Marica Pavkovic, Slobodanka Trpkovska-Terzieva, Tatjana Sotirova, Lidija Cevreska and Aleksandar Stojanovic
Immune thrombocytopenia (ITP) is an autoimmune disease of unknown etiology, characterized by isolated thrombocytopenia and the absence of any underlying cause for thrombocytopenia. Corticosteroids are the standard first line treatment for patients with symptomatic disease, inducing platelet count recovery in 70-80% of patients; but in many cases, steroid tapering or withdrawal is followed by a decrease of platelet count and the need for additional treatment. Splenectomy is still the standard salvage therapy in cases refractory to corticosteroid therapy. In the past decade monoclonal anti-CD20 antibodies (Rituximab) are being increasingly used in patients with refractory ITP and other autoimmune diseases. Recent studies show that Rituximab is useful in the treatment of patients with chronic and refractory ITP. We report two cases with chronic ITP treated with standard dose of Rituximab in four weekly doses and than continue to receive maintenance therapy with Rituximab for 2 years.
Irena Kafeđiska, Dejan Spasovski, Todor Gruev, Mane Grličkov, Kočo Cakalaroski, Vlado Serafimovski, Tatjana Sotirova and Petar Miloševski
Association Between Osteoarticular Scores and Acute Phase Reactant Levels in Rheumatoid Arthritis
The aim of this prospective control study was a quantitative evaluation of the activity of rheumatoid arthritis (RA) in certain time intervals, using articular indexes (set of 28 sensitive and 28 swollen joints), laboratory parameters (Hb, Hct, Er, Le and Plt) and acute phase reactants (ESR, RF, CRP); to determine which of the acute phase reactants is the most useful biochemical marker for the evaluation of disease activity in RA; to quantify the therapeutical and laboratory differences in certain time intervals in the group with and without immunomodulatory therapy with Methotrexate. Sixty patients with RA were included, 27 of who were treated with non-steroid antiinflammatory drugs (NSAIDs) and Methotrexate (MTX). The control group consisted of 33 patients treated only with NSAIDs because of irregular controls. In the first group of patients the disease activity was estimated at four time intervals, and in the control group of patients at three time intervals following the scores of the articular indexes, blood cell counts, ESR and CRP in every patient. In the first group of patients decreased activity of RA was found upon every following control with a consecutive decrease in mean values of the scores of articular indexes with statistically significant differences at the four time intervals. Considering laboratory parameters, there were statistically significant differences in the mean values of Hb, Er, Plt, ESR, (p=0.0462, p=0.0076, p= 0.0058, p= 0.0003). Mean values of CRP did not show statistically significant differences, but the number of patients who were CRP negative increased (there were great standard deviations). In the group of patients treated only with NSAIDs, there were statistically significant differences in the mean values of the scores of articular indexes with an increse at every following control (in favour of progression of the disease). There were no statistically significant differences considering blood cell counts, ESR and CRP (in favour of permanently active disease). In conclusion, CRP is the most useful marker for the prospective follow-up of patients with RA.
Irena Kafeđiska, Dejan Spasovski, Todor Gruev, Nada Marina, Mane Grličkov, Jordan Čalovski, Tatjana Sotirova, Oliver Karanfilski and Stefka Bogdanovska
Association Between Sharp's Radiographic Index and Acute Phase Reactants in Rheumatoid Arthritis
The aim of this study was to evaluate the activity of rheumatoid arthritis (RA) by hand radiography (Sharp's radiographic index), and assessment of acute phase reactants - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF), and to determine their value as prognostic markers for disease outcome in patients with early RA treated with disease modifying antirheumatic drugs (DMARDs)-Methotrexate (MTH); to register and quantify clinical, radiographic and laboratorial differences in certain time intervals in a group of patients treated with immunomodulation therapy with MTH; to determine which of the acute phase reactants would be the most useful marker for evaluation of disease activity in long-term follow-up in RA patients; to select high-risk groups with aggressive course of disease, in order to emphasize the necessity of early and aggressive treatment. Thirty patients with early RA (disease evolution up to 1 year) were evaluated in several time intervals. The score of the Sharp's index showed greater radiographic progression of the joint damage of hands in time intervals between 0-time and 12 months (p=0.0167) and between 0-time and 18 months (p=0.0089). Statistical analysis showed differences in values of CRP in four time intervals (p=0.00002). Considering CRP, there were statistically significant differences among mean values in four time intervals (p=0.0428) (standard deviations showed greater variations). There were no statistically significant differences among mean values of RF in four time intervals (p=0.573). At 0-time in 3 (10%) patients progression of the Sharp's index was found, after 6 months in 13 (39%) patients, while after 12 and 18 months progression of the Sharp's index was found in an identical number of patients, 15 (50%). In most patients high values of CRP and RF were found. Progression of the radiographic damage is especially expressed in patients with high values of ESR, CRP, RF and existence of previous erosions of hands, which are predictors for aggressive course of disease. CRP is the most useful marker for the evaluation of RA activity in the long-term followup of RA patients.
Marica Pavkovic, Rosica Angelovic, Marija Popova-Simjanovska, Oliver Karanfilski, Slobodanka Trpkovska-Terzieva, Tatjana Sotirova, Lidija Cevreska and Aleksandar Stojanovic
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia due to platelet autoantibodies, causing an accelerated clearance of opsonized platelets by phagocytes. The etiology of ITP remains unclear, both genetic and environmental factors may have a role in the disease development. The aim of our study was to investigate a possible association of three single nucleotide polymorphisms (SNP) in the genes for interleukin beta (IL1B-511C/T), tumor necrosis factor beta (TNF+252G/A) and tumor necrosis factor alpha (TNFA-308G/A) with ITP. We have analyzed 125 adult patients with ITP and 120 healthy matched controls. Genotyping was performed by using PCR- RFLP methods.
Our results demonstrated significantly different genotype distributions and allele frequencies for TNFB+252G/A in patients with ITP, p = 0.005 and p = 0.009 with Yates correction. We did not find any significant differences in the genotype distribution or allele frequencies for the other two genes. We have found significantly different genotype distribution and allele frequencies for TNFA- 308G/A between patients with unresponsive and responsive ITP patients, p = 0.016 and p = 0.009. There were no significant differences in genotype distribution and allele frequencies for ILB-511C/T and TNFB+252G/A polymorphisms between those two groups of patients. We did not find any significant differences in genotype distribution and allele frequencies for all three polymorphisms between splenectomized and unsplenectomized ITP patients.
The obtained data indicate that the A allele of TNFB+252G/A is more frequent in these patients than in the controls and that this polymorphism may play a significant role in disease susceptibility. The A allele of TNFA-308G/A was more frequent in patients with unresponsive ITP, indicating that this gene polymorphisms may contribute to therapy resistance.
Dejan Spasovski, Todor Gruev, Nada Marina, Jordan Calovski, Snežana Percinkova, Baskim Osmani, Ljubinka Rajčevska, Kočo Cakalaroski, Tatjana Sotirova, Svetlana Balkanov and Maja Slaninka-Micevska
The Diagnostic Value of N-Acetyl-β-D-Glucosaminidase and Microalbumin Concentrations in Rheumatoid Arthritis
The purpose of this research was to compare the diagnostic values of laboratory variables, to present quantitative evaluations of the diagnostic sifted test with reference to sensitivity and specificity, the predictive value of the positive and negative test and precision of the test for N-acetyl-β-D-glucosa-minidase (NAG), microalbumin, rheumatoid factor (RF), Creactive protein (CRP), DAS 28 index, in early diagnosis of untreated rheumatoid arthritis (RA), and to define the effect of untreated rheumatoid arthritis on glomerular and tubular function. Using a colorimetric assay for the determination of Nacetyl-β-D-glucosaminidase and an immunoturbidimetric assay for the determination of urinary albumin, the samples of serum and urine have been examined in 70 participants (35 RA who were not treated, 35 healthy controls). RF was defined with the test for agglutination (Latex RF test) in the same participants. Out of 35 examined patients with RA, in 13 we found the presence of NAG enzymuria (sensitivity of the test 37.14%), while microalbuminuria appeared in 4 patients (sensitivity of the test 11.42%). RF appeared in 17 patients (sensitivity of the test 48.57%). Four patients were NAG and RF positive, while 3 patients were microalbuminuria and RF positive. Among 18 RF negative patients, 9 patients were NAG positive, and 1 patient presented with microalbuminuria. Among 17 RF positive RA, the presence of NAG was found in 4 patients, and the presence of microalbuminuria in 3 patients. Among 18 RF negative RA, NAG enzymuria appeared in 9 patients. Microalbuminuria was present in 1 patient. In the healthy control group, 8 patients were NAG positive, 2 patients were positive for microalbuminuria. RF appeared in 2 patients. NAG has higher sensitivity than microalbuminuria in the detection of asymptomatic renal lesions in untreated RA.