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which may be mitigated by the new minoxidil formulations&#46; A Cochrane review article has been published on interventions for female AGA&#46; That review included 47 studies and 5&#44;290 patients and concluded that the application of topical minoxidil at concentrations between 2&#37; and 5&#37; is effective and safe&#44; and is superior to other treatments such as the antiandrogens and low-level laser therapy &#40;LLLT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">2</span></a> A number of studies looking at the new formulations of minoxidil have shown improved efficacy and better tolerance of foam presentations versus the hydroalcoholic solution in both men<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">3</span></a> and women<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">4</span></a> with AGA&#44; due to the lower concentration of propylene glycol&#44; which enhances its cosmetic acceptability&#46; 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the use of low doses of oral minoxidil could be a very interesting option in patients with AGA&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antiandrogens</span><p id="par0025" class="elsevierStylePara elsevierViewall">A number of publications with high levels of evidence support the safety of finasteride and dutasteride in men and women with AGA&#44; because of both the low risk of adverse sexual effects &#40;very similar to placebo&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">8&#44;9</span></a> and the inexistent increase in the risk of cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">10&#44;11</span></a> Regarding one of the most relevant novelties in AGA in recent years&#44; the authors draw attention to the appearance of the drug dutasteride as a safe and effective option in AGA&#44; both in men and in women&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">12&#8211;14</span></a> This dual 5&#945;-reductase inhibitor&#44; with a longer half-life than finasteride&#44; has been shown to be more effective that finasteride in predominantly frontal male AGA without presenting additional adverse effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">14&#8211;17</span></a> With respect to new methods of administration of the antiandrogens&#44; the study by Moftah et al&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">18</span></a> stands out because it demonstrates the usefulness and safety of microinjections of dutasteride in female AGA&#46; Those authors described the treatment of 86 women versus 40 controls&#44; finding a 63&#37; improvement in hair density in the active treatment group versus 17&#37; of the control group &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; with no side effects&#46; The local injection of dutasteride into the scalp after nerve block may be a useful therapeutic option in male and female AGA either in monotherapy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; or as a complement to traditional treatment&#46; Our working group has performed a study in 5 men with AGA&#44; observing the efficacy of local injections of dutasteride every 3 months&#44; with no side effects or alterations of hormone levels in the blood &#40;in press &#8211; data not published&#41;&#46; As an alternative to the oral administration of antiandrogens&#44; several articles describe the inhibitory activity of topical 0&#46;25&#37; finasteride on follicular 5-alfa-reductase&#44; with lower levels of systemic absorption than oral finasteride&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">19&#44;20</span></a> Studies of the clinical efficacy of topical 0&#46;5&#37; finasteride performed by Milani et al&#46; are still to be published &#40;personal communication&#41;&#59; those authors have shown an improvement in male AGA at 6 months in 70&#37; of patients treated in monotherapy&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Prostaglandins</span><p id="par0030" class="elsevierStylePara elsevierViewall">Among the prostaglandins &#40;PG&#41;&#44; the PGF2 analogs latanoprost and bimatoprost are known to stimulate hair growth by prolonging the anagen phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">21&#44;22</span></a> However&#44; the concentration of these drugs necessary to improve hairy density in AGA is very high &#40;0&#46;1&#37; latanoprost&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">22</span></a> leading to limitations due to their high cost&#46; Recent research is looking at other drugs that block the PGD2 receptor &#40;GPR44&#41;&#44; which has an inhibitory effect on hair growth and which is known to be elevated in the scalp of patients with AGA&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">23&#8211;25</span></a> Setipiprant &#40;KITH-105&#41; is a orally administered GPR44 receptor inhibitor that is in the clinical trial phase for asthma&#44; but could have a potential application in AGA&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">26</span></a> A phase <span class="elsevierStyleSmallCaps">II</span> clinical trial is underway to evaluate the use of oral setipiprant in comparison with placebo and with finasteride&#44; 1<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; in men aged 18 to 41 years with AGA &#40;NCT02781311&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Physical Therapies</span><p id="par0035" class="elsevierStylePara elsevierViewall">Several methodologically robust articles have demonstrated the usefulness of LLLT in both male and female AGA&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">27&#8211;30</span></a> The periodic stimulation of hair follicles with LLLT favors the conversion of follicles in telogen to follicles in anagen&#44; and the transformation of vellous follicles into terminal follicles due to the induced perifollicular inflammation&#44; which potentiates follicular growth through activation of stem cells in the bulge&#46; Furthermore&#44; local blood flow is increased and inflammatory mediators and VEGF &#40;vascular endothelial growth factor&#41; are released&#44; favoring the growth of pluripotent stem cells and thus stimulating hair growth and thickening&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">27&#8211;30</span></a> In the opinion of the authors&#44; the optimal LLLT protocol for men and women with AGA still remains to be defined&#44; although this therapy appears to be an interesting option with a mechanism of action that differs from traditional therapies&#46; Very interesting articles have been published recently on another physical therapy&#44; microneedling&#44;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">31&#44;32</span></a> a technique that consists of creating microperforations in the scalp in order to produce controlled damage and the release of endogenous growth factors&#44; which stimulate hair growth&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Regenerative Medicine Therapies</span><p id="par0040" class="elsevierStylePara elsevierViewall">In the final group we have included regenerative medicine therapies designed to stimulate follicular stem cells&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Three new studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">33&#8211;35</span></a> one of which is a meta-analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">34</span></a> have been published on the potential usefulness of platelet-rich plasma &#40;PRP&#41; in male and female AGA&#44; showing PRP to achieve increased hair density and number of follicles in anagen with virtually no adverse effects&#46; In the opinion of the authors&#44; this treatment has an excellent safety profile&#44; but its efficacy profile is variable&#44; with a very good response in some patients but more modest in others&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">The initial results have now been published on the usefulness and safety of topical activators of the Wnt&#47;&#946;-catenin pathway in AGA&#58; methyl vanillate&#44;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">36</span></a> valproic acid&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">37</span></a> and SM04554&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">38</span></a> The Wnt&#47;&#946;-catenin pathway regulates activation of the nest of stem cells localized in the follicular bulge&#44; a process necessary for the initiation and maintenance of the follicular anagen phase and whose inhibition has been related with the loss of hair density in AGA&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">36&#8211;38</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">It has recently been reported that pharmacological inhibition of 2 of the signaling pathways implicated in downregulation of the proliferation and differentiation of the follicular bulge stem cells and in initiation of the follicular resting phase&#44; JAK&#47;STAT and mTOR&#47;PI3<span class="elsevierStyleHsp" style=""></span>K&#44; effectively activates hair growth in mouse models and in human follicles in vitro&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">39&#44;40</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0060" class="elsevierStylePara elsevierViewall">It has also been shown that the transient production of reactive oxygen species by photodynamic therapy in vivo in mouse skin induces several signaling pathways that ultimately activate of the nest of hair follicle stem cells&#44; accelerating hair growth&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">41</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">e&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Finally&#44; we would like to comment on stem cell treatments&#46; Basically&#44; there are 2 types of stem cell treatment&#58; E1&#44; which involves hair cloning by the injection of follicular stem cells previously expanded in vitro&#44; producing the growth of new follicles&#59; and E2&#44; adipose-derived stem cells&#46; In the first case&#44; few advances have been reported since the initial studies in mouse models published by McElwee et al&#46; in 2003&#44;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">42</span></a> and the preliminary results of the only clinical trial performed in humans were very limited&#44; with an increase in hair growth of only 6&#37; &#40;McElwee&#44; communication at the World Trichology Conference in Barcelona&#44; 2012&#41;&#46; Although this treatment will be a landmark in the treatment of AGA&#44; further research is still required&#46; The second technique consists of performing liposuction to obtain mesenchymal stem cells&#44; which are then conditioned and injected into the scalp to stimulate hair growth&#46; Preliminary studies have shown the possible usefulness of adipose-derived stem cells in AGA&#44;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">43&#8211;45</span></a> but further studies are needed to confirm the safety and efficacy of this therapy&#46;</p></li></ul></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Alopecia Areata</span><p id="par0070" class="elsevierStylePara elsevierViewall">The therapeutic novelties in the treatment of AA fall into 2 groups&#58; a&#41; new data and forms of application of traditional treatments&#44; and b&#41; new therapies&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">a&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the first group&#44; we draw attention to a review article by Lamb et al&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">46</span></a> on the use of immunotherapy with diphencyprone in 133 patients with AA&#46; A response was observed in 72&#37; of patients&#44; with regrowth of over 90&#37; in 16&#37; of cases&#46; Another important novelty in this first group is the use of pulsed systemic corticosteroids in AA&#46; There is evidence of greater safety and at least the same efficacy when corticosteroids are used in pulses&#46;<a class="elsevierStyleCrossRefs" href="#bib0615"><span class="elsevierStyleSup">47&#44;48</span></a> In a study performed by the research group of Hospital Ram&#243;n y Cajal in Madrid&#44;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">48</span></a> the use of oral dexamethasone at a dose of 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d on 2 consecutive days every week produced regrowth in 25&#47;31 patients with alopecia totalis or universalis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; with mild adverse effects in 32&#37;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">b&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the second group of novel therapies&#44; the possible usefulness of the combination of simvastatin and ezetimibe in AA stands out for its immunomodulator effect&#44; demonstrated in a study in which 14 of 19 patients with extensive AA responded&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">49</span></a> However&#44; other authors have reported significantly lower response rates with this treatment &#40;1&#47;20 patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">50</span></a> The combination of simvastatin and ezetimibe may be a useful concomitant therapy to improve the response to other treatments&#44; but its action in monotherapy would appear to be limited&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The greatest novelty in the field of AA&#44; and one of the most important in trichology in recent years&#44; is the therapeutic usefulness of the anti-Janus kinase &#40;anti-JAK&#41; agents&#44;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">51&#8211;58</span></a> not only for their apparent efficacy&#44; but also because these are the first agents that act against a specific pathogenic target in AA&#46; The JAK pathway is implicated in the activation of CD8 cytotoxic T cells and in the production of interferon-&#947;&#44; which are fundamental to the onset of AA&#46; Their inhibition appears to induce regrowth in these patients&#46; The drugs reported to be potentially useful in AA are tofacitinib<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">55&#8211;58</span></a> &#40;whose approved indication is rheumatoid arthritis&#41;&#44; ruxolitinib<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">51&#44;52&#44;54</span></a> &#40;approved for use in myelofibrosis and polycythemia vera&#41; and baricinitib<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">53</span></a> &#40;pending approval of indication in rheumatoid arthritis&#41;&#46; These drugs are administered orally and have an acceptable safety profile&#59; because of their indications&#44; they are usually prescribed for long-term administration and are well tolerated&#46; In addition&#44; the first study has been published on the usefulness of topical ruxolitinib in AA of the eyebrows&#44;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">52</span></a> and clinical trials are already underway with new topical anti-JAK agents&#44; such as LEO-124249 &#40;NCT02561585&#41;&#46; The main limitation of these treatments is their cost&#46; However&#44; they open new lines of therapeutic research into<span class="elsevierStyleHsp" style=""></span>AA&#46;</p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Scarring Alopecia</span><p id="par0090" class="elsevierStylePara elsevierViewall">The etiology and pathogenesis of frontal fibrosing alopecia &#40;FFA&#41; are currently considered to involve a double autoimmune and hormonal mechanism&#46;<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">59&#8211;61</span></a> This justifies the use both of anti-inflammatory drugs &#40;corticosteroids&#41; to reduce the autoimmune inflammation and of antiandrogens &#40;finasteride and dutasteride&#41;&#46; In recent years&#44; several studies have been published that show the potential usefulness of these drugs in FFA&#44;<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">59&#8211;64</span></a> including a multicenter Spanish study of 355 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">59</span></a> The mechanism by which the antiandrogens act in the FFA is not fully understood&#44; but it would appear that inhibition of the action of male hormones on the root of the follicle helps to stabilize the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">59&#44;61</span></a> Some authors have even reported regrowth after the administration of antiandrogens&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">64</span></a> However&#44; others remain skeptical regarding the use of these drugs in FFA&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">65</span></a> Although their mechanism of action remains unclear&#44; there is evidence that a hormonal factor is responsible for<span class="elsevierStyleHsp" style=""></span>FFA&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">61</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Another important therapeutic novelty in FFA and lichen planopilaris &#40;LPP&#41; is the use of the oral antidiabetic agent pioglitazone&#44; which blocks the peroxisome proliferator-activated receptor-&#947; &#40;PPAR&#947;&#41;&#46; Recent studies have suggested that altered function of PPAR-&#947; may play a role in the initiation of inflammation in LPP and FFA&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">66</span></a> Four studies have been published in which pioglitazone has been used to treat LPP and FFA&#46;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">67&#8211;70</span></a> Results have been variable&#44; with an efficacy of between 20&#37; and 70&#37; and adverse effects in up to 50&#37;&#46; Marquez and Camacho<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">71</span></a> performed a study in 68 women with FFA&#44; with favorable results in 64&#37; after the use of pioglitazone&#46; The authors believe that pioglitazone could be effective in some cases&#44; but intolerance is not uncommon&#44; mainly in the form of lower limb edema and weight gain&#44; leading to drug withdrawal in a significant number of cases&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In the case of folliculitis decalvans &#40;FD&#41;&#44; a Spanish multicenter study including 82 patients<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">72</span></a> concluded that the most effective treatment &#40;improvement in 15&#47;15 patients treated&#41; with the longest period of remission after treatment &#40;7&#46;2 months&#41; was the combination of rifampicin plus clindamycin administered for 10 weeks &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Another therapeutic novelty reported in the literature is the possible usefulness of photodynamic therapy &#40;PDT&#41; with benefit in 9 out of 10 patients with FD&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">73</span></a> However&#44; other authors have reported a negative experience with PDT in 3 out of 3 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">74</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Hair transplant</span><p id="par0105" class="elsevierStylePara elsevierViewall">To complete this review&#44; 2 novel methods stand out in the field of hair transplant&#46; First&#44; the arrival of the new automated robotic systems that reduce operating times and&#44; in some cases&#44; improve the rates of follicular transection in the follicular unit extraction technique&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">75</span></a> However&#44; we consider that results depend more on surgical dexterity than on the device used&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The other novelty is a new technique of follicular extraction&#44; known as partial longitudinal extraction&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">76</span></a> This consists of only partially extracting the follicular units&#44; so that the part of the follicle that remains in the donor region can survive and regenerate an intact follicular unit&#44; thus avoiding the progressive depopulation that occurs in the donor region&#46; The concept is interesting&#44; but still needs to be developed&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">A summary of the most relevant therapeutic novelties in trichology is presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">In recent years we have seen great advances in the therapeutics of trichology&#44; but more importantly&#44; new lines of research have been opened that will allow us to continue advancing&#46; The developments discussed in this review&#44; which has looked at the past 3 years&#44; are more than hope&#44; they are now a reality&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of Interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Androgenetic Alopecia"
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          "titulo" => "Scarring Alopecia"
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            1 => "Androgenetic alopecia"
            2 => "Dutasteride"
            3 => "Alopecia areata"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients&#8217; quality of life&#46; Many new treatments have been introduced in recent years&#46; This review summarizes the main ones in 4 groups&#58; a&#41; For androgenetic alopecia&#44; we discuss new excipients for oral minoxidil&#44; dutasteride&#44; and finasteride as well as new forms of application&#59; prostaglandin agonists and antagonists&#59; low-level laser therapy&#59; and regenerative medicine with Wnt signaling activators and stem cell therapy&#46; b&#41; For alopecia areata&#44; Janus kinase inhibitors are reviewed&#46; c&#41; For frontal fibrosing alopecia&#44; we discuss the use of antiandrogens and&#44; for some patients&#44; pioglitazone&#46; d&#41; Finally&#44; we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La tricolog&#237;a ocupa un &#225;rea importante dentro de la pr&#225;ctica asistencial de los dermat&#243;logos por la frecuencia de las diferentes tricosis y por el gran impacto que producen en la calidad de vida de los pacientes&#46; Durante los &#250;ltimos a&#241;os hemos comprobado la incorporaci&#243;n de muchas novedades terap&#233;uticas en tricolog&#237;a&#46; El objetivo de la presente revisi&#243;n es resumir de una forma pr&#225;ctica las principales novedades terap&#233;uticas tricol&#243;gicas&#44; agrup&#225;ndolas en 4 apartados&#58; a&#41; alopecia androg&#233;nica&#58; nuevos excipientes de minoxidil&#44; dutasterida y finasterida oral y nuevas formas de aplicaci&#243;n de estos antiandr&#243;genos&#44; agonistas y antagonistas de las prostaglandinas&#44; l&#225;ser de baja potencia y medicina regenerativa &#8212;activadores de la v&#237;a Wnt y terapia con c&#233;lulas madre&#8212;&#59; b&#41; alopecia areata&#58; f&#225;rmacos anti-JAK&#59; c&#41; alopecia frontal fibrosante&#58; antiandr&#243;genos y&#44; en algunos pacientes&#44; pioglitazonas&#44; y d&#41; trasplante capilar&#58; nuevos dispositivos tecnol&#243;gicos y nuevas t&#233;cnicas de extracci&#243;n para optimizar la reserva de unidades foliculares&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Va&#241;&#243;-Galv&#225;n S&#44; Camacho F&#46; Novedades terap&#233;uticas en tricolog&#237;a&#46; Actas Dermosifiliogr&#46; 2017&#59;108&#58;221&#8211;228&#46;</p>"
      ]
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A 26-year-old man with androgenetic alopecia at the vertex&#46; Improvement after treatment with injections of dutasteride in monotherapy every 3 months&#46; A&#44; At baseline&#46; B&#44; After a year of treatment&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A 34-year-old woman with alopecia areata universalis&#46; Hair regrowth after treatment with oral minipulses of dexamethasone at a dose of 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d on 2 consecutive days each week&#46; A&#44; At baseline&#46; B&#44; Month 4 of treatment&#46; B&#44; Month 8 of treatment&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A 33-year-old woman with folliculitis decalvans&#46; Clinical improvement after 10 weeks of treatment with rifampicin&#44; 300<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours&#44; plus clindamycin&#44; 300<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours&#46; A&#44; At baseline&#46; B&#44; At the end of treatment&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AGA&#44; androgenetica alopecia&#59; FFA&#44; frontal fibrosing alopecia&#59; JAK&#44; Janus kinase&#59; LLLT&#44; low-level laser therapy&#59; LPP&#44; lichen planopilaris&#59; PGD2-GPR44&#44; prostaglandin D2 receptor&#59; PRP&#44; platelet-rich plasma&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top" style="border-bottom: 2px solid black">Area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top" style="border-bottom: 2px solid black">Novelties in Traditional Treatments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top" style="border-bottom: 2px solid black">New Therapies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8226; Androgenetic alopecia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Effectiveness of minoxidil in male and female AGA<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">1&#44;2</span></a><br>&#8226; New foam formulations of minoxidil to improve cosmetic acceptability<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">3&#44;4</span></a><br>&#8226; Use of niosomes to improve the topical absorption of minoxidil<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">5</span></a><br>&#8226; Low-dose oral minoxidil<br>&#8226; Safety of the 5&#945;-reductase inhibitors<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">8&#8211;11</span></a><br>&#8226; Oral dutasteride in male and female AGA<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">12&#8211;17</span></a><br>&#8226; Effectiveness and safety of PRP<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">33&#8211;35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Dutasteride microinjections<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">18</span></a><br>&#8226; Topical finasteride<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">19&#44;20</span></a><br>&#8226; PGD2-GPR44 inhibitors &#40;setipiprant&#41;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">26</span></a><br>&#8226; LLLT<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">27&#8211;30</span></a><br>&#8226; Microneedling<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">31&#44;32</span></a><br>&#8226; Topical activators of the Wnt&#47;&#946;-catenin pathway<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">36&#8211;38</span></a><br>&#8226; Adipose-derived stem cells<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">43&#8211;45</span></a><br>&#8226; Therapy with stem cells previously expanded in vitro<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8226; Alopecia areata&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Effectiveness of diphencyprone<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">46</span></a><br>&#8226; Pulsed corticosteroids<a class="elsevierStyleCrossRefs" href="#bib0615"><span class="elsevierStyleSup">47&#44;48</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Simvastatin plus ezetimibe<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">49&#44;50</span></a><br>&#8226; Anti-JAK agents&#58; tofacitinib&#44;<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">55&#8211;58</span></a> ruxolitinib&#44;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">51&#44;52&#44;54</span></a> baricitinib<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">53</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8226; FFA&#47;LPP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Usefulness and safety of the antiandrogens &#40;finasteride and dutasteride&#41; in FFA<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">59&#8211;61</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Usefulness of pioglitazone in LPP and FFA<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">67&#44;71</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8226; Folliculitis decalvans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Effectiveness of treatment with rifampicin plus clindamycin<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">72</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Possible usefulness of photodynamic therapy in selected patients<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">73</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8226; Hair transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Novel technological devices&#58; robot&#44; automated systems<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; New technique of follicular extraction&#58; partial longitudinal extraction<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">76</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Summary of the Most Important Therapeutic Novelties in Trichology&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:76 [
            0 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "&#91;accessed 16 Ago 2016&#93;&#46; Available at&#58; <span class="elsevierStyleInterRef" id="intr0010" href="http://www.ncbi.nlm.nih.gov/pubmed/26380504">http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;26380504</span>"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Topical minoxidil&#58; Systematic review and meta-analysis of its efficacy in androgenetic alopecia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;K&#46; Gupta"
                            1 => "A&#46; Charrette"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Skinmed&#46;"
                        "fecha" => "2015"
                        "volumen" => "13"
                        "paginaInicial" => "185"
                        "paginaFinal" => "189"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26380504"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
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                0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            1 => "Z&#46; Fedorowicz"
                            2 => "B&#46; Carter"
                            3 => "R&#46;B&#46; Andriolo"
                            4 => "J&#46; Schoones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD007628.pub3"
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            2 => array:3 [
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              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "V&#46; Kanti"
                            1 => "K&#46; Hillmann"
                            2 => "J&#46; Kottner"
                            3 => "A&#46; Stroux"
                            4 => "D&#46; Canfield"
                            5 => "U&#46; Blume-Peytavi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jdv.13324"
                      "Revista" => array:6 [
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                        "volumen" => "30"
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                          0 => array:2 [
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                        ]
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                  "comentario" => "e2"
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                    0 => array:2 [
                      "titulo" => "A randomized&#44; single-blind trial of 5&#37; minoxidil foam once daily versus 2&#37; minoxidil solution twice daily in the treatment of androgenetic alopecia in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "U&#46; Blume-Peytavi"
                            1 => "K&#46; Hillmann"
                            2 => "E&#46; Dietz"
                            3 => "D&#46; Canfield"
                            4 => "N&#46; Garcia Bartels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2010.09.724"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol&#46;"
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                          0 => array:2 [
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                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Niosomes as a vesicular carrier for topical administration of minoxidil&#58; Formulation and in vitro assessment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "N&#46; Mali"
                            1 => "S&#46; Darandale"
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                        ]
                      ]
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                  ]
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                    0 => array:2 [
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of permanent chemotherapy-induced alopecia with low dose oral minoxidil"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "X&#46; Yang"
                            1 => "K&#46;E&#46; Thai"
                          ]
                        ]
                      ]
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                  ]
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                    0 => array:2 [
                      "doi" => "10.1111/ajd.12350"
                      "Revista" => array:2 [
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                        "fecha" => "2015"
                      ]
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                      "doi" => "10.1016/j.jdcr.2016.02.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAAD Case Rep&#46;"
                        "fecha" => "2016"
                        "volumen" => "2"
                        "paginaInicial" => "212"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
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                            "web" => "Medline"
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              "identificador" => "bib0420"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of 5&#945;-reductase inhibitors on sexual function&#58; A meta-analysis and systematic review of randomized controlled trials"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Liu"
                            1 => "S&#46; Zhao"
                            2 => "F&#46; Li"
                            3 => "E&#46; Li"
                            4 => "R&#46; Kang"
                            5 => "L&#46; Luo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jsxm.2016.07.006"
                      "Revista" => array:2 [
                        "tituloSerie" => "J Sex Med&#46;"
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
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              "etiqueta" => "9"
              "referencia" => array:1 [
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Información de la revista
Vol. 108. Núm. 3.
Páginas 221-228 (abril 2017)
Visitas
25285
Vol. 108. Núm. 3.
Páginas 221-228 (abril 2017)
NOVELTIES IN DERMATOLOGY
Acceso a texto completo
New Treatments for Hair Loss
Novedades terapéuticas en tricología
Visitas
25285
S. Vañó-Galvána,
Autor para correspondencia
drsergiovano@gmail.com

Corresponding author.
, F. Camachob
a Servicio de Dermatología, Unidad de Tricología, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain
b Hospital Virgen Macarena, Sevilla, Spain
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Table 1. Summary of the Most Important Therapeutic Novelties in Trichology.
Abstract

The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients’ quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction.

Keywords:
Hair loss treatments
Androgenetic alopecia
Dutasteride
Alopecia areata
Ruxolitinib
Frontal fibrosing alopecia
Wnt pathway
Low-level laser therapy
Resumen

La tricología ocupa un área importante dentro de la práctica asistencial de los dermatólogos por la frecuencia de las diferentes tricosis y por el gran impacto que producen en la calidad de vida de los pacientes. Durante los últimos años hemos comprobado la incorporación de muchas novedades terapéuticas en tricología. El objetivo de la presente revisión es resumir de una forma práctica las principales novedades terapéuticas tricológicas, agrupándolas en 4 apartados: a) alopecia androgénica: nuevos excipientes de minoxidil, dutasterida y finasterida oral y nuevas formas de aplicación de estos antiandrógenos, agonistas y antagonistas de las prostaglandinas, láser de baja potencia y medicina regenerativa —activadores de la vía Wnt y terapia con células madre—; b) alopecia areata: fármacos anti-JAK; c) alopecia frontal fibrosante: antiandrógenos y, en algunos pacientes, pioglitazonas, y d) trasplante capilar: nuevos dispositivos tecnológicos y nuevas técnicas de extracción para optimizar la reserva de unidades foliculares.

Palabras clave:
Tricología
Alopecia androgénica
Dutasterida
Alopecia areata
Ruxolitinib
Alopecia frontal fibrosante
Vía Wnt
Láser de baja potencia
Texto completo
Introduction

Trichology is an important field within dermatologic practice. The objective of this review article is to provide a practical synopsis of the main therapeutic novelties in trichology, grouping them into 4 areas: androgenetic alopecia (AGA), alopecia areata (AA), scarring alopecia, and hair transplant.

The study methods consisted of the review of articles included in the Pubmed and Medline databases and in the clinicaltrials.gov clinical trials register between 2013 and 2016, and of the preliminary results of therapies presented at international trichology conferences. The authors of this review also describe their personal experience with the different therapies.

Androgenetic Alopecia

New treatment options have recently been introduced for men and women with AGA. Additionally, novel uses of minoxidil and antiandrogens have also been described.

Minoxidil

A recently published meta-analysis has shown the efficacy of minoxidil versus placebo in the treatment of AGA.1 The authors state that the use of minoxidil is significantly limited by poor compliance due to cosmetic issues, which may be mitigated by the new minoxidil formulations. A Cochrane review article has been published on interventions for female AGA. That review included 47 studies and 5,290 patients and concluded that the application of topical minoxidil at concentrations between 2% and 5% is effective and safe, and is superior to other treatments such as the antiandrogens and low-level laser therapy (LLLT).2 A number of studies looking at the new formulations of minoxidil have shown improved efficacy and better tolerance of foam presentations versus the hydroalcoholic solution in both men3 and women4 with AGA, due to the lower concentration of propylene glycol, which enhances its cosmetic acceptability. The possibility of using niosomes to improve the topical absorption of minoxidil is also being investigated.5 Another novelty is the development of nanoxidil, an active substance with a similar structure to minoxidil, but with a lower molecular weight; it should therefore present better penetration and absorption, although no robust scientific studies have yet been published to support this. Although anecdotal, papers have been published that suggest low-dose oral minoxidil (0.25mg/d) may be safe and effective in AGA (Sinclair, personal communication), permanent chemotherapy-induced alopecia,6 and in moniletrix.7 If these results are confirmed, the use of low doses of oral minoxidil could be a very interesting option in patients with AGA.

Antiandrogens

A number of publications with high levels of evidence support the safety of finasteride and dutasteride in men and women with AGA, because of both the low risk of adverse sexual effects (very similar to placebo),8,9 and the inexistent increase in the risk of cancer.10,11 Regarding one of the most relevant novelties in AGA in recent years, the authors draw attention to the appearance of the drug dutasteride as a safe and effective option in AGA, both in men and in women.12–14 This dual 5α-reductase inhibitor, with a longer half-life than finasteride, has been shown to be more effective that finasteride in predominantly frontal male AGA without presenting additional adverse effects.14–17 With respect to new methods of administration of the antiandrogens, the study by Moftah et al.18 stands out because it demonstrates the usefulness and safety of microinjections of dutasteride in female AGA. Those authors described the treatment of 86 women versus 40 controls, finding a 63% improvement in hair density in the active treatment group versus 17% of the control group (P<.05), with no side effects. The local injection of dutasteride into the scalp after nerve block may be a useful therapeutic option in male and female AGA either in monotherapy (Fig. 1) or as a complement to traditional treatment. Our working group has performed a study in 5 men with AGA, observing the efficacy of local injections of dutasteride every 3 months, with no side effects or alterations of hormone levels in the blood (in press – data not published). As an alternative to the oral administration of antiandrogens, several articles describe the inhibitory activity of topical 0.25% finasteride on follicular 5-alfa-reductase, with lower levels of systemic absorption than oral finasteride.19,20 Studies of the clinical efficacy of topical 0.5% finasteride performed by Milani et al. are still to be published (personal communication); those authors have shown an improvement in male AGA at 6 months in 70% of patients treated in monotherapy.

Figure 1.

A 26-year-old man with androgenetic alopecia at the vertex. Improvement after treatment with injections of dutasteride in monotherapy every 3 months. A, At baseline. B, After a year of treatment.

(0.61MB).
Prostaglandins

Among the prostaglandins (PG), the PGF2 analogs latanoprost and bimatoprost are known to stimulate hair growth by prolonging the anagen phase.21,22 However, the concentration of these drugs necessary to improve hairy density in AGA is very high (0.1% latanoprost),22 leading to limitations due to their high cost. Recent research is looking at other drugs that block the PGD2 receptor (GPR44), which has an inhibitory effect on hair growth and which is known to be elevated in the scalp of patients with AGA.23–25 Setipiprant (KITH-105) is a orally administered GPR44 receptor inhibitor that is in the clinical trial phase for asthma, but could have a potential application in AGA.26 A phase II clinical trial is underway to evaluate the use of oral setipiprant in comparison with placebo and with finasteride, 1mg/d, in men aged 18 to 41 years with AGA (NCT02781311).

Physical Therapies

Several methodologically robust articles have demonstrated the usefulness of LLLT in both male and female AGA.27–30 The periodic stimulation of hair follicles with LLLT favors the conversion of follicles in telogen to follicles in anagen, and the transformation of vellous follicles into terminal follicles due to the induced perifollicular inflammation, which potentiates follicular growth through activation of stem cells in the bulge. Furthermore, local blood flow is increased and inflammatory mediators and VEGF (vascular endothelial growth factor) are released, favoring the growth of pluripotent stem cells and thus stimulating hair growth and thickening.27–30 In the opinion of the authors, the optimal LLLT protocol for men and women with AGA still remains to be defined, although this therapy appears to be an interesting option with a mechanism of action that differs from traditional therapies. Very interesting articles have been published recently on another physical therapy, microneedling,31,32 a technique that consists of creating microperforations in the scalp in order to produce controlled damage and the release of endogenous growth factors, which stimulate hair growth.

Regenerative Medicine Therapies

In the final group we have included regenerative medicine therapies designed to stimulate follicular stem cells.

  • a)

    Three new studies,33–35 one of which is a meta-analysis,34 have been published on the potential usefulness of platelet-rich plasma (PRP) in male and female AGA, showing PRP to achieve increased hair density and number of follicles in anagen with virtually no adverse effects. In the opinion of the authors, this treatment has an excellent safety profile, but its efficacy profile is variable, with a very good response in some patients but more modest in others.

  • b)

    The initial results have now been published on the usefulness and safety of topical activators of the Wnt/β-catenin pathway in AGA: methyl vanillate,36 valproic acid,37 and SM04554.38 The Wnt/β-catenin pathway regulates activation of the nest of stem cells localized in the follicular bulge, a process necessary for the initiation and maintenance of the follicular anagen phase and whose inhibition has been related with the loss of hair density in AGA.36–38

  • c)

    It has recently been reported that pharmacological inhibition of 2 of the signaling pathways implicated in downregulation of the proliferation and differentiation of the follicular bulge stem cells and in initiation of the follicular resting phase, JAK/STAT and mTOR/PI3K, effectively activates hair growth in mouse models and in human follicles in vitro.39,40

  • d)

    It has also been shown that the transient production of reactive oxygen species by photodynamic therapy in vivo in mouse skin induces several signaling pathways that ultimately activate of the nest of hair follicle stem cells, accelerating hair growth.41

  • e)

    Finally, we would like to comment on stem cell treatments. Basically, there are 2 types of stem cell treatment: E1, which involves hair cloning by the injection of follicular stem cells previously expanded in vitro, producing the growth of new follicles; and E2, adipose-derived stem cells. In the first case, few advances have been reported since the initial studies in mouse models published by McElwee et al. in 2003,42 and the preliminary results of the only clinical trial performed in humans were very limited, with an increase in hair growth of only 6% (McElwee, communication at the World Trichology Conference in Barcelona, 2012). Although this treatment will be a landmark in the treatment of AGA, further research is still required. The second technique consists of performing liposuction to obtain mesenchymal stem cells, which are then conditioned and injected into the scalp to stimulate hair growth. Preliminary studies have shown the possible usefulness of adipose-derived stem cells in AGA,43–45 but further studies are needed to confirm the safety and efficacy of this therapy.

Alopecia Areata

The therapeutic novelties in the treatment of AA fall into 2 groups: a) new data and forms of application of traditional treatments, and b) new therapies.

  • a)

    In the first group, we draw attention to a review article by Lamb et al.46 on the use of immunotherapy with diphencyprone in 133 patients with AA. A response was observed in 72% of patients, with regrowth of over 90% in 16% of cases. Another important novelty in this first group is the use of pulsed systemic corticosteroids in AA. There is evidence of greater safety and at least the same efficacy when corticosteroids are used in pulses.47,48 In a study performed by the research group of Hospital Ramón y Cajal in Madrid,48 the use of oral dexamethasone at a dose of 0.1mg/kg/d on 2 consecutive days every week produced regrowth in 25/31 patients with alopecia totalis or universalis (Fig. 2), with mild adverse effects in 32%.

    Figure 2.

    A 34-year-old woman with alopecia areata universalis. Hair regrowth after treatment with oral minipulses of dexamethasone at a dose of 0.1mg/kg/d on 2 consecutive days each week. A, At baseline. B, Month 4 of treatment. B, Month 8 of treatment.

    (0.35MB).
  • b)

    In the second group of novel therapies, the possible usefulness of the combination of simvastatin and ezetimibe in AA stands out for its immunomodulator effect, demonstrated in a study in which 14 of 19 patients with extensive AA responded.49 However, other authors have reported significantly lower response rates with this treatment (1/20 patients).50 The combination of simvastatin and ezetimibe may be a useful concomitant therapy to improve the response to other treatments, but its action in monotherapy would appear to be limited.

    The greatest novelty in the field of AA, and one of the most important in trichology in recent years, is the therapeutic usefulness of the anti-Janus kinase (anti-JAK) agents,51–58 not only for their apparent efficacy, but also because these are the first agents that act against a specific pathogenic target in AA. The JAK pathway is implicated in the activation of CD8 cytotoxic T cells and in the production of interferon-γ, which are fundamental to the onset of AA. Their inhibition appears to induce regrowth in these patients. The drugs reported to be potentially useful in AA are tofacitinib55–58 (whose approved indication is rheumatoid arthritis), ruxolitinib51,52,54 (approved for use in myelofibrosis and polycythemia vera) and baricinitib53 (pending approval of indication in rheumatoid arthritis). These drugs are administered orally and have an acceptable safety profile; because of their indications, they are usually prescribed for long-term administration and are well tolerated. In addition, the first study has been published on the usefulness of topical ruxolitinib in AA of the eyebrows,52 and clinical trials are already underway with new topical anti-JAK agents, such as LEO-124249 (NCT02561585). The main limitation of these treatments is their cost. However, they open new lines of therapeutic research intoAA.

Scarring Alopecia

The etiology and pathogenesis of frontal fibrosing alopecia (FFA) are currently considered to involve a double autoimmune and hormonal mechanism.59–61 This justifies the use both of anti-inflammatory drugs (corticosteroids) to reduce the autoimmune inflammation and of antiandrogens (finasteride and dutasteride). In recent years, several studies have been published that show the potential usefulness of these drugs in FFA,59–64 including a multicenter Spanish study of 355 patients.59 The mechanism by which the antiandrogens act in the FFA is not fully understood, but it would appear that inhibition of the action of male hormones on the root of the follicle helps to stabilize the disease.59,61 Some authors have even reported regrowth after the administration of antiandrogens.64 However, others remain skeptical regarding the use of these drugs in FFA.65 Although their mechanism of action remains unclear, there is evidence that a hormonal factor is responsible forFFA.61

Another important therapeutic novelty in FFA and lichen planopilaris (LPP) is the use of the oral antidiabetic agent pioglitazone, which blocks the peroxisome proliferator-activated receptor-γ (PPARγ). Recent studies have suggested that altered function of PPAR-γ may play a role in the initiation of inflammation in LPP and FFA.66 Four studies have been published in which pioglitazone has been used to treat LPP and FFA.67–70 Results have been variable, with an efficacy of between 20% and 70% and adverse effects in up to 50%. Marquez and Camacho71 performed a study in 68 women with FFA, with favorable results in 64% after the use of pioglitazone. The authors believe that pioglitazone could be effective in some cases, but intolerance is not uncommon, mainly in the form of lower limb edema and weight gain, leading to drug withdrawal in a significant number of cases.

In the case of folliculitis decalvans (FD), a Spanish multicenter study including 82 patients72 concluded that the most effective treatment (improvement in 15/15 patients treated) with the longest period of remission after treatment (7.2 months) was the combination of rifampicin plus clindamycin administered for 10 weeks (Fig. 3). Another therapeutic novelty reported in the literature is the possible usefulness of photodynamic therapy (PDT) with benefit in 9 out of 10 patients with FD.73 However, other authors have reported a negative experience with PDT in 3 out of 3 patients.74

Figure 3.

A 33-year-old woman with folliculitis decalvans. Clinical improvement after 10 weeks of treatment with rifampicin, 300mg every 12hours, plus clindamycin, 300mg every 12hours. A, At baseline. B, At the end of treatment.

(0.33MB).
Hair transplant

To complete this review, 2 novel methods stand out in the field of hair transplant. First, the arrival of the new automated robotic systems that reduce operating times and, in some cases, improve the rates of follicular transection in the follicular unit extraction technique.75 However, we consider that results depend more on surgical dexterity than on the device used.

The other novelty is a new technique of follicular extraction, known as partial longitudinal extraction.76 This consists of only partially extracting the follicular units, so that the part of the follicle that remains in the donor region can survive and regenerate an intact follicular unit, thus avoiding the progressive depopulation that occurs in the donor region. The concept is interesting, but still needs to be developed.

A summary of the most relevant therapeutic novelties in trichology is presented in Table 1.

Table 1.

Summary of the Most Important Therapeutic Novelties in Trichology.

Area  Novelties in Traditional Treatments  New Therapies 
• Androgenetic alopecia  • Effectiveness of minoxidil in male and female AGA1,2
• New foam formulations of minoxidil to improve cosmetic acceptability3,4
• Use of niosomes to improve the topical absorption of minoxidil5
• Low-dose oral minoxidil
• Safety of the 5α-reductase inhibitors8–11
• Oral dutasteride in male and female AGA12–17
• Effectiveness and safety of PRP33–35 
• Dutasteride microinjections18
• Topical finasteride19,20
• PGD2-GPR44 inhibitors (setipiprant)26
• LLLT27–30
• Microneedling31,32
• Topical activators of the Wnt/β-catenin pathway36–38
• Adipose-derived stem cells43–45
• Therapy with stem cells previously expanded in vitro42 
• Alopecia areata  • Effectiveness of diphencyprone46
• Pulsed corticosteroids47,48 
• Simvastatin plus ezetimibe49,50
• Anti-JAK agents: tofacitinib,55–58 ruxolitinib,51,52,54 baricitinib53 
• FFA/LPP  • Usefulness and safety of the antiandrogens (finasteride and dutasteride) in FFA59–61  • Usefulness of pioglitazone in LPP and FFA67,71 
• Folliculitis decalvans  • Effectiveness of treatment with rifampicin plus clindamycin72  • Possible usefulness of photodynamic therapy in selected patients73 
• Hair transplant  • Novel technological devices: robot, automated systems75  • New technique of follicular extraction: partial longitudinal extraction76 

Abbreviations: AGA, androgenetica alopecia; FFA, frontal fibrosing alopecia; JAK, Janus kinase; LLLT, low-level laser therapy; LPP, lichen planopilaris; PGD2-GPR44, prostaglandin D2 receptor; PRP, platelet-rich plasma.

Conclusions

In recent years we have seen great advances in the therapeutics of trichology, but more importantly, new lines of research have been opened that will allow us to continue advancing. The developments discussed in this review, which has looked at the past 3 years, are more than hope, they are now a reality.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Please cite this article as: Vañó-Galván S, Camacho F. Novedades terapéuticas en tricología. Actas Dermosifiliogr. 2017;108:221–228.

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