1
P8593 Direct hair growth promoting effects of mycophenolic acid Hoon Kang, MD, PhD, Department of Dermatology, St. Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; Jung Eun Kim, Department of Dermatology, St. Paul’s Hospital, College of Medicine, The Catholic Unviersity of Korea, Seoul, South Korea; Kwanho Jeong, Department of Dermatology, St. Paul’s Hospital, College of Medicine, The Catholic Unviersity of Korea, Seoul, South Korea; Young Min Park, MD, PhD, Department of Dermatology, St. Paul’s Hospital, College of Medicine, The Catholic Unviersity of Korea, Seoul, South Korea Mycophenolic acid (MPA) acts as a cell cycle inhibitor that produces reversible noncompetitive blockade of the purine synthesis pathway enzyme type II isoform of inosine monophosphate dehydrogenase (IMPDH). The major target of MPA is lymphocyte which contains abundant IMPDH. Among several kinds of hair loss disorders, lymphocytic cicatricial alopecia and alopecia areata are most represen- tative hair loss conditions induced by T lymphocyte attack to the hair follicle. Recently, in vitro study demonstrated that MPA effects on cellular proliferation and upregulates some valuable gene expression. Although MPA pharmacokinetic properties on purine synthesis pathway are well defined, the direct effects of MPA on hair follicles have yet to be studied. Therefore, we performed to determine the MPA either have a direct effect in vitro. In addition, we performed to determine how the effect of microneedle directly around the hair follicle. In our preliminary experiments, animal studies showed that topical mycophenolic acid treatment shortens the telogen and cause resting hair follicles entering into the anagen. However, effect of mycophenolic acid has not been fully demonstrated. In this study, we found that human DPCs respond to MPA as examined by hair growth factors responsive RT-PCR assay. We also found that mycophenolic acid treatment increases the phosphorylation of ERK1/2 and b-catenin. We also found that direct b-catenin pathway targets, such as Axin2 and Lef-1, are up-regulated by mycophenolic acid. These data suggest activation of b-catenin pathway by mycophenolic acid. These results suggest that be particularly important to develop new therapeutic option for hair loss. Commercial support: None identified. P7712 Enabling finasteride 1 mg users to further improve hair pattern: A randomized, double-blind, placebo-controlled trial of a novel product Akira Takeda, MD, PhD, Kitasato University School of Medicine, Sagamihara, Japan; Akio Sato, MD, PhD, Tokyo Memorial Clinic, Tokyo, Japan; Geert Cauwenbergh, PhD, Legacy Healthcare, Epalinges, Switzerland; JiaWei Liu, PhD, Legacy Healthcare, Epalinges, Switzerland; Lei Zhang, PhD, Legacy Healthcare, Epalinges, Switzerland; Saad Harti, MBA, Legacy Healthcare, Epalinges, Switzerland Background: The efficacy of finasteride 1 mg, the first-line treatment for male androgenetic alopecia (AGA), tends to reach a plateau after several years’ treatment. Up to date, effective and safe options are limited because current modalities managing AGA have so far not taken into account the 2 key issues particularly relevant to excessive hair loss: the early onset of catagen (due to premature hair follicular cell apoptosis) and the frequently observed sustained microinflammation in the scalp. Objective: We investigated the potential synergic effect of combining the oral finasteride 1 mg, acting on conversion of testosterone to 5a-dihydrotestosterone, with a novel topical antiehair loss product, acting on premature apoptosis and microinflammation in the scalp. Methods: We designed a 12-month, randomized, double-blind, placebo-controlled trial in 20 AGA volunteers already using finasteride 1 mg for at least 3 years. Hair diameters were assessed and compared for hair pattern improvement. Results: The increase of hair diameter in the finasteride 1 mg + novel product group was 37.7% more than that in finasteride 1 mg + placebo group (P ¼.002). No side effects were observed. Conclusion: Our results showed that in addition to 5-a reductase inhibitors, simultaneously addressing both premature cell apoptosis in the hair follicles and microinflammation in the scalp turned out to be an efficient approach in the management of AGA with improved efficacy over the currently referenced modality. In addition, the studied topical product may represent a new option for alopecia subjects, including those under finasteride 1 mg, to improve their hair pattern. Sponsored by Legacy Healthcare. P8227 Frontal fibrosing alopecia and lichen planus pigmentosus Jacqueline Berliner, MD, UCSF Department of Dermatology, San Francisco, CA, United States; Timothy Berger, MD, UCSF Department of Dermatology, San Francisco, CA, United States; Vera Price, MD, UCSF Department of Dermatology, San Francisco, CA, United States Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia predominantly affecting the frontal hairline and eyebrows. FFA shares common histopathologic features with other lymphocyte-mediated cicatricial alopecias, such as lichen planopilaris (LPP), central centrifugal alopecia, and pseudopelade (Brocq), which are distinguished clinically. LPP has been associated with mucocutaneous lichen planus; however, the patterns of lichen planus associated with other lymphocyte-mediated cicatricial alopecias are less well established. We report 2 Hispanic women with FFA and lichen planus pigmentosus (LPPigm), adding to the recent literature on patients with these coexistent conditions. Both women experienced perimenopausal onset of progressive gray-brown macules on the face and neck in a photodistribution. Patient 1 secondarily complained of frontotemporal hair loss. Patient 2 had complete eyebrow loss, but was not aware of the subtle frontotemporal recession observed on examination. The development of LPPigm preceded the onset of FFA in both cases. Biopsy from the temple of patient 1 revealed atrophic vacuolar interface reaction with postinflammatory pigmentary alteration, consistent with atrophic lichen planus actinicus. For Patient 2, biopsy from the neck revealed atrophic lichenoid interface reaction and another from the frontal scalp revealed lymphocyte-mediated cicatricial alopecia. The association of LPPigm with FFA further supports a shared underlying mechanism between lichen planus and the primary lymphocytic alopecias. It has been suggested to look for clinical and histopathologic evidence of FFA in patients with LPPigm. Early recognition of FFA is important to allow for medical intervention to hopefully slow if not prevent progression. Toward this end, it is also important to differentiate LPPigm from conditions with which it is often confused, especially erythema dyschromicum perstans (EDP). EDP, a rare condition, has not been associated with FFA. The role of ethnicity in lichen planus and primary lymphocytic cicatricial alopecias needs to be further elucidated. LPPigm has been documented predominantly in dark-skinned patients. We hypothesize that in patients with FFA, the variant of lichen planus that is associated, is that which is most commonly seen in their given ethnicity. We recommend noting ethnicity in future studies of lichen planus and its various expressions, and in studies of the primary lymphocytic cicatricial alopecias. Commercial support: None identified. P7774 Frontal fibrosing alopecia: A multicenter review of 355 patients Sergio Vano-Galvan, MD, PhD, Ramon y Cajal Hospital, Madrid, Spain; Ana Molina, MD, Fundaci on Jim enez Diaz, Madrid, Spain; Antonio Martorell, MD, Hospital de Manises, Valencia, Spain; Francisco Camacho, MD, PhD, Hospital Virgen Macarena, Sevilla, Spain; Pedro Ja en, MD, PhD, Hospital Ram on y Cajal, Madrid, Spain; Salvador Arias-Santiago, MD, PhD, Hospital de Baza, Granada, Spain Background: Frontal fibrosing alopecia (FFA) is a rare type of scarring hair loss primarily observed in postmenopausal women. The incidence is unknown, but the number of women presenting with this condition has significantly increased in recent years. There are no large multicenter studies about frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. Objective: To describe the epidemiology, comorbidities, clinical aspects, diagnostic findings, and therapeutic choices in a large series of patients diagnosed of FFA. Methods: A retrospective multicenter study was designed including patients diagnosed with FFA. Clinical severity of FFA was classified based on the recession of the frontal and temporal hairline. Response to therapy was assessed as worsening (progression of hairline recession), stabilization (arrest of hairline recession), or improvement (any regrowth of hair in the hairline). Results: A total of 355 patients (343 females, 55 premenopausal, and 12 males) with a mean age of 61 years (range, 23-86) were included in the study. Early menopause (45 years) was detected in 49 patients (14%), with a surgical cause in 31 of them (9%). Forty-six patients (13%) underwent hysterectomy. Severe FFA was observed in 131 patients (37%). The independent factors associated with severe FFA after multivariant analysis were: eyelashes loss (OR, 5.41; P ¼ .020), corporal hair involvement (OR, 5.24; P ¼.22), and the presence of facial papules (OR, 4.48; P ¼ .034). Finasteride was used in 102 patients, with improvement in 48 (47%) and stabilization in 54 (53%). Dutasteride was used in 18 patients, with improvement in 8 (44%) and stabilization in 10 (56%). Conclusions: Frontal fibrosing alopecia is a type of cicatricial alopecia that usually affects postmenopausal women. However, this entity may appear in premenopausal women or in men. Interestingly, we found a high rate of women with FFA presenting early menopause or with hysterectomy, emphasizing the hormonal pathogenesis of FFA. Treatment with oral antiandrogens and intralesional steroids may be useful. Commercial support: None identified. AB90 JAM ACAD DERMATOL MAY 2014

Frontal fibrosing alopecia: A multicenter review of 355 patients

Embed Size (px)

Citation preview

Page 1: Frontal fibrosing alopecia: A multicenter review of 355 patients

P8593Direct hair growth promoting effects of mycophenolic acid

Hoon Kang, MD, PhD, Department of Dermatology, St. Paul’s Hospital, College ofMedicine, The Catholic University of Korea, Seoul, South Korea; Jung Eun Kim,Department of Dermatology, St. Paul’s Hospital, College of Medicine, TheCatholic Unviersity of Korea, Seoul, South Korea; Kwanho Jeong, Departmentof Dermatology, St. Paul’s Hospital, College of Medicine, The Catholic Unviersityof Korea, Seoul, South Korea; Young Min Park, MD, PhD, Department ofDermatology, St. Paul’s Hospital, College of Medicine, The Catholic Unviersityof Korea, Seoul, South Korea

Mycophenolic acid (MPA) acts as a cell cycle inhibitor that produces reversiblenoncompetitive blockade of the purine synthesis pathway enzyme type II isoform ofinosine monophosphate dehydrogenase (IMPDH). The major target of MPA islymphocyte which contains abundant IMPDH. Among several kinds of hair lossdisorders, lymphocytic cicatricial alopecia and alopecia areata are most represen-tative hair loss conditions induced by T lymphocyte attack to the hair follicle.Recently, in vitro study demonstrated that MPA effects on cellular proliferation andupregulates some valuable gene expression. Although MPA pharmacokineticproperties on purine synthesis pathway are well defined, the direct effects ofMPA on hair follicles have yet to be studied. Therefore, we performed to determinethe MPA either have a direct effect in vitro. In addition, we performed to determinehow the effect of microneedle directly around the hair follicle. In our preliminaryexperiments, animal studies showed that topical mycophenolic acid treatmentshortens the telogen and cause resting hair follicles entering into the anagen.However, effect of mycophenolic acid has not been fully demonstrated. In this study,we found that human DPCs respond to MPA as examined by hair growth factorsresponsive RT-PCR assay. We also found that mycophenolic acid treatment increasesthe phosphorylation of ERK1/2 and b-catenin. We also found that direct b-cateninpathway targets, such as Axin2 and Lef-1, are up-regulated by mycophenolic acid.These data suggest activation of b-catenin pathway by mycophenolic acid. Theseresults suggest that be particularly important to develop new therapeutic option forhair loss.

AB90

cial support: None identified.

Commer

P7712Enabling finasteride 1 mg users to further improve hair pattern: Arandomized, double-blind, placebo-controlled trial of a novel product

Akira Takeda, MD, PhD, Kitasato University School of Medicine, Sagamihara,Japan; Akio Sato, MD, PhD, Tokyo Memorial Clinic, Tokyo, Japan; GeertCauwenbergh, PhD, Legacy Healthcare, Epalinges, Switzerland; JiaWei Liu,PhD, Legacy Healthcare, Epalinges, Switzerland; Lei Zhang, PhD, LegacyHealthcare, Epalinges, Switzerland; Saad Harti, MBA, Legacy Healthcare,Epalinges, Switzerland

Background: The efficacy of finasteride 1 mg, the first-line treatment for maleandrogenetic alopecia (AGA), tends to reach a plateau after several years’ treatment.Up to date, effective and safe options are limited because current modalitiesmanaging AGA have so far not taken into account the 2 key issues particularlyrelevant to excessive hair loss: the early onset of catagen (due to premature hairfollicular cell apoptosis) and the frequently observed sustained microinflammationin the scalp.

Objective: We investigated the potential synergic effect of combining the oralfinasteride 1 mg, acting on conversion of testosterone to 5a-dihydrotestosterone,with a novel topical antiehair loss product, acting on premature apoptosis andmicroinflammation in the scalp.

Methods: We designed a 12-month, randomized, double-blind, placebo-controlledtrial in 20 AGA volunteers already using finasteride 1 mg for at least 3 years. Hairdiameters were assessed and compared for hair pattern improvement.

Results: The increase of hair diameter in the finasteride 1 mg + novel product groupwas 37.7% more than that in finasteride 1 mg + placebo group (P ¼ .002). No sideeffects were observed.

Conclusion: Our results showed that in addition to 5-a reductase inhibitors,simultaneously addressing both premature cell apoptosis in the hair follicles andmicroinflammation in the scalp turned out to be an efficient approach in themanagement of AGAwith improved efficacy over the currently referenced modality.In addition, the studied topical product may represent a new option for alopeciasubjects, including those under finasteride 1 mg, to improve their hair pattern.

d by Legacy Healthcare.

Sponsore

J AM ACAD DERMATOL

P8227Frontal fibrosing alopecia and lichen planus pigmentosus

Jacqueline Berliner, MD, UCSF Department of Dermatology, San Francisco, CA,United States; Timothy Berger, MD, UCSF Department of Dermatology, SanFrancisco, CA, United States; Vera Price, MD, UCSF Department of Dermatology,San Francisco, CA, United States

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopeciapredominantly affecting the frontal hairline and eyebrows. FFA shares commonhistopathologic features with other lymphocyte-mediated cicatricial alopecias, suchas lichen planopilaris (LPP), central centrifugal alopecia, and pseudopelade (Brocq),which are distinguished clinically. LPP has been associated with mucocutaneouslichen planus; however, the patterns of lichen planus associated with otherlymphocyte-mediated cicatricial alopecias are less well established. We report 2Hispanic women with FFA and lichen planus pigmentosus (LPPigm), adding to therecent literature on patients with these coexistent conditions. Both womenexperienced perimenopausal onset of progressive gray-brown macules on theface and neck in a photodistribution. Patient 1 secondarily complained offrontotemporal hair loss. Patient 2 had complete eyebrow loss, but was not awareof the subtle frontotemporal recession observed on examination. The developmentof LPPigm preceded the onset of FFA in both cases. Biopsy from the temple ofpatient 1 revealed atrophic vacuolar interface reaction with postinflammatorypigmentary alteration, consistent with atrophic lichen planus actinicus. For Patient2, biopsy from the neck revealed atrophic lichenoid interface reaction and anotherfrom the frontal scalp revealed lymphocyte-mediated cicatricial alopecia. Theassociation of LPPigm with FFA further supports a shared underlying mechanismbetween lichen planus and the primary lymphocytic alopecias. It has beensuggested to look for clinical and histopathologic evidence of FFA in patients withLPPigm. Early recognition of FFA is important to allow for medical intervention tohopefully slow if not prevent progression. Toward this end, it is also important todifferentiate LPPigm from conditions with which it is often confused, especiallyerythema dyschromicum perstans (EDP). EDP, a rare condition, has not beenassociated with FFA. The role of ethnicity in lichen planus and primary lymphocyticcicatricial alopecias needs to be further elucidated. LPPigm has been documentedpredominantly in dark-skinned patients. We hypothesize that in patients with FFA,the variant of lichen planus that is associated, is that which is most commonly seenin their given ethnicity. We recommend noting ethnicity in future studies of lichenplanus and its various expressions, and in studies of the primary lymphocyticcicatricial alopecias.

cial support: None identified.

Commer

P7774Frontal fibrosing alopecia: A multicenter review of 355 patients

Sergio Vano-Galvan, MD, PhD, Ramon y Cajal Hospital, Madrid, Spain; AnaMolina, MD, Fundaci�on Jim�enez Diaz, Madrid, Spain; Antonio Martorell, MD,Hospital de Manises, Valencia, Spain; Francisco Camacho, MD, PhD, HospitalVirgen Macarena, Sevilla, Spain; Pedro Ja�en, MD, PhD, Hospital Ram�on y Cajal,Madrid, Spain; Salvador Arias-Santiago, MD, PhD, Hospital de Baza, Granada,Spain

Background: Frontal fibrosing alopecia (FFA) is a rare type of scarring hair lossprimarily observed in postmenopausal women. The incidence is unknown, but thenumber of women presenting with this condition has significantly increased inrecent years. There are no large multicenter studies about frontal fibrosing alopecia(FFA) that could give clues about its pathogenesis and best treatment.

Objective: To describe the epidemiology, comorbidities, clinical aspects, diagnosticfindings, and therapeutic choices in a large series of patients diagnosed of FFA.

Methods: A retrospective multicenter study was designed including patientsdiagnosed with FFA. Clinical severity of FFA was classified based on the recessionof the frontal and temporal hairline. Response to therapy was assessed as worsening(progression of hairline recession), stabilization (arrest of hairline recession), orimprovement (any regrowth of hair in the hairline).

Results: A total of 355 patients (343 females, 55 premenopausal, and 12 males) witha mean age of 61 years (range, 23-86) were included in the study. Early menopause(45 years) was detected in 49 patients (14%), with a surgical cause in 31 of them(9%). Forty-six patients (13%) underwent hysterectomy. Severe FFAwas observed in131 patients (37%). The independent factors associated with severe FFA aftermultivariant analysis were: eyelashes loss (OR, 5.41; P ¼ .020), corporal hairinvolvement (OR, 5.24; P ¼ .22), and the presence of facial papules (OR, 4.48; P ¼.034). Finasteride was used in 102 patients, with improvement in 48 (47%) andstabilization in 54 (53%). Dutasteride was used in 18 patients, with improvement in8 (44%) and stabilization in 10 (56%).

Conclusions: Frontal fibrosing alopecia is a type of cicatricial alopecia that usuallyaffects postmenopausal women. However, this entity may appear in premenopausalwomen or in men. Interestingly, we found a high rate of womenwith FFA presentingearly menopause or with hysterectomy, emphasizing the hormonal pathogenesis ofFFA. Treatment with oral antiandrogens and intralesional steroids may be useful.

cial support: None identified.

Commer

MAY 2014