RESUMEN
Scalp psoriatic itch is a common, bothersome, yet understudied, condition with numerous associated treatment challenges. The aim of this study was to enhance our understanding of the pathophysiology of scalp psoriatic itch. Immunohistochemical analysis of known neuroimmune mediators of pruritus was conducted using scalp biopsies from 27 Hispanic psoriatic patients. Patients were categorized into mild/moderate or severe itch groups according to their itch intensity rating of scalp itch. Protease activated receptor (PAR2), substance P, transient receptor potential (TRP)V3, TRPM8 and interleukin-23 expression all correlated significantly with itch intensity. The pathophysiology of scalp psoriasis is largely non-histaminergic, mediated by PAR2, interleukin-23, transient receptor potential channels, and substance P.
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Psoriasis , Cuero Cabelludo , Humanos , Cuero Cabelludo/patología , Sustancia P , Prurito , Psoriasis/metabolismo , Hispánicos o LatinosRESUMEN
Botulinum toxin type A (Botox) is thought to have antipruritic effects through inhibition of pruritic factors, including acetylcholine, substance P, and glutamate. The aim of this randomized, single-blind, placebo-controlled trial was to test the effect of botulinum toxin type A on cowhage, a non-histaminergic model for chronic itch. Botulinum toxin type A was injected into the arm of 35 healthy subjects, with a saline control injected into the contralateral arm. Thermal sensory parameters (warmth and heat thresholds and heat pain intensity) and itch intensity after cowhage application were examined on test areas. Botulinum toxin type A reduced itch intensity, overall perceived itch (area under the curve (AUC); percentage change from baseline), and peak itch intensity compared with the control at 1 week, 1 month, and 3 months. Botulinum toxin type A had no effect on thermal thresholds or heat pain intensity. In conclusion, botulinum toxin type A reduced cowhage itch for at least 3 months, which suggests that botulinum toxin type A is a potential long-lasting treatment for localized, non-histaminergic itch.
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Toxinas Botulínicas Tipo A , Humanos , Toxinas Botulínicas Tipo A/efectos adversos , Antipruriginosos/efectos adversos , Método Simple Ciego , Prurito/tratamiento farmacológico , Prurito/inducido químicamente , Dimensión del Dolor , Método Doble CiegoRESUMEN
There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.
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Acetaminofén , Antipruriginosos , Acetaminofén/efectos adversos , Antipruriginosos/efectos adversos , Geles , Histamina/efectos adversos , Humanos , Proyectos Piloto , Prurito/inducido químicamente , Prurito/diagnóstico , Prurito/tratamiento farmacológicoRESUMEN
BACKGROUND: Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia for which therapy is often ineffective and there is no cure. OBJECTIVES: Looking for a new targetable molecule in the treatment of LPP, we sought to verify whether IL-17 expression is increased in scalp biopsies from patients with active scalp lesions of LPP. METHODS: Horizontal sections of hematoxylin and eosin-stained slides from 40 scalp biopsies of active LPP were retrospectively collected and stained with the monoclonal antibody against IL-17 (Abcam, Cambridge, MA; ab79056, dilution 1:100). Twenty biopsies from patients with chronic telogen effluvium served as controls because of their morphological resemblance to the normal scalp. Statistical analysis was performed using IBM SPSS Statistics for Windows (IBM Corporation, Armonk, NY). RESULTS: The main finding was the positive cytoplasmic expression of IL-17 in the perifollicular fibrosis of the affected follicles in LPP which was statistically significant compared with the controls ( P < 0.0001). The labeled cells were identified as fibroblasts based on their spindle shape and fascicular concentric arrangement in tight perifollicular distribution. Although most of the LPP specimens (n = 35; 87.5%) also revealed cytoplasmic IL-17 expression in the lichenoid inflammatory infiltrate, the results were not statistically significant ( P = 0.1351). CONCLUSION: Our immunohistochemistry results show that blocking the IL-17 inflammatory pathway may interfere with the progression of the perifollicular fibrosis and inflammation in LPP.
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Interleucina-17 , Liquen Plano , Humanos , Estudios Retrospectivos , Liquen Plano/patología , Alopecia/patología , Cuero Cabelludo/patología , Biopsia , Cicatriz/patología , FibrosisRESUMEN
Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN-associated itch is difficult because its aetiology is still unknown. This study aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)-31, its receptor complex components IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMRß), and oncostatin M (OSM), which is a ligand of OSMR ß, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL-31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL-31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMRß (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL-31 were T cells (27.0% of total IL-31-expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL-31RA-expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMRß was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL-31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL-31RA and OSMRß (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN-associated itch.
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Interleucinas/metabolismo , Subunidad beta del Receptor de Oncostatina M/metabolismo , Oncostatina M/metabolismo , Prurigo/metabolismo , Prurito/metabolismo , Receptores de Interleucina/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: One of the hallmarks of bullous pemphigoid (BP) is moderate to severe chronic itch. Managing this is difficult because little is known about the mechanisms of itch in BP. OBJECTIVE: We sought to elucidate the pathophysiologic mechanisms of itch in BP. METHODS: The expression of itch mediators in lesions of 24 patients with BP and 6 healthy individuals were examined through immunofluorescence staining. Furthermore, the expression of itch mediators and itch severity was correlated. RESULTS: Itch severity was correlated with eosinophils, substance P, neurokinin 1R, interleukin (IL) 31 receptor A, oncostatin M receptor-ß, IL-13, periostin, and basophils. There was also a trend between itch severity and IL-31 expression. Most of the cells expressing IL-31 or neurokinin 1R were identified as eosinophils. Intraepidermal nerve fiber density was decreased. Other itch mediators, including mast cells, IL-4, thymic stromal lymphopoietin, transient receptor potential vanilloid 1 and ankyrin 1, and protease activated receptor 2 were not significantly correlated with itch severity. LIMITATIONS: The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations. CONCLUSIONS: Multiple factors are involved in BP-associated itch, including eosinophils, substance P, neurokinin 1R, IL-31, IL-31 receptor A, oncostatin M receptor-ß, IL-13, periostin, and basophils. They could be useful therapeutic targets.
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Penfigoide Ampolloso/fisiopatología , Prurito/etiología , Piel/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Basófilos/fisiología , Moléculas de Adhesión Celular/análisis , Enfermedad Crónica , Citocinas/inmunología , Eosinófilos/fisiología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Interleucina-13/análisis , Masculino , Persona de Mediana Edad , Subunidad beta del Receptor de Oncostatina M/análisis , Penfigoide Ampolloso/inmunología , Receptores de Interleucina/análisis , Receptores de Neuroquinina-1/análisis , Índice de Severidad de la Enfermedad , Piel/química , Piel/inmunología , Sustancia P/análisis , Células Th2/inmunologíaRESUMEN
Research suggests that itch and psychiatric diseases are intimately related. In efforts to examine the prevalence of psychiatric diagnoses in patients with chronic itch not due to psychogenic causes, we conducted a retrospective chart review of 502 adult patients diagnosed with chronic itch in an outpatient dermatology clinic specializing in itch and assessed these patients for a co-existing psychiatric disease. Psychiatric disease was identified and recorded based on ICD-10 codes made at any point in time which were recorded in the patient's electronic medical chart, which includes all medical department visits at the University of Miami. Fifty-five out of 502 (10.9%) of patients were found to have a comorbid psychiatric diagnosis based on ICD-10 codes. The most common psychiatric diagnoses were anxiety disorders (45.5%), followed by major depressive disorder (36.4%). There was no significant association of any specific type of itch to a particular psychiatric disorder. No unique itch characteristics were noted in patients with underlying psychiatric diagnoses.
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Trastorno Depresivo Mayor , Trastornos Mentales , Adulto , Trastornos de Ansiedad , Comorbilidad , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Prurito/diagnóstico , Prurito/epidemiología , Estudios RetrospectivosAsunto(s)
Prurito , Calidad de Vida , Estudios Transversales , Humanos , Prurito/complicaciones , Encuestas y CuestionariosRESUMEN
Atopic dermatitis (AD) is a common chronic skin disease that is characterized by intense pruritus and has high impairment of quality of life. AD is often described as "the itch that rashes, rather than the rash that itches". Several studies suggest that mechanisms of central modulation play an important role in the development and maintenance of chronic itch. Therefore, treating the neurosensory aspects of itch is an important part in the management of chronic itch. However, little attention has been paid to the role of the central nervous system in the processing of itch in AD. Targeting itch-related anatomical structures in the brain with non-invasive treatments such as psychological interventions and transcranial Direct Current Stimulation (tDCS) could have an antipruritic effect in AD. Therefore, in this review article, we discuss the current progress in brain imaging research of itch, as well as the efficacy of non-invasive interventions for itch relief in this patient group.
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Encéfalo , Dermatitis Atópica , Prurito , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Enfermedad Crónica , Dermatitis Atópica/diagnóstico por imagen , Dermatitis Atópica/fisiopatología , Dermatitis Atópica/psicología , Dermatitis Atópica/terapia , Humanos , Prurito/diagnóstico por imagen , Prurito/fisiopatología , Prurito/psicología , Prurito/terapiaRESUMEN
Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL)-31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRß) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL-31, IL-31RA, and OSMRß in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRß were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves through epidermal neoplastic T cells and keratinocytes to transmit itch.
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Interleucinas/metabolismo , Linfoma Cutáneo de Células T/metabolismo , Subunidad beta del Receptor de Oncostatina M/metabolismo , Prurito/metabolismo , Receptores de Interleucina/metabolismo , Anciano , Biopsia , Femenino , Humanos , Inmunohistoquímica , Masculino , Índice de Severidad de la EnfermedadAsunto(s)
Neurodermatitis , Prurigo , Humanos , Prurigo/diagnóstico , Prurigo/tratamiento farmacológico , Prurito/diagnósticoAsunto(s)
Dermatitis Atópica/psicología , Sustancia Gris/diagnóstico por imagen , Hipotálamo/diagnóstico por imagen , Estrés Psicológico/complicaciones , Adulto , Dermatitis Atópica/etiología , Femenino , Humanos , Hipotálamo/patología , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Proyectos Piloto , Estrés Psicológico/fisiopatología , Adulto JovenRESUMEN
A cross-sectional study of geriatric patients was performed to provide a comprehensive description of the prevalence and clinical characteristics of chronic itch affecting Hispanic geriatric subjects in Mexico. Participants were recruited from both nursing homes and geriatric ambulatory care centers. Patients without dementia were evaluated using an itch intensity and characteristic questionnaire and were assessed for itch-related dermatoses (n = 302). Data on medications and underlying systemic diseases were obtained from medical records. The prevalence of chronic itch was 25% in this population. Of those with chronic itch, 69% had xerosis, 28% had itch-related dermatoses, and 96% had documented comorbidities. The most common comorbidities were diabetes mellitus (OR = 2.3, 95% CI 1.3-3.9, p = 0.003) and chronic venous insufficiency (OR = 4.4, 95% CI 1.6-12.2, p = 0.002). The most common areas where patients experienced itch were legs (54%), back (45%), scalp (28%) and arms (27%). Patients experienced the greatest amount of itch in the winter (77%) and during the night (65%). Chronic itch is a common problem in the studied Hispanic geriatric population, and its presence significantly correlates with xerosis, diabetes, and venous insufficiency.
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Prurito/epidemiología , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Estaciones del Año , Enfermedades de la Piel/epidemiología , Encuestas y Cuestionarios , Insuficiencia Venosa/epidemiología , Escala Visual AnalógicaRESUMEN
Pruritus of end-stage renal disease (ESRD) is a multifactorial symptom of complex etiology not yet fully understood. In this study we have investigated the cerebral perfusion patterns at rest in ESRD patients on hemodialysis, compared with those in healthy volunteers. We have also studied the brain responses evoked by experimental itch induction in ESRD, after stimulating the two distinct histamine and cowhage itch pathways, and compared them with the responses evoked in healthy volunteers. To identify potential structural alterations in ESRD patients compared with a group of age-matched healthy volunteers, we calculated the density of gray matter for the entire brain using a voxel-based morphometric analysis. Our results indicated that gray matter density was significantly reduced in ESRD patients in the frontal, parietal, temporal, and occipital cortices, as well as in the S1, precuneus, and insula, whereas the brain stem, hippocampus, amygdala, midcingulate cortex, and nucleus accumbens displayed an increased gray matter density. Functionally, we found a significantly higher brain perfusion at baseline associated with ESRD pruritus in the anterior cingulate, insula, claustrum, hippocampus, and nucleus accumbens. The brain responses evoked by cowhage itch, which are mediated by protease-activated receptors (PAR2), displayed significant differences compared with responses in healthy individuals and were correlated with perceived itch intensity in a dual, complex manner. The inverse correlations in particular suggested that a negative feedback mechanism modulated itch intensity, when elicited in a preexistent chronic itch background.
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Corteza Cerebral/fisiopatología , Fallo Renal Crónico/complicaciones , Prurito/fisiopatología , Adulto , Anciano , Mapeo Encefálico , Corteza Cerebral/irrigación sanguínea , Femenino , Sustancia Gris/fisiopatología , Histamina/farmacología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Plasticidad Neuronal/fisiología , Prurito/inducido químicamente , Prurito/etiología , Adulto JovenRESUMEN
B-type natriuretic peptide (BNP) is an itch-selective neuropeptide that was shown to play a role in both histaminergic and nonhistaminergic itch in mice. It was also shown that elevated serum BNP is linked to increased pruritus in nondiabetic hemodialysis patients. This study examined plasma BNP levels of 77 patients and N-terminal pro-BNP levels of 33 patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity. Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale and in particular for patients with chronic pruritus of unknown origin. On the basis of this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, pharmacological and ablation strategies determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord. These data support that BNP and N-terminal pro-BNP levels are associated with chronic itch and may be used in clinical setting.
RESUMEN
We have previously identified that a structural membrane protein Caveolin-1 (Cav1) is involved in the regulation of aberrant keratinocyte proliferation and differentiation. The aim of this study was to elucidate the role of Cav1, Caveolin-2 (Cav2), and Cavin-1 in the pathogenesis of psoriasis vulgaris and between psoriasis subtypes. We utilized human biopsies from validated cases of psoriasis vulgaris (n = 21) at the University of Miami Hospital and compared the expression of Cav1, Cav2, and Cavin-1 by immunohistochemistry staining with that in normal healthy age-/sex-/location-matched skin (n = 15) and chronic spongiotic dermatitis skin samples (as control inflammatory skin condition) and quantified using QuPath. Distinct subtypes of psoriasis included guttate, inverse, nail, plaque, palmoplantar, and pustular. All biopsy samples exhibited a trend toward downregulation of Cav1, with nail, plaque, and palmoplantar psoriasis exhibiting the most pronounced effects. Only nail and pustular psoriasis samples exhibited significant downregulation of Cav2 and Cavin-1, suggesting Cav1 to be the main caveolar contributor to the pathogenesis of psoriasis. Together, these data support caveolae as pathophysiological targets in nail and pustular psoriasis, whereas Cav1 seems to be a general biomarker of multiple subtypes of psoriasis.