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Objectives: Systemic sclerosis (SSc) is a rare, chronic connective tissue disease involving multiple organ systems, including the eye. We evaluated the detailed clinical ocular manifestations of outpatients with SSc.Methods: Demographics, disease duration and subtype, nailfold capillaroscopy (NFC) patterns and laboratory parameters encompassing the autoantibody profile of 51 SSc patients were evaluated, and a general ocular examination was performed for each participant.Results: Twenty-nine patients (56.86%) had eyelid skin alterations, 26 (50.98%) had retinal abnormalities, 26 (50.98%) had cataracts, 8 (15.69%) had conjunctival changes, 7 (13.73%) had iris abnormalities, 33 (64.71%) suffered from dry eye disease (DED), and 11 (21.57%) suffered from glaucoma. Significant positive correlations were found between NFC data and both tear breakup time and Ocular Surface Disease Index test values.Conclusions: Eyelid skin abnormalities, DED and retinal abnormalities are among the most common SSc-related ocular involvements. Diverse ophthalmic findings are attributed to the heterogeneity of SSc. [ABSTRACT FROM AUTHOR]

The human precorneal tear film is a special body fluid, since it is a complex mixture of proteins, lipids, small bioactive molecules, and their concentrations and relative distribution represent not only the metabolic state of the ocular surface but also the systemic and local homeostasis of the outer eye and the human body. This suggests that biochemical analysis of the precorneal tear film composition may provide a non-invasive tool for diagnosis and monitoring of disease progression or treatment efficacy in human medicine. However, collecting tears is demanding, and obtaining reproducible and unaltered samples is challenging because of the small sample volumes of tears. Several methods are available for tear collection as a preparatory step of precorneal tear film analysis, and the collection method used has to be assessed since it has a critical impact on the effectiveness of the assays and on the quality of the results. Each sampling method has advantages and disadvantages; therefore, it is not easy to choose the appropriate collecting method for tear collection. To overcome these limitations various methods have been recommended by different authors for special aspects of specific tests. The aim of our review was to evaluate tear sampling methods with regard to our ongoing biochemical analysis. *Contributed equally. [ABSTRACT FROM AUTHOR]

Background: Soluble, human low affinity Fcγ receptors, such as sFcγRII and sFcγRIII, are known to play a pathologic role in different diseases. Sandwich ELISAs had previously been applied for the specific detection and determination of these soluble receptors. In these ELISAs, commercial monoclonal antibodies (Ab) were used as capture antibodies with monoclonal or polyclonal antibodies serving as detector Abs. Increased levels of cell-free FcγRIII have been detected in patients with lupus but the functions and levels of sFcγRII have not been fully characterized yet. Objectives: The aim of this work was to determine the ligand binding capacities and levels of soluble FcγRII and FcγRIII in sera of patients with systemic lupus erythematosus (SLE). Moreover, correlation between the levels of sFcγRII and sFcγRIII and the clinical activity of the disease were investigated. Methods: Sera of 47 patients with SLE, and 51 healthy subjects were analyzed. In the newly developed indirect sandwich ELISAs commercial monoclonal anti-FcγRs are used as capture antibodies, and the ligand of FcγRII and FcγRIII, an artificial immune complex (IC), serves as a detection component replacing the second antibodies used in previous methods. Results: The ligand binding capacity of both soluble FcγRII and sFcγRIII were elevated in the sera of SLE patients compared to control samples. This increase was significant in patients with the active disease (n = 30; p < 0.01). It was also revealed that a substantial part of the soluble Fcγ receptors in these patients was bound in vivo to circulating IC. Conclusion: These newly developed ELISAs are probably more phisiologically relevant than other previous assays because they detect the circulating receptors on the basis their in vitro ligan binding capacities. Therefore this method can separately measure the levels of the soluble, free FcγRs and those bound circulating IC in vivo. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of longterm rituximab (RTX) therapy for rheumatoid arthritis (RA) and study correlations among B cell depletion, clinical response, and autoantibody production., Methods: Seventy-seven patients with moderate or high RA activity received RTX and were re-treated every 6 months regardless of clinical response. All patients received at least 5 cycles. We assessed 28-joint Disease Activity Score (DAS28), IgM rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) levels at baseline, after 15 days, and then every 6 months for 24 months. Absolute CD19+ B lymphocyte counts were determined in 50 patients using high-sensitivity flow cytometry (hsFACS) by reading 100,000 events., Results: After 6, 12, 18, and 24 months, 51.6%, 51.9%, 73.3%, and 83.8% of patients, respectively, showed good European League Against Rheumatism responses. Significant and sustained decreases in IgM RF and ACPA levels were observed as early as 6 months and 12 months, respectively. The baseline mean absolute B cell number was 0.234 g/l. B cell numbers diminished significantly after the very first infusion by Day 15 (0.104 g/l; p = 0.007); they further decreased until 24 months (0.0013 g/l; p < 0.001). One RTX infusion resulted in incomplete depletion in 76.7% of patients. Upon RTX treatment, changes in CD19+ B cell numbers positively correlated with changes in DAS28 (r = 0.963, p = 0.008) and IgM RF (r = 0.859, p = 0.028), but not with changes in ACPA production (r = 0.726, p = 0.102). The correlations between B cell numbers and DAS28 were observed in both ACPA-seropositive (r = 0.999, p < 0.0001) and ACPA-negative patient subpopulations (r = 0.962, p = 0.009). The correlation between CD19+ cell numbers and IgM RF was observed only in the ACPA-positive population (r = 0.944, p = 0.005) but not in seronegative patients (r = 0.398, p = 0.435). No safety issues arose., Conclusion: In RA, clinical response to RTX is associated with the extent of B cell depletion and with autoantibody production. Changes in CD19+ B cell numbers correlate with those in disease activity and, in seropositive patients, also with IgM RF, but not with ACPA production. We found that hsFACS may be a useful method to more accurately assess incomplete B cell depletion.

A case of a young man with fever of unknown origin is presented. This diagnosis can be frustrating for both patients and physicians because the diagnostic workup often involves numerous noninvasive and invasive procedures that sometimes fail to explain the fever. In the presented case some of the imaging diagnostic findings suggested malignant hematological disorder. However, histopathological and microbiological investigation proved vertebral osteomyelitis caused by Staphylococcus haemolyticus. Diagnosis was established by positron emission tomography, magnetic resonance imaging, and culture and histopathological analysis of a spinal biopsy. 3 months of antibiotic therapy was curative. Biopsy and microbiological investigation may be necessary in patients with fever, back pain and evidence of a spinal lesion on imaging, even if neoplastic disease is suspected.

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFa) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA., Objectives: To assess the effects of adalimumab treatment on FMD, ccIMT and PWV in early RA., Methods: Eight RA patients with a disease duration < or =1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reactive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint disease activity score (DAS28)., Results: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP levels (P = 0.04) and DAS28 (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P= 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038)., Conclusions: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.

The purpose of this study was to investigate plasma homocysteine (Hcy) levels in patients with systemic sclerosis (SSc) and to study the association between plasma Hcy, C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), and the clinical manifestations in SSc. Associations of Hcy level, C677T MTHFR polymorphism, and macrovascular diseases were investigated in 152 patients with SSc and 58 controls. No significant differences in Hcy levels and MTHFR genotypes were found in SSc patients compared to controls or in SSc patients with limited cutaneous compared to diffuse disease. Significantly higher Hcy concentration was observed in patients with macroangiopathy/thromboembolic events compared to patients without such clinical manifestations (p < 0.05). There was significant correlation between age and macrovascular disorders, between Hcy level and the disease duration (r = 0.164; p < 0.05). Seventy-one percent of patients with macrovascular disorders had MTHFR polymorphism. In addition, 45% of patients with hyperhomocysteinemia had pulmonary hypertension. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc patients. Elevated Hcy levels may be associated with disease duration and the evolution of macrovascular disorders and pulmonary hypertension in SSc.

Recent results suggest that B cells may have multiple pathogenic roles in systemic sclerosis (SSc) and there may be increased incidence of B cell lymphomas in SSc. Here, we assessed the prevalence of lymphomas in a large SSc cohort. We analyzed data of 218 Hungarian patients undergoing follow-ups in our institutions between 1995 and 2007. During this follow-up period, there were three SSc patients, who eventually developed B cell lymphoma. The first case is a woman with diffuse cutaneous form of SSc (dcSSc) including pulmonary, cardiac, gastrointestinal, and renal manifestations and anti-topoisomerase I antibody positivity. B cell chronic lymphocytic leukemia (B-CLL) with Zap70 expression (Rai I stage) developed 2 years after the onset of SSc. The second case is a woman with dcSSc presenting with pulmonary, cardiac, and gastroesophageal manifestations. Twenty-one months after disease onset, a chronic small lymphocytic B cell non-Hodgkin's lymphoma was diagnosed from retroperitoneal lymph nodes. Our third case is a woman with dcSSc and no internal organ manifestations. She also developed Zap70-positive B-CLL, stage Rai I 9 months after the onset of SSc. Thus, there were three cases of B cell lymphoma among our 218 SSc patients (1.38%). The association of scleroderma and non-Hodgkin's lymphoma may be a rather uncommon feature; however, the incidence of lymphoma among Hungarian SSc patients may be 1.9-2.5 times higher than that in the general population. In our three patients, B cell lymphoma developed within 2 years after the onset of SSc. Altered B cell function implicated in the pathogenesis of SSc may lead to the development of lymphoid malignancies.

Skin vasculitis may be associated with infections and autoimmune diseases. Furthermore, vasculitis may appear as a paraneoplastic symptom. A 19-year-old male patient was examined with swollen joints and papules presented on lower extremitis. Laboratory results showed high erythrocyte sedimentation ratio, positive C reactive protein, increased number of leukocytes and high circulating immune complex level. Histopatology of skin biopsy specimen proved vasculitis. ANCA was not present. No other changes could be observed besides skin involvement. Symptoms disappeared on 0.5-mg/bwkg methylprednisolon therapy. Few weeks later, enlarged cervical lymph nodes developed besides fever and weight loss. Biopsy indicated the presence of mixed cell type Hodgkin lymphoma. Appropriate examinations revealed clinical stage III/B with favorable prognosis (IPS=2). After eight cycles of ABVD therapy complete remission was achieved as confirmed by FDG-PET. As a consequence of the treatment of Hodgkin lymphoma, vasculitis also disappeared. The present case report calls to attention the importance of careful examinations to exclude other diseases, especially malignancies that may remain at the background of cutaneous vasculitis. Treatment of the primary disease also results in the improvement of secondary skin vasculitis.

Background: Soluble, human low affinity Fcgamma receptors, such as sFcgammaRII and sFcgammaRIII, are known to play a pathologic role in different diseases. Sandwich ELISAs had previously been applied for the specific detection and determination of these soluble receptors. In these ELISAs, commercial monoclonal antibodies (Ab) were used as capture antibodies with monoclonal or polyclonal antibodies serving as detector Abs. Increased levels of cell-free FcgammaRIII have been detected in patients with lupus but the functions and levels of sFcgammaRII have not been fully characterized yet., Objectives: The aim of this work was to determine the ligand binding capacities and levels of soluble FcgammaRII and FcgammaRIII in sera of patients with systemic lupus erythematosus (SLE). Moreover, correlation between the levels of sFcgammaRII and sFcgammaRIII and the clinical activity of the disease were investigated., Methods: Sera of 47 patients with SLE, and 51 healthy subjects were analyzed. In the newly developed indirect sandwich ELISAs commercial monoclonal anti-FcgammaRs are used as capture antibodies, and the ligand of FcgammaRII and FcgammaRIII, an artificial immune complex (IC), serves as a detection component replacing the second antibodies used in previous methods., Results: The ligand binding capacity of both soluble FcgammaRII and sFcgammaRIII were elevated in the sera of SLE patients compared to control samples. This increase was significant in patients with the active disease (n = 30; p < 0.01). It was also revealed that a substantial part of the soluble Fcgamma receptors in these patients was bound in vivo to circulating IC., Conclusion: These newly developed ELISAs are probably more phisiologically relevant than other previous assays because they detect the circulating receptors on the basis their in vitro ligan binding capacities. Therefore this method can separately measure the levels of the soluble, free FcgammaRs and those bound circulating IC in vivo.

Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by fibrosis and destruction of the microvasculature. Increased deposition of collagen and other extracellular matrix components affects not only the skin but most of the internal organs including lungs, heart, kidneys and the gastrointestinal (GI) tract. Within the GI tract, esophageal involvements are most frequently seen features. However, abnormalities in the small intestine, colon and anorectum may also occur. A retrospective study was performed to investigate the frequency and clinical relevances of GI involvement in patients with SSc. Charts of altogether 246 SSc patients were reviewed. This patient population included 40 males and 206 females, with a mean age of 54.2 years. In general, 176 of 246 patients (71.5%) had GI symptoms. Esophageal involvement including gastro-esophageal reflux disease (GERD), aperistalsis, pseudodiverticuli, etc. was the most common (62.6%). In addition, diseases of the stomach (31.7%), dysfunctions of the colon and anorectum (11.4%), as well as sclerosis of the biliary tract and other pancreato-biliary disorders (9.8%) also occurred. Diarrhea and malabsorption resulted in cachexia and other secondary complications leading to death in two cases. Our results support that GI manifestations are rather common in SSc. Apart from the esophagus, other GI complications in SSc are usually mild, however, early recognition is necessary to improve quality of life.

Objective: There are few large cohort studies available on the association of systemic and thyroid autoimmune diseases. In this study, we wished to determine the association of Hashimoto's thyroiditis (HT) and Graves' disease (GD) with systemic autoimmune diseases., Methods: One thousand five hundred and seventeen patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), Sjögren's syndrome (SS) and polymyositis/dermatomyositis (PM/DM) were included in the study. The HT and GD were diagnosed based on thorough clinical evaluation, imaging and fine-needle aspiration cytology (FNAC). The frequency of HT and GD in these diseases was assessed. In addition, 426 patients with HT or GD were assessed and the incidence of SLE, RA, SSc, MCTD, SS and PM/DM among these patients was determined. Prevalence ratios indicating the prevalences of GD or HT among our autoimmune patients in comparison to prevalences of GD or HT in the general population were calculated., Results: Altogether 8.2% of systemic autoimmune patients had either HT or GD. MCTD and SS most frequently overlapped with autoimmune thyroid diseases (24 and 10%, respectively). HT was more common among MCTD, SS and RA patients (21, 7 and 6%, respectively) than GD (2.5, 3 and 1.6%, respectively). The prevalences of HT in SLE, RA, SSc, MCTD, SS and PM/DM were 90-, 160-, 220-, 556-, 176- and 69-fold higher than in the general population, respectively. The prevalences of GD in the same systemic diseases were 68-, 50-, 102-, 76-, 74- and 37-fold higher than in the general population, respectively. Among all thyroid patients, 30% had associated systemic disease. In particular, 51% of HT and only 16% of GD subjects had any of the systemic disorders. MCTD, SS, SLE, RA, SSc and PM/DM were all more common among HT patients (20, 17, 7, 4, 2 and 2%, respectively) than in GD individuals (2, 5, 5, 1, 2 and 1%, respectively)., Conclusion: Systemic and thyroid autoimmune diseases often overlap with each other. HT and GD may be most common among MCTD, SSc and SS patients. On the other hand, these systemic diseases are often present in HT subjects. Therefore it is clinically important to screen patients with systemic autoimmune diseases for the co-existence of thyroid disorders.