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Indian Journal of Dermatology 2023Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic...
Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD). While recent reports have described cases of new-onset mycosis fungoides (MF) following treatment with dupilumab for AD, to our knowledge only one patient has been delineated with the progression to SS. We present an additional case of a patient who was diagnosed with SS following treatment with dupilumab for adult-onset AD and asthma. We examine SS as a possible side effect of dupilumab while also discussing management and theories to explain this phenomenon.
PubMed: 37822402
DOI: 10.4103/ijd.ijd_580_22 -
Journal Der Deutschen Dermatologischen... Sep 2021Mycosis fungoides (MF) and Sézary syndrome (SS) are primary cutaneous T-cell lymphomas (CTCL) with not yet fully understood etiology and pathogenesis. Conceptually, MF...
Mycosis fungoides (MF) and Sézary syndrome (SS) are primary cutaneous T-cell lymphomas (CTCL) with not yet fully understood etiology and pathogenesis. Conceptually, MF and SS are classified as distinct entities arising from different T helper cell subsets. MF is the most common CTCL entity, while SS is very rare. MF presents clinically with patch, plaque and/or tumor stages, but can also evolve as erythroderma, which in turn is pathognomonic for SS. SS is characterized by a detectable tumor-cell burden (Sézary cells) in the peripheral blood consistent with advanced-stage disease and a poor prognosis. In early-stage disease of MF, which is the predominant form, the prognosis is generally favorable. However, in up to 30 % of patients, there is progression of skin lesions, which can ultimately lead to visceral involvement. The histological manifestation of MF can be subtle in early-stage disease and therefore a careful clinicopathological correlation is paramount. The treatment of MF/SS is dependent on the disease stage. Therapeutic options include both skin-directed and systemic regimens. Apart from allogeneic stem cell transplantation (alloSCT), there is as yet no curative therapy for MF/SS. Accordingly, the treatment approach is symptom oriented and aims to reduce the tumor burden and improve health-related quality of life. However, the therapeutic landscape for CTCL is constantly being expanded by the discovery of novel therapeutic targets.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Quality of Life; Sezary Syndrome; Skin Neoplasms
PubMed: 34541796
DOI: 10.1111/ddg.14610 -
Blood Dec 2021
Topics: Gene Expression Profiling; Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 34914833
DOI: 10.1182/blood.2021013433 -
International Journal of Molecular... Mar 2022Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic... (Review)
Review
Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic system. Cutaneous malignancies are usually affected by epigenetic changes. However, there is limited knowledge regarding the epigenetic changes associated with cutaneous lymphomas. In this review, we focused on cutaneous T-cell lymphomas such as mycosis fungoides, Sézary syndrome, and anaplastic large cell lymphoma. With regard to epigenetic changes, we summarize the detailed chemical modifications categorized into DNA methylation and histone acetylation and methylation. We also summarize the epigenetic modifications and characteristics of the drug for cutaneous T-cell lymphoma (CTCL). Furthermore, we discuss current research on epigenetic-targeted therapy against cutaneous T-cell lymphomas. Although the current method of treatment with histone deacetylase inhibitors does not exhibit sufficient therapeutic benefits in all cases of CTCL, epigenetic-targeted combination therapy might overcome this limitation for patients with CTCL.
Topics: Epigenesis, Genetic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 35408897
DOI: 10.3390/ijms23073538 -
Blood Advances Sep 2023The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and...
The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-sequencing of 26,411 CD3+CD4+ and CD26+/CD7+ and 33 841 CD3+CD4+ and CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome and mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment. Surprisingly, we identified ≥200 mutations in hematopoietic stem cells from multiple patients with Sézary syndrome. Mutations in key oncogenes were also present in peripheral Sézary cells, which also showed the hallmarks of recent thymic egression. Together our data suggest that CTCL arises from mutated lymphocyte progenitors that acquire TCRs in the thymus, which complete their malignant transformation in the periphery.
Topics: Humans; Sezary Syndrome; Dipeptidyl Peptidase 4; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Receptors, Antigen, T-Cell
PubMed: 37531660
DOI: 10.1182/bloodadvances.2022008562 -
Oncology Research and Treatment 2017
Topics: Drug Therapy; Humans; Mycosis Fungoides; Photochemotherapy; Radiotherapy Dosage; Radiotherapy, High-Energy; Sezary Syndrome; Skin Neoplasms
PubMed: 28423383
DOI: 10.1159/000475528 -
Cancers Jan 2023Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary... (Review)
Review
Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary cutaneous lymphoma. In about 25% of patients with mycosis fungoides, the disease may progress to higher stages. The pathogenesis and risk factors of progression in mycosis fungoides and Sézary syndrome are not yet fully understood. Previous works have investigated inter- and intrapatient tumor cell heterogeneity. Here, we overview the role of the tumor microenvironment of mycosis fungoides and Sézary syndrome by describing its key components and functions. Emphasis is put on the role of the microenvironment in promoting tumor growth or antitumor immune response, as well as possible therapeutic targets. We focus on recent advances in the field and point out treatment-related alterations of the microenvironment. Deciphering the tumor microenvironment may help to develop strategies that lead to long-term disease control and cure.
PubMed: 36765704
DOI: 10.3390/cancers15030746 -
Chinese Clinical Oncology Feb 2019Sezary syndrome (SS) is a primary cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, lymphadenopathy and leukemic involvement of the peripheral blood. The... (Review)
Review
Sezary syndrome (SS) is a primary cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, lymphadenopathy and leukemic involvement of the peripheral blood. The high relapse rates and a poor prognosis complicate its clinical course and treatment. The phenotypic characterization and genomic/transcriptomic approaches revealed high heterogeneity of Sezary cells, identifying a wide spectrum of biomarkers implicated in the development of this lymphoma. In this context, we discuss the major malignancy-related biomarkers reported in the literature for the diagnosis, prognosis and staging of SS. The hope for a single reliable diagnostic marker appears increasingly unrealistic, but the discovery of multiple potential biomarkers, with pathogenetic implications, paves the road to promising personalized therapies in SS.
Topics: Biomarkers; Humans; Prognosis; Sezary Syndrome
PubMed: 30525758
DOI: 10.21037/cco.2018.11.02 -
Cytometry. Part B, Clinical Cytometry Mar 2021
Topics: Antigens, CD; Flow Cytometry; Humans; Immunophenotyping; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 32083391
DOI: 10.1002/cyto.b.21872