V. Queyrel

High-dose intravenous immunoglobulins dramatically reverse systemic capillary leak syndrome.

Objective:The objective of this study was to report the dramatic improvement of patients with systemic capillary leak syndrome obtained with high-dose intravenous immunoglobulins. Design:Systemic capillary leak syndrome is a rare and life-threatening disorder characterized by hypotension that can lead to shock, weight gain, hypoalbuminemia, and elevated hematocrit secondary to unexplained episodic capillary fluid extravasation into the interstitial space. Because its cause is unknown, systemic capillary leak syndrome treatment has remained largely supportive. Main Results:Intravenous immunoglobulins administration to a patient with refractory systemic capillary leak syndrome yielded dramatic improvement. The patient is still alive 11 yrs after systemic capillary leak syndrome diagnosis and receives intravenous immunoglobulins monthly. Later, based on that result, intravenous immunoglobulins were successfully given to two other patients during the acute phase of systemic capillary leak syndrome. Both are still alive 8 and 1.5 yrs after receiving intravenous immunoglobulins at the onset of each flare. Conclusions:Intravenous immunoglobulins were effective against systemic capillary leak syndrome symptoms in three patients, but their exact mechanism remains unknown. Their immunomodulatory effect merits further investigation.

Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study

Objective To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). Methods Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05). Results Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12). Conclusions The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit. Trial registration number NCT01295736.

Urinary bikunin determination provides insight into proteinase/proteinase inhibitor imbalance in patients with inflammatory diseases.

Abstract Bikunin (BK) is a Künitz-type proteinase inhibitor responsible for most of the antitryptic activity of urine and so is known as the urinary trypsin inhibitor. As its excretion increases in inflammatory conditions, it is often considered to be a positive acute phase protein (APP). However, the gene for BK is downregulated in inflammation. In human plasma the major part of BK is covalently linked through a glycosaminoglycan chain to one or two homologous peptide heavy chains, thus forming high molecular weight proteinase inhibitors called preαinhibitor (PαI) and inter-α-inhibitor (IαI), respectively. The C-terminal parts of these heavy chains are very sensitive to proteolysis. Neutrophil proteinases in particular are able to release from IαI and PαI BK (M r about 25000) which retains its antitryptic activity and is quickly excreted in urine. It was therefore an early supposition that the higher urinary excretion of BK occurring during inflammatory diseases should be, at least in some respect, related to a partial proteolysis of IαI and PαI. In this study we observed that BK, determined as antitryptic activity, was clearly increased in urine from 35 patients with inflammatory diseases varying in origin and severity (76.5±75.5 IU/g vs. reference value <10 IU/g creatinine). This increase seems mainly to be associated with polymorphonuclear leukocyte activation, monitored by human leukocyte elastase (HLE) determination rather than with the acute phase response assessed by C-reactive protein (CRP) measurement. For all the patients we found that the urinary levels of BK and serum concentration of intact IαI correlated inversely (r=−0.36; p=0.03), in agreement with the presumed precursorproduct relationship linking IαI and BK. We also proved that urinary BK was significantly higher, and serum IαI was significantly lower, in samples with plasma HLE values above the reference: 90 μg/l. Taken together, our results demonstrate that BK, the urinary excretion of which is increased in inflammatory conditions, originates, at least partly, from IαI and PαI by proteolytic cleavage. Consequently, urinary BK determination provides information on the severity of systemic proteolysis occurring in inflammation. We also demonstrated that during inflammatory diseases IαI and PαI concentrations in serum are dependent on their increased utilization as well as on the regulation of their biosynthesis.

Pneumocystis jirovecii colonization in patients with systemic autoimmune diseases: prevalence, risk factors of colonization and outcome

OBJECTIVES To determine the rate and identify risk factors of Pneumocystis jirovecii (P. jirovecii) colonization among patients with systemic autoimmune diseases. METHODS We conducted an observational study in patients with systemic autoimmune diseases in an internal medicine department. Each week, five patients with systemic diseases were randomly selected for colonization screening. Patients complaining of recent respiratory symptoms were excluded. P. jirovecii PCR was performed on induced sputum samples. Univariate and multivariate logistic regression analyses of clinical and biological data were performed to determine predictors of Pneumocystis colonization. Pneumocystis pneumonia occurrence in P. jirovecii-positive PCR patients was recorded during a 1-year follow-up. RESULTS P. jirovecii was detected in 11/67 (16%) subjects. Comparing the features in P. jirovecii-positive and P. jirovecii-negative PCR patients, only male gender was significantly associated with Pneumocystis colonization. In multivariate analysis with regard to gender, the higher prevalence of P. jirovecii colonization in men was largely explained by higher daily CSs [odds ratio (OR) = 1.6; 95% CI 1.1, 2.3] and lower total lymphocyte level (OR = 0.9; 95% CI 0.8, 0.99). No P. jirovecii-positive PCR patient developed Pneumocystis pneumonia during the 1-year follow-up, but corticosteroid amounts were significantly lower at the end of follow-up than on inclusion. CONCLUSION This is the first study on P. jirovecii colonization in patients with systemic autoimmune diseases. We found a high prevalence of colonization and identified CS therapy and lymphocyte counts as risk factors for colonization. We recommend screening for P. jirovecii colonization in patients with systemic autoimmune diseases receiving immunosuppressant treatment. Further studies are needed to determine the role of subclinical colonization in disease transmission and the persistence of Pneumocystis colonization.

Le syndrome des anti-synthétases : un sous-groupe des myopathies inflammatoires à ne pas méconnaître**

Purpose. – Antisynthetase syndrome (AS) is frequently revealed by interstitial lung disease and arthritis. There are mechanic’s hand, Raynaud’s phenomenon and anti aminoacyl t-RNA synthetase antibodies. The anti JO-1 antibody is the most frequently identified . We report five cases of antisynthetase syndrome with particular clinical features and good response to corticosteroids. Methods. – There are three women and two men with a median age of 59 years at presentation (range: 44–77). Three patients progressively developed AS: the symptoms are dyspnea (three), Raynaud‘s phenomenon (one), purpura (one) and hyperkeratosis, scaling and fissuring on the lateral sides of the fingers (two). Patients always had skin signs: hyperkeratosis and scaling (five), purpura (one), Raynaud’s phenomenon with normal capillaroscopy (two). Lung disease is present in the five cases with interstitial lesions in CT scans (five), trouble of CO diffusion (three/three) and lymphocytic alveolitis (two/two). Moderate muscular disorders are present in five cases (moderate elevated muscular enzyme: five, positive muscle histology: two). Anti-JO-1 antibodies are present in five cases. AS is associated with connective tissue diseases: rheumatoid polyarthritis in one case and Gougerot-Sjogren in three cases. No malignant tumour is associated. Patients have received oral corticosteroid treatment (five/five) with high doses of intravenous perfusions (three/five) with, initially, a good response. For only one patient, immunosuppressive treatment was necessary because of the articular relapse. The interstitial lung disease had a good response to corticosteroids therapy alone in four cases. Because of the relapse during the tapering off of corticosteroids, corticosteroids were increased in one case and immunosuppressive therapy was required in one case. Conclusion. – The prognosis of AS depends of the interstitial lung disease. High doses of corticosteroids are required. In our study, the response to corticosteroids is good. Immunosuppressive agents must be added in severe and progressive form of interstitial lung disease in AS.

Effective immune restoration after immunosuppressant discontinuation in a lupus patient presenting progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system with JC virus. Few cases have been described in lupus patients. We describe biopsy-proven PML in a lupus patient receiving mycophenolate mofetil and corticosteroids. Although the patient received no antiviral treatment, the polymerase chain reaction test for JC virus became negative in cerebrospinal fluid after immunosuppressant discontinuation and the patient survived. We discuss the restoration of immune efficiency after immunosuppressant discontinuation in this case and compare the clinical, radiological and histological features with the inflammatory PML form described in human immunodeficiency virus-infected patients.

Catatonia and systemic lupus erythematosus: a clinical study of three cases.

Catatonia may be encountered in psychiatric disorders, but also in general medical conditions. Cases of catatonia associated with systemic lupus erythematosus (SLE) are rare. Several articles have described this symptomatic association, as well as its management, using electroconvulsive therapy, plasma exchange or benzodiazepines. We report three cases here of patients who presented with catatonia during a lupus relapse, in whom treatment with lorazepam improved the catatonic symptomatology, thus allowing the associated condition to be treated. We touch on several points about the diagnosis, etiology and treatment of catatonia, when it is associated with SLE.

Purpura rhumatoide de l'adulte et infection a parvovirus B19@@: association fortuite ou vascularite induite par le parvovirus B19@@

Introduction. – Henoch-Schoenlein purpura has been reported to be associated with parvovirus B19 infection, particularly in children and rarely in adults. We report the case of a 42-year-old patient presenting with this association. Exegesis. – A 42-year-old patient was admitted to our medical center because of lower limb purpura. Henoch-Schoenlein purpura diagnosis was confirmed on histological findings (kidney biopsy) and concomitantly parvovirus B19 infection was proved by serological test (IgM+). Association of Henoch-Schoenlein purpura and parvovirus B19 infection has already been described. However, none of the reported studies demonstrated clearly the link between these two diseases. With regard to this observation, we wonder about the systematic use of the parvovirus B19 serological test in patients presenting first Henoch-Schoenlein purpura. Indeed, parvovirus B19-induced vasculitis is habitually controlled with intravenous immunoglobulins. Conclusion. – A prospective study should explore the link between Henoch-Schoenlein purpura and primary parvovirus B19 infection. Moreover, we should evaluate intravenous immunoglobulins’ efficacy in Henoch-Schoenlein purpura associated with active parvovirus B19 infection in order to improve the prognosis of this disease.

Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography.

BACKGROUND/OBJECTIVES Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation. METHODS AND RESULTS We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis. CONCLUSION Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further.

Maladie de Still de l’adulte et angiosarcome hépatique, une association fortuite ou un syndrome paranéoplasique : à propos d’un cas

Adult-onset Stills disease is a systemic disorder without specific histological feature. Diagnosis requires to rule out any other disorder including neoplasia. Nevertheless, patients with paraneoplastic adult-onset Stills disease have been reported. We report a patient with an adult-onset Stills disease who presented with a liver involvement at onset. Two years later, a liver angiosarcoma was diagnosed. This report underlines the difficulty of the diagnosis of the adult-onset Stills disease even in the presence of Yamaguchi et al.s [J Rheumatol 19 (1992) 424-30] and Fautrel et al.s [Medicine 81 (2002) 194-200] classification criteria and may suggest a link between the initial clinical picture and the discovery nearly two years later, of a liver angiosarcoma.