**4. Platelet‐rich plasma in the treatment of alopecia**

#### **4.1. Platelets**

Platelets are one of the shapely structured elements of the peripheral blood and do not have cell nuclei. The number of platelets ranges from 150,000 to 350,000/mm<sup>3</sup> in peripheral blood and they are functioning primarily in hemostasis [49]. They take active role in wound healing, angiogenesis, and inflammation owing to the numerous proteins, cytokines, and bioactive factors they contain [49, 50]. In addition, they induce the migration and adherence of bone marrow‐origin cells into angiogenesis territory and the differentiation of endothelial cell progenitors to the mature endothelial cells [51].

The platelets have three main storage sites; α granules, dense granules, and lysosomes [52]. The major growth factors (GF) and cytokines already stored in α granules are; transforming growth factor‐β (TGF‐β), platelet‐derived growth factor (PDGF), insulin‐like growth factor (IGF‐I, IGF‐II), fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and endothelial cell growth factor (ECGF) [49, 53, 54]. The activation of platelets induces degranulation of GFs which are already restored. The secreted GFs bind to the transmembrane receptors on mesenchymal stem cells, osteoblasts, fibroblasts, endothelial cells, and epidermal cells and then induce the internal signal transduction pathway. They initiate the healing process such as cell proliferation, differentiation, chemotaxis, angiogenesis, matrix formation, osteoid production, and collagen synthesis [49, 53].

The dense granules of the platelets have bioactive factors such as serotonin, histamine, dopamine, calcium, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and catecholamine. These substances have significant effects in wound healing. They have effects such as boosting the capillary permeability, vasoconstriction, hauling and activating the macrophages, tissue modulation, and regeneration [49, 54].

#### **4.2. Platelet‐rich plasma**

PRP is an autologous, biologically active concentration, composed of many growth factors (GF), cytokines, and plasma proteins [55]. It came into use since 1970s owing to its effects to promote the wound healing to a cellular level [54]. Platelet concentration in PRP is at least 1,000,000/μg/L in 5 mL and the growth factor concentration is 3–5 times higher than peripheral blood [49]. Platelet gel concentration which is higher or lower than 1,500,000 was associated with decreased angiogenic features of endothelial cells [56].

There are four different PRP subgroups available; pure PRP, leukocyte and PRP (L‐PRP), platelet‐rich fibrin matrix (PRFM), and leukocyte‐ and platelet‐rich fibrin matrix. Clinically, pure PRP and L‐PRP are widely used. The one widely used in cosmetic dermatology is the pure PRP [57].

*In vitro* studies indicate a dose‐dependent positive correlation between the platelet concentration and human mesenchymal stem cells and fibroblast proliferation and type 1 collagen production [58]. It is reported that PRP increased the proliferation of fibroblasts and their transformation into myofibroblasts as well as the synthesis of collagen and matrix remodeling proteins [59, 60].

#### **4.3. Preparation of platelet‐rich plasma**

**4. Platelet‐rich plasma in the treatment of alopecia**

genitors to the mature endothelial cells [51].

phages, tissue modulation, and regeneration [49, 54].

ated with decreased angiogenic features of endothelial cells [56].

**4.2. Platelet‐rich plasma**

cell nuclei. The number of platelets ranges from 150,000 to 350,000/mm<sup>3</sup>

Platelets are one of the shapely structured elements of the peripheral blood and do not have

and they are functioning primarily in hemostasis [49]. They take active role in wound healing, angiogenesis, and inflammation owing to the numerous proteins, cytokines, and bioactive factors they contain [49, 50]. In addition, they induce the migration and adherence of bone marrow‐origin cells into angiogenesis territory and the differentiation of endothelial cell pro-

The platelets have three main storage sites; α granules, dense granules, and lysosomes [52]. The major growth factors (GF) and cytokines already stored in α granules are; transforming growth factor‐β (TGF‐β), platelet‐derived growth factor (PDGF), insulin‐like growth factor (IGF‐I, IGF‐II), fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and endothelial cell growth factor (ECGF) [49, 53, 54]. The activation of platelets induces degranulation of GFs which are already restored. The secreted GFs bind to the transmembrane receptors on mesenchymal stem cells, osteoblasts, fibroblasts, endothelial cells, and epidermal cells and then induce the internal signal transduction pathway. They initiate the healing process such as cell proliferation, differentiation, chemotaxis,

angiogenesis, matrix formation, osteoid production, and collagen synthesis [49, 53].

The dense granules of the platelets have bioactive factors such as serotonin, histamine, dopamine, calcium, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and catecholamine. These substances have significant effects in wound healing. They have effects such as boosting the capillary permeability, vasoconstriction, hauling and activating the macro-

PRP is an autologous, biologically active concentration, composed of many growth factors (GF), cytokines, and plasma proteins [55]. It came into use since 1970s owing to its effects to promote the wound healing to a cellular level [54]. Platelet concentration in PRP is at least 1,000,000/μg/L in 5 mL and the growth factor concentration is 3–5 times higher than peripheral blood [49]. Platelet gel concentration which is higher or lower than 1,500,000 was associ-

There are four different PRP subgroups available; pure PRP, leukocyte and PRP (L‐PRP), platelet‐rich fibrin matrix (PRFM), and leukocyte‐ and platelet‐rich fibrin matrix. Clinically, pure PRP and L‐PRP are widely used. The one widely used in cosmetic dermatology is the pure PRP [57]. *In vitro* studies indicate a dose‐dependent positive correlation between the platelet concentration and human mesenchymal stem cells and fibroblast proliferation and type 1 collagen production [58]. It is reported that PRP increased the proliferation of fibroblasts and their transformation into myofibroblasts as well as the synthesis of collagen and matrix remodeling proteins [59, 60].

in peripheral blood

**4.1. Platelets**

324 Hair and Scalp Disorders

PRP is prepared with 20–60 mL of plasma [61] by means of automatic devices under aseptic conditions at 20–22°C. It must be prepared using anticoagulants containing citrate dextrose solution formula A (ACD‐A) or sodium citrate in order to inhibit PRP aggregation [53]. The blood elements are separated according to their molecular weights by means of centrifugal method in manual double spin method. Respectively, red blood cells (RBC) are the heaviest, white blood cells (WBC) are moderate, and the platelets are the lightest ones. The platelets are first separated from RBC and WBC by means of light‐spin centrifuge that they become available in concentrated form in the top part of buffy coat layer. Subsequently, heavy‐spin centrifuge separates the supernatant plasma and more concentrated platelets are obtained. Bottom part of the tube holds the platelets and the upper part retains the platelet‐poor plasma (PPP). Thrombin is used as an activator to obtain coagulation and thus "activated PRP" is extracted by means of GF degranulation [49, 53]. Approximately, 70% of GFs is released in 10 min and almost 100% is released in an hour and a small amount of GF continues to be produced for up to 8–10 days during the life of platelets [62]. For this reason, PRP should be administered soon after it is prepared.

The platelet‐rich fibrin matrix (PRFM) is developed to retard GF secretion from the platelets, which is a dense fibrin matrix generated by adding CaCl<sup>2</sup> during the secondary centrifuge that induces the conversion of autogenous thrombin from prothrombin. Platelet activation decreases as the thrombin amount reduces, so the platelets secrete their GFs slowly in a period of 7 days. Therefore, it is used in fat grafting and soft tissue augmentation. At the same time, fibrin matrix serves as a building block in wound healing [49, 57].

L‐PRP is a subtype of PRP consisting of the platelet, leucocyte, and red blood cells. It is produced by the collection of PPP and all buffy coats following the centrifuge of anticoagulant blood. Whereas Leukocyte‐PRFM is a subform made up of platelet and leucocyte‐rich fibrin polymerized clot. It is produced without using anticoagulant and activator [57].

Another platelet activation type is the method which stimulates PDGF and VEGF secretion and enables collagen‐PRP gel formation, performed by using type I collagen [63].

A great number of commercial kits came into use in addition to manual PRP preparation. However, different technologies introduce products with different biology and unclear effect profile. There are various PRP preparation methods in the literature, which contain different protocols, different centrifugal techniques, and different cellular components [61].

#### **4.4. Indications**

Various indications of PRP in dermatology are outlined in **Table 1** [53, 57, 64].

#### **4.5. Method**

The patients should be informed and a signed consent form should always be obtained prior to the application. The patient is required stop taking anticoagulants such as aspirin and


**Table 1**. Dermatological indications of PRP.

other nonsteroidal antiinflammatory medications at least 2 weeks before the application. Local anaesthesia should be given, if required, under aseptic circumstances. Different application methods are available, which may be preferred by the clinicians and for the comfort of the patient. First method is the retrograde injection of PRP deep‐to‐surface at a rate of 0.05–0.1 mL/cm<sup>2</sup> per each centimeter. The second one is the administration of PRP either by puncturing holes over the scalp by means of 1 mm microneedle roller or by means of mesotherapy gun. The third method is the application of PRP before or after the implantation in order to assist the hair transplantation, keeping the follicular grafts in PRP for 15 minutes prior to implantation or the application in order to speed up the wound healing in donor's excision line [53].

There is no consensus on the parameters such as the frequency, depth (interfollicular, intradermal, or subcutaneous), and the dose of the application.

#### **4.6. Contraindications**

Contraindications of PRP are listed on **Table 2** [63–65].

Pregnancy and breastfeeding period

Acute and chronic infections

Autoimmune disorders

Sensitivity to blood and blood products

Hepatopathy (liver disease)

Malignancies

Thrombocytopenia and hypofibrinogenemia

**Table 2**. Contraindications of PRP.

#### **4.7. Side effects**

The incidence of adverse effects is quite low since PRP application is an autologous one. Local side effects due to injection such as rash, ecchymosis, pain, and infection are mild and temporal. It does not have any risk of transmitting infections such as hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV). Risk of allergy is low as the patient's own blood is used [53, 65].

#### **4.8. Evidence for efficacy of platelet‐rich plasma in various conditions**

#### *4.8.1. Androgenetic alopecia*

other nonsteroidal antiinflammatory medications at least 2 weeks before the application. Local anaesthesia should be given, if required, under aseptic circumstances. Different application methods are available, which may be preferred by the clinicians and for the comfort of the patient. First method is the retrograde injection of PRP deep‐to‐surface at a rate of

puncturing holes over the scalp by means of 1 mm microneedle roller or by means of mesotherapy gun. The third method is the application of PRP before or after the implantation in order to assist the hair transplantation, keeping the follicular grafts in PRP for 15 minutes prior to implantation or the application in order to speed up the wound healing in donor's

There is no consensus on the parameters such as the frequency, depth (interfollicular, intra-

dermal, or subcutaneous), and the dose of the application.

Contraindications of PRP are listed on **Table 2** [63–65].

per each centimeter. The second one is the administration of PRP either by

0.05–0.1 mL/cm<sup>2</sup>

Skin rejuvenation

326 Hair and Scalp Disorders

Striae distensae Chronic wounds Fat grafting Laser resurfacing Lichen sclerosus

Dermal volume augmentation

Scar revision; acne, and traumatic scars

**Table 1**. Dermatological indications of PRP.

Alopecia; androgenetic alopecia, and alopecia areata

excision line [53].

**4.6. Contraindications**

Pregnancy and breastfeeding period

Sensitivity to blood and blood products

Thrombocytopenia and hypofibrinogenemia

**Table 2**. Contraindications of PRP.

Acute and chronic infections Autoimmune disorders

Hepatopathy (liver disease)

Malignancies

AGA is characterized by progressive hair follicle miniaturization and its treatment is quite challenging [66, 67]. The two medications approved by Food and Drug Administration (FDA) are minoxidil and finasteride. Dermatologists and plastic surgeons tend to prefer new treatment methods due to limited effects and adverse effect profile of these agents. In recent years, a good number of studies have been carried out on the effectivity of PRP in an AGA treatment.

#### *4.8.1.1. The mechanism of platelet‐rich plasma in androgenetic alopecia*

PRP enhances the proliferation of dermal papilla (DP) cells and protect the cells against apoptosis by increasing Bcl‐2 protein level. Moreover, it stimulates the Akt signalization which has antiapoptotic effects on cell survival and also stimulates extracellular signal‐regulated kinase (ERK) that regulates the cell growth. In this way, it promotes cell growth and extends the survival of hair follicles. B‐catenin is expressed in the external root sheath in the bulge area of human anagen hair follicle and ensures the differentiation of stem cells into the hair follicle cells and other adult cells. B‐catenin activity in DP cells of the patients treated with PRP is upregulated, inducing the differentiation of stem cells into hair follicle cells and stimulating the hair growth. In addition, FGF‐7 expression in DP cells increases, ensuring that the anagen phase of hair growth cycle is extended. Enhanced VEGF and PDGF boosts the perifollicular vascular plexus with proangiogenic effect. Active PRP injected to the mice *in vivo* is indicated to induce the acceleration of telogen‐to‐anagen transition [68].

The first study performed on PRP indicated that both the survival of follicular units are increased and follicular density is augmented in the patients of hair plantation since the follicular grafts were soaked in PRP for 15 minutes prior to implantation [69]. Various studies in the literature indicated that PRP stimulates a number of active features such as growth rate, hair count, hair density, hair shaft diameter, hair root strength, anagen hair, telogen hair, terminal hair density, epidermal keratinocytes, hair follicular bulge cells, and lead to increase in small blood vessels in hair follicle, prevents dermal papilla apoptosis, extent anagen phase, and enhances hair regrowth [70–74]. The carrier which contains dalteparin/protamine micro particles (DP MP) (low‐molecular‐weight heparin) was used to enhance the efficiency of PRP. DP MP ensures adsorption, stabilization, and slow secretion of GFs. PRP containing DP MP is observed to increase the hair thickness significantly compared to PRP alone [75]. In another study, PRP containing CD34+ cell has been tried on patients with AGA and a significant increase has been observed in hair thickness [76].

#### *4.8.2. Alopecia areata*

AA targets the anagen hair follicles in which spontaneous remission may be observed [77–79]. Although immunosuppressive agents can generally be used in the treatment of AA and regarded as an organ specific autoimmune disease, there is not any curative or preventive treatment of the disease [80]. Therefore, PRP has been introduced in recent years as an alternative treatment.

#### *4.8.2.1. The mechanism of platelet‐rich plasma on alopecia alopecia*

PRP has also an antiinflammatory effect in addition to its effect on the induction of proliferation. Endogen lipid molecules called "lipoxin" derived from cellular arachidonic acid serve in the resolution of the inflammation. Lipoxins retard the arrival of new neutrophils into the inflammation area and support the neutrophil apoptosis to organize the resolution. PRP promotes lipoxin A4 (LXA4) secretion and suppresses the cytokine secretions to limit the inflammation [81]. The fact that inflammatory cytokines play a part in the etiopathogenesis of AA led to an argument that PRP could be effective in AA treatment with antiinflammatory effect.

There is limited number of studies in the literature on the use of PRP in the treatment of AA. A recent study indicated a significant increase in hair growth, an increase in Ki‐67 which is the cellular proliferation marker and a degradation in the rate of relapse, in AA patients treated with intralesional PRP, compared with the patients treated with both placebo and intralesional triamcinolone acetonide (TrA). Furthermore, it has been observed that both groups taking PRP and TrA had less rash and irritancy as well as reduced dystrophic hair in dermoscopy. A complete remission rate of 60% has been achieved in the group treated with PRP at the end of the treatment [79].

In another study carried out with 20 AA patients, PRP was well tolerated, no adverse effect was observed and improvement in hair growth was seen. Minimal response to treatment and relapse was observed in only one patient [82].

PRP treatment applied on an ophiasis‐type alopecia areata patient, resistive to corticosteroid treatment, yielded a successful result and hair regrowth was observed. PRP is suggested to be an alternative treatment in AA patients resistive to corticosteroid treatment and in the patients with side effects of steroid injection [83].

### **5. Laser and light sources in the treatment of alopecia**

Laser (light amplification by stimulated emission of radiation)/light sources have become popular in dermatology practice on various disorders. Recently, these devices have been tried for the treatment of male and female pattern hair loss and alopecia areata with variable success rates. The laser beam having the coherent, monochromatic, and polarized characteristics that differs it from the ordinary light. The low‐energy laser light penetrates the surface in a defined position and does not damage the skin [84]. There is a consensus among many authors that current laser/light sources are safe methods if they can be used properly and also these treatment modalities can be used alone or in combination with other treatments. The literature reveals that the texture and quality of hair improves even if there is no hair regrowth by the use of laser/light sources [85].

#### **5.1. Androgenetic alopecia**

study, PRP containing CD34+

years as an alternative treatment.

PRP at the end of the treatment [79].

relapse was observed in only one patient [82].

patients with side effects of steroid injection [83].

**5. Laser and light sources in the treatment of alopecia**

*4.8.2. Alopecia areata*

328 Hair and Scalp Disorders

increase has been observed in hair thickness [76].

*4.8.2.1. The mechanism of platelet‐rich plasma on alopecia alopecia*

cell has been tried on patients with AGA and a significant

AA targets the anagen hair follicles in which spontaneous remission may be observed [77–79]. Although immunosuppressive agents can generally be used in the treatment of AA and regarded as an organ specific autoimmune disease, there is not any curative or preventive treatment of the disease [80]. Therefore, PRP has been introduced in recent

PRP has also an antiinflammatory effect in addition to its effect on the induction of proliferation. Endogen lipid molecules called "lipoxin" derived from cellular arachidonic acid serve in the resolution of the inflammation. Lipoxins retard the arrival of new neutrophils into the inflammation area and support the neutrophil apoptosis to organize the resolution. PRP promotes lipoxin A4 (LXA4) secretion and suppresses the cytokine secretions to limit the inflammation [81]. The fact that inflammatory cytokines play a part in the etiopathogenesis of AA led to an argument that PRP could be effective in AA treatment with antiinflammatory effect. There is limited number of studies in the literature on the use of PRP in the treatment of AA. A recent study indicated a significant increase in hair growth, an increase in Ki‐67 which is the cellular proliferation marker and a degradation in the rate of relapse, in AA patients treated with intralesional PRP, compared with the patients treated with both placebo and intralesional triamcinolone acetonide (TrA). Furthermore, it has been observed that both groups taking PRP and TrA had less rash and irritancy as well as reduced dystrophic hair in dermoscopy. A complete remission rate of 60% has been achieved in the group treated with

In another study carried out with 20 AA patients, PRP was well tolerated, no adverse effect was observed and improvement in hair growth was seen. Minimal response to treatment and

PRP treatment applied on an ophiasis‐type alopecia areata patient, resistive to corticosteroid treatment, yielded a successful result and hair regrowth was observed. PRP is suggested to be an alternative treatment in AA patients resistive to corticosteroid treatment and in the

Laser (light amplification by stimulated emission of radiation)/light sources have become popular in dermatology practice on various disorders. Recently, these devices have been tried for the treatment of male and female pattern hair loss and alopecia areata with variable success rates. The laser beam having the coherent, monochromatic, and polarized characteristics AGA is the most common form of hair loss that may affect up to 70% of men and 40% of women in their lifetime [86, 87]. The aim of the treatment is to stop miniaturization and induce hair thickening and regrowth [88]. Finasteride and minoxidil are the most common therapeutic drugs used for AGA [87]. But new treatment modalities are under investigation. Laser/light sources for AGA have become popular in the last few years.

Photobiomodulation is a term that is used to describe the effects of lower level light energy (650–900 nm) on the cellular level. The exact mechanism of photobiomodulation that stops or reduces hair loss in patients is not well known [85, 89]. Low‐level visible light treatment (LLLT) modulates the gen expression of 5α‐reductase and vascular endothelial growth factor (VEGF) and consequently stimulates hair growth through androgen metabolism and angiogenesis [90]. It was previously reported that helium‐neon (He‐Ne) laser (632.8 nm) irradiation stimulates cellular activities like deoxyribonucleic acid (DNA) and protein synthesis, mitochondrial electron transport, and adenosine triphosphate (ATP) generation [91]. Low‐level laser irradiation prolonged the duration of anagen phase and caused the catagen and telogen follicles to reenter into the anagen phase in a study in mice treated with He‐Ne laser. It was revealed that He‐Ne laser with a dose of 1 J/cm<sup>2</sup> shows stimulatory effects on hair growth with a significant increase in percentage of anagen, but a suppression of hair growth was observed at a dose of 5 J/cm<sup>2</sup> . Cells with low growth rate or under stress conditions, give better response to low‐level laser irradiation [90]. Low level of reactive oxygen species (ROS) occurred due to low doses of irradiation show stimulatory effects on cell metabolism, while high level of ROS due to high doses of irradiation show inhibitory effects [92–94].

Subsequently, paradoxical hypertrichosis was reported for many times after using laser and intense pulsed light (IPL) photoepilation therapy for hair removal [95–99]. It is not exactly known, how these light sources can induce hair growth. One possible mechanism is the activation of silent hair follicles or the synchronization of hair growth cycles by direct light stimulation [89]. Radmanesh et al. identified different mechanisms for developing hypertrichosis after the IPL. First, certain wavelengths of IPL show photostimulator effects on hair follicle germinative and stem cells, directly or indirectly and facilitate hair regeneration and growth. The stem cells in the bulge area of the hair follicle are usually inactive. The second mechanism is the stimulation of the secretion of the mediators and cytokines that stimulate hair growth by IPL. Keratinocyte growth factor and fibroblast growth factor are two well known trichostimulatory cytokines and they have stimulatory effects on hair follicles and epidermal cells. They maintain epidermal proliferation and hair growth. The individual differences and the properties of the devices may also affect the paradoxical hypertrichosis [98].

There are various studies showing the positive effects of laser/light treatments in AGA. In a previous study, the effects of laser on cancer were investigated in mice. The dorsal hair of mice was shaved and the low‐powered ruby laser (694 nm) therapy was given toward this area. They did not find any evidence of cancer but observed accelerated hair growth in laser‐ treated sides [100]. In a clinical study, seven patients with a diagnosis of AGA were exposed to LLLT twice weekly for 20 min for 3–6 months. An increase in the number of terminal hair, a decrease in the number of vellus hair, and an increase in shaft diameter were observed in this study but these changes were not statistically significant [89].

To assess the effect of a 1550 nm fractional erbium‐glass laser in a female pattern hair loss, 28 patients received 10 treatments at 2‐week interval. At the end of the study, a marked increase in hair density and hair shaft thickness and significant improvement at the frontal hair recess were seen in patients. It was revealed that 1550 nm fractional erbium‐glass laser may be a safe and effective treatment option for female pattern hair loss (FPHL) [101]. In a clinical study, the effects of a 1550 nm fractional erbium‐glass laser on the hair cycle in an alopecia mouse model and on the treatment of male pattern hair loss were investigated. In the human pilot study, an increase in hair density and an improvement of growth rate were observed. In the animal study, the effect on hair stimulation was dependent upon the energy levels, densities, and irradiation intervals. Fractional laser irradiation can promote anagen hair growth and induce transition from the telogen phase to the anagen phase. It was shown that Wnt 5‐α and β‐catenin expressions play a role in hair growth were induced by laser irradiation [102].

In a study of 32 patients with male and female androgenetic alopecia, the efficacy and safety of LLLT were evaluated. A Laser comb (655 nm) was used as monotherapy or as a concomitant therapy with minoxidil and finasteride. Eight patients showed significant improvement, 20 patients showed moderate improvement while no improvement was observed in four patients. Improvement was observed in both monotherapy and the dual therapy group [103]. Previously, a Laser comb has been tested in 110 patients with AGA in a double‐blind, sham device‐controlled, multicenter, and 26‐week trial. Significant increase in mean terminal hair density was observed in patients in the LLLT group when compared to patients in the sham device group [104]. Jimenez et al. reported a statistically significant increase in terminal hair density after 26 weeks of low‐level laser comb device treatment compared with sham treatment in patients with FPHL and male pattern hair loss (MPHL) [105].

#### **5.2. Alopecia areata**

As there is no cure for alopecia areata which is an autoimmune disease and may improve spontaneously in 34–50% of patients, clinicians search for new treatment modalities such as laser/light sources [86, 106, 107].

There are limited studies about laser irradiation for alopecia areata. In a study, clinicians used 308 nm xenon chloride excimer laser (XeCl) for two patients with alopecia areata for 11–12 sessions within a 9–11 weeks period. They observed homogeneous and thick hair growth. The exact mechanism was not clear, but immunosuppressive effects of laser irradiation by inducing T‐cell apoptosis and interrupting autoaggressive immune cascade were held responsible [108]. In a study with nine patients with AA, 308‐nm excimer laser was used for lesions twice a week for 12–24 sessions. They observed hair regrowth in patients with AA partialis [109].

In a previous study, researchers chose a single representative lesion that was unresponsive to the other treatments. One half of the lesion was exposed to the 308‐nm laser while the other part was not treated. After 27 sessions, only the treated area showed hair regrowth, suggesting it was not a spontaneous recovery [110].

The 308‐nm excimer laser was used for patients with AA twice a week for 24 sessions. And it is reported as an effective treatment for patchy AA of the scalp and in some cases with AA of the beard area, but patchy lesions of the extremities and alopecia totalis were unresponsive [111]. It was also used for children with patchy AA successfully. Atopic diathesis was considered as a poor prognostic factor in this study [112].

Waiz et al. used pulsed infrared diode (904 nm) laser on 16 patients with 34 resistant alopecia areata patches. They observed hair regrowth with a rate of 94%. They suggest that laser may alter the cellular membrane or change the exposed antigen which was previously hidden to become hidden again [84].

Yoo et al. treated a patient with recalcitrant AA with fractional laser therapy weekly for 24 weeks. Hair regrowth was observed after 1 month treatment. After 3 months 30–40% of lesions were covered with terminal hair. Complete recovery occurred after 6 months of fractional laser therapy. One of the possible mechanisms of fractional laser induced hair regrowth is inducing T‐cell apoptosis or decreasing inflammation. Another mechanism is about microscopic thermal columns in the dermis that were made by laser therapy. A healing process starts including lymphocyte infiltrations. It may scatter perifollicular lymphocyte infiltration and cause a decrease in perifollicular lymphocytic infiltration. Fractional laser may stop disease progression by increasing anagen phase. Furthermore, minor trauma and wound healing induced by fractional laser therapy may facilitate hair growth [113].

Three patients with ophiasis, a special pattern of AA, were enrolled in a study. Two of the patients were treated with nonablative 1550 nm erbium glass fractional laser (NAFL) and one of the patients treated with both NAFL and ablative 10,600 nm carbon dioxide fractional laser (AFL). The clinicians observed that patients who have AA for 1 year or less respond to treatment better than patients with long‐term disease. They considered NAFL treatment may have beneficial effects on early ophiasis lesions [114].
