Usefulness of serum procalcitonin and point-of-care multiplex PCR gastro-intestinal panel in acute diarrhoea or colitis in the emergency department.

INTRODUCTION: Acute infectious diarrhoea is one of the most common diseases worldwide. Procalcitonin (PCT) is useful for antibiotic stewardship in lower respiratory tract infections but has been poorly studied in infectious diarrhoea. Our objective is to describe the PCT concentrations according to diarrhoea aetiology. METHODS: This is a single-center prospective cohort study involving adults consulting the emergency department (ED) for an acute diarrhoea or colitis. Serum PCT was measured and a stool sample was tested with FilmArray® Gastro-Intestinal Panel. The primary endpoint is the PCT concentration according to each type of pathogen identified using Gastro-Intestinal-panel and/or stool cultures at ED admission. RESULTS: 125 patients were included: 80 had an acute infectious diarrhoea, 21 an acute colitis and 24 another illness causing diarrhoea. The median (interquartile ranges) PCT values (ng/ml) were 0.13 (0.08-0.28), 0.07 (0.06-0.54), 0.13 (0.09-0.26) and 0.05 (0.03-0.17), respectively if there was a bacteria (n = 41), parasite (n = 3), virus (n = 10) or no pathogen identified and 0.34 (0.13-1.03) if the diarrhoea was due to another illness (n = 24). CONCLUSION: In patients admitted to the ED with an acute infectious diarrhoea or acute colitis, PCT remained low when a bacteria was identified. It may not be informative in current practice to guide antibiotic therapy.

Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study.

With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28-42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk.Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study.

BACKGROUND: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). RESULTS: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]. CONCLUSIONS: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).

Lower Rate of Daily Smokers With Symptomatic COVID-19: A Monocentric Self-Report of Smoking Habit Study.

Background: Identification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial. Methods: PCR-positive in- and outpatients with symptomatic COVID-19 from a large French University hospital were systematically interviewed for their smoking status, use of e-cigarette, and nicotinic substitutes. The rates of daily smokers in in- and outpatients were compared using the same smoking habit questionnaire to those in the 2019 French general population, after standardisation for sex and age. Results: The inpatient group was composed of 340 patients, median age of 66 years: 203 men (59.7%) and 137 women (40.3%), median age of both 66 years, with a rate of 4.1% daily smokers (CI 95% [2.3-6.9]) (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age of 44 years: 62 men (44.6%, median age of 43 years) and 77 women (55.4%, median age of 44 years). The daily smoker rate was 6.1% (CI 95% [2.7-11.6], 5.1% of men and 6.8% of women). Amongst inpatients, daily smokers represented 2.2 and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in patients with symptomatic COVID-19, as compared to that in the French general population after standardisation by age and sex, with standardised incidence ratios (SIRs) of 0.24 [0.12-0.48] for outpatients and 0.24 [0.14-0.40] for inpatients. Conclusions: Daily smoker rate in patients with symptomatic COVID-19 is lower as compared to the French general population.

Predictive factors for secondary intensive care unit admission within 48 hours after hospitalization in a medical ward from the emergency room.

BACKGROUND: Unplanned transfer to an ICU within 48 hours of admission from the emergency department (ED) can be considered an adverse event. Screening at risk for such an event is a challenge for ED staff. Our purpose was to identify the clinical and biological variables which may be identified in the ED setting and can predict short-term unplanned secondary transfer to the intensive care setting. METHODS: This was a three-year retrospective case controlled monocentric study. The cases were patients transferred to a medical ICU within 48 hours of admission to the general wards from the ED. Each case was matched to two controls (patients not transferred to the ICU) based on age, gender, year of admission, and hospital unit. A conditional logistic regression was performed. RESULTS: Three hundred nineteen patients, including 107 cases and 212 controls, were studied. Community-acquired pneumonia (CAP) was the most frequent diagnosis (23% of cases) followed by sepsis (16%). We identified six predictive factors of an unplanned short-term transfer to the ICU. Former smoking status, fever between 38°C and 40°C, dyspnea as the chief complaint in the ED, a lower MEDS score, an elevated acute physiology age chronic health evaluation score, and the ordering of an arterial blood gas each correlate with secondary transfer to an intensive care setting. CONCLUSION: We report a higher risk of short-term unscheduled ICU transfer in patients meeting these criteria. These patients should be closely monitored and frequently re-evaluated before being transferred to a general ward.

Safety and effectiveness of transjugular renal biopsy for systemic lupus erythematosus and antiphospholipid antibody syndrome patients taking antithrombotics.

BACKGROUND: Renal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients. METHODS: All SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications. RESULTS: Two hundred and fifty-six TJRBs-119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics-were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups. CONCLUSIONS: TJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.

The management of emergency hospital visits for inflammatory bowel diseases: A French national expert consensus report.

BACKGROUND: Management of inflammatory bowel diseases (IBD) in the emergency department is often suboptimal. AIMS: To develop a national consensus checklist of indicators to facilitate decision-making in emergency departments concerning hospitalisation and referral for abdominopelvic computed tomography (CT). METHODS: A Delphi survey was used to obtain consensus on a checklist of clinical and biological variables. 119 healthcare professionals experienced in treating IBD were invited to participate. Panellists were provided with a literature survey and invited to agree or disagree with items on a prototype checklist. Two successive rounds of voting were organised. RESULTS: The prototype checklist included fifteen clinical or laboratory indicators for hospitalisation or CT. Four indicators were not retained in the Delphi process and four additional indicators added. The final indicators retained were: abdominal signs/symptoms of disease exacerbation, intravenous morphine titration, fever, vomiting, dehydration, recent intestinal surgery, ano-perineal abscess, bowel obstruction, haemodynamic instability, anaemia, acute kidney failure and elevated C-reactive protein. Consensus for the retained indicators was >88%. CONCLUSIONS: Use of this consensus checklist for the management of IBD in the emergency department may help improve standards of care and thus reduce the burden of these diseases.

Combination of the National Early Warning Score (NEWS) and inflammatory biomarkers for early risk stratification in emergency department patients: results of a multinational, observational study.

OBJECTIVES: The National Early Warning Score (NEWS) helps to estimate mortality risk in emergency department (ED) patients. This study aimed to investigate whether the prognostic value of the NEWS at ED admission could be further improved by adding inflammatory blood markers (ie, white cell count (WCC), procalcitonin (PCT) and midregional-proadrenomedullin (MR-proADM). DESIGN: Secondary analysis of a multinational, observational study (TRIAGE study, March 2013-October 2014). SETTING: Three tertiary care centres in France, Switzerland and the USA. PARTICIPANTS: A total of 1303 adult medical patients with complete NEWS data seeking ED care were included in the final analysis. NEWS was calculated retrospectively based on admission data. MAIN OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality. Secondary outcome was intensive care unit (ICU) admission. We used multivariate regression analyses to investigate associations of NEWS and blood markers with outcomes and area under the receiver operating curve (AUC) as a measure of discrimination. RESULTS: Of the 1303 included patients, 54 (4.1%) died within 30 days. The NEWS alone showed fair prognostic accuracy for all-cause 30-day mortality (AUC 0.73), with a multivariate adjusted OR of 1.26 (95% CI 1.13 to 1.40, p<0.001). The AUCs for the prediction of mortality using the inflammatory markers WCC, PCT and MR-proADM were 0.64, 0.71 and 0.78, respectively. Combining NEWS with all three blood markers or only with MR-proADM clearly improved discrimination with an AUC of 0.82 (p=0.002). Combining the three inflammatory markers with NEWS improved prediction of ICU admission (AUC 0.70vs0.65 when using NEWS alone, p=0.006). CONCLUSION: NEWS is helpful in risk stratification of ED patients and can be further improved by the addition of inflammatory blood markers. Future studies should investigate whether risk stratification by NEWS in addition to biomarkers improve site-of-care decision in this patient population. TRIAL REGISTRATION NUMBER: NCT01768494; Post-results.

Is procalcitonin a useful biomarker for the risk stratification of facial cellulitis?

BACKGROUND: Facial cellulitis is an infectious disease that may require emergency surgical drainage based on clinical assessment. To date, no biological marker has been reported to be useful for risk stratification. Procalcitonin (PCT) is a diagnostic and prognostic sepsis biomarker. We aimed to study the usefulness of PCT dosage for the risk-stratification of facial cellulitis. PATIENTS AND METHODS: This was a monocentric prospective study conducted in a referral center for maxillofacial emergencies. Patients with a diagnosis of facial cellulitis were included and underwent a PCT measurement at admission. The main criterion was the requirement for surgical drainage. RESULTS: Seventy consecutive patients were included in a 7-months period, mean age 35 ± 14 years. Surgical drainage was required for 48 patients (68%). Serum PCT concentrations were strictly negative in most patients (median [IQR]: 0.05 µg/L [0.05; 0.10]). Only 6 patients (9%) had PCT values above the clinical threshold of 0.25 µg/L. At a threshold of 0.1 µg/L, PCT was 30% sensitive and 100% specific for surgical drainage requirement. CONCLUSION: PCT level usually remains in a low range in facial cellulitis and seems to have a limited added value for risk stratification.

Unscheduled return visits to the emergency department: consequences for triage.

OBJECTIVES: The objective was to conduct a survey of unscheduled revisits (URs) to the emergency department (ED) within 8 days of a prior visit, to test the hypothesis that patients making these URs are disproportionately likely to suffer short-term mortality or manifest a need for any admission to the hospital (adverse events [AEs]) at the time of the UR, compared to patients triaged at the same level who did not have an unscheduled ED revisit within 8 days. METHODS: This was a 1-year retrospective study of patients with an UR to the ED of an urban, 1,600-bed tertiary care center and teaching hospital. The criteria for inclusion as an UR were: 1) making an emergency visit to our adult ED during 2008, without being admitted to our hospital nor being transferred to another hospital; and 2) subsequently making an UR to the same ED within 8 days following the first one. Patients who were contacted by members of our staff and specifically asked to make return visits to our ED (such as those who returned for wound care follow-up visits), and those who made more than five visits to our ED during 2008, were excluded. AEs were defined as death or hospitalization within 8 days of the second visit. RESULTS: During 2008, there were 946 patients with URs (2% of patients treated and released after the first ED visit), and 931 were analyzed (n = 15 missing values). Associated with the second visit, an AE was noted for 276 (30%) patients. Eight variables were significantly associated with AE: age ≥ 65 years, previously diagnosed cancer, previously diagnosed cardiac disease, previously diagnosed psychiatric disease, presence of a relative at the time of the UR, arrival with a letter from a general practitioner at the time of the UR, a higher level of severity assigned at triage for the UR than for the first ED visit, and having had blood sample analysis performed during the first visit. The median triage score for the UR was not significantly different from that group's median triage score for the first ED visit, whereas the proportion of admissions to the hospital (29%) or to the intensive care unit (ICU; 2%) was greater overall in the UR group than in the patients making their first ED visit. CONCLUSIONS: The authors observed that 2% of patients had an UR. This UR population was at greater risk of AE at the time of their URs compared to their initial visits, but the median triage nurse score was not significantly different between the first visit and the UR. This suggests that the triage score should be systematically upgraded for UR patients.

Factors associated with adverse events resulting from medical errors in the emergency department: two work better than one.

BACKGROUND: The Emergency Department (ED) is an environment at risk for medical errors. OBJECTIVE: Our aim was to determine the factors associated with the adverse events resulting from medical errors in the ED among patients who were admitted. METHODS: This was a prospective observational study. For a 1-month period, we included all ED patients who were subsequently admitted to the medical ward. Detection of medical errors was made by the admitting physician and then validated by two experts who reviewed all available data and medical charts pertaining to the patient's hospital stay, including the first review from the ward physician. Related adverse events resulting from medical errors were then classified by type and severity. Adverse events were defined as medical errors that needed an intervention or caused harm to the patient. Univariate analysis examined relationships between characteristics of both patients and physicians and the risk of adverse events. RESULTS: From 197 analyzed patients, 130 errors were detected, of these, 34 were categorized as adverse events among 19 patients (10%). Seventy-six percent of these were categorized as proficiency errors. The only factors associated with a lower risk of adverse events were the transition of care involving a handoff within the ED (0% vs. 19%; p = 0.03) and the involvement of a resident (junior doctor) in addition to the senior physician (37% vs. 67%; p < 0.01). CONCLUSIONS: In our study, the involvement of more than one physician was associated with a lower risk of adverse events.

Prognostic factors in non-exertional heatstroke.

PURPOSE: To identify the prognostic factors associated with mortality in heat-related illness. METHODS: Multi-center observational cohort-study in 16 emergency departments (ED) belonging to the teaching hospital network of the Paris area. The cohort comprised all patients admitted to one of the EDs during the August 2003 heat wave in Paris and having a core temperature >38.5 degrees C. Baseline clinical and biological data in ED, patient's course and 1-year survival rate were recorded. Potential prognostic factors associated with death were assessed by Cox proportional-hazards analysis. RESULTS: A total of 1,456 patients were included. Mean age was 79 +/- 19 years. Critically ill conditions were noted in 391 patients (27%), but only 72 (5%) were admitted into an intensive care unit. The survival rate was 57% at 1 year as compared to an expected 90% (P < 0.001). Nine independent prognostic factors were identified: previous treatment with diuretics, living in an institution, age >80 years, cardiac disease, cancer, core temperature >40 degrees C, systolic arterial pressure <100 mmHg, Glasgow coma scale <12 and transportation to hospital by ambulance. We defined three risk groups: low, intermediate and high risk, with a 1-year survival rate of 85, 61 and 18%, respectively. CONCLUSIONS: We observed a low survival rate and developed a risk score based on easily obtained variables that may be useful to clinicians managing casualties from future heat waves.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

OBJECTIVE: Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. DESIGN: Single-center prospective study. SETTING: University hospital. PATIENTS: Two hundred seventy-six patients scheduled for elective major aortic surgery. INTERVENTIONS: Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1). MEASUREMENTS AND MAIN RESULTS: Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. CONCLUSIONS: Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

Assessment of the accuracy of procalcitonin to diagnose postoperative infection after cardiac surgery.

BACKGROUND: Cardiopulmonary bypass induces a nonspecific inflammatory response. Procalcitonin has been advocated as a specific biomarker for infection. The authors studied the accuracy of procalcitonin to diagnose postoperative infection after cardiac surgery and compared it with those of C-reactive protein, white blood cell count, and interleukins 6 and 8. METHODS: The authors prospectively included 100 patients scheduled to undergo elective cardiac procedures with cardiopulmonary bypass. Blood samples were taken before surgery and each day over the 7-day postoperative period, and measurement of procalcitonin, C-reactive protein, white blood cell count, and interleukins 6 and 8 were performed. Diagnosis of infection was performed by a blinded expert panel. Data are expressed as value [95% confidence interval]. RESULTS: Infection was diagnosed in 16 patients. Procalcitonin was significantly higher in infected patients, with a peak reached on the third postoperative day. Only the areas under the receiver operating curve of procalcitonin (0.88 [0.71-0.95]) and C-reactive protein (0.72 [0.58-0.82]) were significantly different from the no-discrimination curve, and that of procalcitonin was significantly different from those of C-reactive protein, white blood cell count, and interleukins 6 and 8. A procalcitonin value greater than 1.5 ng/ml beyond the second day diagnosed postoperative infection with a sensitivity of 0.93 [0.70-0.99] and a specificity of 0.80 [0.70-0.87]. Procalcitonin was significantly higher in patients who died (27.5 [1.65-40.5] vs. 1.2 [0.7-1.5] ng/ml; P < 0.001). CONCLUSION: Procalcitonin is a valuable marker of bacterial infections after cardiac surgery.

Dantrolene and heatstroke: a good molecule applied in an unsuitable situation.

Because they share one pathognomonic sign (major hyperthermia), classic or environmental heatstroke and malignant hyperthermia have often been confronted from the therapeutic point of view. As expected and according to major physiopathological discrepancies between both syndromes, analysis of published data does not support effectiveness of dantrolene in heatstroke despite its significant reduction in mortality in malignant hyperthermia. If cooling methods still represent the cornerstone of the heatstroke therapeutic approach, the magnitude of heat-related deaths and the morbidity associated with the August 2003 French heatwave have highlighted the need for more ambitious methods of treatment.

Hepatitis C virus infection in systemic lupus erythematosus: a case-control study.

OBJECTIVE: Viruses might be one of the elements that trigger systemic lupus erythematosus (SLE). Steroid therapy may influence the natural history of virus infections. The most frequent extrahepatic manifestations of hepatitis C virus (HCV) including arthralgia, myalgia, sicca syndrome, and antinuclear antibodies, may mimic a connective tissue disease, particularly SLE. Reports on the association between SLE and HCV infection are scarce. We investigated the association of HCV infection and SLE. METHODS: Retrospective case-control monocentric study of 19 patients with SLE and anti-HCV antibodies versus 42 randomized SLE patients without anti-HCV antibodies, matched for age and sex, coming from our cohort of 700 patients with SLE. SLE and HCV-infection features were reviewed. RESULTS: Mode of infection was blood product transfusion, drug addiction, or unknown. Prevalence of lupus clinical manifestations, antinuclear, anti-dsDNA, anti-extractable nuclear antigen antibodies, and complement levels was not different between HCV positive and negative SLE patients. Prevalence of cryoglobulin was higher in SLE patients with anti-HCV antibodies (p < 0.04), but none had a mixed cryoglobulinemia syndrome. ALT activity was increased in 11 HCV positive patients and 13 had detectable HCV RNA. Liver biopsy showed cirrhosis in 2 and mild fibrosis and activity in 5. One patient treated with interferon-alpha had a sustained virological response without SLE flare. Steroid therapy did not seem to alter HCV course. CONCLUSION: SLE in HCV positive patients shows higher prevalence of cryoglobulin without mixed cryoglobulinemia syndrome. HCV infection has moderate signs of biochemical and liver pathological severity. SLE by itself or treated with steroids does not seem to worsen HCV infection.

The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome.

OBJECTIVE: To characterize the frequency, clinical signs, and genotypic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a series of 394 patients of various ethnic origins who have recurrent inflammatory syndromes. METHODS: Sequencing of the coding region of the TNFRSF1A gene was performed in 128 patients in whom there was a high suspicion of TRAPS, and denatured high-performance liquid chromatography was used to systematically screen for TNFRSF1A in 266 patients with recurrent inflammatory syndrome and no or only 1 Mediterranean fever gene (MEFV) mutation. RESULTS: TNFRSF1A mutations were found in 28 (7.1%) of 394 unrelated patients. Nine (32%) of the 28 patients had a family history of recurrent inflammatory syndromes. In 13 patients, the length of the attack of inflammation was fewer than 5 days. Three of the mutations (Y20H, L67P, and C96Y) were novel. Two mutations, R92Q and (mainly) P46L, found in 12 and 10 patients, respectively, had lower penetrance compared with other mutations. TNFRSF1A mutations were found in patients of various ethnic origins, including those at risk for familial Mediterranean fever (FMF): Armenians, Sephardic Jews, and especially Arabs from Maghreb. Only 3 (10.7%) of the 28 patients had amyloidosis. CONCLUSION: TRAPS is an underdiagnosed cause of recurrent inflammatory syndrome. Its presence in the population of persons of Mediterranean ancestry and the short duration of the attacks of inflammation can lead to a fallacious diagnosis of FMF. Because an accurate diagnosis in patients with recurrent inflammatory syndromes is crucial for proper clinical management and treatment, genetic screening for TNFRSF1A is warranted.