RESUMO
BACKGROUND: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series. OBJECTIVES: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. METHODS: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs. RESULTS: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. CONCLUSION: Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.
Assuntos
Infecções por HIV , Histoplasmose , Hidrocefalia , Meningite , Vasculite , Adulto Jovem , Humanos , Masculino , Adulto , Feminino , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Itraconazol/uso terapêutico , Infecções por HIV/tratamento farmacológico , Antifúngicos/uso terapêutico , Sistema Nervoso Central , Meningite/diagnóstico , Hidrocefalia/induzido quimicamente , Hidrocefalia/tratamento farmacológico , Vasculite/induzido quimicamente , Vasculite/tratamento farmacológicoAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa , Fármacos Gastrointestinais/efeitos adversos , Vasculite/induzido quimicamente , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , HumanosRESUMO
OBJECTIVES: The aims of this study were to describe clinical and laboratory manifestations of patients with levamisole-adulterated cocaine-induced vasculitis/vasculopathy and to propose a skin classification according to the distribution and severity of lesions. METHODS: We report the characteristics of 30 patients admitted with levamisole-adulterated cocaine-induced vasculitis/vasculopathy in 4 high-complexity institutions in Colombia, from December 2010 to May 2017. We compare our findings with the main published series. RESULTS: Median age was 31 years (interquartile range, 27-38 years) with a male-to-female ratio of 5:1. Eighty-three percent of the patients had retiform purpura affecting the limbs, buttocks, face, or abdomen; 73% had ear necrosis, 50% cutaneous ulcers, 17% genital necrosis, 13% oral ulcers, and 10% digital necrosis. Cutaneous involvement was classified according to the frequency of the compromised corporal area, and purpuric lesions were stratified in 4 grades of severity. Anti-neutrophil cytoplasmic autoantibodies were positive in 85% of the cases, lupus anticoagulant in 73%, and antinuclear autoantibodies in 57%; rheumatoid factor was negative in all cases. We found nephritis in 17 cases (57%). Prednisolone was used in most of the patients (70%), with other immunosuppressive agents being used in a lower percentage. Improvement was observed in 93% of the patients, but symptoms recurred in 40%, attributed to relapses in consumption. End-stage chronic renal disease developed in 10% of the cases, and 1 patient died. CONCLUSIONS: Because of rising cocaine consumption and levamisole adulteration frequency, levamisole-adulterated cocaine-induced vasculitis/vasculopathy is becoming more common. Detailed characterization of skin involvement coupled with multiple antibody positivity is essential for a diagnosis. Renal involvement is frequent, clinically and histologically heterogeneous, and potentially serious.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína , Glomerulonefrite , Levamisol , Púrpura , Vasculite , Adjuvantes Farmacêuticos/efeitos adversos , Adjuvantes Farmacêuticos/farmacologia , Adulto , Autoanticorpos/sangue , Cocaína/farmacologia , Colômbia , Inibidores da Captação de Dopamina/farmacologia , Contaminação de Medicamentos , Feminino , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Glomerulonefrite/terapia , Humanos , Levamisol/efeitos adversos , Levamisol/farmacologia , Masculino , Necrose , Administração dos Cuidados ao Paciente/métodos , Púrpura/induzido quimicamente , Púrpura/diagnóstico , Púrpura/imunologia , Púrpura/terapia , Pele/patologia , Resultado do Tratamento , Vasculite/induzido quimicamente , Vasculite/diagnóstico , Vasculite/imunologia , Vasculite/terapiaRESUMO
Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.
Assuntos
Benzoatos/efeitos adversos , Toxidermias/etiologia , Quelantes de Ferro/efeitos adversos , Síndromes Mielodisplásicas/tratamento farmacológico , Triazóis/efeitos adversos , Urticária/induzido quimicamente , Vasculite/induzido quimicamente , Idoso , Biópsia , Deferasirox , Toxidermias/patologia , Feminino , Humanos , Urticária/patologia , Vasculite/patologiaRESUMO
BACKGROUND:: Varicose veins and the complications of venous disease are common disorders in humans. OBJECTIVE:: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. METHODS:: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. RESULTS:: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. STUDY LIMITATIONS:: Relatively small number of experimental animals used. CONCLUSIONS:: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/farmacologia , Soluções Esclerosantes/farmacologia , Escleroterapia/métodos , Tetradecilsulfato de Sódio/administração & dosagem , Varizes/terapia , Animais , Bleomicina/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Injeções Intravenosas , Lipossomos , Coelhos , Soluções Esclerosantes/administração & dosagem , Soluções Esclerosantes/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/tratamento farmacológico , Veias/efeitos dos fármacosRESUMO
Abstract: Background: Varicose veins and the complications of venous disease are common disorders in humans. Objective: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Methods: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Results: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Study limitations: Relatively small number of experimental animals used. Conclusions: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.
Assuntos
Animais , Coelhos , Soluções Esclerosantes/farmacologia , Tetradecilsulfato de Sódio/administração & dosagem , Varizes/terapia , Bleomicina/farmacologia , Escleroterapia/métodos , Antibióticos Antineoplásicos/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Soluções Esclerosantes/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/tratamento farmacológico , Veias/efeitos dos fármacos , Bleomicina/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Injeções Intravenosas , LipossomosRESUMO
PURPOSE OF REVIEW: To understand the clinical spectrum of cocaine-levamisole-induced vasculitis. Worldwide recreational drug consumption is high among the adult population from various social strata. The use of cocaine with levamisole, a frequently added antiparasitic diluent, favors the manifestations of vasculitic lesions, especially in the skin. RECENT FINDINGS: New insights into immunological mechanisms involved in the pathogenesis of the disease. There are still many unknown aspects in the pathogenesis of this disease, such as the immune system interaction with p-ANCAs and the release of inflammatory NETs (neutrophil extracellular traps), which are the origin of auto-antigens and tissue damage, manifesting as vasculitic purpura on the skin. The clinical presentation constitutes a challenge for the clinician to be able to distinguish it from small-vessel vasculitides. This paper intends to improve the understanding of this condition, exhibiting the broad clinical spectrum of local and systemic manifestations of cocaine-levamisole-induced vasculitis, to facilitate a timely diagnosis, in order to take corrective measures and avoid sequelae, along with tissue damage and the consequent deformities and permanent scars.
Assuntos
Cocaína/efeitos adversos , Drogas Ilícitas/efeitos adversos , Levamisol/efeitos adversos , Vasculite/induzido quimicamente , Anticorpos Anticitoplasma de Neutrófilos , Armadilhas Extracelulares , Humanos , Vasculite/imunologiaRESUMO
Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.
Assuntos
Humanos , Feminino , Idoso , Triazóis/efeitos adversos , Urticária/induzido quimicamente , Vasculite/induzido quimicamente , Benzoatos/efeitos adversos , Síndromes Mielodisplásicas/tratamento farmacológico , Quelantes de Ferro/efeitos adversos , Toxidermias/etiologia , Urticária/patologia , Vasculite/patologia , Biópsia , Toxidermias/patologiaRESUMO
BACKGROUND: Adverse cutaneous drug reactions are frequent in hospital settings and are responsible for increased morbidity, mortality, and socioeconomic costs. The objective of this study was to identify high risk factors in hospitalized patients with adverse cutaneous drug reactions. METHODS: This descriptive and retrospective study was performed with data from 117 patients admitted to a quaternary hospital over 44 months. We reviewed their epidemiological data, suspected drugs, clinical presentation, histopathological diagnosis, and outcome. Statistical analysis was performed using the chi-squared test with a significance level of 5%. RESULTS: Anticonvulsants were responsible for 23.9% of cases followed by antibiotics (22.2%). In 29% of cases, patients were taking multiple medications that could have triggered their reactions. The most common clinical forms were exanthema (37.6%), drug reaction with eosinophilia and systemic symptoms (DRESS) (14.5%), and Stevens-Johnson syndrome/toxic epidermal necrolysis (12.8%). Anticonvulsants were associated with severe forms of adverse drug reactions. Most patients (89.7%) presented clinical improvement after treatment. There was a relationship between the use of anticonvulsants and atypical lymphocytes in the dermal infiltrate, as well as the clinical form DRESS and atypical lymphocytes in the dermal infiltrate. CONCLUSIONS: The use of anticonvulsants was a high risk factor for severe clinical forms of drug reactions. The presence of atypical lymphocyte infiltrates in the dermis could indicate the use of anticonvulsants.
Assuntos
Antibacterianos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Toxidermias/etiologia , Exantema/induzido quimicamente , Pustulose Exantematosa Aguda Generalizada/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dermatite Esfoliativa/induzido quimicamente , Toxidermias/patologia , Toxidermias/terapia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/patologia , Eritema Multiforme/induzido quimicamente , Feminino , Síndrome Mão-Pé/etiologia , Hospitais , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Síndrome de Stevens-Johnson/etiologia , Urticária/induzido quimicamente , Vasculite/induzido quimicamente , Adulto JovemRESUMO
The vasculities are complex diseases. Their cutaneous manifestations are very important and often mirror several pathologies. Cocaine use has been related to both, vasculitis and thrombotic vasculopathy and pseudovasculitis. A new syndrome has been described in association with its adulteration with levamisole. It can be very serious, leading patients to death. This is relevant as levamisole-adultered cocaine seems to be increasingly offered to consumers. Our goal is to report the first two cases in Mexico, which faces an important raise in cocaine use, emphasizing that a high suspicion based on certain characteristics allows for early recognition and adequate treatment.
Las vasculitis son enfermedades complejas con manifestaciones cutáneas importantes que pueden traducir diversas patologías. El uso de cocaína está relacionado con casos tanto de vasculitis y vasculopatía trombótica, como de pseudovasculitis. Recientemente se ha descrito una condición peculiar asociada a su forma adulterada con levamisol, la cual puede ser incluso mortal, y cuya frecuencia va en aumento. Nuestro objetivo es reportar los primeros dos casos de alta sospecha en México, que enfrenta un incremento en el consumo de cocaína, enfatizando en que ciertas características y la realización de determinados estudios permiten la identificación temprana y el tratamiento adecuado de esta condición.