RESEARCH LETTER

Comparative long-term efficacy of P ¼ .591. Histology evaluation was obtained in 3

phenol-croton oil chemical peels for (12%) patients. The most common adverse event was
persistent melasma at varied Croton temporary postinflammatory hyperpigmentation
tiglium oil concentrations seen in 44% of patients for CO \1% and 30% for
To the Editor: Patients with persistent melasma strive CO [1%, which underwent spontaneous recovery
to achieve long-term remission despite rigorous with strict sun-protection. Such evolution is also
compliance to traditional dermatologic therapy observed during periorbital dark circle treatment
such as topicals and lasers.1 Phenol formulations with phenol-croton oil peels.4 Extremely relevant
have been used with success for melasma when clinical-histopathological supplementary Figures S1
mixed with castor oil (Ricinus communis oil), but to S6 and Dataset are available via Mendeley at 10.
there is a dearth of literature regarding results with 17632/jf7k2g5cdy.2.
phenol-croton oil peels (Croton tiglium oil [CO]) at Limitations of our study include a modest number
different concentrations for the treatment of mel- of cases, retrospective design, and the lack of
asma.2,3 In this retrospective international cohort patients treated with lighter concentrations of croton
study, we aimed to compare the safety and efficacy oil, such as 0.1% to 0.4%. A careful selection of
in those treated with medium concentration of CO patients, including those who failed previous treat-
(0.7%-0.9%, CO \1%) versus at higher concentration ments despite strict compliance, and perimeno-
(1.1%-1.6%, CO [1%) for the treatment of recalci- pausal women who are no longer planning to
trant melasma. become pregnant, might have contributed to the
The primary outcome was the relative improve- favorable outcomes. This cohort study included 12
ment in the modified Melasma Area Severity Index patients with skin type IV, adding to the current
(mMASI) compared to baseline. Wilcoxon’s signed literature of safety of phenol-croton oil peels in skin
rank test was performed with P \ .05 considered of color individuals.5
statistically significant. Secondary outcomes: propor- In conclusion, our study provides preliminary
tion of remission (achieving mMASI #1 at the last evidence to support deep chemical peel for the
follow-up), physician Global Aesthetic Improvement treatment of melasma refractory to topical and
Scale, and side effects. Statistics were calculated oral treatments. Moreover, CO \1% had increased
using Stata/SE 17.0 (StataCorp). relative improvement in mMASI compared to CO
Twenty-six females (mean age 46 years) were [1%, however both were effective and had
included, 42% had skin type IV (range: II-IV), 92% similar side effect profiles, suggesting that for
received full face treatment. Routine electrocardio- melasma, contrary to the treatment of deep
graphic screening and intraoperative monitoring wrinkles, higher concentrations of croton oil are
revealed no abnormalities. 65% of patients had CO not required to achieve a significant long-term
[1% peels, baseline mMASI ¼ 6, interquartile range clinical improvement.
(IQR) 5 to 8, with 8 (IQR: 6-9) for CO \1%, and 6 The authors are grateful for Carolina Morais, MD for
(IQR: 4-7) for CO [1%. The median follow-up was the collaboration and expertise of the histopathology
46 months (IQR: 23-87), with 144 months (IQR: 24- evaluation.
168) for CO\1% and 44 (11-77) for CO[1%, Table I.
The longest follow-up was 15 years for CO \1%, and Mayra B. C. Maymone, MD, DSc,a Fatima N.
11 years for CO [1%. Mirza, MD, MPH,a Denise Steiner, MD, PhD,b
The relative improvement in mMASI was greater Felipe Ribeiro, MD,b Marina Landau, MD,c
in CO \1%, median 100% (IQR: 100-100) compared Carolina Marçon, MD, PhD,d Tereza C.
to CO [1%, median 88% (IQR: 83-100), P \.001. For Celidonio, MD,e Seaver L. Soon, MD,f and
individual improvement see Fig 1. There was a Carlos G. Wambier, MD, PhD,a for the
significant difference between baseline and post- International Peeling Society
treatment mMASI (P \.001) for both concentrations.
From the Department of Dermatology, The Warren
The median physician Global Aesthetic
Alpert Medical School of Brown University, Prov-
Improvement Scale was 5 (much improved) for
idence, Rhode Islanda; Department of Derma-
both CO\1% and CO[1%. Overall, 85% maintained
tology, University of Mogi das Cruzes, Mogi das
remission, 78% for CO \1% and 88% for CO [1%,
Cruzes, Brazilb; Arena Dermatology, Herzliya,
Israelc; Carolina Marçon Dermatologia, S~ ao
Paulo, Brazild; Tereza Celidonio Dermatologia,
ª 2024 by the American Academy of Dermatology, Inc.

J AM ACAD DERMATOL n 2024 1

2 Research Letter J AM ACAD DERMATOL
n 2024

Table I. Characteristics of 26 women with persistent melasma treated with phenol-croton oil peel formulas
Characteristics Overall Croton oil \1% Croton oil [1%
Total, n (%) N = 26 (100) n = 9 (35) n = 17 (65)
Age median (IQR), y 46 (39-56) 44 (40-46) 46 (39-60)
Skin type median (min-max) 3 (2-5) 4 (4-4) 3 (2-4)
Baseline mMASI median (IQR) 6 (5-8) 8 (6-9) 6 (4-7)
Histology confirmation, n (%) 3 (12) 1 (11.1) 2 (12)
Previous treatments*
Peelings
Superficial, n (%) 12 (46) - 12 (71)
Medium-depth, n (%) 2 (8) - 2 (12)
Lasers
1064-nm nanosecond 6 (23) - 6 (35)
1064-nm picosecond 1 (4) - 1 (6)
2940 nm 2 (8) - 2 (12)
10,600 nm 2 (8) - 2 (12)
Microneedling 2 (8) - 2 (12)
Oral isotretinoin 1 (4) - 1 (6)
Phenol-croton oil peel
Year of procedure x (SD), y 2017 (4.7) 2015 (6.1) 2019 (3.4)
Follow-up time median (IQR), mo 46 (23-87) 144 (24-168) 44 (11-77)
Facial surface treated, %
Full face 24 (92) 9 (100) 15 (88)
Segmental peels 2 (8) - 2 (12)
Croton oil, % (volume/volume)
0.7 8 (31) 8 (89) -
0.8 1 (4) 1 (11) -
1.1 1 (4) - 1 (6)
1.2 12 (46) - 12 (71)
1.6 4 (15) - 4 (23)
Outcomes
Post mMASI median (IQR) 0 (0-1) 0 (0-0) 1 (0-1)
Relative mMASI improvement, % 100% (84-100) 100% (100-100) 88% (83-100)
(IQR)
mMASI median improvement (IQR) 6 (5-8) 7 (6-8) 5 (4-7)
Remission (achieved mMASI #1), 22 (85) 7 (78) 15 (88)
n (%)
Baseline versus post mMASIy P \ .001 P = .009 P \ .001
Physician GAIS median (IQR) 5 (5-5) 5 (5-5) 5 (4-5)
Side effects, %
Postinflammatory 9 (35) 4 (44) 5 (30)
hyperpigmentation
Acne 1 (4) - 1 (6)

GAIS, Global Aesthetic Improvement Scale; mMASI, modified Melasma Area Severity Index.
*Percentage of patient cohort receiving each treatment. Percentages do not add to 100 as patients may have received multiple treatments.
IQR ¼ Interquartile range, expressed as first quartile to third quartile.
y
Two-tailed Wilcoxon’s signed rank test was applied.

ao Paulo, Brazile; and The Skin Clinic MD, San

S~ the journal stating that all patients gave consent
Diego, California.f with the understanding that this information
may be publicly available.
Funding sources: None.
IRB approval status: Not applicable.
Patient consent: Consent for the publication of
recognizable patient photographs or other iden- Key words: chemical peels; chloasma; croton oil;
tifiable material was obtained by the authors deep chemical peel; Fintzi’s formula; Hetter’s
and included at the time of article submission to formula; melasma; phenol; phenol-croton oil;
J AM ACAD DERMATOL Research Letter 3
VOLUME jj, NUMBER j

Fig 1. Persistent melasma. Relative improvement (% difference in modified Melasma Area

Severity Index scores) among 26 patients treated with phenol-croton oil chemical peeling, per
croton oil concentration (\1% and [1%).

phorbol esters; photoaging; phytochemistry; PKC; REFERENCES

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