Search

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.

Resume Introduction. – L'infection a cytomegalovirus est souvent asymptomatique, les formes graves sont l'apanage de l'immunodeprime. Nous rapportons un nouveau cas d'hepatite aigue a cytomegalovirus (CMV) compliquee de thrombose portale chez un immunocompetent. Exegese. – Un homme de 29 ans presenta une hepatite aigue a CMV confirmee par la presence de la proteine pp65 et de l'ADN viral dans le sang. Elle fut compliquee d'une thrombose portable d'evolution rapidement favorable sous traitement anticoagulant. Aucune autre cause de thrombose portale ne fut decelee. Onze cas de thrombose majeure compliquant une infection aigue a CMV chez un immunocompetent ont ete rapportes dans la litterature anglosaxonne et francaise. L'absence de cause locale et generale, la resolution en l'absence de traitement anticoagulant, le risque eleve de thrombose chez les sujets seropositifs a la fois pour le virus de l'immunodeficience humaine et le CMV, et chez les transplantes renaux seropositifs pour le CMV suggerent une relation causale. Diverses hypotheses physiopathogeniques ont ete evoquees : presence d'anticorps antiphospholipides, absents dans notre observation, induction d'un phenotype procoagulant des cellules endotheliales infectees, induction d'une proliferation des cellules musculaires lisses. Conclusion. – L'infection aigue a CMV peut etre consideree comme une cause possible de thrombose majeure.

Resume Propos. – La malade de Still de l'adulte (MSA) est une maladie systemique rare qui se caracterise par une fievre hectique, une eruption cutanee, des arthralgies ou arthrites, des douleurs pharyngees, une organomegalie, et biologiquement par une hyperleucocytose a polynucleaires neutrophiles, une cytolyse hepatique et une hyperferritinemie a fraction glycosylee effondree. La physiopathologie de la maladie n'est pas connue mais des donnees recentes de la litterature apportent un eclairage nouveau. Actualites et points forts. – La mise en evidence de taux tres eleves de ferritine, IL-8, IL-6, IL-18 and TNF-α au cours de la MSA rend compte d'une activation marquee des macrophages. L'IL-18, synthetisee par les macrophages actives, semble avoir le role cle dans la pathogenie de la maladie. Les taux d'IL-18 sont en effet particulierement eleves au cours de la MSA comparativement a d'autres rhumatismes articulaires inflammatoires comme la polyarthrite rhumatoide et sont correles aux taux de ferritine et a l'activite de la maladie. Son augmentation pourrait expliquer des signes tels que la cytolyse hepatique ou l'atteinte articulaire. La cause de l'activation des macrophages au cours de la MSA n'est pas connue. Elle pourrait etre le fait d'agents infectieux tels que des virus et d'un controle inapproprie de la reponse lymphocytaire T, secondaire a un deficit d'activite des lymphocytes Natural Killer, comme cela a ete montre au cours de la forme systemique de l'arthrite juvenile idiopathique. Cette activation excessive pourrait expliquer l'apparition d'un syndrome hemophagocytaire, complication grave de la maladie de Still de l'enfant et de l'adulte. Perspectives. – Un deficit en lymphocytes cytotoxiques au cours de la MSA constitue une piste etiologique interessante a la lumiere des donnees recentes sur la physiopathologie de la forme pediatrique de la maladie. La MSA pourrait alors constituer une forme particuliere de deficit immunitaire.

The cytomegalovirus (CMV) infection is most often asymptomatic. The grave forms concern the immunocompromised patients. We report a new case pf acute CMV hepatitis complicated with portal thrombosis in an immunocompetent patient.A 29 year old man has presented a CMV hepatitis proved by the presence of pp65 protein and the viral DNA in serum. This infection was complicated by a portal thrombosis and the evolution was rapidly favourable under anticoagulant treatment. Eleven cases of major thrombosis complicating acute CMV infection in immunocompetent patients were previously reported in the English and French literature. The absence of local and general cause, the remission without anticoagulation, the elevated risk of thrombosis in both HIV and CMV seropositive patients, and in CMV seropositive renal transplant patients suggest a causal relation. Various pathogenic hypotheses were raised: presence of antiphospholipid antibodies, absent in our case, procoagulant phenotype induction of infected endothelial cells, proliferation induction of smooth cells.The acute CMV infection can be considered such as a possible cause of major thrombosis.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown origin. It is characterized by hectic fever, evanescent rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and high serum level of ferritin with low glycosylated fraction.An increased serum level of ferritin, IL-8, IL-6, IL-18 and TNF-alpha indicates that macrophages are highly activated in AOSD. Interleukin 18 (IL-18) seems to be a key cytokine in the pathogenesis of AOSD. Serum IL-18 levels are increased in AOSD patients compared to other systemic inflammatory diseases such as rheumatoid arthritis and they are well correlated with serum ferritin levels and disease activity. IL-18 could cause acute liver injury and arthritis. Macrophages could be activated by infectious agents such as viruses and by an inadequate control of T cell response secondary to depressed Natural Killer lymphocyte function, similarly to that observed in systemic juvenile idiopathic arthritis. Sustained macrophage activation can lead to the hemophagocytic syndrome, a severe complication of both AOSD and systemic juvenile idiopathic arthritis.Cytotoxic cell functions should be probably studied in AOSD as they were in the hemophagocytic syndrome and systemic juvenile idiopathic arthritis because AOSD, characterised by a marked macrophage activation may be related to an immunological deficiency.