Progressive multifocal leukoencephalopathy in patients with systemic lupus erythematosus: a systematic literature review.

OBJECTIVE: To determine risk factors for progressive multifocal leukoencephalopathy (PML) in systemic lupus erythematosus (SLE) patients, and understand how underlying disease or treatment for SLE may be associated with PML in this population. METHODS: Studies published in English between January 1, 1984 and October 31, 2014 that reported PML in adult SLE patients were included. Immunosuppression was defined as exposure to ≥1 immunosuppressant drug of interest at PML diagnosis: belimumab, rituximab, mycophenolate mofetil, azathioprine, cyclophosphamide, methotrexate and high-dose corticosteroids (>15 mg/day). Minimal immunosuppression was defined as low-dose corticosteroids (≤15 mg/day) and/or anti-malarials. RESULTS: Thirty-five publications met our inclusion criteria: four observational studies, two large case series, and 29 case reports that described 35 cases. Reported PML incidence rates among SLE patients based on observational studies ranged from 1.0 to 2.4 cases/100,000 person-years. Of the 35 case reports, three cases were exposed to no immunosuppressant drugs at PML diagnosis, five cases had minimal immunosuppression, 23 cases had immunosuppression, and four cases were indeterminate. CONCLUSIONS: The evidence from this literature review suggests that, while PML is a very rare disease in SLE patients, there does appear to be an increased risk of PML associated with SLE compared to the general population, potentially due to immunosuppression, other contributing factors in their underlying disease, treatments prescribed to manage disease, or some combination of these factors. Additional large observational studies, designed to assess exposure to drugs of interest and complicated treatment histories, are needed to provide further evidence about potential mechanisms contributing to the onset of PML in SLE patients.

Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjogren syndrome: a case-control study.

OBJECTIVES: To assess subclinical central nervous system (CNS) involvement in primary Sjögren syndrome (pSS), by comparing standard brain MRI, in-depth neuropsychological testing and (99m)Tc-ECD brain single-photon emission computed tomography (SPECT) of patients with pSS with matched controls. METHODS: 10 women (<55 years old), with pSS defined using European-American criteria, presence of anti-SSA and/or anti-SSB antibodies and no history of neurological involvement were prospectively investigated, and compared with 10 age- and sex-matched controls. All subjects underwent, within 1 month, brain MRI, neuropsychological testing, including overall evaluation and focal cognitive function assessment, and (99m)Tc-ECD brain SPECT. RESULTS: (99m)Tc-ECD brain SPECT abnormalities were significantly more common in patients with pSS (10/10) than controls (2/10; p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial disorders, were also significantly more common in patients with pSS (8/10) than controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant correlation to be established between neuropsychological assessment and (99m)Tc-ECD brain SPECT abnormalities in patients with pSS (r(s) = 0.49, p<0.01). MRI abnormalities in patients and controls did not differ significantly. CONCLUSIONS: Neuropsychological testing and (99m)Tc-ECD brain SPECT seem to be the most sensitive tools to detect subclinical CNS dysfunction in pSS. The strong correlation between cortical hypoperfusion in (99m)Tc-ECD brain SPECT and cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS. These data should be confirmed in a larger study.

Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients.

OBJECTIVE: To characterise major infectious complications and analyse potential risk factors in patients with Wegener granulomatosis (WG). METHODS: Data from 113 patients with WG (69 male) followed at least once between January 1984 and March 2006 in our internal medicine department, were analysed retrospectively. RESULTS: A total of 35 patients (mean (SD) age at WG diagnosis: 50.2 (13.05) years) developed 53 major infections. Infections were: bronchopneumonias (n = 19), herpes zoster recurrences (n = 9), cellulitis (n = 4), prostatitis (n = 4), spondylodiscitis and septic arthritis (n = 3), digestive tract infections (n = 2), Enterococcus faecalis or Staphylococcus aureus septicaemia (n = 2), viral hepatitis B reactivations (n = 2), post transfusion HIV infection with fatal cerebral toxoplasmosis, oesophageal candidiasis, disseminated herpes simplex and cytomegalovirus infection, cytomegalovirus retinitis, herpetic keratitis, herpetic stomatitis, Serratia sp. node suppuration and fever resolving under broad spectrum antibiotics (n = 1 each). Half of the major infectious episodes occurred within 3 years after WG diagnosis. Eight (7%) patients died, with two (2%) infection-related deaths. Patients diagnosed with WG before 1996 had a significantly higher rate of infection than those diagnosed later (48% vs 24%, p = 0.02). Cyclophosphamide and corticosteroids were independently associated with significantly higher risk of major infection (p<0.05 and <0.001, respectively). All patients treated since 1993 received antipneumocystosis prophylaxis. CONCLUSION: Cyclophosphamide and corticosteroids were associated with higher risk of infection. Despite systematic cotrimoxazole prophylaxis, major infections, mostly bronchopneumonias and herpes zoster recurrences, were still common in the course of WG.

Factors influencing influenza-vaccination in adults under immunosuppressive therapy for a systemic inflammatory disease.

OBJECTIVE: The aim of this study was to evaluate flu vaccination rates and influencing factors in patients with systemic inflammatory diseases. METHODS: All patients presenting with a systemic inflammatory disease and taking immunosuppressants, who were hospitalized or had consulted in our internal medicine department between January 2 and 31, 2006, were included in the study. The information concerning flu vaccination was collected with a standardized form. RESULTS: One hundred and thirty-seven patients (mean age 53.1+/-17.6years; 40 [29%] male patients) were included: 39 (28%) had received flu vaccination in 2005 including 14 (16.7%) of the 84 patients with no other indication for flu vaccination than IS-induced immunodepression and 25 (47.2%) of the 53 patients with other flu vaccination indication(s) (p<0.001). The most frequent reasons for non-vaccination were: absence of physician recommendation (58%), fear of adverse effects (35%) and concern on vaccine clinical effectiveness (5%). The vaccination rate was significantly higher (49%) among patients who remembered having received a voucher from the French National Health Insurance Agency versus 18% among those who did not (OR=4.2 [95%CI, 1.92-9.19] p<0.05). This correlation remained significant after adjustment for confounding factors in a logistic regression model. CONCLUSION: Influenza-vaccination coverage is low in patients receiving immunosuppressive therapy for systemic inflammatory diseases. We have to increase the influenza-vaccination coverage in this population.

[Cardiopulmonary function before and after cyclophosphamide treatment in severe systemic sclerosis: comparison of monthly intravenous bolus and autologous haematopoietic stem cell transplantation]. / Etude de la fonction cardiopulmonaire avant et après traitement par cyclophosphamide dans la sclérodermie systémique sévère: comparaison de deux modes d'administration (Intensification thérapeutique suivie d'autogreffe de cellules souches hématopoïétiques périphériques ou bolus mensuels intraveineux).

PURPOSE: Cyclophosphamide in monthly intravenous bolus is used to treat severe forms of systemic sclerosis with pulmonary involvement. Since 1996, cyclophosphamide therapeutic intensification with autologous haematopoietic stem cells transplantation allowed significant improvement in skin and functional scores in severe systemic sclerosis. Cyclophosphamide potential cardiotoxicity in this setting has been questioned. METHODS: To analyse cyclophosphamide potential cardiopulmonary toxicity (as graded with WHO classification), we retrospectively studied all severe systemic sclerosis patients treated with cyclophosphamide either during autologous haematopoietic stem cells transplantation procedure (group A) or intravenous cyclophosphamide (group B) recruited in 7 French centers volunteers for the study. Parameters to evaluate heart and lung functions at inclusion, then at last follow-up between 6 and 12 months after start of treatment, were compared using the Mann-Whitney test. RESULTS: (Mean+/-standard deviation): Groups A (N=14) and B (N=13) were similar at the beginning of the study in terms of skin, renal, heart and lung involvement. Cyclophosphamide total dose (/m(2)) received in group A was superior (P=0.02) to the one in group B. After respective follow-up of 10+/-2.8 (group A) and 9.9+/-2.7 (group B) months, cyclophosphamide cardio toxicity (group A: N=3; group B: N=2), evolution of the left ventricular ejection fraction and arterial and pulmonary pressures did not differ in the two groups. CONCLUSION: In spite of higher cyclophosphamide doses during autologous haematopoietic stem cells transplantation than bolus treatment, cardiopulmonary toxicity appeared not increased. The ongoing European ASTIS trial will compare the respective benefits of these 2 cyclophosphamide regimens in severe Systemic sclerosis.

[Laryngeal amyloidosis: a rare cause of hoarseness]. / Amylose laryngée: une cause rare de dysphonie.

INTRODUCTION: The larynx is a rare site of deposition for amyloidosis. Diagnosis may be delayed and evoked in patients with prolonged hoarseness. We have reported two cases of laryngeal amyloidosis. EXEGESIS: One man and one woman suffered from hoarseness during one and three years, respectively. Laryngoscopic examination showed diffuse infiltration of the larynx. Amyloidosis was confirmed by the characteristic Congo-red staining of laryngeal biopsies. The search for other localizations of amyloidosis was negative. No monoclonal plasma cell proliferation was detected. Both patients received endoscopic CO2 laser excision. In one case, chemotherapy was initially associated due to dystrophic plasma cells in bone marrow aspiration and then withdrawn because of clinical failure. With a 6-month follow-up, hoarseness remained stable. CONCLUSION: Laryngeal amyloidosis is an essentially localized disease revealed by hoarseness. Treatment is endoscopic by laser excision. In nearly half of the cases in the literature, it had to be repeated due to localized recurrent lesions. Long-term prognosis of localized laryngeal amyloidosis is better than systemic AL amyloidosis.

Impact of HIV on clinical presentation and outcomes of tuberculosis treatment at primary care level.

Little is known on how human immunodeficiency virus (HIV) infection impacts pediatric tuberculosis (TB) in primary care. We compared TB type, HIV care and case fatality rates between 5685 adults and 830 children with TB treated at primary care clinics in Kinshasa, Democratic Republic of Congo. Children represented a substantial burden (13%) of TB, and presented predominantly with difficult to diagnose smear-negative TB and extra-pulmonary TB. The HIV co-infection rate was lower in children than in adults, and fewer children than adults received antiretroviral therapy during anti-tuberculosis treatment. Case fatality was four times higher in HIV-infected than non-infected children. Child-friendly point-of-care TB diagnostics and decentralized pediatric TB-HIV care should receive greater attention.

Mortality among tuberculosis patients in the Democratic Republic of Congo.

SETTING: Kinshasa, Democratic Republic of Congo. OBJECTIVE: To identify programmatic interventions for improved survival in patients receiving treatment for tuberculosis (TB) at primary care clinics. DESIGN: Retrospective cohort of adult patients initiating anti-tuberculosis treatment between January 2006 and May 2007. RESULTS: Among 5685 patients, 390 deaths occurred during anti-tuberculosis treatment, of which half (52%) did so during the first 2 months. Patients with smear-negative pulmonary TB were at greater risk of death in the first 2 months of treatment (human immunodeficiency virus [HIV] positive HR 1.49, 95%CI 0.89-2.49; HIV-negative HR 1.77 95%CI 1.06-2.95), but not thereafter. Patients with extra-pulmonary TB were at increased risk of death in the first 2 months of anti-tuberculosis treatment if they were non-HIV-infected (HR 2.42, 95%CI 1.52-3.85), and were half as likely to die during the remainder of treatment (HIV-positive HR 0.46, 95%CI 0.22-0.97; HIV-negative HR 0.47, 95%CI 0.23-0.94). Antiretroviral therapy (ART) reduced the risk of death by an estimated 36% (HR 0.64, 95%CI 0.37-1.11). CONCLUSION: High mortality in the first months of anti-tuberculosis treatment could be reduced by addressing diagnostic delays, particularly for extra-pulmonary and smear-negative TB cases and, in HIV-infected patients, by initiation of ART soon after starting anti-tuberculosis treatment.

Microarray profiling of human white adipose tissue after exogenous leptin injection.

BACKGROUND: Leptin is a secreted adipocyte hormone that plays a key role in the regulation of body weight homeostasis. The leptin effect on human white adipose tissue (WAT) is still debated. OBJECTIVE: The aim of this study was to assess whether the administration of polyethylene glycol-leptin (PEG-OB) in a single supraphysiological dose has transcriptional effects on genes of WAT and to identify its target genes and functional pathways in WAT. MATERIALS AND METHODS: Blood samples and WAT biopsies were obtained from 10 healthy nonobese men before treatment and 72 h after the PEG-OB injection, leading to an approximate 809-fold increase in circulating leptin. The WAT gene expression profile before and after the PEG-OB injection was compared using pangenomic microarrays. Functional gene annotations based on the gene ontology of the PEG-OB regulated genes were performed using both an 'in house' automated procedure and GenMAPP (Gene Microarray Pathway Profiler), designed for viewing and analyzing gene expression data in the context of biological pathways. RESULTS: Statistical analysis of microarray data revealed that PEG-OB had a major down-regulated effect on WAT gene expression, as we obtained 1,822 and 100 down- and up-regulated genes, respectively. Microarray data were validated using reverse transcription quantitative PCR. Functional gene annotations of PEG-OB regulated genes revealed that the functional class related to immunity and inflammation was among the most mobilized PEG-OB pathway in WAT. These genes are mainly expressed in the cell of the stroma vascular fraction in comparison with adipocytes. CONCLUSION: Our observations support the hypothesis that leptin could act on WAT, particularly on genes related to inflammation and immunity, which may suggest a novel leptin target pathway in human WAT.