In was improved significantly with 2.5 watts Er,Cr:YSSG laser

In this study, we tried to brighten out not only if Er,Cr:YSSG laser could resolve gingival
hyperpigmentation but also which power of this laser could be the best. We had additional
purposes in the present study:

First, to apply defined indices to clearly show the Er,Cr:YSSG laser effects on gingival
hyperpigmentation and to compare with other studies.

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Second, to compare patients with themselves and with other patients in the way of gingival
pigmentation.

Third, to follow-up patients for a 6-month period and evaluate pigmentation recurrences.

In order to address our aims, we designed a split mouth clinical trial which randomly
allocated to treated and untreated and also 2.5 watts and 4.5 watts Er,Cr:YSSG laser in 4
quarters. We used Dummett (113) and Hedin (114) indices for gingival pigmentation which
are previously described to evaluate color intensity and extent of pigmented area,
respectively. Furthermore, visual analog scale (VAS) (115) was used in order to assess the
amount of pain perception of patients due to laser treatment.

Up to our knowledge, there are 5 studies which evaluate Er,Cr:YSSG laser on gingival
hyperpigmentation (92, 105-108). They recruited between 1 to10 patient/s and the studies
was done in Islamic Republic of Iran, Iraq, Turkey, and Thailand countries. The follow-up
period of patients varied between 4 weeks to 12 months.

Gingival depigmentation

In our study, Dummett oral pigmentation index (DOPI) (113) was improved significantly
when patients treated with 2.5 watts Er,Cr:YSSG laser after 7 days and 1, 3, and 6 months in
comparison to before treatment (p=0.002, p=0.003, p=0.003, and p=0.003, respectively).
Additionally, Dummet index was improved significantly in 6-month follow-up in comparison
to 7-day and 1-month follow-ups (p=0.002 and p=0.034, respectively).

Also Hedin index (114) was improved significantly with 2.5 watts Er,Cr:YSSG laser in all
mentioned follow-up periods in comparison to before treatment (p=0.002 for each). In 6-
month follow-up, Hedin index was improved significantly in comparison to 7-day, 1-month,
and 3-month follow-ups (p=0.023, p=0.038, and p=0.046, respectively).

Almost all similar studies with Er,Cr:YSSG laser were case reports and the researchers
describe the gingiva pigmentation condition. However, general results were similar to our
study.

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In Berk et al. (92) study, 1.5-1.75 watts Er,Cr:YSSG laser was used for gingival
hyperpigmentation in two patients. They did not use any specific index to describe their
results; However, they found gingiva completely lacking of pigmentation in both cases with a
small reddish part in maxillary gingiva in one case.

In Fekrazad and Chiniforush (105) case report, they applied a 1.5 watt Er,Cr:YSSG laser for
a black gingiva in right upper jaw. They mentioned complete healing was observed in 4-
week follow-up. Unfortunately, no defined index was used to describe the gingiva
improvement.

Abdullah and Al-shmaah (106) had studied 10 patients with gingival pigmentation. They
found that 2-2.5 watts Er,Cr:YSSG laser could improve Dummett index mean score from 3 to
0.5, immediately after treatment. The patients examined every week and it was observed that
Dummett index mean score improved to 0.4, 0.2, 0, 0, and 0 in 1 to 5 weeks follow-ups
(p<0.001). These results are similar to our findings. At last, Er,Cr:YSSG laser was applied with 1-1.75 and 1.75 watts for gingival depigmentation in Suthprasertporn (107) and Kusakci (108). In our study, Er,Cr:YSSG laser was used with 4.5 watts for depigmentation for the first time. In our study, similar findings was observed with 4.5 watts Er,Cr:YSSG laser for gingival depigmentation. Dummett and Hedin indices improved significantly in 7-day, 1-, 3- and 6- month follow-ups in comparison to before treatment (p=0.003 for Dummett index in 6- month, p=0.002 for the remaining). Additionally, we found no significant difference in Dummett and Hedin indices between 2.5 and 4.5 watts Er,Cr:YSSG laser settings, neither in follow-ups nor in total (p>0.05).

In other studies, with different lasers, depigmentation results were similar to ours. Basha et
al. (116) observed 3 watts Nd:YAG (1064 nm) laser could significantly decrease Dummett
index after 6 month in comparison to before treatment (p<0.001) and it was comparable to surgery results (p=0.294). Hedge et al. (42) found Er:YAG and CO2 lasers could decrease Dummett and Hedin indices after 6 months of treatment (p<0.001 for each). However, no significant difference was observed between 3 different methods of depigmentation (p>0.05).

Pigmentation recurrence

Although gingival depigmentation is an important measure to assess the rule of various
methods in treatment of gingival pigmentation, pigmentation recurrence may limit their

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benefits. Pigmentation recurrence or repigmentation is a usual concern in depigmentation
methods and extent, intensity and time of recurrence influence the quality of a measure, e.g.
lasers.

In our study, we found 5 cases (41.7%) with repigmentation in both 2.5 (cases #1, 2, 4, 5, and
11) and 4.5 (cases #2, 4, 5, 8, and 11) watts Er,Cr:YSSG laser.

We found only one case with repigmentation in 30-day follow-up in 2.5 watts group (case
#11). Considering Dummett and Hedin indices, this case had 100% recurrence in
pigmentation intensity since 30-day follow-up and 33.3% recurrence in pigmentation extent
since 3-month follow-up. However, in the other side of gingiva which was treated with 4.5
watts, repigmentation occurred only in 6-month follow-up (100% in intensity and 33.3% in
extent).

For the remaining of cases we found 33.3-66.7% recurrence in pigmentation intensity and
25-50% in pigmentation extent.

Various studies reported different rate of repigmentation in different time intervals.
Therefore, it is not completely understood why repigmentation occurred in some cases and
not occurred in the remaining.

As an example, Nakamura et al. (88) found no repigmentation with CO2 laser after 12
months and only 4 patients (out of 10) had repigmentation after 24 months. Additionally,
Berk et al. (92) and Kusakci (108) found no repigmentation in Er,Cr:YSSG laser treatment
after 6 months in their case reports.

On the other hand, Suthprasertporn (107) found slight repigmentation in one case (out of 2)
when depigmented with Er,Cr:YSSG laser after 11 months.

Also, Basha et al. (116) found Nd:YAG treatment result in repigmentation after 6 months.
Both Dummett index mean scores of 2.5 and 4.5 watts Er,Cr:YSSG laser after 6 months in
our study was lower than study (0.58±0.66 and 0.5±0.67 vs. 0.8±0.41).

We had also smaller repigmentation size considering Hedin index at 6-month follow-up, in
both 2.5 and 4.5 watts Er,Cr:YSSG laser than Nd:YAG laser treatment in Basha et al. (116)
study (0.58±0.66 and 0.58±0.79 vs. 0.8±0.41).

However, Basha et al. (116) observed that Hedin and Dummett indices score significantly
decreased in 6-month follow-up in comparison to before treatment (p<0.001) and it was also comparable to surgery results (p=0.294). Similar to our findings, repigmentation in Hedge et al. (42) study with CO2 and Er:YAG lasers was as soon as 1 month considering Hedin index with 1 case (2.9%) in Er:YAG laser Page 91 group with grade I and 2 case (5.7%) in CO2 laser group with grade II. In 6-month follow-up, repigmentation was seen in 10 cases (28.6%) in Er:YAG group and 8 cases (22.9%) in CO2 group. Repigmentation mechanism after depigmentation is not well-understood. Migration theory implies, active melanocytes from peripheral pigmented tissues may migrate to treated area and cause repigmentation (20). It is claimed that migrated melanocytes are come from the gingival areas with less accessibility such as the gingival margins and interdental papilla (20). However, Giannelli et al. (117) found no features of residual hyperpigmentation after 180 days in patients who were treated by Er:YAG and Diode laser for gingival hyperpigmentation. They stated that radical ablation of hyperpigmented gingiva with Er:YAG and Diode lasers in their studies, may be the reason of reducing repigmentation probability in long-term. The reasons of difference in repigmentation rate after various treatments are still unknown. However, treatment technique, follow-up duration, pigmentation assessment criteria, hormonal, genetics and ethnics factors, amount of UV exposure and nature and setting of lasers may play rules in this issue (117-121). At last, it should be remained that Erbium family lasers, including Er,Cr:YSSG laser, absorb the water and consequently these lasers have the least thermal injury and tissue penetration (1 micrometer). In thicker parts of gingiva including mid-zone of papillae, a higher energy dose may be needed to completely depigment the epithelium to the basal layer. Using low penetrating lasers may result in higher repigmentation rates due to incomplete depigmenting procedure (42). Pain perception Patient's comfort and pain feeling after Er,Cr:YSSG laser treatment was one of the main objectives of our study. Therefore, we used Visual Analog Scale (VAS) in order to quantify pain level of patients. In our study, VAS means in the first and seventh day after laser treatment were 1±0.73 and 1.00 ±1.85 for 2.5 watts and 1±0.95 and 1.08±2.06 for 4.5 watts Er,Cr:YSSG laser, respectively. Indeed, only 3 patients (25%) felt pain in both groups, 7 days after laser treatment. In Basha et al. study (116), VAS means for Nd:YAG and surgical stripping were 3.45±1.70 and 5.10 ±1.25 in the first postoperative and 0.5±1.0 and 1.15±0.81 in 7th day postoperative, Page 92 respectively. Although 7th day VAS results are similar to our results, our patients feel lesser pain in the first day after Er,Cr:YSSG laser treatment. Abdullah and Al-shmaah (106) found even lower VAS with Er,Cr:YSSG laser than ours; VAS score means immediately after treatment and one week post-operation were 0.2 and 0, respectively. However, in the same patients who were treated with diode laser on the other side of mouth, VAS score means in immediate and one-week post-operative check-ups were 4.6 and 1.6, respectively. In other case reports with Er,Cr:YSSG laser (92, 105, 107, 108), patients stated no or very mild pain immediately after treatment and in the follow-ups. In general, laser therapy for gingival depigmentation would result in lower pain perception in comparison to surgical modalities which might be due to coagulation of proteins and also sealing end of sensory nerves in wound location (98). Also, Erbium family lasers have the least thermal injury and tissue penetration among other utilized lasers and it might be the reason of lower pain perception in patients treated with Erbium lasers. Erbium lasers have high absorption in water and by this way, inhibits high temperature damage to soft tissue, blood vessels, and sensory nerves (98, 111). These mechanisms may result in faster wound healing and lower rate of pain perception in Erbium laser treated patients, consequently. Page 93 CONCLUSION Page 94 In the present study, we aimed to determine amount of Er,Cr:YSSG laser on gingival hyperpigmentation in patients with no history of smoking, related drug consuming history, periodontal problems (e.g. gingivitis and periodontitis), and previous treatment for gingival hyperpigmentation. Additionally we tried to evaluate and compare the effects of 2.5 and 4.5 watts settings in Er,Cr:YSSG laser on gingival depigmentation, recurrence rate, and amount of pain perception. Finally we designed a split-mouth randomized clinical trial with 12 patients who treated with 2.5 and 4.5 watts Er,Cr:YSSG laser in two random quadrants of lower or upper jaw which is randomly assigned. The remaining jaw left untreated as controls. Our general findings in this study could be concluded as: Both 2.5 and 4.5 watts Er,Cr:YSSG laser could significantly decline intensity and extent of gingival pigmentation as evaluated by Dummett and Hedin indices in first follow-up The first case of repigmentation observed in one month after treatment which was grade 1 in Dummett index and grade 0 in Hedin index in 2.5 watts group Altogether, repigmentation was obvious in 5 patients (41.7%) in both 2.5 and 4.5 watts Er,Cr:YSSG laser with grade 2 and lower in Dummett index and/or grade 2 and lower in Hedin index Gingival pigmentation as evaluated by Dummett and Hedin indices was still significantly lower in 6-month follow-up in comparison to before treatment, despite gingival repigmentation was occurred in some cases Pain perception, as assessed by VAS, was very low (with mean VAS score about 1 of 10) in both 2.5 and 4.5 watts and remained very low (with mean VAS score about 1 of 10) when evaluated in 7 days after treatment. In other words, in 7-day follow-up, only 3 patients (25%) still had pain related to Er,Cr:YSSG laser in both groups of 2.5 and 4.5 watts.