RESUMEN
The COVID-19 outbreak has been declared the sixth Public Health Emergency of International Concern certified by the World Health Organization. With the extensive application of COVID-19 vaccines, rare but serious adverse reactions have gradually emerged, among which systemic capillary leak syndrome (SCLS) deserves our attention. SCLS is difficult to diagnose. Not only can it exacerbate various diseases, but also can lead to pulmonary edema, kidney failure, and even death. We summarized and discussed case reports of SCLS induced by COVID-19 vaccines to raise awareness of COVID-19 vaccine-associated rare diseases. We conducted a comprehensive search in Web of Science, PubMed and Embase and collected case reports of SCLS induced by COVID-19 vaccine before February 19, 2024. We identified and analyzed 12 articles, encompassing 15 cases. We synthesized the data to summerize possible mechanisms of SCLS, clinical manifestations, differential diagnoses, and therapeutic approaches. Most SCLS occurred after vaccination with the Pfe-Biontech mRNA vaccine (9/15) and following the second vaccination (10/15). Almost all patients experienced hypotension (13/15) and tachycardia (11/15). Most patients received intravenous fluids (9/15) and corticosteroids (9/15). 11 patients were recovered and were discharged, while 4 patients died. Inflammation and endothelial cell damage may be linked to SCLS and COVID-19 vaccines. These findings highlight the necessity of focusing on serious adverse reactions of COVID-19 vaccines and the urgency to reconsider the safety of COVID-19 vaccines.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Síndrome de Fuga Capilar , Humanos , Síndrome de Fuga Capilar/etiología , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , COVID-19/complicaciones , Persona de Mediana Edad , Femenino , Masculino , Anciano , Adulto , SARS-CoV-2/inmunología , Vacunación/efectos adversos , Hipotensión/etiologíaRESUMEN
Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.
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Protocolos de Quimioterapia Combinada Antineoplásica , Síndrome de Fuga Capilar , Linfohistiocitosis Hemofagocítica , Linfoma de Células B Grandes Difuso , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Síndrome de Fuga Capilar/etiología , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/terapia , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vincristina/uso terapéutico , Masculino , Ciclofosfamida/uso terapéutico , Prednisona/uso terapéutico , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Rituximab/uso terapéutico , Persona de Mediana EdadRESUMEN
Systemic capillary leak syndrome (SCLS) is a rare and life-threatening disorder characterised by leaking of intravascular fluid to extravascular tissues. An association with immunotherapy and COVID-19 vaccination has been reported as potential triggers. A case of a patient in her 70s developing SCLS after the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination with a history of metastatic melanoma treated with nivolumab (PD-1 monoclonal antibody) and ipilimumab (anti-CTLA4 monoclonal antibody) is reported. The aetiology and management of SCLS are also reviewed in this case context.
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COVID-19 , Síndrome de Fuga Capilar , Ipilimumab , Melanoma , Nivolumab , Humanos , Melanoma/tratamiento farmacológico , Síndrome de Fuga Capilar/inducido químicamente , Nivolumab/efectos adversos , Femenino , Ipilimumab/efectos adversos , Anciano , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Vacuna BNT162/efectos adversos , SARS-CoV-2 , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
Idiopathic systemic capillary leak syndrome (ISCLS) is a rare, recurrent condition with dramatically increased blood vessel permeability and, therefore, induction of systemic edema, which may lead to organ damage and death. In this issue of the JCI, Ablooglu et al. showed that ISCLS vessels were hypersensitive to agents known to increase vascular permeability, using human biopsies, cell culture, and mouse models. Several endothelium-specific proteins that regulate endothelial junctions were dysregulated and thereby compromised the vascular barrier. These findings suggest that endothelium-intrinsic dysregulation underlies hyperpermeability and implicate the cytoplasmic serine/threonine protein phosphatase 2A (PP2A) as a potential drug target for the treatment of ISCLS.
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Síndrome de Fuga Capilar , Permeabilidad Capilar , Proteína Fosfatasa 2 , Humanos , Animales , Ratones , Síndrome de Fuga Capilar/patología , Síndrome de Fuga Capilar/metabolismo , Proteína Fosfatasa 2/metabolismo , Proteína Fosfatasa 2/genética , Endotelio Vascular/metabolismo , Endotelio Vascular/patologíaRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which is mainly characterized by joint swelling, pressure pain and joint destruction. Some patients may suffer from a variety of serious complications, which require prompt diagnosis and treatment. Otherwise, the patient condition may deteriorate rapidly, leading to premature death. OBJECTIVE: We reported a case of RA combined with hyperferritinemic syndrome and capillary leak syndrome (CLS) that was successfully treated with tocilizumab (TCZ), with the aim of improving diagnostic ideas for clinicians and consequently improving the diagnosis and treatment of the hyperferritinemic syndrome and CLS. CASE SUMMARY: A 55-year-old female patient was admitted to the Department of Infectious Diseases of our hospital due to "recurrent fever for more than 1 month and aggravation for 3 days." The patient was diagnosed with fever of unknown origin (lung infection?) and received anti-infective therapy with large encirclement of anti-bacterial, antifungal and empirical anti-tuberculosis successively during hospitalization in the Department of Infectious Diseases. Yet her condition continues to progress. The patient was eventually diagnosed with RA combined with hyperferritinemic syndrome and CLS. Then she received glucocorticoids (GC) (160 mg qd) combined with intravenous immunoglobulin (IVIG, 20 g/d, for 3 days). We considered that the patient also had an overwhelming proinflammatory cytokine storm, so she received a strong anti-inflammatory treatment with TCZ (400 mg qm). The patient symptoms and follow-up chest CT showed significant improvement following treatment. CONCLUSION: TCZ has good efficacy in the treatment of RA combined with hyperferritinemic syndrome and CLS and is expected to be a promising treatment.
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Anticuerpos Monoclonales Humanizados , Artritis Reumatoide , Síndrome de Fuga Capilar , Hiperferritinemia , Humanos , Femenino , Persona de Mediana Edad , Hiperferritinemia/tratamiento farmacológico , Hiperferritinemia/etiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Síndrome de Fuga Capilar/tratamiento farmacológico , Síndrome de Fuga Capilar/etiología , SíndromeRESUMEN
A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The pneumonia that had been present since admission worsened, and a drug-induced skin rash appeared. On day 17, she presented with respiratory failure and shock, complicated by hemoconcentration and hypoalbuminemia. This was considered capillary leak syndrome due to pneumonia and drug allergy, so she was started on pulse steroid therapy and IVIG, and was intubated on the same day. On day 18, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was started due to worsening blood gas parameters despite ventilatory management. Bronchoalveolar lavage fluid was serous, and both blood and sputum cultures yielded negative. The patient was weaned from VV-ECMO on day 26 as the pneumonia improved with recovery of hematopoiesis. She was disoriented, and a CT scan on day 28 revealed cerebral hemorrhage. Her strength recovered with rehabilitation. After induction chemotherapy, RUNX1::RUNX1T1 mRNA was not detected in bone marrow. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.
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Síndrome de Fuga Capilar , Oxigenación por Membrana Extracorpórea , Leucemia Mieloide Aguda , Neumonía , Insuficiencia Respiratoria , Humanos , Femenino , Adulto , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Quimioterapia de Inducción , Síndrome de Fuga Capilar/complicaciones , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapiaRESUMEN
We present a case study of a young male with a history of 22q11.2 deletion syndrome (22qDS), diagnosed with systemic capillary leak syndrome (SCLS) who presented with acute onset of diffuse anasarca and sub-comatose obtundation. We hypothesized that his co-presentation of neurological sequelae might be due to blood-brain barrier (BBB) susceptibility conferred by the 22q11.2 deletion, a phenotype that we have previously identified in 22qDS. Using pre- and post-intravenous immunoglobulins (IVIG) patient serum, we studied circulating biomarkers of inflammation and assessed the potential susceptibility of the 22qDS BBB. We employed in vitro cultures of differentiated BBB-like endothelial cells derived from a 22qDS patient and a healthy control. We found evidence of peripheral inflammation and increased serum lipopolysaccharide (LPS) alongside endothelial cells in circulation. We report that the patient's serum significantly impairs barrier function of the 22qDS BBB compared to control. Only two other cases of pediatric SCLS with neurologic symptoms have been reported, and genetic risk factors have been suggested in both instances. As the third case to be reported, our findings are consistent with the hypothesis that genetic susceptibility of the BBB conferred by genes such as claudin-5 deleted in the 22q11.2 region promoted neurologic involvement during SCLS in this patient.
Asunto(s)
Síndrome de Fuga Capilar , Síndrome de DiGeorge , Humanos , Masculino , Niño , Síndrome de Fuga Capilar/diagnóstico , Barrera Hematoencefálica , Células Endoteliales , Permeabilidad , InflamaciónRESUMEN
A 29-year-old Japanese woman was admitted to our hospital with a fever, cardiogenic shock, and cardiac arrest. Laboratory data indicated multiple organ failure in addition to hemoconcentration, hypoalbuminemia, and myocardial damage. The coronary angiography findings were normal, and fulminant myocarditis was suspected. Venoarterial peripheral extracorporeal membrane oxygenation and an Impella CP left ventricular assist device were initiated, along with the administration of positive inotropic agents. However, hypovolemic shock and hypoalbuminemia progressed along with severe anemia, and the patient died 18 hours after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019.
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COVID-19 , Síndrome de Fuga Capilar , Humanos , Síndrome de Fuga Capilar/etiología , Síndrome de Fuga Capilar/diagnóstico , Femenino , COVID-19/complicaciones , Adulto , Resultado Fatal , SARS-CoV-2 , Oxigenación por Membrana Extracorpórea , Choque Cardiogénico/etiología , Choque Cardiogénico/diagnósticoRESUMEN
Clarkson disease, or monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. The specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here, we characterize an autonomous vascular endothelial defect in ISCLS that was recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs were functionally hyperresponsive to permeability-inducing factors like VEGF and histamine, in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of N(γ)-nitro-l-arginine methyl ester (l-NAME) ameliorated vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyperactivation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach.
Asunto(s)
Síndrome de Fuga Capilar , Modelos Animales de Enfermedad , Óxido Nítrico Sintasa de Tipo III , Factor A de Crecimiento Endotelial Vascular , Animales , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratones , Síndrome de Fuga Capilar/metabolismo , Síndrome de Fuga Capilar/patología , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Histamina/metabolismo , Mediadores de Inflamación/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Proteína Fosfatasa 2/metabolismo , Proteína Fosfatasa 2/genética , MasculinoRESUMEN
OBJECTIVE: Capillary leak syndrome (CLS) is characterized by severe systemic edema without specific treatment, resulting in a high mortality rate. This study investigated whether there is organ edema in neonatal CLS patients and specific treatment strategies to improve patient prognosis. METHODS: Thirty-seven newborns diagnosed with CLS were included in this study. (1) Routine point-of-care ultrasound (POCUS) was used to identify whether the patients had visceral edema or fluid collection. (2) All patients were treated with 3% NaCl intravenously, and the clinical manifestations, laboratory indices and outcomes were compared before and after treatment. RESULTS: (1) Diffuse severe edema was found in 92.0% of the patients. (2) The POCUS examination revealed that CLS patients exhibited significant visceral edema in addition to diffuse severe edema, which included pulmonary edema in 67.6%, cerebral edema in 37.8%, severe intestinal edema in 24.3%, severe myocardial edema in 8.1%, pericardial effusion in 5.4%, pleural effusion in 29.7% and peritoneal effusion in 18.9%. Two patients (5.45%) had only myocardial edema without other manifestations. (3) Before and after the intravenous injection of 3% NaCl, there were no significant differences in the serum sodium or potassium levels of CLS patients, while the hemoglobin and hematocrit levels were significantly lower after treatment (p < 0.01). Her plasma ALB concentration and arterial pressure returned to normal levels after the treatment was completed. (4) All the patients survived, and no side effects or complications were observed during or after treatment with 3% NaCl. CONCLUSIONS: (1) In addition to diffuse severe edema, visceral edema and effusion are common and important clinical manifestations of neonatal CLS and need to be detected by routine POCUS. (2) The intravenous injection of 3% NaCl is a safe, effective and specific treatment strategy for neonatal CLS, with a survival rate of 100% and no adverse effects.
Asunto(s)
Síndrome de Fuga Capilar , Humanos , Recién Nacido , Femenino , Síndrome de Fuga Capilar/diagnóstico por imagen , Síndrome de Fuga Capilar/terapia , Cloruro de Sodio/uso terapéutico , Estudios Prospectivos , Edema , Volumen SanguíneoRESUMEN
AIM: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. METHODS: All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. RESULTS: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99-17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. CONCLUSION: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.
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COVID-19 , Síndrome de Fuga Capilar , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , Niño , Masculino , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Fuga Capilar/epidemiología , Síndrome de Fuga Capilar/etiología , Síndrome de Fuga Capilar/diagnóstico , Femenino , Adolescente , Preescolar , Lactante , Suecia/epidemiologíaRESUMEN
Increased vascular permeability is a prevalent feature in a wide spectrum of clinical conditions, but no effective treatments to restore the endothelial barrier are available. Idiopathic systemic capillary leak syndrome (ISCLS) is a life-threatening Paroxysmal Permeability Disorder characterized by abrupt, massive plasma extravasation. This condition serves as a robust model for investigating therapeutic approaches targeting interendothelial junctions. We conducted a single-center, interventional in vitro study at the Referral Center for ISCLS in Italy, involving four diagnosed ISCLS patients, aiming at investigating the effects of FX06, a Bß15-42 fibrin-derived peptide binding to VE-Cadherin, on endothelial barrier exposed to intercritical and acute ISCLS sera. The Transwell Permeability Assay was used to assess the permeability of human umbilical vein endothelial cells (HUVECs) exposed to ISCLS sera with or without FX06 (50 µg/ml). Acute ISCLS serum was also tested in a three-dimensional microfluidic device. Nitric oxide (NO), VE-Cadherin localization, and cytoskeletal organization were also assessed. In two and three-dimensional systems, ISCLS sera increased endothelial permeability, with a more pronounced effect for acute sera. Furthermore, acute sera altered VE-Cadherin localization and cytoskeletal organization. NO levels remained unchanged. FX06 restored the endothelial barrier function by influencing cellular localization rather than VE-Cadherin levels. In conclusion, FX06 prevents and reverts the hyperpermeability induced by ISCLS sera. These preliminary yet promising results provide initial evidence of the in vitro efficacy of a drug targeting the underlying pathophysiological mechanisms of ISCLS. Moreover, this approach may hold potential for addressing hyperpermeability in a spectrum of clinical conditions beyond ISCLS.
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Síndrome de Fuga Capilar , Humanos , Síndrome de Fuga Capilar/metabolismo , Células Endoteliales , Permeabilidad Capilar , Endotelio Vascular , Cadherinas/metabolismo , ItaliaRESUMEN
Systemic Capillary Leak Syndrome (SCLS) is a rare disease that causes severe distributive shock provoked by infection or vaccination. SCLS is clinically diagnosed by a triad of distributive shock, paradoxical hemoconcentration, and hypoalbuminemia. SCLS associated with coronavirus disease (COVID-19) in adults has not been reported yet in Japan. Case 1: A 61-year-old woman with fever, sore throat, headache, and muscle pain was admitted to our emergency department with suspected COVID-19. She had been diagnosed with SCLS 3 years earlier. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen and polymerase chain reaction (PCR) tests were negative at admission. She went into shock in the emergency department and was treated for septic shock. The following day, the SARS-CoV-2 PCR test was positive. She did not respond to fluid resuscitation and catecholamine and finally died. Case 2: A 58-year-old man was admitted to our hospital for de-saturation due to COVID-19. He got into shock on day 3. SCLS was suspected, and 5 g of intravenous immunoglobulin and 5% albumin were administered for sepsis treatment. He responded to the aggressive fluid therapy within 48 h and was finally discharged. COVID-19 can trigger SCLS, and early recognition of SCLS is crucial for survival. Primary care physicians should consider SCLS when they observe distributive shock and paradoxical hemoconcentration deviations from the natural course of COVID-19.
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COVID-19 , Síndrome de Fuga Capilar , Choque , Masculino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Síndrome de Fuga Capilar/complicaciones , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/terapia , Japón , COVID-19/complicaciones , COVID-19/diagnóstico , SARS-CoV-2 , Choque/complicaciones , Choque/diagnósticoRESUMEN
The unprecedented impact and sequelae of COVID-19 infection are not yet fully understood, and better understanding of the pathophysiology of these infections is needed. Endothelial dysfunction might be common sequelae associated with COVID-19, and increased inflammatory responses, oxidative stress, proinflammatory cytokines, and impaired mitochondrial function also contribute to the pathophysiology of post COVID-19 medical disorders. Systemic capillary leak syndrome following COVID-19 infection, both new onset and exacerbation of a prior disorder, has been reported. The pathophysiology of SCLS is uncertain; it likely develops during transient vascular endothelial dysfunction or endotheliopathy and inflammation resulting from circulating humoral factors. Here, we report a case of adult patient with 2 episodes of systemic capillary leak syndrome following prior COVID-19 infection. This patient had a transient response to intravenous IgG.
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COVID-19 , Síndrome de Fuga Capilar , Adulto , Humanos , Síndrome de Fuga Capilar/complicaciones , COVID-19/complicaciones , Edema/complicaciones , Progresión de la Enfermedad , Endotelio VascularRESUMEN
Vascular dysfunction resulting from endothelial hyperpermeability is a common and important feature of critical illness due to sepsis, trauma, and other conditions associated with acute systemic inflammation. Clarkson disease [monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS)] is a rare, orphan disorder marked by spontaneous and recurrent episodes of hypotensive shock and peripheral edema due to widespread vascular leakage in peripheral tissues. Mortality from acute flares approaches 30% due to lack of effective therapies. We evaluated a monoclonal antibody (4E2) specific for the endothelial receptor tyrosine kinase Tie2 in ISCLS models. 4E2 activated Tie2 in ISCLS patient-derived endothelial cells and reduced baseline and proinflammatory mediator-induced barrier dysfunction. 4E2 also reduced mortality and/or vascular leakage associated with systemic histamine challenge or influenza infection in the SJL/J mouse model of ISCLS. These findings support a critical role for Tie2 dysregulation in ISCLS and highlight a viable therapeutic approach to this catastrophic disorder.
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Síndrome de Fuga Capilar , Sepsis , Ratones , Animales , Humanos , Síndrome de Fuga Capilar/complicaciones , Células Endoteliales , Ligandos , Anticuerpos , Receptor TIE-2RESUMEN
Brucellosis can lead to pathological changes of multiple systems. Capillary leak syndrome (CLS) is a clinical syndrome caused by different reasons, mainly characterized by hypotension, hypoproteinemia and systemic edema. The condition is critical and the clinical manifestations are complex, and multiple organ dysfunction syndrome (MODS) may occur in severe cases. CLS caused by brucellosis is extremely rare. The diagnosis and treatment of a patient with brucellosis complicated with CLS and MODS was analyzed in this paper, in order to improve the knowledge of clinicians about brucellosis and its complications.
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Brucelosis , Síndrome de Fuga Capilar , Humanos , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/etiología , Síndrome de Fuga Capilar/terapia , Insuficiencia Multiorgánica/etiología , Brucelosis/complicacionesRESUMEN
We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine. This patient initially presented with dyspnoea and chest pain, with non-pitting oedema and clear lung fields. The diagnosis of ISCLS was made based on the clinical syndrome and laboratory evidence of polycythaemia and hypoalbuminaemia. An enlarging pericardial effusion was diagnosed on transthoracic echocardiogram. Daily point-of-care ultrasound (POCUS)-guided volume management and serial transthoracic echocardiograms contributed to avoidance of refractory shock, cardiac tamponade and critical care admission.
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Vacunas contra la COVID-19 , Síndrome de Fuga Capilar , Derrame Pericárdico , Humanos , Síndrome de Fuga Capilar/inducido químicamente , Síndrome de Fuga Capilar/complicaciones , Taponamiento Cardíaco , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Derrame Pericárdico/inducido químicamente , Derrame Pericárdico/complicacionesRESUMEN
Systemic capillary leak syndrome (SCLS) is a rare and complex adverse effect of immune checkpoint inhibitors (ICIs). The diagnosis of drug-induced SCLS is based on diffuse infusions of exudative fluid into the interstitial areas and the exclusion of other causes. The best management of ICIs-induced SCLS is not settled, though proper supportive care and corticosteroids were commonly applied as the first-line treatment. In our patient with advanced gastroesophageal junction squamous cell carcinoma, although ICIs-induced SCLS was successfully controlled with corticosteroids, the patient soon experienced cancer progress and died of pulmonary infections. Based on our experience and the reported cases by other hospitals, different stages of SCLS might respond differently to the same treatment. Therefore, a grading of ICIs-induced SCLS might help to stratify the patient for different treatment strategies. Besides, corticosteroids-sensitive patients, though waived from deadly SCLS, might be at higher risk of cancer progress and subsequent infections due to the application of corticosteroids. Considering that the inflammatory factors should be closely involved in the development of ICIs-induced SCLS, targeted therapy against the driver inflammatory cytokine might offer treatment regimens that are more effective and safer.
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Síndrome de Fuga Capilar , Carcinoma de Células Escamosas , Humanos , Síndrome de Fuga Capilar/inducido químicamente , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma de Células Escamosas/complicaciones , Corticoesteroides/uso terapéuticoRESUMEN
Introduction: Complement system has a postulated role in endothelial problems after hematopoietic stem cell transplantation (HSCT). In this retrospective, singlecenter study we studied genetic complement system variants in patients with documented endotheliopathy. In our previous study among pediatric patients with an allogeneic HSCT (2001-2013) at the Helsinki University Children´s Hospital, Finland, we identified a total of 19/122 (15.6%) patients with vascular complications, fulfilling the criteria of capillary leak syndrome (CLS), venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) or thrombotic microangiopathy (TMA). Methods: We performed whole exome sequencing (WES) on 109 patients having an adequate pre-transplantation DNA for the analysis to define possible variations and mutations potentially predisposing to functional abnormalities of the complement system. In our data analysis, we focused on 41 genes coding for complement components. Results: 50 patients (45.9%) had one or several, nonsynonymous, rare germline variants in complement genes. 21/66 (31.8%) of the variants were in the terminal pathway. Patients with endotheliopathy had variants in different complement genes: in the terminal pathway (C6 and C9), lectin pathway (MASP1) and receptor ITGAM (CD11b, part of CR3). Four had the same rare missense variant (rs183125896; Thr279Ala) in the C9 gene. Two of these patients were diagnosed with endotheliopathy and one with capillary leak syndrome-like problems. The C9 variant Thr279Ala has no previously known disease associations and is classified by the ACMG guidelines as a variant of uncertain significance (VUS). We conducted a gene burden test with gnomAD Finnish (fin) as the reference population. Complement gene variants seen in our patient population were investigated and Total Frequency Testing (TFT) was used for execution of burden tests. The gene variants seen in our patients with endotheliopathy were all significantly (FDR < 0.05) enriched compared to gnomAD. Overall, 14/25 genes coding for components of the complement system had an increased burden of missense variants among the patients when compared to the gnomAD Finnish population (N=10 816). Discussion: Injury to the vascular endothelium is relatively common after HSCT with different phenotypic appearances suggesting yet unidentified underlying mechanisms. Variants in complement components may be related to endotheliopathy and poor prognosis in these patients.
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Síndrome de Fuga Capilar , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Humanos , Niño , Estudios Retrospectivos , Síndrome de Fuga Capilar/etiología , Proteínas del Sistema Complemento , Enfermedad Veno-Oclusiva Hepática/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. There is only a single case series about polycythemia in children with SCLS, but none on polycythemia in children with PLE. We present a 10-year-old girl with hypoalbuminemia, polycythemia, and edema who died as a result of an SCLS attack and a 1-year-old girl with PLE who was successfully treated with eculizumab. Our experience suggests that hematologists should be alert for SCLS and PLE in children with relative polycythemia.