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Familial Mediterranean Fever (FMF) is the most frequent monogenic auto-inflammatory disease. FMF is an autosomal recessive disease, which affects populations from Mediterranean origin and is associated with MEFV gene mutations encoding for the protein pyrin. Pyrin activation enhances the secretion of interleukin 1 by myelo-monocytic cells. Main features of the disease are acute attacks of serositis mainly located on the abdomen, less frequently on chest and joints, accompanied by fever and biological inflammatory markers elevation. Usually attacks last 1 to 3 days and spontaneously stop. A daily oral colchicine intake of 1 to 2mg/day is able to prevent attack's occurrence, frequency, intensity and duration among most patients. Colchicine is also able to prevent the development of inflammatory amyloidosis, the most severe complication of FMF. This state of the art article will focus on the diagnosis of FMF, the treatment and an update on the pathophysiology including the recent described dominant form of MEFV-associated new auto-inflammatory diseases.

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OBJECTIVE: The ENVOL study was designed to assess the psychosocial impact of disease and therapy in a French cohort of cryopyrin-associated periodic syndromes (CAPS) patients (and caregivers) treated with canakinumab. METHODS: The ENVOL study was a multicenter, observational study of CAPS patients given ≥1 canakinumab dose. Data were collected before treatment, at 6 and 12 months afterward, and at the last visit. Patients and caregivers completed questionnaires assessing changes from the 12 months of pretreatment to 12 months prior to interview. Data were analyzed retrospectively. RESULTS: The study included 10 physicians and 68 patients (53 adults, 15 children). Sixty-five patients (95.6%) were still receiving canakinumab at the last visit (median 5 years after starting therapy). The mean ± SD score for patient-reported general health increased from 7 ± 2.9 before canakinumab to 2.7 ± 2.7 after treatment (P < 0.001). Physical and emotional symptoms resolved or improved in a substantial proportion of patients, including bodily pain (38 of 46 patients), fever (32 of 39), skin disease (35 of 41), fatigue (31 of 47), self-confidence (29 of 46), and energy (34 of 47). Social activity, relationships, sexuality, and energy measures improved in >40% of respondents. Caregivers spent a median of 3 versus 0.5 hours/week on care in the 12 months of pretreatment versus 12 months prior to interview (P < 0.001). Following treatment, patients required fewer consultations with general practitioners (mean ± SD per patient per year: 5.2 ± 7.4 versus 8.5 ± 7.2 pretreatment), internists/rheumatologists/dermatologists (2.0 ± 2.1 versus 3.7 ± 3.9), and pediatricians (1.8 ± 1.5 versus 4.4 ± 4.2). CONCLUSION: Long-term treatment with canakinumab achieves a highly relevant improvement in the physical, emotional, and social lives of patients with CAPS, accompanied by a marked reduction in support required from caregivers and in health care consultations.

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BACKGROUND: Leg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing and recurrence of LUs is lacking. OBJECTIVES: To determine clinical and biological factors associated with SCD-LU complete healing and recurrence. METHODS: This prospective, observational cohort study was conducted at two adult SCD referral-centre sites (2009-2015) and included 98 consecutive patients with at least one LU lasting ≥ 2 weeks. The primary end points compared patients with healed vs. nonhealed LUs at week 24, and patients with vs. without recurrence during follow-up. RESULTS: The median (interquartile range) LU area, duration and follow-up were, respectively, 6·2 cm2 (3-12·8), 9 weeks (4-26) and 65·8 weeks (23·8-122·1). At week 24, LUs were healed in 47% of patients, while 49% of LUs recurred. Univariate analyses identified inclusion LU area < 8 cm2 (82% vs. 35%; P < 0·001), inclusion LU duration < 9 weeks (65% vs. 35%; P = 0·0013) and high median fetal haemoglobin level (P = 0·008) as being significantly associated with complete healing at week 24, and low lactate dehydrogenase level (P = 0·038) as being associated with recurrence. Multivariate analyses retained LU area < 8 cm2 (odds ratio 6·73, 95% confidence interval 2·35-19. 31; P < 0·001) and < 9 weeks' duration (OR 3·19, 95% confidence interval 1·16-8·76; P = 0·024) as being independently associated with healing at week 24. Factors independently associated with recurrence could not be identified. CONCLUSIONS: SCD-LU complete healing is independently associated with the clinical characteristics of LUs rather than the clinical or biological characteristics of SCD.

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Sickle cell patients in acute pain situation experiment cognitive, behavioral and emotional changes that can accentuate their pain and disrupt communication with caregivers. On the other hand, caregivers have to face pain assessment difficulties and their own psychological reactions to their patient's pain. The gap between the patient's experience and caregiver's evaluation can lead to conflict and non-adherence treatment, and have a direct impact on the sickle cell disease prognosis. There is nothing inevitable about these phenomena, whose knowledge allows the action and opens up prospects for improving the management of sickle cell disease pain. This article is a narrative review updating the interactions between acute pain and some configurations, such as the inability to discern emotions, catastrophizing, post-traumatic stress or feeling ostracized. The overestimation of patient's addiction by caregivers also influences the pain itself. Open communication, as well as some treatments, medicated or not, a consistent institutional organization and a multidisciplinary approach altogether have an analgesic role by acting on pain cognitive and emotional components.

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PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06-0.68; p = 0.009]. CONCLUSIONS: iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION: NCT00748423.

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Going abroad is considered to be a risk for acute complications in patients with sickle cell disease (SCD). Our objective was to describe the risk in our cohort of adult SCD patients. Complications occurring during a trip were recorded from adults with SCD seen at a routine visit in a referral centre and during hospitalizations for acute complications. One hundred and eight patients participated; mean age=26.8 (± SD 7.3; range 18-56) years. Eighty-two patients travelled in the previous year, half of them in Africa. Among patients going to endemic areas, 68% of patients received chemoprophylaxis against malaria. Health problems occurred in 53 (65%) travellers: vaso-occlusive crisis (VOC) (68%), fever (19%), diarrhoea (19%), broncho-pulmonary symptoms (11%), headaches (8%), vomiting (6%), and cutaneous wound (4%). Sixteen patients required hospitalization; no specific infection was diagnosed. The prevalence of VOC during the trip was higher than the frequency of VOC during the year before. Patients who developed severe complications were not the most symptomatic patients from SCD. Our study showed that going abroad is associated with a large number of acute complications in adults with SCD. Complications were mostly VOC, and severity was unpredictable. Prevention should be improved.

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Fever is often present during painful vaso-occlusive crisis (VOC) in sickle-cell disease (SCD), but does not always indicate infection. The aim of our study was to test procalcitonin as a marker of invasive bacterial infection in VOC. Consecutive SCD adults hospitalized for VOC were included. Data were collected at admission and within 24 h after the onset of fever. We distinguished patients with clinically defined and microbiologically documented invasive bacterial infection from patients with no evidence of invasive bacterial infection and who fared well without antibiotics. One hundred and twelve patients were enrolled (61% females, median age 23 years, 88% homozygous SCD). All patients with procalcitonin (PCT) level ≥1 µg/L had an invasive bacterial infection, but two patients (33%) with an invasive bacterial infection had a PCT level <1 µg/L. High levels of PCT indicate invasive bacterial infection. However, a single low PCT level without follow-up measurement cannot rule out an invasive bacterial infection and should not withhold the prescription of antibiotics.

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