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1.
Molecules ; 24(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505853

RESUMO

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.


Assuntos
Ativação do Complemento/efeitos dos fármacos , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Leucocitose/sangue , Lipossomos/farmacologia , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Colesterol/química , Convertases de Complemento C3-C5/química , Convertases de Complemento C3-C5/farmacologia , Proteínas do Sistema Complemento/química , Proteínas do Sistema Complemento/metabolismo , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/patologia , Venenos Elapídicos/química , Venenos Elapídicos/farmacologia , Humanos , Hipotensão/sangue , Hipotensão/induzido quimicamente , Leucocitose/induzido quimicamente , Leucopenia/sangue , Leucopenia/induzido quimicamente , Lipossomos/química , Nanopartículas/química , Polietilenoglicóis/química , Ratos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Zimosan/química , Zimosan/farmacologia
2.
J Med Case Rep ; 13(1): 190, 2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31228952

RESUMO

BACKGROUND: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are two forms of thrombotic microangiopathies. They are characterized by severe thrombocytopenia, microangiopathic hemolysis, and thrombosis, leading to a systemic inflammatory response and organ failure. Plasmapheresis is used to treat thrombotic microangiopathies. A different entity known as atypical hemolytic uremic syndrome has garnered more clinical recognition because reported cases have described that it does not respond to standard plasmapheresis. Diclofenac potassium is a non-steroidal anti-inflammatory drug that is used to treat pain. CASE REPORT: A 35-year-old Hispanic man presented to our emergency department with complaints of generalized malaise, fever, and an evanescent skin rash. During admission, he reported the use of diclofenac potassium for back pain on a daily basis for 1 week. He was noted to have peripheral eosinophilia, so he was admitted for suspected drug reaction involving eosinophilia and systemic symptoms. His initial laboratory work-up showed microangiopathic hemolytic anemia and thrombocytopenia. He also experienced a seizure, encephalopathy, and had a PLASMIC score of 7, thus raising concerns for thrombotic thrombocytopenic purpura. He underwent emergent plasmapheresis, which improved his clinical condition. The diagnosis was confirmed by assessing the levels of disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, which was less than 3%. In addition, his skin biopsy was positive for patchy complement deposition, demonstrating complement dysregulation. CONCLUSION: Thrombotic thrombocytopenic purpura is a rare condition that can be acquired. Our case is rare because it represents the first report of diclofenac potassium-induced thrombotic thrombocytopenic purpura with subjacent complement activation and dysregulation. Early recognition and aggressive management led to a favorable outcome.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Adulto , Proteínas do Sistema Complemento/metabolismo , Síndrome de Hipersensibilidade a Medicamentos/metabolismo , Humanos , Masculino , Plasmaferese , Púrpura Trombocitopênica Trombótica/metabolismo
3.
G Ital Dermatol Venereol ; 154(4): 488-491, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31251007

RESUMO

Telaprevir is a specific inhibitor of the hepatitis C (HCV) serine protease 3. Cutaneous side effects have been reported with telaprevir. Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare yet severe adverse drug-induced reaction characterized by exfoliative dermatitis and maculopapular rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and myriad internal organ involvement. We report a case of DRESS due to telaprevir. A 64-year-old Caucasian man with chronic hepatitis C developed a progressive diffuse, painful maculopapular exanthema with fever, facial edema, lymphadenopathy at week 11 of chronic hepatitis C therapy with telaprevir, Peg-Interferon alfa-2a, and ribavirin. He had no exposures to any other medications. He presented an eosinophilia (up to 6.29 X 109 cells/L), skin biopsy was consistent with a drug reaction. The HCV treatment was stopped and methylprednisolone 0.75 mg/kg/day was started. Cutaneous and systemic symptoms had a rapid resolution in few days. Telaprevir can activate severe skin reactions that can mimic an infectious disease, therefore early diagnosis and discontinuation of chronic hepatitis C treatment is mandatory.


Assuntos
Antivirais/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Oligopeptídeos/efeitos adversos , Antivirais/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/fisiopatologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem
4.
Pediatr Dermatol ; 36(4): e99-e101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31132165

RESUMO

Lymphadenopathy is a common sign for drug reaction and eosinophilia with systemic symptoms (DRESS) syndrome, but hilar and mediastinal lymphadenopathy may be underreported. We describe a 7-year-old boy who started taking ethosuximide for absence seizures and presented with diffuse rash, fever, elevated transaminases, facial swelling, and hilar and mediastinal lymphadenopathy. His mediastinal lymphadenopathy was concerning for lymphoma, which led to more invasive testing to rule out malignancy. This report highlights an unusual and likely underreported presenting sign of DRESS syndrome in children.


Assuntos
Corticosteroides/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/efeitos adversos , Linfadenopatia/induzido quimicamente , Biópsia por Agulha , Criança , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/patologia , Eosinofilia/induzido quimicamente , Eosinofilia/fisiopatologia , Epilepsia Tipo Ausência/diagnóstico , Etossuximida/uso terapêutico , Seguimentos , Humanos , Imuno-Histoquímica , Linfadenopatia/patologia , Linfadenopatia/fisiopatologia , Masculino , Mediastino/patologia , Recidiva , Medição de Risco
10.
An Sist Sanit Navar ; 42(1): 89-92, 2019 Apr 25.
Artigo em Espanhol | MEDLINE | ID: mdl-30895969

RESUMO

The DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a serious pharmacodermia which must be taken into account when establishing an optimal early treatment to prevent a systemic and potentially lethal evolution. Pharmacodermias are the third most frequent cause of adverse effects during surgical hospitalization, after nosocomial infections and intraoperative complications. In most cases, they pose a challenge to the surgeon, since their onset is nonspecific and, therefore, can be easily mistaken for a surgery complication. We present the case of a 54-year-old man, healthy and without relevant background, who was operated on two times due to spontaneous abdominal bleeding. Three weeks after the last surgery, and coinciding with the administration of oral metamizole, the patient developed a DRESS syndrome. The initial unspecific deterioration, characteristic of this syndrome, is the main cause of the delay in diagnosis and correct treatment, causing the resulting evolution to systemic affectation.


Assuntos
Dipirona/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Diagnóstico Tardio , Diagnóstico Diferencial , Dipirona/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fatores de Tempo
11.
JAMA Dermatol ; 155(6): 666-672, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30916737

RESUMO

Importance: Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. Objective: To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. Design, Setting, and Participants: A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. Exposures: Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. Main Outcomes and Measures: The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. Results: Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. Conclusions and Relevance: Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.


Assuntos
Dapsona/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/prevenção & controle , Antígeno HLA-B13/genética , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Adulto , Alelos , China , Clofazimina/administração & dosagem , Estudos de Coortes , Dapsona/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Quimioterapia Combinada , Feminino , Humanos , Incidência , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rifampina/administração & dosagem
12.
Am J Case Rep ; 20: 345-348, 2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30877266

RESUMO

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic life-threatening reaction comprised of fevers, rash, and leukocytosis with eosinophilia. Though characteristically associated with leukocytosis, there are rare case reports of DRESS-induced agranulocytosis. DRESS is most frequently caused by antiepileptic medications; however, it has very rarely been reported in relation to oxacillin. We describe a case of oxacillin-induced DRESS associated with agranulocytosis. CASE REPORT A 52-year-old male was admitted for an epidural abscess secondary to oxacillin-sensitive Staphylococcus aureus, for which an extended course of oxacillin and rifampin was initiated. On day 22 of therapy, the patient developed a fever of 38.7°C (101.6°F) with rigors. His complete blood cell count revealed new leukopenia (1.8×10³/uL) with 16% eosinophils and 3% atypical lymphocytes. Antibiotics were transitioned from oxacillin and rifampin to vancomycin, cefepime, and rifampin for presumed sepsis of unclear etiology. On day 23, he was noted to have a pruritic erythematous blanching papular rash on his chest, trunk, neck, and left upper extremity. Infectious workup was unrevealing, and his fever curve up-trended to 39.3°C (102.7°F) with no clinical improvement on broad-spectrum antimicrobials, suggestive of a non-infectious etiology of his rash and fevers. His rash evolved into confluent red patches, and eosinophilia rose to 21%, which was concerning for a drug reaction. His RegiSCAR score was calculated to be 6, consistent with definite DRESS. Leukopenia resolved (6.3×10³/uL) 4 days after discontinuing oxacillin. His epidural abscess was ultimately treated with daptomycin, and DRESS was managed supportively with antihistamines and triamcinolone cream. CONCLUSIONS We highlight this case because of the rarity of DRESS with agranulocytosis related to oxacillin. Beta-lactam antibiotics are widely used, and while DRESS is an uncommon condition, clinicians should consider this diagnosis when managing patients with fevers, leukopenia, and rash.


Assuntos
Antibacterianos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Oxacilina/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Estafilocócicas/tratamento farmacológico
13.
J Am Acad Dermatol ; 81(1): 123-128, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30738120

RESUMO

BACKGROUND: Although hypersensitivity reactions are well characterized for certain medications, vancomycin-associated drug-induced hypersensitivity syndrome (DIHS), or drug reaction with eosinophilia and systemic symptoms (DRESS), has yet to be defined. OBJECTIVE: To better define the clinical phenotype of vancomycin-associated DIHS. METHODS: A retrospective case series was conducted over an 8-year period at a single, academic institution. A total of 29 cases of DIHS/DRESS were identified, of which 4 were attributed to vancomycin. A literature review was performed; it identified 28 additional cases of vancomycin-induced DIHS. Vancomycin-associated acute interstitial nephritis was also reviewed to detect additional, previously uncharacterized cases of systemic hypersensitivity. The review yielded 11 additional cases. RESULTS: In this literature review and retrospective series, the incidence of renal dysfunction among vancomycin-induced cases (75% and 68% of cases in the series and literature, respectively) was notably higher than the overall reported incidence in DIHS (10%-40%). The degree of renal impairment was also significantly increased in the retrospective series (a median 4.98-fold change in baseline creatinine level vs a 2.25-fold increase in non-vancomycin-associated cases [P = .011]). LIMITATIONS: The principal limitation of this study is the small sample size. Other notable limitations include the retrospective nature of the study and absence of confirmatory renal biopsies. CONCLUSION: Although the current understanding of DIHS/DRESS is imperfect, our findings suggest that vancomycin-induced cases present with a unique phenotype characterized by a higher burden of renal involvement.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Vancomicina/efeitos adversos , Centros Médicos Acadêmicos , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Síndrome de Hipersensibilidade a Medicamentos/fisiopatologia , Eosinofilia/induzido quimicamente , Eosinofilia/epidemiologia , Eosinofilia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Estados Unidos , Vancomicina/uso terapêutico , Adulto Jovem
14.
J Am Acad Dermatol ; 80(3): 608-616, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30612984

RESUMO

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are frequent in inpatient oncology. Early intervention might reduce morbidity, mortality, and hospitalization costs; however, current clinical and histologic features are unreliable SCAR predictors. There is a need to identify rational markers of SCARs that could lead to effective therapeutic interventions. OBJECTIVE: To characterize the clinical and serologic features of hospitalized patients with cancer who developed SCARs. METHODS: Retrospective review of 49 hospitalized cancer patients with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL] 6, IL-10, and tumor necrosis factor [TNF] α) or elafin, and a prior dermatology consultation. Patients were categorized as having a simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement. RESULTS: Fifteen out of 49 patients (30.6%) were deceased at 6 months from time of dermatologic consultation. Elafin, IL-6, and TNF-α were significantly higher in patients who died compared with patients who were still alive at 6 months. IL-6 and IL-10 were significantly higher in patients with a drug-related complex rash. LIMITATIONS: Retrospective design, limited sample size, and high-risk patient population. CONCLUSION: In cancer patients with SCARs, elafin, IL-6, and TNF-α levels might predict a poor outcome. Agents directed against these targets might represent rational treatments for the prevention of fatal SCARs.


Assuntos
Citocinas/sangue , Síndrome de Hipersensibilidade a Medicamentos/sangue , Elafina/sangue , Mortalidade Hospitalar , Neoplasias/tratamento farmacológico , Síndrome de Stevens-Johnson/sangue , Adulto , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Superfície Corporal , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Edema/etiologia , Eosinofilia/etiologia , Face , Feminino , Febre/etiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Hospitalização , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Linfócitos/patologia , Masculino , Púrpura/etiologia , Estudos Retrospectivos , Síndrome de Stevens-Johnson/etiologia , Fator de Necrose Tumoral alfa/sangue
15.
J Dermatol ; 46(3): 226-233, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30663091

RESUMO

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi-organ systemic drug reaction characterized by hematological abnormalities and reactivation of human herpesvirus-6 (HHV-6). DIHS/DRESS is typically associated with a limited number of drugs, such as the anticonvulsants. Our group has treated 12 patients for DIHS/DRESS due to lamotrigine (LTG), but their presentation differed from that of patients with DIHS/DRESS caused by other drugs. The aim of the present study was to identify significant differences between DIHS/DRESS caused by LTG versus other drugs. We retrospectively reviewed data of 12 patients with DIHS/DRESS caused by LTG and 32 patients with DIHS/DRESS due to other drugs. The increase in alanine aminotransferase level was significantly milder in the LTG group than the DIHS/DRESS group due to other drugs. The percentage of atypical lymphocytes in the blood during DIHS/DRESS was lower in the LTG group. Serum levels of lactate dehydrogenase and thymus and activation-regulated chemokine were also lower in the LTG group. There were fewer DIHS/DRESS patients with HHV-6 reactivation in the LTG group than in the group treated with other drugs. Lymphocyte transformation after DIHS/DRESS onset was faster in the LTG group. The two groups did not differ with respect to the interval from first drug intake to rash, white blood cell count, blood eosinophilia or DRESS score. There were no significant histopathological differences between the two groups. The features of LTG-associated DIHS/DRESS and DIHS/DRESS due to other drugs differ.


Assuntos
Anticonvulsivantes/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Lamotrigina/efeitos adversos , Adulto , Síndrome de Hipersensibilidade a Medicamentos/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Am J Clin Dermatol ; 20(2): 217-236, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30652265

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DReSS), also known as drug-induced hypersensitivity syndrome (DiHS), is an uncommon severe adverse reaction to medications. It is important to recognize it as it is potentially fatal and can cause significant morbidity. From the first reports of drug reactions related to certain anticonvulsants characterized by fever, liver enzyme elevation, and skin changes, our continuously growing understanding of this entity has allowed us to describe its physiopathology and clinical features even further. The relationship of genetic factors, viral activation, and specific drug exposure is now known to play a role in this disease. There is still not a widely accepted marker for DReSS/DiHS, but the spectrum of clinical and laboratory features has now been better outlined. The mainstay of treatment is the use of systemic corticosteroids, but other options such as intravenous immunoglobulin, cyclosporine, mycophenolate mofetil, rituximab, and cyclophosphamide have been described. We present a comprehensive review of the literature on DReSS/DiHS, focusing on its history, etiopathogenesis, diagnosis, therapeutic approach, and outcome.


Assuntos
Corticosteroides/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Fatores Imunológicos/uso terapêutico , Anticonvulsivantes/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/terapia , Humanos , Imunossupressores/uso terapêutico
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