Factors predictive of leg-ulcer healing in sickle cell disease: a multicentre, prospective cohort study.

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.

Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow.

Plasma therapy consists in bringing to a patient in need - in general suffering a severe, resistant to current therapy, and even lethal infection - plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917-1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013-2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.

Maternal mortality among women with sickle-cell disease in France, 1996-2009.

OBJECTIVE: To describe maternal mortality among women with sickle-cell disease in France. STUDY DESIGN: Data from the national confidential enquiry into maternal deaths and from reference centres for sickle-cell disease were examined to identify women with this disease who died in France during 1996-2009. The maternal mortality ratio among women with sickle-cell disease was estimated and compared with the ratio in the general population. Characteristics of these women and their pregnancies and circumstances of their deaths were examined in detail. RESULTS: Fifteen maternal deaths occurred among an estimated 3300 live births to women with sickle-cell disease, for a maternal mortality ratio of 454 per 100000 live births (95% CI [254; 750]), versus 9.4/100000 in the general population. Ten women were homozygous (SS) for sickle-cell disease, and five were composite heterozygotes. The episode leading to death appeared in the antepartum period for seven women (47%). Two women died of septic shock during pregnancy, one at 6 weeks, the other at 24 weeks. The other 13 women (87%) died postpartum. Thirteen deaths were directly attributable to sickle-cell disease. The other two maternal deaths, both considered direct obstetric causes, were due to amniotic fluid embolism and septic shock after post-amniocentesis chorioamnionitis. The expert committee on maternal mortality judged seven of these 15 deaths (47%) to be avoidable. CONCLUSION: Sickle-cell disease is responsible for a major excess risk of maternal death in France, due mainly to direct complications of the disease.

[The impact of screening sickle-cell carriers in the general population. A retrospective study in the Paris screening center]. / L'impact du dépistage du trait drépanocytaire en population. Une étude rétrospective au Centre d'information et de dépistage de la drépanocytose (Paris).

BACKGROUND: Since 2006 the CIDD, the Paris information and screening center for sickle-cell disease, provides free assistance for adults who may be at risk of having children with sickle-cell disease. Recently, an increasing number of parents of a silent-carrier newborn detected by systematic neonatal screening are attending the center. We present a retrospective study of the impact of such information and screening on people. METHODS: The study involved 81 silent-carrier men and women aged 18 to 45 years, interviewed using a telephone questionnaire (n=70) or during consultation (n=11) one to three years after screening. RESULTS: The study group represented 12% of individuals attending the center with the same characteristics. In general, the information delivered concerning sickle-cell disease and silent-carriers was well understood although concerns about personal and family history and the correctness of prior knowledge revealed a lack of information input from the environment (media, schools, health professionals). Poorly assimilated information involved three subjects: the difference between trait and disease; the difference between type of hemoglobin and blood group; and Mendelian transmission. The screening result was not a cause of separation among couples and was often passed on to family or friends. Disparities in adherence to prenatal diagnosis and termination of pregnancy were mainly related to different representations of disease severity. CONCLUSION: Joint screening of newborns and their parents is a good measure for adults, who are satisfied with being informed despite the psychological difficulties involved. However the implication for children detected remains a relevant issue because of the persistent perception of the trait as a pseudo-disease and the risk of reification of a biological difference between relatives.

Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity.

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P < 0.001) or MAT 10/22 (46%, P < 0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls.

The risk of going abroad in sickle cell disease: a study of 148 adults.

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.

Is procalcitonin a marker of invasive bacterial infection in acute sickle-cell vaso-occlusive crisis?

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.

Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy.

BACKGROUND: To confirm allergy to beta-lactam (BL), a basophil activation test in flow cytometry based on CD63 up-regulation was described. CD203c is a more recent basophil activation marker and up to day there is no consensus about which marker is the more sensitive one. CD203c has not yet been evaluated in the diagnosis of BL allergy. OBJECTIVE: The aim of the study was to compare the reliability of CD203c to CD63 for the diagnosis of amoxicillin (AX) allergy, which is nowadays the most frequent BL allergy. METHODS: Twenty-seven patients with an immediate positive skin test (ST) to AX, 20 had had anaphylaxis with AX and 7 had urticaria and/or angioedema, were compared with 14 controls with no allergy to BL and to six patients with delayed positive ST to AX. RESULTS: In the anaphylaxis group, AX induced up-regulation of CD203c in the basophils of 12 patients out of 20 (60%) and of CD63 in four patients (20%) (P<0.02). Two patients out of seven with urticaria or angioedema had a positive result with CD203c and CD63. In patients who had anaphylaxis, ampicillin (AMP) induced CD203c up-regulation in eight out of 12 (67%) patients tested, and CD63 up-regulation in 4 out of 12 (33%) (all patients who had anaphylaxis could not be tested with AMP). False-positive results were observed with CD203c as well as CD63, and for 10 patients indeed this was confirmed by a negative drug provocation test. The origin of conflicting results between CD63 and CD203c might be at least the targeting of basophils based on anti-IgE labelling. Among IgE(+) gated cells, by means of CD33, a marker of monocytes, a contamination up to 50% by monocytes was detected. In contrast to CD63, CD203c is an activation marker specific of basophils with a basal low-level expression in resting basophils. Thus, IgE and CD203c double targeting of basophils avoids the contamination by monocytes. CONCLUSION: CD203c seems to be a more sensitive activation marker of basophils than CD63 for the diagnosis of amoxicillin allergy.

Sickle cell leg ulcers: a frequently disabling complication and a marker of severity.

BACKGROUND: Leg ulcers are a poorly known and underestimated complication of sickle cell disease (SCD), but in our experience they often appear as a severely disabling condition, associated with the most severe forms of the disease. OBJECTIVES: To assess the characteristics, complications, repercussion on quality of life and associations of SCD ulcers. METHODS: Case series of 20 patients followed in a French referral centre for SCD and who had previous/present leg ulcers. RESULTS: Median ulcerated area was 12 cm2 and median time spent with ulcers was 29.5 months. Locoregional infections developed in 85%, ankle stiffness in 50% and mood disorders in 85%. Ninety per cent of patients needed analgesics, 20% being opioids. Median loss of time from work was 12.5 months. The Short Form 36 Health Survey showed physical and mental component summary scores of 41.5 and 40.7, respectively, indicating severe alteration close to that found in lung cancer or haemodialysis. Two categories of SCD leg ulcers were distinguished, defined by a 1-year duration cut off. The 'prolonged' ulcers had larger surfaces, tended to recur more frequently and led to more infection and depression. Several SCD complications were associated with leg ulcers, notably priapism, pulmonary hypertension, stroke and acute chest syndrome. CONCLUSIONS: Leg ulcers are a major complication of SCD, given their severe consequences and frequent association with other specific organ damage, and they constitute in their 'prolonged' form a severely disabling condition that remains an important therapeutic challenge.

Unusual sites of Salmonella osteoarthritis in patients with sickle cell disease: two cases.

Salmonella osteoarticular infections involve mainly long bones such as the femur, tibia, and humerus in patients with sickle cell disease (SCD). We report here two unusual cases of Salmonella osteoarthritis affecting sacroiliac and sternoclavicular joints in two patients with SCD, one patient also being followed for rheumatoid arthritis. Because of misleading presentation, diagnosis of septic osteoarthritis in patients with SCD requires a high index of suspicion and an early treatment.

[Sickle cell disease in France in 2006: results and challenges]. / La drépanocytose en France en 2006: acquis et défis.

Sickle cell disease is currently recognized as the most frequent genetic disease screened in the neonatal period in France, and begins to be funded by Public Health Authorities. Despite these issues, SCD is still largely unknown, in particular by general public and practitioners, and education about the disease has to be intensified. Respective roles of proximate and reference centres have to be better defined. Screening of heterozygous patients remains to be organized. Limits of definition of a severe form, and therapeutic options need to be debated.

[Current developments on sickle cell disease]. / Actualité de la drépanocytose.

Sickle cell disease is a genetic autosomal recessive disease of hemoglobin. The disease results from a mutation of the sixth codon of the beta-globin gene, which induces the synthesis of an abnormal hemoglobin called hemoglobin S (HbS). The polymerisation of deoxy HbS molecules causes a chronic hemolytic anemia and vaso-occlusive phenomenons. The disease affects mainly people from West Indies and Sub saharian Africa. Due to recent movements of these populations over the past years, sickle cell disease has spread across all continents. Painful crises, severe infections such as septicemia, meningitis, osteomyelytis, acute anemia episodes, and severe vaso-occlusive events, mainly neurological, are the most frequent complications affecting children. Recent progresses in the care of patients have deeply modified the prognosis. The mean life expectancy of patients is now above 40 years. The conventional treatment includes antibiotics and immunizations, analgesics, and blood transfusion. The effects of chronic blood transfusion, hydroxyurea and bone marrow transplantation are the subject of current comparative evaluations.

Two novel CD1 E alleles identified in black African individuals.

CD1 gene (CD1A to CD1E) products are involved in non-peptide antigen presentation, such as lipids and glycolipids, to T cells. With a similar function to MHC, namely antigen presentation, these genes nevertheless displayed a much lower level of polymorphism as compared to MHC. We report here two additional CD1E variants identified in black African individuals, designated herein CD1E*05 and CD1E*06. While the former differs from the common (wild type) allele sequence by two substitutions at nucleotide positions 217 and 229 of exon 2, the latter only by a single base change at position 91 of exon 3. These substitutions lead to amino acid changes at position 73 and 77 of the alpha1 domain in the former and at position 30 of the alpha2 domain in the latter. Identification of these additional variants suggests that the CD1 locus, especially the CD1E gene, is much more polymorphic than previously assumed.

Seroprevalence of human herpes virus 8 antibody in populations at high or low risk of transfusion, graft, or sexual transmission of viruses.

BACKGROUND: The routes of transmission of human herpes virus 8 (HHV-8) remain unclear. In particular, HHV-8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti-HHV-8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV-8 transmission. STUDY DESIGN AND METHODS: A total of 1431 persons or patients at low or high risk of sexually, blood-, or graft-transmitted viral infections were tested by means of a standardized immunofluorescence serologic assay detecting anti-HHV-8. RESULTS: The persons or patients could be classified into three distinct groups according to anti-HHV-8 prevalence: a low prevalence group (0.0% to 5.0%), including healthy blood donors, healthy pregnant women, multiply transfused patients with thalassemia major, and IV drug users; an intermediate prevalence group (5.0% to 20.0%), including organ donors, kidney transplant recipients, and multiply transfused patients with sickle cell disease; a high prevalence group (>20.0%), including HIV-negative persons at high risk of sexually-transmitted viral infections, and HIV-infected homosexual men and heterosexuals. CONCLUSION: The sexual route appears to be the main route of HHV-8 transmission; bloodborne transmission of HHV-8, if it exists, is rare. In contrast, organ transplantation recipients might be exposed to HHV-8 transmission by the transplanted organ, which raises the issue of systematic screening of organ donors.