Combination Treatment of Melasma with Pulsed CO2 Laser Followed ...

BOOKREPORT CASE REVIEW

Combination Treatment of Melasma with Pulsed CO2 Laser Followed by Q-Switched Alexandrite Laser: A Pilot Study Keyvan Nouri, MD, Leyda Bowes, MD, Tim Chartier, MD, Ricardo Romagosa, BS, and James Spencer, MD, MS Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida

background. Melasma is very difficult to treat and often refractory to treatment with topical creams and pigmented-lesion lasers. objective. Pulsed CO2 laser alone is compared with the combination of pulsed CO2 laser followed by Q-switched alexandrite laser in the treatment of dermal-type melasma. This combination is proposed to be effective by first destroying the abnormal melanocytes with the pulsed CO2 laser and then selectively eliminating the dermal melanin with the alexandrite laser. methods. Four patients were randomly chosen for each treat-

ment arm. There were multiple follow-up visits for examination by an objective blinded investigator. results. All patients in the combination laser group showed complete resolution, and two patients in the CO2 laser only group had peripheral hyperpigmentation in the long-term follow-up evaluation. conclusion. These laser therapies are safe, as there was no scarring and no infection. The combination laser therapy was highly effective in removing the hyperpigmentation and all patients in this group showed complete resolution without any peripheral hyperpigmentation.

MELASMA IS A COMMON acquired symmetric hypermelanosis that is most commonly seen on the sunexposed areas of the face in women of childbearing age. This patchy macular condition is very difficult to treat and often refractory to treatment with topical creams and pigmented-lesion lasers. In the past, attempts to treat melasma with lasers that specifically target melanin, such as the 510 nm pigmented lesion dye, ruby, alexandrite, and Nd:YAG, have yielded disappointing results.1–4 Treatment of melasma with lasers has been considered to be ineffective. At this time, lasers are being used successfully to treat other pigmented lesions such as lentigenes, café au lait spots, and nevi of Ota. The common denominator of melasma, whatever the pathophysiology, is an increased number and activity of melanocytes resulting in a large amount of melanosome transfer to the epidermis and dermis.5 The clinical characteristics of this condition vary according to the location of the increase in melanin. The deeper the melanin, the more difficult it is to treat. Wood’s lamp examination of this condition helps to distinguish between epidermal and dermal melasma.5 This is impor-

tant because more superficial pigmentation is much easier to treat with topical therapy. Dermal melasma has not been successfully treated with any topical regiments. This is probably due to the fact that the dermal pigment is especially pronounced in the perivascular melanophages resisting the action of any topical therapy, much like a tatoo.5 Melasma is very commonly resistant to all treatments, and is therefore very frustrating to the patient and clinician. Topical therapy can yield some improvement, but rarely does it cure this condition permanently. Such treatment protocols are particularly not useful for dermal-type melasma. A myriad of different combinations of topical therapies have been tried with minimal to moderate success. Use of tretinoin cream (0.1%) for 40 weeks has been shown to lead to improvement of this condition in 68% of the patients treated.6 It was also associated with a 36% decrease in the amount of epidermal melanin and no significant change in the amount of dermal melanin.6 Topical application caused moderate erythema and desquamation in 88% of the patients treated.6 Sanchez and Vazquez7 treated 46 women using hydroquinone 3% solution with moderate to marked improvement in 36% of the patients with minimal side effects. However, treatment may cause uneven depigmentation, contact dermatitis, exogenous ochronosis, and postinflammatory hyperpigmentation.8 Some investigators have reported that combination therapy using hydro-

Address correspondence and reprint requests to: James M. Spencer, MD, Mount Sinai Medical Center, Division of Dermatologic Surgery, 5 East 98th St., 12th Floor, New York, NY 10029.

© 1999 by the American Society for Dermatologic Surgery, Inc. • Published by Blackwell Science, Inc. ISSN: 1076-0521/99/$14.00/0 • Dermatol Surg 1999;25:494–497

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quinone, tretinoin, and topical steroids works better than monotherapy for the treatment of melasma. 9,10 Deep chemical peels and dermabrasion have been used to treat melasma. These modalities are associated with a some degree of side effects such as postinflammatory hyperpigmentation, hypopigmentation, keloid formation, hypertrophic scars, and atrophy, especially in darker individuals where melasma is much more common anyway.8 Azelaic acid 20% was shown to be as effective as 4% hydroquinone cream with fewer side effects.11 Adverse effects include mild erythema, pruritus, scaling, and burning.12 All of these topical treatments achieve minimal to moderate resolution of the pigment with some side effects in roughly 60% of patients. The other 40% most probably encompass the percentage of dermal or mixed melasma. By developing a combination laser treatment that targets both epidermal and dermal melanin pigment, it may be possible to cure melasma of all types. The 950 msec pulsed CO2 laser is capable of removing the epidermis in a controlled fashion with minimal thermal conduction downward. A single pass with this laser will remove hyperpigmentation in the epidermis by removing the epidermis itself and by destroying the melanocytes producing the excess melanin. Following removal of the epidermis, the denuded dermis can then be treated with the Q-switched alexandrite laser, which will target dermal melanin. We predict deeper penetration into the dermis, as there is no epidermis to filter the energy. During the healing phase, the epidermis will be regenerated from the appendiceal units. It is possible that these new melanocytes will not produce localized areas of hyperpigmentation. In addition, in order to treat melasma with success, emphasis must be placed on the importance of avoiding excess sun exposure and wearing protective broadspectrum sunscreen.13 Of note, it is also crucial that the patients be educated about other factors that exacerbate melasma such as pregnancy, oral contraceptives, and certain antiseizure medications.

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mal-type melasma diagnosed by Wood’s lamp examination underwent a 14-day course of tretinoin 0.05% cream, hydroquinone 4% cream, and hydrocortisone 1% cream, all applied topically in the morning and at bedtime. The diagnosis of melasma was made clinically by the size, appearance, and distribution of the hyperpigmentation, as well as the clinical history of the lesions. After 2 weeks, four of the patients were randomly picked to be treated with one pass of the Coherent® 950 msec pulsed CO2 laser with a computerized pattern generator set at 300 mJ/cm2 followed by another pass with the Q-switched alexandrite pigmented dye laser at a fluence of 6 J/cm2. The other four patients were treated with the pulsed CO2 laser alone. For each of the treatment groups, the patients were treated in only one area affected by melasma measuring 1 cm2 on the face either with pulsed CO2 laser alone or with combination therapy. Lidocaine and epinephrine were used as local anesthetic prior to laser treatment. Bactroban ointment was applied after the procedure. This was followed by vigilon dressing for 1 week and then was left open. Patients came for multiple follow-up visits at 4 weeks, 12 weeks, and 24 weeks post-laser therapy. At these follow-up visits pictures were taken and there was examination by an objective blinded investigator to note any significant improvement or worsening at the treatment sites. Criteria for evaluations were as follows: normal, pink, hyperpigmented, hypopigmented, or pink with hyperpigmented border. The patients were advised to avoid excessive sun exposure during this time and to wear a broad-spectrum sunscreen with a sun protection factor (SPF) of 15 or greater.

Materials and Methods Institutional review board approval was obtained and all patients signed the approved informed consent document. Eight patients with skin types IV–VI who suffer from derTable 1. Results of Combination Treatment with Pulsed CO2 Laser Followed by the Q-Switched Alexandrite Laser Patient Number 5 (RD) 6 (LR) 7 (XO) 8 (AS)

4–6-Week Follow-Up Pink slightly atrophic plaque Pink patch Pink atrophic plaque Pink patch

$6-Month Follow-Up Normal skin Normal skin Very light pink Normal skin

Figure 1. 24-week follow-up of patient with combination laser treatment.

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Table 2 Results of Treatment with Pulsed CO2 Laser Alone Patient Number

$6-Month Follow-Up

4–6-Week Follow-Up

1 (OC) 2 (SC)

Pink patch Pink patch

3 (PS)

Pink patch with peripheral hyperpigmentation

4 (EW)

Slightly pink patch with peripheral hyperpigmentation

Results and Discussion These laser therapies are safe, as there was no scarring and no infection. No statistically significant conclusions can be made about the differences in efficacy between these laser modalities because of the small number of patients being studied. The combination laser therapy was highly effective in removing the hyperpigmentation as all patients in this group showed complete resolution (Table 1 and Figure 1). The CO2 laser only group was less effective. Two patients got peripheral hyperpigmentation after treatment; both were in the CO2 laser only group (Table 2 and Figure 2). In both treatment arms, all patients treated with either the pulsed CO2 laser alone or the pulsed CO 2 laser plus the alexandrite laser showed complete resolution of melasma within the treatment area. The photograph in Figure 2 greatly deemphasizes the marked peripheral hyperpigmentation seen clinically by the blinded investigator. The peripheral hyperpigmentation seen with this treatment modality may represent lower energy at the edges resulting in postinflammatory hyperpigmentation in the areas that have intact melanocytes. The pathophysiology of melasma is still unknown. Melasma may be caused by an abnormal epidermis or by abnormal melanocytes. The CO2 laser destroys these cells and the alexandrite laser removes

Normal skin Slightly pink patch within the treatment area with mild peripheral hyperpigmentation Slightly pink patch within the treatment area with peripheral hyperpigmentation Slight hypopigmentation within the treatment area

any pigment left in the dermis. If melasma were caused by an abnormal dermis, these laser therapeutic modalities would not work. Single laser therapy targeting melanin with such devices as the Q-switched alexandrite, Q-switched ruby, 510 nm pigmented dye, and Nd:YAG are able to treat superficial melanin containing lesions such as lentigenes and deeper dermal lesions such as nevi of Ota successfully, but have been shown to be ineffective in treating melasma.1–4 It may be that the melanocytes in areas of melasma are overactive and that the inflammation following laser treatment leads to rapid reoccurrence or even darkening of the treated areas. In this pilot study we were trying to gain information on the initial safety and efficacy of using these lasers for melasma. Two to 3-year follow-up evaluations would ideally be needed to assess the long-term effects of these laser treatment modalities. For future studies, a split-face design would eliminate individual variability which may confound treatment evaluations. The use of a colorimeter would allow quantification of the differences in pigmentation following treatment. Due to the fact that this is a pilot study, and that the patients were somewhat apprehensive about treating their melasma for fear of scarring or worsening of their melasma, we decided to treat only one small test spot in an inconspicuous area of the face. No adverse effects were noted with combination laser therapy, and since only one pass with the CO2 laser was utilized, healing; time was relatively short. Larger studies in the future are warranted to assess the efficacy of combination laser therapy for dermal conditions in which single laser therapy has been slow (such as tattoos) or ineffective (such as melasma).

References

Figure 2. 24-week follow-up of patient with only pulsed CO2 laser treatment.

1. Grekin RC, Shelton RM, Geisse JK, Frieden I. 510 nm pigmented lesion dye laser: its characteristics and clinical uses. J Dermatol Surg Oncol 1993;19:380–7. 2. Taylor CR, Anderson RR. Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser. J Dermatol Surg Oncol 1994;20:592–7. 3. Tse Y, Levine VJ, McClain SA, Ashinoff R. The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the

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neodymium:yttrium-aluminum-garnet laser. J Dermatol Surg Oncol 1994;20:795–800. Goldberg DJ. Benign pigmented lesions of the skin: treatment with the Q-switched ruby laser. J Dermatol Surg Oncol 1993;19:376–9. Sanchez NP, Pathak MA, Sato S, Fitzpatrick TB, Sanchez JL, Mihm MC Jr. Melasma: a clinical, light microscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol 1981;4:698–710. Griffiths CE, Finkel LJ, Ditre CM, Hamilton TA, Ellis CN, Voorhees JJ. Topical tretinoin (retinoic acid) improves melasma. Br J Dermatol 1993;129:415–21. Sanchez IL, Vazquez M. A hydroquinone solution in the treatment of melasma. Int J Dermatol 1982;21:55–8.

Commentary As the authors point out, melasma is a frustrating condition because it can be very resistant to treatment. Although we can effect improvement with topicals and peels, melasma recurs when the patient is re-exposed to sunlight.1 Treatment of melasma with laser to this point has been unsuccessful with worsening of the melasma in some reports.2 The concept of treating both the epidermal and dermal components of melasma explored in this study is a good one. The authors prefer the combination treatment of pulsed CO2 and Alexandrite because the patients had no hyperpigmentation peripheral to the treatment zone in this arm of the study. However, within the treatment zone, both pulsed CO2 alone and pulsed CO2 plus Alexandrite worked equally well. As a pilot study the authors have introduced a very interesting idea. A follow-up study with split face design will help clarify a few issues. Melasma is a condition with extreme individual variability. Some patients with significant melasma respond to medical therapy alone and some patients are extremely recalcitrant to most approaches. A randomized study design, particularly in such a small study group, does not correct for all the “good responders” being put in one study arm. Another issue


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8. Grimes PE. Melasma: etiologic and therapeutic considerations. Arch Dermatol 1995;131:1453–7. 9. Kligman AM, Willis I. A new formula for depigmenting human skin. Arch Dermatol 1975;111:40–8. 10. Pathak MA, Fitzpatrick TB, Kraus EW. Usefulness of retinoic acid in the treatment of melasma. J Am Acad Dermatol 1986;15:894–9. 11. Balina LM, Graupe K. The treatment of melasma 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol 1991;30:893–5. 12. Fitton A, Goa KL. Azelaic acid. Drugs 1991;41:780–98. 13. Vazquez M, Sanchez IL. The efficacy of a broad-spectrum sunscreen in the treatment of melasma. Cutis 1983;32:92–6.

that a split face design would clarify is the occurrence of the peripheral hyperpigmentation to the treatment zone. This pigment may have been post-inflammatory. A tendency for post inflammatory pigmentation is also extremely variable from individual to individual. If a patient received both treatments and the etiology of the pigment is post inflammatory, it should be present surrounding both treatment areas. The authors are to be commended for their new therapeutic approach to melasma. Further study is necessary to evaluate efficacy, optimal pigmented laser choice, and longevity of result.

Naomi Lawrence, MD Marlton, New Jersey

References 1. Lawrence N, Cox SE, Brody HJ. Treatment of melasma with Jessner’s solution vs glycolic acid: a comparison of clinical efficacy and evaluation of the predictive ability of Wood’s light examination. J Amer Acad Dermatol 1997;36:589–93. 2. Taylor CR, Anderson RR. Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser. J Dermatol Surg Oncol 1994;20:592–7.