Aclaración sobre el artículo "Púrpura bullonecrótica de distribución esporotricoide por Scedosporium apiospermum": desenlace y nueva presentación clínica / Clarification on "Bullous Necrotic Purpura Caused by Scedosporium apiospermum Presenting With a Sporotrichoid Pattern": New Clinical Presentation and Outcome

No disponible

Improvements in the outcome of children with meningococcal disease.

Recent years have seen a marked reduction in the mortality of children with meningococcal disease in paediatric intensive care units (PICU); the reasons for this improvement are multifactorial. The mortality rates for critically ill children overall have improved and reasons for this are probably increased centralisation of PICU services and that fewer critically ill children are now looked after on adult units. Specific treatment pathways for sepsis have improved with the publication of clinical guidelines for children and initiatives such as the Surviving Sepsis Campaign. There is a continuing need to focus on the care delivered to children before reaching PICU and to minimise the morbidity suffered by survivors of this disease.

Improved survival of children with sepsis and purpura: effects of age, gender, and era.

BACKGROUND: To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands). METHODS: Between 1988 and 2006, all 287 children consecutively admitted with sepsis and purpura were included in various sepsis studies. Data regarding age, gender, ethnicity, serogroup of Neisseria meningitidis, severity, therapy, and survival were collected prospectively. These data were pooled into one database and analyzed retrospectively. RESULTS: The case fatality rate (CFR) from sepsis and purpura was 15.7%. During the study period, survival improved significantly. Younger age was significantly associated with more severe disease and a higher CFR. Children under the median age of 3.0 years had an increased risk of case fatality (odds ratio 4.3, 95% confidence interval 2.1 to 9.2; p < 0.001). Gender was not associated with CFR. However, males did have higher Paediatric Risk of Mortality scores, fewer PICU-free days, and more presence of shock. The course of sepsis and purpura was not related to ethnic origin. A causative organism was isolated in 84.3% of cases. N. meningitidis was the major organism (97.5%). Although N. meningitidis serogroup B was observed more often in younger children, serogroups were not associated with severity or survival. During the study period, the use of inotropic agents and corticosteroids changed substantially (less dopamine and more dobutamine, norepinephrine, and corticosteroids). CONCLUSION: Age and gender are determinants of severity of paediatric sepsis and purpura. Survival rates have improved during the last two decades.

Natural history and therapy of 66 patients with mixed cryoglobulinemia.

Cryoglobulinemia, a relatively uncommon disorder, is classified into types I, II, and III, with type II consisting of a monoclonal immunoglobulin possessing activity toward a polyclonal component. Many disease associations and therapies have been described but clinical trials are few, and the natural history, causes, therapy, and pathways of cryoglobulinemia require further investigation. Here, we describe the symptoms, comorbidities, treatments, and response of 66 patients with type II cryoglobulinemia by examining the records of all patients evaluated at Mayo Clinic, Rochester, Minnesota, between 3/2/1994 and 11/27/2000, using our prospective dysproteinemia database. Symptoms varied greatly among patients and during the disease course. Most common were purpura (55% of patients), renal disease (26%), edema (24%), neuropathy (18%), and arthralgia (21%). Renal disease required the most aggressive intervention. Laboratory findings did not correlate with disease manifestations or severity. Only age was a significant predictor of mortality. Ten patients had cryoglobulinemia without an identified comorbidity. Thirty-three patients had viral hepatitis alone, 6 had a lymphoproliferative disorder alone, and 5 had a rheumatologic disease alone. Ten patients had a combination of disorders, such that hepatitis C was identified in a total of 40 patients, lymphoproliferative disorders in 16, and rheumatologic disease in 8. Twenty-two different treatments were administered. Corticosteroids were the most common treatment, followed by interferon with or without ribavirin. Type II cryoglobulinemia is a nonfatal disease most frequently associated with hepatitis C. Treatment is generally directed at the underlying condition. Not all patients require treatment, and many can be followed and treated symptomatically.

Can generic scores (Pediatric Risk of Mortality and Pediatric Index of Mortality) replace specific scores in predicting the outcome of presumed meningococcal septic shock in children?

OBJECTIVE: To compare, in children with septic shock and purpura, the accuracy in predicting death of two specific scores (the MenOPP bedside clinical [MOC] score of Gedde Dahl and the score of Groupe Francophone de Réanimation Pédiatrique [GFRP]), the C-reactive protein (CRP) level, and the two pediatric generic scores (the Pediatric Risk of Mortality [PRISM] and Pediatric Index of Mortality [PIM] scores). DESIGN: Prospective, population-based study with analysis of previous comparative studies. SETTING: A 14-bed pediatric intensive care unit in a university hospital. PATIENTS: All children admitted consecutively to the pediatric intensive care unit with septic shock and purpura (n = 58, with 16 deaths [27.6%]) from January 1993 to May 2000. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The MOC and GFRP scores and the CRP level were prospectively determined at admission. The PRISM score was prospectively calculated within 24 hrs of admission or at the time of death, and the PIM score was calculated retrospectively between 1993 and 1997 and then prospectively from admission data. The nonparametric estimate of the area under the receiver operating characteristic curves (AUC) was calculated from the raw data using the Wilcoxon-Mann-Whitney two-sample statistic, and the standard error of the AUCs was calculated with DeLong's method. All the scores had an AUC >0.80, the PRISM probability of death having the best one (0.96 +/- 0.02). The PRISM value, which is easier to calculate, had an AUC of 0.95 +/- 0.02. The PRISM score performed significantly better than the PIM score (AUC, 0.83 +/- 0.06; p <.01) and the CRP level (AUC, 0.80 +/- 0.06; p <.01); however, there was no significant difference between the MOC (AUC, 0.91 +/- 0.04) and GFRP scores (AUC, 0.87 +/- 0.05). Analyzing literature and calculating AUCs from original data of previous studies, we observed that the superiority of the PRISM score had never been demonstrated in meningococcal diseases. CONCLUSIONS: The PRISM score performed better than the PIM score, and was not surpassed by specific scores. Thus, we propose its use for outcome prediction in children with septic shock and purpura. However, if the PRISM score is to be used as inclusion criterion for clinical trials, it should be evaluated within a few hours after admission.

Complement activation in relation to capillary leakage in children with septic shock and purpura.

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.

Management strategy in purpura fulminans with multiple organ failure in children.

Purpura fulminans (PF), which describes the necrosis of soft tissue secondary to diffuse microvascular thrombosis induced by transient protein C deficiency associated with meningococcal sepsis, is unusual despite the approximately 15000 cases of bacterial meningitis which occur annually in the USA. PF has a reported mortality of 50 per cent secondary to multiple organ failure which commonly accompanies the syndrome and is associated with major long-term morbidity in those who survive. Children who develop multiple organ failure in association with purpura fulminans are difficult management problems and benefit from the unique surgical and critical care resources available in burn centres. We describe our recent experience with three such patients and suggest a management strategy, the key components of which include early excision and closure of deep wounds, aggressive critical care management and long-term follow-up should delayed epiphyseal growth occur.

Surgical intervention for the complications of meningococcal-induced purpura fulminans.

Purpura fulminans is an infrequent but sometimes catastrophic illness that usually complicates a viral, rickettsial or bacterial infection. This communication presents a retrospective review of 152 patients with meningococcemia hospitalized at Children's Medical Center of Dallas from January, 1983, through December, 1993. Eighteen (11.9%) of the 152 patients developed purpura fulminans. Thirteen (72%) of the 18 patients with purpura fulminans needed one or more surgeries including skin grafts, local debridement, microvascular flaps or amputations. Five patients (28%) died.

Epidemic meningococcemia and purpura fulminans with induced protein C deficiency.

Patients with epidemic infections caused by Neisseria meningitidis serogroup C were studied to assess the relationship of abnormal coagulation parameters to prognosis. Patients were categorized into stages within the first hour of observation according to severity of illness. During the epidemic years 1986 through 1991, 113 patients with bacteriologically proven N. meningitidis infection were observed, 15 of whom died. Purpura fulminans was seen in 28 patients, of whom 14 (50%) died. Among the 14 surviving patients who had purpura fulminans, 10 suffered gangrene with deforming autoamputation secondary to the dermal microvascular thrombosis and hemorrhagic necrosis. Evaluation of the induced diffuse intravascular coagulation in 59 patients included studies of the naturally occurring anticoagulants, focusing on protein C and protein S. The magnitude of the declining levels of protein C, the degree of thrombocytopenia, and the presence of fibrin split products are directly related to the clinical severity of the illness (P = .0053). Thus, in individuals with severe disease expression, the risk of purpura fulminans with death or deformity was significantly increased when the platelet count was < 50,000 cells/mm3 (P = .0001) and protein C levels were low (P = .0158). The immaturity of the protein C system in children who are < 4 years of age may contribute to the rapid and more frequent pathogenesis of purpura fulminans. Therapy directed at replacement of the naturally occurring anticoagulants, such as protein C, may ultimately improve the prognosis for individuals with purpura fulminans.

Coagulopathy as a predictor of outcome in meningococcal sepsis and the systemic inflammatory response syndrome with purpura.

OBJECTIVE: To identify simple, contemporary predictors of both morbidity and mortality in pediatric patients with purpuric sepsis syndrome in order to provide a basis for future study of innovative interventions. DESIGN: Retrospective study. SETTING: An 18-bed multidisciplinary intensive care unit (ICU) in a large pediatric hospital. PATIENTS: A total of 53 patients, ranging in age from 18 days to 17 yrs (mean 4.9 yrs) with either culture-proven meningococcal sepsis or the systemic inflammatory response syndrome with purpura, who were admitted to the ICU during the period from January 1, 1982 through March 15, 1992. METHODS: A computerized database was constructed containing the characteristics of these patients at presentation, during the first 24 hrs of hospitalization, and on discharge. Single variables were screened for significance between "good" (intact survival) and "poor" (mortality or survival with significant morbidity) outcome groups. Those variables found to be most significant were then tested for sensitivity, specificity, and predictive value. The best predictors identified in this manner were then compared with the two most-cited prognosticating strategies as applied to these patients. MEASUREMENTS AND MAIN RESULTS: Coagulopathy (defined as a partial thromboplastin time > 50 secs or serum fibrinogen concentration < 150 mg/dL [4.4 mumol/L]) at the referral site or on ICU admission was identified as an excellent predictor of poor outcome: sensitivity, specificity, positive and negative predictive values of a low serum fibrinogen value, being 81%, 95%, 93%, and 88%, and of prolonged partial thromboplastin time, being 95%, 90%, 86%, and 97%, respectively. Classical prognosticating strategies were found to be inadequately associated with mortality, yet comparable with coagulopathy in identifying patients destined for clinically important morbidity. CONCLUSIONS: We conclude that: a) outcome of pediatric patients with meningococcal sepsis or the systemic inflammatory response syndrome with purpura can be predicted rapidly, more easily, and with overall accuracy superior to classical prognostication strategies by the simple presence or absence of coagulopathy; b) when applied to a contemporary population, classical prognostication strategies lack value for prediction of mortality, yet remain valid for prediction of "poor outcome" (significant morbidity + mortality); c) when evaluating treatment strategies for such patients, the presence of serious coagulopathy may potentially be useful as an index of illness severity.

Risk factors for death in meningococcal disease.

Of 2.139 cases of meningococcal infections notified in France from 1985 to 1989, 10% died. The risk factors for death and for purpura fulminans (extensive purpuric rash associated with cardiovascular collapsus) were studied using multifactorial analysis. The purpura fulminans was the major risk factor for death (representing 22% of the cases and 77% of the deaths in our study). In the absence of purpura fulminans, significant risk factors for death were: serogroup A or infrequent serogroup infection, an age over 50 years, and the occurrence of a septicaemia. In the presence of purpura fulminans, significant risk factors for death were an age under one year or over 10 years, and an infection with negative cultures from blood and cerebrospinal fluid. The main risk factor for purpura fulminans was the occurrence of septicaemia. Purpura fulminans appears to be a simple and specific clinical entity reflecting the high level of endotoxin released during meningococcal septicaemia.

Púrpura en el desnutrido / Purpura in the malnourished

Se revisaron los expedintes clínicos de 333 niños desnutridos que ingresaron al Servicio de Nutrición del Instituto Nacional de Pediatría, desde enero de 1985 hasta diciembre de 1988. La púrpura se presentó en 42 niños (12.6 por ciento), en una relación 1:1 con respecto al sexo. Esta fue más frecuente en los niños pequeños. El 61% cursó con niveles bajos de hemoglobina; en 26 casos se determinaron niveles de folatos y de vitamina B12; hubo deficiencia de folatos en 10 pacientes. El 38 por ciento presentó trombocitopenia; pero en ausencia de complicaciones no hubo sangrado. El 95% presentó datos clínicos de infecciones, especialmente en el tracato gastrointestinal, corroborados por cultivo en 22 casos. Se aislaron principalmente gérmentes Gram negativos y estafilococo. La mortalidad global fue de 16.5 por ciento y en los niños con púrpura de 28 por ciento, que es más baja a la obsevada por otros autores.

Adult overwhelming meningococcal purpura. A study of 35 cases, 1977-1989.

The study objective was to describe the clinical, biologic, and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit. Thirty-five patients (greater than or equal to 13 years of age) with meningococcal infection, circulatory shock, and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and had been previously healthy. The female-to-male ratio was 3:1. Mortality was 54.3%, with most deaths occurring within the first 48 hours, usually secondary to irreversible shock with multiple organ failure. Ischemic complications (eight cases), prolonged heart failure (seven cases), and secondary septicemia (five cases) were the chief complications among survivors. Initial hemodynamic study after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13 mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile suggesting a greater myocardial depression than usually observed in gram-negative bacillary septic shock. Univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome: a plasma fibrinogen level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x 10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal purpura is still associated with high mortality and morbidity. Low fibrinogen level at time of admission may permit early recognition of the most severely ill patients.

[Epidemiology of autopsy verified infection]. / Epidemiologie der autoptisch verifizierten Sepsis.

In a retrospective study of 35,220 autopsies performed from 1950 to 1984 in our department, septicaemia was found in 707 cases (2% of all autopsies). The incidence of pyaemia decreased after 1960, whereas that of septicaemia increased significantly. This increase was observed in surgical and medical departments due to patients suffering from neoplastic disease who died of septicaemia (40% of our cases). In the paediatric departments, however, mortality from septicaemia decreased slowly, but continuously. Age distribution revealed two peaks, one in infancy and one in patients older than 60 years. Over the past decade the mean age increased significantly (15 years on average). In blood cultures gram negative bacteria were found more often than gram positive strains.

Hypothesis: senile purpura is a prognostic feature in elderly patients.

In a consecutive series of 1125 elderly Chinese patients admitted acutely into the geriatric unit of a general hospital over a 6-month period, 53 (5%) had senile purpura (SP). The prevalence of SP increased exponentially with age and was higher in men than in women. The mean hospital stay of patients with SP was significantly longer than in the non-SP group. SP may have prognostic significance in the elderly.

Electrolyte changes caused by hydrotherapy in purpura fulminans.

Purpura fulminans is a rare manifestation of meningococcemia that in its full-blown form has a predictive death value of 61%. Those patients who survive usually develop gangrenous lesions that involve skin and underlying structures, mostly of the extremities and sometimes of the cheeks. Experience with early excision and skin grafting of these lesions has generally been unsatisfactory since, due to the unique pathophysiology of the disease and involvement of the most distal branches of the cutaneous circulation, the lesions are not completely demarcated until well after complete recovery from the acute phase of the disease. Recently there was an outburst of purpura fulminans in Southern California and other parts of the country. During the months of January and February 1986 we were consulted on five cases. These ranged from two months to six years in age and consisted of two boys and three girls. One two-month-old died during the acute phase, another six-year-old remained in shock and in need of hemodynamic and respiratory support and succumbed three weeks after the onset of the disease, during which time all four extremities showed progressive necrosis. Of the three patients that survived, one three-year-old girl resolved her purpuric lesions except for small necrotic patches on the buttocks that did not require surgical intervention. The other two children were left with gangrenous lesions of the upper and lower extremities over 30% of total body surface area. One of these two patients demonstrated an electrolyte disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura.

Because of the possible involvement of cytokines in gram-negative septicemia, we investigated serum levels of tumor necrosis factor alpha, interleukin-1 beta, alpha interferon, and gamma interferon in children with gram-negative sepsis and purpura fulminans. We studied 55 patients (ages, 1 month to 19 years) with a clinical diagnosis of sepsis and purpuric lesions who were in shock or had three or more other biologic risk factors. The mortality rate was correlated with the number of risk factors present on admission to the hospital (P = 0.03). Tumor necrosis factor alpha was elevated in 91 percent of the 35 patients tested, interleukin-1 in 21 percent of the 33 patients tested, and gamma interferon in 19 percent of the 32 tested. Alpha interferon levels were within normal limits in the 32 patients tested. Serum levels of tumor necrosis factor alpha were positively correlated with the number of risk factors (P less than 0.05) and negatively correlated with blood fibrinogen levels (P = 0.01). Tumor necrosis factor alpha, interleukin-1, and gamma interferon were significantly higher in patients who died than in the survivors. Alpha interferon levels were similar in the two groups. Serum concentrations of both interleukin-1 and gamma interferon were correlated with concentrations of tumor necrosis factor alpha. These data provide evidence that serum levels of tumor necrosis factor alpha, interleukin-1, and gamma interferon correlate with the severity of meningococcemia in children. The findings may have implications for new therapeutic approaches.

[Frequency of adrenal hemorrhage in fatal forms of purpura fulminans in children. Etiopathogenic and therapeutic considerations]. / Fréquence des hémorragies surrénaliennes au cours des formes fatales de purpura fulminans de l'enfant. Considérations étio-pathogéniques et thérapeutiques.

Between 1971 and 1985, 43 children died of purpura fulminans in our intensive care unit: 11 had autopsy and adrenal haemorrhage was observed in 8 (73%). All these patients had an extensive purpura and a severe disseminated intravascular coagulation. Our series confirms the findings of previous studies: 69 autopsies showed 51 cases (74%) of macroscopic adrenal haemorrhage. Adrenal haemorrhage may be only one manifestation of multiple system organ failure consecutive to septic shock; however, its association with low plasma cortisol levels (as previously reported) suggests that glucocorticoid replacement therapy should be reconsidered in purpura fulminans.