-
The Australasian Journal of Dermatology May 2024
PubMed: 38693689
DOI: 10.1111/ajd.14300 -
Journal of the European Academy of... Apr 2024Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis...
BACKGROUND
Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response.
OBJECTIVE
To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab.
METHODS
We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL.
RESULTS
Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements.
CONCLUSION
Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.
PubMed: 38687283
DOI: 10.1111/jdv.20053 -
The Journal of Investigative Dermatology Apr 2024Advanced-stage cutaneous T-cell lymphomas (CTCLs) are notorious for their highly aggressive behavior, resistance to conventional treatments, and poor prognosis,...
Advanced-stage cutaneous T-cell lymphomas (CTCLs) are notorious for their highly aggressive behavior, resistance to conventional treatments, and poor prognosis, particularly when large-cell transformation occurs. PEG10 has been recently proposed as a potent driver for large-cell transformation in CTCL. However, the targeting of PEG10 continues to present a formidable clinical challenge that has yet to be addressed. In this study, we report an important post-translational regulatory mechanism of PEG10 in CTCL. USP9X, a deubiquitinase, interacted with and deubiquitinated PEG10, thereby stabilizing PEG10. Knockdown of USP9X or pharmacological targeting of USP9X resulted in a prominent downregulation of PEG10 and its downstream pathway in CTCL. Moreover, USP9X inhibition conferred tumor cell growth disadvantage and enhanced apoptosis in vitro, an effect that occurred in part through its regulation on PEG10. Furthermore, we demonstrated that inhibition of USP9X obviously restrained CTCL tumor growth in vivo and that high expression of USP9X is associated with poor survival in patients with CTCL. Collectively, our findings uncover USP9X as a key post-translational regulator in the stabilization of PEG10 and suggest that targeting PEG10 stabilization through USP9X inhibition may represent a promising therapeutic strategy for advanced-stage CTCL.
PubMed: 38677662
DOI: 10.1016/j.jid.2024.02.039 -
Journal of Fungi (Basel, Switzerland) Apr 2024While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or... (Review)
Review
While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical picture is attributed to the complex interplay of host characteristics (hygiene and aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance and species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions. Thus, a literature examination was performed to provide a comprehensive analysis on rare and atypical superficial mycosis as well as an update on certain fungal clinical manifestations and their significance. The research and standard data extraction were performed using PubMed, Medline, Scopus, and EMBASE databases, and a total of 222 articles were identified. This review covers published research findings for the past six months.
PubMed: 38667966
DOI: 10.3390/jof10040295 -
Frontiers in Cell and Developmental... 2024This review systematically describes the application of mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the... (Review)
Review
This review systematically describes the application of mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL's intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models' strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4 T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.
PubMed: 38665428
DOI: 10.3389/fcell.2024.1372881 -
Archives of Dermatological Research Apr 2024
Topics: Humans; Mycosis Fungoides; Signal Transduction; Skin Neoplasms; Cytokines; Treatment Outcome; Male; Female; Middle Aged; Phototherapy; Neoplasm Staging; Biomarkers, Tumor; Adult; Aged
PubMed: 38662241
DOI: 10.1007/s00403-024-02859-8 -
Actas Dermo-sifiliograficas Jun 2024Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and...
BACKGROUND AND OBJECTIVES
Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL.
MATERIAL AND METHOD
This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals.
RESULTS
A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported.
CONCLUSIONS
Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.
Topics: Humans; Bexarotene; Male; Female; Aged; Retrospective Studies; Middle Aged; Aged, 80 and over; Skin Neoplasms; Adult; Tetrahydronaphthalenes; Mycosis Fungoides; Sezary Syndrome; Spain; Lymphoma, T-Cell, Cutaneous; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38653368
DOI: 10.1016/j.ad.2024.04.017 -
Acta Dermatovenerologica Croatica : ADC Dec 2023Mycosis fugnoides (MF) is an indolent cutaneous T-cell lymphoma (CTLC) and is the most common of all cutaneous lymphomas. An increased risk for developing a second...
Mycosis fugnoides (MF) is an indolent cutaneous T-cell lymphoma (CTLC) and is the most common of all cutaneous lymphomas. An increased risk for developing a second primary malignancy in patients with CTCL has been described in several studies, with a range from 1.04 to 2.4 (1-4). Caucasian males are at higher risk for MF development. MF is often diagnosed at ages between 55 and 67 years, and second malignancy usually occurs 5 or 6 years after the diagnosis of MF was established (5). The most common second primary malignancies include non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung carcinoma, bladder carcinoma, and melanoma. Even though a higher incidence rate of all NHL was described in patients with MF (15/1000) in comparison with the general population (0.32/1000), there are still only a few cases of B-cell NHL following MF described in the literature (6,7). We describe a rare case of a patient with MF and simultaneous large cell transformation (LCT) and a small B-cell lymphocytic lymphoma/chronic lymphocytic leukemia (B-CLL). In 2017, an 82-year-old man previously treated for MF presented with two fast growing tumorous lesions with ulceration on the right tight (Figure 1). A biopsy was performed, and a diagnosis of MF with LCT was established (Figure 2). During hospitalization, mild leukocytosis (12.2 x109 L-1), lymphocytosis (64%, total count of 7.81 x109 L-1), and anemia were found. Bone marrow biopsy was not performed due to low pain threshold. Bone marrow aspirate showed 70% of atypical lymphocytes and few "smudged" cells. Immunophenotyping by flow cytometry detected 49% monoclonal kappa+ B-cells with phenotypic features typical for B-CLL (CD5+, CD23+, kappa +). Of overall bone marrow cells, the ratio of monoclonal kappa + B-cells with the B-CLL phenotype was 21%. Immunophenotyping of peripheral blood showed up to 50% monoclonal kappa+ B-cells with phenotypic features typical for B-CLL (CD5+, CD23+, kappa +). Of overall peripheral blood cells, the ratio of monoclonal kappa+ B-cells with the B-CLL phenotype was 28%. Multi-sliced computed tomography was within normal ranges. A flow cytometry showed lymphocytes with phenotypic findings for CD20+ B-CLL. A diagnosis of MF with LCT (CD30+) clinical grade IIB (T3, N0, M0) and B-CLL was established. The patient was treated with fractionated superficial irradiation that resulted in applanation and regression of the tumorous lesions. No hematologic treatment was indicated other than regular follow-up. On dermatologic follow up for 2 years, the patient was stable, with no active skin lesions and no progression of MF. The patient was subsequently lost to follow-up. This is a rare case of MF with LCT and B-CLL occurring simultaneously. Large cell transformation in patients with MF can occur in 20-55% of advanced MF, as in our case, and this something physicians must be aware of, so repeated biopsies are advised (8). We also should keep in mind that patients with MF are at higher risk of developing a second malignancy. Of those second malignancies, a coexistence of lymphoproliferative disorders in two lineages, T-cell and B-cell, such as CTCL and B-CLL, is very uncommon, and only a few cases have been published (6,7,10). In most of these cases, CTCL preceded B-CLL, and with the only established explanation being increased risk of second malignancy in patients with CTCL (3,5,10). Other explanatory hypotheses include neoplastic stem cells, a genetic predisposition to malignancy, the use of immunosuppressive agents for the treatment for a first neoplasm, viral agents, and modulation of the B-cell system by monoclonal T-cell proliferation (1,5,6,9,10). Regular follow-up is mandatory for all patients with CTCL as well as MF, in order to identify the disease progression but for the timely detection of second malignancies.
Topics: Humans; Male; Cell Transformation, Neoplastic; Leukemia, Lymphocytic, Chronic, B-Cell; Mycosis Fungoides; Skin Neoplasms; Aged, 80 and over
PubMed: 38651850
DOI: No ID Found -
Acta Dermatovenerologica Croatica : ADC Dec 2023Cutaneous T-cell lymphomas (CTCLs) are rare diseases characterized by infiltration of malignant T-cells into the skin. We evaluated the prevalence, epidemiology, and...
INTRODUCTION
Cutaneous T-cell lymphomas (CTCLs) are rare diseases characterized by infiltration of malignant T-cells into the skin. We evaluated the prevalence, epidemiology, and therapy of CTCLs, focusing on its most well-known subtypes, namely mycosis fungoides (MF) and Sézary syndrome (SS).
PATIENTS AND METHODS
We retrospectively analyzed the medical data of patients with a histologically confirmed diagnosis of CTCL presenting to our outpatient department during a 5-year period from January 2015 to December 2019.
RESULTS
We evaluated the files of 102 patients, of whom 67% were men and 33% women. The overall mean age was 59.1±14.1 (24-86) years. Ninety-two patients (90%) were diagnosed with MF and ten patients (10%) with SS. According to ISCL/EORTC, the majority of patients initially classified as stage IA (34%) and IB (45%). Disease frequency decreased at advanced stages (II: 4%; III: 7%; IV: 10%). Forty-five patients (44.1%) received only skin-directed therapy (SDT). Twenty patients (19.6%) progressed from SDT to systemic therapy (ST). Thirty-seven patients (36.3%) received ST combined with SDT (TS) from the start of treatment. Overall, fifty different therapeutic approaches of TS were initiated due to lack of response to therapy or disease progression.
CONCLUSION
Management of CTCLs aims to maintain patient quality of life while minimizing side-effects. As CTCLs are usually incurable diseases, the focus of treatment is on symptom control and prevention of disease progression. Due to the large patient group and the long observation period, our study allows for a valid evaluation of the frequency and therapy of MF and SS in a university outpatient clinic in Germany. We favor topical therapies in early stages with more invasive therapies in advanced stages.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Aged; Adult; Skin Neoplasms; Aged, 80 and over; Lymphoma, T-Cell, Cutaneous; Sezary Syndrome; Mycosis Fungoides; Young Adult
PubMed: 38651844
DOI: No ID Found