A e s t h e t i c M e d i c i n e c h e s t
tips for topical management of localized pigmentation
for many aesthetic patients with localized pigmentation concerns, topical interventions—and uV avoidance—will provide benefit.
When confronted with complaints of localized evidence to prove carcinogenicity. Importantly, unsuper-
pigmentary alterations, first and foremost, it
vised use of hydroquinone and use of unapproved formula-
is essential to identify and treat any underly-
tions is reportedly linked to ochronosis and unwanted side
ing dermatoses and stress the importance
effects. Therefore, patient education is crucial. Take time
of sun protection. Patients must use sunscreens—prefer-
to assure patients of the safety of the prescription agent
ably containing physical blockers like titanium dioxide
you recommend—when used as you direct—and describe
or zinc oxide—on all sun-exposed skin on a daily basis.
clearly the intended duration of therapy. Ideally, patients
Additionally, patients should practice UV avoidance
will not fear the use of hydroquinone, but they will have a
through the use of physical barriers like hats and clothing
healthy respect for the agent, reducing the risk for abuse
In the case of melasma or PIH, topical treatment options
Another topical treatment option is azelaic acid (AzA),
include retinoids, azelaic acid, hydroquinone, chemical
which may offer optimal benefit when combined with
peels, and cosmeceuticals. Reassurance and time are also
a topical corticosteroid. In a prospective, single-blinded,
essential elements of the treatment regimen that are some-
right/left comparison study, 40 Indian patients with melas-
times overlooked by the physician and the patient.1
ma were instructed to apply AzA cream 20% to one half
The selection of a particular retinoid may depend on the
of the face for 24 weeks and to apply clobetasol 0.05% for
preference of the prescriber or patient. Recent research sug-
eight weeks followed by AzA cream 20% for next 16 weeks.
gests that tazarotene 0.1% cream may offer better efficacy
Sequential therapy was associated with more significant
than adapalene 0.3% gel for the management of post-inflam-
improvement than monotherapy (p<0.01).4
matory hyperpigmentation. Findings come from a con-
Triple combination fixed therapy (fluocinolone aceton-
trolled, blinded trial involving 180 subjects with PIH related
ide 0.01%, hydroquinone 4%, tretinoin 0.05%) has become
to acne.2 Investigators evaluated improvement of both PIH
a standard intervention, as well, with evidence suggesting
and acne among subjects, who included African-Americans,
that the combination is more effective than hydroquinone
Asians, and Hispanics. While 20 percent of patients in the
monotherapy. In a multicenter randomized control trial of
tazarotene 0.1% cream group had complete resolution at
Southeast and East Asian patients (n=260), 129 individu-
week 16, only seven percent of patients in the adapalene
als were assigned to the triple combination group, and
0.3% gel group achieved complete resolution at this point.
131 were assigned to treatment with hydroquinone alone.
Hydroquinone remains a workhorse of melasma man-
During the eight-week study, assessments of Melasma GSS,
agement, despite recent controversy. The supervised use
MASI, and patient satisfaction were made. Triple combina-
of prescription topical hydroquinone had no more than a
tion therapy offered superior efficacy to monotherapy in
theoretical risk of malignancy, developing ochronosis, or
GSS and other variables, although it was associated with
other long-term safety side effects.3 There is no substantial
A e s t h e t i c M e d i c i n e c h e s t
• My own compound containing HQ, kojic acid, triamcino-
lone, and tretinoin in special base
Should patients develop irritation/al ergy to triple
combination therapy, dual combinations can be used
• Start with salicylic acid to help concomitant acne
• Otherwise, studies favor glycolic acid
Chemical peels in combination with topicals
• Increase the percentage strength of hydroquinone if needed• Consider dermabrasion for special cases• ALWAYS EMPHASIZE UV PROTECTION
Salicylic acid peels have been shown useful in PIH, includ-
ing for patients with darker skin types. In an open-label trial, 25 patients were treated with five salicylic acid peels
Numerous case reports and studies have been performed
(20- 30% concentration) provided at two-week intervals.
over the last decade highlighting the use of products such
Patients underwent two weeks of pre-treatment with
as zinc, arbutin, kojic acid, vitamin C based compounds,
hydroquinone 4%. Four of five patients with Fitzpatrick
and green tea extracts, as newer therapies for treating
type V or VI had greater than 75 percent improvement in
our melasma patients. One example of a novel therapy
for melasma that has recently appeared in the literature
Laser therapy can be effective for hyperpigmentation
demonstrates the effects of topical methimazole.6 Topical
with durable improvement, and may be used with topical
methimazole is a potent peroxidase inhibitor under
medications, like tretinoin, or vitamin C. n
investigation for the management of hyperpigmentation. Peroxidase is important in the final steps of melanogenesis
Seemal R. Desai, MD is on staff at University of
and in some tyrosinase free cells. Even at high concentra-
Texas Southwestern Medical Center and in pri-
tions, methimazole is not melanocytotoxic. Kasraee, et al.
showed 20 patients with no TSH, free thyroxine, or free iodothyronine levels. The drug is odorless and very well tol-erated. Though more randomized, controlled large cohort trials are needed to further elucidate the role of products
Adapted from an article appearing in Practical
such as methimazole, zinc, arbutin, and others, these recent
Dermatology. To read more, including further discussion of
studies give some hope to our patients suffering from
device-based treatments, visit: http://bmctoday.net/practical-
melasma for more novel therapies in our armamentarium
against this often devastating condition.
1. Taylor S, Grimes P, Lim J,et al. Postinflammatory hyperpigmentation. J Cutan Med Surg. 2009 Jul-Aug;13(4):183-91.
2. Tanghetti E, Dhawan S, Green L, et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream
Superficial chemical peels are generally effective for the
and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. J Drugs Dermatol. 2010
management of PIH and melasma when properly applied.
3. Nordlund JJ, Grimes PE, Ortonne JP. The safety of hydroquinone. J Eur Acad Dermatol Venereol. 2006 Aug;20(7):781-7.
Standard options include glycolic acid 20-70%, salicylic acid
4. Sarkar R, Bhalla M, Kanwar AJ. A comparative study of 20% azelaic acid cream monotherapy versus a sequential therapy
20-30%, TCA 10-25%, or Jessner’s solution. Pre-treatment
in the treatment of melasma in dark-skinned patients. Dermatology. 2002;205(3):249-54.
5. Chan R, Park KC, Lee MH, et al. A randomized controlled trial of the efficacy and safety of a fixed triple combination
with a course of hydroquinone 4% topically (if available) is
(fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian
thought to improve outcomes. Any patient using topical
patients with moderate to severe melasma. Br J Dermatol. 2008 Sep;159(3):697-703.
retinoids should discontinue their use for seven days prior
6. Malek J, Chedraoui A, Nikolic D, et al. Successful treatment of hydroquinone-resistant melasma using topical methima-zole. Dermatol Ther. 2013 Jan-Feb;26(1):69-72.
to the peel. They may continue to use a non-comedogenic,
7. Burns RL, Prevost-Blank PL, Lawry MA, et al. Glycolic acid peels for postinflammatory hyperpigmentation in black
patients. A comparative study. Dermatol Surg. 1997 Mar;23(3):171-4.
8. Grimes PE. The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg. 1999;
Support for the use of glycolic acid peels comes from a
study that involved 19 subjects randomized to apply a twice-
9. Kauvar AN. Successful treatment of melasma using a combination of microdermabrasion and Q-switched Nd:YAG lasers. Lasers Surg Med. 2012 Feb;44(2):117-24.
daily regimen of 2% hydroquinone/10% glycolic acid gel,
10. Rendon M, Berneburg M, Arellano I, Picardo M. Treatment of melasma. J Am Acad Dermatol 2006;54: S272-81
along with tretinoin 0.05% cream nightly or to undergo six
11. Relyveld GN, Menke HE, Westerhof W. Progressive macular hypomelanosis: an overview. Am J Clin Dermatol. 2007;8(1):13-9. http://www.afterglowskincare.ca/concerns/melasma.php
consecutive glycolic acid peels (up to 68%) with no addition-
12. Dr Linda Martin, MBBS (UNSW) Hons 1, Research Fellow, Department of Dermatology, St George Hospital, Sydney,
al topical therapy. Overall, patients treated with peels alone
NSW; Associate Professor Dedee Murrell, FAAD, Head of Dermatology, St George Hospital; Dr Richard Wittal, FACD, and Dr John Le Guay, FACD, both from the Vitiligo Clinic, Skin and Cancer Foundation, Darlinghurst, Sydney, NSW. http://www.
showed a trend for more rapid and greater improvement.7
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GUIDELINES ON STRUCTURAL REGULARITY Note: This document aims at providing guidelines on the subject “structural regularity”, which may be used both from researchers and practical engineers. This version of the document is proposed by the research groups of the universities of Catania and Florence, Italy, as a basis of discussion for all the people interested to the subject. This version