Tattoos: risks and complications, clinical and histopathological approach.

BACKGROUND: Skin modification through tattoos is as old as humanity itself. However, this trend is on the rise, and with the use of different types of pigments and application practices, both cutaneous and systemic complications can arise. Adverse reactions can be grouped into five classes: inflammatory, infectious, neoplastic, aesthetic, and miscellaneous. On histopathology, inflammatory reactions can exhibit a lichenoid pattern or present as spongiotic dermatitis, granulomatous reactions, pseudolymphoma, pseudoepitheliomatous hyperplasia, or scleroderma/morphea-like changes. This article reviews tattoo complications, including their clinical and histopathological characteristics. METHODS: An open search was conducted on PubMed using the terms "tattoo", "complications", and "skin". No limits were set for period, language, or publication type of the articles. RESULTS: Reactions to tattoos are reported in up to 67% of people who get tattooed, with papulonodular and granulomatous reactions being the most common. Some neoplastic complications have been described, but their causality is still debated. Any pigment can cause adverse reactions, although red ink is more frequently associated with them. Patients with pre-existing dermatoses may experience exacerbation or complications of their diseases when getting tattoos; therefore, this procedure is not recommended for this patient group. CONCLUSIONS: Dermatological consultation is recommended before getting a tattoo, as well as a histopathological examination in case of complications. In patients who develop cutaneous inflammatory reactions following tattooing, additional studies are recommended to investigate systemic diseases such as sarcoidosis, pyoderma gangrenosum, atopic dermatitis, and neoplasms. It is important for physicians to be trained in providing appropriate care in case of complications.

IL-7-dependent and -independent lineages of IL-7R-dependent human T cells.

Infants with biallelic IL7R loss-of-function variants have severe combined immune deficiency (SCID) characterized by the absence of autologous T lymphocytes, but normal counts of circulating B and NK cells (T-B+NK+ SCID). We report 6 adults (aged 22 to 59 years) from 4 kindreds and 3 ancestries (Colombian, Israeli Arab, Japanese) carrying homozygous IL7 loss-of-function variants resulting in combined immunodeficiency (CID). Deep immunophenotyping revealed relatively normal counts and/or proportions of myeloid, B, NK, and innate lymphoid cells. By contrast, the patients had profound T cell lymphopenia, with low proportions of innate-like adaptive mucosal-associated invariant T and invariant NK T cells. They also had low blood counts of T cell receptor (TCR) excision circles, recent thymic emigrant T cells and naive CD4+ T cells, and low overall TCR repertoire diversity, collectively indicating impaired thymic output. The proportions of effector memory CD4+ and CD8+ T cells were high, indicating IL-7-independent homeostatic T cell proliferation in the periphery. Intriguingly, the proportions of other T cell subsets, including TCRγδ+ T cells and some TCRαß+ T cell subsets (including Th1, Tfh, and Treg) were little affected. Peripheral CD4+ T cells displayed poor proliferation, but normal cytokine production upon stimulation with mitogens in vitro. Thus, inherited IL-7 deficiency impairs T cell development less severely and in a more subset-specific manner than IL-7R deficiency. These findings suggest that another IL-7R-binding cytokine, possibly thymic stromal lymphopoietin, governs an IL-7-independent pathway of human T cell development.

Alopecia Areata in Latin America: Where are We and Where are We Going?

Alopecia areata (AA) represents an underrecognized burden in Latin America (LA), severely impacting quality of life (QoL). This impact is exacerbated by limited access to specialized dermatologic care and therapies for AA within and among nations. Many of the unmet needs for AA globally also exist in LA. The region has geographic, ethnic, cultural, and economic conditions. With new AA medicines targeting immunologic pathways on the horizon, LA must prepare regarding regulatory issues, reimbursement, awareness, and education to give adequate and timely treatment for patients with AA. To address these issues, the Americas Health Foundation convened a panel of six dermatologists from Argentina, Brazil, Colombia, and Mexico who are experts in AA and its comorbidities for a 3-day virtual meeting to discuss AA diagnosis and treatment in LA and create a manuscript offering recommendations to address discussed barriers. This publication examines unmet AA needs in LA, treatment, and innovative therapies and recommends improving AA care. Access constraints to conventional and novel medicines hinder appropriate treatments for patients. Therapy initiation delays can affect QoL, mental health, and disease progression. People with AA face stigmas, discrimination, and misconceptions owing to a lack of disease awareness. With promising new treatments for AA on the horizon, all stakeholders must coordinate efforts to enhance LA's AA management landscape and improve patient outcomes.

Cell signaling in cutaneous T-cell lymphoma microenvironment: promising targets for molecular-specific treatment.

Cutaneous T-cell lymphomas (CTCL) result from the infiltration and proliferation of a population of T cells in the skin, inducing changes in the activity of both T cells and surrounding skin cells. In the CTCL microenvironment, cell interactions mediated by cell signaling pathways are altered. Defining changes in cell signaling enables to understand T-cell deregulations in the CTCL microenvironment and thus the progression of the disease. Moreover, characterizing signaling networks activated in CTCL stages can lead to consider new molecular biomarkers and therapeutic targets. Focusing on mycosis fungoides (MF), the most frequent variant of CTCL, and Sézary syndrome (SS), its leukemic variant, this review highlights recent molecular and genetic findings revealing modifications of key signaling pathways involved in (1) cell proliferation, cell growth, and cell survival such as MAP kinases and PI3K/Akt; (2) immune responses derived from TCR, TLR, JAK/STAT, and NF-kB; and (3) changes in tissue conditions such as extracellular matrix remodeling, hypoxia, and angiogenesis. Alterations in these signaling networks promote malignant T-cell proliferation and survival, T-cell migration, inflammation, and suppression of immune regulation of malignant T cells, making a skin microenvironment that allows disease progression. Targeting key proteins of these signaling pathways, using molecules already available and used in research, in clinical trials, and with other disease indications, can open the way to different therapeutic options in CTCL treatment.

Tattoos: risks and complications, clinical and histopathological approach

Abstract Background Skin modification through tattoos is as old as humanity itself. However, this trend is on the rise, and with the use of different types of pigments and application practices, both cutaneous and systemic complications can arise. Adverse reactions can be grouped into five classes: inflammatory, infectious, neoplastic, aesthetic, and miscellaneous. On histopathology, inflammatory reactions can exhibit a lichenoid pattern or present as spongiotic dermatitis, granulomatous reactions, pseudolymphoma, pseudoepitheliomatous hyperplasia, or scleroderma/morphea-like changes. This article reviews tattoo complications, including their clinical and histopathological characteristics. Methods An open search was conducted on PubMed using the terms "tattoo", "complications", and "skin". No limits were set for period, language, or publication type of the articles. Results Reactions to tattoos are reported in up to 67% of people who get tattooed, with papulonodular and granulomatous reactions being the most common. Some neoplastic complications have been described, but their causality is still debated. Any pigment can cause adverse reactions, although red ink is more frequently associated with them. Patients with pre-existing dermatoses may experience exacerbation or complications of their diseases when getting tattoos; therefore, this procedure is not recommended for this patient group. Conclusions Dermatological consultation is recommended before getting a tattoo, as well as a histopathological examination in case of complications. In patients who develop cutaneous inflammatory reactions following tattooing, additional studies are recommended to investigate systemic diseases such as sarcoidosis, pyoderma gangrenosum, atopic dermatitis, and neoplasms. It is important for physicians to be trained in providing appropriate care in case of complications.

Induction of transplantation tolerance by allogeneic donor-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells.

Several studies have shown that recipient-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are involved in transplantation tolerance. However, it is not clear whether allogeneic donor-derived Tregs are able to regulate T cell alloreactivity after solid organ allograft transplantation. Related studies in experimental bone marrow transplantation have shown that allogeneic donor-derived Tregs are capable of promoting early and long-term allogeneic hematopoietic engraftment, accompanied by tolerance to donor and recipient antigens. However, in these models, donor-derived Tregs are syngeneic with respect to the T responder cells. The role of Tregs in solid organ transplantation models where recipient-derived T responder and donor-derived Tregs are allogeneic has been scarcely studied. In order to determine whether allogeneic Tregs were able to regulate T cell alloreactivity, CD4(+)CD25(-) and CD8(+) T responder cells were cultured with stimulator dendritic cells in several responder-stimulator strain combinations (C57BL/6-->BALB/c, BALB/c-->C57BL/6 and C3H-->BALB/c) in the presence of responder-derived, stimulator-derived or 3rd-party-derived Tregs. Then, the frequency of IFN-gamma+ alloreactive T cells was determined by means of ELISPOT assay. The results of this study demonstrate that, regardless of the responder-stimulator strain combination, both responder-derived and stimulator-derived Tregs, but not 3rd-party-derived Tregs, significantly inhibited CD4(+) and CD8(+) T cell alloreactivity. The effect of allogeneic stimulator-derived Tregs was dependent on IL-10 and TGF-beta and reversed by exogenous IL-2. In vivo experiments in nu/nu recipients reconstituted with CD4(+)CD25(-) T responder and Tregs showed that recipient and donor-derived, but not 3rd-party-derived Tregs, significantly enhanced skin allograft survival. Importantly, T cells from both recipient-derived and donor-derived Treg-reconstituted nu/nu recipients exhibited donor-specific unresponsiveness in vitro. These results show that allogeneic donor-derived Tregs significantly inhibit T cell alloreactivity and suggest their potential use in the induction of transplantation tolerance.

Inmunopatogenia del pénfigo vulgar y el pénfigo foliáceo / Immunopathogenesis of pemphigus vulgaris and pemphigus foliaceus

El pénfigo vulgar y el pénfigo foliáceo son enfermedades ampollosas autoinmunes mediadas por autoanticuerpos dirigidos contra proteínas de los desmosomas, las desmogleínas 1 y 3. Están asociadas con moléculas del complejo mayor de histocompatibilidad (HLA) que por su estructura tienen la capacidad de presentar péptidos antigénicos de las desmogleínas. En los individuos afectados se han descrito la presencia de linfocitos T y B autorreactivos y alteraciones en la regulación del sistema inmune con desequilibrio de las respuestas Th1/Th2. No se conocen con precisión los mecanismos de daño pero la investigación actual indica que los anticuerpos tienen un papel patogénico, inician diferentes cascadas de señalización que provocan la acantólisis y apoptosis de los queratinocitos. El conocimiento de la inmunopatogenia de las enfermedades ampollosas autoinmunes ha permitido el desarrollo y la puesta en práctica de nuevas alternativas terapéuticas.

Pemphigus vulgaris and pemphigus foliaceus are autoimmune blistering diseases mediated by antibodies against desmosomal proteins. They are strongly associated with major histocompatibility complex alleles with the ability to present antigenic peptides of desmogleins. In the affected individuals the presence of auto-reactive T and B lymphocytes, and alterations in the immune system regulation with imbalance of the Th1/Th2 responses have been described. Damage mechanisms are not yet precisely known but current investigation indicates that antibodies play an important pathogenic role: they start different signaling cascades that lead to acantholysis and apoptosis of keratinocytes. Better knowledge of the pathogenesis of autoimmune blistering diseases has been the basis for the development and implementation of new therapeutic approaches.