Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis.

OBJECTIVE: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). METHODS: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. RESULTS: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). CONCLUSIONS: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

A novel myelin protein zero (V136G) homozygous mutation causing late onset demyelinating polyneuropathy with brain white matter lesions.

Although less common than peripheral myelin protein 22 (PMP22) duplication, there are mutations in myelin protein zero (MPZ) responsible for Charcot-Marie-Tooth disease (CMT) with a number of different clinical profiles. We report here a novel MPZ homozygous mutation, with a peculiar pattern characterized by a late-onset demyelinating profile. In addition, the patient presented brain white matter lesions seemingly ascribable to the mutation.

Síndrome de leucoencefalopatía posterior en relación con angiopatía amiloide / Posterior leukoencephalopathy syndrome associated with amyloid angiopathy

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Detection of anti-heat shock protein 90 beta (Hsp90beta) antibodies in cerebrospinal fluid.

Antibodies against heat shock protein 90 beta (Hsp90beta) recognize the antigen on the cell surface of the oligodendrocyte precursor cells and cause a decrease of oligodendrocyte population in cell cultures. These antibodies have been found in patients with multiple sclerosis (MS). This report describes an original and sensitive method to detect anti-Hsp90beta antibodies in cerebrospinal fluid (CSF) using a western blot procedure. We have developed the method for autoantibody detection using Hsp90beta from cell membrane fraction instead of commercial Hsp90beta as antigen. The presence of anti-Hsp90beta antibodies in CSF of MS patients may play a pathogenic role in MS, and a large-scale study is needed to establish a possible diagnostic value of these antibodies in MS patients.

Siete años del programa de intercambio de jeringuillas en el Centro Penitenciario de Pamplona (España) / Seven years of the needle exchange program in the prison centre in Pamplona (Spain)

En la prisión de Pamplona, capital de Navarra, Comunidad Autónoma situada al norte de España, alrededor del 35% delos internos han tenido o tienen problemas relacionados con el uso de drogas por vía intravenosa. Las Administraciones Penitenciarias responsables de la asistencia sanitaria a los presos, deben garantizar el derecho a la salud de los internos en similarescondiciones a las de población general y esto incluye la implementación de programas de reducción del daño como son los programas de intercambio de jeringuillas (PIJ).En noviembre de 1998, se inició un programa piloto de intercambio de jeringuillas (PIJ) en la prisión que continúa en la actualidad. Diferentes instituciones han participado en su elaboración, implementación, coordinación y evaluación. El intercambio en el PIJ de Pamplona es de tipo personalizado, es decir, lo realiza un profesional, lo que ofrece la posibilidad de realizarintervención sanitaria.En 7 años de funcionamiento del PIJ no han existido incidentes reseñables, ni con los usuarios ni con los trabajadores del Centro. El programa ha alcanzado un porcentaje de devoluciones del 93% y es utilizado por el 40% de los VIH positivos. No se ha detectado aumento del consumo de droga inyectada, ha desaparecido el uso de jeringas ilegales y no se ha documentado ningún caso de sero-conversión frente al VIH o al VHC. El seguimiento continuo del programa, así como la opinión de los usuarios y del personal trabajador del Centro se consideran los factores clave para el éxito del mismo

In the prison of Pamplona, capital city of Navarra, a region in the north of Spain, around 35% of the prisoners currently have or have had problems related with intravenous consumption of drugs. The National Department of Prisons which is in charge of the provision of health care to the prisoners, has the mandate to provide similar health programs to those available for the general population. This includes the implementation of harm reduction programs such as needle exchange programs (NEP).In November 1998, a pilot NEP was started in the prison of Pamplona which is still functioning. Different institutions have participated in the development, implementation, coordination and evaluation of the program. Needle exchange in the NEP in Pamplona is personal, which means that a health care worker provides the sterile kits. This allows for undertaking otherhealth interventions.In the seven years the NEP has been operating, no problems have aroused among the program users neither among the prisons staff. The program has achieved a 93% of needle devolutions, and 40% of HIV positive prisoners use it. No increase of injecting drug consumption has been observed. Illegal syringes are not used anymore in the prison and no case of HIV or HCV sero-conversion has been documented. The continuous evaluation of the program and the positive attitude of users andprison’s staff are crucial in the success of the NEP in Pamplona

Exposure to non-arsenic pesticides is associated with lymphoma among farmers in Spain.

OBJECTIVES: To estimate the risk of lymphoma among farmers in Spain. METHODS: This is a multicentre case control study conducted in Spain. Cases were subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification in four hospitals between 1998-2002. Hospital controls were frequency matched to the cases by sex, age, and centre. All subjects were interviewed about jobs ever held in lifetime for at least one year and the exposures in those jobs were recorded. The risk of lymphomas among subjects ever having had a job as a farmer was compared with all other occupations. Farmers were analysed according to the type of farming job performed: crop farming, animal farming, and general farming. Occupational exposure was summarised into 15 main categories: organic dust, radiation, contact with animals, PAH, non-arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran), arsenic pesticides, contact with meat, contact with children, solvents, asbestos, soldering fumes, organic colourants, polychlorinated biphenyls, ethylene oxide, and hair dyes. RESULTS: Although farmers were not at an increased risk of lymphoma as compared with all other occupations, farmers exposed to non-arsenic pesticides were found to be at increased risk of lymphoma (OR = 1.8, 95% CI 1.1 to 2). This increased risk was observed among farmers working exclusively either as crop farmers or as animal farmers (OR = 2.8, 95% CI 1.3 to 5.8). Risk was highest for exposure to non-arsenic pesticides for over nine years (OR = 2.4, 95% CI 1.2 to 2.8). CONCLUSIONS: Long term exposure to non-arsenic pesticides may induce lymphomagenesis among farmers.

Diagnóstico radiológico / Radiologic diagnosis

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[Nasal encephalocele: differential diagnosis with nasal glioma]. / Encefalocele nasal: diagnóstico diferencial con el glioma nasal.

Congenital nose neoplasms are infrequent, between them neurogenic tumors of the middle line include nasal gliomata (glial ectopies) and nasal encephaloceles, according to an existing or lacking communicating link with the intracranial cavity. We report one congenital naso-encephalocele case in a 16-year-old girl suffering from repeated meningitis events after several nasal polypectomies performed in other departments. She underwent complete removal through fronto-neurosurgical and paralateronasal approach, being the young woman asymptomatic for 3 years. We discuss about both intranasal gliomata and encephaloceles, certainly of not easy pathologic identification, stressing the decisive value of imaging techniques, as magnetic resonance, in order to clearcut both the diagnosis and the therapeutical planning.

[Focal myositis: report of a case in pediatric age and review of the literature]. / Miositis focal: a propósito de un caso en edad pediátrica y revisión de la literatura.

INTRODUCTION AND CLINICAL CASE: We present the case of a 13 years old boy with a year-old history of a painful tumour on the external and distal third of the right thigh. The imaging tests suggested a soft tissue tumour but the muscle biopsy revealed the typical findings of focal myositis. Focal myositis is a benign inflammatory pseudotumour of the skeletal muscle recognized as a distinct clinicopathological entity, but there have been descriptions of the cases initially diagnosed as focal myositis that have latter behaved as evident polymyositis. We have not found laboratory data to support a diagnosis of polymyositis in our patient. CONCLUSION: Although focal myositis is considered a self-limited disease, we believe a long-term clinical and biochemical follow-up is warranted, to confirm the absence of recurrence signs and/or the development of a generalized myopathy.

Transthyretin Tyr77 familial amyloid polyneuropathy: a clinicopathological study of a large kindred.

More than 40 point mutations (producing different clinical manifestations) have been described in diverse points of the plasma protein transthyretin (TTR). The Met30 is considered the most common mutation, the Tyr77 mutation being the second most prevalent. However, data from patients with this late mutation are scarce, and usually come from isolated case reports or tables. The Tyr77 mutation is not as well characterized as the Met30 mutation, especially with respect to such aspects as prognosis or possible treatment by liver transplantation. We therefore present the clinical and pathological features of an extensive family with the Tyr77 TTR mutation, comprising 12 affected individuals over four generations. Six living individuals were followed over a 10-year period. Retrospective data were obtained with regard to the deceased family members. We found that an initial and sometimes prolonged carpal tunnel syndrome, beginning between the 6th and 7th decades, characterizes the Tyr77 mutation. In most cases this evolved to generalized peripheral nerve involvement, restrictive cardiomyopathy, and intestinal malabsortion. Although survival is usually high, there are progressive cases that should be candidates for liver transplant, before severe impairment has developed.

Differential expression of neurofilament triplet proteins in carcinoid tumours: an immunohistochemical study.

Neurofilaments (NFs) are specific intermediate filaments to neural cells. Mammalian NFs are protein triplets composed of three major subunits with respective molecular weights of approximately 70, 150 and 200 kD. Using an immunohistochemical method, 13 carcinoid tumours from different sites were examined for the presence of these three subunits by means of monospecific antisera. All tumours contained cells that were positive for the 70 Kd subunit; nine cases contained cells immunoreactive for the 150 Kd subunit and only three of them for the 200 kD subunit. The results indicate that the 70 kD subunit is a good overall marker of carcinoid tumours. The 150 and 200 kD subunits are more likely to be absent in carcinoids, both typical and atypical.