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1.
J Am Acad Dermatol ; 87(2): 306-313, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35364216

RESUMO

BACKGROUND: Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. OBJECTIVE: To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. RESULTS: A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. LIMITATIONS: These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. CONCLUSIONS: Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.


Assuntos
Alopecia em Áreas , Inibidores de Janus Quinases , Adulto , Alopecia em Áreas/induzido quimicamente , Alopecia em Áreas/tratamento farmacológico , Citidina Trifosfato/uso terapêutico , Humanos , Inibidores de Janus Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Resultado do Tratamento
2.
J Am Acad Dermatol ; 84(6): 1594-1601, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32926985

RESUMO

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.


Assuntos
Alopecia em Áreas/diagnóstico , Consenso , Dermatologia/normas , Carga Global da Doença , Alopecia em Áreas/epidemiologia , Alopecia em Áreas/etiologia , Alopecia em Áreas/terapia , Comorbidade , Técnica Delphi , Dermatologia/métodos , Dermoscopia , Folículo Piloso/diagnóstico por imagem , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/patologia , Humanos , Cooperação Internacional , Guias de Prática Clínica como Assunto , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
3.
J Am Acad Dermatol ; 83(1): 123-130, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32165196

RESUMO

BACKGROUND: A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. OBJECTIVE: To produce an international consensus statement on the use and utility of various treatments for AA. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. RESULTS: In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. LIMITATIONS: The study included a comprehensive list of systemic treatments for AA but not all treatments used. CONCLUSION: Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.


Assuntos
Alopecia em Áreas/terapia , Administração Oral , Administração Tópica , Corticosteroides/uso terapêutico , Fatores Etários , Alopecia em Áreas/tratamento farmacológico , Terapia Combinada , Terapias Complementares , Técnica Delphi , Fármacos Dermatológicos/uso terapêutico , Prova Pericial , Humanos , Injeções Intralesionais , Fototerapia , Índice de Gravidade de Doença , Resultado do Tratamento
4.
J Cutan Pathol ; 47(2): 128-134, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31605498

RESUMO

BACKGROUND: The purpose of the study was to compare the histopathologic and immunophenotypic features of central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP) to better characterize and differentiate these two clinical entities. CCCA remains an ill-defined and still-unsettled histologic entity and many hair loss experts regard CCCA to be histologically indistinguishable from LPP. Given the overlapping histologic features of these two lymphocyte-predominant cicatricial alopecias, and the lack of consensus regarding the significance of proposed distinctions, dermatopathologists face difficulty in providing clinicians and patients certainty with a definitive diagnosis of CCCA vs LPP. METHODS: We performed a retrospective review of 51 scalp biopsies of patients with either the clinical diagnosis of CCCA (27 cases) or LPP (24 cases). Clinical information, histologic features of hematoxylin-eosin-stained sections, and a panel of immunohistochemical markers were evaluated on scalp biopsies. Tested parameters were quantified, and statistical analysis was performed. RESULTS: Our study found no differences on either histologic assessment or immunophenotypic characterization between cases of classic LPP and CCCA. CONCLUSION: The conclusion of this study is that the inflammatory infiltrates in CCCA and LPP are not only histologically similar but also immunophenotypically indistinguishable.


Assuntos
Alopecia , Líquen Plano , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/imunologia , Alopecia/patologia , Feminino , Humanos , Líquen Plano/imunologia , Líquen Plano/patologia , Masculino , Pessoa de Meia-Idade
5.
J Am Acad Dermatol ; 71(5): 969-72, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25228111

RESUMO

BACKGROUND: Lichen planopilaris (LPP) is a lymphocyte-mediated cicatricial alopecia mostly involving the bulge region of the hair follicle. The origin of LPP is unknown. Therapy for LPP often does not prevent disease progression. We describe histologic and immunohistologic features that aid in diagnosis and provide an explanation for disease progression in LPP. OBJECTIVE: We sought to demonstrate a decrease in the number of catagen-/telogen-phase follicles and to confirm the loss of cytokeratin 15 (CK15) expression in the stem cells of LPP-affected follicles. METHODS: In all, 144 LPP cases were retrieved; 55 cases were stained immunohistochemically, targeting the CK15 antigen with 40 cases ultimately analyzed for CK15 expression. RESULTS: Catagen/telogen phase was significantly decreased or absent in all cases of LPP, a novel clue useful in histologic diagnostics. The loss of CK15+ stem cells in most affected follicles in LPP was also confirmed, with unaffected follicles retaining CK15+ stem cells. LIMITATIONS: Limited tissue for analysis remained in the clinical sample tissue blocks. CONCLUSION: Damaged follicles that have lost their CK15+ stem cells disappear when they enter catagen phase. CK15+ stem cell loss explains the clinical observation that LPP progresses despite immunosuppressive therapies. Finally, the absence of catagen/telogen hair follicles is a helpful diagnostic clue for LPP.


Assuntos
Folículo Piloso/fisiopatologia , Queratina-15/metabolismo , Líquen Plano/fisiopatologia , Células-Tronco/metabolismo , Cabelo/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Líquen Plano/patologia , Células-Tronco/fisiologia
6.
J Am Acad Dermatol ; 62(6): 968-78, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20392521

RESUMO

BACKGROUND: Safety and efficacy of up to 3 courses of alefacept intramuscular (IM) in the treatment of chronic plaque psoriasis have been demonstrated in earlier trials. OBJECTIVE: We sought to determine the safety and efficacy of up to 5 courses of alefacept IM in treating plaque psoriasis. METHODS: A standard treatment course was defined as 15 mg of alefacept IM once weekly for 12 weeks, followed by 12 weeks of treatment-free observation. Patients with chronic plaque psoriasis, who had previously received alefacept IM, received up to 3 additional courses (A, B, and C). Efficacy was evaluated by Physician Global Assessment. RESULTS: Safety profiles were similar to those for a single course of treatment. There were no cumulative adverse effects. At 2 weeks postdosing, 16%, 22%, and 19% of patients were rated clear or almost clear by Physician Global Assessment in courses A, B, and C, respectively, with 35%, 42%, and 42% achieving this response at any time during these courses. Patients who achieved clear or almost clear at 2 weeks postdosing remained so for a median duration of 214 and 126 days after courses A and B, respectively. LIMITATIONS: This was an extension study and therefore contained no control group. CONCLUSIONS: Up to 5 courses of alefacept IM may provide extended treatment-free, symptom-free periods in responders while maintaining the safety profile.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Alefacept , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Esquema de Medicação , Feminino , Humanos , Injeções Intramusculares , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Indução de Remissão
7.
J Am Acad Dermatol ; 58(3): 395-402, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18280336

RESUMO

BACKGROUND: Alopecia areata (AA) is a T-cell-mediated autoimmune disease. Efalizumab is a T-cell-targeted therapy approved for the treatment of psoriasis. OBJECTIVE: To assess the efficacy and safety of efalizumab in the treatment of moderate-to-severe AA. METHODS: Sixty-two patients were enrolled into this phase II, placebo-controlled trial. The trial consisted of three 12-week periods-a double-blind treatment period, an open-label efalizumab treatment period, and a safety follow-up. RESULTS: There were no statistical differences between treatment groups in percent hair regrowth, quality-of-life measures, or changes in biologic markers of disease severity after 12 or 24 weeks. In both groups, there was an approximately 8% response rate for hair regrowth (at 12 weeks). Efalizumab was well tolerated. LIMITATIONS: Numbers were too small for certain analyses. CONCLUSION: A 3- to 6-month trial of efalizumab was not effective in promoting hair regrowth in this small cohort of patients with moderate-to-severe AA.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Adulto , Alopecia em Áreas/fisiopatologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Biomarcadores/metabolismo , Estudos de Coortes , Método Duplo-Cego , Feminino , Cabelo/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Falha de Tratamento
8.
Clin Geriatr Med ; 18(1): 121-33, vii, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11913736

RESUMO

This article contains a brief review of hair follicle biology, followed by a presentation of the workup of elderly patients who present with hair loss or hirsutism. Common hair disorders, such as graying, telogen effluvium, androgenic alopecia, senescent alopecia, alopecia arcuata, hirsutism, and hypertrichosis, are discussed.


Assuntos
Alopecia/fisiopatologia , Hirsutismo/fisiopatologia , Idoso , Alopecia/diagnóstico , Alopecia/terapia , Alopecia em Áreas/diagnóstico , Alopecia em Áreas/terapia , Cor de Cabelo/fisiologia , Folículo Piloso/fisiologia , Hirsutismo/diagnóstico , Hirsutismo/terapia , Humanos
11.
J Am Acad Dermatol ; 49(5): 816-25, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14576659

RESUMO

BACKGROUND: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis. OBJECTIVE: To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed. METHODS: Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10. RESULTS: Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%). CONCLUSION: A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.


Assuntos
Autoanticorpos/efeitos dos fármacos , Autoanticorpos/imunologia , Linfócitos T CD4-Positivos/imunologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Alefacept , Reações Antígeno-Anticorpo , Bacteriófago phi X 174/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/farmacologia , Toxoide Tetânico/imunologia
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