Alexandros Garyfallos

Clinical expression and morbidity of systemic lupus erythematosus during a post-diagnostic 5-year follow-up: a male:female comparison

The aim of this study was to analyse the prevalence of the most relevant clinical features of the diagnosis of systemic lupus erythematosus (SLE) in a sample of male patients with lupus as well as the incidence of the main causes of morbidity in a 5-year period after the diagnosis. A further aim of this study was to investigate the impact of gender on expression and morbidity of SLE. Data were collected from the medical records of 59 male and 535 female patients with SLE who were diagnosed at the hospitals in the region of Thessaloniki. Several differences in the expression and morbidity of the disease were found in relation to the gender of the patient. Male patients had a higher prevalence of thromboses, nephropathy, strokes, gastrointestinal tract symptoms and antiphospholipid syndrome when compared with female patients, but tended to present less often with arthralgia, hair loss, Raynaud’s phenomenon and photosensitivity as the initial clinical manifestations. During the 5-year follow-up, positive associations have been found between male gender and the incidence of tendonitis, myositis, nephropathy and infections, particularly of the respiratory tract. In conclusion, this study has provided information regarding the features of clinical expression and morbidity in male patients, and has shown that gender is a possible factor that can influence the clinical expression of SLE.

Evaluation of the Renal Mechanisms for Urate Homeostasis in Uremic Patients by Probenecid and Pyrazinamide Test

The tubular transport of urate was studied in 47 uremic patients and in 20 normal subjects using probenecid and pyrazinamide tests. There was a marked increase in urate excretion per nephron as the renal function deteriorated. Presecretory reabsorption of urate per nephron, which was almost complete in normal subjects, showed a diminution with increasing severity of chronic renal failure. Until the creatinine clearance had decreased to less than 10 ml/min, the secreted urate per nephron remained almost constant, while in the end stage of renal failure it was markedly decreased. With the progression of renal disease, the postsecretory reabsorption of urate per nephron diminished. In patients with a creatinine clearance less than 10 ml/min, it was 4 times lower than in normal subjects. These findings indicate that urate secretion does not contribute to the increase of urate excretion per nephron at any level of renal failure, whereas the impairment of both reabsorptive components accounts for the augmented urate excretion per nephron in uremic patients.

Left atrial volume and N-terminal pro-B type natriuretic peptide are associated with elevated pulmonary artery pressure in patients with systemic sclerosis.

Early detection of pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) is essential as it leads to substantial morbidity and mortality irrespective of its etiology. The aim of our study was to determine whether noninvasive biochemical and/or echocardiographic indices can predict the presence of PH in these patients. We prospectively studied 66 patients (mean age of 57.7u2009±u200912.1xa0years, 63 women) with SSc without clinical manifestations of heart failure. All patients underwent standard and tissue Doppler echocardiography. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) levels were also measured. In 24 (36%) patients, the diagnosis of PH was established by echocardiography (systolic pulmonary artery pressure value ≥40xa0mmHg). Left atrial (LA) volume, NT-proBNP, ADMA, ratio of early transmitral filling velocity to early diastolic velocity of the mitral annulus (mitral E/Em), and right ventricular myocardial performance index (MPI) were univariate predictors of PH. In multivariate analysis, NT-proBNP, LA volume, and right ventricular MPI were independent predictors of PH in SSc patients. LA volume and NT-proBNP may be useful noninvasive markers for the prediction of elevated pulmonary artery pressure in patients with SSc. These parameters should be considered when assessing this population for risk stratification and for identification of patients demanding further investigation and institution of specific therapy for the disease at the time when it is most likely to be effective.

Micro- and macrovascular treatment targets in scleroderma heart disease

Cardiac involvement in systemic sclerosis (SSc) is a frequent visceral complication that considerably affects the prognosis of the disease. The pathophysiologic hallmark is myocardial fibrosis which can progress leading to arrhythmia, right and/or left heart dysfunction and failure. Symptoms range from unusual to prominent and from mild to dramatic, but clinically overt disease is a poor prognostic factor. Primary myocardial involvement is related to focal ischemia due to transient coronary spasm, and the available data support that microvascular functional and structural abnormalities rather than macrovascular coronary involvement represent the main underlying mechanism of the disease. However, the existence and prevalence of atherosclerotic coronary artery disease in SSc remain to be determined, as several studies have generated conflicting reports. Despite the lack of effective targeted therapy for SSc itself, sensitive and quantitative techniques have demonstrated the ability of vasodilators to improve myocardial function and perfusion and to prevent the evolution of subclinical heart involvement to decompensated heart failure. Further research will provide a better understanding of the disease by detecting the potent contribution of coronary artery involvement, explaining differences in accelerated atherosclerosis between SSc and other autoimmune disorders, and opening directions for the development of novel treatment strategies for this life-threatening complication of SSc.

Investigation of juvenile idiopathic arthritis susceptibility loci: results from a Greek population.

The strategy of studying the putative role of RA susceptibility genetic factors in the development of juvenile idiopathic arthritis (JIA), an autoimmune disease characterized by persistent chronic arthritis, has been proven highly successful so far. Moreover, accumulated evidence indicates that an ethnic heterogeneity of genetic factors exists for rheumatic disorders. We investigated whether five single nucleotide polymorphisms (SNPs), previously found to be associated with JIA in various populations so far, are also associated with JIA in Greece. The sample set consisted of 128 Caucasian JIA patients and 221 healthy controls from Northern Greece. Five Single Nucleotide Polymorphisms (SNPs) markers, namely TRAF1/C5 rs10818488, PTPN22 rs2476601, STAT4 rs7574865, CD247 rs1773560 and PTPN2 rs7234029 SNPs were genotyped in a case-control study with Restriction Fragment Length Polymorphisms (RFLPs) or Taqman primer-probe sets. This study demonstrated for the first time in a Greek population that the PTPN22, TRAF1/C5 and CD247 polymorphisms examined are associated with an increased susceptibility to JIA, thus suggesting that the respective risk alleles may confer susceptibility to clinically distinct disorders. However, our results did not demonstrate any association of STAT4 and PTPN2 SNPs with the disease in our population, thus highlighting the importance of comparative studies in different ethnic populations.

Predictors of physicians' attitudes toward sharing information with patients and addressing psychosocial needs: a cross-sectional study in Greece.

Sharing information with patients and addressing their psychosocial needs are recognized as fundamental practices of patient-centered physicians. Our study explored predictors of physicians patient-centered attitudes and yielded a better understanding of the relative influences of job satisfaction, employment status, specialty, previous communication skills training, and sociodemographic factors. Physicians who participated in 13 identical workshops offered throughout Greece were invited to complete a battery of anonymous questionnaires (demographics, job satisfaction scale, Patient–Practitioner Orientation Scale-Sharing subscale, and Physician Belief Scale). Prediction models were used to identify predictors of patient-centered attitudes. In total, 400 fully completed questionnaires were returned (response rate 79.8%). Job satisfaction, previous training in communication skills, younger age and lower socioeconomic status were predictors of positive attitudes toward sharing information with patients. Job satisfaction, previous training in communication skills, and stronger religious beliefs were predictors of higher psychosocial orientation. Job satisfaction and training in communication skills should be ensured in the effort to develop and maintain patient-centered attitudes in physicians. Religious beliefs, age, and socioeconomic status should be taken into consideration in the effort to help physicians become aware of their biases.

Longterm Beneficial Effect of Canakinumab in Colchicine-resistant Familial Mediterranean Fever

Objective. To assess the efficacy and safety of the interleukin-1β (IL-1β) inhibitor canakinumab in all adolescent and adult patients with familial Mediterranean fever (FMF) identified from the Greek National Registry for off-label drug use between 2010 and 2015. Methods. In this retrospective longitudinal outcome study, clinical and laboratory data were collected from 14 patients (7 men) aged median 38.5 years (range 13–70), with median disease duration of 14 years, and active FMF despite colchicine (n = 9) or both colchicine and anakinra (n = 5). Results. All patients continued to receive canakinumab at last visit (median of 18 mos, range 13–53), which was initially given as monotherapy (n = 8) or in combination with colchicine and/or corticosteroids, every 4 (n = 7), 6 (n = 2), or 8 weeks (n = 5). Eleven patients (79%), including 6 receiving monotherapy, achieved complete clinical remission within 2 months (median), while normalization of all laboratory variables denoting inflammation occurred in 92% at 3 months (median). The remaining 3 patients achieved partial responses. Responses were sustained in all but 4 patients, who relapsed. Reducing the canakinumab administration interval from 8 or 6 weeks to 4 weeks led to suppression of disease activity in the relapsing patients. On the other hand, drug administration interval could be safely increased in 2 patients in remission. Corticosteroid doses were significantly reduced during followup. Canakinumab was well tolerated; 1 patient experienced a urinary tract infection and another one a viral gastroenteritis. Conclusion. Treatment with canakinumab in an individualized dosing scheme results in rapid and sustained remission in colchicine-resistant FMF.

Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population.

BackgroundJuvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by persistent chronic arthritis. Disease risk is believed to be influenced by both genetic and environmental factors. It is well established that the PTPN22 single nucleotide polymorphism (SNP) rs2476601 is associated with JIA susceptibility. It was recently reported in an Australian study that this association is restricted to females and is not observed in males. A significant source of inconsistency amongst the literature on autoimmune disease susceptibility genes stems from an inability to replicate genetic findings across different racial or ethnic groups. We therefore attempted to generate further evidence of the female-specific association of rs2476601 in a homogeneous Greek population.FindingsWe genotyped rs2476601 in 128 Caucasian JIA patients (70.3xa0% female) and 221 healthy controls (28.1xa0% female) from Northern Greece. Overall, PTPN22 was associated with increased risk of JIA in this Greek sample (ORu2009=u20092.3, 95xa0% CI 1.1 – 5.1, pu2009=u20090.038). Sex-stratified analyses showed that, once again, the risk association was restricted to females (Female: ORu2009=u200919.9, 95xa0% CI 1.2 – 342, pu2009=u20090.0016; Male: ORu2009=u20091.1, 95xa0% CI 0.3 – 3.1, pu2009=u20090.94) supporting the prior findings.ConclusionsOur data demonstrates that this sex-specific pattern of association is broadly applicable to different populations, and provides further impetus to undertake mechanistic studies to understand the impact of sex on PTPN22 in JIA.

Prevalence and clinical manifestations of ankylosing spondylitis in young Greek males.

Increased awareness and sensitivity of general physicians have increased the early diagnoses of seronegative arthritis in young patients, while new agents such as anti-TNF blockers have significantly changed the treatment of the disease. To investigate the prevalence, the clinical manifestations, and the ability for military service of young Greek males (18–30xa0years old) with ankylosing spondylitis (AS) in the pre-anti-TNF era. We retrospectively studied the AS cases recorded from 1989 to 1995 of the rheumatology department of the largest General Military Hospital in Greece; the diagnosis was based on the modified New York criteria for AS. A total of 285 AS cases were diagnosed among 357,184 young men. The overall prevalence of AS on December 1995 was estimated at 8.2 cases per 10,000 young men (95xa0% C.I. 7.2–9.2). All the patients had chronic back pain. Two hundred forty (84xa0%, 95xa0% C.I. 79–88xa0%) patients presented sacroiliitis of whom 163 (68xa0%, 95xa0% C.I. 62–73xa0%) were bilateral. Two hundred five patients (72xa0%, 95xa0% C.I. 66–77xa0%) had peripheral joint involvement. Thirty-one patients presented with anterior uveitis (11xa0%, 95xa0% C.I. 8–15xa0%). One patient had IgA nephropathy. None had gut involvement. HLA-B27 antigen was found in 257 patients (90xa0%, 95xa0% C.I. 86–93xa0%). Ninety-one patients (32xa0%, 95xa0% C.I. 27–38xa0%) had permanent discharge from the military service, while 128 (45xa0%, 95xa0% C.I. 39–51xa0%) were able for auxiliaries attendances. The prevalence of AS for the age group 18–30xa0years old in this young Greek men cohort was significantly lower than in other Caucasian European populations, and the clinical manifestations were considered as mild.

B-type natriuretic peptide in rheumatic diseases: a cardiac biomarker or a sophisticated acute phase reactant?

Natriuretic peptides (NP) are secreted by cardiomyocytes and are reliable markers of cardiac dysfunction and cardiovascular risk by reflecting myocardial stress due to various etiologies. Clinical and occult heart involvement is frequently observed in patients with rheumatic diseases and is associated with increased morbidity and mortality. Cardiac disease in autoimmune disorders encompasses different pathophysiological mechanisms including inflammation and involving either the myocardium or the coronary/pulmonary vessels. Although the major trigger for the synthesis and release of NP is myocardial strain, there is also some support for the concept that inflammation stimulates the neurohormonal system of the heart leading to increased production of NP. Recent studies have focused on the association of NP and inflammation in the context of rheumatic diseases, suggesting that up-regulation of neurohormonal axis in these conditions is linked with inflammation. Additionally the NP have a well-documented role in the diagnostic work-up of patients with connective tissue disease who are at increased risk of developing pulmonary hypertension, as the right ventricular overload results in increased NP synthesis and release. However the precise role of NP in the assessment and the management of cardiovascular risk in patients with rheumatic diseases is yet to be established. In the current article we discuss the pathophysiologic mechanisms involved in enhanced NP expression in patients with rheumatic disorders and their potential clinical implication in daily practice.