ABSTRACT
Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, including AIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.
ABSTRACT
Two adolescent females presented to outpatient clinic with isolated, non-scaly, asymptomatic hypopigmented macules and patches on the arm(s). Both cases had Wood's lamp exams notable for extralesional punctiform coral-red perifollicular fluorescence on the back and faint intralesional enhancement. In one case, biopsy was performed and deemed consistent with progressive macular hypomelanosis. The patient had complete response to antimicrobial therapy and sun exposure.
Subject(s)
Anti-Infective Agents , Hypopigmentation , Female , Humans , Hypopigmentation/diagnosis , Hypopigmentation/drug therapy , Hypopigmentation/pathology , BiopsySubject(s)
Erythromelalgia , Biopsy , Erythromelalgia/diagnosis , Erythromelalgia/drug therapy , Humans , Skin/pathologySubject(s)
Dermatomyositis , Lichen Planus , Lupus Erythematosus, Cutaneous , Lupus Erythematosus, Systemic , Dermatomyositis/chemically induced , Dermatomyositis/diagnosis , Dermatomyositis/drug therapy , Humans , Hydroxychloroquine/adverse effects , Lichen Planus/chemically induced , Lupus Erythematosus, Cutaneous/chemically induced , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Cutaneous/drug therapy , Lupus Erythematosus, Systemic/drug therapyABSTRACT
Introdução: Melasma é distúrbio de pigmentação que acomete principalmente mulheres em idade fértil com fototipos elevados. Polypodium leucotomos tem atividade antioxidante, fotoprotetora e imunomodulatória, sendo tratamento adjuvante do melasma. Objetivo: Avaliar a eficácia, em relação à qualidade de vida e à melhora objetiva, do uso de PL no tratamento do melasma. Métodos: Estudo prospectivo e individualizado. Nove voluntárias portadoras de melasma foram submetidas ao tratamento com Polypodium leucotomos durante 45 dias. Escores MELASQoL, DLQI e MASI foram calculados no D0 e no D45. Realizou-se a análise de variância Anova com pós-teste de Tukey para comparação entre D0 e D45 (p < 0,05). Resultados: Todas as pacientes eram do sexo feminino, com média de idade de 37,18 ± 6,78 anos, história familiar de melasma em 55,6%, e fotoexposição desprotegida e uso de estrogênio em 88,9%. Após 45 dias de tratamento com Polypodium leucotomos houve redução significativa do MELASQoL e DLQI (p < 0,05) e melhora do MASI em 55,6% das pacientes. Conclusões: Houve melhora do MASI em 55,6% das pacientes após 45 dias de tratamento. A despeito da discreta melhora no MASI, houve reflexo na melhora dos escores de qualidade de vida (DLQI e MELASQoL).
Introduction: Melasma is a pigmentation disorder that mainly affects women of childbearing age with high phototypes. Polypodium leucotomos has antioxidant, photoprotective and immuno-modulatory activity, and can be considered as an adjunctive treatment for melasma. Objective: To evaluate the efficacy, in relation to quality of life and objective improvement, of the use of Polypodium leucotomos in the treatment of melasma. Methods: Prospective and individualized study. Nine volunteers with melasma were submitted to treatment with Polypodium leucotomos for 45 days. MELASQoL, DLQI and MASI scores were calculated at the beginning (D0) and 45 days after (D45). Analysis of variance ANOVA with Tukey post-test for comparison be-tween D0 and D45 (p <0.05). Results: All patients were females, mean age of 37.18 ± 6.78 years. Family history of melasma in 55.6%; 88.9% with unprotected photoexposure and use of estrogen. After 45 days of treatment with Polypodium leucotomos there was a significant reduction of ME-LASQoL and DLQI (p <0.05) and improvement of MASI in 55.6% of the patients. Conclusions: There was improvement of MASI in 55.6% of patients after 45 days of treatment. In spite of the slight improvement in MASI, there was a reflex in the improvement of quality of life scores (DLQI and MELASQoL).
