When local phytotherapies meet biomedicine. Cross-sectional study of knowledge and intercultural practices against malaria in Eastern French Guiana.

ETHNOPHARMACOLOGICAL RELEVANCE: In French Guiana, traditional phytotherapies are an important part of self-healthcare, however, a precise understanding of the interactions between local phytotherapies and biomedicine is lacking. Malaria is still endemic in the transition area between French Guiana and Brazil, and practices of self-treatment, although difficult to detect, have possible consequences on the outcome of public health policies. AIM OF THE STUDY: The objectives of this research were 1) to document occurences of co-medication (interactions between biomedicine and local phytotherapies) against malaria around Saint-Georges de l'Oyapock (SGO), 2) to quantify and to qualify plant uses against malaria, 3) and to discuss potential effects of such co-medications, in order to improve synergy between community efforts and public health programs in SGO particularly, and in Amazonia more broadly. MATERIALS AND METHODS: This cross-sectional study was conducted in 2017 in SGO. Inhabitants of any age and nationality were interviewed using a questionnaire (122 questions) about their knowledge and habits regarding malaria, and their use of plants to prevent and treat it. They were invited to show their potential responses on a poster illustrating the most common antimalarial plants used in the area. In order to correlate plant uses and malaria epidemiology, all participants subsequently received a medical examination, and malaria detection was performed by Rapid Diagnostic Test (RDT) and Polymerase Chain Reaction (PCR). RESULTS: A total of 1566 inhabitants were included in the study. Forty-six percent of them declared that they had been infected by malaria at least once, and this rate increased with age. Every person who reported that they had had malaria also indicated that they had taken antimalarial drugs (at least for the last episode), and self-medication against malaria with pharmaceuticals was reported in 142 cases. A total of 550 plant users was recorded (35.1% of the interviewed population). Among them 95.5% associated pharmaceuticals to plants. All plants reported to treat malaria were shared by every cultural group around SGO, but three plants were primarily used by the Palikur: Cymbopogon citratus, Citrus aurantifolia and Siparuna guianensis. Two plants stand out among those used by Creoles: Eryngium foetidum and Quassia amara, although the latter is used by all groups and is by far the most cited plant by every cultural group. Cultivated species accounts for 91.3% of the use reports, while wild taxa account for only 18.4%. CONCLUSIONS: This study showed that residents of SGO in French Guiana are relying on both traditional phytotherapies and pharmaceutical drugs to treat malaria. This medical pluralism is to be understood as a form of pragmatism: people are collecting or cultivating plants for medicinal purposes, which is probably more congruent with their respective cultures and highlights the wish for a certain independence of the care process. A better consideration of these practices is thus necessary to improve public health response to malaria.

Changes in malaria epidemiology in France and worldwide, 2000-2015.

In 2015, 212 million new cases of malaria were reported, causing 429,000 deaths. The World Health Organization (WHO) estimated a 41% decrease in the number of new cases worldwide between 2000 and 2015. The number of deaths from malaria fell by 62% worldwide and by 71% in Africa. In mainland France, malaria is mainly imported by travelers or migrants from endemic areas, in particular sub-Saharan Africa (95%). In France, the number of imported malaria cases, mainly due to Plasmodium falciparum (85%), was estimated at about 82,000 for the period 2000-2015. Over the same period, 6,468 cases of malaria were reported in the French armed forces, of which 2,430 cases (37.6%) were considered as imported because occurring outside of endemic areas. The number of malaria cases also fell between 2000 and 2015 in Mayotte and French Guiana, a malaria transmission zone. Mayotte has entered the elimination of malaria with less than 15 cases per year. In French Guiana, between 300 and 500 cases have been reported annually in recent years. The decline in morbidity and mortality is usually attributed to vector control measures and improved access to effective treatments. However, the Anopheles mosquitoes that transmit the disease have developed resistance against most insecticides. Similarly, malaria parasites have developed resistance against most of the antimalarial drugs used as prevention or treatment, even the latest marketed combinations such as artemisinin-based combination therapies.

Native versus deglycosylated IgM in anti-MAG neuropathy: Correlation with clinical status - Study of 10 cases.

BACKGROUND/PURPOSE: In anti-myelin associated glycoprotein (anti-MAG) neuropathies, there is evidence that anti-MAG antibodies are pathogenic but numerous studies report the absence or a weak correlation between the titers of these antibodies and disease course. In this study we assessed the relationships between MAG and glycosylated moieties located on Fc fragment of IgM anti-MAG. MATERIAL AND METHODS: IgM were extracted from the serum of 8 patients with anti-MAG neuropathy and in 2 patients with anti-MAG antibodies without anti-MAG neuropathy. Anti-MAG activity was performed with pre- and post-deglycosylated IgM extracts using indirect immunofluorescence (IIF) and ELISA. Sera from 49 patients with IgM monoclonal gammopathy without neurological disease were tested as control group (CG). Results were compared to clinical scores. For 4 patients the affinity constant of IgM with MAG was analyzed pre- and post-deglycosylated, using surface plasmon resonance technology (SPR). RESULTS: The relationships between MAG and glycosylated moieties of IgM anti-MAG were confirmed by kinetic and immunological assays. Deglycosylation resulted in a decrease in anti-MAG titers. Post-deglycosylation anti-MAG titers trended with changes in IgM titers and allowed quantifying anti-MAG antibodies without a saturation of the testing method. After deglycosylation, the titers better represented pathogenic activity and help to follow a given patient's clinical status prospectively. Six patients from CG (12.2%) had anti-MAG antibody titers over positive threshold: 1000 Bühlmann-Titer-Units (BTU) supporting the hypothesis of neutral intermolecular interactions between IgM and MAG. Deglycosylation allowed distinguishing infra clinical forms from neutral relationships forms, when the titers are weak but this assay remains essentially a diagnostic tool.

French expert opinion for the management of juvenile dermatomyositis.

A guideline group consisting of a pediatric rheumatologist, internists, rheumatologists, immunologists, a physiotherapist and a patient expert elaborated guidelines related to the management of juvenile dermatomyositis on behalf of the rare autoimmune and autoinflammatory diseases network FAI2R. A systematic search of the literature published between 2000 and 2015 and indexed in PubMed was undertaken. Here, we present the expert opinion for diagnosis and treatment in juvenile dermatomyositis.

Diagnostic potential of sarcoplasmic myxovirus resistance protein A expression in subsets of dermatomyositis.

AIMS: To elucidate the diagnostic value of sarcoplasmic expression of myxovirus resistance protein A (MxA) for dermatomyositis (DM) specifically analysing different DM subforms, and to test the superiority of MxA to other markers. METHODS: Immunohistochemistry for MxA and retinoic acid-inducible gene I (RIG-I) was performed on skeletal muscle samples and compared with the item presence of perifascicular atrophy (PFA) in 57 DM patients with anti-Mi-2 (n = 6), -transcription intermediary factor 1 gamma (n = 10), -nuclear matrix protein 2 (n = 13), -melanoma differentiation-associated gene 5 (MDA5) (n = 10) or -small ubiquitin-like modifier activating enzyme (n = 1) autoantibodies and with no detectable autoantibody (n = 17). Among the patients, nine suffered from cancer and 22 were juvenile-onset type. Disease controls included antisynthetase syndrome (ASS)-associated myositis (n = 30), immune-mediated necrotizing myopathy (n = 9) and inclusion body myositis (n = 5). RESULTS: Sarcoplasmic MxA expression featured 77% sensitivity and 100% specificity for overall DM patients, while RIG-I staining and PFA reached respectively 14% and 59% sensitivity and 100% and 86% specificity. In any subset of DM, sarcoplasmic MxA expression showed higher sensitivity than RIG-I and PFA. Some anti-MDA5 antibody-positive DM samples distinctively showed a scattered staining pattern of MxA. No ASS samples had sarcoplasmic MxA expression even though six patients had DM skin rash. CONCLUSIONS: Sarcoplasmic MxA expression is more sensitive than PFA and RIG-I expression for a pathological diagnosis of DM, regardless of the autoantibody-related subgroup. In light of its high sensitivity and specificity, it may be considered a pathological hallmark of DM per se. Also, lack of MxA expression in ASS supports the idea that ASS is a distinct entity from DM.

Predictors of antimalarial self-medication in illegal gold miners in French Guiana: a pathway towards artemisinin resistance.

BACKGROUND: Malaria is endemic in French Guiana (FG), South America. Despite the decrease in cases in the local population, illegal gold miners are very affected by malaria (22.3% of them carried Plasmodium spp.). Self-medication seems to be very common, but its modalities and associated factors have not been studied. The aim of this study was to evaluate parasite susceptibility to drugs and to document behaviours that could contribute to resistance selection in illegal gold miners. METHODS: This multicentric cross-sectional study was conducted in resting sites along the FG-Surinamese border. Participating gold miners working in FG completed a questionnaire and provided a blood sample. RESULTS: From January to June 2015, 421 illegal gold miners were included. Most were Brazilian (93.8%) and 70.5% were male. During the most recent malaria attack, 45.5% reported having been tested for malaria and 52.4% self-medicated, mainly with artemisinin derivatives (90%). Being in FG during the last malaria attack was the main factor associated with self-medication (adjusted OR = 22.1). This suggests that access to malaria diagnosis in FG is particularly difficult for Brazilian illegal gold miners. Treatment adherence was better for persons who reported being tested. None of the 32 samples with Plasmodium falciparum presented any mutation on the pfK13 gene, but one isolate showed a resistance profile to artemisinin derivatives in vitro. CONCLUSIONS: The risk factors for the selection of resistance are well known and this study showed that they are present in FG with persons who self-medicated with poor adherence. Interventions should be implemented among this specific population to avoid the emergence of artemisinin resistance.

Asymptomatic Plasmodium falciparum and vivax infection in the neighborhood of Blondin, Saint-Georges-de-l'Oyapock District, French Guiana.

Optimized elimination strategies are needed to control transmission of malaria. As part of an elimination campaign, active detection of asymptomatic Plasmodium carriers by highly sensitive methods is deemed necessary. Asymptomatic carriage leads to complex scientific, ethical, and operational issues regarding individual or collective detection and treatment. To address this issue, a crosssectional study was carried out in French Guiana to determine the prevalence of asymptomatic Plasmodium carriage during an inter-epidemic season in the whole population of a neighborhood of Saint-Georges-de-l'Oyapock, along the Brazilian border. Fifty-eight participants out of 63 residents were screened. The median age was 23.3 years (range: 2 months-72 years), with a male/female sex-ratio of 0.56. The majority of the participants (74%, N = 43/58) reported a history of malaria, 12% (N = 7/58) during the past 12 months. All rapid diagnostic tests for malaria were negative. Among the 58 participants, malaria prevalence detected by nested-PCR (Polymerase Chain Reaction) was 3.6% (N = 2/56). Two asymptomatic carriers of Plasmodium were identified: one child with Plasmodium vivax and one adult with Plasmodium falciparum. These two carriers were treated and did not develop malaria within the eight months following the diagnosis. This study confirmed the presence of asymptomatic parasitaemias outside hyperendemic areas. However, the benefits of such an active detection and patient treatment to eliminate malaria in French Guiana need to be evaluated at a larger scale.

Peg-IFNα/ribavirin/protease inhibitor combination in hepatitis C virus associated mixed cryoglobulinemia vasculitis: results at week 24.

BACKGROUND: The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon α (PegIFN)-α plus ribavirin and/or rituximab. About 30-40% of patients are non-responders or relapsers to such combination. OBJECTIVE: To analyse the safety and efficacy of Peg-IFNα/ribavirin/protease inhibitor combination in HCV-MC vasculitis. PATIENTS AND METHODS: Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFNα/ribavirin was associated to telaprevir (375 mg three times daily, for 12 weeks, (n=15)) or boceprevir (800 mg three times daily, for 44 weeks, (n=8)) for 48 weeks. RESULTS: The median age was 59 (52.5-66) years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06 g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15 g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). CONCLUSIONS: Peg-IFNα/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.

Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren's syndrome-associated lymphoproliferation.

OBJECTIVE: Primary Sjögren's syndrome (SS) is an autoimmune disease associated with a high risk of developing non-Hodgkin's lymphoma. This study was undertaken to determine the nature of B cells driving lymphoproliferation in primary SS. METHODS: B cell subsets and function were analyzed in peripheral blood from 66 adult patients with primary SS (including 14 patients with B cell lymphoproliferative disease [LPD]) and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme-linked immunosorbent assay. RESULTS: We observed an expansion of an unusual CD21-/low B cell population that correlated with lymphoproliferation in patients with primary SS. A majority of CD21-/low B cells from patients with primary SS expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment, since their Ig genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21-/low B cells from patients with primary SS remained responsive to Toll-like receptor (TLR) stimulation. Molecules specifically expressed in CD21-/low B cells that are likely to induce their unresponsive stage were detected in gene array analyses. CONCLUSION: Patients with primary SS who display high frequencies of autoreactive and unresponsive CD21-/low B cells are susceptible to developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.

[Antiphospholipid antibodies in practice]. / Anticorps antiphospholipides en pratique.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of thrombotic or obstetrical events associated with the presence in the serum of patients of antibodies that are associated with thrombosis. For the diagnosis of APS, the presence of either lupus anticoagulant, anticardiolipin or anti-ß2-glycoprotein1 antibodies of IgG or IgM isotype is required through laboratory testing. Other autoantibodies such as antiphosphatidylethanolamin or antiphosphatidylserin/prothrombin complex antibodies may be interesting in the diagnosis of APS when common antiphospholipid antibodies are missing. These autoantibodies are still under evaluation for their diagnostic contribution. Despite numerous attempts, the assays that are available for the identification of antiphospholipid antibodies have not been standardized yet, which leads to high variability between reagents and laboratories. Thus, to optimize the biological monitoring of APS syndromes, it is mandatory to have consecutive samples analyzed in the same laboratory.

Routine use of Zenit RA, a novel chemiluminescent immunoanalyzer in autoimmune disease diagnosis.

The detection of antibodies is useful to diagnose and/or to classify autoimmune diseases as connective tissue diseases and vasculitis. Zenit RA is a fully automated immunoanalyzer. The aim of this study was to compare the predictive and discriminative performance of the Zenit RA anti-cyclic citrullinated peptide (CCP), anti-cardiolipin (aCL) and anti-ß 2 glycoprotein 1 (aB2GP1) tests to conventional ELISAs on clinically well-defined groups of patients and to daily evaluate the determination of anti-extractable nuclear antigen (ENA), anti-double stranded DNA (dsDNA), anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies in a hospital laboratory. Reagents available on Zenit RA analyzer exhibit good diagnostic performances, regarding sensitivity, specificity, positive and negative predictive values. Global agreements between Zenit RA and conventional tests were from 90 to 98 % (Kappa-values ranging 0.56-0.94): 96 % for anti-CCP, 90-94 % for aCL and aB2GP1, 94 % for anti-dsDNA, 97 % for anti-ENA, 98 % for anti-MPO and 95 % for anti-PR3 antibodies. Zenit RA analyzer is easy to rapidly detect the most common autoantibodies in autoimmune diseases. This system has a potential to provide clinically useful data within a short time. Because of the flexibility of its work modalities, it is well adapted to determine antigenic specificities in daily practice.

Factors influencing the efficacy of two injections of a pandemic 2009 influenza A (H1N1) nonadjuvanted vaccine in systemic lupus erythematosus.

OBJECTIVE: To assess the factors influencing the efficacy of 2 injections of a pandemic 2009 influenza A (H1N1) vaccine in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a single-center, observational prospective study of 111 patients who were vaccinated with a monovalent, inactivated, nonadjuvanted, split-virus vaccine during December 2009 and January 2010 and received a second dose of vaccine 3 weeks later. The antibody response was evaluated using the hemagglutination inhibition assay according to the guidelines recommended for the pandemic vaccine, consisting of 3 immunogenicity criteria (i.e., a seroprotection rate of 70%, a seroconversion rate of 40%, and a geometric mean ratio [GMR] of 2.5). RESULTS: The 3 immunogenicity criteria were met on day 42 (seroprotection rate 80.0% [95% confidence interval (95% CI) 72.5-87.5%], seroconversion rate 71.8% [95% CI 63.4-80.2%], and GMR 10.3 [95% CI 2.9-14.2]), while only 2 criteria were met on day 21 (seroprotection rate 66.7% [95% CI 57.9-75.4%], seroconversion rate 60.4% [95% CI 51.3-69.5%], and GMR 8.5 [95% CI 3.2-12.0]). The vaccine was well tolerated. Disease activity, assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, the British Isles Lupus Assessment Group score, and the Systemic Lupus Activity Questionnaire, did not increase. In the multivariate analysis, vaccination failure was significantly associated with immunosuppressive treatment or a lymphocyte count of ≤ 1.0 × 109/liter. The second injection significantly increased the immunogenicity in these subgroups, but not high enough to fulfill the seroprotection criterion in patients receiving immunosuppressive treatment. CONCLUSION: Our findings indicate that the efficacy of the vaccine was impaired in patients who were receiving immunosuppressive drugs or who had lymphopenia. A second injection increased vaccine immunogenicity without reaching all efficacy criteria for a pandemic vaccine in patients receiving an immunosuppressive agent. These results open possibilities for improving anti-influenza vaccination in SLE.

Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: results of a multicentric study.

Ro52 antigen has recently been identified as TRIM21 protein, but the clinical significance of anti-Ro52/TRIM21 antibodies remains controversial. The aim of this multicentric study was to investigate the significance of anti-Ro52 antibodies without anti-SSA/Ro60 antibodies in various connective diseases. Sera were selected by each laboratory using its own method (ELISA, immunodot or Luminex technology), and then performed with ANA Screen BioPlex™ reagent (BIO-RAD). Among the 247 screened sera, 155/247 (63%) were confirmed as anti-Ro52 positive and anti-SSA/Ro60 negative. These sera were analyzed for the detection of other antibodies in relation with clinical settings. Isolated anti-Ro52 antibodies were detected in 89/155 (57%) sera. For the remaining sera (66/155), the main antibodies associations were Sm/SmRNP or Chromatin (n=38; 57%), Jo1 (n=17; 26%) and CenpB (n=9; 14%). Clinical data from the 155 patients showed high prevalence in autoimmune diseases (73%) including myositis or dermatomyositis (n=30), lupus (n=23); Sjögren and/or sicca syndrome (n=27); CREST or Systemic sclerosis (n=11) and autoimmune hepatitis (n=11). We found that pulmonary manifestations were often associated with the presence of anti-Ro52 antibodies (n=34, 22%), in addition with anti-tRNA synthetases, anti-SRP or anti-Ku antibodies (18/34) or isolated in half of cases (16/34). Separate detection of anti-Ro52 antibodies might be useful in related antisynthetase syndrome diagnosis. The presence of anti-Ro52 antibodies should probably precede development of autoimmune disease and must induce sequential follow-up of positive patients, particularly in interstitial lung disease progression.

Non-anti-MAG DADS neuropathy as a variant of CIDP: clinical, electrophysiological, laboratory features and response to treatment in 10 cases.

BACKGROUND AND PURPOSE: Some patients within the spectrum of chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) have distal acquired demyelinating symmetric (DADS) neuropathy, usually associated with anti-myelin-associated-glycoprotein (MAG) IgM monoclonal gammopathy. The aim of this retrospective study was to investigate patients with DADS neuropathy without anti-MAG antibodies, and study their response to immunotherapy. METHODS: Patients were selected on the basis of (i) 'Definite CIDP' according to the EFNS/PNS Guideline criteria, (ii) The presence of disproportionately prolonged motor latencies resulting in a terminal latency index (TLI) ≤ 0.25 in at least two motor nerves and (iii) The absence of anti-MAG antibodies on ELISA. Response to immunotherapy was defined as persistent improvement by at least one point on the INCAT disability score. RESULTS: Data from 146 CIDP patients were analysed, and 10 patients were included. Six had clinically pure sensory neuropathy, and four had sensorimotor neuropathy. Ataxia was present in nine patients, generalized areflexia in seven and postural tremor in two. Five of the 10 patients had abnormal sensory potentials only in the upper limbs. An associated condition was found in nine patients: two chronic lymphocytic leukaemias, four IgG monoclonal gammopathies (one associated with non-Hodgkin's lymphoma) and two IgM monoclonal gammopathies of unknown significance. Patients were mostly improved with intravenous immunoglobulin (IVIg), corticosteroids, plasma exchanges, or a combination thereof. CONCLUSION: DADS neuropathy without anti-MAG antibodies is more likely to be considered a variant of CIDP. In addition, such patients should be systematically investigated for an associated haematological or immunological condition.

Hepatitis C virus-associated polyarteritis nodosa.

OBJECTIVE: To analyze the main characteristics and outcome of polyarteritis nodosa (PAN)-type vasculitis associated with hepatitis C virus (HCV). METHODS: We reported the characteristics and outcome of 31 patients chronically infected with HCV who satisfied the American College of Rheumatology and Chapel Hill criteria for PAN, seen between 1990 and 2009 in a university center. RESULTS: Among a cohort of 161 patients with HCV-related vasculitis, 31 (19.3%) were diagnosed as having PAN. The median age was 64.5 years (interquartile range 49.5-70.5 years), with 54.8% women. Compared with HCV-associated mixed cryoglobulinemia (HCV-MC) vasculitis, HCV-PAN displayed a more severe and acute clinical presentation with more frequent fever and weight loss (P < 0.0001), severe hypertension (P = 0.0006), gastrointestinal tract involvement (P < 0.0001), severe acute sensory-motor multifocal mononeuropathy (P < 0.0001), kidney and liver microaneurysms (P = 0.002), and increased C-reactive protein level (P < 0.0001). Complete clinical remission of vasculitis was achieved in 79.3% of HCV-PAN patients compared to 57.5% of HCV-MC patients (P = 0.05). In multivariate analysis, skin involvement (odds ratio [OR] 2.81, 95% confidence interval [95% CI] 1.27-6.33) and PAN-type vasculitis (OR 3.01, 95% CI 1.16-8.96) were independently associated with a complete clinical response of HCV vasculitis. A glomerular filtration rate <70 ml/minute (OR 0.54, 95% CI 0.24-1.21) was negatively associated with a complete clinical response of HCV vasculitis. The 5-year survival rate was 86% in the entire cohort, regardless of the vasculitis type. CONCLUSION: HCV-PAN accounts for 19.3% of our cohort of HCV vasculitis. HCV-PAN displays a more severe and acute clinical presentation and a higher rate of clinical remission.

[Cryofibrinogenemia]. / Les cryofibrinogénémies.

Cryofibrinogenemia (CF) is an unrecognized disorder and is rarely symptomatic. CF represents 10 % of the whole cryoproteins. Mean age at diagnosis is between 50 and 60 years. The skin is the most frequently involved organ, in 80 % of patients at diagnosis. Skin lesions include purpura, livedo and Raynaud's phenomenon. In severe cases, skin ulcerations or necrosis and gangrene may occur. Arterial thrombosis is frequently reported (20 to 40 % of cases). Defect in the fibrinolysis process may lead to the cryofibrinogen accumulation and clotting in small and medium arteries and provide a rationale for the use of fibrinolytic agents at least in the most severe cases. In this article, we review the clinical presentation, pathogenesis and treatment of CF.

[Cryoglobulinemic peripheral neuropathy in hepatitis C virus infection: clinical and anatomical correlations of 22 cases]. / Corrélations anatomocliniques des neuropathies périphériques cryoglobulinémiques secondaires à l'hépatite C. Série consécutive de 22 cas.

INTRODUCTION: Cryoglobulinemic neuropathies caused by hepatitis C virus are frequent and may have severe clinical outcomes. The aim of this study was to clarify the clinical and anatomical correlations of these neuropathies. METHODS: Between 1992 and 2007, 22 consecutive patients with cryoglobulinemic neuropathies caused by hepatitis C virus were retrospectively included. Patients were evaluated clinically, electrophysiologically and underwent a neuromuscular biopsy. The group of patients with vasculitis on nerve biopsy was compared with the group without vasculitis. RESULTS: All the neuropathies were axonal with 11 polyneuropathies and 11 mononeuropathies multiplex. The seven patients with medium-sized vasculitis on the nerve biopsy presented an acute sensorimotor mononeuropathy multiplex in six cases (85%), with ischemic conduction block in three cases (42%) and wallerian degeneration in four cases (57%). Among the four patients with small-sized vasculitis, two had a mononeuropathy multiplex (50%) without conduction block (0%) and with wallerian degeneration in one case (25%). The 11 patients without vasculitis (nine lymphocytic perivascular infiltrates and two non inflammatory biopsies) had a polyneuropathy in eight cases (72%) without conduction block and wallerian degeneration (0%). The type of neuropathy was different in the group of patients with vasculitis compared with the group without vasculitis. The neuropathies with vasculitis were significantly different with more frequent mononeuropathies multiplex (p<0.05), acute early stage (p<0.01), disability (p<0.05) and wallerian degeneration (p=0.01). CONCLUSION: Among hepatitis C patients with cryoglobulinemia, neuropathies with small-sized vasculitis show a pattern between severe mononeuropathies multiplex with medium-sized vasculitis and moderate polyneuropathies with lymphocytic perivascular infiltrates. In cryoglobulinemic vasculitis with hepatitis C, the severity of the neuropathy depends on the nature of the cellular inflammation and the size of the vessel involvement.

Evaluation of the LIAISON ANA screen assay for antinuclear antibody testing in autoimmune diseases.

Antinuclear antibodies (ANA) are widely detected by immunofluorescence on HEp-2 cells in patients with connective tissue diseases and other pathological conditions. We evaluated the first-automated chemiluminescence immunoassay for the detection of ANA (LIAISON ANA screen, DiaSorin). This study was carried out simultaneously in two laboratories by testing 327 patient samples with clinically defined connective diseases, 273 routine samples for ANA screening, and 300 blood donors. A total of 268 out of 337 IIF-positive sera were positive with LIAISON ANA screen (79.5% of agreement) and 240 out of 263 IIF-negative sera were negative with LIAISON ANA screen (91.2% of agreement). After resolution of discrepant results, the concordance reached, respectively, 94.9% and 98.8%. The specificity was 99.3% and the sensitivity was 94%. Unlike results obtained by other ANA screening assays, we observed acceptable sensitivity and specificity. Despite the presence of HEp-2 cell extract, we failed to detect some antibodies as antinucleolar, antinuclear envelope, and antiproliferating cell nuclear antigen. This automated assay allows quick process to results and exhibits satisfactory sensitivity for the detection of the main ANA specificities of connective tissue diseases.