What’s new in Hair – October 2018 | Dr. Sergio Vañó-Galván

Tofacitinib for the treatment of lichen planopilaris: A case series

Dermatol Ther. 2018 Sep 27:e12656. doi: 10.1111/dth.12656
Yang CC, Khanna T, Sallee B, Christiano AM, Bordone LA.

Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia. Severe cases are challenging. Some new therapies have emerged in the last years as potentially useful (low-dose oral naltrexone, low level light therapy, platelet rich plasma…). In this interesting study, Yang et al. describe 10 patients with recalcitrant LPP who were treated with oral tofacitinib 5 mg twice or three times daily for 2-19 months, either as monotherapy or adjunctive therapy to other ongoing treatments (intralesional triamcinolone, hydroxychloroquine and tacrolimus ointment). LPP Activity Index (LPPAI) before and after treatment was measured in 7 patients and was significantly different (6.22 before treatment, 3.08 after treatment; p value = .0014). No relevant adverse effects were reported.
Based on these results, treatment with oral tofacitinib either as monotherapy or adjunctive therapy can be useful in patients with recalcitrant LPP, opening a new line of research in the treatment of LPP.


Risk factors associated with frontal fibrosing alopecia: a multicentre case-control study

Clin Exp Dermatol. 2018 Sep 26. doi: 10.1111/ced.13785
Moreno-Arrones OM, Saceda-Corralo D, Rodrigues-Barata AR, Castellanos-González M, Pugnaire MA, Grimalt R, Hermosa-Gelbard A, Bernárdez C, Molina-Ruiz AM, Ormaechea-Pérez N, Fernández-Crehuet P, Vaño-Galván S.

Frontal fibrosing alopecia (FFA) is probably the current most frequent cicatricial alopecia. Although the aetiology of FFA has not yet been elucidated, four factors have been postulated to participate in its aetiopathogenesis: genetics, sex hormones, autoimmunity and potential environmental factors. The objective of this study was to identify possible environmental and hormonal factors related to FFA. The authors conducted a multicentre case–control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease.
Interestingly, for women: there was a statistical association between alopecia and his- tory of pregnancy, use of facial sunscreen and hormone replacement therapy or raloxifene, exposure to alkylphenolic compounds, and presence of rosacea, lichen planus pigmentosus or hypothyroidism. For men, there was a statistical association between alopecia and use of facial sunscreens or antiaging creams.
Although case-control studies may have risk of biases, this study shows interesting results that may open new lines of research in the pathogenesis of FFA.


Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata: A Systematic Review and Meta-analysis

JAMA Dermatol. 2018 Oct 1;154(10):1145-1151
Lee S, Kim BJ, Lee YB, Lee WS.

Alopecia areata (AA) is a chronic and relapsing hair follicle-specific autoimmune disease that leads to non-scarring hair loss. Diphenylcyclopropenone (DPCP) and squaric acid dibutyl ester have been commonly used as contact allergens for the therapeutic modality known as “contact immunotherapy”, which is one of the preferred treatments for severe AA. The objective of this metanalysis was to summarize the clinical outcomes of contact immunotherapy for AA according to standardized criteria for therapeutic hair regrowth and several prognostic factors.
Forty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with AA (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups), while the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater, atopic history, and nail involvement were associated with poorer therapeutic outcomes. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment.


Serum level of IL-4 predicts response to topical immunotherapy with diphenylcyclopropenone in alopecia areata

Exp Dermatol. 2018 Jul 26. doi: 10.1111/exd.13758
Gong Y, Zhao Y, Zhang X, Qi S, Li S, Ye Y, Yang J, Caulloo S, McElwee KJ, Zhang X.

In this interesting basic research study, the authors investigated predictors of response to topical diphenylyclopropenone (DPCP) immunotherapy in patients with alopecia areata (AA). They included 84 AA patients who were treated with DPCP. Serum cytokine levels were measured in 33 AA patients pre- and post-treatment, and in 18 healthy controls, using ELISA assays.
A total of 56.1% of patients responded to DPCP with satisfactory hair regrowth; the response rate was negatively correlated with hair loss extent. Before DPCP treatment, higher serum IFN-γ and IL-12 cytokine levels were observed in AA patients compared to healthy controls. Non-responders to DPCP had significantly elevated serum IL-4 pre-treatment (3.07-fold higher) and lower IL-12 levels compared with responders. After DPCP treatment, non-responders had persistently high IL-4, increased IL-12, negligible decrease in IFN-γ and decreased IL-10. Post-treatment DPCP responders exhibited significantly decreased IFN-γ and IL-12, and increased IL-4 and IL-10. Development of adverse side-effects was significantly associated with higher pre-treatment serum IgE levels.
In conclusion, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavourable and favourable predictors of DPCP therapeutic effect, respectively. In addition, pre- treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application.


Olfactory receptor OR2AT4 regulates human hair growth

Nat Commun. 2018 Sep 18;9(1):3624. doi: 10.1038/s41467-018-05973-0
Chéret J, Bertolini M, Ponce L, Lehmann J, Tsai T, Alam M, Hatt H, Paus R.

Interesting study of the research group of Dr. Paus, in which they show a new finding: the epithelium of human hair follicles, particularly the outer root sheath, expresses OR2AT4. This receptor is an olfactory receptor that has been shown to stimulate keratinocyte proliferation in the skin.
They also demonstrated that the specific stimulation of OR2AT4 by a synthetic sandalwood odorant (Sandalore®) prolonged human hair growth ex vivo by decreasing apoptosis and increasing production of the anagen-prolonging growth factor IGF-1. In contrast, co-administration of the specific OR2AT4 antagonist Phenirat® and silencing of OR2AT4 inhibited hair growth.
This study opens a new line of research, identifying that human hair follicles can engage in olfactory receptor-dependent chemosensation and require OR2AT4-mediated signalling to sustain their growth. It suggests that olfactory receptors may serve as a target in hair loss therapy.


The value of dermoscopy in diagnosing eyebrow loss in patients alopecia areata and frontal fibrosing alopecia

J Eur Acad Dermatol Venereol. 2018 Oct 5. doi: 10.1111/jdv.15279
Waśkiel A, Rakowska A, Kurzeja M, Czuwara J, Sikora M, Olszewska M, Rudnicka L.

In this clinical study, the research group of Dr. Rudnicka investigated the differences between the dermoscopic features of eyebrow loss in alopecia areata (AA) and frontal fibrosing alopecia (FFA). They included 50 patients with scalp AA with madarosis, 50 patients with scalp FFA with madarosis and 50 healthy controls.
Empty follicular and eccrine duct openings were observed in all patients and presented predominantly as yellow dots. Exclamation mark hairs were only detected in patients with AA (30%). Tapered hairs, broken hairs, black dots and Pohl-Pinkus constrictions were observed in 14%, 36%, 26% and 4% of patients with AA respectively, 4%, 16%, 2% and 0% of patients with FFA respectively, and they were not present in healthy controls. Dystrophic hairs and whitish areas were observed only in patients with FFA (28% and 32%, respectively). Eyebrow regrowth in distinct directions was present in 32% of patients with FFA, 8% of patients with AA and 4% of healthy controls. Diffuse erythema was detected in 60% of patients with AA and FFA and 56% of healthy controls. Vellus hairs and upright regrowing hairs were observed in patients with AA (62% and 58%, respectively), FFA (60% and 84%, respectively) and healthy controls (100% and 100%, respectively).
In conclusion, this study may be very useful for the differential diagnosis of patients with isolated eyebrow alopecia. The most characteristic dermoscopic features of eyebrow loss in AA include exclamation mark hairs, tapered hairs, broken hairs and black dots. FFA of the eyebrows is characterized by the presence of dystrophic hairs, white areas and eyebrow regrowth in distinct directions.

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