Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.

BACKGROUND: G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells. METHODS: In a phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 to 180 µg per kilogram of body weight) or subcutaneously weekly, every other week, or monthly (5 to 1600 µg per kilogram) in patients who had heavily pretreated relapsed or refractory multiple myeloma that had progressed with established therapies (a median of six previous lines of therapy) or who could not receive these therapies without unacceptable side effects. The primary end points - the frequency and type of dose-limiting toxic effects (study part 1 only), adverse events, and laboratory abnormalities - were assessed in order to select the recommended doses for a phase 2 study. RESULTS: At the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the two subcutaneous doses recommended for a phase 2 study (405 µg per kilogram weekly [30 patients] and 800 µg per kilogram every other week [44 patients]), common adverse events were cytokine release syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); all but one cytokine release syndrome event were of grade 1 or 2. One dose-limiting toxic effect of grade 3 rash was reported in a patient who had received talquetamab at the 800-µg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab at the 405-µg dose level) and 4.2 months (in those who had received it at the 800-µg dose level), the percentages of patients with a response were 70% (95% confidence interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of response was 10.2 months and 7.8 months, respectively. CONCLUSIONS: Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade. Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.).

Let­7f­5p Regulated by Hsa_circ_0000437 Ameliorates Bleomycin-Induced Skin Fibrosis.

The current treatment of skin fibrosis is limited in its effectiveness due to a lack of understanding of the underlying mechanisms. Previous research has shown a connection between microRNAs (miRNAs) and the development of skin fibrosis. Therefore, investigating miRNA for the treatment of skin fibrotic diseases is highly important and merits further exploration. In this study, we have discovered that let-7f-5p could suppress the proliferation, migration, and expression of collagen type I alpha 1 (COL1A1) in human dermal fibroblasts (HDFs). It was further determined that let-7f-5p could target thrombospondin-1 (THBS1), thereby inhibiting the TGF-ß2/Smad3 signaling pathway and exerting its biological effects. Additionally, let-7f-5p is regulated by Hsa_circ_0000437, which acts as a sponge molecule for let-7f-5p and consequently regulates the biological function of HDFs. Furthermore, our findings indicate that in vivo overexpression of let-7f-5p leads to a reduction in dermal thickness and COL1A1 expression, effectively inhibiting the progression of bleomycin (BLM)-induced skin fibrosis in mice. Hence, our research enhances the comprehension of the Hsa_circ_0000437/let-7f-5p/THBS1/TGF-ß2/Smad3 regulatory network, highlighting the potential of let-7f-5p as a therapeutic approach for the treatment of skin fibrosis.

F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

PYR-41, an inhibitor of ubiquitin-activating enzyme E1, attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous studies have shown that PYR-41 has effects on anti-inflammatory, but whether it has therapeutic effects on allergic dermatitis is unclear. The aim of this research was to explore the therapeutic effects of PYR-41 on atopic dermatitis. The effects of PYR-41 on the activation of NF-κB signaling pathway and the expression of inflammatory genes in HaCat cells were tested by western blot and qPCR. A mouse model was built, and the AD-like skin lesions were induced by 2,4-dinitrochlorobenzene (DNCB). Then, the treatment effects of PYR-41 were examined by skin severity score, ear swelling, ELISA, and qPCR. The results showed that PYR-41 can significantly reduce the K63-linked ubiquitination level of nuclear factor-κB essential modulator (NEMO) and tumor necrosis factor receptor associated factor 6 (TRAF6), inhibit the proteasomal degradation of IκBα, thereby activate TNF-α-induced NF-κB signaling pathway in HaCat cells. In addition, DNCB-treated mice have significant reduction in symptoms after treated by PYR-41, including reduced ear thickening and reduced skin damage. Serum tests showed that PYR-41 significantly reduced the expression of IgE, IFN-γ, and TNF-α. In conclusion, the current results suggest that PYR-41 has potential to reduce the symptoms of atopic dermatitis.

Identifying risk factors of anti-TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease.

OBJECTIVES: While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX-induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients. METHODS: In this single-centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance. RESULTS: A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow-up of 3.0 [1.5-4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024-1.148), p = .005], in addition to female sex [2.210 (1.187-5.310), p = .016] and diagnosis of CD [1.695 (1.241-1.877), p = .011]. Considering IFX therapeutic TC cut-offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159). CONCLUSIONS: Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients.

Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review.

INTRODUCTION: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Camrelizumab-induced oral lichenoid reaction with subepithelial CD4+ T-cell infiltration.

INTRODUCTION: Camrelizumab is a novel anti-programed cell death-1 (PD-1) antibody that has been investigated for the treatment of various malignancies. Increasing immune-related adverse events have been reported in clinical practice, with CD4+ T-cell-mediated-reactive cutaneous capillary endothelial proliferation being the most common. Camrelizumab-induced oral lichenoid reaction (OLR) appears to be a rare adverse effect compared with other anti-PD therapies induced OLR, with the main pathogenesis of activated CD8+ T cells mediating autoimmune reactions. Herein, we report a rare case of camrelizumab-induced OLR and a possible pathogenic mechanism of subepithelial CD4+ T-cell infiltration. CASE REPORT: A 57-year-old male patient, who was diagnosed with metastatic esophageal squamous cell carcinoma three years prior, presented with a two-month history of oral erosion that developed while under camrelizumab therapy. Diffuse erythematous and erosive lesions surrounded by bilateral white lesions on the buccal mucosa were detected in his physical examination. Hematoxylin and eosin staining of the lesions revealed the presence of basal keratinocyte degeneration and band-like subepithelial T-cell infiltration. The immunostaining for CD4 on T-cell was positive, while CD8 were sporadically positive. Flow cytometry showed a gradual increase in the CD4+ T-cell proportion in the peripheral blood, with the CD8+ T-cell percentage almost unchanged and in the normal range. We obtained a score of 6 based on the Naranjo algorithm, which means a probable adverse drug reaction. MANAGEMENT AND OUTCOME: The patient exhibited notable improvement after two weeks of treatment with topical glucocorticoid without regulating his immunotherapy, and remained in stable condition in the follow-up. DISCUSSION: This case may offer new insight to clinicians on the pathogenesis of anti-PD-1-induced OLR. More critically, it may provide some ideas for a more precise anti-PD therapy or corresponding combination therapy for patients becoming resistant to immunotherapy due to exhausted CD4+ T-cell responses in the tumor microenvironment.

Efficacy and safety of adapalene gel as a reactive treatment for cetuximab-induced skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck: A historical cohort comparison study.

INTRODUCTION: Despite the common occurrence of cetuximab (Cmab)-induced skin toxicity, management strategies are not well established. The traditional mainstay method consists of topical steroids, which, if used excessively, may give rise to other concerns. Alternatively, adapalene can activate epidermal growth factor receptor pathways to potentially alleviate these toxicities. METHODS: We prospectively studied 31 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who were eligible to use adapalene gel as a reactive treatment for topical steroid-refractory skin toxicity. For comparison, we retrospectively reviewed 99 patients with R/M SCCHN (historical control cohort) whose skin toxicity was mainly treated with topical steroids. We compared the frequency and severity of Cmab-induced skin toxicity, Cmab therapy status (e.g., dose modification), side effects caused by topical steroids and adapalene gel itself, and other medical interventions. RESULTS: Adapalene gel was used by eight patients (25.8%) in the prospective cohort. Patients in the historical control cohort more frequently required escalation of topical steroid potency (34.3% vs. 12.9%, p = 0.022). Although there was no statistically significant difference in the frequency of grade ≥3 facial skin rash and paronychia between the two cohorts, the prospective cohort showed a significantly shorter time to complete recovery from grade 2/3 paronychia (16 vs. 47 days, p = 0.017). Further, while no skin infections were observed in the prospective cohort, 13 patients in the historical control cohort developed skin infections, especially periungual infection (0% vs. 13.1%, p = 0.024). In addition, no patients in the prospective cohort received a dose reduction of Cmab due to skin toxicities, compared to 20 patients in the historical control cohort (0% vs. 20.2%, p = 0.003). No apparent adapalene gel-related side effects were observed. CONCLUSIONS: Adapalene gel may be an effective management option for topical steroid-refractory Cmab-induced skin toxicities and could improve compliance with Cmab therapy.

Granulysin-mediated reduction of PDZRN3 induces Cx43 gap junctions activity exacerbating skin damage in trichloroethylene hypersensitivity syndrome.

Trichloroethylene (TCE)-induced hypersensitivity syndrome (THS) has been a concern for many researchers in the field of environmental and occupational health. Currently, there is no specific treatment for THS, leaving patients to contend with severe infections arising from extensive skin lesions, consequently leading to serious adverse effects. However, the pathogenesis of severe skin damage in THS remains unclear. This study aims to investigate the specific danger signals and mechanisms underlying skin damage in THS through in vivo and in vitro experiments. We identified that cell supernatant containing 15 kDa granulysin (GNLY), released from activated CD3-CD56+NK cells or CD3+CD56+NKT cells in PBMC induced by TCE or its metabolite, promoted apoptosis in HaCaT cells. The apoptosis level decreased upon neutralization of GNLY in the supernatant by a GNLY-neutralizing antibody in HaCaT cells. Subcutaneous injection of recombinant 15 kDa GNLY exacerbated skin damage in the THS mouse model and better mimicked patients' disease states. Recombinant 15 kDa GNLY could directly induce cellular communication disorders, inflammation, and apoptosis in HaCaT cells. In addition to its cytotoxic effects, GNLY released from TCE-activated NK cells and NKT cells or synthesized GNLY alone could induce aberrant expression of the E3 ubiquitin ligase PDZRN3, causing dysregulation of the ubiquitination of the cell itself. Consequently, this resulted in the persistent opening of gap junctions composed of connexin43, thereby intensifying cellular inflammation and apoptosis through the "bystander effect". This study provides experimental evidence elucidating the mechanisms of THS skin damage and offers a novel theoretical foundation for the development of effective therapies targeting severe dermatitis induced by chemicals or drugs.

Air pollution and skin diseases: A comprehensive evaluation of the associated mechanism.

Air pollutants deteriorate the survival environment and endanger human health around the world. A large number of studies have confirmed that air pollution jeopardizes multiple organs, such as the cardiovascular, respiratory, and central nervous systems. Skin is the largest organ and the first barrier that protects us from the outside world. Air pollutants such as particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) will affect the structure and function of the skin and bring about the development of inflammatory skin diseases (atopic dermatitis (AD), psoriasis), skin accessory diseases (acne, alopecia), auto-immune skin diseases (cutaneous lupus erythematosus(CLE) scleroderma), and even skin tumors (melanoma, basal cell carcinoma (BCC), squamous-cell carcinoma (SCC)). Oxidative stress, skin barrier damage, microbiome dysbiosis, and skin inflammation are the pathogenesis of air pollution stimulation. In this review, we summarize the current evidence on the effects of air pollution on skin diseases and possible mechanisms to provide strategies for future research.

Skin and ophthalmic complications of chloroquine and hydroxychloroquine in patients with rheumatoid arthritis and systemic lupus erythematous.

Immunosuppressive agents are routinely used to control autoimmunity. However, some adverse events are correlated to their clinical applications. The aim of this study was to study the clinical findings and ocular and cutaneous side effects of chloroquine (CQ) and hydroxychloroquine (HCQ), as current immunomodulators, in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This descriptive study was performed on 360 individuals referred to the Rheumatology clinic during 2003-2020. Demographic characteristics and other information were collected from patients with RA and SLE. Skin and ocular complications were evaluated in patients who were on treatment with CQ and HCQ. Study populations consisted of 199 subjects with RA and 161 cases with SLE. The frequencies of skin and ocular complications in all patients treated with CQ and HCQ were 32 (17.65%) and 94 (51.9%), respectively. The prevalence of skin complications in patients with RA and SLE was 20 (10.05%) and 22 (13.66%), respectively. The frequencies of ocular complications in patients with RA and SLE were, respectively, 58 (29.4%) and 36 (22.5%). Multiple logistic regression analysis revealed that ophthalmic complications of CQ and HCQ in all patients were dependent on the effects of the duration of drug uses, disease duration, and cumulative doses (p < 0.05), unlike skin complications. Disease types had no effect on ocular complications. Based on these findings, treatment with CQ and HCQ participates in some skin and ocular complications in patients with RA and SLE which are largely associated with the duration of disease and treatment.

Dermatologic adverse events caused by biologic treatments - Pathogenesis and management.

Biologics are approved for various dermatologic, allergic, rheumatic, and gastroenterologic inflammatory diseases, as well as for numerous malignancies. The dermatologic adverse events from treatment with biologics may resemble primary inflammatory diseases but differ in pathogenesis. In this article, we describe five different pathogenic mechanisms of dermatologic adverse events. By studying these mechanisms, we hope to gain valuable insights into the pathogenesis of primary inflammatory diseases. In addition, in this article, we provide recommendations for the treatment and management of the dermatological adverse events induced by biologics.

Sarcoid-like Reactions to Immune Checkpoint Inhibitors. / Reacciones sarcoideas relacionadas con inhibidores de puntos de control inmunitario.

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression.

[Translated article] Sarcoid-like Reactions to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression.

Di-(2-ethylhexyl) phthalate aggravates psoriasis-like skin lesions: In vitro and in vivo evaluation.

Di-(2-ethylhexyl) phthalate (DEHP), which is a widely used phthalate (PAE), has recently received public attention owing to it causing health problems. The aim of this study was to elucidate the aggravating effects of DEHP on psoriasis and skin toxicity. Human keratinocyte (HaCaT) cells were treated with gradient concentrations of DEHP, and mice with imiquimod (IMQ)-induced psoriasiform dermatitis were hypodermically injected with 40 µg/kg/day of DEHP for seven consecutive days. The skin condition was assessed based on the psoriasis area and severity index score, which indicated the deterioration of IMQ-induced psoriasis-like skin lesions after DEHP exposure. To further analyze the effect of DEHP on psoriasis, the proliferation, inflammation, and tight junction (TJ) damage were examined, which correlated with the development and severity of psoriasis. The results showed that DEHP promoted proliferation both in vivo and in vitro, which manifested as epidermal thickening; an increase in cell viability; upregulation of Ki67, CDK2, cyclinD1, and proliferating cell nuclear antigen; and downregulation of p21. An excessive inflammatory response is an important factor that exacerbates psoriasis, and our results showed that DEHP can trigger the release of inflammatory cytokines as well as the infiltration of T cells. TJ disorders were found in mice and cells after DEHP treatment. Additionally, p38 mitogen-activated protein kinase (MAPK) was strongly activated during this process, which may have contributed to skin toxicity caused by DEHP. In conclusion, DEHP treatment promotes proliferation, inflammation, TJ disruption, and p38 MAPK activation in HaCaT cells and psoriasis-like skin lesions.

How to recognize and manage skin toxicities associated with immune checkpoint inhibitors: a practical approach.

Immune checkpoint inhibitors (ICIs) have revolutionized treatment strategies in the field of oncology. Their favourable outcomes in terms of efficacy and side-effect profile can be thwarted by the development of immune-related adverse events (irAEs). Cutaneous irAEs are relatively common in patients undergoing immunotherapy and include common inflammatory dermatoses (e.g. eczematous, psoriasiform and lichenoid phenotypes), maculopapular eruptions, pruritus and immunobullous disorders. Most of these reactions can be managed without ICIs having to be stopped completely; however, there are some life-threatening toxicities that dermatologists and oncologists should be aware of. In this review, we focus on how to recognize the commonly associated cutaneous irAEs, touching upon rarer reactions and red flags; finally, we provide guidance on their management.

Cetuximab severe cutaneous toxicity a gateway for bacteremia: case report.

EGFR inhibitors used in the treatment of metastatic wild-RAS colorectal cancer in combination with chemotherapy are associated with dermatologic side events that are low grade in most cases. We report a case of severe cutaneous toxicity secondary to cetuximab associated with bacterial cellulitis. A 57-year-old woman with metastatic adenocarcinoma of the colon, receiving FOLFIRI and Cetuximab as a first-line treatment, presented with a severe erythematous rash and xerosis resistant to local treatment with moisturizing emollients. Few days later, the patient becomes febrile, and the rash becomes more diffuse with a sandpaper appearance on the face, neck, chest, and flexor creases with exfoliation of large areas of skin. A bacterial cellulitis secondary to a dermatologic severe toxicity of Cetuximab was suspected. The patient started on antibiotics and local treatment with good response. This is a life-threatening cutaneous toxicity of cetuximab with secondary bacterial infection. Early recognition of cutaneous side effects of EGFR inhibitors is important to prevent such type of toxicities.

Pinnae and facial hypertrichosis induced by cetuximab.

INTRODUCTION: Anti-EGFR targeted anti-cancer treatment is associated with various skin adverse events. Cetuximab is often associated with acneiform papules and skin disorders. Hypertrichosis cited in face pinnae and eyelash trichomegaly are seldom described. CASE REPORT: A 72-year-old female cancer patient presented deteriorating facial-pinnae hypertrichosis and eyelash prolongation post cetuximab infusion. MANAGEMENT AND OUTCOME: Consecutive cetuximab administration led to exaggerating hairy skin side effects, fully alleviated when the drug was discontinued. DISCUSSION: To the best of our knowledge, this is the first reported case of an anti-EGFR-associated diffuse pinnae hypertrichosis presentation in a female patient in literature. This distinct entity can be easily diagnosed and manipulated with early drug withdrawal. An extensive review of relevant basic molecular research is provided to increase physicians' awareness.

MEK inhibitor-induced paronychia in a paediatric population: A tertiary centre experience.

The cutaneous toxicity of MEK inhibitors may limit treatment adherence. The authors present a retrospective study of 41 paediatric patients with NF-1 undergoing therapy with selumetinib and propose a treatment algorithm.

[Dermatologic side effects with use of lithium]. / Efectos adversos dermatológicos con uso de litio.

Lithium is a mood stabilizer recommended by most clinical guidelines as the gold standard to prevent relapses in the treatment of Bipolar Affective Disorder. It is highly effective, but unfortunately, it causes adverse effects at several levels, including the skin. AIM: To review the frequency, presentation, evolution, and management of adverse dermatologic effects caused by this drug. METHODS: We performed a narrative review using Scielo, Web of Science (WoS), and Google Scholar search engines, using keywords in Spanish and English. RESULTS: The skin presentations that appear most frequently are the progression of previously existing or newly diagnosed psoriasis, alopecia, acne, follicular inflammation, and maculopapular eruptions. CONCLUSIONS: Lithium produces and/or exacerbates a series of dermatological conditions of different severity, even at therapeutic levels, which are not usually severe but, even so, should not be underestimated since it can affect adherence to the drug.