease in SST. The most common form of cryotherapy is ice. By inducing local anesthesia, ice has a mechanism of action that reduces pain and swelling characteristic of the inflammatory response sustained after injury.[7,8] One study revealed that topical cold treatment not only affects the skin’s surface, but extends to a depth of up to 4cm. At this depth, the cooling acts to diminish the activation threshold of tissue nociceptors and also slows the conduction velocity of pain nerve signals. Another study revealed that ice and ethyl chloride’s capacities to cool the skin to below 10ºC results in a desensitization of sensory receptors, thereby producing local anesthesia.
To place T spray’s average cryotherapy value of 12.8ºC in reference to other commonly utilized means of cryotherapy, one recent study showed that cold gel packing demonstrated surface temperature 10.6ºC, ethyl chloride cooled the temperature to 4.3ºC, and ice block rubbing changed the temperature to 3.7ºC. The cold temperature achieved by using T spray falls within the range achieved by other means of cryotherapy that have been shown to produce local anesthetic effects and could thereby relieve pruritus.
It should be noted that 0.1% T cream provides 0.100mg of triamcinolone while each gram of T spray provides 0.147mg of triamcinolone. Unfortunately, there is no commercially available triamcinolone cream formulation to match the exact microgram concentration in T spray. Therefore, the 0.1% T cream, which is the most commonly prescribed concentration, served as the closest possible steroid cream comparator and represents a limitation in this experiment. Another limitation in this study is the lack of an exact vehicle comparator, which could not be formulated in a stabilized manner by the manufacturer.
This is the first report using an infrared camera to quantitatively determine the extent to which a topical product is able to change the temperature of the skin on contact. In the future, this quantitative methodology could be applied to other topical, anti-inflammatory drugs that claim to have soothing temperature effects and even perhaps serve as a means of comparison of antipruritus efficacy. Studies into T spray’s ability to relieve edema, pain, and localized blood flow would be beneficial in understanding the anti-inflammatory properties of this medicated spray. This product was found to be safe to use in patients with either acute or chronic dermatitis and was found to be beneficial in various anatomic areas of the body that are more difficult to reach. This experiment not only provides insight into T spray’s mechanism of action on itch, but also reinforces subjective reports that T spray’s inherent cooling properties are advantageous in the management of pruritus.
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