FormalPara Key Summary Points

Lichen planopilaris (LPP) is a rare chronic unremitting condition with permanent hair loss.

The current treatments are suboptimal and unsuitable for long-term use because of adverse effects.

Four cases of classical LPP, of which two were refractory to previous therapies, are described.

The patients were successfully treated with a novel botanical formulation, named Dr. UGro Gashee, as a sole therapy.

The roles of three main phytoactive ingredients in the formulation in targeting pathophysiological mechanisms responsible for LPP are discussed.

Introduction

Lichen planopilaris (LPP), believed to be a variant of lichen planus, is a chronic, smoldering, and progressive scarring alopecia characterized by hair loss, fibrosis, and inflammation. Pruritus, tenderness, and burning of the scalp are often associated symptoms. Although LPP affects both men and women, it is more prevalent in women aged 30–60 years [1]. Inflammation in LPP is mainly lymphocytic and confined to the isthmus and infundibular levels of the perifollicular and interfollicular dermis; this pathobiology represents a cell-mediated autoimmune attack of the hair bulge likely caused by the loss of hair follicle immune privilege (HFIP) [2].

Although a standard treatment for LPP has not been defined, the most common treatment regimen involves topical/intralesional high-potency steroids and oral hydroxychloroquine. Treatments with tetracyclines, pioglitazone, isotretinoin, cyclosporine, mycophenolate mofetil, methotrexate, calcineurin inhibitors, systemic steroids [1], and naltrexone [3] have also been reported. Combinations of some of the treatments mentioned above with procedures, such as low-level light therapy [4] or platelet-rich plasma (PRP) [5], have been reported as therapeutic approaches. These approaches are suboptimal, as is evident from the variable and often contradictory results [1]. Furthermore, a high potential for adverse effects makes these treatments unsuitable for long-term use. Without effective treatment, LPP typically results in an unrelenting course, affecting wider areas of the scalp with erythema and white perifollicular keratotic casts. The end results include smooth, shiny atrophic scarred plaques devoid of follicular ostia and indicative of scarring permanent hair loss. There is an unmet need for effective and safe treatments for this chronic condition.

Gashee contains a proprietary formulation of at least 12 phytoactive ingredients designed to modulate multiple biological pathways that cause hair loss favorably. We retrospectively reviewed records of patients with histologically proven LPP treated with topical Gashee lotion (cosmeceutical) alone or in combination with oral Gashee supplements (nutraceutical). Here, we report four patients with classical LPP treated exclusively with Gashee botanical formulations using the topical form alone or in combination with the oral form.

Case Presentations

All patients provided written consent to publish the data and images in this report. Approval from an Institutional Review Board was not required, given the retrospective description of clinical findings in routine care of the patients.

Patient 1

A 56-year-old white Hispanic woman had a 10-year duration of progressive hair loss and a paternal family history of hair loss. She reported intermittent scalp irritation, pruritus, and hair shedding. Examination revealed atrophic scarring and hair loss, extending across the vertex, mid-scalp, and frontal regions of the head. Follicular erythema and areas of perifollicular casting were visible on trichoscopy. The patient had a history of frequent use of hair dyes, blow dryers, and curling irons on her hair. Trichoscopy revealed perifollicular scaling and erythema (Fig. 1). A biopsy obtained from the mid-frontal scalp showed histological features consistent with LPP. Several years of treatment with intralesional triamcinolone 5–10 mg/cc, 5% minoxidil foam, and clobetasol 0.05% ointment were suboptimal. After the patient discontinued all previous treatments, twice daily use of topical Gashee lotion combined with four daily capsules of Gashee oral supplements was started. She continued her usual routine of dyeing, blow-drying, and curling hair. Reduced erythema, new hair growth, and increased coverage of the affected regions of the head were observed after 5 months of treatment (Figs. 2 and 3). The patient reported complete cessation of hair shedding and all the symptoms and had no adverse effects. Owing to supply issues, she discontinued the oral Gashee. However, she continued to experience continuing growth and absence of symptoms at 7 months of follow-up using only topical Gashee (Fig. 4).

Fig. 1
figure 1

Trichoscopy image of patient 1. Trichoscopic image of a patient diagnosed with lichen planopilaris, showing perifollicular casts and erythema

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Fig. 2
figure 2

Frontal and mid-scalp regions of patient 1. Images of the frontal and mid-scalp regions of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 5 months of treatment with Gashee lotion and oral supplements

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Fig. 3
figure 3

Frontal to crown regions of patient 1. Images of the frontal region extending to the crown of the head of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 5 months of treatment with Gashee lotion and oral supplements

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Fig. 4
figure 4

Frontal. Mid-scalp and crown regions of patient 1. Images of the frontal and mid-scalp (i) and the frontal region extending to the crown of the head (ii) of patient 1, at 7 months after stopping Oral gashee and using topical Gashee as a sole treatment

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Patient 2

A 54-year-old African American woman had a 2-year duration of hair loss, visible hair shedding, and scalp irritation and pruritus. Examination revealed areas of thinning hairline in the frontal and temporal regions. Trichoscopy showed perifollicular casts and erythema (Fig. 5). The patient had not tried any previous hair loss treatment. A biopsy showed histological findings consistent with LPP. Twice daily use of the topical Gashee formulation in combination with four daily capsules of Gashee oral supplements was implemented. A reduction in erythema and significantly increased hair coverage were observed in the temple areas of the head after 6 weeks of treatment (Figs. 6 and 7). The patient reported a cessation of all the symptoms and had no adverse effects.

Fig. 5
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Trichoscopy image of patient 2. Trichoscopic image of a patient diagnosed with lichen planopilaris, showing perifollicular casts and erythema

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Fig. 6
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Left temporal region of patient 2. Images of the left temporal region of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 6 weeks of treatment with Gashee lotion and oral supplements

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Fig. 7
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Right temporal region of patient 2. Images of the right temporal region of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 6 weeks of treatment with Gashee lotion and oral supplements

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Patient 3

Patient 3 was a 38-year-old white female with a 10-month history of hair loss, severe itch, irritation, redness, and hair shedding. Examination revealed erythema, atrophic plaques, and visible thinning in the frontal, mid-scalp, and vertex areas. She had been treated with triamcinolone acetonide 40 mg/cc scalp for 4 months and had used tacrolimus 0.1% ointment twice daily. She discontinued all treatments 6 months prior to presentation due to a lack of improvement. A biopsy revealed features of LPP, and she was started on topical Gashee, which she initially used once a day for a month. She experienced some irritation at the application site, prompting her to revert to a once every other day regimen that led to the resolution of the irritation. Within 6 weeks of usage, all LPP symptoms had resolved. At 4 months, she showed complete resolution of erythema, and evidence of significant hair regrowth (Figs. 8 and 9), without adverse effects.

Fig. 8
figure 8

Top of head and vertex viewed from the back of patient 3. Images of the top of the head and vertex of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 4 months of treatment with Gashee lotion

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Fig. 9
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Top of head and vertex viewed from the front of patient 3. Images of the top of the head and vertex of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 4 months of treatment with Gashee lotion

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Patient 4

A 29-year-old African American male had acne keloidalis nuchae (AKN) in the nuchal area and scalp-wide hyperpigmented atrophic plaques affecting most of the remaining scalp with progressive miniaturization and loss of hair follicles. The scalp was swollen and chaffed. He had symptoms of hair shedding, pruritus, and scalp irritation. Trichoscopy revealed perifollicular casts and erythema, combined with hyperpigmentation of interfollicular spaces (Fig. 10). A biopsy of these lesions confirmed LPP. The disease progressed despite treatment with intralesional steroid triamcinolone 5 mg/cc injections and topical betamethasone 0.05% solution. A regimen of twice-daily use of the topical Gashee formulation was started. The patient noted the resolution of all the symptoms. On examination, his scalp was supple and uninflamed. There was thickening and lengthening of hair, resulting in areas of new hair growth and cessation of disease progression within 3 months. The improvement was sustained at the last observation, at 7 months follow-up (Figs. 11 and 12). A repeat biopsy taken from a region adjacent to the previous one revealed less number of inflammatory cells and more follicular activity associated with an increased number of adipocytes (Figs. 13 and 14). The patient reported no adverse effects.

Fig. 10
figure 10

Trichoscopy image of patient 4. Trichoscopic image of a patient diagnosed with lichen planopilaris, showing hyperpigmentation, perifollicular casts, and erythema

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Fig. 11
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Top of head and vertex of patient 4. Images of the top of the head and vertex of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 7 months of treatment with Gashee lotion

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Fig. 12
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Left side view of patient 4. Images of the left side view of a patient diagnosed with lichen planopilaris, obtained before (i) and after (ii) 7 months of treatment with Gashee lotion

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Fig. 13
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Hematoxylin and eosin staining of the vertex of patient 3 before starting the use of the Gashee lotion. The vertical section at ×2 (i) and ×4 (ii) magnification shows scarring and moderate perifollicular lymphocytic infiltration

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Fig. 14
figure 14

Hematoxylin and eosin staining of the vertex of patient 3 at 7 months after using the Gashee lotion. The transverse section at ×2 (i) and ×4 (ii) magnification, showing scarring, moderate perifollicular lymphocytic infiltration, increased number of follicles with mixed anagen and catagen phase as well as several vellus hair follicles, with an increased number of adipocytes and absence of inflammation

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Discussion

In this report, we focused on patients diagnosed with classical LPP and excluded patients diagnosed with frontal fibrosing alopecia (FFA) or fibrosing alopecia in patterned distribution (FAPD). These latter variants have a different mechanistic part that influences different symptomatology and therapeutic approaches [9].

We report four patients diagnosed with classical LPP who received marked benefit from a natural treatment, using a topical botanical alone or in combination with its oral formulation. All patients consistently showed a significant improvement in surrogate indicators of LPP activity, including a reduction in inflammation, complete resolution of symptoms, and signs of hair regrowth. In addition, they reported a high satisfaction level and the absence of adverse effects. We are not aware of prior reports on botanical formulas or natural treatments for LPP.

All patients were treated exclusively with the formulation, avoiding the need for high-potency steroids or other pharmaceuticals that have conventionally been used to treat LPP and have potential adverse effects. To elucidate the mechanism for the observed improvements, we examined the ingredient list. We found that, of 12 reported ingredients of Gashee [6], at least 3 can modulate multiple LPP mechanistic pathways, such as the JAK/STAT pathway, which induces increased interferon-gamma (IFN-γ) activity and loss of immune privilege in LPP [10]; the antifibrotic peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway, which is downregulated in LPP [10]; the profibrotic and catagen-inducing transforming growth factor-beta1 (TGF)-β1/SMAD, which is increased in LPP [12]; and proinflammatory cytokines such as interferons (IFNs) and tumor necrosis factor-alpha (TNF)-α, the levels of which are increased in LPP [13].

Direct causes of hair loss in LPP include TGF-β, which induces catagen in hair [14], IFN-γ, which leads to an immune attack on hair bulge, and TNF-α, which induces apoptosis of dermal papillae cells (Table 1).

Table 1 Lichen planopilaris (LPP)-relevant properties of various Gashee components
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The possible mechanisms underlying the improvement of LPP by a botanical are further discussed below.

Inhibition of JAK/STAT

JAK1 and JAK3 are significantly upregulated in dermal inflammatory cells of patients with LPP. Upregulation of JAK1 is believed to result in increased IFN-γ activity, which may cause the loss of HFIP, especially in the bulge region [37]. This may explain the reported success in treating LPP with the JAK inhibitor, tofacitinib [10]. Two major ingredients, curcumin [15,16,17] and fenugreek [24, 25], in both the topical and oral Gashee, as well as green tea extract [32, 33] in topical Gashee, are JAK/STAT inhibitors (Table 1).

Upregulation of PPAR-γ

PPAR-γ normally inhibits fibrosis at the involved tissue points. The following findings evidence the implication of reduced PPAR-γ activity in the causation of LPP: reduced PPAR-γ activity in LPP tissue compared with that in non-LPP involved tissue [12], a significant reduction in the expression of PPAR-γ [38], a transcription factor in LPP, and success in the treatment of LPP with a PPAR agonist, pioglitazone [11]. Curcumin [19, 20] and fenugreek [27], found in both topical and oral Gashee, as well as green tea [34], found only in topical Gashee, have been shown to upregulate PPAR-γ (Table 1).

Inhibition of TGF-β1/SMAD

TGF-β1, SMAD2, and SMAD3 transcripts was upregulated in LPP-involved tissue compared with noninvolved tissue of the same patient [12]. TGF-β/SMAD causes hair loss by pushing hair into catagen [14, 39] while causing fibrosis by inducing epithelial–mesenchymal transition through downregulation of PPAR-γ [12]. Curcumin [18] and fenugreek [26] have been shown to inhibit TGF-β1/SMAD activity (Table 1).

Modulation of Proinflammatory Cytokines

The levels of the proinflammatory cytokine IFN-γ are increased in LPP-involved tissue compared with uninvolved tissue. IFN-γ plays a central role in LPP by canceling the HFIP in the bulge and stem cell exhaustion [37].

Furthermore, thiazolidinediones were reported to cause improvements in LPP, reduce proinflammatory nuclear transcription factors (nuclear factor-κβ and nuclear factor of activated T-lymphocytes), proteolytic enzymes (matrix metalloproteinase-9), and inflammatory interleukins (interleukin [IL]-1β, IL-2, and IL-6), and other inflammatory molecules (TNF) [40].

Curcumin [21,22,23] and fenugreek [28,29,30,31], present in the topical and oral Gashee formulations, and green tea [35, 36], found only in the topical formulation, are potent antiinflammatory agents (Table 1).

Limitations

The limitations of the present study include a small sample size, retrospective nature, and lack of controls. While the improvements seen in patients are not consistent with the natural history of treatment-refractory LPP, a prospective and well-controlled study will help evaluate the use and optimal dosing, efficacy, and safety profile of topical and oral Gashee formulations or their combination.

Conclusions

Current treatments for classic LPP, a typically refractory and progressive disease, are suboptimal and associated with potential adverse effects that complicate long-term use. Treatment-refractory LPP responded to the plant-based natural treatment Gashee. Our findings suggest that the role of botanicals in the treatment of LPP, including optimal dosing, warrants further investigation in larger controlled trials.