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Anticorpos Monoclonais Humanizados , Vesícula , Epidermólise Bolhosa , Prurido , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Prurido/tratamento farmacológico , Epidermólise Bolhosa/tratamento farmacológico , Epidermólise Bolhosa/complicações , Vesícula/tratamento farmacológico , Feminino , Masculino , Adulto , Resultado do TratamentoAssuntos
Anticorpos Monoclonais Humanizados , Vesícula , Epidermólise Bolhosa , Prurido , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Prurido/tratamento farmacológico , Epidermólise Bolhosa/tratamento farmacológico , Epidermólise Bolhosa/complicações , Vesícula/tratamento farmacológico , Feminino , Masculino , Adulto , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Venomous snakebite is a neglected yet an important public health problem in China, and few studies have focused on them so far. The aim of this study is to investigate clinical characteristics of snakebites patients in a tertiary hospital in Hangzhou, southeast China. METHODS: A total of 416 snakebite cases were included in this retrospective study. The data were collected from the medical records including demographics, clinical manifestations, management and outcomes. RESULTS: Of the 416 patients with venomous snakebites, 248 were male, and the average age was 54.6 years. The majority of cases occurred in rural in May to September. Out of all the venomous bites, Gloydius brevicaudus accounted for the highest percentage (55.3%). Hands were the most vulnerable site to snakebites (47.4%). Patients had clinical manifestations of pain (100%), swelling (100%), wound necrosis (25.7%), hemorrhagic blister (18.3%), and blister (8.7%). Three hundred and ninety-two patients received antivenom administration, and most were treated within six hours after bites. Twenty-six patients received surgical treatments, and 90 patients developed venom-induced consumption coagulopathy. No deaths have occurred in this study. CONCLUSION: Hangzhou is one of the regions with high affecting of snakebites in China. The results of this study will increase the understanding of the clinical characteristics of venomous snakebites in Hangzhou area.
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Crotalinae , Mordeduras de Serpentes , Serpentes Peçonhentas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/terapia , Centros de Atenção Terciária , Estudos Retrospectivos , Vesícula/induzido quimicamente , Vesícula/tratamento farmacológico , Incidência , Antivenenos/uso terapêutico , China/epidemiologiaRESUMO
BACKGROUNDPemphigus, a rare autoimmune bullous disease mediated by antidesmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area and require long-term maintenance systemic therapy.METHODSSkin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-Seq using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed.RESULTSWe demonstrated the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from patients with pemphigus. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T cell receptor-mediated signaling. Tregs are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-ß stimulation. Finally, intralesional corticosteroid injection improved chronic blisters and reduced skin TLSs in patients with pemphigus.CONCLUSIONThrough this study we conclude that skin TLSs are associated with the persistence of chronically recurrent blisters in patients with pemphigus, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.TRIAL REGISTRATIONClinicalTrials.gov NCT04509570.FUNDINGThis work was supported by National Research Foundation of South Korea (NRF-2021R1C1C1007179) and Korea Drug Development Fund, which is funded by Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (grant RS-2022-00165917).
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Doenças Autoimunes , Pênfigo , Humanos , Corticosteroides , Autoanticorpos , Doenças Autoimunes/tratamento farmacológico , Vesícula/tratamento farmacológico , Linfócitos T CD4-Positivos , Quimiocina CXCL13 , Desmogleína 3 , Pênfigo/tratamento farmacológicoRESUMO
Hailey-Hailey disease (HHD) is a rare genetic benign condition resulting in blisters predominantly on the skin folds. The inheritance is autosomal dominant with complete penetrance, but a variable expressivity in affected family members. It can be triggered by a vast variety of factors such as sweating, weight gain, infection, trauma, pregnancy, and ultraviolet radiation, but the major cause of the disease is a mutation in the ATP2C1 gene. The lesions are typically distributed symmetrically within intertriginous regions such as the retroarticular folds, axillae, inguinal, and perianal regions and presents as flaccid vesicles and blisters on erythematous skin, giving rise to erosions, fissures, and vegetations. There is no specific therapy for HHD. The therapeutic approach to HHD involves the control of exacerbating factors, secondary infections, and cutaneous inflammation. Because of the rarity of the disease, evidence of efficacy for topical or systemic therapies is mainly based on small observational studies, case reports, and clinical experience. We present a case of HHD successfully treated by photodynamic therapy (PDT) with a topical liposomal chlorin photosensitizer.
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Pênfigo Familiar Benigno , Fotoquimioterapia , Humanos , Pênfigo Familiar Benigno/tratamento farmacológico , Pênfigo Familiar Benigno/genética , Pênfigo Familiar Benigno/patologia , Vesícula/tratamento farmacológico , Raios Ultravioleta , ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Herpes simplex, a common infection caused by the herpes simplex virus (HSV), is transmitted through contact of the skin/mucous membrane and establishes latency in the sensory ganglia for the rest of the life of the host. HSV occasionally reactivates and forms blisters around the lips or genitalia in some patients. Repeated overt symptoms, and, much more frequent, subclinical reactivation in the mucosa, make the host retain anti-HSV immunity continuously, resulting in maintaining steadily elevated antibody titer at any point after infection. Clinical symptoms differ in primary infection and recurrence. Primary infections sometimes manifest as severe symptoms such as fever and lymphadenopathy in addition to blisters/erosions of the skin, gingiva, lips, and oral mucosa, while recurrent herpes is generally mild. Diagnosing typical herpes simplex is not difficult, but when the course and manifestations are typical, definitive tests to identify HSV infection are limited since serology is not useful except with primary infection. For treatment, safe and effective oral antiviral drugs are available. Patient-initiated therapy is a new method of administration labeled in Japan. Amenamevir, an inhibitor of viral helicase primase, is available in Japan and labeled in addition to herpes zoster. These new diagnostic and therapeutic tools should be used for better management of herpes simplex.
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Herpes Simples , Herpes Zoster , Humanos , Japão , Vesícula/tratamento farmacológico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Simplexvirus , Herpes Zoster/tratamento farmacológico , Antivirais/uso terapêutico , Antivirais/farmacologiaRESUMO
To evaluate the outcomes of secukinumab and acitretin use in children with generalized pustular psoriasis (GPP), we compared the efficacy and adverse events of secukinumab in 20 children and acitretin in 16 children with GPP from January 1, 2019, to January 30, 2022. Among the 20 patients treated with secukinumab, the average time for pustules to fade, temperature to normalize, and C-reactive protein (CRP) to normalize was 3.83, 2.46, and 3.91 days, respectively. All patients recovered (Japanese Dermatological Association severity index score: 0/1) in 3 weeks. The adverse events were abnormal liver enzyme (10%), atopic dermatitis-like lesions (10%), herpes simplex (5%), and neutropenia (10%). For the patients treated with acitretin, the average time for pustules to fade, temperature to normalize, and CRP to normalize was 6, 6.14, and 8.73 days, respectively. The adverse events included mucocutaneous dryness (75%), dyslipidemia (37.5%), and abnormal liver enzyme (25%). These findings demonstrate that secukinumab has more favorable outcomes than acitretin, and secukinumab was well tolerated by the pediatric patients with GPP.
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Psoríase , Dermatopatias Vesiculobolhosas , Humanos , Criança , Acitretina/efeitos adversos , Psoríase/tratamento farmacológico , Psoríase/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença Aguda , Doença Crônica , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Vesícula/tratamento farmacológicoRESUMO
BACKGROUND: Checkpoint inhibitor (CPI) therapy has significantly improved overall survival in several cancers including metastatic melanoma (MM) and in the adjuvant setting. Cutaneous immune-related adverse events (irAEs) secondary to CPIs are commonly observed; however, autoimmune blistering disorders such as bullous pemphigoid (BP) are rare. OBJECTIVES: To review the prevalence, incidence risk, clinicopathological features and management of toxicity in bullous cutaneous irAEs associated with CPI therapy. METHODS: A multicentre, retrospective, observational study of CPI-associated bullous irAEs in adults with all cancers across four UK specialist centres between 2006 and 2019. RESULTS: In total, 7391 patients were identified. CPI-associated bullous irAEs including BP (n = 16) occurred in 0·3% (n = 22). The median age of onset was 76 years, and there was a male predominance. Most patients had cutaneous melanoma (73%, n = 16), of which 81% (13 of 16) were BRAF wildtype. Grade 1, 2, 3 and 4 skin toxicity occurred in 9%, 45%, 41% and 5%, respectively. The mucosae were involved in 27%, and 25% of confirmed cases of BP did not present with bullae. The median time to onset of bullous irAEs was 12 months, with a median total symptom duration of 6 months. Single PD-1/PD-L1 agents had a longer time to onset of symptoms than combination therapy (median 12 vs. 7 months, respectively). Overall, 91%, 64% and 9% of patients required one, two or three lines of treatment, respectively. Two cases occurred after completion of CPIs (1 and 3 months). Of the 20 cases that presented while on CPIs this was permanently discontinued in 55% (11 of 20) and temporarily held in 20% (four of 20). In the four held cases of CPI, bullous eruption reflared in 50%. CONCLUSIONS: CPI-associated bullous skin toxicity is a rare cutaneous irAE occurring in approximately 0·3% of cases over 13 years of treated patients in this series. Not all cases are diagnostic of BP, but management remains the same. There is a prolonged latency of onset compared with other cutaneous irAEs, with a median time of 12 months, and they can occur after cessation of therapy. Discontinuation of CPIs may be required. Recognizing bullous irAEs promptly and referral to dermatology are essential to optimize management and improve patient outcomes and tumour responses. What is already known about this topic? Checkpoint inhibitor (CPI)-associated bullous pemphigoid is a rare dermatological immune-related adverse event (irAE) that has been reported in small case series and reports. What does this study add? This is the largest multicentre, observational study conducted in the UK over the longest period of 13 years, which demonstrates an overall incidence of bullous cutaneous irAEs secondary to CPIs of 0·3%. Clinical presentation is variable, with one-quarter of patients with bullous pemphigoid presenting without bullae, and mucosal involvement was noted in 27%. Prolonged pruritus is frequently a prodromal symptom. The median time to diagnosis is 12 months and irAEs rarely present after cessation of treatment. Time to onset of symptoms is longer with a single CPI, but with a shorter duration of symptoms compared with combination CPI therapy. Most patients had cutaneous melanoma, of which 81% were BRAF wildtype.
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Inibidores de Checkpoint Imunológico , Melanoma , Penfigoide Bolhoso , Neoplasias Cutâneas , Idoso , Feminino , Humanos , Masculino , Vesícula/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/diagnóstico , Receptor de Morte Celular Programada 1 , Proteínas Proto-Oncogênicas B-raf , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Melanoma Maligno CutâneoRESUMO
BACKGROUND: There is a paucity of literature on pediatric autoimmune bullous disorders (AIBD) in the Indian population. We aimed to retrospectively evaluate the clinico-demographic profile of pediatric AIBDs in our patients and their response to various therapeutic modalities. MATERIALS AND METHODS: This was a retrospective chart review of patients enrolled in our immunobullous disease clinic from November 2013 to August 2019. The clinical records of all the patients aged less than 18 years old with a definitive diagnosis of AIBD were reviewed based on clinical, histopathological, and immunological features. RESULTS: Forty out of 1209 patients with AIBD (3.3%) belonged to the pediatric age group. Pemphigus vulgaris (PV) was the most common AIBD (24, 60%) followed by chronic bullous disease of childhood (CBDC) at 15% (6) and pemphigus foliaceus (PV) at 12.5% (5). Subepidermal blistering disorders had a significantly younger age of onset (P = 0.04) compared to intraepidermal blistering disorders but higher frequency of achieving complete remission off therapy (P = 0.02). The mean time to achieve remission was significantly shorter in PV patients treated with a combination of rituximab and corticosteroids compared to those treated with oral prednisolone and oral immunosuppressive adjuvants (P = 0.001). Rituximab was tolerated well in all 12 pemphigus patients. Oral lesions in PV patients took significantly longer time to achieve remission compared to the cutaneous lesions (P = 0.001). CONCLUSION AND RELEVANCE: PV was the most common pediatric AIBD in Indian patients. Rituximab was a safe and effective modality of treatment in moderate to severe pediatric pemphigus.
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Doenças Autoimunes , Pênfigo , Dermatopatias Vesiculobolhosas , Humanos , Criança , Adolescente , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Pênfigo/epidemiologia , Rituximab/uso terapêutico , Estudos Retrospectivos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Dermatopatias Vesiculobolhosas/epidemiologia , Vesícula/tratamento farmacológico , DemografiaRESUMO
Mucous membrane pemphigoid (MMP) is a heterogeneous group of rare, chronic, subepithelial autoimmune blistering diseases (AIBDs) with predominant involvement of mucous membranes that can be sight-threatening and life-threatening. Rituximab (RTX) has demonstrated its efficacy in severe MMP refractory to conventional immunosuppressants in small series that differed in RTX scheme, concomitant therapies, and outcome definitions. In a meta-analysis involving 112 patients with MMP treated with RTX, complete remission (CR) was reported in 70.5% of cases. Herein, we report the largest retrospective monocentric study on RTX efficacy in a series of 109 severe and/or refractory patients with MMP treated with RTX with a median follow-up period of 51.4 months. RTX was administered in association with immunomodulatory drugs (dapsone, salazopyrine) without any other systemic immunosuppressant in 104 patients. The RTX schedule comprised two injections (1 g, 2 weeks apart), repeated every 6 months until CR or failure, with a unique consolidation injection (1 g) after CR. The median survival times to disease control and to CR were 7.1 months and 12.2 months, respectively. The median number of RTX cycles required to achieve CR in 85.3% of patients was two. The larynx was the lesional site that took the longest time to achieve disease control. One year after RTX weaning, CR off RTX was obtained in 68.7% of cases. CR off RTX with only minimum doses of immunomodulatory drugs was achieved in 22.0% of patients. Further, 10.1% of patients were partial responders and 4.6% were non-responders to RTX. Relapse occurred in 38.7% of cases, of whom 91.7% had achieved CR again at the last follow-up. In MMP, CR was achieved in a longer time and after more rituximab cycles than in pemphigus, especially for patients with MMP with anti-type VII collagen reactivity. RTX with concomitant immunomodulatory drugs was not responsible for an unusual proportion of adverse events. This large study confirms that RTX is an effective therapy in patients with severe and/or refractory MMP, corroborating previous findings regarding the effects of RTX on AIBDs such as pemphigus.
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Doenças Autoimunes , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Pênfigo , Doenças Autoimunes/terapia , Vesícula/tratamento farmacológico , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Mucosa , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Pênfigo/tratamento farmacológico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.
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Dermatologia , Penfigoide Bolhoso , Venereologia , Corticosteroides/uso terapêutico , Idoso , Vesícula/tratamento farmacológico , Humanos , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Qualidade de VidaRESUMO
We report a patient with bullous pemphigoid (BP) who was successfully treated with dupilumab monotherapy. To clarify the underlying mechanism of this effective treatment, we investigated the dynamics of a variety of cytokine-producing T cells before and after treatment in the circulation and in blister fluid using flow cytometry. The patient was a 72-year-old woman who had a pruritic eruption consisting of erythema and tense blisters on the whole body. The skin biopsy and direct immunofluorescence of the skin were typical for BP. The serum level of anti-BP180NC16a antibodies was 111 U/ml. Flow cytometric analyses revealed that the proportions of circulating interleukin (IL)-4-, IL-13-, and IL-31-producing CD4+ and CD8+ T cells were substantially higher in our BP patient than in healthy subjects. Moreover, IL-4- and IL-13-producing CD4+ and CD8+ T cells were much higher in the blister fluids than in the circulation, whereas IL-31-producing CD4+ and CD8+ T cells were only slightly higher in the blister fluids. The proportions of circulating interferon (IFN)-γ-producing CD4+ and CD8+ T cells in the circulation were slightly lower in the patient than in healthy subjects. There was no significant difference in the circulating IL-17-producing CD4+ and CD8+ T cells between the patient and healthy subjects, although IL-17-producing CD4+ and CD8+ T cells were slightly higher in the blister fluids. Treatment with dupilumab promptly improved the pruritus and skin lesions, and anti-BP180 antibodies became negative. After treatment with dupilumab, the proportions of circulating IL-4- and IL-13-producing CD4+ T cells mainly decreased and IL-17- and IL-31-producing CD4+ T cells slightly decreased. There were no significant differences in the proportions of circulating IFN-γ-producing CD4+ and CD8+ T cells between before and after treatment. These results suggest that T-helper (Th)2 cells are involved in the pathogenesis of BP, and dupilumab exerts its effect mainly by suppressing Th2 cytokines.
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Interleucina-4 , Penfigoide Bolhoso , Idoso , Anticorpos Monoclonais Humanizados , Vesícula/tratamento farmacológico , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Citocinas , Feminino , Humanos , Interleucina-13 , Interleucina-17 , Penfigoide Bolhoso/tratamento farmacológicoRESUMO
One of the most important steps for preventing deaths due to snake bites is to administer snake antivenom to the eligible patients in a swift manner. In our study, we aimed to investigate whether procalcitonin is useful for predicting the clinical severity and the necessity of antivenom therapy at the early stages in patients presenting with snake bite. A total of 78 patients over the age of 18 who applied to the emergency department within the first 24 hours were included in this retrospective cross-sectional study. Age and sex of patients, severity of snake bites, total antivenom vials administered, observation periods and outcomes were recorded. Patients were graded according to their clinical severity after the snake bite. Procalcitonin, complete blood count and biochemical parameters of the patients were recorded. According to their clinical severity, the patients' grades were as follows: 21 (26.9%) patients were grade 0; 21 patients (26.9%) were grade 1; 16 patients (20.5%) were grade 2; and 20 patients (25.6%) were grade 3. Snake antivenom was administered to 57 (73.1%) patients. There was a statistically significant difference between procalcitonin levels of patients in respect to their grade (P < 0.001). Sensitivity and specificity of procalcitonin levels of 13.45 and above were 100% and 100% respectively, both for the need of antivenom administration and for the blister formation in the patients. According to our study, we believe that elevated procalcitonin levels should alert the clinicians for possible blister formation, higher clinical severity, and increased requirement for antivenom administration.
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Antivenenos , Mordeduras de Serpentes , Antivenenos/uso terapêutico , Vesícula/tratamento farmacológico , Estudos Transversais , Humanos , Pró-Calcitonina/uso terapêutico , Estudos Retrospectivos , Mordeduras de Serpentes/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. This especially concerns plants with ethnomedical records on their use in treatment of viral infections. AIM OF THE STUDY: To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. MATERIALS AND METHODS: The ethno-medical survey was performed in the Kagera region of Tanzania. The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. RESULTS: THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 µg/ml (selectivity index >476) and 0.14 µg/ml (selectivity index >7143) respectively. The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. CONCLUSIONS: Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions.
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Erythrina , Plantas Medicinais , Infecções Respiratórias , Antivirais/uso terapêutico , Vesícula/tratamento farmacológico , Carboidratos/farmacologia , Etanol/farmacologia , Herpesvirus Humano 2 , Humanos , Casca de Planta , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Vírus Sinciciais Respiratórios , Infecções Respiratórias/tratamento farmacológico , Tanzânia , Água/farmacologiaRESUMO
Wound infection is frequently reported following snakebite (SB). This study is retrospective. It was conducted in the emergency department and the Intensive Care Unit (ICU) of Cayenne General Hospital between 1 January 2016 and 31 July 2021. We included 172 consecutive patients hospitalized for SB envenoming. All patients were monitored for wound infection. Sixty-three patients received antibiotics at admission (36.6%). The main antibiotic used was amoxicillin-clavulanate (92.1%). Wound infection was recorded in 55 cases (32%). It was 19% in grade 1, 35% in grade 2, and 53% in grade 3. It included abscess (69.1%), necrotizing fasciitis (16.4%), and cellulitis (21.8%). The time from SB to wound infection was 6 days (IQR: 3-8). The main isolated microorganisms were A. hydrophila and M. morganii (37.5% and 18.8% of isolated organisms). Surgery was required in 48 patients (28.1%), and a necrosectomy was performed on 16 of them (33.3%). The independent factors associated with snakebite-associated infection were necrosis (p < 0.001, OR 13.15, 95% CI: 4.04-42.84), thrombocytopenia (p = 0.002, OR: 3.37, 95% CI: 1.59-7.16), and rhabdomyolysis (p = 0.046, OR: 2.29, 95% CI: 1.02-5.19). In conclusion, wound infection following SB is frequent, mainly in grade 2 and 3 envenomed patients, especially those with necrosis, thrombocytopenia, and rhabdomyolysis. The main involved bacteria are A. hydrophila and M. morganii.
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Infecções Bacterianas/etiologia , Mordeduras de Serpentes/complicações , Infecção dos Ferimentos/etiologia , Adulto , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/cirurgia , Vesícula/complicações , Vesícula/tratamento farmacológico , Vesícula/cirurgia , Feminino , Guiana Francesa , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/complicações , Necrose/tratamento farmacológico , Necrose/cirurgia , Estudos Retrospectivos , Rabdomiólise/complicações , Rabdomiólise/tratamento farmacológico , Rabdomiólise/cirurgia , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/cirurgia , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Trombocitopenia/cirurgia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/cirurgiaAssuntos
Vesícula/diagnóstico , Dermatoses do Pé/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Administração Oral , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Vesícula/tratamento farmacológico , Vesícula/microbiologia , Pré-Escolar , Diagnóstico Diferencial , Feminino , Dermatoses do Pé/tratamento farmacológico , Dermatoses do Pé/microbiologia , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologiaRESUMO
The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty-four healthy male volunteers received a two-and-a-half-day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two-and-a-half-day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti-inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti-inflammatory effects of such compounds in a minimally invasive manner.
Assuntos
Clobetasol , Lipopolissacarídeos , Corticosteroides , Anti-Inflamatórios/uso terapêutico , Vesícula/tratamento farmacológico , Clobetasol/farmacologia , Clobetasol/uso terapêutico , Citocinas , Drogas em Investigação , Eritema/tratamento farmacológico , Glucocorticoides/farmacologia , Voluntários Saudáveis , Humanos , Masculino , Prednisolona/farmacologiaRESUMO
The widespread use of immune checkpoint inhibitors in several malignancies has revealed new immune-related adverse events. Bullous pemphigoid (BP) is an antibody-driven autoimmune disease characterized by skin inflammation and fluid-filled bullae. Herein, a 69-year-old man with lung squamous cell carcinoma developed multiple vesicles and tense bullae 3 weeks after the initiation of a programmed death-1 (PD-1) inhibitor, pembrolizumab, and chemotherapy. Biopsy revealed a subepidermal bulla with lymphocytic and eosinophil infiltration, and immunohistochemical studies predominantly showed CD4+ cells, a few CD8+ cells, and the occasional CD20+ lymphocyte. The serum anti-BP180 antibody level, as well as the interleukin-6 and interleukin-10 levels, were elevated compared to the lower levels of tumor necrosis factor-α. Eosinophil levels were high and consistent with the development of blisters. A diagnosis of BP associated with PD-1 inhibitor therapy was made, and the Common Terminology Criteria for Adverse Events classification was grade 3. Immunotherapy was permanently discontinued, and the patient's bullous lesions failed to react to high-dose systemic corticosteroids combined with minocycline and niacinamide. Intermittent blister recurrence occurred in 2 months, eventually improving with the administration of two courses of intravenous immunoglobulin. At 5 weeks of follow-up, the patient's tumor was reduced on a computed tomographic scan. Despite stable BP treatment, however, he repeatedly developed complications due to the complexity of his underlying disease and could not be treated with anti-tumor therapy. Early recognition and management of serious immune-related bullous dermatologic toxicity are essential for patient safety.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Penfigoide Bolhoso , Masculino , Humanos , Idoso , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/diagnóstico , Inibidores de Checkpoint Imunológico/efeitos adversos , Vesícula/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Esteroides/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/complicaçõesRESUMO
Las porfirias son un grupo complejo y heterogéneo de defectos en la vía de la síntesis del hemo. La porfiria hepato eritropoyética es un subtipo muy poco frecuente y de presentación en la infancia, con compromiso cutáneo predominante. Describimos el caso clínico de una paciente de 5 años, que se presenta con lesiones cutáneas e hipertricosis, se confirma el diagnóstico por elevación de uroporfirinas en orina y secuenciación del gen UROD.
Porphyria is a complex and heterogeneous group of heme synthesis disorder. Hepato-erythropoietic porphyria is a very rare subtype that onsets in childhood, and shows predominant skin involvement. We describe the clinical case of a 5-year-old patient who showed skin lesions and hypertrichosis and whose diagnosis was confirmed due to increased uroporphyrins in urine and UROD gene sequencing
A porfiria é um grupo complexo e heterogêneo de distúrbios da síntese do grupo heme. A porfiria hepato-eritropoiética é um subtipo muito raro que se inicia na infância e mostra envolvimento predominante da pele. Descrevemos o caso clínico de uma paciente de 5 anos que apresentou lesões cutâneas e hipertricose e cujo diagnóstico foi confirmado por aumento de uroporfirinas na urina e sequenciamento do gene UROD.