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Aim: We investigated the clinical relevance of SLC19A1 genetic variability for methotrexate (MTX) toxicity in rheumatoid arthritis patients using a haplotype-based approach. Patients & methods: Two hundred and twelve unrelated rheumatoid arthritis patients and 89 lymphoblastoid cell lines were used to investigate the effect of SLC19A1 SNPs and haplotypes on MTX adverse events and treatment discontinuation. Results: Two putatively functional SNPs in high linkage disequilibrium, rs1051266 and rs1131596, were associated with protection (hazard ratio: 0.33; 95% CI: 0.16–0.69; adjusted p = 0.021 and hazard ratio: 0.38; 95% CI: 0.17–0.27; adjusted p = 0.021, respectively) of discontinuation of MTX treatment owing to toxicity. These SNPs were also associated with protection from infections. SLC19A1 haplotype analysis found significant associations with MTX discontinuation owing to toxicity (p = 0.025). Quantification of SLC19A1 mRNA in cell lines suggested that rs1131596 was not a major causal variant. Conclusion: Individual SNP and haplotype analyses suggest that rs1051266 could be a functional variant altering MTX toxicity; however, validation in independent studies is needed. Original submitted 23 May 2012; Revision submitted 3 September 2012

Leflunomide is a disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Cytochromes P450, mainly CYP1A2 and CYP2C19, may be involved in the transformation of leflunomide to leflunomide metabolite (A77 1726, 2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide). The aim of this study was to investigate whether genetic polymorphisms in CYP1A2 and CYP2C19 influence leflunomide pharmacokinetics, treatment response, and the occurrence of adverse drug reactions (ADRs). The study included 67 patients with RA and 4 patients with polyarthritis resembling RA and psoriasis treated with leflunomide. A77 1726 steady-state plasma concentrations were determined by validated high-performance liquid chromatography with UV detection. A population pharmacokinetic model was developed to estimate the oral clearance (CL/F) and volume of distribution (V/F). A genotyping approach was used to determine C-163A, C-729T, and T-739G in the CYP1A2 gene as well as single nucleotide polymorphisms that characterize CYP2C19*2, *3, *4, and *17 alleles. A large interindividual variability in trough A77 1726 steady-state plasma concentrations was observed (from 1.9 to 156.9 mg/l). A77 1726 CL/F was 71% higher in carriers of the CYP2C19*2 allele compared with noncarriers. The A77 1726 average steady-state plasma concentration was associated with the treatment response. Patients with a greater decrease in C-reactive protein (CRP) had higher average steady-state plasma A77 1726 concentrations: 49.7 +/- 39.0 mg/l in patients with DeltaCRP of more than 8.5 mg/l compared with 24.8 +/- 13.7 mg/l in patients with DeltaCRP ofor=8.5 mg/l (p = 0.015). No association of A77 1726 steady-state plasma concentrations with the occurrence of ADRs was observed. Our results suggest that genetic variability in leflunomide-metabolizing enzymes influences leflunomide metabolite concentrations that are associated with the treatment response but not with leflunomide-induced toxicity.

Objective: To develop response criteria for polymyalgia rheumatica (PMR) for monitoring treatment and comparing alternative treatments regimens. Methods: 76 patients, mean (SD) age 68.7 (7.7) years, were enrolled. Corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) were the only drugs allowed during the observation period. Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), α2 globulin, serum iron, pain, physician's global assessment (PGA), morning stiffness (MST), muscle tenderness (MT), myalgia, and the elevation of upper limbs (EUL) were determined regularly. The daily corticosteroid and NSAID doses as the corticosteroid response time were recorded. To ensure evaluation of an adequate number of patients (n = 57) week 24 was chosen for final analysis. Results: ESR, CRP, α2 globulin, pain, PGA, MST, myalgia, MT, and EUL showed significant improvement (p

Objective. Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr. Methods. Outcome parameters were the SLE Disease Activity Index (SLEDAI ), the European Consensus Lupus Activity Measure (ECLAM ), the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR), a global damage index (DI ) and required treatment. In 10 diVerent European rheumatology centres, all SLE patients who were evaluated in the last 3 months of 1994, and who had been diagnosed with SLE at least 10 yr ago, were included in the study. Results. It should be stressed that our results are confined to a patient cohort, defined by a disease duration of at least 10 yr, and who are still under clinical care at the diVerent centres in Europe. These SLE patients still showed some disease activity, related to symptoms of the skin and musculoskeletal systems, next to the presence of renal involvement. A total of 72% of the patients needed treatment with prednisolone (7.5 mg). The cumulative damage was overall related to clinical features of the central nervous system (14%) and renal involvement (14%), next to deforming arthritis (14%), osteoporosis (15%) and hypertension (40%). The prevalences of obesity, Cushing appearance and diabetes are highly suggestive that the ongoing treatment and that in the past might have had an impact on the total sum of endorgan damage. Conclusions. After 10 yr, a high proportion of patients in our cohort continued to show evidence of active disease, defined by the SLEDAI as well as ECLAM. The DI was related to the involvement of the central nervous system, renal involvement and the presence of hypertension.

Vaccines have undoubtedly brought overwhelming benefits to mankind and are considered safe and effective. Nevertheless, they can occasionally stimulate autoantibody production or even a recently defined syndrome known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is scarce data regarding autoimmune response after seasonal/influenza A (H1N1) vaccine in patients with autoimmune inflammatory rheumatic disease (AIRD). The objective of our study was therefore to determine autoimmune response in a large group of AIRD patients vaccinated against seasonal and/or H1N1 influenza. We conducted a prospective cohort study with a 6-month follow-up. Two-hundred and eighteen patients with AIRD (50 vaccinated against seasonal influenza, six against H1N1, 104 against both, 58 non-vaccinated controls) and 41 apparently healthy controls (nine vaccinated against seasonal influenza, three against H1N1, 18 against both, 11 non-vaccinated controls) were included. Blood samples were taken and screened for autoantibodies [antinuclear antibody (ANA), anti-extractable nuclear antigen (anti-ENA), anticardiolipin (aCL) IgG/IgM antibodies, anti-beta 2-glycoprotein I (anti-β2GPI)] at inclusion in the study, before each vaccination, 1 month after the last vaccination and 6 months after inclusion. For non-vaccinated participants (patients and healthy controls) blood samples were taken at the time of inclusion in the study and 6 months later. We report that after the administration of seasonal/H1N1 vaccine there were mostly transient changes in autoantibody production in AIRD patients and in healthy participants. However, a small subset of patients, especially ANA-positive patients, had a tendency towards anti-ENA development. Although no convincing differences between the seasonal and H1N1 vaccines were observed, our results imply that there might be a slight tendency of the H1N1 vaccine towards aCL induction. Although seasonal and H1N1 vaccines are safe and effective, they also have the potential to induce autoantibodies in selected AIRD patients and healthy adults. Follow-up of such individuals is proposed and further research is needed.

In an attempt to demonstrate whether clinically selected joints of the hand in active rheumatoid disease had consistent MRI findings, 45 patients were examined, in whom one joint in each was selected by both the referring clinician and patient as being active and symptomatic. Such joints, in order to be included in the study, were required to conform to ARA criteria of activity and usually mild to moderate X-ray changes. The joints were imaged using spin-echo sequences with T1W and T2W precontrast images, followed by T1W images after intravenous administration of Gd-DTPA. Different patterns of joint abnormalities were found. In 27 joints MRI findings suggested highly active synovitis and/or destructive pannus. In four, crescentic enhancement was thought to be compatible with simple synovitis, but in 23 rounded masses of synovial proliferation were characterized by marked, diffuse contrast enhancement on T1W postcontrast images, which corresponded well with high signal intensity on T2W images. Synovial proliferation in a further 12 joints was shown by only moderate stippled contrast enhancement and nonhomogeneous intermediate to high signal intensity on T2W images. These findings were thought to represent less active synovitis and pannus. MRI did not demonstrate inflammatory activity in six joints. In two of these pannus was of low signal intensity on T2W images, without contrast enhancement after Gd-DTPA infection presumed fibrotic and inert, and four were normal on all pulse sequences. These results suggest that clinical features of synovitis, even in carefully selected joints clinically, do not produce a homogeneous group when examined by MRI imaging. Indeed, a spectrum exists from presumed marked, active synovitis to total normality. If MRI is to be used as a clinical and research tool in the assessment of rheumatoid disease, and its therapeutic manipulation, these results are of some importance, since the variable findings indicate an appreciable heterogeneity of appearances in joints thought clinically to be of relatively uniform severity.

Leflunomide is a disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Its safety and efficacy was initially described in 1995.1 In vitro studies have demonstrated that CYP1A2 is one of the main leflunomide metabolising enzymes.2 We have previously shown that polymorphisms in CYP1A2 may be associated with leflunomide toxicity in patients with RA.3 As leflunomide metabolite directly inhibits dihydroorotate dehydrogenase (DHODH),4 we investigated whether the DHODH A40C polymorphism (rs3213422) that causes substitution of Lys7 to Gln is associated with leflunomide toxicity. Our study included 105 patients with RA, of whom 62 tolerated the leflunomide treatment well (group A), while 43 patients discontinued …

Glutathione S-transferases (GST); GST-mu1 (GSTM1), GST-pi1 (GSTP1) and GST-theta1 (GSTT1) have peroxidase activity towards cytotoxic metabolites produced in inflammatory reactions, the main feature of rheumatoid arthritis (RA). Genetic polymorphisms in GSTM1, GSTP1 and GSTT1 modify the enzyme conjugation capacity and may be associated with the activity of RA.A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RA patients. Disease activity was assessed by the disease activity score of 28 joint counts (DAS28) twice for each patient and mean DAS28 values were calculated.The patients with GSTT1-0 genotype had a higher risk for developing high activity RA than the patients with GSTT1 genes present (p=0.028, OR=2.761, 95% CI=1.114-6.843). An interaction between the GSTT1 polymorphism and smoking was observed. In the group of smokers, the carriers of a homozygous deletion GSTT1 had an 8.5-fold higher risk for developing high disease activity than the patients with the GSTT1-1 genotype (p=0.004, OR=8.640, 95% CI=1.995-37.426). GSTM1 and GSTP1 polymorphisms were not associated with the disease activity.Our results suggest that the presence of the GSTT1-0 genotype contributed to higher disease activity in RA patients. The risk for developing highly active RA was the highest in smokers with the GSTT1-0 genotype.

Leflunomide is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). In vitro studies demonstrated that cytochromes P450 (CYPs), mainly CYP1A2 and CYP2C19, might be involved in leflunomide activation. The aim of our study was to investigate whether genetic polymorphisms of CYP1A2, CYP2C19, and CYP2C9 influence leflunomide toxicity.A genotyping approach was used to determine CYP1A2*1F, CYP2C19*2, CYP2C19*17, CYP2C9*2, and CYP2C9*3 alleles in 105 RA patients.Leflunomide treatment was well tolerated by 62 patients, whereas 43 patients discontinued the treatment within the first year due to toxicity. Patients with CYP1A2*1F CC genotype had a 9.7-fold higher risk for overall leflunomide-induced toxicity than did the carriers of CYP1A2*1F A allele [P = 0.002, odds ratio = 9.708, 95% confidence interval = 2.276-41.403]. No significant association between the CYP2C19 and CYP2C9 genotypes and the leflunomide toxicity was observed.Our results suggest that the CYP1A2*1F allele may be associated with leflunomide toxicity in RA patients.

Methotrexate (MTX) is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 A80G), P-glycoprotein (MDR1 G2677T>A/C and C3435T), 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TS 2R→3R), methionine synthase (MS A2756G) and methionine synthase reductase (MTRR A66G) modify MTX transport and metabolic effects and may influence the treatment response. A genotyping approach was used to determine the studied polymorphisms in 213 RA patients. We observed that 56 (26.3%) patients discontinued MTX treatment due to poor response and/or toxicity. RFC1 A80G and MDR1 C3435T polymorphisms increased the risk for overall MTX toxicity (P = 0.039, OR = 3.574, 95% CI = 1.065–11.993 and P = 0.032, OR = 7.801, 95% CI = 1.194–50.960 respectively), while MTHFR A1298C polymorphism had a protective effect on overall MTX toxicity (P = 0.027, OR = 0.170, 95% CI = 0.035–0.820). Our results suggest that genetic polymorphisms in the folate metabolic pathway and MTX transporters modify the toxicity but not the efficacy of MTX treatment.

With the broad employment of immunosuppressive therapy, the incidence of Pseudallescheria boydii infections is rising. We report a first case of the localized subcutaneous P. boydii infection in a patient with microscopic polyangiitis. Favorable outcome related to the treatment with voriconazole adds to the growing body of evidence supporting the use of this particular agent in P. boydii infections.

Leflunomide is a new isoxazole drug with disease modifying properties for the treatment of rheumatoid arthritis (RA). Hypertension has been mentioned as a common side effect of the treatment. It was found in up to 10.6% of patients receiving 25 mg leflunomide in a phase II study.1 New onset hypertension occurred in 3.7% of patients in a phase III European study,2 and in 2.1% of patients, with a mean increase in systolic and diastolic blood pressure of 2.2 and 1.9 mm Hg, respectively, in an American phase III study.3 There was no evidence that hypertension was related to an impairment of renal function or proteinuria. The changes in blood pressure during leflunomide treatment have not been studied in detail. Thirty consecutive patients fulfilling the American Rheumatism Association criteria for RA were recruited into a prospective study and treated with standard doses of leflunomide. Other enrolment criteria included stable treatment with non-steroidal anti-inflammatory drugs up to the maximum recommended dose and/or corticosteroid treatment …

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention tothepersistence of disease activity in the long term are scarce. At this moment reliable figures are only knownabout the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome ofSLE patients with a disease duration of greater than 10 y.Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2 ‐ 11% of the patients,seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the diseasecourse in most patients was characterized by periods of tiredness (42 ‐ 60%), arthritis (20 ‐ 25%), skin involvement such as malar rash (32 ‐ 40%), migraine (15 ‐ 20%), anaemia(15%) and leucopenia (17 ‐ 19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.

textabstractOBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.

Methotrexate (MTX) is a disease-modifying antirheumatic drug (DMARD) used for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms in AMP deaminase ( AMPD1 ), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase ( ATIC ), inosine triphosphate pyrophosphorylase ( ITPA ) and methylenetetrahydrofolate dehydrogenase ( MTHFD1 ) were shown to be associated with disease activity, MTX treatment response and MTX-induced toxicity in patients with RA.1,–,6 The aim of our study was to test these associations in Slovenian patients with RA treated with MTX. Our study included 211 patients with RA who were previously characterised.7 Among them, 98 patients were receiving MTX monotherapy, 57 co-treated with one or more DMARD and 56 discontinued MTX before enrolment owing to MTX inefficacy and/or toxicity. The 28-joint count Disease Activity Score (DAS28) …

In a sixty-one-year-old patient with chronic polyarthritis, two life-threatening septic events were observed over a period of 6 months. The patient also had a selective IgG3 deficiency. The susceptibility to infection and chronic polyarthritis observed in this patient were very likely a consequence of the selective IgG3 deficiency.

Objective The aim of our study was to determine the prevalence of Sjogren's syndrome (SS) in Slovenia. Methods A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe. The participants were asked six simple questions for assessing both ocular and oral involvement. Information on co-morbidities and related treatment was collected at the same time. All participants were subjected to a Schirmer-I test, an unstimulated salivary flow test, as well as serological studies (rheumatoid factor, antinuclear antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies). When indicated, Rose Bengal score, salivary scintigraphy and histopathological investigation of the minor salivary glands were carried out until three out of the six European classification criteria for SS were shown to be negative or until SS was diagnosed. Results Out of the 889 invited subjects, 332 (37.3%) participated in our study: 183 females, mean age (+/- S.D.) 52.2 +/- 13.7 yr (range 20-84) and 149 males, mean age (+/- S.D.) 56.3 +/- 12.9 yr (range 23-84). After the first visit, 244 of the 332 (73.5%) participants proved to be negative for three out of the six above-mentioned criteria, and were eliminated from further tests. The remaining 88 participants were consecutively subjected to Rose Bengal score, salivary scintigraphy and minor salivary gland biopsy. Fifteen participants refused to perform either one or more of the proposed tests at the second study stage. Two females of the 332 study participants [0.60% (exact 95% CI 0.07%, 2.16%)] fulfilled the criteria for primary SS. Conclusions The estimated prevalence of definite SS in Slovenia is 0.60%.

The aim of this prospective 24-month follow-up study was to compare clinical features with radiological and magnetic resonance imaging (MRI) findings in evaluating synovial proliferation in the hand joints of 31 patients with rheumatoid arthritis (RA). A single joint was used for the follow-up of each patient.Thirty-one small hand joints were examined by conventional radiography and MRI before and after 24 months of treatment. MRI assessment of disease progression (volume and/or signal intensity of the synovial proliferation on T1 weighted precontrast, T1 weighted postcontrast and T2 weighted images) was compared with a clinical assessment of the chosen joints, and with a plain x-ray film evaluation (Larsen's score).Of 26 joints which clinically improved (14 markedly and 14 slightly) during the study, on MRI 16 showed improvement, 8 showed no change, and 2 showed deterioration. Four clinically unchanged joints appeared improved on MRI. One joint deteriorated clinically and on MRI. Overall, there was a 58% congruence between clinical and MRI findings. On x-ray 23 joints showed no change; nine of these were also unchanged on MRI, while 13 showed improvement and one deterioration. Only in 2 out of 8 joints showing deterioration on x-ray were the MRI findings in accordance. In the remaining six joints MRI showed improvement. The congruence between x-ray and MRI was therefore 36%.The long-term follow-up of rheumatoid synovial proliferation of the small joints in the hand using contrast enhanced MRI is feasible and may provide additional information regarding disease activity. Important advantages over conventional radiography methods are its ability to demonstrate qualitative differences of synovial proliferation within bone erosions, and demonstrate not only deterioration, but also the improvement of inflammatory disease.

SUMMARY Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Od-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA. The results of the study confirm that in joints in which inflammatory active pannus is shown by contrast-enhanced MRI, progression of bone-destructive changes can be expected.

When the characteristic symptoms for an interstitial pulmonary disease arise in patients with rheumatoid arthritis, a drug-induced alveolitis should be considered in the differential diagnosis. In such cases, the administration of the drug and gold salts should be stopped.The cases of three patients with rheumatoid arthritis (RA) who had been treated with gold salts for 2 months (A), 23 months (B), and 36 months (C) are presented. The total dose of sodium aureothiomalate amounted to 280 mg for patient A, 1150 mg for patient B, and 2190 mg for patient C. Clinical signs, X-rays of the lungs, pulmonary function tests, and laboratory tests were evaluated for the three patients while, for patient A BAL as well as provocation tests were additionally performed before and after therapy. In this case, the histological picture of the lungs is presented; biopsies were taken during the first BAL.The clinical complaints of all 3 patients were similar, with the alveolitis being observed as diffuse in one case and above all in the upper regions in two cases on radiology. This led to differing degrees of diffusion disorders in the lungs. In patient A, the diagnosis was made in the stage of progressive fibrotic alveolitis and was treated with D-penicillamine. All 3 patients received steroids over 3-6 months and the gold salts were stopped. Because of the long duration and doubtful differential diagnosis for patient A with either rheumatoid lung or gold salt alveolitis, a provocation test with sodium aureothiomalate was performed. All 3 patients had blood eosinophilia while, in case A, a thrombopenia was also found.A gold salt alveolitis can occur as a side effect of gold salts in addition to skin vasculitis and hematological disorders. When the gold salt administration is not stopped a fibrotic alveolitis can develop. The provocation test can be diagnostically useful to distinguish between a rheumatoid lung and gold salt alveolitis.

We report a 32-yr-old woman who suffered a stroke as a consequence of arteritis of both internal carotid arteries confirmed by selective carotid arteriography. Laryngeal inflammation and kidney biopsy proven focal crescentic glomerulonephritis were also present in this patient. Anti-neutrophil cytoplasmic autoantibodies with specificity for proteinase 3 were detected in high titre during the active phase of the disease. This overlap syndrome with features indicating both Takayasu's arteritis and Wegener's granulomatosis suggests a common pathogenesis for these diseases.

In view of the association of congenital heart block with maternal antibody to cellular antigen Ro (SSA), and one report linking anti-Ro with myocarditis in a patient with myositis an association between anti-Ro antibodies and cardiac disease was sought in adults with systemic lupus erythematosus (SLE). Among 67 patients with SLE, of whom 36 were anti-Ro positive, a significantly higher prevalence of myocarditis and conduction defects was found in the anti-Ro positive group (eight of 36) than in those who were anti-Ro negative (one of 31) and healthy controls (one of 50). Of the 36 anti-Ro positive patients with SLE, three had symptoms diagnostic of myocarditis, and an electrocardiogram showed first degree atrioventricular block and unifascicular block in three cases (including one with myocarditis), right bundle branch block alone (two cases), and first degree atrioventricular block alone (one case). Complete atrioventricular block was not seen. In the anti-Ro negative group there was no myocarditis and only one case of conduction defect (right bundle branch block). Among healthy controls only one of 50 had first degree atrioventricular block. It is concluded that myocarditis and conduction defects are reasonably common in adults with SLE and are associated with anti-Ro antibodies.

To ascertain if the polymorphism of HLA-DR, DQA and DQB alleles and QAP and QBP promoters influences the production of aCL and anti-β2-GP1 in SLE. While the role of HLA-antigens in directing various autoantibody responses is relatively well known, the effect of promoters is less established. Sixty-five consecutive unrelated Slovenian SLE patients (all female, mean age ± SD 36 ± 8.3 years, mean follow-up 93 months) and 74 unrelated healthy adults were investigated. aCL and anti-β2-GP1 were determined by ELISA. The patients and controls were typed for DRB1, DQB1, QAP and QBP alleles by PCR-SSO, using the 12th IHW primers, probes and protocols. The subtyping of DQB1 alleles as well as DQA1 typing was carried out with selected Dynal SSP primers. Allelic and deduced haplotypic frequencies in patients and controls were compared using Fisher's exact test. 32 (49%) and 16 (25%) of 65 SLE patients were positive for IgG, IgM and/or IgA aCL and anti-β2-GP1, respectively. The frequency of the DQB1*0202 allele was significantly higher in the aCL (P = 0.001) and anti-β2-GP1 (P = 0.001) negative patients than in controls. Conversely, the DQB1*0301 allele and its promoter QBP3.1 were underestimated in the aCL (P = 0.06) and anti-β2-GP1 (P = 0.001) negative patients compared with controls. The DQB1*0202 allele may have a preventive role in provoking autoimmune response against both tested aPL. While the DQB1*0301 allele and its promoter QBP3.1 were underestimated in anti-β2-GP1 negative patients, they did not seem to protect from β2-GP1 specific autoimmune response in SLE patients. In contrast, we have already observed positive correlation of anti-Ro antibody response with the DQB1*0202 allele and the significantly underestimated DQB1*0301 allele and its promoter QBP3.1 in the same group of anti-Ro positive SLE patients.

A device has been constructed that permits rapid, repeatable measures of visual acuity while minimizing many of the patient and examiner errors in subjective acuity testing. The Baylor acuity meter utilizes digital logic circuitry to implement a carefully controlled psychophysical "staircase" testing procedure in a small portable unit. Comparisons of the acuity meter with conventional measurement techniques on 51 subjects yield correlations of +.74 and +.81. A test-retest correlation of +.96 was found.

An unusual low-vision remedy was encountered in which a simple dime-store marble was used in near vision tasks. Although the marble was found satisfactory as a low-vision aid, the patient could be better assisted with a commercially available magnifier of lesser dioptric power. This case serves to demonstrate a patient's ingenuity in independently solving his own low vision problem.