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Journal of Clinical Medicine Jan 2024Subacute cutaneous lupus erythematosus (SCLE) is a condition that might pose a diagnostic challenge. The aim of this study was to assess the usefulness of...
Dermoscopy for the Differentiation of Subacute Cutaneous Lupus Erythematosus from Other Erythematous Desquamative Dermatoses-Psoriasis, Nummular Eczema, Mycosis Fungoides and Pityriasis Rosea.
Subacute cutaneous lupus erythematosus (SCLE) is a condition that might pose a diagnostic challenge. The aim of this study was to assess the usefulness of videodermoscopy in the differentiation of SCLE from other erythematous-desquamative dermatoses. Consecutive patients with SCLE ( = 27), psoriasis ( = 36), nummular eczema ( = 30), mycosis fungoides ( = 26), and pityriasis rosea ( = 20) referred to our Department of Dermatology were recruited for this study. A representative lesion was visualized using a Canfield D200 Videodermatoscope (Canfield Scientific GmbH, Bielefeld, Germany) and evaluated for the following parameters: vessels (morphology and distribution), scales (color and distribution), follicular findings, colors and morphologies, and presence of specific clues. SCLE was predominantly characterized by a polymorphous vascular pattern (92.6%) of unspecific distribution (92.6%) over a pink-red background (74.1%). Gray-brown dots were present in 10 (37.0%) cases, and pigmentation was noted in 15 (55.6%) patients, including peripheral pigmentation in 7 (25.9%) patients. Videodermoscopic evaluation showed significant differences between SCLE and psoriasis, which was characterized by regularly distributed dotted vessels. Although some common dermoscopic features with MF were noted, the presence of yellow structureless areas and red dots/globules favored the diagnosis of MF. In conclusion, a polymorphic vascular pattern, especially in association with gray-brown dots and/or peripheral pigmentation, is a valuable clue for the differentiation of SCLE from other erythematous-desquamative dermatoses.
PubMed: 38276083
DOI: 10.3390/jcm13020577 -
Frontiers in Medicine 2023Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma.... (Review)
Review
Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients treated with chlormethine gel combined with phototherapy ( = 5), retinoids ( = 16), or mogamulizumab ( = 3) are presented. These different combination regimens showed promising results. Most patients had a complete or partial response following treatment and the combinations were well-tolerated over extended treatment periods. Patients receiving chlormethine gel with retinoids had long-term periods of remission, even after treatment discontinuation. Durations of response of up to 3 years were observed in these patients. This long-term disease control may be the result of disease-modifying effects of chlormethine. Previous studies have shown targeted reductions in malignant T-cell clones in patients treated with chlormethine gel as well as improved post-treatment responses. Further research is needed to determine the effectiveness and safety of combination treatment regimens with chlormethine gel and to assess the impact chlormethine gel has on disease control.
PubMed: 38274457
DOI: 10.3389/fmed.2023.1308491 -
Nature Communications Jan 2024Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements...
Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements in the treatment of hematopoietic malignancies, particularly blood cancers. Yet their impact is constrained against tumors of hematopoietic origin manifesting in the skin. In this study, we employ a clonality-supervised deep learning methodology to dissect key pathological features implicated in mycosis fungoides, the most common cutaneous T-cell lymphoma. Our investigations unveil the prominence of the IL-32β-major histocompatibility complex (MHC)-I axis as a critical determinant in tumor T-cell immune evasion within the skin microenvironment. In patients' skin, we find MHC-I to detrimentally impact the functionality of natural killer (NK) cells, diminishing antibody-dependent cellular cytotoxicity and promoting resistance of tumor skin T-cells to cell-surface targeting therapies. Through murine experiments in female mice, we demonstrate that disruption of the MHC-I interaction with NK cell inhibitory Ly49 receptors restores NK cell anti-tumor activity and targeted T-cell lymphoma elimination in vivo. These findings underscore the significance of attenuating the MHC-I-dependent immunosuppressive networks within skin tumors. Overall, our study introduces a strategy to reinvigorate NK cell-mediated anti-tumor responses to overcome treatment resistance to existing cell-surface targeted therapies for skin lymphoma.
Topics: Humans; Mice; Female; Animals; Up-Regulation; Mycosis Fungoides; Killer Cells, Natural; Lymphoma, T-Cell, Cutaneous; Proteins; Skin Neoplasms; Histocompatibility Antigens; Major Histocompatibility Complex; Histocompatibility Antigens Class I; Tumor Microenvironment
PubMed: 38272918
DOI: 10.1038/s41467-024-45083-8 -
Scientific Reports Jan 2024Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Despite having a wide variety of therapeutic agents available for the treatment of...
Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Despite having a wide variety of therapeutic agents available for the treatment of MF, patients often suffer from a significant decrease in quality of life and rarely achieve long-term remission or complete cure, highlighting a need to develop novel therapeutic agents for this disease. The present study was undertaken to evaluate the efficacy of a novel anti-tumor agent, GZ17-6.02, which is composed of curcumin, harmine, and isovanillin, against MF in vitro and in murine models. Treatment of HH and MyLa cells with GZ17-6.02 inhibited the growth of both cell lines with IC50 ± standard errors for growth inhibition of 14.37 ± 1.19 µg/mL and 14.56 ± 1.35 µg/mL, respectively, and increased the percentage of cells in late apoptosis (p = .0304 for HH; p = .0301 for MyLa). Transcriptomic and proteomic analyses revealed that GZ17-6.02 suppressed several pathways, including tumor necrosis factor (TNF)-ɑ signaling via nuclear factor (NF)-kB, mammalian target of rapamycin complex (mTORC)1, and Pi3K/Akt/mTOR signaling. In a subcutaneous tumor model, GZ17-6.02 decreased tumor volume (p = .002) and weight (p = .009) compared to control conditions. Proteomic analysis of tumor samples showed that GZ17-6.02 suppressed the expression of several proteins that may promote CTCL growth, including mitogen-activated protein kinase (MAPK)1, MAPK3, Growth factor receptor bound protein (GRB)2, and Mediator of RAP80 interactions and targeting subunit of 40 kDa (MERIT)40.
Topics: Humans; Animals; Mice; Phosphatidylinositol 3-Kinases; Proteomics; Quality of Life; Gene Expression Profiling; Mycosis Fungoides; Antineoplastic Agents; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Mammals
PubMed: 38263212
DOI: 10.1038/s41598-024-52544-z -
Anais Brasileiros de Dermatologia 2024An increased risk of Secondary Malignancies (SMs) in Mycosis Fungoides (MF) has been suggested previously. However, the relationship between this risk and the features...
BACKGROUND
An increased risk of Secondary Malignancies (SMs) in Mycosis Fungoides (MF) has been suggested previously. However, the relationship between this risk and the features of MF is not well-known.
OBJECTIVE
To investigate the rate and types of SMs in a large cohort of MF patients focusing on the associated features of these patients.
METHODS
The demographic features, subtype, and stage of MF, as well as the temporal relationship between the diagnosis of MF and the development of SMs were determined. Major clinical features of MF in this group were compared with MF patients without association of SMs.
RESULTS
Among 730 MF patients with a mean follow-up period of 67.9 ± 52.4 months, 56 SMs were identified in a total of 52 (7.1%) patients. While 28.8% of patients were previously diagnosed with other malignancies, then subsequently had a diagnosis of MF, it was vice versa in 53.8% of patients. Most of the SM-associated MF patients had early-stage (80.7%) and classical type of MF (86.5%) without a significant difference from MF patients without association of SMs; 85.5% and 72.5%, respectively. The most commonly identified SMs were hematologic malignancies (64.3%) including lymphomatoid papulosis (n = 22), Hodgkin's lymphoma (n = 4), non-Hodgkin's lymphoma (n = 5), polycythemia vera (n = 2). Other most commonly associated malignancies were breast cancer (n = 4), prostate cancer (n = 3), renal cell carcinoma (n = 2), melanoma (n = 2), and Kaposi's sarcoma (n = 2).
STUDY LIMITATIONS
A single tertiary dermatology center study with a retrospective design.
CONCLUSION
Apart from the well-known lymphomatoid papulosis association, systemic hematological malignancies were also quite common in the large cohort of MF patients.
Topics: Humans; Mycosis Fungoides; Male; Female; Middle Aged; Skin Neoplasms; Adult; Neoplasms, Second Primary; Aged; Retrospective Studies; Risk Factors; Young Adult; Neoplasm Staging; Adolescent; Aged, 80 and over; Time Factors; Follow-Up Studies
PubMed: 38262820
DOI: 10.1016/j.abd.2023.06.004 -
International Journal of Molecular... Jan 2024Psoriasis and atopic dermatitis fall within the category of cutaneous immune-mediated inflammatory diseases (IMIDs). The prevalence of IMIDs is increasing in... (Review)
Review
Psoriasis and atopic dermatitis fall within the category of cutaneous immune-mediated inflammatory diseases (IMIDs). The prevalence of IMIDs is increasing in industrialized societies, influenced by both environmental changes and a genetic predisposition. However, the exact immune factors driving these chronic, progressive diseases are not fully understood. By using multi-omics techniques in cutaneous IMIDs, it is expected to advance the understanding of skin biology, uncover the underlying mechanisms of skin conditions, and potentially devise precise and personalized approaches to diagnosis and treatment. We provide a narrative review of the current knowledge in genomics, epigenomics, and proteomics of atopic dermatitis and psoriasis. A literature search was performed for articles published until 30 November 2023. Although there is still much to uncover, recent evidence has already provided valuable insights, such as proteomic profiles that permit differentiating psoriasis from mycosis fungoides and β-defensin 2 correlation to PASI and its drop due to secukinumab first injection, among others.
Topics: Humans; Dermatitis, Atopic; Multiomics; Proteomics; Psoriasis; Skin Neoplasms; Immunomodulating Agents
PubMed: 38256115
DOI: 10.3390/ijms25021042 -
Hematology Reports Dec 2023Post-transplant lymphoproliferative disease is a rare disorder with an annual incidence of 0.5% to 3.7%. Development of this disorder carries with it a poor prognosis....
Post-transplant lymphoproliferative disease is a rare disorder with an annual incidence of 0.5% to 3.7%. Development of this disorder carries with it a poor prognosis. In this report, we describe a rare case of post-transplant primary cutaneous T-cell lymphoma (PT-CTCL) mycosis fungoides stage IIB in a patient following kidney transplantation, as well as a review of PT-CTCL reported in the literature. The treatment following diagnosis included bexarotene, cyclosporine, and prednisone. Currently, the patient is free from disease. This information aims to add to the knowledge of the prevalence and management of PT-CTCL.
PubMed: 38247992
DOI: 10.3390/hematolrep16010002 -
The Oncologist Mar 2024Duvelisib, a small-molecule phosphatidylinositol 3-kinase-δ,γ inhibitor, has shown efficacy for mycosis fungoides (MF) at dosage ranges of 25-100 mg twice daily (BID),...
Duvelisib, a small-molecule phosphatidylinositol 3-kinase-δ,γ inhibitor, has shown efficacy for mycosis fungoides (MF) at dosage ranges of 25-100 mg twice daily (BID), but with significant toxicity. We conducted a retrospective cohort study of patients with advanced MF treated with low-dose duvelisib (15 mg every other day to BID), in an effort to minimize toxicity. A total of 7 patients were included. The overall response rate on duvelisib was 71%, with the remaining patients maintaining stable disease. Mean modified Severity Weighted Assessment Tool score improved by 57.4% and mean percent body surface area involved improved by 52%. Median progression-free survival was 10.3 months. Adverse events occurred in 4 of 7 patients, the most common being fatigue (2/7; grades 1-2), nausea (2/7; grades 1-2), and transaminitis (2/7; grade 3). Overall, low-dose duvelisib showed efficacy for advanced MF with less toxicity, providing a rationale for its use as monotherapy and potentially combinatorial therapy.
Topics: Humans; Retrospective Studies; Mycosis Fungoides; Isoquinolines; Skin Neoplasms; Purines
PubMed: 38243388
DOI: 10.1093/oncolo/oyad345 -
Frontiers in Oncology 2023Topical chlormethine (CL) is recommended as a first-line treatment for early-stage mycosis fungoides (MF) and in 2017, the European Medicines Agency approved the CL gel...
BACKGROUND
Topical chlormethine (CL) is recommended as a first-line treatment for early-stage mycosis fungoides (MF) and in 2017, the European Medicines Agency approved the CL gel formulation to treat adult patients. More recently, to increase patient compliance and adherence, clinicians have developed flexible protocols that allow the concomitant use of CL gel with topical corticosteroids in daily practice regimens. Therefore, sharing real-life data on CL gel use and side effects management may help improve the use of this agent.
OBJECTIVES
To expand knowledge about the actual use of CL gel in patients with MF, the present study assessed the improvement of MF skin lesions after CL gel treatment and provided information on the management of cutaneous adverse events (AEs) in a real-life setting.
METHODS
This was an Italian retrospective study conducted among six dermatology referral centers. Patients ≥18 years affected by MF and in treatment with CL gel (160 µ/g), alone or in combination according to routine clinical practice, between December 2019 and December 2021 were considered. The study's primary aim was to evaluate the effectiveness of CL gel in terms of overall response rate (ORR) after 3 months of treatment.
RESULTS
A total of 79 patients (61% male) with different stages of MF (84% early stage) were included. CL gel was prescribed mainly in association with topical corticosteroids (66% of patients). ORR after 3 months of treatment was 42%, with no differences between early- and advanced-stage MF. Response rates improved over time up to 97% after 18 months of treatment. Overall, 66 AEs were reported in 67% of patients; most were hyperpigmentation (45%) and irritant contact dermatitis (37%). Six AEs led to treatment discontinuation, and five out of six (83%) patients who reported these events resumed treatment after interruption. No AEs were classified as severe.
CONCLUSIONS
Our observations support the use of CL gel in patients with early- and advanced-stage MF, making it a valuable treatment option.
PubMed: 38239642
DOI: 10.3389/fonc.2023.1298296 -
Anais Brasileiros de Dermatologia 2024Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is...
Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.
Topics: Humans; Antibodies, Monoclonal; Psoriasis; Quality of Life; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Interleukin-12; Interleukin-23
PubMed: 38238209
DOI: 10.1016/j.abd.2023.08.004