Search

International audience; Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome. ND belong to internal medicine as a great number of patients with ND suffer from an underlying condition (such as hematological malignancy, inflammatory bowel disease, auto-immune and auto-inflammatory diseases). ND are diagnoses of exclusion and physicians should always consider differential diagnoses, particularly skin infections. Here, we review the pathophysiology and classification of the main ND (i.e., subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) and Intercellular IgA dermatoses, aseptic pustulosis of the folds, Sweet syndrome, neutrophilic eccrine hidradenitis, pyoderma gangrenosum, erythema elevatum diutinum, neutrophilic urticarial dermatosis and neutrophilic panniculitis), their clinical and histopathological features, and we highlight the investigations that are useful to identify ND-associated diseases and to exclude the differential diagnoses.

Actinic cheilitis is a premalignant condition that can progress to squamous cell carcinoma with a higher propensity for metastasis than cutaneous squamous cell carcinoma. Optimal treatment for actinic cheilitis has not been established, and evidence-based estimates of clinical cure in the dermatology literature are limited. Here, we review and synthesize outcome data published for patients with actinic cheilitis after treatment with various modalities. A systematic review was conducted in MEDLINE, Embase and the Cochrane library for English, French and German-language studies and references of included articles from inception to 20 January 2020. Studies were included if they reported on at least six patients with biopsy-proven actinic cheilitis. After quality appraisal, results of studies with the strongest methodology criteria were synthesized. 18 studies of 411 patients (published 1985 to 2016) were included. The majority of the studies were case series. Carbon dioxide laser ablation and vermilionectomy were associated with the most favourable outcomes with fewest recurrences. Chemical peel and photodynamic therapy were associated with higher recurrence. Adverse effects generally resolved in the weeks following treatment and cosmetic outcomes were favourable overall. In conclusion, there is a lack of high-quality comparative studies evaluating different treatment options for actinic cheilitis. The included publications used various outcome measures; however, the majority reported on the recently defined core outcome sets. These results suggest that both carbon dioxide laser ablation and vermilionectomy are effective treatments for actinic cheilitis. Prospective head-to-head studies are needed to compare these treatment modalities and to assess patient preferences.

T-cell lymphomas are a heterogeneous group of malignancies involving T lymphocytes and generally characterized by a poor prognosis. Among them, cutaneous T-cell lymphomas (CTCL) involve primarily the skin. The most frequent CTCL are mycosis fungoides and Sézary syndrome (SS) (1). There is no cure for advanced-stage CTCL, the remissions are generally rare and short, and the overall survival is around 5 years with an impaired quality of life. Thus, the development of new treatments inducing longstanding responses in CTCL is a major unmet need (2). Because Sézary cells express several Treg markers as PD-1, ICOS, CD39 or CCR8 (3), we analyzed the expression of CD51, the αV integrin, which is expressed with the β8 integrin on Treg cells (4). CD51 is involved in the production of active form of TGF-β, a cytokine with immunosuppressive properties that promotes tumor escape. Thus, targeting the αVβ8 integrin with a specific antibody has been shown to inhibit TGF-β activation while not inhibiting cell adhesion (5). Our results revealed that CD51 is significantly overexpressed in circulating lymphocytes from SS patients as compared to healthy individuals. Interestingly, CD51 is not associated with the β8 integrin but with CD29 (β1 integrin), and CD61 (β3 integrin) in some patients.CD51/CD29 and/or CD51/CD61 heterodimers appear as potential therapeutic targets in T-cell lymphoma, which may be associated with the production of active TGF-β. Targeting these heterodimers with specific antibodies to prevent the release of active TGF-β could improve patient’s antitumor immune response. They could also represent depleting targets through NK or CAR-T cells activities as shown in diffuse intrinsic pontine glioma and glioblastoma for CD51/CD61 heterodimer (6). 1. Dobos G, et al. Epidemiology of Cutaneous T-Cell Lymphomas: A Systematic Review and Meta-Analysis of 16,953 Patients. Cancers. 11 oct 2020;12(10).2. Scarisbrick JJ, et al. The changing therapeutic landscape, burden of disease, and unmet needs in patients with cutaneous T-cell lymphoma. Br J Haematol. févr 2021;192(4).3. Giustiniani J, et al. CCR8 is a new therapeutic target in cutaneous T-cell lymphomas. Blood Adv. 2022 Feb 24.4. Stockis J, et al. Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8. Proc Natl Acad Sci U S A 2017 Nov 21;114(47).5. Tsui P, et al. The TGF-β inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan. mAbs. janv 2017;9(1):104-13.6. Cobb D, de Rossi J, Liu L, An E, Lee D. Targeting of the alphav beta3 integrin complex by CAR-T cells leads to rapid regression of diffuse intrinsic pontine glioma and glioblastoma J Immunother Cancer 2022. Citation Format: Jérôme Giustiniani, Anne Marie-Cardine, Sadjia Belkhelouat, Martine Bagot, Armand Bensussan, Nicolas Ortonne, Adèle De Masson. Targeting the CD51/TGF-beta pathway: a potential innovative cancer immunotherapy in T-cell lymphomas. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3644.

Mogamulizumab, an anti-CCR4 monoclonal antibody, has been shown to increase progression-free survival in cutaneous T-cell lymphoma.We hypothesized that besides the targeted depletion of Sézary cells (SCs), mogamulizumab may reshape the immune tumour microenvironment.Both malignant and benign compartments from 26 patients with B2 stage Sézary syndrome before mogamulizumab initiation were prospectively analysed using KIR3DL2 and TCRVβ markers, serological markers and molecular assessments of clonality.Prior to mogamulizumab, the benign subset of CD4Mogamulizumab likely contributes to the restoration of efficient immunity and reshapes not only the malignant lymphocyte subset but also the benign subset. These results have potential implications for optimal therapeutic sequences and/or combinations. What is already known about this topic? Management of Sézary syndrome (SS) involves successive therapies that participate as cause and consequence in the emergence of resistant clones, on a background of immunodeficiency. We and others have reported the complex and dynamic heterogeneity of Sézary cells (SCs) during disease progression. Mogamulizumab therapy, by targeting the skin-homing receptor CCR4, mainly expressed by SCs, has been shown to increase progression-free survival in patients with SS. What does this study add? Using multicolour flow cytometry, we provide quantification of CCR4 and immune checkpoint molecules on malignant SCs and benign CD4

Applying next-generation sequencing to paired skin and marrow biopsies, Delaleu et al describe an entity they term “myelodysplasia cutis,” comprising histologic features of histiocytoid Sweet syndrome in the skin and a clonally related myelodysplasia in the bone marrow. This can be distinguished from forms of histiocytoid Sweet syndrome not associated with myelodysplastic syndromes, as well as classical neutrophilic Sweet syndrome associated with various malignant and nonmalignant diseases and leukemia cutis where the infiltrating cells are myeloblasts.

Amyopathic dermatomyositis (ADM) is a subtype of DM defined by the presence of cutaneous signs of DM with no evidence of muscle weakness or abnormal muscle enzymes for ≥ 6 months.1 Classical DM (CDM) is characterized by modification of circulating lymphocytes 4, type I interferon (IFN) signature 2, elevation of serum pro-inflammatory cytokines 3. Pathophysiology of ADM is less studied. We analysed circulating T cells by flowcytometry (using specific monoclonal antibodies), peripheral blood mononuclear cells type I IFN signature by PCR and serum cytokine levels by ELISA in a series of 17 ADM and 15 CDM patients. [...]