Self-reported disease severity in women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), pathology with net feminine predominance, is one of the most complex autoimmune diseases and has major impact on patients' life. The aim is to identify patient and disease-related factors associated with self-perceived disease severity in female SLE patients. This cross-sectional study enrolled 73 women fulfilling the 2012 Systemic Lupus International Collaborating Clinic (SLICC) criteria. SLE disease activity was assessed by the Systemic Lupus Activity Measure (SLAM) score and overall damage by the SLICC/American College of Rheumatology (ACR) index. Patients' general characteristics, associated conditions as well as SLE specific clinical involvements and therapeutic principles were also noted. Fatigue was assessed by FACIT-fatigue scale. Self-perceived disease severity was assessed using numerical rating scales (1-10 NRSs), to evaluate the disease severity at inclusion (1-10 NRS now) and worst severity anytime during disease history (1-10 NRS worst ever). In regard to worst ever lupus severity, 54.8% of patients responded with 9 or 10, while none with 1 or 2 even if only 22.9% of the patients responded with 7 or more for disease severity at inclusion (1-10 NRS now). Women with higher 1-10 NRS now answers had also higher 1-10 NRS worst ever, SLAM, SLICC, and FACIT-fatigue scores. They associated more frequently anxiety/depression diagnosis, antiphospholipid syndrome, joint involvement as well as treatments with corticosteroids. Self-reported disease severity worst ever, anxiety/depression diagnosis, fatigue, and the daily dose of corticosteroids were independently associated with patients' perception on lupus severity at inclusion: OR (95% CI), 2.13 (1.15-3.94) p = 0.017, 6.67 (1.11-39.97) p = 0.038, 1.10 (1.02-1.19) p = 0.018, and 1.11 (1.02-1.21) p = 0.020, respectively. The vast majority of patients identified severe and very severe events during their disease history, results that raise awareness of burden concerning lupus occurrence in women's life. Self-perceived lupus severity is multifactorial, influenced also by factors less considered in the SLE management like fatigue and the depression/anxiety disorders, but also by the previous patient's experience.

Is there still a place for erythrocyte sedimentation rate and C-reactive protein in systemic lupus erythematosus?

The inflammatory response during systemic lupus erythematosus (SLE) flares is known to be atypical, characterized by a disproportionately lower C-reactive protein (CRP) elevation when compared with erythrocyte sedimentation rate (ESR). Thus, in these patients, the analysis of inflammatory markers might be challenging in daily clinical practice. Clinicians need frequently to distinguish lupus reactivations and infectious conditions, and the significance of ESR and CRP seems to be different. Even though a non-specific marker of inflammation, ESR utility in SLE should not be neglected and it appears to be a useful biomarker for SLE activity assessment. Describing a specific cut-off for ESR in SLE is important for patients' follow-up, and levels up to 25-30 mm/h have been proposed as an upper limit of the normal range. Regarding CRP, even though higher baseline levels are described in SLE when compared with controls, including in remission periods, its response during flares seems to be incomplete and not always correlated with disease activity; while CRP values greater than 10 mg/l could be indicative for severe flares, when there is no serositis or arthritis, higher CRP levels above 50-60 mg/l may be associated with infection.

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients.

BACKGROUND: The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. AIM: To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. METHODS: 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE's criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS's criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive "criteria" APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-P2 glycoprotein I antibodies (aß2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aß2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/ without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aß2 GPI (IgG and IgM ) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the "non-criteria" APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. CONCLUSIONS: IgG aß2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the "non-criteria" APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the "non-criteria" APLAs with the antiDNA and complement C3 levels were also observed.

A rare case of digestive hemorrhage in an elderly patient: diagnosis and treatment difficulties.

Abdominal pain represents one of the most common clinical conditions. However, there are some challenging cases in which an extensive work-up is mandatory for the diagnosis. We present the case report of a 65-year-old man admitted to our department for diffuse abdominal pain, nausea, vomiting, diarrhea, painful joints and rectal tenesmus. He initially had an urticarial rash, followed by palpable purpura involving the lower extremities. The diarrheic stools evolved towards melena. Endoscopic examination of the upper gastrointestinal tract showed hiatal hernia, superficial erosions in the stomach and multiple areas of deep and superficial ulcerations disseminated from the second to the third portion of the duodenum. Terminal ileum intubation at colonoscopy showed redness, edema, swelling, petechiae and ecchymosis, irregular erosions and ulcers. Endoscopic biopsy specimens showed non-specific inflammation. Computed tomography showed moderate ascites, small pleural effusion, mesenteric lymphadenopathy and small bowel wall thickening at the level of the second duodenum, proximal jejunum and segments of ileum. The urine analysis revealed microscopic hematuria with nephrotic range proteinuria, red cells and cellular casts. Therapy with corticosteroids and pulses of cyclophosphamide was started with significant clinical improvement. Three weeks after the first admission, the patient developed an acute peritonitis due to an intestinal perforation and acute mesenteric ischemia of the small bowel. We concluded that the patient had a Henoch-Schönlein type vasculitis with acute mesenteric ischemia and perforation of the small bowel.

Diffuse polypoid lesions of the digestive tract in severe hypogammaglobulinemia.

We present a case report of diffuse polypoid lesions of the digestive tract in which multiple endoscopic techniques (upper endoscopy, colonoscopy, and capsule endoscopy) were performed in order to complete and refine the diagnosis in a patient with severe hypogammaglobulinemia with recurrent infections, bronchiectasies and diffuse nodular lymphoid hyperplasia of the digestive tract. In patients with hypogammaglobulinemia, the endoscopic evaluation of the digestive tract might be mandatory, even in asymptomatic patients. The complete assessment should include the upper endoscopy and colonoscopy with multiple biopsies and, if possible, capsule endoscopy.

Platelet histogram indices and cardiovascular disease in patients with rheumatoid arthritis.

UNLABELLED: BACKGROUND; Previous studies reported the increased prevalence of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) compared to the general population. However, the predictors for the development of CVD in patients with RA were not clearly established, and the role of thrombosis mechanisms was inconsistently characterized in these patients. The aim of this study was to evaluate the platelet histogram indices, as markers of platelet activation, in patients with RA with or without CVD. MATERIAL AND METHODS: In 64 pts with RA (mean age: 58.0 +/- 12.7 yrs) we performed the standard clinical evaluation and biochemical workup with platelet histogram, including mean platelet volume (MPV) and platelet distribution width (PDW) as markers of platelet activation. We divided the study population into two groups: A - 41 patients with RA without CVD and B - 23 patients with RA and CVD (ischemic heart disease, peripheral artery disease or cerebrovascular disease). The values of MPV and PDW were also analyzed in an age- and sex-mached control group of 20 subjects without RA and CVD and in a group of 62 patients with CVD without RA (stable angina). RESULTS: The platelets number was similar in both groups, but the platelet histogram showed higher values for MPV (9.6 vs. 8.6 fL, p < 0.01) and PDW (16.1 vs. 14.0, p < 0.01) in patients with RA and CVD, reflecting greater platelet activation in these patients. MPV values were lower in patients with RA, but the values of PDW were higher in these patients comparing to control. Patients with RA with CVD have higher values of PDW than patients with CVD, but without RA, showing an increased platelet activation in RA. The PDW values correlate with fibrinogen (0.63; p = 0.003) but not with CRP or ESR, while the MPV was not correlated with the inflammatory markers in patients with RA. CONCLUSIONS: The pathogensis of CVD in patients with RA may be linked to an increased prothrombotic activity which might be evaluated by platelet histogram indices.

Evaluation at patients with ventricular arrhythmias and coronary artery disease of myocardial revascularization effects.

UNLABELLED: The aim of this study was to determine the relations between myocardial revascularization therapy--coronary artery bypass graft (CABG) and coronary angioplasty (PTCA)--and ventricular potentially malignant arrhythmia (VPMA) (coupled VPC, VPC > 10/hour, NSVT--Morganroth classification), in patients (pts) with stable CAD. METHODS: 765 patients with stable angina and ventricular potentially malignant arrhythmia were evaluated angiochoronarographically, echographically, by programmed electrical stimulation (PES), standard ECG, Holter ECG, radiologically, and by stress test. From 765 patients with CAD and VPMA 169 pts. (22.9% of cases) were revascularized, 77 pts. (10.06% of cases) by CABG surgery and 82 pts. (10.71% of cases) by PTCA with or without stenting. RESULTS: From pts. with inducible sustained ventricular tachycardia by programmed electrical stimulation PES + (129 pts. 16.86% of cases), 19 pts. (2.5% of cases) were with CABG vs 9 pts. (1.17% of cases) with PTCA (p > 0.05). In 333 pts. with arrhythmogenic myocardic ischemia detected by Holter ECG/24 hours (Holter +) the distribution of myocardial revascularization was similar (40 pts., 5.22% of cases with CABG vs 46 pts., 6.01% of cases with PTCA) (p > 0.05). The study included 225 pts. with positive stress test, 45 pts. were revascularized, 18 pts. (2.35% of cases) with CABG and 27 pts. (3.52% of cases) with PTCA (p > 0.05). Revascularized pts. represent an increased percent with prior myocardial infarction in the subgroup with CABG vs. PTCA (39% of cases, p < 0.05 vs. 25% of cases, p < 0.05). Revascularized pts. presented similar distributions of VPMA in subgroups with CABG and PTCA. CONCLUSIONS: VPMA was not influenced by myocardial revascularization, CABG or PTCA, the incidence being similar (50.94% vs 47.2%; p < 0.05) with pts. drug treated.

Endothelial dysfunction in inflammatory rheumatic diseases.

The importance of cardiovascular disease in inflammatory rheumatic diseases was recognized as one of the determinants of increased mortality in these patients. An increased cardiovascular disease was reported in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but also in other rheumatic diseases. Several hypotheses were elaborated, but the chronic inflammatory status seems to be a primordial factor. Therefore, the diagnostic and treatment of cardiovascular disease, even in subclinical status, should be one of most important goals in the global management of these patients. The endothelial dysfunction is now regarded as an important and early step in the processes that promote atherosclerosis. In patients with inflammatory rheumatic diseases, the presence of the endothelial dysfunction was reported and linked with several clinical or biological features of each disease. Moreover, the potential benefits on the endothelial dysfunction of several therapies were assessed especially in patients with RA or SLE. The aim of this article is to review the impact of the endothelial dysfunction and the methods to improve it in patients with these conditions.

Young woman with polyserositis, ovarian cystic mass and increased level of CA-125. Case report of peritoneal and pleural tuberculosis.

A 21-year-old woman was addressed to our department for progressive abdominal swelling, fatigue and fever. The clinical examination, the ultrasound examination and the computed tomography showed the presence of polyserositis (ascites and pleural effusion) and revealed a cystic mass at the level of right ovary. The laboratory work-up showed an increased level of CA-125, suggesting a malignancy. The thoracoscopy with visualization of the pleura revealed disseminated small white spots. The laparoscopic exploration of the pelvis and of the peritoneum also showed the same disseminated lesions and a cystic-like mass at the level of the right ovary which was excised and diagnosed as a benign cyst. At the analysis of the frozen and paraffin sections, the diagnostic of pleural and peritoneal tuberculosis was made and the specific quadruple treatment was started with a good evolution at two months and with the normalization of the CA-125 level. This case report underlines the importance of tuberculosis in the differential diagnosis of patients with polyserositis and increased levels of CA-125.

Polycystic hepatic disease.

Polycystic hepatic disease is a very rare hereditary disease. Most of the patients have no symptoms but sometimes they present abdominal discomfort, fever, jaundice. Almost half of the patients associate renal cysts. Rarely, the cysts may appear in other organs such as the pancreas, the spleen or the lung. We present a case of polycystic hepatic disease. In our patient the cysts replace almost the entire hepatic structure. However, the hepatic functional tests were normal.

Giant iliac artery aneurysm--a rare cause of hydronephrosis.

The presence of arterial aneurysm--an abnormal dilatation of an arterial segment due to various causes--might lead to compression effects and to various symptoms. Finding an etiology for unilateral hydronephrosis represents in some cases a real challenge for the clinician and targeted investigations must be ordered for the diagnostic approach. The abdominal ultrasound examination is one of the first imaging modalities but the abdominal computed tomography is helpful for definitive conclusions. We present a rare case of unilateral hydronephrosis due to a giant left iliac artery aneurysm in a 77-year-old male with history of peripheral artery disease.

A rare case of pulmonary emphysema.

Alpha-1-antitrypsin deficiency (AAT) is one of the three most common lethal genetic diseases in the caucasian population (together with cystic fibrosis and Down syndrome). Its primary manifestation is early-onset panacinar emphysema. Slowly progressive dyspnea is the primary symptom, although some patients initially have symptoms of cough, sputum production, or wheezing. A minority of patients develops hepatic cirrhosis. We present a case of a 40 year-old male, light smoker, with chronic obstructive lung disease with predominance of panacinar emphysema, with AAT deficiency (72 mg/dl; normal values = 200-300 mg/dl) complicated with cor pulmonale and chronic respiratory failure. The main clinical consequence of AAT deficiency is the early onset of panacinar emphysema, typically more severe at the lung bases. Smoking plays an important part in the natural history of the disease, both increasing the severity and decreasing the age at onset of emphysema.

Vibroarthrography--a possible functional non-invasive method for early detection damaged cartilage joint.

The vibroacoustic signals emitted by the diarthrodial articulation during a normal movement differentiates a healthy case from a pathologic one, due to alteration in forms and contact surfaces. The differences are shown by a various dynamics of the vibroacoustic spectra. Parametric representation of the acquired signals, filtering and clinical interpretation of those allow classification and fast recognition of a normal/pathologic status of the investigated articulation by the physician. Our method of acquiring the sound and vibration signals is effectuated completely non-invasive, with a set of translators using Pulse - sounds and vibrations analyzers (a matrix of prepolarised microphones with measurement domain in infrasound scale and piezoelectric acceleration transducers). A comparative study of vibroacoustic and thermal spectra, with early alterations revealed by knee nuclear magnetic resonance, correlates vibroacoustic and thermic spectra alterations with morphological ones, by determining certain limits between normal and pathological morphofunctional patterns. This prospective comparative study will help us evaluate the method in terms of sensibility, specificity, negative and positive predictive value, indices that assure the diagnostic power to the method.

Is interleukin-18 correlated with endothelial dysfunction and platelet activation in patients with unstable angina?

UNLABELLED: The aim of the study was to assess the interaction between interleukin-18 (IL-18, a cytokine with a central role in the inflammatory cascade) and the presence of endothelial dysfunction and prothrombotic profile in patients with unstable angina and proven coronary artery disease. MATERIAL AND METHODS: The study EDIT-ACS (Endothelial Dysfunction, Inflammation and Thrombosis in Acute Coronary Syndromes) was set in the Cardiology Department of our Institute, and inclusions were performed between June-November 2004. We included 40 consecutive patients with unstable angina hospitalized in our Department (mean age = 60.2 +/- 8.8 years, 57.5% male), as well as 20 normal pts as a control population,matched for age and sex (mean age = 61.9 +/- 8.6 years, 58.3% male). All pts had the following biological studies performed: interleukin-18 (IL-18), C-reactive protein (CRP), fibrinogen, leukocyte count, and Von Willebrand factor, as well as platelet activity parameters (mean platelet volume, MPV and platelet distribution width, PDW). All pts had echographic studies of flow mediated dilatation (FMD) and measurement of carotid intima-media thickness (C-IMT), and underwent coronary angiography as well. RESULTS: We found that patients in the highest quartile of IL-18 had higher levels of CRP (11.9 +/- 4.2 vs 6.8 +/- 3.4 mg/l, p<0.01), von Willebrand factor (166% vs 150%, p=0.08), PDW (14.5 vs 13.2, p=0.04), MPV (11.2 vs 10.2, p=0.02), as well as a higher number of coronary stenoses (mean no. of affected vessels 2.5 vs 1.1, p<0.001), trend towards higher carotid IMT (0.92 mm vs 0.81 mm, p=0.06). They also have significant endothelial dysfunction (FMD of 5 % vs 8.5% for 4th quartile and 1st quartile respectively). Pts with higher levels of IL-18 associated a worse short term (in hospital prognosis) with 60% of pts in the 4th quartile having adverse events, versus 22% in the lowest quartile. CONCLUSIONS: High levels of interkleukin-18 are associated with endothelial dysfunction (high von Willebrand factor and low brachial FMD) and platelet activation (high MPV and PDW values), in pts with a higher number of affected coronary arteries but similar global atherosclerotic burden. This could explain the association between high levels of IL-18 and worse short-term prognosis in pts with unstable angina.

Hypertension in obese patients: a dysmetabolic hypertension with a possible adipocyte dysfunction mechanism.

Large longitudinal studies showed the epidemiological link between obesity and hypertension. During last years, multiple possible mechanisms involved in this association were identified. Adipose tissue has an important role in the genesis of hypertension in obese patients through several pathways: insulin resistance, leptin, renin-angiotensin-aldosteron system and mediators of inflammation (TNF-alpha, IL-6). Adipocyte may be the major player in the development of insulin resistance and hypertension, elements of the metabolic syndrome, responsible for the cardiovascular complications.

Relationship between serum gamma-glutamyl transferase and pulse pressure in apparently healthy middle-aged subjects.

UNLABELLED: Higher values of pulse pressure (PP)--the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP)--are associated with an increased cardiovascular risk; SBP and DBP values are correlated with serum levels of gamma-glutamyl transferase (GGT), both in drinkers and non-drinkers subjects. Moreover, some studies showed that high levels of serum GGT might be related with an increased cardiovascular risk. However, few studies analyzed the relationship between GGT and PP. In 72 subjects (18 male; 54 women), middle-aged (mean age: 36.63 yrs; limits: 24-54 yrs), apparently healthy, we performed the measurements of: weight, height (from which we calculated the body mass index [BMI]), SBP, DBP, PP, standard biochemical workup, including GGT (UI/l). RESULTS: PP values are correlated with SBP (r=0.74, p<0.001), but not with DBP (r=0.15, p=NS) values. GGT is significantly correlated with SBP (r=0.28, p=0.01), DBP (r=0.29, p=0.01), and BMI (r=0.41, p<0.001). Mean values of PP are significantly higher in those with a GGT>20 than those with GGT<20 (48.69 vs. 43.85 mmHg, p<0.05); similarly, mean values of SBP (131.66 vs. 116.81 mmHg, p=0.0004) and DBP (82.59 vs. 73.52 mmHg, p=0.0008) are higher in the group with GGT>20. We observed an ascending trend of the mean value of GGT in the different groups of PP; therefore, mean value of GGT was 19.21, 22.65, 23.18 in the PP<40, PP=40-60, respectively PP>60 groups. However, the correlation between PP and GGT was not significant, both in univariate analysis (r=0.14, p=NS) and after adjusting for SBP, DBP, BMI (r=0.12, p=NS). When we analyzed subgroups, the relationship between GGT and PP was more evident in women and in subjects with increased values of BMI. CONCLUSIONS: GGT values are significantly correlated with SBP and DBP, but not with PP, in middle-aged, apparently healthy subjects; even though the highest values of GGT are associated with an increased PP value, further studies would be necessary in order to explain this link.

New insights into the pathogenesis and prognosis of aortic sclerosis.

Aortic valve disease includes a wide spectrum of conditions, from leaflets thickening to hemodynamically significant aortic stenosis and is one of the most important causes of morbidity and mortality worldwide. Studies performed during the last years bring consistent evidence that these lesions of the aortic valves share remarkable similarities with atherosclerotic lesions. They also reveal new risk factors for its development, which are superposed in fact with the major risk factors for atherosclerosis. Moreover, large prospective studies reported an increased risk for cardiovascular events and for total and cardiovascular mortality in patients with aortic sclerosis. Hence, recent papers also propose therapeutic targets, using statins for delaying the progression of the disease.

Subclinical atherosclerosis, carotid intima-media thickness and the cardiovascular risk.

The refinement and the improvement of the cardiovascular risk factors assessment became one of the high priorities in the global approach of cardiovascular diseases. Recent studies showed that increased carotid intima media thickness (IMT) is a relatively simple noninvasive marker of the global atherosclerotic disease, even in the asymptomatic stage. There is a strong link between IMT and both traditional and emerging cardiovascular risk factors, and IMT also predicts the occurrence of major cardiovascular events. Thus, IMT, as a marker of subclinical atherosclerosis, might improve the risk assessment in asymptomatic patients at risk.

Pulse pressure and inflammatory markers in apparently healthy premenopausal women.

Several epidemiological studies showed that pulse pressure (PP), as a marker of large arterial stiffness, is an independent predictor of cardiovascular risk. A high pulse pressure may induce lesions of the vessel walls and of the endothelium of the large arteries. Now, inflammation represents one of the most extensively studied pathways involved in the pathogenesis of cardiovascular disease. The aim of the present study was to evaluate if usual markers of systemic inflammation were correlated with pulse pressure. In fifty-four apparently healthy premenopausal women, without any known disease, we performed anthropometrical and blood chemistry measurements, together with the standard measurements of blood pressure. Mean values of fibrinogen are significantly more elevated in PP > 50 mmHg group than in PP < 50 mmHg group (364.79 +/- 71.07 vs. 329.31 +/- 57.81, P < 0.05). Fibrinogen was also significantly correlated with PP (r = 0.27, P < 0.05). However, after controlling for age the correlation between PP and fibrinogen was not significant (r = 0.18, P = NS). ESR was significantly correlated with PP (r = 0.31, P < 0.05) and systolic blood pressure (SBP) (r = 0.32, P < 0.05) but not with diastolic blood pressure (DBP). After controlling for age the correlation between PP and erythrocyte sedimentation rate (ESR) was not significant (r = 0.20, P = NS), but after controlling for body mass index (BMI) this correlation became significant (r = 0.28, P < 0.05). White blood cell (WBC) was not correlated with age, SBP, DBP, PP, age and BMI and the mean values of WBC were increased in the PP > 50 mmHg group, but not significantly (6637.93 +/- 1615.19 vs. 6416.67 +/- 1427.57, P = NS). In our study we found that ERS and fibrinogen values are related to pulse pressure values. Otherwise, blood pressure values, including pulse pressure, were correlated with the age of the subjects and the correlation between pulse pressure and inflammatory markers (ESR and fibrinogen) was not significant after controlling for age. After controlling for BMI, the correlation between ESR and PP remains significant.