Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury

Herein, we describe a confirmed case of Loxosceles spider bite that illustrates the critical complications seen in loxoscelism, including skin necrosis, rhabdomyolysis, hemolysis, coagulopathy, acute kidney failure, and electrolyte disorders. Upon initial assessment, laboratory studies revealed the following: the white blood cell count was 29 400 WBCs/mm(3), hemoglobin was 9.2g/dL, and the platelet count was 218000cells/mm(3). Coagulation studies revealed the following: international normalized ratio, 1.83; activated partial-thromboplastin time, 62s; D-dimer, 600 ng/mL (normal range < 500 ng/mL); free protein S, 37% (normal range = 64-114%); protein C, negative; and antithrombin III, negative. Various serum levels were abnormal: urea, 110mg/dL; creatinine, 3.1 mg/dL; indirect bilirubin, 3.8 mg/dL; creatine kinase, 1631 U/L, lactate dehydrogenase, 6591 U/L; potassium 6.2mmol/L. Urine tests were positive for hemoglobin and bilirubin. In addition, concentrations of interleukin-6 and tumor necrosis factor-alpha were notably elevated in the serum. In conclusion, physicians must be alert to the possibility of loxoscelism when a patient presents with the clinical and laboratory findings described above, especially if the patient resides in an endemic area. Advances in our understanding of multiple pathways and mediators that orchestrate the response to Loxosceles venom might reveal new possibilities for the management of loxoscelism. (C) 2007 Elsevier Ltd. All rights reserved.

Early and late effects of bone marrow-derived mononuclear cell therapy on lung and distal organs in experimental sepsis

We tested the hypothesis that bone marrow-derived mononuclear cells (BMDMCs) at an early phase of cecal ligation and puncture (CLP)-induced sepsis may have lasting effects on: (1) lung mechanics and histology, (2) the structural remodelling of lung parenchyma, (3) lung, kidney, and liver cell apoptosis, and (4) pro- and anti-inflammatory cytokines and growth factors. At day 1, BMDMC significantly reduced mortality, as well as caspase-3, interleukin (IL)-6 and IL-1 beta vascular endothelial growth factor, platelet-derived growth factor, hepatocyte growth factor, and transforming growth factor-beta, but increased IL-10 mRNA expression in lung tissue in septic mice contributing to endothelium and epithelium alveolar repair and improvement of lung mechanics. BMDMC also prevented the increase of apoptotic cells in lung, liver, and kidney. At day 7, these early functional and morphological effects were preserved or further improved. In conclusion, in the present model of sepsis, the beneficial effects of early administration of BMDMCs on lung and distal organs were preserved, possibly by paracrine mechanisms. (C) 2011 Elsevier B.V. All rights reserved.

Hantavirus infection associated to a staphylococcal sepsis. Report of one case

We report a previously healthy 36-year-old male who developed a pulmonary syndrome caused by Hantavirus infection He was admitted to an intensive care unit in shock awl respiratory failure and died four hours after admission. Blood cultures were positive for Staphylococcus aureus This patient could be an index case that shows, for the first time, an association of Hantavirus Pulmonary Syndrome with Staphylococcus nitwits infection similar to what happens with other viruses (Rev Med Chile 2010, 138: 338-340).

IRF8 Mutations and Human Dendritic-Cell Immunodeficiency

BACKGROUND The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guerin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained. METHODS We evaluated an infant presenting with features of severe immunodeficiency, including early-onset disseminated BCG disease, who required hematopoietic stem-cell transplantation. We also studied two otherwise healthy subjects with a history of disseminated but curable BCG disease in childhood. We characterized the monocyte and dendritic-cell compartments in these three subjects and sequenced candidate genes in which mutations could plausibly confer susceptibility to BCG disease. RESULTS We detected two distinct disease-causing mutations affecting interferon regulatory factor 8 (IRF8). Both K108E and T80A mutations impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA. The K108E variant was associated with an autosomal recessive severe immunodeficiency with a complete lack of circulating monocytes and dendritic cells. The T80A variant was associated with an autosomal dominant, milder immunodeficiency and a selective depletion of CD11c+CD1c+ circulating dendritic cells. CONCLUSIONS These findings define a class of human primary immunodeficiencies that affect the differentiation of mononuclear phagocytes. They also show that human IRF8 is critical for the development of monocytes and dendritic cells and for antimycobacterial immunity. (Funded by the Medical Research Council and others.)

HEMODYNAMIC AND PERFUSION END POINTS FOR VOLEMIC RESUSCITATION IN SEPSIS

Sepsis is the systemic inflammatory response syndrome secondary to a local infection, and severe sepsis and septic shock are the more devastating scenarios of this disease. In the last decade, considerable achievements were obtained in sepsis knowledge, and an international campaign was developed to improve the treatment of this condition. However, sepsis is still one of the most important causes of death in intensive care units. The early stages of sepsis are characterized by a variety of hemodynamic derangements that induce a systemic imbalance between tissue oxygen supply and demand, leading to global tissue hypoxia. This dysfunction, which may occur in patients presenting normal vital signs, can be accompanied by a significant increase in both morbidity and mortality. The early identification of high-risk sepsis patients through tissue perfusion markers such as lactate and venous oxygen saturation is crucial for prompt initiation of therapeutic support, which includes early goal-directed therapy as necessary. The purpose of this article was to review the most commonly used hemodynamic and perfusion parameters for hemodynamic optimization in sepsis, emphasizing the physiological background for their use and the studies that demonstrated their effectiveness as goals of volemic resuscitation.

Generalized Pustular Psoriasis in Childhood

Generalized pustular psoriasis is a rare form of psoriasis consisting of a generalized eruption of sudden onset with erythema and sterile pustules. In children, generalized pustular psoriasis is even more uncommon and may present as a severe and potentially life-threatening disorder. In this study, we present demographics, clinical aspects, treatment response, and follow-up of seven children with generalized pustular psoriasis. Retrospective study reviewing the records of seven children with generalized pustular psoriasis including age, gender, age of onset, presence of scalp and nail involvement, family history, concomitant diseases, precipitating factors, treatment modalities, and outcome. Age of first symptoms ranged from 1 month to 11 years. All patients received systemic retinoids at one time of the follow-up period. Other treatment modalities included immunosuppressive drugs, biologics, phototherapy, and sulfasalazine. Two patients presented with severe constitutional illness, secondary infection and septic shock, including one fatal outcome. All further cases have remained free of recurrences for a mean period of up to 3 years. In our study, generalized pustular psoriasis presented a wide clinical spectrum in children ranging from mild, asymptomatic outbreaks to more severe, life-threatening episodes. One fatality was observed. Children generally responded well to systemic retinoids. Further studies and long-term follow-up periods are needed to define potential trigger factors, efficacy and safety of different treatment modalities in children with generalized pustular psoriasis.

Undifferentiated Spondyloarthritis: A Longterm Followup

Objective. To analyze the longterm followup of a series of Brazilian patients with undifferentiated spondyloarthritis (uSpA). Methods. Prospective study analyzing a group of 111 patients with the diagnosis of uSpA, fulfilling the European Spondylarthropathy Study Group and the Amor criteria, who were followed for 5 to 10 years in a single university referral center. Patients had their outcome analyzed at 5, 7, and 10 years. Results. There was a predominance of men (81.1%), white ethnicity (78.4%), and positive HLA-B27 (61.3%), with a mean age at onset of 27.2 years. Twenty-seven patients presented development to ankylosing spondylitis (AS; 24.3%) and 3 to psoriatic arthritis (PsA; 2.7%), while 25 patients (22.5%) went into remission during the followup. Univariate logistic regression analysis revealed that ethnicity, HLA-B27, buttock pain, inflammatory low back pain, ankle involvement, grade I sacroiliitis at the beginning of the study, and the use of sulfasalazine were statistically associated with progression to AS. Multivariate logistic regression analysis revealed that HLA-B27 (p = 0.035, OR 6.720.95% CI 11.45-39.43) and buttock pain (p = 0.009, OR 6.211, 95% CI 1.591-24.25) were statistically associated with progression to AS. Conclusion. In a longterm followup of 111 Brazilian patients with uSpA, HLA-B27 and buttock pain were significant predictors of progression to a definite disease. (First Release May 1 2010; J Rheumatol 2010;37:1195-9; doi:10.3899/jrheum.090625)

Chronic polyarthritis as the first manifestation of juvenile systemic lupus erythematosus patients

Objective: To evaluate the prevalence of chronic polyarthritis in juvenile systemic lupus erythematosus (JSLE) and to describe the manifestations, treatments, and outcomes in these patients. Methods: From January 1983 to July 2010, 5419 patients were followed up at the Pediatric Rheumatology Unit of the University Hospital and 271 (5%) of them had JSLE (American College of Rheumatology [ACR] criteria). `Rhupus` was classified as the overlap of juvenile idiopathic arthritis (International League of Associations for Rheumatology [ILAR] criteria) and JSLE. We evaluated demographic data, polyarthritis and other clinical manifestations, disease activity and damage, laboratory exams, radiographic findings, treatments, and outcomes. Results: The prevalence of chronic polyarthritis in this JSLE population was 2.6% (7/271). This articular involvement was the initial manifestation in all seven JSLE patients. The median duration of chronic polyarthritis was 11 months (range 2-15 months). Interestingly, rhupus with chronic polyarthritis and limitation of movement, presence of rheumatoid factor, autoantibodies, and/or radiographic abnormalities (juxtaarticular osteopenia, joint-space narrowing, or erosions) was evidenced in three patients. No patient had deformities of hands and feet associated with Jaccoud`s arthropathy or osteonecrosis. All patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs, naproxen 10-15 mg/kg/day) when polyarthritis diagnosis was established. Prednisone and antimalarials were administered at JSLE diagnosis. The three non-responsive rhupus patients were treated in conjunction with immunosuppressive drugs (methotrexate, azathioprine, and/or cyclosporine). Conclusions: Chronic polyarthritis was a rare lupus manifestation in active pediatric patients. The interesting overlap between chronic arthritis and lupus, called rhupus suggests a new entity with a different clinical profile and a poor response to treatment with NSAIDs alone. In addition, the occurrence of this association in JSLE patients could be classified as a clinical sub-group of JSLE with possible specific genetic determinants. Lupus (2011) 20, 960-964.

Fluid Replacement With Hypertonic or Isotonic Solutions Guided by Mixed Venous Oxygen Saturation in Experimental Hypodynamic Sepsis

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoneotic solution Would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 Minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

Pathogenic role of anti-endothelial cell antibodies in autoimmune rheumatic diseases

Anti-endothelial cells antibodies have been detected in numerous autoimmune and inflammatory diseases, including systemic lupus erythematous, rheumatoid arthritis, vasculitis and sarcoidosis. Anti-endothelial cells antibodies bind to endothelial cell antigens and induce endothelial damage. Their effects on the endothelial cell have been considered responsible, at least in part, by the vascular injury which occurs in these pathological conditions. Lupus (2009) 18, 1233-1238.