Erythema is a common adverse effect following laser procedures involving the face and can be perceived as embarrassing or even disabling to patients.1 Management options to date have included preoperative adjustment of laser energy settings and postoperative maneuvers, including various topical preparations as well as cooling sprays, light modalities and/or dressings. These options, however, offer limited efficacy and are sometimes cumbersome such that no one alternative has been universally accepted to be optimal.
In August 2013, the FDA approved a topical formulation of brimonidine 0.33% gel (Mirvaso, Galderma Laboratories, L.P.) as the first treatment specifically indicated for facial erythema associated with rosacea in adults.2 Brimonidine is a highly selective alpha-2-adrenergic receptor agonist with potent cutaneous vasoconstrictive properties targeting vascular smooth muscle.3 It has proven to be efficacious at temporarily diminishing the appearance of erythema associated with rosacea when applied to the face on a daily basis.4 Topical use of brimonidine appears to be associated with a low incidence of generally mild adverse effects that are primarily limited to the skin.4
In this article, we share a case study utilizing brimonidine 0.33% gel applied topically following fractional ablative laser for the management of post-laser erythema (PLE).
Therapeutic Alternatives
Conservative treatments for PLE have been reported utilizing a variety of topical preparations. Emollients containing petrolatum, paraffin or mineral oil represent some of the ingredients commonly cited.1,5-7 These formulations have the advantage of helping to restore an external barrier after epithelial disruption following fractional laser. They can prevent excessive moisture loss and provide a barrier against infection without posing a high risk for sensitization. Cosmetically, however, these preparations are greasy and there use can be associated with acneiform eruptions. Interestingly, topical vitamin C has also been reported in 1 study to be associated with improvement in PLE when applied in an aqueous vehicle, but not when applied in a cream emollient.8
The use of sunscreen agents following fractional laser is also common. Generally, these products are applied following reepithelialization with the intent of preventing hyperpigmentation and erythema — both of which may be exacerbated by ultraviolet light exposure. Following laser procedures the skin may be more vulnerable to ultraviolet sources likely due to lower levels of keratinization and reduced melanin content. For optimal effectiveness, however, sunscreens need to be applied every few hours. Additionally, although the incidence of hyperpigmentation may be reduced, in 1 study erythema levels were reported to remain unaltered.8
Antibacterial ointments have been touted as beneficial in promoting early healing and preventing infection. These properties may likewise be beneficial in minimizing the redness following laser procedures. Currently, there is a paucity of literature regarding the potential risks or benefits of using topical antibiotics on laser resurfaced skin. Even the possibility of clearing staphylococcal nasal carriage with mupirocin prior to laser resurfacing to decrease potential skin infections remains debatable.9,10 Prophylactic use of topical antibiotics may also be associated with increased risk of developing hypersensitivity or even bacterial resistance.
Use of topical steroids, such as hydrocortisone 1% cream, has also been advocated for reducing PLE.5 Steroids remain somewhat controversial as they can potentiate infection, produce tachyphylaxis or even trigger rebound erythema with prolonged use.
One split-face trial described the application of spring water (Avène, Pierre Fabre Dermo-Cosmetique) following ablative fractional laser. In this study, the water was sprayed 10 times per minute over 10 minutes followed by the application of an emollient cream. Further spray applications were allowed after discharge. Visual self-assessment scales recorded at 10 minutes and 48 hours post-procedure demonstrated a modest, but significant improvement in erythema as well as other parameters such as pain and dryness.11
At least 2 reports in the literature describe the utilization of light sources (dual 405-420 nm plus 850-900 nm or 635 nm alone) applied following ablative laser to reduce erythema. Modest treatment associated reductions in PLE were noted in both studies. A disadvantage included that patients were required to attend suitably equipped medical facilities for 15- to 20-minute treatment sessions. They also had to participate on at least 6 or 7 consecutive days to achieve these results.12,13
Finally, dressings are not uncommonly employed following fractional ablative laser procedures. Certain semi-occlusive dressings, such as hydrocolloid gels, have been described to be advantageous in promoting wound healing from superficial burn injuries.14 Similarly, early use of dressings during the first 2 or 3 days following laser resurfacing may increase patient comfort, while reducing anxiety and promoting reepithelialization.15 Occlusive silicone dressings in particular have been specifically reported to reduce the severity and duration of PLE.16 Though dressings generally deliver a straightforward and effective method for providing wound care, their application can be cumbersome and their use may be associated with significant additional cost.
Case Report: Brimonidine Application to Decrease PLE
Our 38-year-old male patient presented for ablative fractional carbon dioxide (CO2) laser resurfacing for indications, including photoaging and dyspigmentation. He was treated utilizing the Lumenis UltraPulse CO2 (Lumenis Aesthetic) laser set to deliver a fractional ablative laser pattern. After the procedure, the treated areas were covered in a thin layer of petrolatum followed by the application of a dressing over 4 days.
Once the dressing was removed, his face was inspected to be sure full re-epithelialization had taken place. At this time, confluent PLE was found to be evenly affecting both sides of the patient’s face. Treatment options were discussed. The patient consented to receive split-face treatment utilizing only petrolatum on the right side as a control and applying brimonidine 0.33% gel to the left side. Digital photographs were captured 30 minutes following treatment application on day 1 (Figures 1-3).
Figure 1. Thirty minutes post-treatment. Split-face: frontal view. Control (right) vs treated.
Figure 2. Split-face: right lateral view. Right-side: control (petrolatum only).
Figure 3. Split-face: left lateral view. Left-side: treated with brimonidine 0.33%.
Discussion
In our patient, the application of brimonidine 0.33% gel resulted in a notable reduction in PLE as demonstrated in the split-face photos 30 minutes following application. The patient was pleased with the initial effects and chose to continue to apply brimonidine on a daily basis to his full face over a subsequent 2-week period. He reported only a minor tingling feeling following application of the product. This sensation was transient and resolved without intervention after approximately 10 to 15 minutes.
Similar to the data utilizing brimonidine in rosacea, our patient reported the duration of erythema reduction was approximately 12 hours. The patient elected to discontinue use of brimonidine gel after 14 days as he reported his PLE had subsided significantly by that time.
Given the paucity of convenient and efficacious alternatives, it would appear that topical brimonidine represents a promising novel therapy for PLE. This unique therapeutic alternative may be particularly appropriate for men who are generally less comfortable utilizing “redness cover-up” cosmetics (often green-tinted) that are available over-the-counter.
As noted, our patient experienced only minimal self-limited adverse skin sensations following brimonidine application. This is in keeping with the majority of the available data on topical use of brimonidine on the skin. Several small trials have noted predominantly transient skin-related side effects including irritation, erythema, burning sensation, dryness and pruritus. Importantly, rebound erythema and tachyphylaxis have generally not been problematic in these early trials with topical use of brimonidine on the skin for up to 28 days.3 As a cautionary note, a publication containing a few more recent case reports speculated that several adverse effects may be more common in clinical use than suggested in the initial trials. Noted side effects included erythema worse than baseline, flushing and burning.17
It is prudent to also keep in mind that brimonidine was initially approved by the FDA in 1996 as a topical treatment for open-angle glaucoma.18 Intraocular use of this preparation was uncommonly associated with systemic effects including hypotension. Reassuringly, however, the relative bioavailability of brimonidine up to a concentration of even 0.5% when applied topically on rosacea affected skin is very low (about 5%-9%) compared to brimonidine 0.1% drops instilled directly onto the conjunctiva of the eyes. When utilizing brimonidine for PLE, however, one must consider that bioavailability may vary because the drug is being applied to patients whose skin barrier function may still be recovering following fractional laser ablation. Notably, evidence in mice supports the assertion that significant recovery of barrier function to drug diffusion has already occurred by day 2 or 3 following CO2 fractional ablation.19
Patient Outcome
Our patient experienced a significant reduction in PLE within minutes after applying brimonidine 0.33% gel topically. By his report, this product diminished erythema quite consistently over approximately 12 hours following its initial application. This allowed our patient to return to work within 5 days without concern for what might otherwise have been considered to be disconcerting levels of PLE.
The daily use of brimonidine 0.33% gel for PLE in our patient over 2 weeks was well-tolerated. He noted only transient facial “tingling” subsequent to application and there were no clinically apparent systemic adverse effects.
Conclusion
Persistent erythema following laser procedures can be both a vexing problem for patients and a difficult management dilemma for treating physicians. Immediate erythema following fractional laser is an expected consequence that generally resolves after several days. Prolonged erythema, however, has been defined as that which persists at least 4 weeks beyond the time of the procedure. Such protracted PLE has been reported to affect about 12.5% of those undergoing these procedures and can persist for 3 months or more.20 As the popularity of fractional ablative laser procedures continues to increase, finding a more universally accepted management for PLE is an important consideration. In this case study, the use of topical brimonidine gel provided a convenient therapy that effectively reduced PLE in our patient. Moreover, this therapy allowed our patient to comfortably return to social function and employment earlier than he may have otherwise.
Additional study is warranted to confirm these findings and further evaluate the safety and efficacy of brimonidine for PLE. Topically applied, this preparation appears particularly promising for those patients with persistent PLE who are uncomfortable with cosmetic cover-ups or find their condition to be prolonged or recalcitrant to other interventions.
Dr. Torres is a practicing dermatologist at Affiliated Dermatologists in Morristown, NJ, as well as a Mohs and cosmetic surgeon. He also teaches Mohs and cosmetic surgery in a Procedural Dermatology Fellowship accredited by the Accreditation Council for Graduate Medical Education (ACGME).
Dr. Lortie is a procedural dermatology Mohs surgery fellow at Affiliated Dermatologists in Morristown, NJ.
Dr. Rogachefsky is a practicing dermatologist and the Program Director of the ACGME-approved Procedural Dermatology Fellowship at Affiliated Dermatologists & Dermatologist Surgeons in Morristown, NJ.
Disclosure: The authors report no relevant financial relationships.
References
1. Nanni CA, Alster TS. Complications of carbon dioxide laser. Dermatol Surg. 1998;24(3):315-320.
2. Galderma receives FDA approval of Mirvaso [news release]. Fort Worth, TX: Galderma Laboratories, L.P.; August 26, 2013. https://www.galderma.com/Media/Press-releases/articleType/ArticleView/articleId/41/Galderma-Receives-FDA-Approval-of-Mirvaso. Accessed June 21, 2014.
3. Fowler J, Jarratt M, Moore A, et al. Once-daily brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema: Results of two multicentre, randomized and vehicle controlled studies. Br. J. Dermatol. 2012;166(3):633-641.
4. Fowler J Jr, Jackson M, Moore A, et al. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies. J Drugs Dermatol. 2013;12(6):650-656.
5. Weinsein C, Ramirez OM, Posner JN. Postoperative care following CO2 laser resurfacing: avoiding pitfalls. Plast Reconstr Surg.1997;100(7):1855-1866.
6. Sullivan SA, Dailey RA. Complications of laser resurfacing and their management. Ophthal Plast Reconstr Surg. 2000;16(6):417-426.
7. Tanzi EL, Alster TS. Single-pass carbon dioxide versus multiple-pass Er:YAG laser skin resurfacing: a comparison of postoperative wound healing and side-effect rates. Dermatol Surg. 2003;29(1):80-84.
8. Wanitphakdeedecha R, Phuardchantuk R, Manuskiatti W. The use of sunscreen starting on the first day after ablative fractional skin resurfacing. J Eur Acad Dermatol Venereol. Published online ahead of print December 10, 2013.
9. Bellman B, Brnadt FS, Holtmann M, Bebell WR. Infection with methicillin-resistant Staphylococcus aureus after carbon dioxide resurfacing of the face. Successful treatment with minocycline, rifampin, and mupiricin ointment. Dermatol Surg. 1998;24(2):279-882.
10. Manuskiatti W, Fitzpatrick RE, Goldman MP, Krejci-Papa N. Prophylactic antibiotics in patients undergoing laser resurfacing of the skin. J Am Acad Dermatol. 1999;40(1):77-84.
11. Sulimovic L, Licu D, Ledo E, et al. Efficacy and safety of a topically applied Avène spring water spray in the healing of facial skin after laser resurfacing. Dermatol Surg. 2002;28(5):415-418.
12. Trelles M, Elman M, Slatkine M, Harth Y. Accelerated reduction of post-skin-resurfacing erythema and discomfort with a combination of non-thermal blue and near infrared light. J Cosmet Laser Ther. 2005;7(2):93-96.
13. Oh IY, Kim BJ, Kim MN, Kim CW, Kim SE. Efficacy of light-emitting dioide photomodulation in reducing erythema after fractional carbon dioxide laser resurfacing: a pilot study. Dermatol Surg. 2013;39(8):1171-1176.
14. Wasiak J, Cleland H, Campbell F, Spinks A. Dressings for superficial and partial thickness burns. Cochrane Database Syst Rev. 2013;3:CD002106.
15. Newman JP, Fitzgerald P, Koch RJ. Review of closed dressing after laser resurfacing. Dermatol Surg. 2000;26(6):562-571.
16. Batra RS, Ort RJ, Jacob C, Hobbs L, Arndt KA, Dover JS, Evaluation of a silicone occlusive dressing after laser skin resurfacing. Arch Dermatol. 2001;137(10):1317-1321.
17. Routt ET, Levitt JO. Rebound erythema and burning from a new topical brimonidine tartrate gel 0.33%. J Am Acad Dermatol. 2014;70(2):e37-e38.
18. Benkali K, Leoni M, Rony F, et al. Comparative pharmacokinetics and bioavailability of brimonidine following ocular administration and dermal application of brimonidine tartrate ophthalmic solution and gel in subjects with moderate to severe facial erythema of rosacea. Br J Dermatol. Published online ahead of print February 7, 2014.
19. Chen WY, Fang CL, Al-Suwayeh SA, Yang HH, Li YC, Fang JY. Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing: optimization of the applied dose for postoperative care. Lasers Med Sci. 2013;28(5):1363-1374.
20. Metelisa AI, Alster TS. Fractionated laser skin resurfacing treatment complications: a review. Dermatol Surg. 2010;36(3):299-306.
Erythema is a common adverse effect following laser procedures involving the face and can be perceived as embarrassing or even disabling to patients.1 Management options to date have included preoperative adjustment of laser energy settings and postoperative maneuvers, including various topical preparations as well as cooling sprays, light modalities and/or dressings. These options, however, offer limited efficacy and are sometimes cumbersome such that no one alternative has been universally accepted to be optimal.
In August 2013, the FDA approved a topical formulation of brimonidine 0.33% gel (Mirvaso, Galderma Laboratories, L.P.) as the first treatment specifically indicated for facial erythema associated with rosacea in adults.2 Brimonidine is a highly selective alpha-2-adrenergic receptor agonist with potent cutaneous vasoconstrictive properties targeting vascular smooth muscle.3 It has proven to be efficacious at temporarily diminishing the appearance of erythema associated with rosacea when applied to the face on a daily basis.4 Topical use of brimonidine appears to be associated with a low incidence of generally mild adverse effects that are primarily limited to the skin.4
In this article, we share a case study utilizing brimonidine 0.33% gel applied topically following fractional ablative laser for the management of post-laser erythema (PLE).
Therapeutic Alternatives
Conservative treatments for PLE have been reported utilizing a variety of topical preparations. Emollients containing petrolatum, paraffin or mineral oil represent some of the ingredients commonly cited.1,5-7 These formulations have the advantage of helping to restore an external barrier after epithelial disruption following fractional laser. They can prevent excessive moisture loss and provide a barrier against infection without posing a high risk for sensitization. Cosmetically, however, these preparations are greasy and there use can be associated with acneiform eruptions. Interestingly, topical vitamin C has also been reported in 1 study to be associated with improvement in PLE when applied in an aqueous vehicle, but not when applied in a cream emollient.8
The use of sunscreen agents following fractional laser is also common. Generally, these products are applied following reepithelialization with the intent of preventing hyperpigmentation and erythema — both of which may be exacerbated by ultraviolet light exposure. Following laser procedures the skin may be more vulnerable to ultraviolet sources likely due to lower levels of keratinization and reduced melanin content. For optimal effectiveness, however, sunscreens need to be applied every few hours. Additionally, although the incidence of hyperpigmentation may be reduced, in 1 study erythema levels were reported to remain unaltered.8
Antibacterial ointments have been touted as beneficial in promoting early healing and preventing infection. These properties may likewise be beneficial in minimizing the redness following laser procedures. Currently, there is a paucity of literature regarding the potential risks or benefits of using topical antibiotics on laser resurfaced skin. Even the possibility of clearing staphylococcal nasal carriage with mupirocin prior to laser resurfacing to decrease potential skin infections remains debatable.9,10 Prophylactic use of topical antibiotics may also be associated with increased risk of developing hypersensitivity or even bacterial resistance.
Use of topical steroids, such as hydrocortisone 1% cream, has also been advocated for reducing PLE.5 Steroids remain somewhat controversial as they can potentiate infection, produce tachyphylaxis or even trigger rebound erythema with prolonged use.
One split-face trial described the application of spring water (Avène, Pierre Fabre Dermo-Cosmetique) following ablative fractional laser. In this study, the water was sprayed 10 times per minute over 10 minutes followed by the application of an emollient cream. Further spray applications were allowed after discharge. Visual self-assessment scales recorded at 10 minutes and 48 hours post-procedure demonstrated a modest, but significant improvement in erythema as well as other parameters such as pain and dryness.11
At least 2 reports in the literature describe the utilization of light sources (dual 405-420 nm plus 850-900 nm or 635 nm alone) applied following ablative laser to reduce erythema. Modest treatment associated reductions in PLE were noted in both studies. A disadvantage included that patients were required to attend suitably equipped medical facilities for 15- to 20-minute treatment sessions. They also had to participate on at least 6 or 7 consecutive days to achieve these results.12,13
Finally, dressings are not uncommonly employed following fractional ablative laser procedures. Certain semi-occlusive dressings, such as hydrocolloid gels, have been described to be advantageous in promoting wound healing from superficial burn injuries.14 Similarly, early use of dressings during the first 2 or 3 days following laser resurfacing may increase patient comfort, while reducing anxiety and promoting reepithelialization.15 Occlusive silicone dressings in particular have been specifically reported to reduce the severity and duration of PLE.16 Though dressings generally deliver a straightforward and effective method for providing wound care, their application can be cumbersome and their use may be associated with significant additional cost.
Case Report: Brimonidine Application to Decrease PLE
Our 38-year-old male patient presented for ablative fractional carbon dioxide (CO2) laser resurfacing for indications, including photoaging and dyspigmentation. He was treated utilizing the Lumenis UltraPulse CO2 (Lumenis Aesthetic) laser set to deliver a fractional ablative laser pattern. After the procedure, the treated areas were covered in a thin layer of petrolatum followed by the application of a dressing over 4 days.
Once the dressing was removed, his face was inspected to be sure full re-epithelialization had taken place. At this time, confluent PLE was found to be evenly affecting both sides of the patient’s face. Treatment options were discussed. The patient consented to receive split-face treatment utilizing only petrolatum on the right side as a control and applying brimonidine 0.33% gel to the left side. Digital photographs were captured 30 minutes following treatment application on day 1 (Figures 1-3).
Figure 1. Thirty minutes post-treatment. Split-face: frontal view. Control (right) vs treated.
Figure 2. Split-face: right lateral view. Right-side: control (petrolatum only).
Figure 3. Split-face: left lateral view. Left-side: treated with brimonidine 0.33%.
Discussion
In our patient, the application of brimonidine 0.33% gel resulted in a notable reduction in PLE as demonstrated in the split-face photos 30 minutes following application. The patient was pleased with the initial effects and chose to continue to apply brimonidine on a daily basis to his full face over a subsequent 2-week period. He reported only a minor tingling feeling following application of the product. This sensation was transient and resolved without intervention after approximately 10 to 15 minutes.
Similar to the data utilizing brimonidine in rosacea, our patient reported the duration of erythema reduction was approximately 12 hours. The patient elected to discontinue use of brimonidine gel after 14 days as he reported his PLE had subsided significantly by that time.
Given the paucity of convenient and efficacious alternatives, it would appear that topical brimonidine represents a promising novel therapy for PLE. This unique therapeutic alternative may be particularly appropriate for men who are generally less comfortable utilizing “redness cover-up” cosmetics (often green-tinted) that are available over-the-counter.
As noted, our patient experienced only minimal self-limited adverse skin sensations following brimonidine application. This is in keeping with the majority of the available data on topical use of brimonidine on the skin. Several small trials have noted predominantly transient skin-related side effects including irritation, erythema, burning sensation, dryness and pruritus. Importantly, rebound erythema and tachyphylaxis have generally not been problematic in these early trials with topical use of brimonidine on the skin for up to 28 days.3 As a cautionary note, a publication containing a few more recent case reports speculated that several adverse effects may be more common in clinical use than suggested in the initial trials. Noted side effects included erythema worse than baseline, flushing and burning.17
It is prudent to also keep in mind that brimonidine was initially approved by the FDA in 1996 as a topical treatment for open-angle glaucoma.18 Intraocular use of this preparation was uncommonly associated with systemic effects including hypotension. Reassuringly, however, the relative bioavailability of brimonidine up to a concentration of even 0.5% when applied topically on rosacea affected skin is very low (about 5%-9%) compared to brimonidine 0.1% drops instilled directly onto the conjunctiva of the eyes. When utilizing brimonidine for PLE, however, one must consider that bioavailability may vary because the drug is being applied to patients whose skin barrier function may still be recovering following fractional laser ablation. Notably, evidence in mice supports the assertion that significant recovery of barrier function to drug diffusion has already occurred by day 2 or 3 following CO2 fractional ablation.19
Patient Outcome
Our patient experienced a significant reduction in PLE within minutes after applying brimonidine 0.33% gel topically. By his report, this product diminished erythema quite consistently over approximately 12 hours following its initial application. This allowed our patient to return to work within 5 days without concern for what might otherwise have been considered to be disconcerting levels of PLE.
The daily use of brimonidine 0.33% gel for PLE in our patient over 2 weeks was well-tolerated. He noted only transient facial “tingling” subsequent to application and there were no clinically apparent systemic adverse effects.
Conclusion
Persistent erythema following laser procedures can be both a vexing problem for patients and a difficult management dilemma for treating physicians. Immediate erythema following fractional laser is an expected consequence that generally resolves after several days. Prolonged erythema, however, has been defined as that which persists at least 4 weeks beyond the time of the procedure. Such protracted PLE has been reported to affect about 12.5% of those undergoing these procedures and can persist for 3 months or more.20 As the popularity of fractional ablative laser procedures continues to increase, finding a more universally accepted management for PLE is an important consideration. In this case study, the use of topical brimonidine gel provided a convenient therapy that effectively reduced PLE in our patient. Moreover, this therapy allowed our patient to comfortably return to social function and employment earlier than he may have otherwise.
Additional study is warranted to confirm these findings and further evaluate the safety and efficacy of brimonidine for PLE. Topically applied, this preparation appears particularly promising for those patients with persistent PLE who are uncomfortable with cosmetic cover-ups or find their condition to be prolonged or recalcitrant to other interventions.
Dr. Torres is a practicing dermatologist at Affiliated Dermatologists in Morristown, NJ, as well as a Mohs and cosmetic surgeon. He also teaches Mohs and cosmetic surgery in a Procedural Dermatology Fellowship accredited by the Accreditation Council for Graduate Medical Education (ACGME).
Dr. Lortie is a procedural dermatology Mohs surgery fellow at Affiliated Dermatologists in Morristown, NJ.
Dr. Rogachefsky is a practicing dermatologist and the Program Director of the ACGME-approved Procedural Dermatology Fellowship at Affiliated Dermatologists & Dermatologist Surgeons in Morristown, NJ.
Disclosure: The authors report no relevant financial relationships.
References
1. Nanni CA, Alster TS. Complications of carbon dioxide laser. Dermatol Surg. 1998;24(3):315-320.
2. Galderma receives FDA approval of Mirvaso [news release]. Fort Worth, TX: Galderma Laboratories, L.P.; August 26, 2013. https://www.galderma.com/Media/Press-releases/articleType/ArticleView/articleId/41/Galderma-Receives-FDA-Approval-of-Mirvaso. Accessed June 21, 2014.
3. Fowler J, Jarratt M, Moore A, et al. Once-daily brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema: Results of two multicentre, randomized and vehicle controlled studies. Br. J. Dermatol. 2012;166(3):633-641.
4. Fowler J Jr, Jackson M, Moore A, et al. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies. J Drugs Dermatol. 2013;12(6):650-656.
5. Weinsein C, Ramirez OM, Posner JN. Postoperative care following CO2 laser resurfacing: avoiding pitfalls. Plast Reconstr Surg.1997;100(7):1855-1866.
6. Sullivan SA, Dailey RA. Complications of laser resurfacing and their management. Ophthal Plast Reconstr Surg. 2000;16(6):417-426.
7. Tanzi EL, Alster TS. Single-pass carbon dioxide versus multiple-pass Er:YAG laser skin resurfacing: a comparison of postoperative wound healing and side-effect rates. Dermatol Surg. 2003;29(1):80-84.
8. Wanitphakdeedecha R, Phuardchantuk R, Manuskiatti W. The use of sunscreen starting on the first day after ablative fractional skin resurfacing. J Eur Acad Dermatol Venereol. Published online ahead of print December 10, 2013.
9. Bellman B, Brnadt FS, Holtmann M, Bebell WR. Infection with methicillin-resistant Staphylococcus aureus after carbon dioxide resurfacing of the face. Successful treatment with minocycline, rifampin, and mupiricin ointment. Dermatol Surg. 1998;24(2):279-882.
10. Manuskiatti W, Fitzpatrick RE, Goldman MP, Krejci-Papa N. Prophylactic antibiotics in patients undergoing laser resurfacing of the skin. J Am Acad Dermatol. 1999;40(1):77-84.
11. Sulimovic L, Licu D, Ledo E, et al. Efficacy and safety of a topically applied Avène spring water spray in the healing of facial skin after laser resurfacing. Dermatol Surg. 2002;28(5):415-418.
12. Trelles M, Elman M, Slatkine M, Harth Y. Accelerated reduction of post-skin-resurfacing erythema and discomfort with a combination of non-thermal blue and near infrared light. J Cosmet Laser Ther. 2005;7(2):93-96.
13. Oh IY, Kim BJ, Kim MN, Kim CW, Kim SE. Efficacy of light-emitting dioide photomodulation in reducing erythema after fractional carbon dioxide laser resurfacing: a pilot study. Dermatol Surg. 2013;39(8):1171-1176.
14. Wasiak J, Cleland H, Campbell F, Spinks A. Dressings for superficial and partial thickness burns. Cochrane Database Syst Rev. 2013;3:CD002106.
15. Newman JP, Fitzgerald P, Koch RJ. Review of closed dressing after laser resurfacing. Dermatol Surg. 2000;26(6):562-571.
16. Batra RS, Ort RJ, Jacob C, Hobbs L, Arndt KA, Dover JS, Evaluation of a silicone occlusive dressing after laser skin resurfacing. Arch Dermatol. 2001;137(10):1317-1321.
17. Routt ET, Levitt JO. Rebound erythema and burning from a new topical brimonidine tartrate gel 0.33%. J Am Acad Dermatol. 2014;70(2):e37-e38.
18. Benkali K, Leoni M, Rony F, et al. Comparative pharmacokinetics and bioavailability of brimonidine following ocular administration and dermal application of brimonidine tartrate ophthalmic solution and gel in subjects with moderate to severe facial erythema of rosacea. Br J Dermatol. Published online ahead of print February 7, 2014.
19. Chen WY, Fang CL, Al-Suwayeh SA, Yang HH, Li YC, Fang JY. Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing: optimization of the applied dose for postoperative care. Lasers Med Sci. 2013;28(5):1363-1374.
20. Metelisa AI, Alster TS. Fractionated laser skin resurfacing treatment complications: a review. Dermatol Surg. 2010;36(3):299-306.
Erythema is a common adverse effect following laser procedures involving the face and can be perceived as embarrassing or even disabling to patients.1 Management options to date have included preoperative adjustment of laser energy settings and postoperative maneuvers, including various topical preparations as well as cooling sprays, light modalities and/or dressings. These options, however, offer limited efficacy and are sometimes cumbersome such that no one alternative has been universally accepted to be optimal.
In August 2013, the FDA approved a topical formulation of brimonidine 0.33% gel (Mirvaso, Galderma Laboratories, L.P.) as the first treatment specifically indicated for facial erythema associated with rosacea in adults.2 Brimonidine is a highly selective alpha-2-adrenergic receptor agonist with potent cutaneous vasoconstrictive properties targeting vascular smooth muscle.3 It has proven to be efficacious at temporarily diminishing the appearance of erythema associated with rosacea when applied to the face on a daily basis.4 Topical use of brimonidine appears to be associated with a low incidence of generally mild adverse effects that are primarily limited to the skin.4
In this article, we share a case study utilizing brimonidine 0.33% gel applied topically following fractional ablative laser for the management of post-laser erythema (PLE).
Therapeutic Alternatives
Conservative treatments for PLE have been reported utilizing a variety of topical preparations. Emollients containing petrolatum, paraffin or mineral oil represent some of the ingredients commonly cited.1,5-7 These formulations have the advantage of helping to restore an external barrier after epithelial disruption following fractional laser. They can prevent excessive moisture loss and provide a barrier against infection without posing a high risk for sensitization. Cosmetically, however, these preparations are greasy and there use can be associated with acneiform eruptions. Interestingly, topical vitamin C has also been reported in 1 study to be associated with improvement in PLE when applied in an aqueous vehicle, but not when applied in a cream emollient.8
The use of sunscreen agents following fractional laser is also common. Generally, these products are applied following reepithelialization with the intent of preventing hyperpigmentation and erythema — both of which may be exacerbated by ultraviolet light exposure. Following laser procedures the skin may be more vulnerable to ultraviolet sources likely due to lower levels of keratinization and reduced melanin content. For optimal effectiveness, however, sunscreens need to be applied every few hours. Additionally, although the incidence of hyperpigmentation may be reduced, in 1 study erythema levels were reported to remain unaltered.8
Antibacterial ointments have been touted as beneficial in promoting early healing and preventing infection. These properties may likewise be beneficial in minimizing the redness following laser procedures. Currently, there is a paucity of literature regarding the potential risks or benefits of using topical antibiotics on laser resurfaced skin. Even the possibility of clearing staphylococcal nasal carriage with mupirocin prior to laser resurfacing to decrease potential skin infections remains debatable.9,10 Prophylactic use of topical antibiotics may also be associated with increased risk of developing hypersensitivity or even bacterial resistance.
Use of topical steroids, such as hydrocortisone 1% cream, has also been advocated for reducing PLE.5 Steroids remain somewhat controversial as they can potentiate infection, produce tachyphylaxis or even trigger rebound erythema with prolonged use.
One split-face trial described the application of spring water (Avène, Pierre Fabre Dermo-Cosmetique) following ablative fractional laser. In this study, the water was sprayed 10 times per minute over 10 minutes followed by the application of an emollient cream. Further spray applications were allowed after discharge. Visual self-assessment scales recorded at 10 minutes and 48 hours post-procedure demonstrated a modest, but significant improvement in erythema as well as other parameters such as pain and dryness.11
At least 2 reports in the literature describe the utilization of light sources (dual 405-420 nm plus 850-900 nm or 635 nm alone) applied following ablative laser to reduce erythema. Modest treatment associated reductions in PLE were noted in both studies. A disadvantage included that patients were required to attend suitably equipped medical facilities for 15- to 20-minute treatment sessions. They also had to participate on at least 6 or 7 consecutive days to achieve these results.12,13
Finally, dressings are not uncommonly employed following fractional ablative laser procedures. Certain semi-occlusive dressings, such as hydrocolloid gels, have been described to be advantageous in promoting wound healing from superficial burn injuries.14 Similarly, early use of dressings during the first 2 or 3 days following laser resurfacing may increase patient comfort, while reducing anxiety and promoting reepithelialization.15 Occlusive silicone dressings in particular have been specifically reported to reduce the severity and duration of PLE.16 Though dressings generally deliver a straightforward and effective method for providing wound care, their application can be cumbersome and their use may be associated with significant additional cost.
Case Report: Brimonidine Application to Decrease PLE
Our 38-year-old male patient presented for ablative fractional carbon dioxide (CO2) laser resurfacing for indications, including photoaging and dyspigmentation. He was treated utilizing the Lumenis UltraPulse CO2 (Lumenis Aesthetic) laser set to deliver a fractional ablative laser pattern. After the procedure, the treated areas were covered in a thin layer of petrolatum followed by the application of a dressing over 4 days.
Once the dressing was removed, his face was inspected to be sure full re-epithelialization had taken place. At this time, confluent PLE was found to be evenly affecting both sides of the patient’s face. Treatment options were discussed. The patient consented to receive split-face treatment utilizing only petrolatum on the right side as a control and applying brimonidine 0.33% gel to the left side. Digital photographs were captured 30 minutes following treatment application on day 1 (Figures 1-3).
Figure 1. Thirty minutes post-treatment. Split-face: frontal view. Control (right) vs treated.
Figure 2. Split-face: right lateral view. Right-side: control (petrolatum only).
Figure 3. Split-face: left lateral view. Left-side: treated with brimonidine 0.33%.
Discussion
In our patient, the application of brimonidine 0.33% gel resulted in a notable reduction in PLE as demonstrated in the split-face photos 30 minutes following application. The patient was pleased with the initial effects and chose to continue to apply brimonidine on a daily basis to his full face over a subsequent 2-week period. He reported only a minor tingling feeling following application of the product. This sensation was transient and resolved without intervention after approximately 10 to 15 minutes.
Similar to the data utilizing brimonidine in rosacea, our patient reported the duration of erythema reduction was approximately 12 hours. The patient elected to discontinue use of brimonidine gel after 14 days as he reported his PLE had subsided significantly by that time.
Given the paucity of convenient and efficacious alternatives, it would appear that topical brimonidine represents a promising novel therapy for PLE. This unique therapeutic alternative may be particularly appropriate for men who are generally less comfortable utilizing “redness cover-up” cosmetics (often green-tinted) that are available over-the-counter.
As noted, our patient experienced only minimal self-limited adverse skin sensations following brimonidine application. This is in keeping with the majority of the available data on topical use of brimonidine on the skin. Several small trials have noted predominantly transient skin-related side effects including irritation, erythema, burning sensation, dryness and pruritus. Importantly, rebound erythema and tachyphylaxis have generally not been problematic in these early trials with topical use of brimonidine on the skin for up to 28 days.3 As a cautionary note, a publication containing a few more recent case reports speculated that several adverse effects may be more common in clinical use than suggested in the initial trials. Noted side effects included erythema worse than baseline, flushing and burning.17
It is prudent to also keep in mind that brimonidine was initially approved by the FDA in 1996 as a topical treatment for open-angle glaucoma.18 Intraocular use of this preparation was uncommonly associated with systemic effects including hypotension. Reassuringly, however, the relative bioavailability of brimonidine up to a concentration of even 0.5% when applied topically on rosacea affected skin is very low (about 5%-9%) compared to brimonidine 0.1% drops instilled directly onto the conjunctiva of the eyes. When utilizing brimonidine for PLE, however, one must consider that bioavailability may vary because the drug is being applied to patients whose skin barrier function may still be recovering following fractional laser ablation. Notably, evidence in mice supports the assertion that significant recovery of barrier function to drug diffusion has already occurred by day 2 or 3 following CO2 fractional ablation.19
Patient Outcome
Our patient experienced a significant reduction in PLE within minutes after applying brimonidine 0.33% gel topically. By his report, this product diminished erythema quite consistently over approximately 12 hours following its initial application. This allowed our patient to return to work within 5 days without concern for what might otherwise have been considered to be disconcerting levels of PLE.
The daily use of brimonidine 0.33% gel for PLE in our patient over 2 weeks was well-tolerated. He noted only transient facial “tingling” subsequent to application and there were no clinically apparent systemic adverse effects.
Conclusion
Persistent erythema following laser procedures can be both a vexing problem for patients and a difficult management dilemma for treating physicians. Immediate erythema following fractional laser is an expected consequence that generally resolves after several days. Prolonged erythema, however, has been defined as that which persists at least 4 weeks beyond the time of the procedure. Such protracted PLE has been reported to affect about 12.5% of those undergoing these procedures and can persist for 3 months or more.20 As the popularity of fractional ablative laser procedures continues to increase, finding a more universally accepted management for PLE is an important consideration. In this case study, the use of topical brimonidine gel provided a convenient therapy that effectively reduced PLE in our patient. Moreover, this therapy allowed our patient to comfortably return to social function and employment earlier than he may have otherwise.
Additional study is warranted to confirm these findings and further evaluate the safety and efficacy of brimonidine for PLE. Topically applied, this preparation appears particularly promising for those patients with persistent PLE who are uncomfortable with cosmetic cover-ups or find their condition to be prolonged or recalcitrant to other interventions.
Dr. Torres is a practicing dermatologist at Affiliated Dermatologists in Morristown, NJ, as well as a Mohs and cosmetic surgeon. He also teaches Mohs and cosmetic surgery in a Procedural Dermatology Fellowship accredited by the Accreditation Council for Graduate Medical Education (ACGME).
Dr. Lortie is a procedural dermatology Mohs surgery fellow at Affiliated Dermatologists in Morristown, NJ.
Dr. Rogachefsky is a practicing dermatologist and the Program Director of the ACGME-approved Procedural Dermatology Fellowship at Affiliated Dermatologists & Dermatologist Surgeons in Morristown, NJ.
Disclosure: The authors report no relevant financial relationships.
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