Summary
Background
Shared decision‐making tools (SDMt) are visual tools developed to promote joint medical decisions between physicians and patients. There is a paucity of such tools in dermatology.
Objectives
To develop and validate a SDMt for use in specialized consultation for vitiligo.
Methods
A prospective cross‐sectional study was carried out from March 2019 to March 2020. We first conducted a qualitative study of topics discussed by patients and clinicians during therapeutic decision‐making in the setting of a specialized consultation for vitiligo using an anchored‐theory method, which allowed conceptualization of the SDMt. The usefulness of the SDMt was evaluated by a working group of multidisciplinary health workers and patients with vitiligo. Consensus on the final tool was obtained through an e‐Delphi method.
Results
We recruited 30 patients with vitiligo for the qualitative study, which identified 91 topics related to therapeutic decision‐making. Hierarchical clustering analysis confirmed the distribution of these topics in two subgroups (general treatment goals and priorities, and topics specific to each treatment). The consensus of a multidisciplinary group was used to develop the SDMt. The tool was comprised of eight A5 cards, which addressed face repigmentation; body repigmentation (limited area); body repigmentation (extended area); partial or complete depigmentation; coping with the disease; stabilization of disease; maintaining repigmentation; and disease information. Cognitive interviews confirmed the satisfaction, readability and usefulness of the SDMt. The SDMt was then translated and culturally validated in English.
Conclusions
We developed a tool for shared decision‐making in nonsegmental vitiligo, which we translated and cross‐culturally validated in a US patient population with vitiligo to ensure its generalizability.
Vitiligo is an autoimmune disease in which CD8+ T cells destroy melanocytes, leading to patchy, depigmented lesions of the skin. To investigate possible immune processes in the skin that could explain the patchy appearance of vitiligo inflammation, we performed single-cell RNA-sequencing on cells isolated from the skin using a modified suction blistering technique. We compared the transcriptomes of cells isolated from lesional and non-lesional skin of six vitiligo subjects with active, spreading lesions as well as normal skin from six healthy subjects. Using differential gene analysis to cluster more than 18,000 cell transcriptomes in an unbiased fashion, we were able to identify the cellular components of the skin: melanocytes, keratinocytes, and Langerhans cells, as well as subgroups of immune cells. Consistent with previous findings by our group and others, this approach revealed an IFNγ signature in vitiligo lesions. This method identified 87 ligand-receptor pairs that may promote vitiligo pathogenesis, including CXCR6 and CXCL16 that were just recently implicated in vitiligo. The data set also revealed that Langerhans cells actively express many genes which have known risk alleles for vitiligo, highlighting a potential pivotal role in the development of vitiligo. Overall, single-cell RNA-sequencing of the skin infiltrate in vitiligo lesions is providing robust data that confirms many previous findings, but adds additional layers of nuance missed by conventional studies of bulk material. This level of resolution will yield powerful insight into the identification of novel drug targets in previously unknown signaling pathways in vitiligo and other diseases of the skin.
Vitiligo is an autoimmune disease of the skin in which CD8+ T cells kill melanocytes, leading to skin depigmentation. The IFNg-dependent chemokines CXCL9 and CXCL10 are highly expressed in human vitiligo lesions, and CXCL10 is required for depigmentation in our mouse model of vitiligo. New drugs are being developed to target this pathway as a novel treatment strategy. In order to further characterize the immune infiltrate in vitiligo lesions and improve our ability to quantify disease activity for future clinical trials, we adapted a suction blistering technique to access skin interstitial fluid for protein analysis by ELISA and cell immunophenotyping by flow cytometry. Using separate groups to first define and later validate candidate biomarkers, we observed that CD8+ T cell number and CXCL9 protein concentration were consistently elevated in lesional skin, but not in non-lesional skin or healthy subjects. Surprisingly, CXCL10 protein was not reliably detected in lesional skin. Phenotyping of the T cells in the skin interstitial fluid revealed that nearly all CD8+ T cells in the skin express both CXCR3, the chemokine receptor for CXCL9 and CXCL10, and PD1, an immune checkpoint inhibitor. While the absolute number of T regulatory cells (Tregs) in the skin was the same between lesional and non-lesional skin, the ratio of CD8+ T cells to Tregs was elevated in active vitiligo lesions, suggesting that this ratio is key to modulating inflammation and tolerance within vitiligo lesions. These results suggest that CD8+ T cell number and CXCL9 protein concentration in the skin may serve as biomarkers of active disease and treatment response, and that the suction blistering technique can provide new insight into the immune infiltrate in vitiligo.
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