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Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T‐cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T‐cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF. [ABSTRACT FROM AUTHOR]

Background Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon (IFN)-α (subtypes 2a and 2b) has been used to treat MF/SS since 1984; however, its production was recently stopped. The recombinant pegylated (PEG) form of IFN-α-2a remains the only alternative IFN treatment, although it has not been approved for use in MF/SS. Objectives To assess the effectiveness and safety of PEG-IFN-α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in a real-world setting. Methods We conducted an international, multicentre retrospective study of patients with MF and SS (of any stage) treated with PEG-IFN-α-2a from July 2012 to February 2022. Patients were included across 11 centres in 10 countries. The primary endpoints were to determine the TTNT of PEG-IFN-α-2a and adverse events (AEs) in MF/SS. Results In total, 105 patients were included [mean (SD) age 61 (13.1) years]; 42 (40.0%) had stage IA–IIA and 63 (60.0%) had stage IIB–IVB disease. PEG-IFN-α-2a was combined with other therapies in 67 (63.8%) patients, most commonly with extracorporeal photopheresis (36%) and bexarotene (22%). Patients with stage I–IIA disease achieved an overall response rate (ORR) of 57%; the ORR in those with stage IIB–IVB disease was 51%. Combination treatment resulted in a median TTNT of 10.4 months (range 0.6–50.7) vs. 7.0 months (range 0.7–52.4) for those who received monotherapy (P < 0.01). Overall, the mean (SD) TTNT was 9.2 (10.6) months and the ORR was 53.3% (n = 56). A complete response was seen in 13% of patients and a partial response in 40%. AEs were described in 68.6% (n = 72) of patients. Flu-like symptoms (n = 28; 26.7%), lymphopenia (n = 24; 22.9%) and elevated liver function (n = 10; 9.5%) were the most frequently reported. Grade 3–4 AEs were reported in 23 (21.9%) patients, mostly related to myelosuppression. Conclusions PEG-IFN-α-2a for MF/SS resulted in an ORR of 53.3% and a mean (SD) TTNT of 9.2 (10.6) months. Combination regimens were superior to monotherapy and doses of 180 µg PEG-IFN-α-2a weekly were related to a higher ORR. [ABSTRACT FROM AUTHOR]

Mogamulizumab is a first‐in‐class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration authorisation for mycosis fungoides and Sézary syndrome following failure of at least one previous course of systemic therapy and now is available in Europe. One of the most common treatment‐related side effects observed has been the mogamulizumab‐associated rash (MAR), which affects up to a quarter of patients and is the most frequent adverse event leading to drug discontinuation. The aim of this study is to perform a systematic review of the literature on patients diagnosed with MAR and other mogamulizumab‐related cutaneous events to describe the clinical and histological characteristics, the management in clinical practice and to assess whether these events have prognostic implications. In total, 2073 records were initially identified through a literature search, 843 of which were duplicates. After screening for eligibility and inclusion criteria, 49 articles reporting mogamulizumab‐associated cutaneous events were included. Totally, 1516 patients were retrieved, with a slight male prevalence as for the available data (639 males and 570 females, i.e. 52.9% vs. 47.1%). Regarding the reported clinicopathological findings of the cutaneous reactions, the five most common patterns were spongiotic/psoriasiform dermatitis (22%), eruptions characterized by the presence of papules and/or plaques (16.1%), cutaneous granulomatosis (11.4%), morbilliform or erythrodermic dermatitis (9.4%) and photodermatitis (7.1%). Our results highlight how the majority of the reported cutaneous adverse events on mogamulizumab are of mild‐to‐moderate entity and generally manageable in clinical practice, though prompt recognition is essential and case‐by‐case assessment should be recommended. Future research will need to focus on the MAR prognostic implications and to identify genomic and molecular markers for a more rapid and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background: T-cell leukemia originating from large granular lymphocytes (T-LGL leukemia) is a rare lymphoid neoplasia characterized by clonal proliferation of large granular T lymphocytes expressing αβ or γδ T-cell receptor (TCR) on the cell membrane. γδT-LGL leukemia, accounting for approximately 17% of all T-LGL leukemia cases, is associated with autoimmune diseases. However, the features of γδT-LGL leukemia in patients with rheumatologic diseases are still insufficiently characterized. Methods: In this retrospective study, 15 patients with rheumatologic diseaseassociated γδT-LGL leukemia were included. The patients were obtained from a single center from 2008 to 2023. Data related to clinical characteristics and rheumatologic diagnoses were collected. Immunophenotype evaluations as well as T-lymphocyte clonality (based on TCR-γ, TCR-β, and TCR-δ gene rearrangements), and signal transducer and activator of transcription (STAT) three and STAT5B mutation analyses (by next-generation sequencing) were performed on blood, bone marrow, and spleen samples. Results: All but one patient had rheumatoid arthritis (RA). In 36% of patients, manifestations of γδT-LGL leukemia were present before or concurrently with clinical manifestations of RA. Splenomegaly was observed in 60% of patients and neutropenia (<1.5 × 109/L) was detected in 93% of cases. CD4-/CD8- and CD4-/CD8+ subtypes were detected in seven cases each. Mutations in STAT3 were detected in 80% of patients; however, STAT5B mutations were not detected. Evaluations of T-cell clonality and variant allele frequencies at STAT3 in the blood, bone marrow, and spleen tissue revealed an unusual variant of CD4-/CD8- γδT-LGL leukemia with predominant involvement of the spleen, involvement of the bonemarrow to a less extent, and no tumor cells in peripheral blood. Conclusion: The mechanism by which γδT-LGL leukemia may induce the development of RA in some patients requires further investigation. Cases of RA-associated γδT-LGL leukemia with neutropenia and splenomegaly but no detectable tumor-associated lymphocytes in peripheral blood (the so-called splenic variant of T-LGL leukemia) are difficult to diagnose and may be misdiagnosed as Felty syndrome or hepatosplenic T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Hypopigmented mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma, a type of extranodal non-Hodgkin lymphoma. This report presents the case of a 9-year-old boy with a 2-year history of asymptomatic, hypopigmented skin lesions that were resistant to topical treatment. He was initially treated for a fungal skin infection and had received multiple courses of topical antifungals and steroids but showed no improvement, which led to further evaluation and a referral to a dermatologist. A skin biopsy was performed, and the diagnosis of hypopigmented MF was confirmed through skin histopathology and immunohistochemistry study. His lesions responded well to cycles of narrowband ultraviolet B phototherapy, showing almost complete clearance after 4 months without any side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Mycosis fungoides and Sézary syndrome can impair multiple dimensions of health-related quality of life due to physical symptoms including pruritus, treatment side effects, time and financial burdens associated with high healthcare utilization, and psychological distress. There are several areas of unmet needs around health-related quality of life in this population, and the optimal way to measure health-related quality of life isn't yet clear. Mycosis fungoides (MF) and Sézary syndrome (SS) can impair multiple dimensions of health-related quality of life (HRQoL). Currently, there is no standardized assessment tool for measuring HRQoL in patients with MF/SS. Here, we describe the existing literature on multiple dimensions of HRQoL in MF/SS with a special focus on the gaps in the current knowledge and identify future directions necessary to assess the HRQoL of patients with this disease. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Archives of Dermatological Research. The letter discusses the spatiotemporal changes and functional alterations of T-cell substates gene expression during the progression of mycosis fungoides (MF), a type of cutaneous T-cell lymphoma (CTCL). The authors conducted a mass cytometry experiment comparing the proportion difference of T-cell substates in MF patients' skin and lymphatic tissues and peripheral blood. They found that CD8+ T-cell exhaustion and CD4+ T helper cell type-1 (Th1) were significantly higher in skin tissues compared to lymphatic tissues and peripheral blood. The authors also analyzed publicly available single-cell RNA-seq datasets to identify landmark genes affecting the dynamic changes of T-cell substates during the progression of MF. They concluded that this study expands our understanding of MF disease and provides potential biomarkers for future immunotherapy. [Extracted from the article]

Background Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce. Objectives To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP. Methods This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation. Results Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months–18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0–14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0–19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01–88.99). Conclusions We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP. [ABSTRACT FROM AUTHOR]

Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders. In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome. Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology. [ABSTRACT FROM AUTHOR]

Summary: Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second‐line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab‐associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: We present a case of multiple tumefactive demyelinating lesions (TDLs) emerging 24 months after the second cycle of alemtuzumab treatment. Methods: A woman with relapsing-remitting multiple sclerosis (MS) discontinued fingolimod treatment due to gestational desire, which resulted in a severe disease exacerbation. Alemtuzumab was initiated, accompanied by regular clinical, radiological, and immunological monitoring. Results: She relapsed prior to the second cycle, exhibiting 12 T1Gd+ lesions, and peripheral blood showed an increase in B-cells and a decrease in T-cells. At 24 months following the second cycle, she developed cognitive impairment and multiple T1Gd+ lesions, including TDLs, were evident on the brain MRI. We found not only an increase in B-cells but also in Th1 central memory cells. Th1/Th17 cells increased 3 months before the detection of TDLs. Conclusions: TDLs can appear 24 months after the second cycle of alemtuzumab treatment in MS. The increase in Th1/Th17 cells could be a candidate biomarker for TDLs in alemtuzumab-treated MS patients. [ABSTRACT FROM AUTHOR]

Posttransplantation primary cutaneous T‐cell lymphomas (PT‐CTCL) are a rare complication of sustained immunosuppression in the posttransplant setting. When present, PT‐CTCLs are typically EBV− and exhibit features of mycosis fungoides/Sézary syndrome or CD30+ lymphoproliferative disorders. We present a case of a 75‐year‐old individual who developed skin lesions 30 years after liver transplantation. Pathologic evaluation of the skin biopsy revealed involvement by a clonal, EBV+ T‐cell population of gamma/delta lineage with no evidence of systemic disease. Comprehensive genomic profiling was performed, confirming focal one‐copy loss of 6q23.3, altogether consistent with the extremely rare and unusual diagnosis of primary cutaneous EBV+ extranodal NK/T‐cell lymphoma of gamma/delta T‐cell lineage in the posttransplantation setting. [ABSTRACT FROM AUTHOR]

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered. [ABSTRACT FROM AUTHOR]

A phase 1 study was conducted to investigate the combination of interleukin-15 (IL-15) and avelumab in patients with relapsed or refractory T-cell lymphoma. IL-15 is known to stimulate NK and T-cell functions, and previous studies have shown that it can enhance the activity of anti-tumor monoclonal antibodies. Avelumab is an anti-PDL1 antibody that functions as an immune checkpoint inhibitor. The study enrolled eight patients, and although the maximum tolerated dose was not established due to early closure, two patients with PTCL-NOS had a partial response and two had stable disease. The results of this study can inform ongoing efforts to improve immunotherapy for T-cell lymphomas. [Extracted from the article]

Platelets engage in HIV-1 infection by interacting with immune cells, which has been realized broadly. However, the potential interaction between platelets and CD8+ T cells remains unidentified. Here, treatment-naive individuals with HIV-1, complete immunological responders to antiretroviral therapy, and healthy controls were enrolled. First, we found that treatment-naive individuals with HIV-1 had low platelet numbers and high CD8+ T-cell counts when compared with complete immunological responders to antiretroviral therapy and healthy controls, leading to a low platelet/CD8+ T-cell ratio in peripheral blood, which could effectively differentiate the status of HIV-1 infection. Moreover, cytokines that may have been derived from platelets were higher in the plasma of people with HIV-1 despite viral suppression. Furthermore, we demonstrated that platelet–CD8+ T-cell aggregates were elevated in treatment-naive individuals with HIV-1, which positively correlated with HIV-1 viral load but negatively correlated with CD4+ T-cell count and CD4/CD8 ratio. Finally, we revealed that platelet–CD8+ T-cell aggregates correlate with enhanced activation/exhaustion and pyroptosis/apoptosis compared with free CD8+ T cells. Moreover, platelet-induced caspase 1 activation of CD8+ T cells correlated with IL-1β and IL-18 plasma levels. In brief, we reveal the importance of platelets in HIV-1 infection, which might secrete more cytokines and mediate CD8+ T-cell phenotypic characteristics by forming platelet–CD8+ T-cell aggregates, which are related to poor prognosis. [ABSTRACT FROM AUTHOR]

Copyright of Conocimiento Enfermero is the property of Colegio Oficial de Enfermeria de Madrid and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article presents a study on the outcomes of extracorporeal photopheresis (ECP) treatment in Black patients with cutaneous T-cell lymphoma (CTCL). The study found that there were no significant differences in response rates or duration of response between Black and White patients. However, it did identify certain factors that may be associated with disease progression in Black patients. The study suggests that these patients should be closely monitored and alternative treatments should be considered if there are signs of disease progression. The article was authored by researchers from Johns Hopkins University School of Medicine and is available as an Open Access article. [Extracted from the article]

Abstract Cutaneous T‐cell lymphomas (CTCLs) are unique non‐Hodgkin lymphomas due to the proliferation of skin‐homing T cells. Sezary syndrome (SS), a subtype of CTCL, typically presents as erythroderma with specific blood involvement and seldomly evolves from tumor‐stage mycosis fungoides (MF). The article examines the case of a 62‐year‐old female patient who developed SS while under atezolizumab treatment for tumor‐stage transformed MF. Postdiagnosis, she underwent treatments including topical corticosteroids, phototherapy, and other drug regimens, experiencing both complete responses and relapses over the years. Three years postdiagnosis, her condition deteriorated with facial tumor lesions, confirmed as MF. Despite multiple treatments, including oral drugs, radiation therapy, and a range of other therapeutic agents, her condition did not show sustained improvement. The patient was then administered atezolizumab, an antibody targeting programmed death ligand 1 (PD‐L1). Although initial results saw a disappearance of her skin tumors, the subsequent cycles led to symptoms consistent with stage IVA1 SS, coupled with an evident shift in malignant T‐cell clone dominance. Atezolizumab, a humanized monoclonal antibody, impedes the interaction of PD‐L1 with its receptor PD1, which is notably overexpressed in malignant T‐cells of SS. This case illustrates the emergence of SS during the course of atezolizumab treatment for a transformed MF condition, underlining the potential risks and complexities in using PD‐L1 inhibitors for treating CTCL.