Assuntos
Condiloma Acuminado , Exantema , Neoplasias Cutâneas , Sífilis Cutânea , Sífilis , Humanos , Sífilis/complicações , Sífilis/diagnóstico , Sífilis Cutânea/complicações , Sífilis Cutânea/diagnóstico , Condiloma Acuminado/complicações , Condiloma Acuminado/diagnóstico , Neoplasias Cutâneas/complicações , Exantema/complicaçõesAssuntos
Condiloma Acuminado , Exantema , Neoplasias Cutâneas , Sífilis Cutânea , Sífilis , Humanos , Sífilis/complicações , Sífilis/diagnóstico , Sífilis Cutânea/complicações , Sífilis Cutânea/diagnóstico , Condiloma Acuminado/complicações , Condiloma Acuminado/diagnóstico , Neoplasias Cutâneas/complicações , Exantema/complicaçõesRESUMO
Background: Coronavirus disease 2019 (COVID-19) disease and vaccines have been associated to various skin reactions, which are mostly similar amongst them. New onset of vitiligo and hypopigmentations have been described following COVID-19 vaccination, but never after COVID-19 infection. Objectives: We present the case of a 45-year-old woman, who developed vitiligo 2 weeks after COVID-19 disease. Skin lesions stabilized after 1 month of initial spreading. Results: Vitiligo is a relatively common acquired pigmentary disorder, possibly caused by a T CD8+ cell-mediated autoimmune process, which may be enhanced after the immune activation of COVID-19 disease. Molecular mimicry and bystander activation have been advocated as possible pathogenic mechanisms of vitiligo after COVID-19 vaccination. The same mechanisms may also be involved as possible vitiligo triggers during COVID-19 disease. Conclusions: Clinicians should be aware of this possible autoimmune cutaneous reaction to COVID-19 disease.
RESUMO
BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.
Assuntos
Dermoscopia , Infestações por Ácaros/patologia , Rosácea/microbiologia , Rosácea/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Dermatoses Faciais/diagnóstico por imagem , Dermatoses Faciais/microbiologia , Dermatoses Faciais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infestações por Ácaros/diagnóstico por imagem , Estudos Prospectivos , Rosácea/diagnóstico por imagem , Índice de Gravidade de Doença , Pele/diagnóstico por imagem , Pele/microbiologia , Pele/patologia , TrombiculidaeAssuntos
Apoptose/genética , Caspase 10/genética , Caspase 8/genética , Mutação , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia , Proteína ADAMTS13/genética , Proteína ADAMTS13/metabolismo , Adolescente , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Biomarcadores , Caspase 10/metabolismo , Caspase 8/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Proteólise , Púrpura Trombocitopênica Trombótica/tratamento farmacológicoRESUMO
Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Gastroenteropatias/genética , Doenças do Sistema Nervoso/genética , Farmacogenética/métodos , Variantes Farmacogenômicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Quimioterapia de Consolidação/efeitos adversos , Feminino , Gastroenteropatias/induzido quimicamente , Deleção de Genes , Predisposição Genética para Doença , Glutationa Transferase/genética , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Modelos Logísticos , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Reação em Cadeia da Polimerase Multiplex , Mutação , Doenças do Sistema Nervoso/induzido quimicamente , Testes Farmacogenômicos/métodos , Fenótipo , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Valor Preditivo dos Testes , Pirofosfatases/genética , Receptor A2A de Adenosina/genética , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59-100%) and a specificity of 87% (CI 70-96%). Positive and negative predictive values were 71% (CI 42-92%) and 96% (CI 82-100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.
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In the last few years the improvements of chemotherapy regimens and supportive care has progressively ameliorated the prognosis of children suffering from Acute Myeloid Leukemia (AML). However, a still high percentage of children do not respond to first line treatments or relapse and need to undergo further treatments. The need to explore new agents other than chemotherapy has been highlighted in the last years in order to overcome drug related resistance and toxicity. Recently, novel therapies have been studied within early phases pediatric trials and seem to show encouraging results. In fact, the knowledge of molecular abnormalities related to AML pathogenesis has permitted to identify selective drugs that may represent an important tool for the development of patient-tailored treatments. Nowadays, FLT3, Aurora Kinases, mTORS's and proteasome inhibitors represents the most promising drugs that are being used in pediatric AML studies.
Assuntos
Leucemia Mieloide Aguda/terapia , Terapia de Alvo Molecular/tendências , Aurora Quinase A/metabolismo , Criança , Ensaios Clínicos como Assunto , Humanos , Leucemia Mieloide Aguda/imunologia , Medicina de Precisão , Complexo de Endopeptidases do Proteassoma/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tirosina Quinase 3 Semelhante a fms/metabolismoAssuntos
Proteínas Monoméricas de Montagem de Clatrina/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/fisiopatologia , Fatores de Transcrição/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genéticaAssuntos
Neurofibromatose 1/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Gêmeos Monozigóticos , Criança , Evolução Clonal , Variações do Número de Cópias de DNA , Feminino , Rearranjo Gênico , Humanos , Imunoglobulinas/genética , Neurofibromatose 1/genética , Neurofibromina 1/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Irradiação Craniana , Feminino , Seguimentos , Hematologia/organização & administração , Humanos , Lactente , Itália , Masculino , Oncologia/organização & administração , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoAssuntos
Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Leucemia/complicações , Meningite Criptocócica/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Adolescente , Antineoplásicos/efeitos adversos , Criança , Feminino , Humanos , Leucemia/tratamento farmacológico , Masculino , Meningite Criptocócica/complicações , Meningite Criptocócica/imunologia , Transplante Homólogo , VoriconazolRESUMO
Varicella may be a severe infection in children with malignancy. Varicella vaccination is either not recommended for immunocompromised children or it requires temporary discontinuation of immunosuppression. We prospectively evaluated the feasibility of a varicella vaccination programme of household contacts of varicella-negative children receiving antineoplastic chemotherapy. From April 2004 to April 2005, 207 children were evaluated; in 49 (24 percent) the attending physicians collected no history about previous varicella and performed no serological evaluation before any transfusion. Among the 158 patients with complete history and/or a screening test, 51 (32 percent) were negative, with a total of 110 household contacts eligible for the study. Of these, 13 (12 percent) subjects resulted negative for varicella. In three of them vaccination was not performed due to parental refusal. This study demonstrates the difficulties in implementing a varicella vaccination programme targeting negative household contacts of immunocompromised children. The attitude of paediatric oncologists and parental refusal currently represent the main challenges against the complete success of this strategy in countries where VZV vaccination is not inserted in the general vaccination programme.
Assuntos
Antineoplásicos/efeitos adversos , Cuidadores , Vacina contra Varicela/administração & dosagem , Varicela/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Família , Herpes Zoster/prevenção & controle , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Cuidadores/psicologia , Criança , Pré-Escolar , Suscetibilidade a Doenças , Família/psicologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Projetos Piloto , Estudos Prospectivos , Recusa do Paciente ao Tratamento , Vacinação/psicologiaAssuntos
Transplante de Medula Óssea , Doenças Genéticas Inatas/terapia , Doenças Mitocondriais/terapia , Condicionamento Pré-Transplante , Antifúngicos/administração & dosagem , Soro Antilinfocitário , Antineoplásicos/administração & dosagem , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergilose Broncopulmonar Alérgica/etiologia , Sequência de Bases/genética , DNA Mitocondrial/genética , Transporte de Elétrons/genética , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/patologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Lactente , Leucemia Mieloide/terapia , Melfalan/administração & dosagem , Doenças Mitocondriais/complicações , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Agonistas Mieloablativos/administração & dosagem , Deleção de Sequência , Síndrome , Transplante Homólogo , Falha de Tratamento , Vidarabina/análogos & derivadosRESUMO
Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem-cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13-4 gene have recently been described in patients with FHL. We sequenced the Munc13-4 gene in all patients with haemophagocytic lymphohistiocytosis not due to PRF1 mutations. In 15 of the 30 families studied, 12 novel and 4 known Munc13-4 mutations were found, spread throughout the gene. Among novel mutations, 2650C-->T introduced a stop codon; 441del A, 532del C, 3082del C and 3226ins G caused a frameshift, and seven were mis sense mutations. Median age of diagnosis was 4 months, but six patients developed the disease after 5 years of age and one as a young adult of 18 years. Involvement of central nervous system was present in 9 of 15 patients, activity of natural killer cells was markedly reduced or absent in 13 of 13 tested patients. Chemo-immunotherapy was effective in all patients. Munc13-4 mutations were found in 15 of 30 patients with FHL without PRF1 mutations. Because these patients may develop the disease during adolescence or even later, haematologists should include FHL2 and FHL3 in the differential diagnosis of young adults with fever, cytopenia, splenomegaly and hypercytokinaemia.
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Linfo-Histiocitose Hemofagocítica/genética , Proteínas de Membrana/genética , Mutação/genética , Adolescente , Western Blotting , Criança , Pré-Escolar , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Proteínas de Membrana/metabolismo , Microscopia Confocal , Microscopia Eletrônica , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Citotóxicos/patologia , Linfócitos T Citotóxicos/ultraestruturaRESUMO
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.
Assuntos
Proteínas de Ligação a DNA/genética , Rearranjo Gênico , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes/genética , Fatores de Transcrição/genética , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Proteína de Leucina Linfoide-Mieloide , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Valores de ReferênciaAssuntos
Rearranjo Gênico , Leucemia Mieloide/genética , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Análise Citogenética , Feminino , Humanos , Lactente , Itália/epidemiologia , Leucemia Mieloide/epidemiologia , Leucemia Mieloide/mortalidade , Masculino , Epidemiologia Molecular , Análise de SobrevidaRESUMO
We analyzed the outcome of 167 consecutive children with second CR acute lymphoblastic leukemia (ALL), for whom an unrelated donor (UD) search was activated between 1989 and 1998 at a median time of 2 months after relapse. A suitable donor was identified for 70 patients at 1 year and 6.5 months before and after 1995 from search activation, respectively; a further leukemia relapse occurred during the search in 94 children at a median of 4 months after search activation, 36 of whom underwent UD (14) or other types of transplant (22), beyond second CR, while 58 died of progressive disease. Of 73 patients not experiencing a second relapse, 64 underwent UD (46) or other types of transplant (18), while nine proceeded with chemotherapy, and only four of them survived. The 3-year disease-free survival (DFS) from second CR for the 167 patients is 15.1%, whereas 3-year DFS after transplant for the 60 UD and 40 alternative donor transplanted children is 31.6 and 25.4%, respectively. In conclusion, a further relapse is the main factor adversely affecting outcome of children with second CR ALL. Thus, for these patients, the search should be activated early after relapse and either a UD or an alternative transplant should be performed as early as possible.