**2. Frontal fibrosing alopecia management**

The therapeutic management of FFA remains still challenging due to its unclear pathophysiology, the lack of double-blind prospective studies and the progressive and refractory nature of the disease. In fact, most of the studies about treatment in FFA are based on retrospective cohort studies and case reports. The best therapeutic option in FFA usually combines oral and topical or intralesional treatments. Topical and intralesional corticosteroids are first-line treatments due to their security profile, and 5-alpha reductase inhibitors are currently considered one of the most effective therapies in terms of disease stabilization [10, 11]. FFA is progressive and mostly irreversible, so an early diagnosis and treatment is mandatory to achieve the best results. However, in some cases, a poor outcome can be predicted despite the treatment, especially in patients with the diffuse form [12].

#### **2.1 Topical and intralesional treatments**

Potent topical corticosteroids are considered the first-line treatment and are recommended especially when inflammation signs are present. There is no clear benefit in slowing the progression of the alopecia, but their security profile and capacity to relieve symptoms support their use [13, 14]. Similar indication has the use of topical calcineurin inhibitors, either alone or associated with topical corticosteroids, although one report found a better outcome with them, in terms of stabilization, compared to a group of patients treated with corticosteroids [15, 16]. Topical calcineurin inhibitors are also useful to spare topical corticosteroids. However, topical treatments are not usually used in monotherapy, which makes it difficult for a proper assessment of their real efficacy.

Topical minoxidil has not shown clinical improvement in slowing down the alopecia, but it is useful when androgenetic alopecia is associated or to improve the remaining hair [13].

In the case of eyebrow and eyelash alopecia, the use of a prostaglandin analogue, such as bimatoprost 0.03% eye drops, applied twice daily, may be a therapeutic option [17].

Eyebrow alopecia in FFA usually does not improve with systemic treatment alone, so another associated therapy is recommended [18]. In that case, the use *Treatment of Frontal Fibrosing Alopecia and Lichen Planopilaris DOI: http://dx.doi.org/10.5772/intechopen.106230*

of intralesional corticosteroids, 10 mg/ml of triamcinolone acetonide every three months, may obtain hair regrowth in some patients, especially when the hair loss is partial. A higher concentration of triamcinolone acetonide – 20 mg/ml - can be used in the hairline implantation, every 3 to 6 months, and it may obtain stabilization and even hair regrowth in a considerable number of patients [19].

There is only one study about platelet-rich plasma (PRP) in FFA. These authors reported one patient who had an improvement in the trichoscopic signs and a stoppage in the progression of the alopecia after five treatments, with a one-month interval of injections in the frontotemporal hairline and eyebrows [20].

#### **2.2 Systemic treatments**

Nowadays, oral 5-alpha reductase inhibitors are considered the most effective treatment for FFA. In a report about 102 patients with FFA treated with finasteride (2.5–5 mg/day), which inhibits the isoenzyme type II of 5-alpha reductase, 47% of them showed improvement and 53% of them showed stabilization of the alopecia [19]. Dutasteride is about three times as potent as finasteride at inhibiting type II 5-alpha reductase and more than 100 times as effective at inhibiting type I [21]. A recent study including 224 FFA patients found a significantly higher stabilization rate in those under treatment with dutasteride – around 64% - compared to other systemic treatments, such as finasteride, hydroxychloroquine, doxycycline and isotretinoin [11]. Moreover, the response was dose-dependent, and the most effective dose was five to seven capsules of dutasteride (0.5 mg) per week. Thus, 5-alpha reductase inhibitors are considered, by most authors, the first therapeutic option in patients with FFA, [22] while others considered them as a second-line therapy [23]. Due to its higher effectivity, dutasteride may be a suitable first option, except for childbearing age women, in which finasteride should be considered because of its shortest wash-out period [22].

Antimalarials, such as hydroxychloroquine, may improve symptoms and signs of FFA, with better results seen within the first six months of therapy, although they normally achieve partial responses [24]. Other reports have not found any consistent benefit with the use of hydroxychloroquine [14]. A recent systematic review found that hydroxychloroquine and 5-alpha reductase inhibitors resulted to be the most effective therapies in terms of disease stabilization [10].

Tetracyclines, such as doxycycline, have been used for their anti-inflammatory effects in patients with FFA, often after antimalarial failure, but the response rates are low and not consistent [24, 25].

Treatment with oral prednisone (0.5–1 mg/kg/day), for 3 to 18 months, has been shown to produce a stoppage of the progression of the alopecia in almost 43% of patients, but relapse occurs after its discontinuation [13]. Therefore, the worse security profile in long-lasting treatments, and the relapse when the treatment is stopped, move this therapeutic option from the first-line treatments.

Oral retinoids, isotretinoin (20 mg/day) and acitretin (20 mg/day) have been shown to produce a stoppage in the hairline recession in 76% and 73% of patients, respectively, in a retrospective analysis, in which they were even more effective than finasteride (5 mg/day) in stopping the progression of the alopecia [26]. Isotretinoin may be useful in patients with facial papules, which may improve in two to four months with low doses such as 10 mg/day or even less. The improvement of erythema and perifollicular hyperkeratosis has also been reported in patients under treatment with isotretinoin (10–20 mg/day) [27]. Regarding other oral retinoids, such as

alitretinoin, only one report of a woman has been published, in which she showed improvement after one month with 30 mg/day [28]. Facial papules improvement has also been noted with the use of oral prednisone and hydroxychloroquine, after at least 6 months of treatment [29, 30].

Other treatments, such as griseofulvin or azathioprine have shown inconsistent outcomes or no efficacy [3, 24, 31–33]. Partial responses have been described in around 60% of patients who were treated with mycophenolate mofetil [24]. Stabilization of a few patients who were under treatment with methotrexate has been observed [25, 34].

Low-dose oral minoxidil may improve the background hair thickness, although further studies about its use in FFA are needed [35]. Its addition to the treatment may be interesting to increase hair volume, especially when androgenetic alopecia is present [36]. In some patients with FFA and concomitant androgenetic alopecia, who were treated with oral minoxidil, partial or complete eyebrow regrowth was noted [37]. Therefore, low-dose oral minoxidil (0.25–2.5 mg/day) may be an interesting adjuvant therapy for the treatment of eyebrow alopecia in patients with FFA, particularly in early disease.

Regarding the use of the oral pioglitazone hydrochloride (15 mg/day), a peroxisome proliferator-activated receptor γ (PPAR- γ) agonist, inconsistent results have been found when using it in LPP, but no successful outcomes have been observed in FFA patients [25, 38, 39].

The pan-Janus Kinase (JAK) inhibitor, tofacitinib, 10–15 mg/day, was used in some patients with refractory LPP (8/10) and FFA (2/10), from two to nineteen months; 80% of patients showed a clinical response, including clinical improvement in both FFA patients [40]. Baricitinib, a JAK 1 and 2 inhibitor, was used in a woman with refractory subacute cutaneous lupus erythematosus and FFA and resulted in completed clearance of the former and no further progression of the latter [41]. JAK inhibitors might be used as a therapeutic option in the future. An isolated report about a woman with recalcitrant FFA and LPP, who improved after the treatment with tildrakizumab, an anti p19 interleukin 23 monoclonal antibodies, was also published; the dose the authors used was 100 mg subcutaneously at week zero, 4 and subsequently 12 weekly, for around 4 to 13 months [42].

#### **2.3 Treatments based on light devices**

Some authors found that the excimer laser may be useful in reducing inflammation and perifollicular hyperkeratosis in patients with active LPP and FFA [43]. Photobiomodulation therapy, also known as low-level laser (light) therapy (LLLT), using light-emitting diodes (LEDs), may be an adjuvant option to consider in patients with FFA or LPP. A report found that LEDs may produce an improvement in symptoms and perifollicular hyperkeratosis, because of their anti-inflammatory and immunomodulatory effects, and may even increase the number of thick hairs within the treated area [44]. Moreover, LEDs treatment can also improve eyebrow alopecia in FFA patients, as was found in a study carried out on 16 women, in which an increase in hair count and in the number of thick and mid-thick hairs were noted, especially in cases of partial eyebrow alopecia [45].

A study about Nd:YAG (1064) non-ablative laser, carried out on 5 FFA patients, found improvement in symptoms and in perifollicular hyperkeratosis and follicular erythema in some patients [46]. Moreover, facial papules, lichen planus pigmentosus and hair loss spreading, also improved in some patients.
