RESUMEN
Immune-mediated comorbidities in patients with psoriasiform eczema are common. It can be challenging to manage multiple immune-mediated diseases, especially considering that biologic treatments are prone to causing paradoxical effects. The aim of this retrospective observational case series was to describe the course of both psoriasiform eczema and immune-mediated comorbidities in five patients treated with upadacitinib for psoriasiform dermatitis. Five patients, all male, were included. All the patients suffered from psoriasiform eczema. Moreover, two of the patients suffered from alopecia areata, two from vitiligo, one from ulcerative colitis and one from hidradenitis suppurativa. In all cases, the treatment with upadacitinib was rapidly effective on the eczema. The effectiveness on alopecia areata was good in both cases, while the results on vitiligo were only partial. The only case of ulcerative colitis achieved complete remission, while the case of hidradenitis suppurativa experience partial improvement. In conclusion, upadacitinib was effective in treating not only psoriasiform eczema, but also several immune mediated comorbidities. Additional studies are necessary to determine the efficacy of upadacitinib in alopecia areata, vitiligo and hidradenitis suppurativa.
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Comorbilidad , Eccema , Compuestos Heterocíclicos con 3 Anillos , Psoriasis , Humanos , Masculino , Adulto , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Persona de Mediana Edad , Eccema/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Estudios Retrospectivos , Resultado del Tratamiento , Vitíligo/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inmunología , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inmunologíaAsunto(s)
Alopecia Areata , Liquen Plano , Liquen Escleroso y Atrófico , Humanos , Liquen Plano/diagnóstico , Liquen Plano/complicaciones , Liquen Plano/patología , Liquen Plano/epidemiología , Alopecia Areata/diagnóstico , Alopecia Areata/complicaciones , Alopecia Areata/inmunología , Alopecia Areata/epidemiología , Estudios de Casos y Controles , Femenino , Masculino , Persona de Mediana Edad , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/complicaciones , Liquen Escleroso y Atrófico/patología , Liquen Escleroso y Atrófico/epidemiología , Adulto , Anciano , Adulto Joven , AdolescenteRESUMEN
Alopecia areata is the second most common form of hair loss in humans after androgenetic alopecia. Although a variety of animal models for alopecia areata have been described, currently the C3H/HeJ mouse model is the most commonly used and accepted. Spontaneous hair loss occurs in 15%-25% of older mice in which the lesions wax and wane, similar to the human disease, with alopecia being more common and severe in female mice. Full-thickness skin grafts from mice with spontaneous alopecia areata to young, normal-haired, histocompatible mice provide a highly reproducible model with progressive lesions that makes it useful for drug efficacy and mechanism-based studies. As alopecia areata is a cell-mediated autoimmune disease, transfer of cultured lymph node cells from affected mice to unaffected, histocompatible recipients also promotes disease development and provides an alternative, nonsurgical protocol. Protocols are presented to produce these models such that they can be used to study alopecia areata and to develop novel drug therapies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Full-thickness skin grafts to reproducibly induce alopecia areata in C3H/HeJ mice Basic Protocol 2: Adoptive transfer of cultured lymphoid cells provides a nonsurgical method to induce alopecia areata in C3H/HeJ mice.
Asunto(s)
Alopecia Areata , Modelos Animales de Enfermedad , Ratones Endogámicos C3H , Trasplante de Piel , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/patología , Alopecia Areata/inmunología , Animales , Ratones , Femenino , Masculino , Traslado AdoptivoRESUMEN
Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.
Asunto(s)
Alopecia Areata , Inhibidores de las Cinasas Janus , Metaanálisis en Red , Humanos , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificación , Resultado del Tratamiento , Administración Oral , Purinas/administración & dosificación , Purinas/efectos adversos , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Índice de Severidad de la Enfermedad , PirazolesRESUMEN
Alopecia areata (AA) is nonscarring hair loss characterized by Th1 and concomitant Th2 skewing, particularly in atopic patients. Despite novel developments for adult AA, safe and effective treatments for pediatric patients remain limited. Dupilumab, with a well-studied safety profile, may have therapeutic potential for atopic pediatric AA. To evaluate the ability of dupilumab to regrow hair in pediatric AA patients. We conducted a single-center, retrospective, observational study to evaluate hair regrowth [using Severity of Alopecia Tool (SALT)] with dupilumab in 20 children with both AD and AA (age range 5-16 years, mean 10.8 years; baseline SALT range 3-100, mean 54.4). Patient demographics, atopic history, IgE and SALT scores were collected at 12wk follow-up visits, up to > 72wks, to evaluate hair regrowth. Spearman correlations with clinical data were performed. Patients showed clinical improvement over the follow-up period (range 24 to > 72wks, mean 67.6wks) with significant mean(± SD) reduction in SALT at 48wks versus baseline [20.4(± 35.1) vs 54.4(± 37.6), respectively; p < 0.01] and continued improvement up to > 72wks [2.2(± 4.9), p < 0.01]. Baseline SALT positively correlated with disease duration (r = 0.54, p < 0.01), and negatively correlated with improvement in SALT at weeks 24, 36, and 48 (|r|≥ 0.65, p < 0.01 for all comparisons). Baseline IgE positively correlated with improvement in SALT at week 36 (r > 0.60, p < 0.05). Dupilumab was well-tolerated, with no new safety concerns. These real-world data support the utility of dupilumab to safely treat pediatric AA patients, corroborating the role of Th2 skewing in children with AA and associated atopy, warranting larger clinical trials.
Asunto(s)
Alopecia Areata , Anticuerpos Monoclonales Humanizados , Cabello , Humanos , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Niño , Adolescente , Femenino , Masculino , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Preescolar , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Resultado del Tratamiento , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Índice de Severidad de la Enfermedad , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Estudios de SeguimientoRESUMEN
BACKGROUND: Alopecia areata (AA), an immune-mediated disorder, is marked by temporary, nonscarring hair loss. The bulge area is protected from immune attacks by immune privilege; however, recent studies demonstrated immune cells infiltrating the bulge area. OBJECTIVE: This study aims to investigate the immunohistochemical expression of the sex-determining region Y-box 9 (SOX9) and cluster of differentiation 34 (CD34) in AA patients as markers of hair follicle stem cells (HFSCs) and progenitor cells, respectively. METHODS: Immunohistochemical staining of SOX9 and CD34 was applied on skin samples of 20 AA patients and 20 healthy controls. RESULTS: SOX9 and CD34 were significantly lower in lesional samples of cases compared to perilesional and control skin biopsies. Furthermore, SOX9 level was negatively correlated with the severity of alopecia tool score (SALT score) among the studied AA patients. Moreover, lowered SOX9 expression was present in patients with recurrent attacks. CONCLUSIONS: The significant reduction of stem cell markers (SOX9 and CD34) in our studied AA cases signifies the pathological affection of HFSCs and their progeny in AA. This is thought to cause a loss of competence in generating new hair in some AA cases, which needs to be validated in further research. LIMITATIONS OF THE STUDY: This study has a small sample size.
Asunto(s)
Alopecia Areata , Antígenos CD34 , Inmunohistoquímica , Factor de Transcripción SOX9 , Humanos , Factor de Transcripción SOX9/análisis , Factor de Transcripción SOX9/metabolismo , Alopecia Areata/inmunología , Alopecia Areata/metabolismo , Alopecia Areata/patología , Antígenos CD34/análisis , Antígenos CD34/metabolismo , Masculino , Femenino , Adulto , Adulto Joven , Persona de Mediana Edad , Adolescente , Folículo Piloso/metabolismo , Folículo Piloso/patología , Folículo Piloso/inmunologíaRESUMEN
Corona virus disease 2019(COVID-19) is one of the most serious respiratory pandemic diseases threatening human health for centuries. Alopecia areata (AA) is a sudden patchy hair loss, an autoimmune disease, which seriously affects the image and mental health of patients. Evidence shows that the risk of autoimmune diseases significantly increases after COVID-19, and is positively correlated with the severity, with a significant increase in the risk of alopecia in those over 40 years old. The relationship between COVID-19 and AA has become a hot topic of current research. Strengthening the research on the correlation between COVID-19 and AA can help to identify and protect susceptible populations at an early stage. This article reviews the research progress on the epidemiological background of COVID-19 and AA, the situation and possible mechanisms of AA induced by COVID-19 or COVID-19 vaccination, and potential treatment methods.
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Alopecia Areata , COVID-19 , SARS-CoV-2 , Alopecia Areata/epidemiología , Alopecia Areata/inmunología , Humanos , COVID-19/inmunología , COVID-19/epidemiología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunologíaRESUMEN
The scalp microbiome represents an array of microorganisms important in maintaining scalp homeostasis and mediating inflammation. Scalp microbial dysregulation has been implicated in dermatologic conditions including alopecia areata (AA), dandruff/seborrheic dermatitis (D/SD), scalp psoriasis (SP) and folliculitis decalvans (FD). Understanding the impact of scalp microbial dysbiosis gives insight on disease pathophysiology and guides therapeutic decision making. Herein we review the scalp microbiome and its functional role in scalp conditions by analysis of metagenomic medical literature in alopecia, D/SD, SP, and other dermatologic disease.Increased abundance of Malassezia, Staphylococcus, and Brevibacterium was associated with SD compared to healthy controls. A higher proportion of Corynebacterium, actinobacteria, and firmicutes are present in AA patients, and lower proportions of Staphylococcus caprae are associated with worse clinical outcomes. Decreased prevalence of actinobacteria and Propionibacterium and increased firmicutes, staphylococcus, and streptococcus are associated with scalp psoriasis. Studies of central centrifugal cicatricial alopecia (CCCA) suggest scalp microbial composition contributes to CCCA's pro-inflammatory status. The most common organisms associated with FD include methicillin-resistant S. aureus and S. lugdunensis. Antifungals have been a mainstay treatment for these diseases, while other alternatives including coconut oils and shampoos with heat-killed probiotics have shown considerable potential efficacy by replenishing the scalp microbiome.
Asunto(s)
Microbiota , Cuero Cabelludo , Humanos , Microbiota/efectos de los fármacos , Microbiota/inmunología , Cuero Cabelludo/microbiología , Dermatosis del Cuero Cabelludo/microbiología , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/terapia , Disbiosis/microbiología , Disbiosis/inmunología , Foliculitis/microbiología , Foliculitis/diagnóstico , Foliculitis/tratamiento farmacológico , Foliculitis/terapia , Psoriasis/microbiología , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Psoriasis/terapia , Dermatitis Seborreica/microbiología , Dermatitis Seborreica/tratamiento farmacológico , Dermatitis Seborreica/terapia , Alopecia Areata/microbiología , Alopecia Areata/inmunología , Alopecia Areata/terapia , Alopecia Areata/tratamiento farmacológico , Caspa/microbiología , Caspa/tratamiento farmacológicoRESUMEN
The TEC (tyrosine kinase expressed in hepatocellular carcinoma) family kinases, an important class of protein kinases, play key roles in cell signaling and immune regulation. In this review, the association between the pathogenesis of alopecia areata and the structure and regulatory mechanisms of TEC family kinases in normal physiological processes, is explored. Furthermore, the potential clinical applications of TEC kinases and their inhibitors are highlighted by summarizing current insights into their mechanisms of action, clinical applications, and recent advancements in TEC kinase inhibitor research.
Asunto(s)
Alopecia Areata , Inhibidores de Proteínas Quinasas , Proteínas Tirosina Quinasas , Transducción de Señal , Humanos , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , AnimalesRESUMEN
Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with abnormal immune responses. From an immunological perspective, the better understanding of their physiopathology has demonstrated a large complex network of immune cell subsets and related cytokines that interact with both epidermal and dermal cells. For example, in type-1-associated diseases such as alopecia areata, vitiligo, and localized scleroderma, recent evidence suggests the presence of a type-2 inflammation that is well known in atopic dermatitis. Whether this type-2 immune response has a protective or detrimental impact on the development and chronicity of these diseases remains to be fully elucidated, highlighting the need to better understand its involvement for the management of patients. This mini-review explores recent insights regarding the potential role of type-2-related immunity in alopecia areata, vitiligo, and localized scleroderma.
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Vitíligo , Humanos , Vitíligo/inmunología , Animales , Alopecia Areata/inmunología , Células Th2/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Dermatitis Atópica/inmunología , Dermatitis Atópica/etiología , Esclerodermia Localizada/inmunología , Inflamación/inmunología , Piel/inmunología , Piel/patologíaRESUMEN
Alopecia areata (AA) is an autoimmune inflammatory disease characterized by non-scarring hair loss due to an immune response that targets hair follicles. The current treatment approach for AA involves the use of immunosuppressants and immunomodulators to reduce cytokine levels around affected hair follicles. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential anti-inflammatory agents with diverse beneficial effects in various medical conditions. This study investigates the role of beta-hydroxybutyrate (BHB), a ketone body produced during SGLT2 inhibition, in the pathogenesis of AA. Serum BHB levels were found to be significantly elevated in patients with AA compared with healthy controls, with higher levels correlating with severity of hair loss. BHB treatment increased inflammatory cytokine production in outer root sheath (ORS) cells, mimicking the inflammatory conditions seen in AA. The results suggest that elevated BHB levels may exacerbate the inflammatory immune response in AA patients and may be associated with chronic hair loss and resistance to treatment. Serum BHB levels may serve as a potential marker of poor prognosis in patients with severe AA. Further research is needed to elucidate the precise role of BHB in the pathogenesis of AA and its implications for disease management.
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Ácido 3-Hidroxibutírico , Alopecia Areata , Inflamación , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/sangre , Alopecia Areata/inmunología , Humanos , Ácido 3-Hidroxibutírico/sangre , Adulto , Femenino , Masculino , Estudios de Casos y Controles , Citocinas/metabolismo , Citocinas/sangre , Folículo Piloso/metabolismo , Adulto Joven , Persona de Mediana EdadRESUMEN
Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient's quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.
Asunto(s)
Alopecia Areata , Folículo Piloso , Alopecia Areata/inmunología , Alopecia Areata/genética , Humanos , Animales , Folículo Piloso/inmunología , Folículo Piloso/patologíaRESUMEN
Previous studies demonstrated that Th1 cytokines like IL-2, IL-12 and IFN-γ have initiatory role in alopecia areata (AA) and positive correlation with disease severity. They informed that serum levels of Th17 cytokines, IL-17, IL-22, IL-23 increased in active AA patients and corelated, particularly IL-17, with disease severity. In recent reports it was showed the balance between Th17 and Treg cells is crucial for maintaining tolerance to self-antigens, and an imbalance towards Th17 may contribute to the development of autoimmune diseases like AA. But research on serum Treg markers in AA is limited. It was aimed to investigate whether the Treg cells have a role in the pathogenesis of AA analyzing the serum levels of Treg cytokines IL-35 and TGF-ß in the patients with AA. 42 AA patients and 38 healthy controls were enrolled. Patient demographics, clinical data, disease severity assessed by Severity of Alopecia Tool (SALT) scores were recorded. Serum samples were collected and analyzed for TGF-ß and IL-35 levels using ELISA kits. The cytokine levels in both groups were statistically compared. Their relation with parameters of demographic and severity of disease was evaluated. The patient and control groups had no statistically significant difference, there was 71.4% males and 28.6% females in patient group, while the control group had 63.2% males and 36.8% females, Severity analysis classified 18 patients with mild AA, 19 with moderate AA, and 5 with alopecia totalis/areata universalis. While TGF-ß levels exhibited no significant difference between groups, IL-35 levels were significantly elevated in AA patients (p = 0.002). Logistic regression identified IL-35 as a significant parameter influencing disease status (OR = 1.055). Correlation analysis revealed a weak positive correlation between patient age and IL-35 levels (r = 0.436; p = 0.004). Notably, IL-35 levels displayed a significant decrease in individuals with antinuclear antibody (ANA) positivity. No correlations were identified between cytokine levels and disease severity, prognosis, or disease activity. Elevated IL-35 levels suggest that IL-35 and specific Treg cell subsets can play a role in AA pathogenesis. The nuanced roles of TGF-ß and IL-35 highlight the need for comprehensive studies to interpret their implications in the complex immunopathogenesis of AA. These findings open avenues for further research, positioning IL-35 as a prospective target for investigating and potentially intervening in AA pathogenesis.
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Alopecia Areata , Interleucinas , Índice de Severidad de la Enfermedad , Linfocitos T Reguladores , Factor de Crecimiento Transformador beta , Humanos , Alopecia Areata/sangre , Alopecia Areata/inmunología , Alopecia Areata/diagnóstico , Femenino , Masculino , Interleucinas/sangre , Adulto , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta/sangre , Adulto Joven , Persona de Mediana Edad , Estudios de Casos y Controles , Adolescente , Células Th17/inmunología , Biomarcadores/sangreRESUMEN
Alopecia areata (AA) is an autoimmune disease that develops due to inflammation and causes sudden hair loss. Ithas been observed that family circumstances may contribute to the development of AA. This study aims to assessthe relationship between the development of alopecia areata in children, family functions, and depression andanxiety levels in their parents.Thirty-nine participants diagnosed with AA and 41 healthy controls (HC), agedbetween 8 and 18 years, and their parents participated in the study. The assessment of the children included thecompletion of a socio-demographic data form, the Parenting Style Scale (PSS), and the Revised Children's Anxietyand Depression Scale (RCADS). The parents provided information on a sociodemographic form, the BeckDepression Inventory (BDI), and the Beck Anxiety Inventory (BAI). The children in the control group scoredsignificantly higher on the PSS acceptance/ involvement subscale than those with AA. In the AA group, the numberof authoritative and indulgent (PSS) families was statistically significantly lower than that of the families in the HC,and the number of neglectful families was statistically significantly higher than those of the control group. Totalanxiety and depression t scores (RCADS) were statistically significantly higher in the AA children than in theHC. Our study demonstrates the importance of considering familial factors and parental mental health tounderstand and address alopecia areata in children. Our findings support the psychosomatic component of AA.Implementing comprehensive treatment strategies that target psychological well-being and family dynamics couldprove crucial.
Asunto(s)
Alopecia Areata , Ansiedad , Depresión , Responsabilidad Parental , Humanos , Alopecia Areata/psicología , Alopecia Areata/inmunología , Alopecia Areata/epidemiología , Alopecia Areata/diagnóstico , Niño , Femenino , Masculino , Adolescente , Responsabilidad Parental/psicología , Depresión/psicología , Depresión/epidemiología , Depresión/diagnóstico , Depresión/etiología , Ansiedad/psicología , Ansiedad/epidemiología , Ansiedad/diagnóstico , Ansiedad/etiología , Padres/psicología , Estudios de Casos y ControlesRESUMEN
Biologics and Janus kinase (JAK) inhibitors are immunomodulating and immunosuppressing medications utilized to treat atopic dermatitis (AD), psoriasis (PSO), psoriatic arthritis (PsA), and alopecia areata (AA). Special recommendations must be considered when prescribing vaccinations in this population, as the pneumococcal and herpes zoster vaccine are recommended to patients ≥ 19-years-old (rather than ≥ 65-years-old and ≥ 50-years-old as in the general population, respectively), along with a yearly influenza and up to date COVID-19 vaccination. Additionally, TNF-α and JAK-inhibitors may increase the risk of latent Hepatitis B virus (HBV) reactivation among high-risk patients. Prior to prescribing these medications, a quantitative HepB Surface Antibody (HepB SA) test is performed to determine immunity. This study utilized the SlicerDicer function on EPIC Medical Records to search for any patient ≥ 19-years-old prescribed a biologic or JAK inhibitor for AD, PSO, PsA, or AA between 10/2003 and 10/2023 at a large tertiary institution. Vaccination rates among patients on biologics and JAK inhibitors were low, with rates being significantly lower in patients 19-64 years-old, compared to those ≥ 65 years-old for most disease states (p < 0.01). Among AD, PSO/PsA, and AA patients, on average, 9.39% were vaccinated for influenza, 6.76% for herpes zoster, 16.56% for pneumococcal pneumonia, and 63.98% for COVID-19. Only 3.16% of patients were adequately vaccinated for HepB after an abnormal HepB SA test. Here, extremely low rates of vaccination among patients on biologics and JAK inhibitors at our institution were highlighted, emphasizing the imperative need for ensuring vaccination in this group.
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Alopecia Areata , Artritis Psoriásica , Productos Biológicos , Dermatitis Atópica , Vacunación , Humanos , Persona de Mediana Edad , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Dermatitis Atópica/epidemiología , Masculino , Adulto , Femenino , Alopecia Areata/inmunología , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/epidemiología , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Anciano , Adulto Joven , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/inmunología , Vacunación/estadística & datos numéricos , Inhibidores de las Cinasas Janus/uso terapéutico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/inmunología , Estudios Retrospectivos , SARS-CoV-2/inmunologíaAsunto(s)
Alopecia Areata , Folículo Piloso , Inhibidores de las Cinasas Janus , beta Catenina , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/metabolismo , Alopecia Areata/inmunología , Humanos , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , beta Catenina/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Cabello/metabolismo , Masculino , Femenino , Pirimidinas/farmacología , PiperidinasRESUMEN
Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-ß (TGF-ß), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/ß-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.
Asunto(s)
Alopecia Areata , Vitíligo , Alopecia Areata/inmunología , Alopecia Areata/patología , Alopecia Areata/etiología , Alopecia Areata/metabolismo , Humanos , Vitíligo/inmunología , Vitíligo/patología , Vitíligo/metabolismo , Vitíligo/etiología , Animales , Privilegio Inmunológico , Citocinas/metabolismoRESUMEN
Alopecia areata refers to an autoimmune illness indicated by persistent inflammation. The key requirement for alopecia areata occurrence is the disruption of immune-privileged regions within the hair follicles. Recent research has indicated that neuropeptides play a role in the damage to hair follicles by triggering neurogenic inflammation, stimulating mast cells ambient the follicles, and promoting apoptotic processes in keratinocytes. However, the exact pathogenesis of alopecia areata requires further investigation. Recently, there has been an increasing focus on understanding the mechanisms of immune diseases resulting from the interplay between the nervous and the immune system. Neurogenic inflammation due to neuroimmune disorders of the skin system may disrupt the inflammatory microenvironment of the hair follicle, which plays a crucial part in the progression of alopecia areata.
Asunto(s)
Alopecia Areata , Folículo Piloso , Inflamación Neurogénica , Alopecia Areata/inmunología , Alopecia Areata/etiología , Alopecia Areata/patología , Humanos , Folículo Piloso/inmunología , Folículo Piloso/patología , Inflamación Neurogénica/inmunología , Inflamación Neurogénica/etiología , Neuropéptidos/metabolismo , Neuropéptidos/inmunología , Mastocitos/inmunología , Queratinocitos/inmunología , Queratinocitos/patología , Apoptosis/inmunología , AnimalesRESUMEN
The autoimmunity-promoting cytokine, Interleukin-15 (IL-15), is often claimed to be a key pathogenic cytokine in alopecia areata (AA). Yet, rhIL-15 promotes human hair follicle (HF) growth ex vivo. We have asked whether the expression of IL-15 and its receptor (IL-15R) isoforms is altered in human AA and how IL-15 impacts on human HF immune privilege (HF-IP) in the presence/absence of interferon-γ (IFNγ), the well-documented key AA-pathogenic cytokine, as well as on hair regrowth after experimental AA induction in vivo. Quantitative immunohistomorphometry showed the number of perifollicular IL-15+ T cells in AA skin biopsies to be significantly increased compared to healthy control skin, while IL-15, IL-15Rα, and IL-15Rγ protein expression within the hair bulb were significantly down-regulated in AA HFs. In organ-cultured human scalp HFs, rhIL-15 significantly reduced hair bulb expression of MICA, the key "danger" signal in AA pathogenesis, and increased production of the HF-IP guardian, α-MSH. Crucially, ex vivo, rhIL-15 prevented IFNγ-induced HF-IP collapse, restored a collapsed HF-IP by IL-15Rα-dependent signaling (as documented by IL-15Rα-silencing), and protected AA-preventive immunoinhibitory iNKT10 cells from IFNγ-induced apoptosis. rhIL-15 even promoted hair regrowth after experimental AA induction in human scalp skin xenotransplants on SCID/beige mice in vivo. Our data introduce IL-15 as a novel, functionally important HF-IP guardian whose signaling is constitutively defective in scalp HFs of AA patients. Our data suggest that selective stimulation of intrafollicular IL-15Rα signaling could become a novel therapeutic approach in AA management, while blocking it pharmacologically may hinder both HF-IP restoration and hair re-growth and may thus make HFs more vulnerable to AA relapse.