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Background:Inflammatory joint diseases, such as psoriatic arthritis (PsA), are frequently treated by biologics. Assessment of treatment efficacy is based upon change in clinical activity scores and in tender and swollen joint counts. Although the response to these agents may be attributed to their central anti-inflammatory effects, synovial response may be operating in parallel. The potential beneficial role of intra-articular injection of tumor necrosis factor (TNF) blockers compared to glucocorticoids (GCs) in reducing synovitis was shown by means of clinical and instrumental validated measures (1). The inflamed synovial fluid is rich in mononuclear cells, however, the different mode of action of the in vitro response of these cells to drugs may contribute to the understanding of cellular response to therapeutic agents in central as opposed to peripheral compartments.Objectives:To evaluate the effect of biologics used in the management of PsA on synovial fluid mononuclear cells (SFMCs) in vitro, and to compare their modes of action to GCs that are used to locally alleviate synovial inflammation.Methods:SFMCs were obtained from PsA patients (n=11) during therapeutic knee arthrocentesis. The cells were cultured in vitro for 7 days in the presence of biologics (adalimumab, infliximab, secukinumab and ustekinumab, 10ug/ml) and GCs (betamethasone and methylprednisolone, 1 ug/ml and 10ug/ml) or medium as control. Levels of the secreted TNF were measured by ELISA. Changes in %CD14+CD16+ monocytes were analyzed by flow cytometry.Results:Both TNF inhibitors (adalimumab pp=0.0003) and GCs (betamethasone and methylprednisolone at 1ug/ml pp+CD16+ SFMCs derived from PsA patients (n=11) were significantly reduced by TNF inhibitors (p=0.0003) compared to medium, however, other biologics and GCs did not display similar activity (Fig. 1B).Figure 1.Both TNF inhibitors and GCs block TNF secretion but exhibit different activity on inflammatory CD14+CD16+ monocytes derived from SFMCs of PsA patients. SFMCs were co-cultured for 7 days in the presence of adalimumab, infliximab, secukinumab and ustekinumab at 10ug/ml or with betamethasone and methylprednisolone at 1ug/ml and 10ug/ml. Medium alone was used as a control. (A) Culture supernatants were analyzed for TNF levels by ELISA (n=8). (B) Cells were analyzed for %CD14+CD16+ monocytes by flow cytometry (n=11). All p values were calculated by the non-parametric one-way ANOVA Kruskal-Wallis test and Dunn’s multiple comparison test, *ppp=0.0003.Conclusion:Our data demonstrated marked activity mediated by TNF inhibitors in comparison with other biologics tested for their ability to suppress TNF secretion and inflammatory CD14+CD16+ monocytes. In contrast, GCs suppressed TNF secretion but did not significantly change the proportion of inflammatory CD14+CD16+ monocytes. These findings suggest an additional mechanism of action exerted directly by TNF inhibitors on synovial monocytes and which differs from that of GCs. These results warrant further studies of the therapeutic potential of local peripheral activity of TNF inhibitors for clinical application.Reference:[1]Carubbi F, Zugaro L, Cipriani P, Conchiglia A, Gregori L, Danniballe C, et al. Safety and efficacy of intra-articular anti-tumor necrosis factor alpha agents compared to corticosteroids in a treat-to-target strategy in patients with inflammatory arthritis and monoarthritis flare. Int J Immunopathol Pharmacol. 2016;29:252-66.Disclosure of Interests:None declared

The CNS manifestations of the antiphospholipid syndrome (APS) can mimic multiple sclerosis both clinically and radiologically.To compare evoked potential studies in APS patients and patients with multiple sclerosis with similar neurological disability.30 APS patients with CNS manifestations and 33 patients with definite multiple sclerosis and similar neurological disability underwent studies of visual evoked potentials (VEP), somatosensory evoked potentials (SSEP) in the upper and lower limbs (UL, LL), and sympathetic skin responses (SSR) in the upper and lower limbs.The neurological manifestations in the APS patients included stroke (n = 17), transient ischaemic attacks (n = 10), and severe headache with multiple white matter lesions on brain MRI (n = 3). Abnormal SSEP (LL), and SSR (UL; LL) were seen in APS patients (37%, 27%, and 30%, respectively) but VEP and UL SSEP were rarely abnormal (10% and 6%, respectively in APS v 58% and 33% in multiple sclerosis; p = 0.0005, p = 0.008). Mean VEP latencies were more prolonged in multiple sclerosis (116 ms v 101 ms, p0.001). Only one APS patient had abnormal findings in all three evoked potential studies, compared with seven patients in the multiple sclerosis group (p = 0.04)Abnormal VEPs are uncommon in APS in contrast to multiple sclerosis. Coexisting abnormalities in all other evoked potentials were similarly rare in APS. In patients with brain MRI findings compatible either with multiple sclerosis or APS, normal evoked potential tests, and especially a normal VEP, may support the diagnosis of APS.

To assess the efficacy and safety of vaccination against influenza virus in patients with rheumatoid arthritis, with special emphasis on the effect of disease modifying antirheumatic drugs (DMARDs), including tumour necrosis factor alpha (TNFalpha) blockers.82 rheumatoid patients and 30 healthy controls were vaccinated with a split-virion inactivated vaccine containing 15 mug haemagglutinin (HA) per dose of each of B/Hong Kong/330/2001 (HK), A/Panama/2007/99 (PAN), and A/New Caledonian/20/99 (NC). Disease activity was assessed by tender and swollen joint count, morning stiffness, evaluation of pain, Health Assessment Questionnaire, ESR, and C reactive protein on the day of vaccination and six weeks later. Haemagglutination inhibiting (HI) antibodies were tested by a standard WHO procedure. Response was defined as a fourfold or more rise in HI antibodies six weeks after vaccination, or seroconversion in patients with a non-protective baseline level of antibodies (1/40). Geometric mean titres (GMT) were calculated to assess the immunity of the whole group.Six weeks after vaccination, a significant increase in GMT for each antigen was observed in both groups, this being higher in the healthy group for HK (p=0.004). The percentage of responders was lower in rheumatoid patients than healthy controls (significant for HK). The percentage of responders was not affected by prednisone or any DMARD, including methotrexate, infliximab, and etanercept. Indices of disease activity remained unchanged.Influenza virus vaccine generated a good humoral response in rheumatoid patients, although lower than in healthy controls. The response was not affected by the use of prednisone or DMARDs.

Background: Leflunomide is now an approved agent for the management of adult rheumatoid arthritis (RA). Its active metabolite A771726 inhibits de novo pyrimidine biosynthesis. Although considered to be an immunosuppressive agent, its mechanism of action remains obscure. Objectives: Evaluation of the leflunomide active metabolite A771726 (LEF) effect on interleukin 1s (IL1s), tumour necrosis factor (TNFα), nitric oxide (NO), and stromelysin (metalloproteinase-3 (MMP-3)) production by activated human synovial tissue in culture. Methods: Synovial tissue was obtained during surgery from patients undergoing total knee replacement owing to RA or osteoarthritis (OA), cut into small pieces, and cultured in Petri dishes with test materials as previously described. IL1s, TNFα, NO, and MMP-3 were measured in the culture media after 48 hours incubation with different doses of LEF by methods previously described. Results: LEF (0.3, 3, and 9 µg/ml) inhibited IL1s production in the presence of lipopolysaccharide (LPS; 3 µg/ml) in a dose dependent manner (p

Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known.To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA.The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit.Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain.Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients.

Background Fibromyalgia Syndrome (FMS), considered the result of increased processing of pain by the central nervous system, is a non-inflammatory condition characterized by chronic, widespread musculoskeletal pain and tenderness.Axial spondyloarthritis (SpA) is a group of inflammatory joint disease primarily involving the sacroiliac joints and axial spine. Although FMS and axial SpA differ vastly in their pathogenesis, a considerable clinical overlap may exist between these conditions. Chronic nocturnal back pain and disturbed sleep may accompany either condition. The Assessment of Spondylo-Arthritis international Society (ASAS) has published updated classification criteria for axial SpA with an imaging and clinical arms. We have previously described an increased prevalence of secondary FMS among female SpA patients. Objectives To evaluate the prevalence of axial SpA among FMS patients, utilizing the 2010 ASAS criteria (1). Methods Patients suffering from FMS (ACR 1990 classification criteria) were recruited consecutively from a specialized FMS clinic. Patients were interviewed regarding the presence of SpA features, as defined by the ASAS group (IBP, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn9s/colitis, good response to NSAIDS, family history of SpA) and underwent HLA-B27 testing and CRP measurement. MRI examinations of the sacroiliac joints were performed on a 1.5 T MRI unit using semicoronal T1 weighted, STIR and FSPGR pre- and post-contrast injection sequences. FMS severity was assessed by the FIQ and SF-36 questionnaires and physical examination of the tender points using a dolorimeter. SpA symptom severity was assessed by the BASDAI questionnaire Results 99 unselected patients were recruited and MRI results were available for 74. Sacroiliitis, based on ASAS definition (2), was found among 7 patients, 7 of which fulfilled ASAS SpA classification criteria. 6 patients fulfilled the criteria based on sacroiliitis on imaging and SpA features, one additional patient fulfilled SpA criteria based on HLA-B27 positivity and additional SpA features. Conclusions Imaging findings suggestive of inflammatory SpA were not uncommon among patients presenting with a clinical diagnosis of FMS. Definite sacroiliitis and ASAS criteria SpA positivity were diagnosed among 9.5% of patients and additional changes typical of SpA were frequent. These findings suggest that FMS may mask an underlying SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such co-morbidities. References Sieper J et al. Ann Rheum Dis 2009;68:8(Suppl II):ii1–ii44 Rudwaleit M et al. Ann Rheum Dis 2009; 68(10):1520 Disclosure of Interest J. Ablin Speakers bureau: Pfizer Inc., I. Eshed: None declared, M. Berman: None declared, V. Aloush: None declared, I. Wigler: None declared, D. Caspi: None declared, M. Likhter: None declared, A. Sharabi: None declared, A. Rom-Broyde: None declared, S. Borok: None declared, D. Levartovsky: None declared, Y. Wolman: None declared, D. Paran: None declared, M. Anouk: None declared, O. Elkayam: None declared

Case history A 48 year old man with 17 year history of primary Sjogren syndrome (pSS) presented with a sudden swelling of the left lower limb without pain, fever or any other symptom. The diagnosis of pSS was based on xerophthalmia, xerostomia, and swelling of the parotid glands in the presence of positive antinuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro ( 85 IU ELISA, normal range

OBJECTIVE: To describe a novel iatrogenic immunological reaction produced by minocycline. CASE REPORTS: The clinical course and laboratory results of three women who presented with similar rheumatological manifestations after a prolonged exposure to minocycline are described. All three presented a unique reaction manifested by fever, arthritis/arthralgia and livedo reticularis during treatment with minocycline for acne vulgaris. The clinical syndrome was associated with high titre of serum perinuclear anticytoplasmatic antibodies (p-ANCA) and antimyeloperoxidase antibody (anti-MPO). Symptoms resolved after stopping the drug and recurred promptly after rechallenge in all three patients. CONCLUSIONS: Minocycline, which is widely used in the treatment of acne, often without adequate supervision, may induce arthritis and livedo vasculitis associated with anti-MPO.

The incidence of lower urinary tract infection in 120 women with rheumatoid arthritis and secondary Sjögren's syndrome was evaluated retrospectively. Thirty one patients (26%) had secondary Sjögren's syndrome. Recurrent urinary tract infection was significantly more common in these patients (11/31) than in patients without Sjögren's syndrome (4/89). Habitual leucocyturia was also more common in patients with secondary Sjögren's syndrome (18/31) than in patients with rheumatoid arthritis without Sjögren's syndrome (8/89). Of seven patients with vaginal sicca symptoms, six had recurrent urinary tract infection. Urinary 24 hour mucopolysaccharide excretion in 20 patients with Sjögren's syndrome was similar to the excretion in 10 patients without Sjögren's syndrome. These results show that recurrent urinary tract infection is significantly more common in women with rheumatoid arthritis and secondary Sjögren's syndrome. A local deficit in protective urinary mucosal secretion or other immune mechanisms may be responsible for this susceptibility.

Background Galectin-3 is a β-galactoside-binding lectin that plays an important role in the modulation of immune responses. Galectin-3 levels are increased in rheumatoid arthritis (RA) synovial tissue, synovial fluid and peripheral blood 1 . Recombinant exogenous galectin-3 stimulates pro-inflammatory cytokine secretion by fibroblast-like synoviocytes (FLS) 2 . In a murine, antigen-induced arthritis model, Gal-3-/- mice displayed significantly reduced synovitis and joint erosion compared to WT mice 3 . Objectives To examine the effect of galectin-3 inhibition on toll-like receptor (TLR)-induced secretion of interleukin-6 (IL-6) in FLS from RA and osteoarthritis (OA) patients. Methods FLS from RA and OA patients were harvested from synovial fluid aspirates or directly from synovial tissue obtained during orthopedic surgery. Galectin-3 was inhibited either by siRNA mediated gene-knockdown, or by the galectin ligands thiodigalactoside and modified citrus pectin (MCP). The cells were then stimulated with ligands for TLR-2, 3 and 4; peptidoglycan (PGN), poly(I:C) and lipopolysaccharide (LPS), respectively, and the levels of IL-6 secretion were measured by ELISA. Results Galectin-3 gene knockdown inhibited TLR-2, 3 and 4 induced IL-6 secretion in FLS. Treatment with thiodigalactoside, a galectin oligosaccharide ligand, also decreased TLR-meditated IL-6 secretion. Treatment with MCP, a polysaccharide galectin-3 ligand, attenuated IL-6 secretion due to stimulation with PGN and poly(I:C), but augmented IL-6 secretion following LPS-stimulation, in a dose dependent manner. Conclusions Galectin-3 modulates TLR-induced IL-6 secretion in FLS. Knockdown of galectin-3 inhibits PGN, poly(I:C) and LPS-induced IL-6 secretion. Galectin-3 saccharide ligands can also inhibit TLR-induced IL-6 secretion. Understanding the role of galectin-3 in TLR-induced cytokine secretion may add new insights into the pathological mechanisms of autoimmunity and perhaps aid in the design of galectin-3 inhibitors as potential therapeutics. References Ohshima S, Kuchen S, Seemayer CA, et al. Galectin 3 and its binding protein in rheumatoid arthritis. Arthritis Rheum. 2003; 48(10): 2788-95. Filer A, Bik M, Parsonage GN, et al. Galectin 3 induces a distinctive pattern of cytokine and chemokine production in rheumatoid synovial fibroblasts via selective signaling pathways. Arthritis Rheum. 2009; 60(6): 1604-14. Forsman H, Islander U, Andreasson E, et al. Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis Rheum. 2011; 63(2): 445-54. Disclosure of Interest None Declared

Background Takayasu arteritis (TAK) and Giant cell arteritis (GCA) are classified as two different vasculitides.[1] The differentiation is based on age at onset (under 40y for TAK, above 50y for GCA) and vascular distribution (aorta and its primary branches for TAK and mainly extracranial arteries for GCA). However, both diseases involve large vessels and share histopathology findings. Objectives Our goal is to describe a series of patients above the age of 50y with large vessel arteritis and vascular involvement typical of TAK. Methods Eighteen Patients (median age 64y, 16 females) were selected from 3 centers in Israel. A retrospective review of the cases was preformed with special emphasis on clinical characteristics (including clinical course and outcome), laboratory values and vascular involvement. Vascular imaging by CT angiography, MRI angiography or planar angiography was done in all cases. Results Five patients fulfilled the ACR criteria for GCA, 5 the ACR criteria for TAK, 3 both GCA and TAK criteria, while 5 patients had clear involvement of large vessels without fulfilling the criteria for either disease. The dominant presenting symptoms were constitutional, while only a few patients had cranial or peripheral symptoms. On physical examination, 61% had signs of vascular compromise including: blood pressure arm differences, non palpable limb pulses or vascular bruits. All patients had elevated acute phase reactants, 78% had anemia. Temporal artery biopsy showed giant cell arteritis in 6 out of 9 biopsies. The majority (78%) showed either involvement of the ascending aorta, the aortic arch, descending aorta or a combination of these. The distribution of vessel involvement was as following: carotid arteries in 9 patients, subclavian arteries in 12, axillary arteries in 5, abdominal aorta in 9, mesenteric or celiac trunk in 7, renal arteries in 3, iliac arteries in 7 and femoral arteries in 2. All the patients were treated with prednisone and 50% with steroid sparing drug. Nine out of 15 patients (60%) that have completed at least 1 year of follow-up achieved remission. Three additional patients had a partial remission. Three patients of the remission group relapsed. A comparison between the patients who fulfilled the ACR criteria for GCA and those who fulfilled for TAK showed that the first group was slightly older (70y vs. 64y) and had more constitutional symptoms while the second group had more peripheral symptoms and more vascular involvement signs in physical examination. The acute phase reactants were slightly higher in the GCA group. However, no substantial differences in the distribution of vascular involvement, type of treatment or outcome measures were observed. Conclusions Vascular involvement typical of TAK in patients above the age of 50y with large vessel arteritis seems to be more frequent than previously assumed. The differences between those who fulfill the criteria for each disease are minor. Our findings support the assumption that TAK and GCA represent a spectrum of the same disease. References Fries JF, Hunder GG, Bloch DA, et al. The ACR 1990 criteria for the classification of vasculitis. Arthritis Rheum. 1990;33:1135-6. Disclosure of Interest None Declared

Background Screening for latent tuberculosis (TB) is mandatory before treatment with TNFα blockers. It has been suggested that latent TB based on tuberculin skin test (TST) may be over diagnosed due to Koebner phenomenon in patients with psoriasis. Objectives To assess the effect of the extent of skin and joint involvement on the diagnosis of latent TB and to compare the TST and QuantiFERON-TB Gold (QTF-G) in patients with psoriasis (PSO) and psoriatic arthritis (PsA) to rheumatoid arthritis (RA) patients. Methods Forty-one PSO patients (35 with PsA) and 35 RA patients candidates to receive TNF α were prospectively evaluated for TST, QTF-G, risk factors for latent TB as well as for the severity of the underlying diseases using psoriasis activity severity index (PASI) and the number of painful and swollen joints. Results 41 PSO patients (mean age 49.7, 48% women, 36% treated with MTX) were compared to 35 RA patients (mean age 60 (p=0.006), 70% women, 70% treated with MTX (p=0.02)). No differences were observed in the mean TST (5±6.7 for PSO, 5.8±6.3 for RA), the proportion of positive TST based on 5mm as well as 10 mm, the proportion of QTF-G positive patients (7.2% in PSO vs 12% in RA). The level of agreement between TST and QTF-G was similar between the 2 groups (using TST 5 and TST 10, 74% and 81% for PSO vs 60% and 76% for RA, respectively). Furthermore, no correlation was found between the extent of psoriasis involvement evaluated by PASI and the TST, QTF-G, and the level of agreement between them. The number of tender and swollen joints, the use of MTX or corticosteroids did not affect the diagnosis of screening TB Conclusions The extent of severity of psoriasis does not affect the results of TST and QTF-G in patients with psoriasis. The level of agreement between TST and QTF-G was similar in RA and PSO. Although it remains to be determined with test is preferable in the diagnosis of latent TB, whether the patient suffers from PSO/PsA or RA does not seem to play an important role in this choice. Disclosure of Interest None Declared

Background Monitoring of immune responses is essential in a number of clinical research areas that address immunosuppressed individuals, including oncologic and rheumatic patients. During the past 10 years, our group has been deeply involved in the study of vaccinations in rheumatic patients, with a special concern regarding the impact of drugs. While humoral responsiveness is considered the gold standard for most vaccines, including seasonal influenza, evaluation of cellular immune responses is much less standardized, requires specialized equipment and often suffers from technical limitations that eventually lead to inaccurate and inconsistent results. Since cellular response is essential for supporting virus-specific effector cell functions, reliable assessment techniques are of great importance. Objectives To comparatively assess the cellular immune response to influenza vaccine by 3 different methods, in concomitant with humoral immune response evaluation, in rheumatoid arthritis (RA) patients relative to healthy subjects. Methods Trivalent influenza subunit vaccine was administered to 18 RA patients treated by synthetic DMARDs, mostly methotrexate (MTX), and to 18 healthy controls. Peripheral blood mononuclear cells (PBMCs) and sera were obtained immediately before and ~28 days after vaccination. Three different methods to measure cellular mediated immune responses to influenza vaccination were compared in RA patients and in healthy subjects. These methods included (1) flow cytometric analysis of IL-2 and IFNg production in activated CD4/CD8 T-cells; (2) enzyme-linked immunosorbent assay (ELISA) for the analysis of IFNg secretion and (3) granzyme B activity assay in influenza-stimulated PBMC. The humoral response was evaluated by the hemagglutination inhibition (HI) assay. Results Cellular response: Vaccination induced a significant increase in PBMC IFNg secretion and Granzyme B activity in the RA patients. A significant increase in Granzyme B activity was also measured in the healthy control group, but there was no change in the levels of secreted IFNg. There was no difference in the frequencies of IFN-g/IL-2 producing activated CD4 or CD8 T-cells, as measured by flow cytometry, in both groups, either before or 4 weeks following influenza vaccination. Humoral response: A significant increase in the geometric mean titer (GMT) of HI was demonstrated for the H1N1 and H3N2 influenza strains in both groups. The response rate to HIN1 was significantly higher in DMARDs patients in comparison with healthy controls. The response rate to the H3N2 and B strains was similar in both groups. Conclusions The results of this study confirm previous findings on the preserved humoral immune response of RA patients to influenza vaccination. Among the three methods utilized to cellular immune responsiveness - Granzyme B activity assay was the only one to detect such response in both groups tested. It appears that current available measurement methods for cellular responsiveness to influenza vaccination suffer from inconsistency, and are limited in their ability to reflect gained cellular immunity. Disclosure of Interest None Declared

In 15 patients with rheumatoid arthritis who were in clinical remission the weekly regimen of methotrexate treatment was changed to fortnightly without a change in dose. A total of 13 patients completed a 12 month trial. No change in clinical or laboratory parameters occurred. There was no change in the use of analgesics or non-steroidal anti-inflammatory drugs and the patients remained in remission. Two patients had to be withdrawn after two and four months respectively because of a flare in disease activity. It is suggested that in most patients with rheumatoid arthritis who are treated with methotrexate and whose disease activity is stable a fortnightly regimen can be permitted without affecting drug efficacy.

A 47 year old man presented with seven years of severe psoriatic polyarticular arthritis of progressive, symmetrical, and additive course, affecting the shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, hips, knees, and feet. Also, his skin and nails were completely affected with severe erythroderma. The patient was treated with methotrexate, chrysotherapy, antimalarial drugs, salazopyrine, azathioprine, cyclosporin, minocycline, and intra-articular and systemic corticosteroids. All these treatments consecutively and in …

Previous work has shown that leucocyte adhesiveness/aggregation (LAA), as measured by the leukergy test, correlates well with disease severity in rheumatic patients. As LAA is probably a manifestation of the acute phase reaction various components of the acute phase reaction were measured in order to identify the best marker of disease activity. In addition to LAA, the following variables were measured in 79 patients with various rheumatic diseases and in 10 controls: white blood cell and platelet counts, erythrocyte sedimentation rate, haptoglobin, fibrinogen, C reactive protein, albumin, globulin, caeruloplasmin, alpha 1, alpha 2, beta, and gamma globulin, and haemoglobin concentrations. Patients were graded according to the state of their disease as mild, moderate, or severe. The extent of leucocyte adhesiveness/aggregation in peripheral blood proved to be the best laboratory variable for the grading of disease activity. Correct grading was obtained in 63% of the patients by means of the LAA, compared with 48% with C reactive protein, 41% with caeruloplasmin, 40% with haptoglobin, and 32% with haemoglobin. It is suggested that LAA of the peripheral blood during inflammation may be used as a reliable marker of disease severity.

The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.

In a prospective open study 44 Israeli patients with rheumatoid arthritis were treated with weekly low dose methotrexate (MTX) for up to 36 months. Nine patients withdrew from the study: six because of side effects and three due to inefficacy. One patient died of septicaemia following septic arthritis. Significant improvement, graded by Ritchie articular index, grip strength, physician's global assessment, erythrocyte sedimentation rate (ESR), and platelet counts, was noticed in response to treatment. Seronegative patients had a better clinical response. Transient gastrointestinal symptoms were common and correlated with increases of serum aspartate transaminase (AST). HLA-DR1 and DR7 were significantly associated with increased serum AST concentrations.

An axial computed tomographic (CT) scan of the lumbosacral regions was performed in 65 patients. The patient population was divided into two groups. The first (control) group included 40 elderly patients without calcification of the ligamenta flava. The second group included 25 patients with ankylosing spondylitis. More than 90% of those in the second group showed calcified lumbosacral ligamenta flava. In two patients these calcifications produced spinal stenosis. The diagnostic and practical importance of these findings are discussed.