RESUMO
A 73-year-old man with diabetes mellitus was referred to our department for ultraviolet treatment for erythematous skin lesions with itching. On dipeptidyl peptidase-4 inhibitor (DPP-4i) sitagliptin (Januvia®) for diabetes mellitus, the erythematous skin lesions appeared and spread to the whole body. At the initial visit, erythema multiforme-like skin lesions with crusts were observed on the trunk and extremities, and the patient was suspected to have drug eruption. Histopathology demonstrated eosinophilic infiltration in the superficial dermis and inflammatory cell infiltration in the epidermis. Sitagliptin was discontinued, and erythematous lesions improved with oral prednisolone. Thereafter the patient was treated with phototherapy and betamethasone sodium phosphate infusion for residual prurigo. However, blistering skin lesions appeared 5 months later. Histopathological findings were subepidermal blisters with eosinophilic abscess, and bullous pemphigoid was suspected. CLEIAs for autoantibodies to desmoglein 1 (Dsg1), Dsg3 and BP180 were negative. Direct immunofluorescence showed linear depositions of immunoglobulin G (IgG) and C3 at the epidermal basement membrane zone, and indirect immunofluorescence detected IgG anti-epidermal basement membrane zone antibodies, reacting with the dermal side of 1M NaCl-split normal human skin. IgG antibodies reacted with 200 kDa laminin γ1 (p200) by immunoblotting using dermal extracts. These results indicated that this patient was diagnosed with anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration. Although reports of DPP-4i-related bullous pemphigoid have accumulated, cases of anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration are rarely reported.
Assuntos
Autoanticorpos , Inibidores da Dipeptidil Peptidase IV , Laminina , Penfigoide Bolhoso , Fosfato de Sitagliptina , Humanos , Masculino , Idoso , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/patologia , Penfigoide Bolhoso/tratamento farmacológico , Laminina/imunologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Fosfato de Sitagliptina/efeitos adversos , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Toxidermias/etiologia , Toxidermias/patologia , Toxidermias/diagnóstico , Toxidermias/imunologia , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/complicaçõesAssuntos
Complemento C3/análise , Toxidermias/etiologia , Toxidermias/imunologia , Medicamentos de Ervas Chinesas/efeitos adversos , Dermatopatias Vesiculobolhosas/induzido quimicamente , Dermatopatias Vesiculobolhosas/imunologia , Idoso , Toxidermias/patologia , Feminino , Imunofluorescência , Humanos , Dermatopatias Vesiculobolhosas/patologiaRESUMO
Cutaneous eruptions caused by the combination of Chinese and Western medicine have attracted widespread attention; however, the underlying mechanism remains unclear. This study aimed to evaluate the potential mechanism of cutaneous eruptions in vivo and in vitro using the combination of Shuanghuanglian injection powder (SHL) and aspirin (ASA) as an example. ASA and SHL co-administration induced inflammatory responses in HaCat cells, as evidenced by marked increases in the expression of IL-4 and TNF-α, and the level of apoptosis. Additionally, histopathological investigation of mice skin tissues showed local inflammatory cell infiltration. Western boltting was used to detect the effects of ASA on desmoglein-1 (DSG1) expression; we found that DSG1 expression was down-regulated in vivo and in vitro. Finally, the key components of SHL were administered to HaCat cells with down-regulated DSG1; it was seen that neochlorogenic acid and rutin have a significant effect on HaCat cell apoptosis. These results demonstrate that DSG1 deficiency is a potential cause of cutaneous eruptions caused by the combination of SHL and ASA, and neochlorogenic acid and rutin are the main allergenic components. This study provides a new research strategy for the safety evaluation of integrated traditional Chinese and Western medicine.
Assuntos
Apoptose/efeitos dos fármacos , Aspirina/toxicidade , Desmogleína 1/antagonistas & inibidores , Toxidermias/etiologia , Medicamentos de Ervas Chinesas/toxicidade , Queratinócitos/efeitos dos fármacos , Animais , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/toxicidade , Desmogleína 1/metabolismo , Toxidermias/metabolismo , Toxidermias/patologia , Feminino , Células HaCaT , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-4/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos Endogâmicos ICR , Ácido Quínico/análogos & derivados , Ácido Quínico/toxicidade , Rutina/toxicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Multivitamins are commonly consumed over-the-counter supplements. Drug reactions related to multivitamins are rare and very few cases have been reported. This is a case of a young woman who developed bullous fixed drug eruption to multivitamins.
Assuntos
Vesícula/induzido quimicamente , Toxidermias/etiologia , Complexo Vitamínico B/efeitos adversos , Biotina/efeitos adversos , Vesícula/patologia , Combinação de Medicamentos , Toxidermias/patologia , Feminino , Ácido Fólico/efeitos adversos , Humanos , Piridoxina/efeitos adversos , Ácido Tióctico/efeitos adversos , Vitamina B 12/efeitos adversos , Vitamina B 12/análogos & derivados , Adulto JovemRESUMO
Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D3 analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.
Assuntos
Toxidermias/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Toxidermias/epidemiologia , Toxidermias/imunologia , Toxidermias/patologia , HumanosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis dracunculifolia (Asteraceae) is a commonly used plant in traditional medicine known as "alecrim-do-campo". Popularly it has been used as an immunostimulant, antibiotic, anti-inflammatory among other applications. So far, only a few studies have investigated the B. dracunculifolia anti-inflammatory effect and none has investigated the effectiveness of essential oil on skin diseases. AIM OF THE STUDY: The study aimed at evaluating the topical anti-inflammatory activity of B. dracunculifolia essential oil (BdEO) in mice models of acute and chronic skin inflammation. MATERIALS AND METHODS: BdEO was obtained from leaves and it was analyzed with Gas Chromatograph. Topical anti-inflammatory activity of BdEO (0.1, 0.3 and 1.0 mg/ear) was evaluated in Arachidonic Acid or TPA-induced acute and chronic skin inflammation in mice. Parameters such edema, cell migration and keratinocytes proliferation were evaluated. In addition, safety and a possible mechanism of action for BdEO essential oil were also investigated. RESULTS: Our results indicate that mainly terpenoids compounds compose BdEO. In addition, topical treatment with BdEO inhibited inflammatory parameters in both acute and chronic models of skin inflammation. This protective effect was associated with reduced edema formation, smaller cellular influx into the inflamed tissue and reduction of keratinocytes hyperproliferation. Although BdEO appears to exert its anti-inflammatory effect through a corticosteroid pathway, no local or systemic side effects were observed. CONCLUSION: Taken together, the present results showed that the essential oil obtained by hydrodistillation from B. dracunculifolia leaf samples exhibit remarkable topical anti-inflammatory properties. Therefore, our study demonstrated evidence for BdEO topical anti-inflammatory efficacy and safety, suggesting that it could be considered for developing of a new phytotherapeutic formulation as treatment for skin diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Baccharis/química , Toxidermias/tratamento farmacológico , Óleos Voláteis/farmacologia , Animais , Anti-Inflamatórios/química , Toxidermias/patologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Epiderme/patologia , Feminino , Sistema Linfático/efeitos dos fármacos , Camundongos , Óleos Voláteis/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Receptores de Glucocorticoides/metabolismoRESUMO
BACKGROUND: Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells. PURPOSE: This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects. STUDY DESIGN AND METHODS: A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues. RESULTS: In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model. CONCLUSION: We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Toxidermias/tratamento farmacológico , Flavonas/farmacologia , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Toxidermias/metabolismo , Toxidermias/patologia , Regulação da Expressão Gênica , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/toxicidadeAssuntos
Erupções Acneiformes/tratamento farmacológico , Peróxido de Benzoíla/administração & dosagem , Toxidermias/tratamento farmacológico , Cloridrato de Erlotinib/efeitos adversos , Metilprednisolona/administração & dosagem , Fototerapia/efeitos adversos , Erupções Acneiformes/induzido quimicamente , Erupções Acneiformes/patologia , Administração Tópica , Toxidermias/patologia , Cloridrato de Erlotinib/administração & dosagem , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
AIM: To investigate the relationship between the onsets of multikinase inhibitor (MKI)-associated hand-foot skin reaction (HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib. METHODS: We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival (OS) after the initiation of treatment. RESULTS: The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group. CONCLUSION: Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Toxidermias/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Toxidermias/etiologia , Toxidermias/patologia , Toxidermias/terapia , Feminino , Pé , Mãos , Humanos , Incidência , Neoplasias Hepáticas/mortalidade , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Farmacêuticos/estatística & dados numéricos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Pele/efeitos dos fármacos , Pele/patologia , Sorafenibe , Análise de Sobrevida , Falha de TratamentoRESUMO
Cutaneous eruption is a common drug-adverse reaction, characterised by keratinocytes inflammation and apoptosis. Shuanghuanglian injeciton (SHLI) is a typical Chinese medicine injection, which is used to treat influenza. It has been reported that SHLI has the potential to induce cutaneous adverse eruptions. However, the mechanisms remain unclear. Since desmoglein 1 (DSG1) shows a crucial role in maintaining skin barrier function and cell susceptibility, we assume that DSG1 plays a critical role in the cutaneous eruptions induced by SHLI. In our study, retinoic acid (RA) was selected to downregulate the DSG1 expression, and lipopolysaccharide (LPS) was first used to identify the susceptibility of the DSG1-deficiency Hacat cells. Then, SHLI was administrated to normal or DSG1-deficient Hacat cells and mice. The inflammatory factors and apoptosis rate were evaluated by RT-PCR and flow cytometry. The skin pathological morphology was observed by hematoxylin and eosin (HE) staining. Our results show that treated only with SHLI could not cause IL-4 and TNF-α mRNA increases in normal Hacat cells. However, in the DSG1-deficient Hacat cells or mice, SHLI induced an extreme increase of IL-4 and TNF-α mRNA levels, as well as in the apoptosis rate. The skin tissue showed a local inflammatory cell infiltration when treated with SHIL in the DSG1-deficient mice. Thus, we concluded that DSG1 deficiency was a potential causation of SHLI induced eruptions. These results indicated that keratinocytes with DSG1 deficiency were likely to induce the cutaneous eruptions when stimulated with other medicines.
Assuntos
Apoptose/efeitos dos fármacos , Desmogleína 1/deficiência , Toxidermias , Medicamentos de Ervas Chinesas/efeitos adversos , Queratinócitos/metabolismo , Animais , Apoptose/genética , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Toxidermias/genética , Toxidermias/metabolismo , Toxidermias/patologia , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Queratinócitos/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Tretinoína/farmacologiaRESUMO
Baicalin is the main flavonoid from the roots of an important medicinal plant, Scutellaria baicalensis, which shows a variety biological activities. Psoriasis is a chronic immune-mediated inflammatory disease that affects the skin. The unmet need of psoriasis is that many patients do not respond adequately to available clinical treatment. In this study, we found that baicalin showed inhibited dermal inflammation in a murine model of psoriasis via topical application of imiquimod. After a 5-day topical imiquimod application, baicalin or the control vehicle cream was to applied to the lesions of BALB/c mice for a further 4 days. The erythema, scaling, and thickness of the epidermal layer significantly improved in the baicalin-treated mice. The levels of interleukin-17A, interleukin-22, interleukin-23, and tumor necrosis factor in the skin significantly decreased after baicalin treatment. Baicalin also inhibited imiquimod-induced interleukin-17A production in skin draining lymph node cells. The infiltration of γδ T cells into the skin lesions induced by imiquimod was also suppressed after baicalin treatment. These results suggest that baicalin inhibited skin inflammation through the inhibition of the interleukin-17/interleukin-23 axis in a murine model of psoriasis.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/metabolismo , Toxidermias/tratamento farmacológico , Flavonoides/farmacologia , Psoríase/tratamento farmacológico , Aminoquinolinas/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/química , Modelos Animais de Doenças , Toxidermias/patologia , Feminino , Flavonoides/química , Humanos , Imiquimode , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/patologia , Receptores de Interleucina/metabolismo , Pele/patologiaAssuntos
Berberina/efeitos adversos , Toxidermias/etiologia , Hipoglicemiantes/efeitos adversos , Medicamentos sem Prescrição/efeitos adversos , Fitoterapia/efeitos adversos , Axila , Toxidermias/patologia , Virilha , Humanos , Masculino , Pessoa de Meia-Idade , Preparações de Plantas/efeitos adversosRESUMO
The development of immune checkpoint inhibitors [monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1)] represents a major breakthrough in cancer therapy. Although they present a favorable risk/benefit ratio, immune checkpoint blockade therapies have a very specific safety profile. Due to their unique mechanism of action, they entail a new spectrum of adverse events that are mostly immune related [immune-related adverse events (irAEs)], notably mediated by the triggering of cytotoxic CD4+/CD8+ T cell activation. Cutaneous toxicities appear to be one of the most prevalent irAEs, both with anti-PD-1 and anti-CTLA-4 agents or with the newly developed anti-PD-L1 agents, which corresponds to a class effect. They are observed in more than one-third of the treated patients, mainly in the form of a maculopapular rash (eczema-like spongiotic dermatitis) and pruritus. A wide range of other dermatologic manifestations can also occur, including lichenoid reactions, psoriasis, acneiform rashes, vitiligo-like lesions, autoimmune skin diseases (e.g., bullous pemphigoid, dermatomyositis, alopecia areata), sarcoidosis or nail and oral mucosal changes. In addition, the use of anti-CTLA-4 and anti-PD-1 therapies in combination is associated with the development of more frequent, more severe and earlier cutaneous irAEs compared to single agents. In most cases, these dysimmune dermatologic adverse events remain self-limiting and readily manageable. Early recognition and adequate management, however, are critical to prevent exacerbation of the lesions, to limit treatment interruption and to minimize quality of life impairment. This review describes the variable clinical and histopathologic aspects of dermatologic irAEs induced by immune checkpoint inhibitors. Appropriate treatment and counseling are also proposed, with a step-by-step approach for optimized management by both practicing oncologists and dermatologists.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Toxidermias/etiologia , Neoplasias/tratamento farmacológico , Pele/efeitos dos fármacos , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Fármacos Dermatológicos/uso terapêutico , Toxidermias/diagnóstico , Toxidermias/epidemiologia , Toxidermias/patologia , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Incidência , Neoplasias/imunologia , Fototerapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Qualidade de Vida , Fatores de Risco , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Resultado do Tratamento , Suspensão de TratamentoAssuntos
Anticorpos Monoclonais/efeitos adversos , Terapia Biológica/efeitos adversos , Toxidermias/etiologia , Pênfigo/induzido quimicamente , Adulto , Anticorpos Monoclonais Humanizados , Artrite Reumatoide/tratamento farmacológico , Toxidermias/patologia , Eritema/induzido quimicamente , Eritema/patologia , Feminino , Humanos , Imuno-Histoquímica , Pênfigo/patologia , Pele/patologiaAssuntos
Humanos , Feminino , Adulto , Terapia Biológica/efeitos adversos , Pênfigo/induzido quimicamente , Toxidermias/etiologia , Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Pele/patologia , Imuno-Histoquímica , Pênfigo/patologia , Toxidermias/patologia , Eritema/induzido quimicamente , Eritema/patologia , Anticorpos Monoclonais HumanizadosRESUMO
BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.
Assuntos
Toxidermias/etiologia , Epiderme/patologia , Antagonistas do Ácido Fólico/efeitos adversos , Metotrexato/efeitos adversos , Adulto , Fatores Etários , Idoso , Superfície Corporal , Estudos de Casos e Controles , Toxidermias/diagnóstico , Toxidermias/tratamento farmacológico , Toxidermias/patologia , Feminino , Antagonistas do Ácido Fólico/administração & dosagem , Antagonistas do Ácido Fólico/sangue , Humanos , Leucovorina/uso terapêutico , Masculino , Metotrexato/administração & dosagem , Metotrexato/sangue , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Prognóstico , Insuficiência Renal Crônica/complicações , Taxa de Sobrevida , Complexo Vitamínico B/uso terapêuticoRESUMO
BAY 11-7082 antagonizes I-κB kinase-ß preventing nuclear translocation of nuclear factor-κB (NF-κB); it also inhibits NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation. NF-κB is involved in psoriasis, whereas the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod (IMQ) cream (62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knockout (KO) mice for 7 consecutive days. Sham psoriasis animals were challenged with Vaseline cream. Sham and IMQ animals were randomized to receive BAY 11-7082 (20 mg/kg/i.p.) or its vehicle (100 µl/i.p of 0.9% NaCl). Skin of IMQ animals developed erythema, scales, thickening and epidermal acanthosis. IMQ skin samples showed increased expression of pNF-κB and NLRP3 activation. BAY 11-7082 blunted epidermal thickness, acanthosis and inflammatory infiltrate. BAY 11-7082 reduced pNF-κB, NLRP3, tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß expression, blunted the phosphorylation of signal transducer and activators of transcription 3 (STAT3) and decreased IL-23 levels. In addition, BAY 11-7082 reawakened the apoptotic machinery. NLRP3 KO animals showed a reduced total histological score but persistent mild acanthosis, dermal thickness and expression of pNF-κB and pSTAT3, following IMQ application. Our data suggest that BAY 11-7082 might represent an interesting approach for the management of psoriasis-like dermatitis depending on the dual inhibition of NF-κB and NLRP3.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Inflamassomos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Nitrilas/uso terapêutico , Psoríase/prevenção & controle , Sulfonas/uso terapêutico , Aminoquinolinas , Animais , Apoptose/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Citocinas/genética , Fármacos Dermatológicos/farmacologia , Toxidermias/metabolismo , Toxidermias/patologia , Toxidermias/prevenção & controle , Avaliação Pré-Clínica de Medicamentos/métodos , Imiquimode , Inflamassomos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Nitrilas/farmacologia , Psoríase/induzido quimicamente , Psoríase/metabolismo , Psoríase/patologia , RNA Mensageiro/genética , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/fisiologia , Sulfonas/farmacologiaRESUMO
Rheumatoid arthritis (RA) is a systemic inflammatory disorder that primarily affects the joints, but may exhibit extra-articular, including cutaneous, manifestations such as rheumatoid nodules, rheumatoid vasculitis, granulomatous skin disorders, and neutrophilic dermatoses. A large burden of cutaneous disease may be an indication of RA disease activity and the need for more aggressive treatment. Many of the therapeutic agents used to treat RA can also result in cutaneous adverse effects, which pose their own diagnostic and therapeutic challenges. Anti-TNFα agents, in particular, have a wide variety of adverse effects including psoraisiform eruptions, granulomatous conditions, and cutaneous connective tissue disorders. Herein we provide an update on the clinical presentations and management of RA-associated cutaneous findings as well as drug-induced cutaneous effects, with particular attention to the adverse effects of biologic disease-modifying agents.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Terapia Biológica/efeitos adversos , Dermatopatias/etiologia , Dermatopatias/patologia , Administração Cutânea , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Dermatomiosite/etiologia , Dermatomiosite/patologia , Toxidermias/etiologia , Toxidermias/patologia , Humanos , Erupções Liquenoides/etiologia , Erupções Liquenoides/fisiopatologia , Lúpus Eritematoso Cutâneo/etiologia , Lúpus Eritematoso Cutâneo/patologia , Melanoma/etiologia , Melanoma/patologia , Pioderma Gangrenoso/etiologia , Pioderma Gangrenoso/patologia , Nódulo Reumatoide/patologia , Vasculite Reumatoide/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Síndrome de Sweet/etiologia , Síndrome de Sweet/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Panax notoginseng saponins (PNS) are a patented product in the People's Republic of China, and have extensive effects on the cardiovascular system. Here we report on four elderly patients (one male and three female) with drug eruption induced by PNS injection. All developed a sudden skin rash with pruritus from head to foot, and subsequently accepted hospitalization. In each case, PNS had been used for less than 1 week before appearance of the rash. No specific short-term medications or changes in diet or exposure to environmental factors immediately prior to appearance of the rash were identified. These four patients had some interesting features in common, ie, pustules, fever, and elevated circulating neutrophil counts, which required high-dose, long-term glucocorticoid therapy. To our knowledge, this is the first report of pustular drug eruption induced by PNS and provides a useful reference and warning for clinicians.