Documenti di Didattica
Documenti di Professioni
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Jean-Paul Ortonne, MD,a Amit G. Pandya, MD,b Harvey Lui, MD,c and Doris Hexsel, MDd
Nice, France; Dallas, Texas; Vancouver, British Columbia, Canada;
and Rio Grande do Sul, Brazil
Therapy for solar lentigines is diverse but can be divided into two broad categories: physical therapy and
topical therapy. Physical therapies are frequently used with excellent clinical success rates, but this has to
be balanced against associated side effects and recurrence rates with certain therapies. A range of topical
therapies have been used and, more recently, fixed combinations of topical agents have been investigated.
The Pigmentary Disorders Academy undertook to evaluate the clinical efficacy of the different treatments of
solar lentigines in order to generate a consensus statement on their management. Clinical papers published
during the past 20 years were identified through MEDLINE searches and methodology and outcome were
assessed according to guidelines adapted from the US Preventive Services Task Force (USPSTF) on health
care. The consensus of the group was that first-line therapy for solar lentigines was ablative therapy with
cryotherapy. Although no large-scale studies have been completed, there is also good evidence to suggest
that lasers are an effective treatment. An alternative to ablative therapy is topical therapy and there is good
evidence to support the use of a fixed double combination, as well as retinoids, such as adapalene and
tretinoin. Topical therapy can also be considered as maintenance therapy after the primary therapy has
been applied. Because of the diversity of scoring systems used in the assessment of treatment outcome, the
group recommends the development of treatment guidelines. ( J Am Acad Dermatol 2006;54:S262-71.)
S262
J AM ACAD DERMATOL Ortonne et al S263
VOLUME 54, NUMBER 5
is 3.2 J/cm2. Because this fluence is too high to treat Table I. Lightening of lentigines by treatment
lentigines, a lower fluence is selected by increasing at 6 and 12 weeks as determined by physician
the spot size. This can result in damage to surround- evaluation (n = 75)*
ing tissue and the complications of hypopigmenta- Observer grades
tion and hyperpigmentation.
Poor Fair Good Excellent Clear
The quasicontinuous, frequency-doubled Nd:YAG (0%- (26%- (51%- (76%- (91%-
(532 nm) laser has been studied in 6 Pakistani Treatment 25%) 50%) 75%) 90%) 100%)
patients with solar lentigines and Fitzpatrick skin 6 weeks
type IV.11 The pulse duration applied was 1.6 micro- Liquid nitrogen 8 7 20 44 21
seconds; exposure time was 0.01 second to continu- Q-switched 4 3 10 36 47
ous; and spot size 2 mm. Irradiation was delivered Nd:YAG laser
during 3 to 8 sessions at 4- to 12-week intervals. All Krypton laser 3 5 18 47 27
patients had a greater than 50% improvement and no Diode-pumped 3 8 22 43 24
vanadate laser
recurrence was reported at 24-month follow-up.
12 weeks
Complications included hypopigmentation, mild
Liquid nitrogen 8 9 15 44 24
textural changes, and hyperpigmentation, although Q-switched 0 3 8 29 60
these were mild and resolved in 2 to 6 months. Nd:YAG laser
No cases of purpura were observed. Krypton laser 1 5 14 48 32
The efficacy of laser therapy has been compared Diode-pumped 0 9 20 44 28
with cryotherapy in two studies.12,13 The first of these vanadate laser
was a randomized study involving 13 patients and
99 lesions, which compared CO2 laser, argon laser *Each treatment received 75 observer grades (each of 25 patients
graded by 3 observers). Numbers shown indicate the number of
light, and cryotherapy within the same patient.12 grades achieved following treatment at a particular degree of
Fluences of 3 to 5 J/cm2 and 1 J/cm2 were adminis- lightening.
tered for the CO2 and argon laser techniques, Reprinted from Todd MM, Rallis TM, Gerwels JW, Hata TR. Arch
respectively. Significantly better results, assessed Dermatol 2000;136:841-6. Copyright ª 2001, American Medical
by independent reviewers of patients’ slides, were Association. All rights reserved.
produced by cryotherapy than either of the laser
therapies. Good results were reported in 61% (P\.05 Nd:YAG laser was found to provide superior light-
vs cryotherapy), 62% (P \ .01 vs cryotherapy), and ening compared with the other treatments (Table I).
75% of patients treated with the CO2 laser, argon The level of response at 12 weeks after treatment was
laser, and cryotherapy, respectively. Moderate atro- not reduced over that at 6 weeks. Again at 12 weeks,
phy was reported infrequently for all therapies. Todd the frequency Q-switched Nd:YAG laser was again
et al13 have reported a comparative study of the shown to achieve results significantly superior to
frequency-doubled Q-switched Nd:YAG laser (532 those of the other treatments (P \ .001). From the
nm), the HGM K1 krypton laser (521 nm) (HGM patients’ perspective, a survey showed that they
Medical Systems Inc, Salt Lake City, Utah), the DioLite considered this form of laser therapy to produce
532-nm diode-pumped vanadate laser (Index Corp, the best results (n = 18) followed by diode-pump
Mountain View, Calif), and cryotherapy. A total of vanadate laser (n = 6), cryotherapy (n = 2), and
27 patients with a minimum of 6 lesions on the backs krypton laser (n = 1). The fewest adverse events were
of their hands were enrolled in the study. Each hand reported from use of the Q-switched laser, whereas
was divided into 4 sectors and one treatment applied the krypton laser had the highest. Mild transient
per sector. Treatment with the frequency-doubled erythema was reported for all therapies; hypopig-
Q-switched Nd:YAG laser involved treatment for mentation and/or hyperpigmentation and scarring
30 nanoseconds to a 3-mm spot; comparative treat- occurred infrequently. Laser therapy has also been
ments with the HGM K1 krypton laser and the DioLite compared with facial peels and shown to be
532-nm diode-pumped vanadate laser were 0.2 sec- superior.14
ond on/0.2 second off to a 1-mm spot and 39 ms to
a 1-mm spot, respectively. Independent assessors Intense pulsed light therapy
categorized improvement according to a graded Intense pulsed light (IPL) involves the use of a
scale of the degree of lightening using patient pho- broadband visible light emitted from a noncoherent,
tographs. The 5-point grading scale was as follows: nonlaser, filtered flashlamp. Kawada et al15 have
poor, nonee25%; fair, 26%-50%; good, 51%-75%; reported a greater than 50% improvement in 18 of 45
excellent, 76%-90%; and clear, 91%-100%. At 6 weeks patients (40%) with solar lentigines using this tech-
after treatment, the frequency-doubled Q-switched nique as assessed by observation and photography
S266 Ortonne et al J AM ACAD DERMATOL
MAY 2006
in Asian patients. Each patient received 3 to 5 of postinflammatory pigment changes, whereas TCA
treatments (average number, 4) at 2- to 3-week is able to penetrate deeply but uniformly into the
intervals. No hyperpigmentation or scarring was skin.24
reported. The same group of researchers has con- The efficacy of chemical peels has been compared
ducted a histopathological study to examine the with that of cryotherapy25 and laser therapy.14
changes that occur in the skin with IPL.16 They report The first comparative study involved treating each
that microcrusts appear over the lesions 1 to 2 days hand of 25 patients with multiple solar lentigines
after irradiation. These crusts contain melanin and at random with either 30% TCA or liquid nitrogen
drop off after 2 weeks to reveal a normally pig- spray as a single treatment.25 Patients were evaluated
mented area. It was suggested that crust formation at 8 weeks using photography. At this time, 9 patients
may result from the photothermal effects of IPL. (47%) in the TCA group achieved more than 50%
improvement compared with 15 patients (71%) in
Dermabrasion the cryotherapy group; the difference was signifi-
Dermabrasion is a mechanical abrasive process cant (P \.05). Overall, patients with Fitzpatrick skin
that removes epidermis and superficial dermis. A fine type II achieved moderate or marked improvements
and superficial abrasion is produced by using a low- that were approximately twice those of patients with
rotation motor with brushes or diamond fraises skin type IV. Postinflammatory hyperpigmentation,
mounted on a handpiece. The depth of the derma- atrophy, or residual hypopigmentation were infre-
brasion is controlled by the pressure applied to the quently noted for either therapy. A patient survey
skin and can be varied according to needs. However, indicated that 62% of patients (13/21) believed that
there are certain risks; fine hemorrhagic spots after cryotherapy achieved the best results; 76% (16/21)
treatment can occur indicating a depth of abrasion believed that treatment with TCA was the quickest to
greater than the papillary dermis. In terms of side heal, and 86% (18/21) thought that cryotherapy was
effects, hyperpigmentation and hypopigmentation the most painful treatment.
are generally temporary, but can sometimes per- The comparative study between TCA and laser
sist.17 Recurrence rates of 55% have been described therapy involved 20 patients (Fitzpatrick skin types
at 6 months.3 III-IV) with 37 facial lentigines and indicated greater
Cotellessa et al18 have reported that microabra- improvement with laser therapy.14 Each lentigo was
sion or microabrasion plus 15% trichloroacetic acid divided into medial and lateral halves and frequency-
(TCA) is equally effective in treating women with doubled Q-switched Nd:YAG laser (10 nanoseconds;
multiple hyperpigmented macules of the face. 2-mm spot size; 532 nm) and 35% TCA applied to the
Group 1 was treated at 2-week intervals with micro- medial and lateral halves of each lentigo, respec-
abrasion and group 2 received microabrasion plus tively. Independent assessment of photographs in-
TCA every 3 weeks. All patients underwent up to dicated that 24 patients (65%) showed better results
8 treatments. In group 1 complete remission was in their medial halves (laser therapy) than in their
visually observed in 8 women (40%), partial remis- lateral halves (TCA), 5 (14%) got better results in their
sion in 10 women (50%), and no remission in 2 lateral halves, and 8 patients (21%) showed similar
women (10%). Equivalent numbers for group 2 were improvement with both treatments. No textural
as follows: complete remission in 10 women (50%), changes, hypopigmentation, or hyperpigmentation
partial remission in 8 women (40%), and no remis- were noted after either therapy.
sion in 2 women (10%). The only side effects
reported were mild erythema in all patients, which TOPICAL THERAPY
disappeared after a few hours; mild desquamation A range of topical therapies are currently available
lasted for 3 to 4 days in all patients. for the treatment of solar lentigines. The principal
mode of action is the disruption of melanin forma-
Chemical peels tion. Hydroquinone (HQ) and tretinoin (retinoic acid
Chemical peels to improve irregular pigmentation [RA] or vitamin A acid) are the most widely used
have been performed on the nonfacial area using agents for the treatment of hyperpigmentation; other
glycolic acid,19 TCA,20 Jessner’s solution,21 salicylic topical agents that have been used as monotherapy
acid ointment,22 and salicylic acid liquid.23 Cook and or in combination include mequinol (4-hydroxyani-
Cook24 have used a solution of 40% TCA in combi- sole [4HA]), adapalene (synthetic retinoid), and
nation with 70% glycolic acid to successfully treat azelaic acid. HQ inhibits the conversion of dopa
irregular pigmentation of nonfacial skin, including to melanin by inhibiting the tyrosinase enzyme.
solar lentigines. The principles underlying this treat- Other proposed mechanisms of action for HQ are
ment are that glycolic acid decreases the incidence inhibition of DNA and RNA synthesis, degradation of
J AM ACAD DERMATOL Ortonne et al S267
VOLUME 54, NUMBER 5
Mequinol (4HA)/tretinoin
A fixed combination of 2% 4HA and 4HA/0.01%
RA has been studied in a number of comparative
studies. The first of these compared 4HA/RA with 3%
HQ as well as the components of the combination,
that is, RA and 4HA, in a parallel double-blind trial of
216 patients (Fitzpatrick skin types I-IV) with solar
lentigines on the face and arms.34 The solutions were
applied twice daily for 16 weeks and follow-up was
an additional 24 weeks (Fig 3). At week 16, results
indicated that a significantly higher proportion of
patients achieved clinical success with 4HA/RA
than with HQ on the forearm as measured by the
Physician’s Global Assessment (60% vs 38%; P # .05)
and Lesional Pigmentation (70% vs 50%; P # 0.05).
There was also a trend, albeit not significant, for
greater improvements with 4HA/RA compared with
HQ with in facial lesions on the face as measured by
Fig 3. Treatment of solar lentigines with 2% 4HA and Physician’s Global Assessment (72% vs 58%) and
0.01% RA. Before treatment (A) and after 16 weeks (B) and Lesional Pigmentation (70% vs 65%). The 4HA/RA
24 weeks (C) of treatment shown. (Images courtesy of combination was also more effective than 4HA or RA
Galderma International.) alone on either the face or arms. For all treatment
groups, skin-related adverse events were mild or
moderate and transient.
Hydroquinone/tretinoin Two double-blind randomized controlled trials
A combination study of 0.1% to 0.4% RA plus 5% involving 1175 patients have compared 4HA/RA with
HQ has been conducted in 136 Asian patients with 4HA, RA, or vehicle.35 Patients were required to have
hyperpigmentary disorders, including 90 with senile at least 5 solar lentigines on the forearm or back
lentigines.33 HQ was applied to skin lesions twice of the hand and 5 lesions on the face. One lesion on
daily for several weeks before combination treat- the face and arm had to be 5 mm or larger. Treat-
ment with RA plus HQ twice daily. The concentration ments were applied twice daily for up to 24 weeks.
of RA used depended on location of the lesion; 0.1% Trial 1 had a 24-week no-treatment regression phase
RA was used on the face, 0.2% on the trunk, and 0.4% and trial 2 had a 4-week no-treatment regression
on the lower extremities. The concentration of RA phase. 4HA/RA was statistically superior to each of
was increased if no response was observed at its active components or vehicle in both trials 1 and 2
1 week. An objective measure of the color of the in terms of the Physician’s Global Assessment (P #
treated lesion and the surrounding normal skin was .002). Combined results from trials 1 and 2 indicate
recorded using a narrowband reflectance spectro- that moderate improvement or better was reported
photometer (Mexameter MX 16, Courage&Khazaka with 4HA/RA in 52% and 56% of patients on the
electronic, Cologne, Germany), which actually mea- forearms and face, respectively, compared with 35%
sures melanin and hemoglobin values. At 8 weeks, and 43% in the RA group, 24% and 33% in the 4HA
excellent or good benefits were produced in 58 of 61 group, and 17% and 19% in the vehicle groups,
patients with facial lesions, 2 of 3 patients with trunk respectively. In trial 1 during the 24-week follow-up
J AM ACAD DERMATOL Ortonne et al S269
VOLUME 54, NUMBER 5
Table II. Level of evidence Table IV. Level and quality of evidence for solar
lentigines therapies
A There is good evidence to support the use of this
procedure Quality of Level of Reference
B There is fair evidence to support the use of this Therapy evidence evidence no(s).
procedure Cryotherapy I A 5, 6, 12
C There is poor evidence to support the use of the Laser
procedure Q-switched ruby II-i A 8
D There is fair evidence to support the rejection of the Alexandrite II-i B 9
use of the procedure 532-nm Nd:YAG I A 10, 11, 13
E There is good evidence to support the rejection of the CO2 I-ii B 12
use of this procedure Argon I-ii B 12
HGM K1 krypton I-ii B 13
From Williams HC. Dermatology. In: Stevens A, Raferty J, editors. DioLite 522-nm II-i B 13
Health care needs assessment. Oxford (UK): Radcliffe Medical Press; vanadate
1997. p. 340. Reproduced with permission. IPL III B 15
Dermabrasion III D 18
Chemical peels
Table III. Quality of evidence 30% TCA II-ii C 14, 25
Topical
I Evidence obtained from at least one properly 3% HQ IV C 34, 35
designed, randomized controlled trial 0.01% RA I C 28, 35
II-i Evidence obtained from well designed controlled 0.05% RA I A 28
trials without randomization 0.1% RA I B 30, 35
II-ii Evidence obtained from well designed cohort or case 2% 4HA (mequinol) I B 35
control analytic studies, preferably from more than 2% mequinol 1 0.01% I A 34, 35
one center or research group RA
II-iii Evidence obtained from multiple time series with or 0.1%-0.4% RA 1 II-iii B 33
without the intervention. Dramatic results in 5% HQ
uncontrolled experiments (such as the results of the 2% HQ/cyclodextrin II-i C 28
introduction of penicillin in the 1940s) could also be 0.1%-0.3% Adapalene I B 32
regarded as this type of evidence 0.1% Tazarotene I B 31
III Opinions of respected authorities based on clinical
experience, descriptive studies, or reports of expert 4HA, 4-Hydroxyanisole; HQ, hydroquinone; IPL, intense pulsed
committees light; RA, tretinoin; TCA, trichloroacetic acid.
IV Evidence inadequate owing to problems of metho-
dology (e.g. sample size, or length or comprehen-
An open-label, noncontrolled study has assessed
siveness of follow-up or conflicts in evidence)
the combination of 4HA/RA with sunscreen in 406
From Williams HC. Dermatology. In: Stevens A, Raferty J, editors. patients (Fitzpatrick skin types I-IV) with solar len-
Health care needs assessment. Oxford (UK): Radcliffe Medical tigines on the forearms and face. Treatments were
Press; 1997. p. 340. Reproduced with permission. applied twice daily for 24 weeks, with a 4-week
follow-up phase.36 Of the target lesions treated,
80% and 88% were reported to be clear or almost
phase, 4HA/RA continued to show statistically supe- clear on the arms and face, respectively. Most
rior improvements over the other treatment or vehi- adverse events were mild or moderate and disap-
cle (P # .003). Similar results were reported for trial peared after treatment cessation. The most frequent
2 during the 4-week follow-up phase (P # .002). adverse events were erythema (127 events); bur-
Patients’ assessment of treatment indicated superior- ning/stinging (45 events); skin irritation (45 events);
ity for 4HA/RA over the individual components or desquamation (35 events); and pruritus (30 events).
vehicle in both studies. With regard to maintenance Twenty-two patients discontinued treatment be-
of response, 56% and 70% of patients treated with cause of an adverse event.
4HA/RA maintained the benefit on their forearms and
faces, respectively, at 24 weeks. Most skin-related RECOMMENDATIONS
adverse events were mild or moderate and were The PDA has reviewed the literature on treat-
similar for 4HA/RA and RA groups. The most com- ment of solar lentigines and categorized the clinical
mon adverse event was erythema (56% in 4HA/RA findings for each treatment according to guidelines
or RA groups) and burning/stinging/tingling (34% adapted from the US Preventive Services Task Force
4HA/RA; 36% RA). (USPSTF) on health care (Tables II and III).37
S270 Ortonne et al J AM ACAD DERMATOL
MAY 2006
As a result of reviewing the clinical evidence, as 5. Almond-Roesler B, Zouboulis CC. Successful treatment of solar
shown in Tables II and III, the PDA has categorized lentigines by brief gentle cryosurgery using a Kryomed
device. Br J Dermatol 2000;143:216-8.
each therapeutic option for solar lentigines as shown 6. Zouboulis CC, Rosenberger AD, Adler Y, Orfanos CE. Treat-
in Table IV. ment of solar lentigo with cryosurgery. Acta Derm Venereol
1999;79:489-90.
Consensus statement 7. Stratigos AJ, Dover JS, Arndt KA. Laser treatment of pig-
mented lesionse2000. How far have we gone? Arch Dermatol
The clinical evidence reviewed by the PDA indi-
2000;136:915-21.
cates that cryotherapy is an effective ablative therapy 8. Kopera D, Hohenleutner U, Landthaler M. Quality-switched
for the treatment of solar lentigines. Its use can result ruby laser treatment of solar lentigines and Becker’s nevus:
in substantial lightening in the majority of patients a histopathological and immunohistochemical study. Derma-
by 6 months. Although no large-scale studies have tology 1997;194:338-43.
9. Rosenbach A. Treatment of medium-brown solar lentigines
been completed, there is also good evidence to sug-
using an alexandrite laser designed for hair reduction. Arch
gest that lasers are an effective treatment. Because of Dermatol 2002;138:547-8.
the side effects associated with physical treatments, 10. Chan HH, Fung WKK, Ying S-Y, Kono T. An in vivo trial
patients may require or prefer a topical therapy. comparing the use of different types of 532 nm Nd:YAG lasers
Physical therapies are much faster than topical ther- in the treatment of facial lentigines in Oriental patients.
Dermatol Surg 2000;26:743-9.
apy, with many patients clearing after just one or two
11. Rashid T, Hussain I, Haider M, Haroon TS. Laser therapy
treatment sessions. However, topical therapies are of freckles and lentigines with quasi-continuous frequency-
usually less costly than physical modalities. The doubled, Nd:YAG (532 nm) laser in Fitzpatrick skin type IV:
treatment of choice recommended by the panel in a 24-month follow-up. J Cosmet & Laser Ther 2002;4:81-5.
these circumstances is topical therapy. The strongest 12. Stern RS, Dover JS, Levin JA, Arndt KA. Laser therapy versus
cryotherapy of lentigines: a comparative trial. J Am Acad
clinical evidence exists for a fixed double combina-
Dermatol 1994;30:985-7.
tion therapy of hydroxyanisole mequinol and RA. 13. Todd MM, Rallis TM, Gerwels JW, Hata TR. A comparison of
However, there is also good evidence for the use 3 lasers and liquid nitrogen in the treatment of solar lentig-
of monotherapy with RA, Adapalene, or tazarotene, ines. Arch Dermatol 2000;136:841-6.
which could also be considered in those situations 14. Li Y-T, Yang K-C. Comparison of the frequency-doubled
Q-switched Nd:YAG laser and 35% trichloroacetic acid for
in which choice will depend on patient preference,
the treatment of face lentigines. Dermatol Surg 1999;25:
sensitivity to ingredients, and availability. The com- 202-4.
bination of ablative and topical therapies may also 15. Kawada A, Shiraishi H, Asai M, Kameyama H, Sangen Y,
be beneficial to patients. After cryotherapy, the use Aragane Y, et al. Clinical improvement of solar lentigines
of double combination topical therapy may be used and ephelides with an intense pulsed light source. Dermatol
Surg 2002;28:504-8.
as a maintenance therapy to diminish the risk of
16. Kawada A, Asai M, Kameyama H, Sangen Y, Aragane Y, Tezuka
relapse. T, et al. Videomicroscopic and histopathological investigation
Scoring systems for assessing treatment vary of intense pulsed light therapy for solar lentigines. J Dermatol
considerably between different centers, making it Sci 2002;29:91-6.
difficult to accurately compare outcomes. The group 17. Fulton JE Jr. Dermabrasion, chemabrasion, and laser abrasion;
historical perspectives, modern dermabrasion techniques, and
recommends the development of treatment guide-
future trends. Dermatol Surg 1996;22:619-28.
lines for solar lentigines in order to establish a 18. Cotellessa C, Peris K, Fargnoli MC, Mordenti C, Giacomello
uniform scoring system, which will allow the critical RS, Chimenti S. Microabrasion versus microabrasion followed
appraisal of specific treatments. by 15% trichloroacetic acid for treatment of cutaneous
hyperpigmentation in adult females. Dermatol Surg 2003;29:
We acknowledge the assistance of Dr Christine 352-6.
McKillop in the preparation of this document. 19. Newman N, Newman A, Moy L, Babapour R, Harris AG, Moy RL.
Clinical improvement of photoaged skin with 50% glycolic
REFERENCES acid. Dermatol Surg 1996;22:455-60.
1. Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz 20. Collins PS. Trichloroacetic acid peels revisited. J Dermatol Surg
SI. Fitzpatrick’s dermatology in general medicine. 5th ed. New Oncol 1989;15:933-40.
York: McGraw-Hill; 1999. 21. Monheit GD. The Jessner’s 1 TCA peel: a medium-depth
2. Ortonne J-P. Pigmentary changes of the ageing skin. Br J chemical peel. J Dermatol Surg Oncol 1989;15:945-50.
Dermatol 1990;122(Suppl 35):21-8. 22. Swinehart JM. Salicylic acid ointment peeling of the hands and
3. Hexsel DM, Mazzuco R, Bohn J, Borges J, Gobbato DO. Clinical forearms: effective nonsurgical removal of pigmented lesions
comparative study between cryotherapy and local dermabra- and actinic damage. Dermatol Surg Oncol 1992;18:495-8.
sion for the treatment of solar lentigo on the back of hands. 23. Kligman D, Kligman AM. Salicylic acid peels for the treatment
Dermatol Surg 2000;26:457-62. of photoaging. Dermatol Surg 1988;24:325-8.
4. Gage AA, Meenaghan MA, Natiella JR, Green GW Jr. Sensitivity 24. Cook KK, Cook WR. Chemical peel of nonfacial skin using
of pigmented mucosa and skin to freezing injury. Cryobiology glycolic acid gel augmented with TCA and neutralized based
1979;16:348-61. on visual staging. Dermatol Surg 2000;26:994-9.
J AM ACAD DERMATOL Ortonne et al S271
VOLUME 54, NUMBER 5
25. Lugo-Janer A, Lugo-Somolinos A, Sanchez JL. Comparison of 32. Kang S, Goldfarb MT, Weiss JS, Metz RD, Hamilton TA,
trichloroacetic acid solution and cryosurgery in the treatment Voorhees JJ, et al. Assessment of adapalene gel for the
of solar lentigines. Int J Dermatol 2003;42:829-31. treatment of actinic keratoses and lentigines: a randomized
26. Palumbo A, d’Ischia M, Misuraca G, Prota G. Mechanism of trial. J Am Acad Dermatol 2003;49:83-90.
inhibition of melanogenesis by hydroquinone. Biochem Bio- 33. Yoshimura K, Harii K, Aoyama T, Iga T. Experience with a
phys Acta 1991;1073:85-90. strong bleaching treatment for skin hyperpigmentation in
27. Romero C, Aberdam E, Larnier C, Ortonne JP. Retinoic acid Orientals. Plast Reconstr Surg 2000;105:1097-108.
as modulator of UVB-induced melanocyte differentiation. 34. Jarratt M. Mequinol 2%/ tretinoin 0.01% solution: an effective
Involvement of the melanogenic enzymes expression. J Cell and safe alternative to hydroquinone 3% in the treatment of
Sci 1994;107(Pt 4):1095-103. solar lentigines. Cutis 2004;74:319-22.
28. Petit L, Piérard GE. Analytic quantification of solar lentigines 35. Fleischer AB Jr, Schwartzel EH, Colby SI, Altman DJ, and the
lightening by a 2% hydroquinone-cyclodextrin formulation. Depigmenting Solution Study Group. The combination of 2%
J Eur Acad Dermatol Venereol 2003;17:546-9. 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective
29. Weinstein GD, Nigra TP, Pochi PE, Savin RC, Allan A, Benik K, in improving the appearance of solar lentigines and related
et al. Topical tretinoin for treatment of photodamaged skin. hyperpigmented lesions in two double-blind multicenter clin-
A multicenter study. Arch Dermatol 1991;127:659-65. ical studies. J Am Acad Dermatol 2000;42:459-67.
30. Rafal ES, Griffiths CE, Ditre CM, Finkel LJ, Hamilton TA, Ellis CN, 36. Ortonne J-P, Camacho F, Wainwright N, Bergfelt L, Westerhof
et al. Topical tretinoin (retinoic acid) treatment for liver spots W, Roseeuw D. Safety and efficacy of combined use of 4-
associated with photodamage. N Engl J Med 1992;326:368-74. hydroxyanisole (mequinol) 2%/tretinoin 0.01% solution and
31. Phillips TJ, Gottlieb AB, Leyden JJ, Lowe NJ, Lew-Kaya DA, sunscreen in solar lentigines. Cutis 2004;74:261-4.
Sefton J, et al. Efficacy of 0.1% tazarotene cream for the 37. Williams HC. Dermatology. In: Stevens A, Raftery J, editors.
treatment of photodamage: a 12-month, multicenter, ran- Health care needs assessment. Second series. Oxford (UK):
domized trial. Arch Dermatol 2002;138:1486-93. Radcliffe Medical Press; 1997. p. 340.