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1</a>&#44; A&#41; with no desquamation&#44; erythema&#44; or perilesional hyperkeratosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; B&#41;&#46; There was no variation in the length or thickness of the hair shaft&#44; nor was there any decrease in hair follicle density in the healthy area&#46; The skin had a parchment-like appearance&#44; and some intact hair follicles were present in the hair-loss band&#46; Alopecia was noted in the distal third of the eyebrows&#46; Clinical suspicion prompted a pathologic examination&#46; Hematoxylin-eosin staining revealed the presence of follicular fibrosis without epidermal involvement &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; A&#41;&#46; Higher magnification revealed the absence of lymphocytic infiltrate and an increase in the number of mast cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; B and C&#41;&#46; Tryptase staining revealed the presence of mast cells&#8212;up to 36 per visual field in some sections&#8212;that had even infiltrated the hair follicles &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; A&#41;&#46; With toluidine blue staining&#44; as many as 12 to 13 mast cells were visible per field &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; B&#41;&#46; The difference in the number of mast cells per field is explained by the greater sensitivity and specificity of tryptase compared to the metachromatic staining of toluidine blue&#46; The patient was screened for indolent mastocytosis&#46; Tryptase levels were normal &#40;&#60;<span class="elsevierStyleHsp" style=""></span>13&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41;&#44; but 24-hour urinary N-methylhistamine was 161<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;up to 61&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L being considered normal&#41;&#46; In view of these findings&#44; we ordered long-bone radiography&#44; which revealed no alterations&#44; and bone marrow aspiration&#44; which revealed that mast cells accounted for less than 5&#37; of all cells&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Cicatricial alopecia refers to a group of disorders characterized by irreversible hair loss caused by various processes that culminate in the replacement of hair follicles with fibrous tissue&#46; In primary cicatricial alopecias&#44; the hair follicle is the main target of the inflammatory process&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> In 2001&#44; the North American Hair Research Society presented a histopathologic classification of primary cicatricial alopecias according to predominant cell type and clinical characteristics&#59; frontal fibrosing alopecia was among the forms included in the classification&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> The differential histologic finding of an elevated number of mast cells in our patient prompted us to review the literature in order to explain the pathophysiological role of these cells&#46; We found only 1 case with characteristics similar to those of our patient&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> In that case&#44; the preponderance of mast cells was the key to a diagnosis of indolent systemic mastocytosis&#8212;an entity that was ruled out in our patient&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Mast cells are found in the skin around blood vessels&#44; smooth muscle cells&#44; hair follicles&#44; and nerve endings&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> They can be identified with hematoxylin-eosin staining&#44; special stains such as Giemsa and toluidine blue&#44; and immunohistochemical techniques &#40;c-kit&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Mast cells release mediators &#40;histamine&#44; proteases&#44; growth factors&#44; prostaglandins&#44; and cytokines&#41; that are involved in various processes such as scar formation and tissue remodeling&#44; thereby participating in normal wound healing&#44; and they also participate in the pathogenesis of fibrotic diseases such as scleroderma&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">7&#44;8</span></a> They also act as fibroblast growth factor receptors and vascular endothelial growth factor receptors&#44; thereby promoting angiogenesis&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> a process involved in hair follicle development&#46; The role of mast cells in the pathophysiology of scarring alopecia&#44; although still undetermined&#44; could be similar&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">What happens in other forms of alopecia&#63; On the basis of histologic evidence of perifollicular fibrosis and an increase in mast cells&#8212;which can cause increased elastic fiber synthesis&#8212;it has been suggested that there could be a relationship between mast cells and male-pattern androgenetic alopecia&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> Mast cells have also been implicated in the pathogenesis of alopecia areata&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The reason for elevated histamine metabolite excretion&#44; despite normal tryptase levels and the absence of myeloproliferative disorder&#44; has not been clarified&#46; The amount of methylhistamine produced depends not only on the synthesis and release of histamine but also on the contribution of exogenous histamine from food and beverages and the activity of N-methyltransferase and diamine oxidase enzymes&#44; which decompose histamine into urinary metabolites and can be influenced by alcohol&#44; drugs&#44; and genetic polymorphisms&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> This could explain the high levels of urinary methylhistamine in our patient despite the absence of indolent systemic mastocytosis&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; in light of the case described in this letter&#44; we believe that the pathophysiological role of mast cells in the various forms of scarring and nonscarring alopecia needs to be clarified&#44; as it could lead to the identification of new therapeutic targets&#46; Moreover&#44; although we were unable to demonstrate the presence of associated indolent mastocytosis in our patient&#44; we believe that this diagnosis should be considered when the pathologic features described above are encountered&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Almodovar-Real A&#44; Diaz-Martinez MA&#44; Ruiz-Villaverde R&#44; Naranjo-Sintes R&#46; Mastocitos y alopecia cicatricial&#58; &#191;hay una clara relaci&#243;n fisiopatol&#243;gica&#63;&#46; Actas Dermosifiliogr&#46; 2015&#59;106&#58;854&#8211;857&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#44;<span class="elsevierStyleHsp" style=""></span>Bilateral and symmetric recession of the frontal and temporal hairline with thinning and partial loss of eyebrow hair&#44; especially in the distal third&#46; B&#44;<span class="elsevierStyleHsp" style=""></span>Absence of associated erythema or hyperkeratosis&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#44;<span class="elsevierStyleHsp" style=""></span>Presence of fibrosis replacing and destroying the follicle&#44; and absence of epidermal involvement &#40;hematoxylin-eosin&#44; original magnification &#215; 10&#41;&#46; B&#44;<span class="elsevierStyleHsp" style=""></span>Difference between follicular fibrosis and normal&#44; interwoven collagen fibers &#40;hematoxylin-eosin&#44; original magnification &#215; 40&#41;&#46; C&#44;<span class="elsevierStyleHsp" style=""></span>Absence of lymphocytic infiltrate&#46; Presence of elevated numbers of mast cells &#40;hematoxylin-eosin&#44; original magnification &#215; 200&#41;&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A&#44;<span class="elsevierStyleHsp" style=""></span>Infiltration of mast cells into the follicle &#40;tryptase&#44; original magnification &#215; 100&#41;&#46; B&#44;<span class="elsevierStyleHsp" style=""></span>Elevated number of mast cells observed in the section &#40;toluidine blue&#44; original magnification &#215; 100&#41;&#46;</p>"
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0045" class="elsevierStylePara elsevierViewall">The authors are grateful for the collaboration of Jos&#233; Aneiros Fern&#225;ndez&#44; a pathologist at Hospital Universitario San Cecilio in Granada&#44; for his large contribution to this case&#46;</p>"
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Case and Research Letters
Mast Cells and Scarring Alopecia: Is There a Clear Pathophysiological Relationship?
Mastocitos y alopecia cicatricial: ¿hay una clara relación fisiopatológica?
A. Almodovar-Reala,
Autor para correspondencia
anamariaalmodovar@gmail.com

Corresponding author.
, M.A. Diaz-Martineza, R. Ruiz-Villaverdeb, R. Naranjo-Sintesa
a Unidad de Gestión Clínica de Dermatología Médico Quirúrgica y Venereología, Hospital Universitario San Cecilio, Granada, Spain
b Unidad de Gestión Clínica de Dermatología Médico Quirúrgica y Venereología, Hospital Universitario Virgen de las Nieves, Granada, Spain
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1</a>&#44; A&#41; with no desquamation&#44; erythema&#44; or perilesional hyperkeratosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; B&#41;&#46; There was no variation in the length or thickness of the hair shaft&#44; nor was there any decrease in hair follicle density in the healthy area&#46; The skin had a parchment-like appearance&#44; and some intact hair follicles were present in the hair-loss band&#46; Alopecia was noted in the distal third of the eyebrows&#46; Clinical suspicion prompted a pathologic examination&#46; Hematoxylin-eosin staining revealed the presence of follicular fibrosis without epidermal involvement &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; A&#41;&#46; Higher magnification revealed the absence of lymphocytic infiltrate and an increase in the number of mast cells &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; B and C&#41;&#46; Tryptase staining revealed the presence of mast cells&#8212;up to 36 per visual field in some sections&#8212;that had even infiltrated the hair follicles &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; A&#41;&#46; With toluidine blue staining&#44; as many as 12 to 13 mast cells were visible per field &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#44; B&#41;&#46; The difference in the number of mast cells per field is explained by the greater sensitivity and specificity of tryptase compared to the metachromatic staining of toluidine blue&#46; The patient was screened for indolent mastocytosis&#46; Tryptase levels were normal &#40;&#60;<span class="elsevierStyleHsp" style=""></span>13&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41;&#44; but 24-hour urinary N-methylhistamine was 161<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;up to 61&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L being considered normal&#41;&#46; In view of these findings&#44; we ordered long-bone radiography&#44; which revealed no alterations&#44; and bone marrow aspiration&#44; which revealed that mast cells accounted for less than 5&#37; of all cells&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Cicatricial alopecia refers to a group of disorders characterized by irreversible hair loss caused by various processes that culminate in the replacement of hair follicles with fibrous tissue&#46; In primary cicatricial alopecias&#44; the hair follicle is the main target of the inflammatory process&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> In 2001&#44; the North American Hair Research Society presented a histopathologic classification of primary cicatricial alopecias according to predominant cell type and clinical characteristics&#59; frontal fibrosing alopecia was among the forms included in the classification&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> The differential histologic finding of an elevated number of mast cells in our patient prompted us to review the literature in order to explain the pathophysiological role of these cells&#46; We found only 1 case with characteristics similar to those of our patient&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> In that case&#44; the preponderance of mast cells was the key to a diagnosis of indolent systemic mastocytosis&#8212;an entity that was ruled out in our patient&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Mast cells are found in the skin around blood vessels&#44; smooth muscle cells&#44; hair follicles&#44; and nerve endings&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> They can be identified with hematoxylin-eosin staining&#44; special stains such as Giemsa and toluidine blue&#44; and immunohistochemical techniques &#40;c-kit&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Mast cells release mediators &#40;histamine&#44; proteases&#44; growth factors&#44; prostaglandins&#44; and cytokines&#41; that are involved in various processes such as scar formation and tissue remodeling&#44; thereby participating in normal wound healing&#44; and they also participate in the pathogenesis of fibrotic diseases such as scleroderma&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">7&#44;8</span></a> They also act as fibroblast growth factor receptors and vascular endothelial growth factor receptors&#44; thereby promoting angiogenesis&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> a process involved in hair follicle development&#46; The role of mast cells in the pathophysiology of scarring alopecia&#44; although still undetermined&#44; could be similar&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">What happens in other forms of alopecia&#63; On the basis of histologic evidence of perifollicular fibrosis and an increase in mast cells&#8212;which can cause increased elastic fiber synthesis&#8212;it has been suggested that there could be a relationship between mast cells and male-pattern androgenetic alopecia&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> Mast cells have also been implicated in the pathogenesis of alopecia areata&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The reason for elevated histamine metabolite excretion&#44; despite normal tryptase levels and the absence of myeloproliferative disorder&#44; has not been clarified&#46; The amount of methylhistamine produced depends not only on the synthesis and release of histamine but also on the contribution of exogenous histamine from food and beverages and the activity of N-methyltransferase and diamine oxidase enzymes&#44; which decompose histamine into urinary metabolites and can be influenced by alcohol&#44; drugs&#44; and genetic polymorphisms&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> This could explain the high levels of urinary methylhistamine in our patient despite the absence of indolent systemic mastocytosis&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; in light of the case described in this letter&#44; we believe that the pathophysiological role of mast cells in the various forms of scarring and nonscarring alopecia needs to be clarified&#44; as it could lead to the identification of new therapeutic targets&#46; Moreover&#44; although we were unable to demonstrate the presence of associated indolent mastocytosis in our patient&#44; we believe that this diagnosis should be considered when the pathologic features described above are encountered&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Almodovar-Real A&#44; Diaz-Martinez MA&#44; Ruiz-Villaverde R&#44; Naranjo-Sintes R&#46; Mastocitos y alopecia cicatricial&#58; &#191;hay una clara relaci&#243;n fisiopatol&#243;gica&#63;&#46; Actas Dermosifiliogr&#46; 2015&#59;106&#58;854&#8211;857&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#44;<span class="elsevierStyleHsp" style=""></span>Bilateral and symmetric recession of the frontal and temporal hairline with thinning and partial loss of eyebrow hair&#44; especially in the distal third&#46; B&#44;<span class="elsevierStyleHsp" style=""></span>Absence of associated erythema or hyperkeratosis&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#44;<span class="elsevierStyleHsp" style=""></span>Presence of fibrosis replacing and destroying the follicle&#44; and absence of epidermal involvement &#40;hematoxylin-eosin&#44; original magnification &#215; 10&#41;&#46; B&#44;<span class="elsevierStyleHsp" style=""></span>Difference between follicular fibrosis and normal&#44; interwoven collagen fibers &#40;hematoxylin-eosin&#44; original magnification &#215; 40&#41;&#46; C&#44;<span class="elsevierStyleHsp" style=""></span>Absence of lymphocytic infiltrate&#46; Presence of elevated numbers of mast cells &#40;hematoxylin-eosin&#44; original magnification &#215; 200&#41;&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A&#44;<span class="elsevierStyleHsp" style=""></span>Infiltration of mast cells into the follicle &#40;tryptase&#44; original magnification &#215; 100&#41;&#46; B&#44;<span class="elsevierStyleHsp" style=""></span>Elevated number of mast cells observed in the section &#40;toluidine blue&#44; original magnification &#215; 100&#41;&#46;</p>"
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0045" class="elsevierStylePara elsevierViewall">The authors are grateful for the collaboration of Jos&#233; Aneiros Fern&#225;ndez&#44; a pathologist at Hospital Universitario San Cecilio in Granada&#44; for his large contribution to this case&#46;</p>"
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ISSN: 15782190
Idioma original: Inglés
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2020 Julio 29 42 71
2020 Junio 52 36 88
2020 Mayo 40 47 87
2020 Abril 36 50 86
2020 Marzo 54 35 89
2020 Febrero 6 22 28
2020 Enero 4 19 23
2019 Diciembre 4 19 23
2019 Noviembre 4 4 8
2019 Octubre 3 13 16
2019 Septiembre 1 19 20
2019 Agosto 4 18 22
2019 Julio 4 23 27
2019 Junio 4 40 44
2019 Mayo 4 97 101
2019 Abril 3 77 80
2019 Marzo 2 18 20
2019 Febrero 0 14 14
2019 Enero 2 12 14
2018 Diciembre 2 21 23
2018 Noviembre 2 3 5
2018 Octubre 9 0 9
2018 Septiembre 60 3 63
2018 Agosto 0 11 11
2018 Julio 0 11 11
2018 Junio 0 8 8
2018 Mayo 0 6 6
2018 Abril 0 3 3
2018 Marzo 0 7 7
2018 Febrero 42 7 49
2018 Enero 61 5 66
2017 Diciembre 44 7 51
2017 Noviembre 44 14 58
2017 Octubre 33 10 43
2017 Septiembre 30 6 36
2017 Agosto 45 19 64
2017 Julio 24 13 37
2017 Junio 41 26 67
2017 Mayo 31 25 56
2017 Abril 33 9 42
2017 Marzo 44 29 73
2017 Febrero 83 18 101
2017 Enero 20 5 25
2016 Diciembre 38 16 54
2016 Noviembre 35 13 48
2016 Octubre 29 25 54
2016 Septiembre 0 1 1
2016 Agosto 0 5 5
2016 Julio 4 1 5
2016 Junio 3 1 4
2016 Mayo 0 3 3
2016 Abril 0 1 1
2016 Febrero 0 7 7
2016 Enero 0 1 1
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