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ABSTRACT: Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), are prone to Staphylococcus aureus infections and have a poor prognosis due to treatment resistance. Here, we report that S aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S aureus and recombinant SE significantly inhibit cell death induced by histone deacetylase (HDAC) inhibitor romidepsin in primary malignant T cells from patients with SS. Bacterial killing by engineered, bacteriophage-derived, S aureus-specific endolysin (XZ.700) abrogates the effect of S aureus supernatant. Similarly, mutations in major histocompatibility complex (MHC) class II binding sites of SE type A (SEA) and anti-SEA antibody block induction of resistance. Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide). Multimodal single-cell sequencing indicates T-cell receptor (TCR), NF-κB, and JAK/STAT signaling pathways (previously associated with drug resistance) as putative mediators of SE-induced drug resistance. In support, inhibition of TCR-signaling and Protein kinase C (upstream of NF-κB) counteracts SE-induced rescue from drug-induced cell death. Inversely, SE cannot rescue from cell death induced by the proteasome/NF-κB inhibitor bortezomib. Inhibition of JAK/STAT only blocks rescue in patients whose malignant T-cell survival is dependent on SE-induced cytokines, suggesting 2 distinct ways SE can induce drug resistance. In conclusion, we show that S aureus enterotoxins induce drug resistance in primary malignant T cells. These findings suggest that S aureus enterotoxins cause clinical treatment resistance in patients with SS, and antibacterial measures may improve the outcome of cancer-directed therapy in patients harboring S aureus.
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Linfoma Cutâneo de Células T , Síndrome de Sézary , Neoplasias Cutâneas , Infecções Estafilocócicas , Humanos , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Staphylococcus aureus , NF-kappa B , Linfócitos T , Enterotoxinas/farmacologia , Linfoma Cutâneo de Células T/patologia , Receptores de Antígenos de Linfócitos T , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Resistência a MedicamentosRESUMO
Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches.
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BACKGROUND: Dermatitis artefacta (DA) is a dermatologicopsychiatric illness that is a conscious self-infliction of lesions to accessible regions of the body. The lesions usually do not resemble those of any know skin disease and there are no specific diagnostic tests to recognize them. This makes dermatitis artefacta a very slow, challenging and expensive disease to diagnose. CASE REPORT: We present 5 different clinical cases of dermatitis artefacta treated in the Department of Dermatology, Venereology and Allergology, Medical University of Gdansk in 2011. Detailed anamnesis and physical examination were performed at the day of admission. All patients had biochemical and hematological blood tests, skin biopsies and swabs for bacteriological examination, and photographs were taken. Psychiatric consultation was recommended in all cases. Clinical symptoms before diagnosis lasted from 1 to 10 years. The female-to-male ratio is 1:0.7, with age range of 57-62 years. Of our patients, only 2 refused a psychiatric consultation. Three out of 5 patients denied self-mutilation (2 of those 3 patients finally admitted to self-manipulations). Lesions were usually within the reach of the dominant hand. Two patients have other personality disorders. In 4/5 cases visible improvement after treatment with occlusive dressings were observed. CONCLUSIONS: We discuss and attempt to depict issues associated with collaboration between dermatologists and psychiatrists, reasons for poor recognition of the disease, very long diagnosis and high costs. To conclude, we found that close collaboration between dermatologists and psychiatrists is important in diagnosing and treating DA patients.
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Dermatite/psicologia , Cicatriz/patologia , Cicatriz/psicologia , Dermatite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera/patologia , Úlcera/psicologiaRESUMO
(1) Background: Mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. The aim of this study was to describe the clinical features and epidemiological and diagnostic findings in addition to the treatment modalities and responses in patients with MF. Furthermore, comparisons between patients in the early stage and the advanced stage were evaluated. (2) Methods: A retrospective register-based study based on data collected from the primary cutaneous lymphoma register and medical records was performed at the Department of Dermatology and Venerology at Sahlgrenska University Hospital, Gothenburg, Sweden. (3) Results: Eighty-four patients with a median age of 55 years with MF were included. Most of the patients (n = 73) were diagnosed at the early stage of the disease (IA-IIA). Overall disease progression was seen in 12.5% (n = 9) of the patients. Nine (10.7%) patients were deceased, out of which four (4.8%) deaths were associated with MF-related causes. (4) Conclusions: This study contributes to the knowledge of the epidemiological and clinical features in addition to the diagnostic findings and treatment responses in patients with MF in Sweden.
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Photodynamic therapy with methyl aminolevulinate (MAL-PDT) is an effective treatment of acne vulgaris, but is associated with side effects. We performed a prospective randomized split-face study aimed at optimizing MAL-PDT treatment. Patients (n = 33) were randomized to two or four treatments of PDT with MAL on one cheek and placebo vehicle on the other cheek, 1-2 weeks apart. A 1.5-h pre-treatment with the MAL cream was followed by illumination with red light (20 J/cm2). Assessments were performed before treatment and 4, 10, and 20 weeks after the last treatment. In comparison to baseline, the number of inflammatory lesions at 20 weeks on cheeks treated with MAL-PDT showed a relative decrease of 74% in the group with two treatments and 85% in the group with four treatments. This new treatment regimen for both MAL-PDT and red-light-only PDT, with shortened pre-treatment and reduced light dose, could be an effective modality.