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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 52-year-old male patient&#44; Fitzpatrick&#8217;s phototype V&#44; using 4&#37; hydroquinone on the face for two years due to a diagnosis of melasma&#44; was referred to the Department of Dermatology at Hospital das Cl&#237;nicas&#44; Medical School&#44; S&#227;o Paulo complaining that&#44; despite the treatment&#44; the lesions had worsened&#46; Dermatological examination showed confluent grayish macules on the malar prominence on both sides and brownish macules on the frontal&#44; malar and nasal regions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Among diagnostic hypotheses&#44; the possibility of exogenous ochronosis &#40;EO&#41; secondary to hydroquinone <span class="elsevierStyleItalic">versus</span> post-inflammatory hyperpigmentation was raised&#46; An incisional biopsy was then performed&#44; and histopathology detected a brownish-ochre pigment in the superficial dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; corroborating the suggestion of EO&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was instructed to discontinue the use of hydroquinone and to use sunscreen&#46; As therapy&#44; the 1064<span class="elsevierStyleHsp" style=""></span>nm QS Nd&#58;YAG laser &#40;Etherea&#44; Vydence Medical&#41; was used&#44; first during eight sessions per month &#40;toning mode&#44; fluence between 1&#46;0&#8210;1&#46;3<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span>&#44; spot size of 8<span class="elsevierStyleHsp" style=""></span>mm&#44; frequency of 10<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; followed by four sessions a month with fluence between 4&#8210;5<span class="elsevierStyleHsp" style=""></span>J and spot size of 5<span class="elsevierStyleHsp" style=""></span>mm&#44; with slight improvement &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Subsequently&#44; he underwent seven sessions&#44; one per month&#44; of intense pulsed light &#40;IPL&#59; Etherea&#44; Vydence Medical&#59; 580<span class="elsevierStyleHsp" style=""></span>nm filter&#44; 15<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> fluence&#44; 15<span class="elsevierStyleHsp" style=""></span>ms pulse&#41;&#44; with partial response &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Finally&#44; fractional 10&#44;600<span class="elsevierStyleHsp" style=""></span>nm CO<span class="elsevierStyleInf">2</span> laser &#40;Sculptor&#44; Vydence Medical&#41; was used with a 120<span class="elsevierStyleHsp" style=""></span>nm tip&#44; energy between 80&#8210;100<span class="elsevierStyleHsp" style=""></span>mJ and density of 50<span class="elsevierStyleHsp" style=""></span>MTZ&#47;cm<span class="elsevierStyleSup">2</span> &#40;total of five bimonthly sessions&#41;&#44; with significant lesion improvement &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; After each procedure&#44; betamethasone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;g cream was prescribed daily for one week&#44; in addition to recommendations to avoid sun exposure&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The term ochronosis was first used in 1866 by Virchow&#44; related to the accumulation of an ocher-like brownish-yellow pigment on the histological examination of patients with endogenous ochronosis&#44; a rare autosomal recessive disorder determined by a mutation that results in defective production of the homogentisic acid oxidase &#40;HGO&#41; enzyme with the accumulation of homogentisic acid &#40;HG&#41; in several tissues&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Subsequently&#44; the same patterns of skin pigmentation and histological findings were observed in patients using phenol&#44; hydroquinone&#44; resorcinol&#44; mercury&#44; and picric acid&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> In these cases&#44; however&#44; the lesions were restricted to the sites of exposure to the drug and there were no systemic alterations&#44; thus receiving the name of EO&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4</span></a> Of the involved agents&#44; hydroquinone is responsible for most of the cases and possibly results from the local inhibition of HGO activity&#44; with subsequent accumulation of HG&#44; which polymerizes to form the ochronotic pigment&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Clinically&#44; EO presents as blue-gray macules or papules on photoexposed areas &#40;mainly over bony prominences&#41; of the face and cervical region&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Histopathologically&#44; short&#44; curved&#44; ocher-colored fibers &#40;described as &#8220;banana bodies&#8221;&#41; are identified in the papillary and superficial reticular dermis&#46; In more advanced cases&#44; due to the degeneration of the ochronotic fibers&#44; the deposits appear amorphous and eosinophilic&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">As for treatment&#44; discontinuation of the involved agent is recommended&#44; but it can take years to see any improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Topical treatments are ineffective &#40;trichloroacetic acid&#44; cryotherapy&#41; or little effective &#40;retinoic acid&#44; hydrocortisone&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Lasers are the most promising therapy&#44; but they do not always show satisfactory results&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The first reported modality was the CO<span class="elsevierStyleInf">2</span> laser&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Subsequently&#44; Quality-Switched &#40;QS&#41; lasers started being used with satisfactory results&#44; including Ruby &#40;694<span class="elsevierStyleHsp" style=""></span>nm&#41;&#44; Alexandrite &#40;755<span class="elsevierStyleHsp" style=""></span>nm&#41; and Nd&#58;YAG &#40;1&#44;064<span class="elsevierStyleHsp" style=""></span>nm&#41; lasers&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;4&#44;7</span></a> More recently&#44; improvement has been reported with the use of Intense Pulsed Light &#40;IPL&#59; 570<span class="elsevierStyleHsp" style=""></span>nm filter&#41; and Nd&#58;YAG picosecond laser &#40;1064<span class="elsevierStyleHsp" style=""></span>nm&#41;&#44; as well as laser combinations &#40;QS Nd&#58;YAG followed by CO<span class="elsevierStyleInf">2</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">For the present patient&#44; the modality initially employed was the QS Nd&#58;YAG laser&#44; which acts in ochronosis possibly analogous to the removal of tattoo pigment from the dermis&#58; pigment fragmentation and subsequent phagocytosis and elimination by lymphatic drainage or the transepidermal route&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In the absence of a satisfactory answer&#44; IPL is used&#59; although the mechanism of lesion improvement is better understood in the treatment of epidermal lesions&#44; the use of high energy and filters with higher cutoff points allows greater light penetration and the treatment of dermal lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It is noteworthy&#44; however&#44; that its use in patients with phototypes &#62; IV should often be avoided or a test area is suggested&#44; aiming at observing changes in pigmentation&#46; In the present case&#44; the application was safe and promoted a more significant improvement in relation to the described QS&#46; Finally&#44; the fractional CO<span class="elsevierStyleInf">2</span> laser was used&#44; which possibly promotes extrusion of the pigment through the ablative microzones in the epidermis and dermis&#44; helping to lighten the lesion&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Therefore&#44; the combination of different technologies&#44; wavelengths and firing times resulted in an excellent response in the treatment of this patient&#44; affected by a disease that always constitutes a therapeutic challenge&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0055" class="elsevierStylePara elsevierViewall">William Wiegandt Ceglio&#58; Approval of the final version of the manuscript&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Mariana Figueiroa Careta&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; drafting and editing of the manuscript&#59; collection&#44; analysis&#44; and interpretation of data&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#59; critical review of the manuscript&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Regia Patriota&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the manuscript&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Lu&#237;s Ant&#244;nio Torezan&#58; Approval of the final version of the manuscript&#59; design and planning of the study&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Journal Information
Vol. 98. Issue 1.
Pages 138-140 (1 January 2023)
Visits
7466
Vol. 98. Issue 1.
Pages 138-140 (1 January 2023)
Letter - Therapy
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Exogenous ochronosis successfully treated with the combination of intense pulsed light and fractional CO2 laser
Visits
7466
William Wiegandt Ceglio
Corresponding author
william.wiegandt@hc.fm.usp.br

Corresponding author.
, Mariana Figueiroa Careta, Regia Patriota, Luís Antônio Torezan
Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil
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Dear Editor,

A 52-year-old male patient, Fitzpatrick’s phototype V, using 4% hydroquinone on the face for two years due to a diagnosis of melasma, was referred to the Department of Dermatology at Hospital das Clínicas, Medical School, São Paulo complaining that, despite the treatment, the lesions had worsened. Dermatological examination showed confluent grayish macules on the malar prominence on both sides and brownish macules on the frontal, malar and nasal regions (Fig. 1).

Figure 1.

Patient showing grayish maculae on the malar prominences and brownish maculae on the frontal, malar and nasal regions.

(0.13MB).

Among diagnostic hypotheses, the possibility of exogenous ochronosis (EO) secondary to hydroquinone versus post-inflammatory hyperpigmentation was raised. An incisional biopsy was then performed, and histopathology detected a brownish-ochre pigment in the superficial dermis (Fig. 2), corroborating the suggestion of EO.

Figure 2.

Histopathology of the skin of the left malar region revealing brownish-ocher pigmented clumps in the superficial reticular dermis and a mild interstitial and perivascular lymphohistiocytic infiltrate (Hematoxilin & eosin, 100X).

(0.35MB).

The patient was instructed to discontinue the use of hydroquinone and to use sunscreen. As therapy, the 1064nm QS Nd:YAG laser (Etherea, Vydence Medical) was used, first during eight sessions per month (toning mode, fluence between 1.0‒1.3J/cm2, spot size of 8mm, frequency of 10Hz), followed by four sessions a month with fluence between 4‒5J and spot size of 5mm, with slight improvement (Fig. 3). Subsequently, he underwent seven sessions, one per month, of intense pulsed light (IPL; Etherea, Vydence Medical; 580nm filter, 15J/cm2 fluence, 15ms pulse), with partial response (Fig. 4). Finally, fractional 10,600nm CO2 laser (Sculptor, Vydence Medical) was used with a 120nm tip, energy between 80‒100mJ and density of 50MTZ/cm2 (total of five bimonthly sessions), with significant lesion improvement (Fig. 5). After each procedure, betamethasone 1mg/g cream was prescribed daily for one week, in addition to recommendations to avoid sun exposure.

Figure 3.

Slight improvement of lesions after the use of QS Nd:YAG 1064nm laser (Etherea; Vydence Medical) for eight sessions in toning mode (fluence between 1.0‒1.3J/cm2, 8-mm spot size and frequency of 10Hz), followed by four sessions with a fluence of 4‒5J and a spot size of 5mm.

(0.15MB).
Figure 4.

Partial response after seven sessions of Intense Pulsed Light (IPL; Etherea, Vydence Medical) using a 580nm filter, with a fluence of 15J/cm2 and a single pulse of 15ms.

(0.14MB).
Figure 5.

Significant lesion improvement after five sessions of fractional 10,600nm CO2 laser (Sculptor, Vydence Medical) with 120nm tip, energy between 80‒100mJ and density of 50MTZ/cm².

(0.18MB).

The term ochronosis was first used in 1866 by Virchow, related to the accumulation of an ocher-like brownish-yellow pigment on the histological examination of patients with endogenous ochronosis, a rare autosomal recessive disorder determined by a mutation that results in defective production of the homogentisic acid oxidase (HGO) enzyme with the accumulation of homogentisic acid (HG) in several tissues.1–3

Subsequently, the same patterns of skin pigmentation and histological findings were observed in patients using phenol, hydroquinone, resorcinol, mercury, and picric acid.1,2,4 In these cases, however, the lesions were restricted to the sites of exposure to the drug and there were no systemic alterations, thus receiving the name of EO.2,4 Of the involved agents, hydroquinone is responsible for most of the cases and possibly results from the local inhibition of HGO activity, with subsequent accumulation of HG, which polymerizes to form the ochronotic pigment.2,5

Clinically, EO presents as blue-gray macules or papules on photoexposed areas (mainly over bony prominences) of the face and cervical region.2 Histopathologically, short, curved, ocher-colored fibers (described as “banana bodies”) are identified in the papillary and superficial reticular dermis. In more advanced cases, due to the degeneration of the ochronotic fibers, the deposits appear amorphous and eosinophilic.2,3,5

As for treatment, discontinuation of the involved agent is recommended, but it can take years to see any improvement.3 Topical treatments are ineffective (trichloroacetic acid, cryotherapy) or little effective (retinoic acid, hydrocortisone).2,3 Lasers are the most promising therapy, but they do not always show satisfactory results.2,3 The first reported modality was the CO2 laser.6 Subsequently, Quality-Switched (QS) lasers started being used with satisfactory results, including Ruby (694nm), Alexandrite (755nm) and Nd:YAG (1,064nm) lasers.1,4,7 More recently, improvement has been reported with the use of Intense Pulsed Light (IPL; 570nm filter) and Nd:YAG picosecond laser (1064nm), as well as laser combinations (QS Nd:YAG followed by CO2).8–10

For the present patient, the modality initially employed was the QS Nd:YAG laser, which acts in ochronosis possibly analogous to the removal of tattoo pigment from the dermis: pigment fragmentation and subsequent phagocytosis and elimination by lymphatic drainage or the transepidermal route.7 In the absence of a satisfactory answer, IPL is used; although the mechanism of lesion improvement is better understood in the treatment of epidermal lesions, the use of high energy and filters with higher cutoff points allows greater light penetration and the treatment of dermal lesions.8 It is noteworthy, however, that its use in patients with phototypes > IV should often be avoided or a test area is suggested, aiming at observing changes in pigmentation. In the present case, the application was safe and promoted a more significant improvement in relation to the described QS. Finally, the fractional CO2 laser was used, which possibly promotes extrusion of the pigment through the ablative microzones in the epidermis and dermis, helping to lighten the lesion.10

Therefore, the combination of different technologies, wavelengths and firing times resulted in an excellent response in the treatment of this patient, affected by a disease that always constitutes a therapeutic challenge.

Financial support

None declared.

Authors’ contributions

William Wiegandt Ceglio: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.

Mariana Figueiroa Careta: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.

Regia Patriota: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.

Luís Antônio Torezan: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.

Conflicts of interest

None declared.

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Study conducted at the Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.

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