Survival, mortality and causes of death in inflammatory myopathies.

OBJECTIVE: To investigate the causes of death, survival and clinical factors associated with mortality, in a group of Spanish patients with inflammatory myopathies (IM) followed in the same University Hospital during a 25 year period. METHODS: A cross sectional study was performed, including 107 patients diagnosed with IM according to the Bohan and Peter criteria. Demographical and clinical information were extracted from the charts. Bivariate odds ratio with 95% confidence interval (CI) was used to measure the strength of association between variables. Kaplan-Meyer analysis was used to estimate survival. Univariate and multivariate Cox regression analysis were used to study clinical associations with mortality. RESULTS: Twenty-eight patients (26%) died. Deaths were considered to be disease related in 21 cases. Main causes of death were cancer extension, cardiac involvement and lung involvement. Survival for the whole group was 92, 80 and 71% after 1, 5 and 10 years, respectively. By the log rank test, survival was lower for patients with cancer (p = 0.0001) as well as in those with cardiac involvement (p < 0.00001), compared to patients without these conditions. Cox univariate analysis showed that mortality was associated with higher age at IM onset, left ventricular dysfunction, the presence of cancer and the smoking habit. In Cox multivariate analysis, only left ventricular dysfunction (HR = 4.6; 95%CI 2.0-10.3; p > 0.0001) and the presence of cancer (HR = 3.3; 95%CI 1.4-7.4; p = 0.005) remained associated with mortality. CONCLUSIONS: Although a great improvement has been achieved in the last decades in controlling IM, our study indicates that the mortality rate in this group of patients remains high. Cancer and cardiac involvement are important causes of death, and also prognostic factors for mortality in our group of patients. A careful search for cardiac involvement should be done in every patient with IM.

Menstrual disorders in girls with systemic lupus erythematosus treated with cyclophosphamide.

To study the ovarian toxicity associated with cyclophosphamide in girls with systemic lupus erythematosus (SLE), we retrospectively reviewed the charts of 30 SLE girls aged 16 yr or younger at diagnosis, followed at three university hospitals. Gynaecological history was extracted from the charts or obtained prospectively. Ten had not received cyclophosphamide therapy, six were treated with daily oral cyclophosphamide, 10 with intravenous pulses and four with daily oral and intravenous pulses. Median oral cyclophosphamide dose was 38 g (inter-quartile range 75) and median intravenous dose 12.95 g (inter-quartile range 6.2). Six girls had oligomenorrhoea (20%) and one amenorrhoea (3%). Two treated with oral cyclophosphamide had oligomenorrhoea (33%) and one amenorrhoea (17%), two treated with both oral and intravenous pulses had oligomenorrhoea (50%), and none of those treated with intravenous pulses alone had menstrual disturbances (50% oral vs 0% intravenous pulses; P = 0.016). Girls who had menstrual disturbances had received higher doses of cyclophosphamide than those who did not (medians: 63 vs 15 g; P < 0.05). In summary, menstrual disturbances in SLE girls treated with cyclophosphamide are related to the total dose and perhaps to the administration method.

HLA class I allele (HLA-A2) expression defect associated with a mutation in its enhancer B inverted CAT box in two families.

The present study shows a very highly diminished HLA-A2 cell surface expression with mendelian segregation in two nonrelated Spanish families. The associated haplotype included Cblank-B38-DRB1*1301-DQ6 in both families. cDNA sequence analysis in two members, one of each pedigree, revealed the presence of the commonest HLA-A2 allele (A*0201), without repetitive mutations that could indicate inappropriate or inefficient translation. Further, the coamplified 3'-untranslated region sequence was also the same described for HLA-A2. HLA-A transcription frequency by means of cDNA PCR-based cloning experiments and by Northern blotting pointed out a relatively low number of HLA-A2 mRNA molecules compared with the complementary HLA-A allele. 5'-Regulatory region sequences from two low-expressing HLA-A2 nonrelated individuals showed a unique and identical single point mutation at position -101 (T to C), when compared with all MHC class I alleles sequenced so far. Position -101 is located in the inverted CAT box associated with the MHC class I enhancer B. The fact that this is an extremely well-conserved position leads us to postulate that this change may be the only responsible for the defective expression of HLA-A2.

Prenatal exclusion of paternity by PCR-FLP analysis of VNTR.

A prenatal paternity test was requested by a 30-year-old woman. Variable number of tandem repeat (VNTR) systems were used for DNA analysis by means of amplification and electrophoresis followed by ethidium bromide staining or Southern blotting and oligonucleotide hybridization. Exclusion of paternity could be established on the basis of the great polymorphism and heterozygosity indexes of these genetic systems. This rapid method presents several advantages in contrast with other recombinant DNA techniques such as HLA class II oligotyping or RFLP.

A long term study of 22 children with brucellar arthritis.

Brucellar arthritis remains a serious a problem in Mediterranean countries. In the pediatric group it has not received enough attention. We have analysed the clinical features of 22 children followed in a large hospital for the last 10 years. Fever (68%), malaise (50%), myalgia (18%) and abdominal pain (14%) were the most common systemic symptoms. Three different patterns of arthritis were observed: acute (45%), chronic (41%) and recurrent (14%). Monoarthritis (45%) with hip involvement was very common. Response to treatment with large doses of cotrimoxazol for a long period of time was good. No toxicity was observed.

Both HLA class II and class III DNA polymorphisms are linked to juvenile rheumatoid arthritis susceptibility.

HLA-DR5 and DRw8 are not significantly linked to juvenile rheumatoid arthritis (JRA) in the Spanish population. However, we have found restriction fragment length polymorphisms (RFLPs) beta DR-2.9-kb-EcoRI and C4-14.3-kb-EcoRI, that correlate significantly with JRA. Eighty-six percent of our patients present either HLA-DR5 or the beta DR-2.9-kb-EcoRI allogenotope or lack the C4-14.3-kb-EcoRI allogenotope compared to 48% in controls; however, these particular DR and C4 RFLPs may not represent the corresponding DRB1 or C4 genes but rather neighboring ones which may be relevant to confer JRA susceptibility. The C4-14.3-kb-EcoRI RFLP decrease in patients may reflect a decrease in C4 B "long" phenotypes. Also, both RFLPs are the only markers able to identify most of the JRA patients in our population. On the other hand, the findings of both class II and III genes associated to JRA may reflect the existence of epistatic interactions (cis or trans) within the HLA gene cluster which lead to a particular pathology in certain diseases.

[Critical analysis of the routine use of the direct antiglobulin test in 22,517 cross-matching tests]. / Análisis crítico del empleo rutinario de la prueba de la antiglobulina directa (DAT) en 22,517 pruebas cruzadas.

Routine performance of the direct antiglobulin test (DAT) in pretransfusion testing (PT) is controversial. To evaluate its usefulness, we review the positive DATs found in 22,517 PT performed in our center in the last five years. DAT was positive in 330 PT (1.4%). Eluate studies gave information, not obtained from the rest of PT, in 6 cases. DAT predictive value is low (1.8% of the positive DATs, 0.02% of all PT). Although this predictive value is low, we keep on follow including DAT in PT but we have reduced eluate studies to 1) positive DAT of untransfused patients (to get information of the DAT prior to transfusion and to detected autoimmune haemolytic anaemias) and 2) positive DAT of previously transfused patients with previous negative DAT or changes in its reactivity (for the prompt detection of clinically significant antibodies).

Brucellar arthritis in children and its successful treatment with trimethoprim-sulphamethoxazole (co-trimoxazole).

The clinical characteristics and the response to treatment with high doses of co-trimoxazole in 12 children with brucellar arthritis were analysed retrospectively. The children lived in an urban area and all but two had a history of unprocessed milk or cheese ingestion. Fever and oligoarthritis of the lower extremities were the most common clinical findings. Control of the disease was achieved by three months of treatment. Compliance with the medication was excellent, and no significant side effects occurred.

DR, C4, and Bf allotypes in juvenile rheumatoid arthritis.

HLA-DR, C4, and Bf typing was performed in 99 patients with juvenile rheumatoid arthritis (JRA). DR1 was found with higher frequency in patients with polyarticular JRA than in controls (P less than 0.05). DR3 was more common in patients with fever and/or rash than in those without these manifestations (P less than 0.05). A significant negative association between JRA and C4A6 (P less than 0.05), C4BQ0 (P less than 0.0005), and BfF1 (P less than 0.05) was found. It is possible that a disequilibrium between DR and C4/Bf genes plays a role in the pathogenesis of JRA.