Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish Transplant Registries 1998-2015.

Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland. Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown. Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02). Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.

Attenuated post-exercise heart rate recovery in patients with systemic lupus erythematosus: the role of disease severity and beta-blocker treatment.

Objective Sinus tachycardia is frequently reported in systemic lupus erythematosus (SLE), while there are limited data on post-exercise ability to slow heart rate (i.e. heart rate recovery, HRR) in this group of patients. Methods We studied consecutive 70 patients with SLE and 30 healthy controls. All examined individuals underwent detailed clinical examination, echocardiography, Holter monitoring with heart rate variability and treadmill stress test using Bruce's protocol. HRR values were calculated as the difference between maximum HR during exercise and HR at the first (HRR1) and third (HRR3) minute of rest. Individuals with coronary artery disease, diabetes mellitus and suspected pulmonary hypertension were excluded from further analysis ( n = 15). Results Fifty-five SLE patients were eligible for this study: aged 41.5 ± 12.4 years, 87.3% women, SLICC/ACR-DI score 3.58 ± 1.85. In the SLE group 36.4% patients received beta-blockers, usually for previously detected sinus tachycardia and/or arterial hypertension. Mean HRR1 (36.9 ± 12.6 vs 49.5 ± 18.6, p = 0.0004) and HRR3 (55.5 ± 14.3 vs 69.2 ± 16.4, p = 0.0001) were significantly lower in SLE than in healthy individuals. Significantly negative correlations between SLICC/ACR-DI score and HRR1 ( r = -0.299, p = 0.01), HRR3 ( r = -0.361, p = 0.001) and exercise capacity ( r = -0.422, p < 0.0001) were revealed. Additionally, beta-blocker treatment was also revealed to alter significantly HRR1, HRR3 and exercise capacity in SLE. Conclusion Patients with SLE are characterized by attenuated HRR after exercise. In our study impaired HRR was associated with disease severity and beta-blocker treatment and probably with disease duration. The use of HRR assessment in SLE can be used as an additional marker of cardiac autonomic nervous system dysfunction.

Differential association of juvenile and adult systemic lupus erythematosus with genetic variants of oestrogen receptors alpha and beta.

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, p(corrected) = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, p(corrected) = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, p(corrected) = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, p(corrected) > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease.

Monthly dosing of 75 mg risedronate on 2 consecutive days a month: efficacy and safety results.

UNLABELLED: Postmenopausal women with osteoporosis received 75 mg risedronate on two consecutive days each month or 5 mg daily for 12 months. Changes in bone mineral density and bone turnover markers were similar between treatments. Risedronate 75 mg twice monthly was effective and safe suggesting a new, convenient dosing schedule. INTRODUCTION: Patients perceive less frequent dosing as being more convenient. This 2-year trial evaluates the efficacy and safety of a new monthly oral regimen of risedronate; 1 year results are presented here. METHODS: Postmenopausal women with osteoporosis (n = 1229) were randomly assigned to double-blind treatment with 75 mg risedronate on two consecutive days each month (2CDM), or 5 mg daily. The primary endpoint was the percent change from baseline in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary efficacy was evaluated by mean percent changes from baseline in BMD in LS, total hip, trochanter, and femoral neck, and bone turnover markers (BTMs). RESULTS: Risedronate 75 mg 2CDM was non-inferior to 5 mg daily (treatment difference 0.21; 95% CI -0.19 to 0.62). Mean percent change in LS-BMD was 3.4% +/- 0.16 and 3.6% +/- 0.15 respectively. Mean percent changes in BMD and BTMs were significant and similar for both treatment groups. New vertebral fractures occurred in 1% of subjects with either treatment. Both treatments were generally well tolerated and safe. CONCLUSIONS: Risedronate 75 mg 2CDM was non-inferior in efficacy and did not show a difference in safety vs. 5 mg daily after 12 months, leading to a similar benefit.

Bone turnover rate in postmenopausal women: bimodal distribution?

There is considerable evidence that elevated bone turnover is an independent form of low bone mineral density (BMD) risk factor of osteoporotic fractures. The aim of our study was to test whether a group of postmenopausal women could be divided into subgroups of high and low bone turnover rate using different pairs of bone turnover markers (one resorption, one formation). Cluster analysis was used to obtain high and low bone turnover subgroups within the study group. A magnitude of difference in lumbar spine BMD (expressed as Z-score) between high- and low-turnover groups was used as a criterion of division success. According to this criterion, the division obtained with a urinary type I collagen crosslinked N-telopeptide/bone alkaline phosphatase pair of markers appeared to be the most significant. This method of separation of two subgroups was highly concordant with the division based on the upper thresholds of the normal values for those markers found for the premenopausal women. It seems that the observed existence of high-and low-turnover subject clusters is not an incidental phenomenon, because the effects obtained for the whole study group were further confirmed by the consistent results of cluster analysis, performed separately for two randomly selected subgroups (A and B) from the study group. The results obtained appear to support the view that bone turnover rate in postmenopausal women is distributed in the bimodal fashion. This finding seems to justify further investigations of more elaborated models, enabling clinicians to individually classify their patients as low- or high-turnover cases with higher efficiency, as in the case of cutoff values for single markers.

[The assessment of the value of ultrasound and magnetic resonance imaging in diagnosing hand joint arthritis]. / Ocena przydatnosci ultrasonografii i rezonansu magnetycznego w diagnostyce zapalenia stawów rak.

The main imaging investigation used in diagnosing rheumatoid arthritis is radiography of the hands and feet. It allows visualisation of bone erosions--typical of the disease. However, bone erosions occur during the later stages of the rheumatoid arthritis and are preceded by synovitis. The aims of the study were to use ultrasound (US) and magnetic resonance imaging (MRI) in examining joints in patients suffering from chronic arthritis, and also to assess the value of these methods in diagnostics. In 61 patients with chronic arthritis (39 with rheumatoid arthritis--RA, and 22 with another etiology arthritis), plain radiography, US and MRI of the hands was performed. MRI and US were more sensitivity in visualisation of bone erosions than plain radiography. Both methods showed synovitis in all patients with RA. In detecting bone erosions in the hand joints MRI and US are more sensitive methods than plain radiography. Both methods detect synovitis and tenosynovitis. Inflammatory changes shown using the MRI and US are more intensive in RA than in patients suffering from another etiology arthritis.

[Bone mineral density in patients with irreversible renal failure treated with peritoneal dialysis]. / Gestosc mineralna kosci u chorych z nieodwracalna niewydolnoscia nerek leczonych dializa otrzewnowa.

Frequency of osteoporosis in patients on dialysis varies in different studies depending of method and measured region of bone mineral density (BMD). The aim of the study was to evaluate the frequency of disturbances of BMD in patients on peritoneal dialysis (PD). We studied 100 patients: 56 on PD and 44 on HD. (49F, 51 M.age mean 54 +/- 29) on dialysis for 6 to 104 months. BMD was measured using dual energy X-ray densitometry (DEXA) in L1-L4 segment of the vertebral column, femoral neck and forearm. The results of the BMD were presented as T-score in the standard deviation of the mean peak bone mass according to WHO criteria. Depending on the region of interest (ROI), osteoporosis was diagnosed in 20% to 70% of women and in 4% to 35% of men. In females the lowest values of BMD were found in forearm (T-score = -3.16 SD), in males it was femoral neck (T-score = -2.87 SD). In these ROI's the lowest values of BMD in both genders were found in patients with the level of iPTH higher than 300 pg/ml. We did not find any significant difference in BMD between patients on PD and HD. Values of bone mineral density were not related to the duration of dialysotherapy and cause of irreversible renal failure. On the results of our study it has been concluded that, enhancement of disturbances of BMD in patients on PD is related to the region of interest, gender of the patient and functional status of parathyroid glands.

[Incidence of osteoporosis in patients with rheumatoid arthritis]. / Czestosc wystepowania osteoporozy u chorych na reumatoidalne zapalenie stawów (RZS).

Juxta-articular osteoporosis in rheumatoid arthritis (RA) is an early and specific pathology in this disease, however in RA patients there are also factors predisposing for the development of the generalised bone atrophy. 103 female patients with the diagnosis of RA established according to ACR criteria were included in the study. Its aim was to evaluate the generalised osteoporosis incidence in women suffering from RA as well as to find out how osteoporosis was related to certain clinical symptoms and laboratory findings, the disease process activity, and the treatment used. The mean age of the patients was 57.6 +/- 12 years, and the disease duration was 11.4 +/- 9 years. The bone mineral density (BMD) was measured by DEXA method with a LUNAR device and included: the radial bone in its 1/3 of the shaft's distal part; L1-L4 vertebral region; and the proximal part of the femoral bone. The division into subgroups was done basing on the 1994 WHO criteria. In RA female patients generalised osteoporosis was observed more frequently than in the control group. The study discovered a negative, statistically significant, correlation between BMD values and: the disease duration, the time of joint involvement acc. to Steinbrocker, the degree of functional impairment, the presence of extra-articular lesions, periods of immobilisation. There was also a dependence found upon the presence of positive Waaler-Rose reaction, and upon the therapy with Methotrexate and D-penicillamine, and when the patients were treated with glicocorticosteroids--upon the cumulative dose.

[Bone mineral density in dialysis patients: the optimal region of interest depending on parathormone levels]. / Gestosc mineralna kosci u chorych dializowanych: wybór optymalnego miejsca pomiaru w zaleznosci od poziomu parathormonu.

Frequency of osteoporosis in patients on dialysis with respect to the optimal Region of Interest (ROI) has not been established. Frequency of this complication varies in different studies, especially because of no agreement according to the optimal ROI. We studied 71 patients: 32 on CAPD and 39 on HD (31F, 40m. age mean 56 +/- 29) on dialysis for 3 to 81 months. BMD was measured using dual energy X-ray densitometry (DXA) in L1-L4 segment of the vertebral column, femoral neck and forearm. The results of the BMD were presented as T-score in the standard deviation of the mean peak bone mass according to WHO criteria. Males and females were evaluated separately. Depending on the ROI, osteoporosis was diagnosed in 20 to 68% of women and in 2 to 40% of men. In females the most sensitive region of interest appeared to be forearm, in males it was proximal part of the femur. In these ROI's the lowest values of bone mineral density in both genders were found in patients with the level of iPTH higher than 200 pg/ml. We did not find any significant difference in BMD between patients on CAPD and HD. Values of bone mineral density were not related to the duration of dialysis therapy. On the results of our study it has been concluded, that optimal region of interest for BMD evaluation in dialysed patients depends on gender of the patient and functional status of parathyroid glands but is not related to either the method or duration of dialysis therapy.

MRI evaluation of pathological changes taking place in the hand in patients with rheumatoid arthritis.

The aim of this study was to use magnetic resonance imaging (MRI) to evaluate the pathological changes taking place in the hands of patients with rheumatoid arthritis (RA), and to attempt to characterize early and persistent changes. 42 patients were examined, including 31 women and 11 men in age from 23 to 75, the duration of illness ranged from 1 month to 27 years (average 7.1 years). The MRI examination was performed using a 1,5 T Magnetom 63 SP whole body system. The SE sequence was used in T1-weighted (TR600, TE15) and fat-suppressed images (A-250, TR1155, TE22), obtained with 3 mm scans, matrix 256 x 512. A knee coil was used. In 30 patients erosion was detected on the joint surfaces of the bones, including 7 patients whose erosion was not visible in plain ordinary x-ray photos. In 31 patients bone marrow edema was detectable, including 6 patients in whom advanced pathological changes were absent. In all patients signs were discovered of thickening of the synovial membrane with (30 of 42) or without (12 of 42) the presence of pannus. Periarticular effusion was observed in all patients, and in 6 patients it occurred together with bone marrow edema. Tendonitis was visible in 25 patients who were in an advanced stage of the disease. For 7 patients, the MR examinations prompted an upgrading of the diagnosed phase of rheumatoid arthritis to a more advanced stage, due to the detection of erosion. In patients with a less advanced stage of the disease, MR examination revealed 11 more joints with pathological changes (periarticular effusion) than were detected by ordinary physical examination. Magnetic Resonance Imaging seems to be the examination of choice in patients with rheumatoid arthritis at an unclear or early stage.

[Echocardiographic evaluation of cardiac structures in patients with rheumatoid arthritis]. / Ocena echokardiograficzna struktur serca u chorych na reumatoidalne zapalenie stawów.

Since heart lesions were found at autopsy in 55-60% of rheumatoid arthritis patients, we decided to assess echocardiographically their clinical significance. The study comprised 100 consecutive patients with rheumatoid arthritis (77 females and 23 males) of the mean age 55.7 +/- 12.5 yrs (range 18-83 yrs) and the disease duration of 8.3 +/- 8.0 yrs (range 1-35 yrs). The control group consisted of 100 consecutive age and sex matched patients admitted to university hospital. All the patients underwent echocardiographic examinations in apical and parasternal projections. The activity of the rheumatoid process, the severity of articular lesions, the presence of extraarticular sings as well as HLA DR and DQ antigens were determined clinically and with laboratory tests. Twenty six patients with rheumatoid arthritis had pericardial effusion, 10 revealed the sings of chronic pericarditis, in the control group 4 and 0 respectively (p = 0.001 and p = 0.025). No difference was shown in the wall contractions disturbances, size of the cardiac cavity, or thicknesses of the interventricular septum or posterior wall. In 3 rheumatoid arthritis patients, a valvular heart disease was diagnosed, this number was not significantly different from that in the control group (2 patients). There was no correlation between the lesions observed in the heart and the rheumatoid process activity estimated with clinical and laboratory indices.

24-h ECG monitoring in patients with rheumatoid arthritis.

Although the main cardiac complication in patients with rheumatoid arthritis is subclinical pericarditis, mononuclear cell infiltrations into myocardium may cause cardiac arrhythmias and conduction defects. In order to examine these problems we evaluated 70 patients (53 women and 17 men) aged 18-83 years (average 56.7 +/- 11.2) with classic or definite rheumatoid arthritis, according to diagnostic criteria. Duration of the disease was 1-35 years (average 8.7 +/- 8.4). The control group comprised 70 patients admitted to hospital with degenerative joint disease, a duodenal ulcer, or who required treatment for ophthalmological or laryngeal reasons; these patients were matched for sex and age. In all patients standard 12-lead ECG investigations were performed, as well as 24-h ECG monitoring, using an Oxford Medical System device with two precordial leads CM5 and CS2, according to the Holter method. We analysed heart rate, conduction disturbances, and occurrence of arrhythmias, on the basis of generally assumed ECG criteria. Cardiac arrhythmias were found in 50% of patients with rheumatoid arthritis, and their occurrence was similar to that in the control group. Observed arrhythmias were independent of the progression of arthritis, the type of treatment administered, the familial occurrence of arthritis, the presence of manifestations pertaining to organs, the presence of rheumatoid factor, the stage of the disease according to Steinbrocker, or the presence of immune complexes in serum and HLA Dr antigens, which are regarded as fundamental in the pathogenesis of rheumatoid arthritis.

[A case of primary pulmonary hypertension in a patient with Raynaud's disease]. / Przypadek pierwotnego nadcisnienia plucnego u osoby z choroba Raynauda.

A case of a 50-year female patient with Raynaud's disease is presented. The primary pulmonary hypertension accompanying the underlying condition suggests that the excessive contractibility of the vessels, typical for the Raynaud's disease, may play a role in the etiology of the primary pulmonary hypertension.