Dear Editor:
Melasma is a common acquired hyperpigmentary disorder of the face, but its treatment
remains challenging. A procedure called "laser toning" that uses a low-energy 1064-nm
Q-switched Nd:YAG laser was recently introduced for the treatment of melasma, demonstrating
good results1,2,3. However, the possibility of mottled hypopigmentation is a major
concern with this treatment, because it rarely recovers spontaneously4. The underlying
mechanisms of mottled hypopigmentation are not completely understood. Whether the
hypopigmentation is caused by reduced pigmentation with intact melanocytes or a decrease
or absence of melanocytes remains to be elucidated.
Therefore, this study investigated the changes in melanin and melanocytes in hypopigmented
lesions that develop after low-fluence 1,064-nm Q-switched Nd:YAG laser treatment
for melasma. This study was approved by the institutional review board of Ajou University
Hospital (AJIRB-MED-KSP-12-374).
Patient 1, a 41-year-old woman with Fitzpatrick skin type IV, presented with typical
mottled hypopigmentation after treatment with 1,064-nm Q-switched Nd:YAG laser for
melasma (Fig. 1A). The duration of hypopigmentation was 7 years. Skin biopsies were
obtained from the hypopigmented, hyperpigmented (i.e., melasma), and adjacent perilesional
normal skin areas. Hematoxylin and eosin and Fontana-Masson staining as well as immunohistochemical
staining using melanocyte-specific markers including monoclonal antibodies against
human gp100 (NKI/ beteb; Monosan, Uden, the Netherlands), tyrosinase (Thermo Scientific,
Fremont, CA, USA), and microphthalmia-associated transcription factor (MITF; Leica
Biosystems, Newcastle, UK) were performed. The numbers of MITF+ melanocytes per 1-mm
length of rete ridge were counted. The expression levels of gp100 and tyrosinase were
measured as the ratio of stained area to measured epidermal area.
The general histological findings of the hypopigmented skin were unremarkable. There
was no collagen remodeling or scarring. Fontana-Masson staining demonstrated the almost
complete absence of melanin pigment in hypopigmented skin (Fig. 1B). The number of
melanocytes, as determined by MITF expression, was not substantially different in
lesional skin (n=4) compared to perilesional normal skin (n=5) or melasma skin (n=3).
Consistently, tyrosinase level was not lower in lesional skin than perilesional normal
skin but was higher than that in melasma skin as expected. Interestingly, gp100 expression
was higher in the hypopigmented lesion than perilesional normal skin and even melasma
skin. Similar findings were observed in patient 2, a 49-year-old woman with Fitzpatrick
skin type III who presented with typical mottled hypopigmentation after laser toning
for 1 year (Fig. 2A). Lesional skin biopsy showed the complete absence of melanin
pigment in hypopigmented skin. However, there was no reduction in the number of melanocytes,
and gp100 expression was elevated (Fig. 2B).
The results of the present study clearly demonstrate that the histologic features
of laser toning-induced hypopigmentation are characterized by almost destroyed melanosome
pigments and a preserved the number of melanocytes. However, it is unclear whether
the number of melanocytes is reduced in the hypopigmented skin. One study indicates
hypopigmentation might be due to melanocytopenia5. However, in that study, lesional
skin was not compared with adjacent perilesional normal skin. The other studies suggest
the number of melanocytes in hypopigmented skin is normal6,7. In the present study,
there was no difference in the mean numbers of MITF-stained melanocytes between lesional
skin and perilesional normal skin. Interestingly, we noticed that the levels of the
structural protein gp100 were preserved and rather elevated in lesional skin compared
to perilesional normal skin. Moreover, in patient 1, gp100 levels of hypopigmented
skin were clearly elevated compared to that in hyperpigmented skin. Although the reason
for this result is unclear, these findings nonetheless suggest the melanogenic activity
in the melanocytes was impaired and the cells failed to produce fully matured melanosomes.
Considering that the proposed action mechanism of laser toning is subcellular selective
photothermolysis of melanosomes and not melanocytes, it is speculated that melanocytes
survived but were functionally downregulated such that they did not produce fully
matured melanosomes. The cumulative dose of repetitive laser treatment may affect
melanocyte function, resulting in the development of hypopigmentation. Therefore,
treatment activating or stimulating melanogenesis in the melanocytes would be required.
To this end, treatment with focused narrowband ultraviolet B therapy has been used
with some success8.
In conclusion, laser toning-induced hypopigmentation is characterized by almost destroyed
melanosome pigments and a preserved number of melanocytes, which seem to be functionally
downregulated not to produce fully matured melanosomes. Thus, early intervention aiming
to restore melanocyte function would be required.