Neutrophilic dermatoses.

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.

New biotherapies for the treatment of cutaneous T-cell lymphomas.

Most cutaneous lymphomas are cutaneous T-cell lymphomas, and the most common form is mycosis fungoides. Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma which is characterized by erythroderma and the presence of blood tumor cells. The only potential cure of cutaneous T-cell lymphomas remains allogeneic stem cell transplantation. However, monoclonal antibodies have led to a substantial progress in the treatment of advanced-stage cutaneous T-cell lymphomas. Some of them, such as mogamulizumab (anti-CCR4 monoclobal antibody) or brentuximab vedotin (anti-CD30 coupled to monomethylauristatin E, antibody drug conjugate) have shown efficacy in international randomized controlled studies. Lacutamab, an anti-KIR3DL2 monoclonal antibody, is currently tested in an international, prospective phase 2 trial in cutaneous T-cell lymphomas and peripheral T-cell lymphomas. Finally, immune checkpoint inhibitors have shown clinical benefit in open-label phase 2 studies in cutaneous T-cell lymphomas. This review focuses on the new biotherapies currently used in cutaneous T-cell lymphomas.

Recent advances on cutaneous lymphoma epidemiology.

BACKGROUND: Primary cutaneous lymphomas are a group of T- (CTCL) and B-cell (CBCL) malignancies. These diseases have different clinical presentations and prognosis. Our knowledge on their epidemiology is limited. Aim of this review was to summarize recent findings on the incidence of CTCL and CBCL, how they change over time, and to describe possible causes and consequences. We found that although there are important differences in the epidemiology of cutaneous lymphomas in different countries, the relative frequency of certain, especially rare lymphomas remains stable. Several studies described growing incidences of both CTCL and CBCL. The emergence of new diagnostic criteria, a more precise definition of the entities and new biomarkers enable a better classification of cases.

Image-guided lymph node core-needle biopsy predicts survival in mycosis fungoides and Sézary syndrome.

BACKGROUND: The prognosis of Sézary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated. OBJECTIVES: To determine the prognostic value of LN CNB in MF/SS. METHODS: A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus. RESULTS: We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26-not reached) vs. 14 months (range 5-30), respectively (P < 0·001). In univariate analyses, an age > 75 years, LN short-axis diameter > 15 mm, N3 stage, presence of large-cell transformation, TOX > 60%, PD1 > 25%, Ki67 > 30%, KIR3DL2 > 15%, CD30 > 10% and TCF > 25% were identified as adverse prognostic factors. In multivariate analyses, only an age > 75 years and Ki67 index > 30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis. CONCLUSIONS: CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis.

Actinic cheilitis: a systematic review of treatment options.

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.

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

Chronic graft-versus-host disease and inhibition of interleukin-17: proof of concept in humans.

Psoriasiform chronic graft-versus-host disease (GvHD) is a rare clinical presentation recently described after allogeneic haematopoietic stem cell transplantation. It is characterized by the combination of clinical and pathological characteristics of psoriasis together with pathological features of chronic GvHD. As described for psoriasis, psoriasiform chronic GvHD is characterized by the infiltration of T helper 17 CD8+ T cells producing both interferon-γ and interleukin-17. However, no data are available about the efficacy of interleukin-17 blockade in the treatment of patients with psoriasiform chronic GvHD. What's already known about this topic? Psoriasiform chronic graft-versus-host disease (GvHD) is a rare clinical presentation with a poor durable response to steroids. Animal models and human data suggest that psoriasiform GvHD could be induced through interleukin-17 production by donor T cells. What does this study add? We describe the first case of a patient with psoriasiform GvHD and persistent improvement on treatment with secukinumab, an anti-interleukin-17A antibody.