A significant number of chronic venous ulcers (CVUs) fail to heal despite guideline-conform standards of care. Skin-derived ABCB5⁺ mesenchymal stem cells can dampen the sustained IL-1β‒driven inflammation present in chronic wounds. On the basis of their wound healing‒facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5⁺ mesenchymal stem cells have emerged as a potential candidate for cell-based advanced therapy of nonhealing CVUs. In this interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVUs had emerged as standard therapy resistant received one or two topical applications of 1 × 10⁶ allogeneic ABCB5⁺ mesenchymal stem cells per cm² wound area, in addition to standard treatment. Of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, n = 31), 78% (per-protocol set, n = 27), and 87% (subset of responders, n = 21). In conclusion, the study treatment was well-tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5⁺ mesenchymal stem cells as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy.

There is a paucity of studies examining the safety of venom immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic side effects during rush VIT in a cohort of pediatric patients and adult controls. 72 consecutive cycles of VIT-buildup in 71 children/adolescents aged 7–17 years were retrospectively evaluated and compared to an adult control group (n = 981) with regard to baseline parameters (sex, causative venom, severity of index sting reaction, results of allergy testing, comorbidities) and the incidence of anaphylactic adverse reactions. Compared to adults, severe index sting-induced anaphylaxis was significantly less common in children (P = .001). Children were more likely to suffer from bee venom allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013), but lower serum tryptase concentrations (P = .014). The overall rate of VIT-induced anaphylactic reactions was higher in children than in adults (6.9% vs 2.5%, P = .046 by univariate analysis). In the final binary logistic regression model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04–4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64; confidence interval 1.25–5.57) were associated with an increased risk of treatment-induced anaphylaxis. All pediatric patients finally reached and tolerated the target maintenance dose of 100 µg. The higher anaphylactic reaction rate observed in pediatric patients may be attributed to a greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is usually mild and does not affect further updosing and maintenance of VIT.

Regional lymphomatoid papulosis (LyP) accounts for 2-27% of all LyP cases. Several localized dermatoses have been reported in association with Becker's melanosis (BM), e.g. acneiform lesions or lichen planus. Here, we report on regional LyP confined to the area of BM. A 56-year-old man presented with a 1-year history of a steadily increasing number of multiple pruritic red papules developing on the area of BM, which had occurred on his left shoulder during puberty. Histopathological analysis was consistent with regional LyP. Potent topical steroids followed by oral doxycycline did not achieve improvement, while long-term oral bexarotene treatment ameliorated the skin condition. Recently, the proposed entity of ‘persistent agmination of LyP' (PALP) has extended the clinicopathological observations of regional LyP. Since PALP remains controversial, a unifying concept of localized LyP and PALP will be discussed.

A plethora of data supports a major role of CD4⁺ and CD8⁺ T lymphocytes for the initiation, progression, and maintenance of allergic contact dermatitis. However, in-depth understanding of the molecular mechanisms is still limited. NFATc1 plays an essential role in T-cell activation. We therefore investigated its impact on contact hypersensitivity, the mouse model for allergic contact dermatitis. The contact hypersensitivity response to 2,4,6-trinitrochlorobenzene was diminished in Nfatc1^fl/flxCd4-cre mice (Nfatc1^-/-) compared with that in wild-type mice and associated with a lower percentage of IL-17-producing CD8⁺ T (Tc17) cells in both inflamed skin and draining lymph nodes. In vitro Tc17 polarization assays revealed that Nfatc1^-/- CD8⁺ T cells have a reduced capacity to polarize into Tc17 cells. Applying single-cell RNA sequencing, we realized that NFATc1 controls the T-cell differentiation fate. In the absence of NFATc1, CD8⁺ T cells favor the development of IFN-γ-secreting CD8⁺ T (Tc1) lymphocytes, whereas in its presence, they turn into Tc17 cells. Finally, the adoptive transfer of 2,4,6-trinitrochlorobenzene-sensitized wild-type CD8⁺ T cells restored the contact hypersensitivity response in naïve Nfatc1^-/- mice. Our data demonstrate that NFATc1 contributes to the development of Tc17 cells and might present a promising target to alleviate CD8⁺ T-cell-mediated allergic responses.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition associated with considerable comorbidity. The link between HS and metabolic dysfunction–associated steatotic liver disease (MASLD) is of particular interest owing to shared inflammatory pathways. This study applies the new MASLD nomenclature in a HS cohort. Our study aims to investigate the prevalence of MASLD in HS using transient elastography and to develop a clinical algorithm for assessing the MASLD risk. A cross-sectional study was conducted involving 94 patients with HS. Noninvasive methods were employed to diagnose MASLD. The clinical diagnosis was based on altered transient elastography–controlled attenuation parameter as surrogate for liver steatosis and the presence of cardiometabolic risk factors after excluding secondary causes of steatosis. Statistical analyses included logistic regression models to identify predictors of MASLD risk. The study found a prevalence of MASLD as high as 75% measured by high-accuracy transient elastography among patients with HS. Multivariable logistic regression analysis showed a strong within-cohort association between HS and MASLD. The newly developed clinical algorithm integrating transient elastography and the Fatty Liver Index effectively stratified MASLD risk. Our findings underscore the importance of routine MASLD screening in HS. The proposed clinical algorithm offers a straightforward approach for assessing MASLD risk in HS.