RESUMO
BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.
Assuntos
Linfoma Cutâneo de Células T , Micose Fungoide , NF-kappa B , Fatores de Transcrição NFATC , Fator de Transcrição STAT3 , Neoplasias Cutâneas , Humanos , Micose Fungoide/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias Cutâneas/genética , Linfócitos T/metabolismoRESUMO
BACKGROUND: Some chronic inflammatory skin diseases, such as psoriasis, have been associated with an increased prevalence of non-alcoholic fatty liver disease (NAFLD). Nevertheless, this prevalence in hidradenitis suppurativa (HS) has not been assessed to date. OBJECTIVES: To determine the prevalence of NAFLD in patients with HS and the risk factors associated with this disorder. METHODS: This case-control study enrolled 70 HS patients and 150 age- and gender-matched controls who were evaluated by hepatic ultrasonography (US) and transient elastography (TE) after excluding other secondary causes of chronic liver disease. The diagnosis of NAFLD was established if US and/or TE were altered. RESULTS: The prevalence of NAFLD was significantly increased in patients with HS compared to controls (72.9% vs. 24.7%: P < 0.001). In the multivariable regression model adjusted for age, sex and classic metabolic risk factors for NAFLD, HS was significantly and independently associated with the presence of NAFLD [OR 7.75 confidence interval (CI) 2.54-23.64; P < 0.001]. CONCLUSIONS: Our results show a high prevalence of NAFLD in HS patients independent of classic metabolic risk factors. Therefore, we suggest HS patients to be evaluated for NAFLD and managed accordingly.
Assuntos
Hidradenite Supurativa/complicações , Hidradenite Supurativa/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Calcinosis cutis (CC) is defined as the deposition of calcium salts on the skin and subcutaneous tissue. It is associated with different conditions, including some autoimmune diseases, and it can generate significant inflammation, pain, and functional impairment. Different therapies have been tried with limited results. Intralesional sodium thiosulfate seems a promising therapeutic option. We report a patient with diffuse systemic sclerosis who presented with two symmetrical plaques on both axillae, which caused pain and skin retraction. The clinical diagnosis was consistent with CC, which was confirmed by skin biopsy and ultrasound. The patient was treated with a 250 mg/ml solution of sodium thiosulfate injected into the plaques. Complete resolution was achieved after three monthly sessions. The only reported adverse effect was a transient burning sensation during the injections. Given its effectiveness and safety, we believe that intralesional sodium thiosulfate could become a valid first-line option for the treatment of CC.
Assuntos
Calcinose , Escleroderma Sistêmico , Dermatopatias , Calcinose/diagnóstico por imagem , Calcinose/tratamento farmacológico , Humanos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Dermatopatias/tratamento farmacológico , TiossulfatosAssuntos
Vesícula/diagnóstico , Carcinoma Basocelular/diagnóstico , Hipotricose/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Neoplasias Cutâneas/diagnóstico , Vesícula/etiologia , Vesícula/terapia , Carcinoma Basocelular/complicações , Carcinoma Basocelular/terapia , Evolução Fatal , Humanos , Hipotricose/complicações , Hipotricose/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/terapia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/terapiaRESUMO
No disponible
Assuntos
Humanos , Alopecia/tratamento farmacológico , Mesoterapia/métodos , Dutasterida/administração & dosagem , Inibidores de 5-alfa Redutase/administração & dosagem , MicroinjeçõesRESUMO
No disponible
Assuntos
Humanos , Feminino , Adulto Jovem , Manipulação Quiroprática/efeitos adversos , Hematoma/diagnóstico por imagem , Pescoço/patologia , Diagnóstico Diferencial , Ultrassonografia Doppler em Cores , Hematoma/etiologiaRESUMO
No disponible