Explore the vast range of titles available.

Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD and healthy control skin. We show that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17 , CCL18 and CCL26 . By contrast, we found strong increases in type 22-associated markers ( IL22, AHR ) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation and IL-22 receptor upregulation. Taken together, we demonstrate that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22 -associated responses. Dupilumab-associated head and neck dermatitis has been described in a subset of patients treated with the IL4R-blocker dupilumab. Here the authors characterise the immune cell composition and single-cell transcriptome in comparison with untreated forms of atopic dermatitis in a small cohort showing increases in IL-22-associated genes.

Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients' health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.

Background In early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20–30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood. Methods In patients with advanced-stage MF, we compared patches with longstanding history to newly developed plaques and tumors by using single-cell RNA sequencing, and compared results with early-stage MF as well as nonlesional MF and healthy control skin. Results Despite considerable inter-individual variability, lesion progression was uniformly associated with downregulation of the tissue residency markers CXCR4 and CD69 , the heat shock protein HSPA1A , the tumor suppressors and immunoregulatory mediators ZFP36 and TXNIP , and the interleukin 7 receptor ( IL7R) within the malignant clone, but not in benign T cells. This phenomenon was not only found in conventional TCR-αβ MF, but also in a case of TCR-γδ MF, suggesting a common mechanism across MF subtypes. Conversely, malignant cells in clinically unaffected skin from MF patients showed upregulation of these markers. Conclusions Our data reveal a specific panel of biomarkers that might be used for monitoring MF disease progression. Altered expression of these genes may underlie the switch in clinical phenotype observed in advanced-stage MF.

A 52‐year‐old Caucasian woman was referred for an allergy workup of suspected type I allergy to the interleukin (IL)‐17A inhibitor ixekizumab. Five months after ixekizumab initiation, she suddenly developed intense pruritus and three small wheals at the injection site approximately 30 min after injection, lasting up to 3 days. With each additional application, she experienced a crescendo‐like amplification of skin symptoms. Allergy skin tests with ixekizumab, adalimumab (anti‐TNF‐α), brodalumab (anti‐IL17RA), risankizumab (anti‐IL‐23p19) and tildrakizumab (anti‐IL‐23p19) were performed. Skin prick testing showed positive results for ixekizumab with negative results for all other tested biologics. Intradermal testing, confirmed positive reactivity for ixekizumab already at a lower concentration. Intradermal testing was also positive for undiluted brodalumab, risankizumab and tildrakizumab. Allergy skin tests confirmed type I allergy to ixekizumab and suggested cross‐sensitization to brodalumab, risankizumab and tildrakizumab, for which the patient was treatment‐naïve. Capsule summary A 52‐year‐old woman developed pruritus and wheals at the injection site five months after starting ixekizumab. With each additional application, she experienced a crescendo‐like amplification of symptoms. Allergy skin tests with different biologics were performed. Skin prick testing was positive for ixekizumab. Intradermal testing confirmed positive reactivity for ixekizumab and was also positive for brodalumab, risankizumab, and tildrakizumab. Allergy tests confirmed type I allergy to ixekizumab and suggest cross‐sensitization to brodalumab, risankizumab, and tildrakizumab, for which the patient was treatment‐naïve.

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities. While primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) is aggressive, primary cutaneous follicle centre lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) typically follow an indolent course. To clarify their pathophysiological basis, we perform single-cell RNA sequencing on pcFCL, pcMZL, and pcDLBCL-LT, alongside reactive B-cell rich lymphoid proliferations (rB-LP), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and systemic counterparts. Here we show that the indolent pcMZL, pcFCL, and rB-LP exhibit a persistent germinal centre reaction, not observed in pcDLBCL-LT or gastric MALT lymphoma. Further, pcMZL top expanded clones develop within lesions from naïve and not post-germinal centre B cells as currently presumed. Our data thus indicate that pcMZL and pcFCL, similar to rB-LP may be driven by (a yet unknown) antigen. While our data indicates that pcFCL exhibits some features of true lymphomas, it clearly supports the classification of pcMZL as a lymphoproliferative disease. Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.

Atopic dermatitis (AD) typically starts in infancy or early childhood, showing spontaneous remission in a subset of patients, while others develop lifelong disease. Despite an increased understanding of AD, factors guiding its natural course are only insufficiently elucidated. We thus performed suction blistering in skin of adult patients with stable, spontaneous remission from previous moderate-to-severe AD during childhood. Samples were compared to healthy controls without personal or familial history of atopy, and to chronic, active AD lesions. Skin cells and tissue fluid obtained were used for single-cell RNA sequencing and proteomic multiplex assays, respectively. We found overall cell composition and proteomic profiles of spontaneously healed AD to be comparable to healthy control skin, without upregulation of typical AD activity markers (e.g., IL13, S100As, and KRT16). Among all cell types in spontaneously healed AD, melanocytes harbored the largest numbers of differentially expressed genes in comparison to healthy controls, with upregulation of potentially anti-inflammatory markers such as PLA2G7. Conventional T-cells also showed increases in regulatory markers, and a general skewing toward a more Th1-like phenotype. By contrast, gene expression of regulatory T-cells and keratinocytes was essentially indistinguishable from healthy skin. Melanocytes and conventional T-cells might thus contribute a specific regulatory milieu in spontaneously healed AD skin.

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known about phenotypic and functional properties of malignant T cells in relationship to tissue environments over the course of disease progression. We thus profiled the tumor micromilieu in skin, blood and lymph node in a patient with advanced MF using single-cell RNA sequencing combined with V-D-J T-cell receptor sequencing. In skin, we identified clonally expanded T-cells with characteristic features of tissue-resident memory T-cells (T RM , CD69 + CD27 - NR4A1 + RGS1 + AHR + ). In blood and lymph node, the malignant clones displayed a transcriptional program reminiscent of a more central memory-like phenotype ( KLF2 + TCF7 + S1PR1 + SELL + CCR7 + ), while retaining tissue-homing receptors (CLA , CCR10 ). The skin tumor microenvironment contained potentially tumor-permissive myeloid cells producing regulatory ( IDO1 ) and Th2-associated mediators ( CCL13, CCL17, CCL22 ). Given their expression of PVR, TNFRSF14 and CD80/CD86 , they might be under direct control by TIGIT + CTLA4 + CSF2 + TNFSF14 + tumor cells. In sum, this study highlights the adaptive phenotypic and functional plasticity of MF tumor cell clones. Thus, the T RM -like phenotype enables long-term skin residence of MF cells. Their switch to a T CM -like phenotype with persistent skin homing molecule expression in the circulation might explain the multi-focal nature of MF.

Background: Apremilast, an oral phosphodiesterase 4 inhibitor, is approved in the European Union for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients refractory or contraindicated to or intolerant of other systemic therapies. Objectives: The APPRECIATE study assessed apremilast use in real-world practice and its clinical value to physicians and patients. APPRECIATE was a multinational, observational, retrospective, cross-sectional study. Methods: Apremilast effectiveness at 6 (±1) months was assessed on the basis of psoriasis severity and health-related quality-of-life scores and treatment satisfaction using physician/patient-reported outcomes, respectively. We report the Austrian cohort of 72 patients. Results: At 6 (±1) months, three-quarters of patients remained on apremilast, while physicians and patients reported treatment benefits across all psoriasis symptoms and manifestations. Of patients, the majority were satisfied with their treatment and achieved treatment goals considered most relevant. Patients’ and physicians’ perceptions of treatment effectiveness were aligned, and health-related quality-of-life scores indicated an improvement in the majority of patients. Apremilast tolerability was consistent with the known safety profile. Conclusions: Among psoriasis patients receiving apremilast in Austria, improvement in clinical outcomes were observed and satisfaction with apremilast treatment among patients and physicians was high. Registration: ClinicalTrials.gov NCT02740218

Mycosis fungoides (MF) is a subtype of T-cell lymphoma that is characterised by the infiltration of malignant T cells into the skin. Treatment approaches usually include skin-directed therapies for early-stage disease and, additionally, systemic therapies for advanced stages. Chlormethine hydrochloride gel is recommended as a first-line treatment option for adult patients with MF, with previous studies demonstrating its efficacy. Due to the rarity of this disease, available literature on the optimal treatment of MF with chlormethine gel is limited, creating challenges for making informed clinical decisions. Thus, we share our individual clinical experiences of selected patients on chlormethine combination treatments to increase the real-world evidence for chlormethine gel in patients with MF. We present the cases of five male and two female Caucasian patients above the age of 48 with Stage I-IV MF, presenting with symptoms of skin plaques and lesions. All patients were treated with chlormethine hydrochloride gel in combination with other skin-directed and systemic therapies, including bexarotene, methotrexate, topical steroids, extracorporeal photopheresis, donor lymphocyte infusion and interferon-α (IFN-α) 2a. In most cases, chlormethine combination treatment resulted in disease control, e.g., plaque reduction, stable disease, and partial or complete response. The combination regimens were generally well tolerated, with associated adverse events being inflammation, pruritus and erythema. This case series reports on the efficacy and safety of chlormethine hydrochloride gel in combination with other topical and systemic therapies in reducing the skin lesion severity in patients with Stage I-IV MF in different real-world settings.

In the literature there is no consensus on the correlation between early systemic intervention and better treatment response in psoriasis. Here we present data on the impact of disease duration (<5 years, 5-<10 years, and ≥10 years) on response to tildrakizumab treatment among patients with moderate-to-severe plaque psoriasis from the reSURFACE 1 and reSURFACE 2 phase 3 trials and the TRIBUTE phase 4 study. Overall, there was no significant effect of disease duration on the Psoriasis Area and Severity Index ≤1, ≤3, and ≤5, or the Dermatology Life Quality Index 0-1 response rates. Tildrakizumab was highly effective regardless of the psoriasis disease duration.