**3. Lichen planopilaris management**

There is no curative therapy for LPP. Therefore, the main goal of the treatment is to reduce the inflammatory symptoms and to slow the progression of hair loss, since hair regrowth is not possible when scarring has happened.

No gold standard approach exists to the treatment of LPP. Moreover, the publications about the treatment of LPP are quite sparse and the therapies they are referred to have limited evidence. Only a few of them are controlled trials. Furthermore, the

evidence shows a varied response to therapy, with frequent reports showing poor outcomes [51–53]. There are some recommendations for the treatment of LPP, but no specific therapy guidelines. Hence, daily clinical practice often relies on disease activity, age, comorbidities, and the physician's personal experience [54]. Patients with LPP experience significantly impaired quality of life and mental health associated with disease activity, and the potentially permanent hair loss highlights the importance of early disease detection and treatment [55].

#### **3.1 Topical and intralesional treatments**

Topical steroids are often reported as a first-line treatment, especially the ultrapotent corticosteroid clobetasol propionate, for cases with a limited extent. They help to reduce inflammation and associated symptoms, including burning sensation and itchiness [12, 35]. A proposed protocol consists of using topical steroids twice daily for the first month, followed by an application once a day for 3 months, and then every other day for 3 more months [56].

Monthly intralesional high potency corticosteroids have similar outcomes to topical steroids regarding efficacy. Injections of triamcinolone acetonide at a concentration of 10 mg/mL −2 mL in total - every 4 to 6 weeks until disease stabilization, are recommended for the treatment of LPP by the researchers of the University of British Columbia [57]. They also suggest that if there is no improvement after three months of injections, other treatment options should be considered. There is no clear evidence about which delivery mode is better, although Lyakhovitsky et al. and Mehregan et al., propose that topical and intralesional corticosteroids can be used together to achieve a faster clinical response [58, 59].

Topical calcineurin inhibitors also reduce inflammation and help to induce the early anagen phase of the hair cycle. However, the largest study of topical calcineurin inhibitors, which included ten patients with LPP, reported inflammation improvement in only two patients (one on monotherapy and another one associated with hydroxychloroquine) [58].

Topical minoxidil improves the caliber and condition of the hairs of the background, but irritative and allergic contact dermatitis, in an already inflamed scalp, are common adverse effects [60]. A combination of topical tacrolimus 0.3%, clobetasol propionate 0.05%, and minoxidil 5%, can be applied twice daily as first-line therapy, along with intralesional triamcinolone acetonide. When the disease stabilizes, the clobetasol dose is the one to be decreased or discontinued first, followed by the tacrolimus dose [54].

The efficacy and safety of PRP in cicatricial alopecia, including LPP, remain unknown. In a recent case series of 10 patients with LPP and FFA, who received PRP mesotherapy, no koebnerization or development of new areas of involvement were noted, although the clinical improvement was unclear due to the multitherapy regimens done by the patients [61].

#### **3.2 Systemic treatments**

Oral treatments are indicated for patients with local treatment resistance, more extensive manifestations, scalp involvement ≥10% and those with rapid progression.

Hydroxychloroquine is often preferred as the first-line systemic agent because of its relatively good side-effect profile. There are several case series regarding hydroxychloroquine as monotherapy or in combination with other agents, with

varied outcomes, and overall, treatment response was seen in approximately 50–60% of cases [58, 62, 63]. Conversely, other small case series or single case reports showed little or no response [64]. Action onset occurs after two to three weeks, and the peak of response is achieved after six months. Hydroxychloroquine may be initially administered at 200 mg, twice daily, with the goal to decrease to weight-based dosing of 5 mg/kg/day, for a 6 to 12-month period [54].

Immunomodulators are therapeutic alternatives for patients with difficult-to-control disease. Some options pointed out in the literature are methotrexate, cyclosporine and mycophenolate mofetil [65].

A randomized clinical trial comparing hydroxychloroquine (400 mg daily) and methotrexate (15 mg weekly), for a 6-month period in recalcitrant LPP, found a significant superiority of methotrexate over hydroxychloroquine. Moreover, patients in the hydroxychloroquine group showed only a significant improvement in erythema, while patients in the methotrexate group showed efficacy on pruritus as well as on all the objective variables assessed in the study (erythema, perifollicular erythema, perifollicular scaling, spreading, and follicular keratosis). The negative outcomes observed in the patients belonging to the hydroxychloroquine group could be due to the fact that the study was only focused on recalcitrant cases [66]. In a retrospective study, the response rates of cyclosporine and methotrexate were similar (100% and 85%, respectively), and those treated with cyclosporine achieved partial and complete remission faster than the methotrexate group patients. However, both treatments were less safe compared to mycophenolate mofetil [52].

On the other hand, a randomized controlled trial for evaluating the safety and efficacy of methotrexate (15 mg, oral, per week) versus cyclosporine (3–5 mg/kg/ day), for six months, in patients with refractory LPP, found similar efficacy at the end of the study with both treatments. Nevertheless, the authors proposed methotrexate as the first choice over cyclosporine because of its easier administration, fewer tolerable side effects and lower recurrence rates [67]. Other studies regarding cyclosporine in LPP also revealed considerable outcomes, although high relapse rates are common after its discontinuation [53, 56, 68].

Mycophenolate mofetil may be another potential treatment for patients with severe or recalcitrant LPP who have failed hydroxychloroquine and other immunomodulators [69, 70]. Six studies were included in a recent systematic review and meta-analysis, including 94 patients, in which 69.2% of patients had a good response (partial or complete), with dosages ranging from 1 to 6 g daily, and treatment duration ranging from 2 to 12 months [71].

Limited evidence supports the therapeutic potential of JAK inhibitors for the treatment of recalcitrant LPP, and in most published reports the patients were treated with other concomitant therapies [40]. A report which investigated the usefulness of topical and oral tofacitinib as an adjuvant treatment in 9 patients with recalcitrant LPP, found that both formulations were effective in achieving a positive clinical response. The median time to see any treatment response was 3 months. Authors concluded that although oral tofacitinib led to a more pronounced and sustained improvement, topical therapy may be considered a feasible alternative in some patients [72]. A report about the use of baricitinib in patients with refractory LPP (7/12) and FFA (5/12) (median dose of 3.4 mg and concomitant treatments in all of the patients), showed that 46.5% and 83.8% of patients, respectively, demonstrated an initial reduction in the median Lichen Planopilaris Activity Index (LPPAI) score. However, the response was maintained in only 3 out of 7 LPP patients and in 2 out

of 5 FFA patients, after a median duration of 6 months. Furthermore, 4 patients had previously had a failure with oral tofacitinib treatment, which may predict a possible absence of response to another JAK inhibitor [73].

Oral glucocorticoids should be reserved for very symptomatic patients and those with rapid progression, due to their potential adverse effects and the very high degree of relapse (around 80% of patients) after treatment discontinuation [54, 74]. Some authors utilize short courses in rapidly progressive cases, usually prescribed at 40 mg daily for 1 week, then tapered by 5 mg weekly for 8 weeks, acting as a bridge to the effect of longer-lasting drugs, such as methotrexate [75].

The first study describing the use of low-dose of oral minoxidil (LDOM) in LPP showed that LDOM (median dosage 1 mg/day), with a mean duration of therapy of 21 months, can help to maintain or increase hair thickness in the majority of patients with LPP, in unaffected and potentially affected areas, with an acceptable safety profile. Better results were reported in patients presenting diffuse LPP and with the higher doses of LDOM used in male patients [35].

Regarding low dose naltrexone for the treatment of LPP, only one case series including four patients has been published, which showed some therapeutic benefits, including a decrease in inflammation and in the presence of inflammatory symptoms, along with slowing in the disease progression [76].

Other systemic treatment options, such as doxycycline (100 mg twice daily), have shown limited outcomes [58, 60, 77].

#### **3.3 Treatments based on light devices**

LLLT is an emerging light therapy that has shown effectiveness in treating several inflammatory skin disorders, such as lichen planus. Nevertheless, the reports about its use are limited [78], and there are just two studies about LLLT for the treatment of LPP. The first study, which included a total of 8 patients, showed a global reduction of symptoms, erythema, and perifollicular hyperkeratosis in all patients after 6 months of intervention [79]. Another report showed consistent improvement with reduction of inflammation, the disappearance of symptoms, and evident hair regrowth after 3 and 6 months, in a total of 4 patients whose disease had remained active despite topical and/or systemic treatments [80]. Limitations of this treatment could be the daily regimen and the lack of clear treatment protocol and parameters.

#### **3.4 Hair transplant**

The outcomes of transplantation in patients with LPP vary because of the autoimmune nature, so surgical procedures may trigger the Köebner phenomenon and induce new lesions in recipient and donor areas [47]. Hence, most of the authors believe that transplantation can be considered in patients with clinical remission of at least two years in order to keep the final outcome of transplantation and induce hair regrowth. Regarding the technique, FUE (follicular unit extraction) is preferred due to the following advantages: the absence of suture wounds and linear scars, less bleeding and less postoperative discomfort. Furthermore, these patients require close postoperative follow and long-term observation to determine the final outcomes of the treatment. If perifollicular keratosis or erythema is noted, medical modalities such as topical/intralesional steroid injections and/or oral medications should be given to prevent further hair loss [81, 82].

*Treatment of Frontal Fibrosing Alopecia and Lichen Planopilaris DOI: http://dx.doi.org/10.5772/intechopen.106230*

### **3.5 Therapeutic algorithm for LPP**

A therapeutic algorithm for LPP is proposed in **Figure 2**, with different lines of treatment indicated with the circled numbers.

**Figure 2.** *Therapeutic algorithm for LPP.*
