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The article presents a study on immunophenotyping on skin and blood to determine the severity of skin symptoms of toxic epidermal necrolysis (TEN), a cutaneous adverse drug reaction. It discusses the characterization of TEN, findings on the main leucocytes in TEN blisters at the acute phase based on mass cytometry, and the expansion of unique CDR3 clonotypes in blister cells.

The article presents a case study of a 59-year-old woman who was diagnosed with hydroxyzine-induced hypersensitivity reaction. She has suffered from psoriasis and psoriatic arthritis during her childhood and has been treated with psoralen + ultraviolet A, retinoids, and methotrexate. It states the positive impact of ustekinumab treatment on the patient. Moreover, it notes the failure of the treatment process to prevent the development of her allergic dermatitis caused by hydroxyzine.

Background: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. Methods: To characterize the molecular signatures of chemical‐induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. Results: A clear segregation was observed between allergen‐ and irritant‐induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T‐cell responses. Our results also confirmed that: (a) unique pathways characterize allergen‐ and irritant‐induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine‐learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. Conclusion: These results highlight the value of molecular profiling of chemical‐induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis. [ABSTRACT FROM AUTHOR]

Data on the real long-term influences of in utero drug exposure in pregnant women on childhood development are scarce and remain not well determined and depend on the duration of in utero drug exposure and maternal drug levels. Therapeutic drug monitoring (TDM) during pregnancy may help limit fetal drug exposure while maintaining an effective dose for the treatment of the underlying inflammatory bowel disease (IBD) in women. Most antibody therapies used in patients with IBD are IgG molecules which are actively transported across the placenta, especially during the third trimester of the pregnancy. Here, we propose an up-to-date clinical review to summarize the available findings of serum drug levels in maternal blood during pregnancy, in the cord blood, infants at delivery and in breast milk of patients with IBD treated with biologics. Conversely, in comparison to adalimumab (ADA) levels, which are relatively stable during pregnancy, infliximab (IFX) drug clearance decreased significantly during the last two trimesters of the pregnancy, leading to increasing drug concentrations in the blood of the pregnant women. As most guidelines recommend using live vaccines in infants at the age of one or earlier in case of negative serum drug levels in newborns, statistical models could help clinicians in making a decision to adjust the last dose of the biologic during pregnancy and to determine the optimal date to vaccinate. Altogether, data from the literature offers strong reassurance in terms of safety for anti-TNFα therapies during pregnancy not only for IBD patients who intend to conceive, but also for pregnant women and for the physicians taking care of these patients. ADA and IFX levels in breast milk are detectable, but at very low levels, and therefore, it is recommended to pursue breast feeding under anti-TNFα therapy. Our knowledge on ustekinumab or vedolizumab levels in pregnant women remains unclear and scarce. These drugs are currently not recommended for patients with IBD in clinical practice. Therefore, TDM and proactive dose adjustment are not necessary during pregnancy since its impact on making a clinical decision have not yet been clearly demonstrated in routine practice. Overall, drug concentrations in the cord blood, an infant at birth and postpartum serum concentrations in infants, due to active placental drug transfer, may have a greater impact than the limited drug transfer in breast milk during lactation on the risk of infection and developmental outcomes. Ustekinumab and vedolizumab exposure during pregnancy and lactation are both considered low risk by the recent ECCO guidelines despite the limited data that are currently available. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease, affecting 10–20% of children. Measles vaccination has been reported to have contradictory effects on incidence of AD in children. Therefore, we performed the first prospective, double-blind, placebo-controlled study to analyze the evolution of AD in infants after measles vaccination. The study included 12 infants (10–14 months old) with AD, randomly assigned to two groups: while the first group received a single dose of a standard measles vaccine ROUVAX, the second was treated with placebo (vehicle). Infants were followed-up for 6 months after administration of ROUVAX/placebo for the clinical signs associated with AD, by determination of SCORAD index. In addition, serum was taken before vaccination and 1 month later to determine the presence of seroconversion and to analyze the progression of serum levels of CCL18 (PARC) and E-selectin, known to be distinct serum markers that reflect clinical features of AD. In the vaccinated group, five of six children seroconverted 1 month after treatment and one infant showed a 50% improvement of SCORAD. Serum levels of CCL18 were significantly decreased in two treated infants (of four analyzed for this group) and E-selectin slightly decreased in one infant (of three analyzed by this test). In placebo-treated group the SCORAD improved in one patient and serum levels of CCL18 and E-selectin did not change. These data suggest that measles vaccination not only does not aggravate AD, but may also improve some of the immunological parameters of this allergic disease. Inclusion of a higher number of patients in a similar study should give a more comprehensive overview of the benefit of measles vaccination on the clinical evolution of AD patients, and potentially open new avenues to the clinical application of the anti-inflammatory effect of measles virus proteins. [ABSTRACT FROM AUTHOR]

Irritant contact dermatitis (ICD) is a frequent inflammatory skin disease induced by skin contact with low molecular weight chemicals such as haptens endowed with proinflammatory properties. Allergic contact dermatitis (ACD) is a frequent complication of ICD and is mediated by hapten-specific T cells primed in lymph nodes by skin emigrating dendritic cells. The aim of this study was to analyze the relationship between ICD and ACD to 2,4-dinitrofluorobenezene (DNFB) in C57BL/6 and BALB/C mice, which develop a severe and a moderate skin inflammation, respectively. Upon a single skin painting with DNFB, C57BL/6 developed within hours a more severe dose-dependent ICD response as compared to BALB/C mice, which was associated with enhanced upregulation of IL-1β, IL-6, and IL-10. Skin exposure to a low dose of DNFB resulted, in both strains, in a low ICD that resolved in a few hours. Alternatively, skin painting with either an intermediate or a high DNFB concentration induced an ICD that subsequently gave rise to an ACD reaction whose intensity was proportional to the magnitude of the ICD response and was more severe in C57BL/6 mice than in BALB/C mice. In conclusion, the hapten-induced skin contact irritation conditions the development and the severity of ACD.Journal of Investigative Dermatology (2007) 127, 1430–1435. doi:10.1038/sj.jid.5700726; published online 1 February 2007 [ABSTRACT FROM AUTHOR]