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The Journal of Dermatology Feb 2022Mycosis fungoides (MF) and Sézary syndrome (SS) are representative cutaneous lymphomas. In their early stage, a small number of tumor cells and a large number of... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are representative cutaneous lymphomas. In their early stage, a small number of tumor cells and a large number of non-malignant cells form a Th1-dominant tumor microenvironment. Increase in malignant T cells is accompanied by a decrease in CD8-positive T cells, with a shift toward a Th2-dominant milieu in advanced-stage lesions. The etiologies of MF/SS are diverse, and the underlying pathogenetic mechanisms are yet to be elucidated. Advanced MF/SS is known to be highly sensitive to Staphylococcus aureus, and the majority of deaths are caused by severe infections. The susceptibility to infection is associated with barrier dysfunction and immunosuppression, which are the main symptoms of MF. In recent years, skin-colonizing S. aureus has been identified to not only cause severe infections but also play an important role in the pathogenesis of MF/SS. Staphylococcal superantigens activate the proliferation of tumor cells and induce CD25 upregulation, FOXP3 expression, IL-17 expression, and miR-155 expression. Alpha-toxin eliminates non-neoplastic CD4-positive cells and CD8-positive cells and plays a major role in tumor cell selection. Lipoprotein may also be associated with the induction of Th2-dominant milieu. Antibiotic therapy for S. aureus eradication has been reported to cause considerable clinical improvement in the majority of individuals with advanced cutaneous T-cell lymphoma. Therefore, S. aureus may be a novel target for the treatment of advanced-stage MF/SS in the future.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Staphylococcus aureus; Tumor Microenvironment
PubMed: 34927279
DOI: 10.1111/1346-8138.16288 -
Clinical and Experimental Medicine Dec 2023Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by clonal accumulation of neoplastic T-lymphocytes in the skin. Severe pruritus, one of the most common and distressing symptoms in primary CTCL, can significantly impair emotional well-being, physical functioning, and interpersonal relationships, thus greatly reducing quality of life. Unfortunately, effectively managing pruritus remains challenging in CTCL patients as the underlying mechanisms are, as of yet, not fully understood. Previous studies investigating the mechanisms of itch in CTCL have identified several mediators and their corresponding antagonists used for treatment. However, a comprehensive overview of the mediators and receptors contributing to pruritus in primary CTCL is lacking in the current literature. Here, we summarize and review the mediators and receptors that may contribute to pruritus in primary CTCL to explore the mechanisms of CTCL pruritus and identify effective therapeutic targets using the PubMed and Web of Science databases. Studies were included if they described itch mediators and receptors in MF and SS. Overall, the available data suggest that proteases (mainly tryptase), and neuropeptides (particularly Substance P) may be of greatest interest. At the receptor level, cytokine receptors, MRGPRs, and TRP channels are most likely important. Future drug development efforts should concentrate on targeting these mediators and receptors for the treatment of CTCL pruritus.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Quality of Life; Skin Neoplasms; Mycosis Fungoides; Pruritus; Sezary Syndrome
PubMed: 37555911
DOI: 10.1007/s10238-023-01141-x -
BMC Health Services Research Feb 2021Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.
BACKGROUND
Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.
METHODS
In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998-2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland.
RESULTS
The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998-2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up.
CONCLUSIONS
The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998-2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.
Topics: Delivery of Health Care; Finland; Humans; Mycosis Fungoides; Prevalence; Sezary Syndrome; Skin Neoplasms
PubMed: 33618714
DOI: 10.1186/s12913-021-06109-9 -
Frontiers in Immunology 2023Mycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of...
BACKGROUND
Mycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor of mast cell (MC) responsible for the IgE-independent non-histaminergic itch, has been shown in lesional skin of patients with pruritic skin diseases, including chronic urticaria, prurigo, and mastocytosis. As of yet, limited knowledge exists regarding the MRGPRX2 expression in the skin of patients with MF.
OBJECTIVES
To investigate the number of MRGPRX2-expressing (MRGPRX2+) cells in the skin of patients with MF and its correlation with clinical and laboratory characteristics of the disease.
METHODS
MRGPRX2 was analyzed in lesional and non-lesional skin of MF patients and healthy skin tissues by immunohistochemistry. Co-localization of MRGPRX2 with the MC marker tryptase was assessed by immunofluorescence. Public single-cell RNAseq data was reanalyzed to identify the MRGPRX2 expression on the distinct cell types.
RESULTS
In lesional skin of MF patients, MRGPRX2+ cell number was higher than in non-lesional skin and healthy control skin (mean:15.12 vs. 6.84 vs. 5.51 cells/mm, p=0.04), and correlated with MC numbers (r=0.73, p=0.02). MC was the primary cell type expressing MRGPRX2 in MF patients. The ratio of MRGPRX2+ MCs to MRGPRX2+ cells in lesional and non-lesional skin correlated with the severity of disease (r=0.71, p=0.02 and r=0.67, p=0.03, respectively).
CONCLUSIONS
Our findings point to the role of MRGPRX2 and MC in the pathogenesis of MF that should be investigated in further studies.
Topics: Humans; Mycosis Fungoides; Skin; Receptors, G-Protein-Coupled; Skin Neoplasms; Pruritus; Cell Count; Nerve Tissue Proteins; Receptors, Neuropeptide
PubMed: 38022672
DOI: 10.3389/fimmu.2023.1197821 -
Acta Dermato-venereologica Mar 2022Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous...
Aggressive primary cutaneous T-cell lymphomas include advanced-stage mycosis fungoides (stage ≥ IIB mycosis fungoides), Sézary syndrome, gamma/delta cutaneous lymphoma, nasal type lymphoma, aggressive epidermotropic CD8+ T-cell lymphoma and some cutaneous lymphomas not otherwise specified. To evaluate their long-term prognosis, we conducted a retrospective cohort study of 85 patients diagnosed between 2005 and 2020 with advanced-stage mycosis fungoides (n = 48), Sézary syndrome (n = 28) or aggressive non-mycosis fungoides/Sézary syndrome subtypes (n = 9). The median survival times in these 3 groups were 118.7, 45.7 and 11.2 months, respectively, and the 5-year survival rates were 55.3%, 27.8% and 33.3%, respectively. Multivariate analyses in patients with mycosis fungoides/Sézary syndrome identified age ≥ 70 years, Eastern Cooperative Oncology Group Performance Status ≥ 2, and the high-risk group according to the Cutaneous Lymphoma International Consortium prognostic model, as adverse prognostic factors. Seven patients in this mycosis fungoides/ Sézary syndrome group were in complete long-term remission after treatment with bexarotene, including 4 patients living without any treatment for 16-101 months.
Topics: Aged; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Prognosis; Retrospective Studies; Sezary Syndrome; Skin Neoplasms
PubMed: 35083494
DOI: 10.2340/actadv.v102.1087 -
Acta Dermato-venereologica Sep 2021Mycosis fungoides is a type of cutaneous T-cell lymphoma, which accounts for the majority of cases of cutaneous T-cell lymphoma. Mycosis fungoides can be classified as...
Mycosis fungoides is a type of cutaneous T-cell lymphoma, which accounts for the majority of cases of cutaneous T-cell lymphoma. Mycosis fungoides can be classified as early-stage (IA-IIA) or late-stage (IIB or greater) disease. In early-stage mycosis fungoides, skin-directed therapies are commonly used to manage the disease. Chlormethine, or mechlorethamine, is a topical chemotherapeutic, which has been in use for over 60 years. In 2013, the US Food and Drug Administration approved chlormethine/mechlorethamine gel (Valchlor®) for treatment of stage IA and IB mycosis fungoides. Chlormethine/mechlorethamine gel is an effective therapy; however, its use may be limited by the development of adverse cutaneous reactions. Off-label dosing modifications, as well as co-administration of topical steroids and an aggressive moisturization regimen, can be used to reduce these side-effects. We report here 4 cases of mycosis fungoides treated with chlormethine/mechlorethamine gel at the Comprehensive Skin Cancer Center at Columbia University Irving Medical Center, which provide insights into the use of this therapy in clinical practice.
Topics: Antineoplastic Agents, Alkylating; Humans; Mechlorethamine; Mycosis Fungoides; Skin Neoplasms; Universities
PubMed: 34436621
DOI: 10.2340/00015555-3911 -
Journal of Drugs in Dermatology : JDD Dec 2023Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to...
BACKGROUND
Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to current standard-of-care treatments. Objective: To determine the real-world efficacy and adverse effects of BV use in patients with mycosis fungoides (MF) who were treated with BV at Atrium Health Wake Forest Baptist Medical Center.
METHODS
Study staff performed a retrospective chart review of patients diagnosed with MF who were prescribed BV at Atrium Health Wake Forest Baptist Comprehensive Cancer Center.
RESULTS
Regardless of their response to BV, all patients in our cohort had higher CD30 positivity on subsequent biopsies compared to their initial skin biopsy. Conclusions: Improved understanding of appropriate CD30 testing and evaluation will allow for quicker invention of patients with BV responsive CTCL. J Drugs Dermatol. 2023;22(12):e33-e34. doi:10.36849/JDD.6981e.
Topics: Humans; Brentuximab Vedotin; Retrospective Studies; Immunoconjugates; Skin Neoplasms; Ki-1 Antigen; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous
PubMed: 38051830
DOI: 10.36849/JDD.6981 -
Acta Dermatovenerologica Croatica : ADC Sep 2019Mycosis fungoides is the most common primary cutaneous T cell lymphoma, characterized by erythematous patches and plaque lesions with slow progression to cutaneous...
Mycosis fungoides is the most common primary cutaneous T cell lymphoma, characterized by erythematous patches and plaque lesions with slow progression to cutaneous tumors or extracutaneous involvements in some patients. We aimed to evaluate the clinical characteristics, treatment responses, disease courses, and mortality rates of our MF cases. The data of 100 patients with MF were retrospectively examined from medical records in our clinic between January 2005 and January 2015. Demographic and clinical characteristics of the patients, disease stage, treatment protocols, response to treatment, recurrence, progression, and mortality rates were recorded. The male to female ratio in patients was 1.2. Mean age at onset of disease was 46, and duration of disease ranged from one to 42 years. At time of diagnosis 31 patients were at stage 1A, 31 at stage 1B, 30 at stage 2A, 2 at stage 2B, 1 at stage 3, and 5 at stage 4. Stable disease was observed in 35% of patients, progression in 10%, relapse in 27%, and complete response in 28%. Large cell transformation was found in 3 patients and additional malignity in 11. Thirty-seven patients (37%) were still surviving disease-free. 10 patients had died, three of them due to disease-related conditions. The most common first-line therapy in our study was phototherapy. It was applied to 87% of patients from stage 1A. Our results are generally consistent with current literature, but disease progression and disease-specific mortality rates were significantly lower than the literature, probably due to early phototherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Phototherapy; Retrospective Studies; Skin Neoplasms; Survival Rate; Turkey; Young Adult
PubMed: 31542058
DOI: No ID Found -
Journal of the European Academy of... Sep 2023Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from... (Review)
Review
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from early-stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health-related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem-cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment-related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin-directed therapies (SDTs) as first-line treatment for early-stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid-alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro-environment, in the specific context of MF treatment.
Topics: Humans; Mechlorethamine; Quality of Life; Mustard Gas; Mycosis Fungoides; Skin Neoplasms; Tumor Microenvironment
PubMed: 37262305
DOI: 10.1111/jdv.19237 -
Dermatologie (Heidelberg, Germany) Oct 2022Mycosis fungoides as the most common type and Sézary syndrome as a leukemic variant belong to the rare group of cutaneous T‑cell lymphomas. Both diseases are... (Review)
Review
Mycosis fungoides as the most common type and Sézary syndrome as a leukemic variant belong to the rare group of cutaneous T‑cell lymphomas. Both diseases are considered incurable and show a chronic course. Since there is no curative treatment, maintaining quality of life and relief of symptoms should be important elements when treating patients with mycosis fungoides and Sézary syndrome. Pruritus, which is a common and burdensome symptom of cutaneous T‑cell lymphoma, may negatively impact quality of life. Pruritus and quality of life can be assessed with established measurement tools. Consistent recording enables physicians to recognize restrictions in physical and psychosocial aspects of quality of life early so that therapy can be adapted.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Pruritus; Quality of Life; Sezary Syndrome; Skin Neoplasms
PubMed: 36074143
DOI: 10.1007/s00105-022-05049-7