RESUMO
Netherton syndrome (NS) is a rare genodermatosis with an autosomal recessive pattern of inheritance caused by pathogenic variants in the SPINK5 gene. It is characterized by a triad consisting of atopic diathesis, ichthyosis linearis circumflexa, and hair shaft abnormalities. Ichthyosis linearis circumflexa can be confused with atopic dermatitis leading to a delayed diagnosis. Furthermore, difficulty in making the differential diagnosis with other atopiform, erythrodermic, and ichthyosiform entities that exhibit hair shaft abnormalities represent a challenge. Trichoscopy is an accessible and noninvasive auxiliary diagnostic tool in these cases; the hair shaft abnormalities found in NS are bamboo, golf tee, and matchstick hairs. Identification of a pathogenic variant in the SPINK5 gene through genetic testing is necessary to confirm the diagnosis. Multiple treatment options are available including topical therapy with emollients, corticosteroids, calcineurin inhibitors, antiseptics, and narrowband UVB phototherapy. Systemic treatments comprehend intravenous immunoglobulins, and advances in the understanding of the pathophysiology of NS have led to more directed therapies with biologics such as infliximab, ixekizumab, secukinumab, ustekinumab, and dupilumab. Treatments currently under investigation include inhibitors of kallikrein 5, cathelicidins, drugs activating the transcription factor nuclear factor erythroid-derived 2-like 2, and gene therapy using autologous keratinocytes induced with a lentiviral vector encoding SPINK5.
RESUMO
Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.
Assuntos
Alopecia em Áreas/radioterapia , Hormônios/metabolismo , Fototerapia/métodos , Couro Cabeludo/metabolismo , Raios Ultravioleta , alfa-MSH/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Alopecia em Áreas/metabolismo , Biópsia , Hormônio Liberador da Corticotropina/metabolismo , Folículo Piloso/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/patologia , Imuno-Histoquímica , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Receptor Tipo 2 de Melanocortina/metabolismo , Estudos Retrospectivos , Transdução de Sinais , Pele/metabolismoAssuntos
Pitiríase Liquenoide/radioterapia , Pigmentação da Pele , Pele/efeitos da radiação , Centros de Atenção Terciária , Terapia Ultravioleta , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , México , Pessoa de Meia-Idade , Pitiríase Liquenoide/diagnóstico , Pitiríase Liquenoide/fisiopatologia , Indução de Remissão , Estudos Retrospectivos , Pele/patologia , Pele/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Phototherapy can be an option in unresponsive alopecia areata (AA); however, variable results have been reported with its use. We could not find literature of treatment with UVA-1 in AA. A study was designed to evaluate progressive dosimetry to determine the initial dose and its increments. METHODS: Patients with unresponsive AA were recruited. Twenty-five sessions of 30 J/cm2 were administered. If hair regrowth was <75%, the dose was escalated to 60 J/cm2 . If hair improvement remained <75%, an additional 25 sessions at 120 J/cm2 were indicated. If total hair regrowth occurred before 75 sessions, a final visit was performed for biopsies and severity of alopecia tool (SALT) evaluation. Clinical and histopathological assessments were performed blindly. Adverse effects were recorded. RESULTS: Nine men and 13 women were included; 16 were initially S1 , one S3 , and five S4 . Median age was 32 years and median evolution 10 months. Nine patients achieved an S0 , eight S1 , and five S4 (P = 0.005). The most notable improvement was with 60 J/cm2 (P = 0.02). Biopsies exhibited an absence of inflammation in five patients and mild persistence in 17. An increase of 43.75% in anagen hairs (P ≤ 0.001) was achieved, telogen hairs decreased 16.3% (P = 0.06), and catagen hairs were reduced 22.7% (P = 0.005). Pearson's correlation was -0.82 and P ≤ 0.001, when correlating anagen hairs with final SALT. Improvement has continued for 6 months post treatment. Mild xerosis was observed in all patients, and six (28.6%) developed transient mild hyperpigmentation. CONCLUSIONS: This study provides a basis for UVA-1 dosimetry evaluating its therapeutic value in AA.