Israel Medical Association Journal

The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease. 

Objectives: To assess the nature of joint problems encountered in a geriatric inpatient population and evaluate the contribution of a rheumatologist.

Methods: We reviewed the rheumatology consultations that were conducted in a geriatric medical center over a 10 year period.

Results: A total of 474 consultations were held; most of these patients (86%) were hospitalized in the acute geriatric departments, 10% in the rehabilitation ward and 4% in the long-term care wards. Some patients were seen more than once. The rheumatologic joint problem was the main reason for hospitalization in 53% of these patients. Monoarthritis was the most frequent complaint (50%), followed by pauci-articular arthritis (two to five joints) in 30% of patients. Arthrocentesis, diagnostic and therapeutic, was performed in 225 patients, most of them on knee joints (81%). The most frequent diagnosis was osteoarthritis with acute exacerbation (28%), followed by gout (18%), pseudo-gout (9%) and rheumatoid arthritis (9%). In 86 cases (18%) the diagnosis was a non-specific rheumatologic problem: arthralgia, non-specific generalized pain, or fibromyalgia.

Conclusions: Prompt and appropriate evaluation, as well as arthrocentesis and treatment initiation, including local injections, were made possible by the presence of an in-house rheumatologist. 

Objectives: To assess the changes in ACPA titers in patients with RA after treatment with infliximab as a first biological agent, and to correlate these variations with non-infusion-related adverse effects.

Methods: In a prospective multicenter observational study involving 48 research centers, we assessed 139 patients with established moderate-to-severe RA diagnosed according to American College of Rheumatology criteria. Samples were collected before and 6–12 months after treatment.

Results: The mean age of the study patients was 50.6 years old, and 118 were female (84.9%). Statistically significant variations in ACPA titers were noted in 47 patients (before and after treatment) (P = 0.012). Overall, ACPA titers were decreased in 32 (65.3%) and increased in 15 (34.7%). No correlation was found between severe or mild adverse effects in patients presenting variations in ACPA titers.

Conclusions: The present study showed that infliximab affected ACPA titers, promoting mainly a decrease; however, this was not related to the occurrence of non-infusion-related adverse effects.

Objectives: To determine the outcome of RA with respect to disease activity and the rate of remission, as measured by the DAS-28, in a real-world inception cohort.

Methods: We conducted an observational cross-sectional study of a single-center real-world inception cohort of 101 consecutive patients being treated for RA in 2009–2010 in a rheumatology outpatient clinic. Patients were managed at the discretion of the attending rheumatologist with the goal of achieving remission. DAS-28 scores were calculated and analyzed by clinical and treatment variables derived from the medical files.

Results: Mean patient age was 58.6 ± 13.4 years and mean duration of disease 10.7 ± 7.9 years. Disease remission (DAS-28 < 2.6) was achieved in 26.7% of patients and low disease activity (> 2 .6 DAS-28 < 3.2) in 17%. Monotherapy with a conventional disease-modifying anti-rheumatic drug (C-DMARD, 21% of patients at last follow-up) was associated with a significantly lower mean DAS-28 score and C-reactive protein level than combined C-DMARD treatment (79% of patients), and with shorter disease duration than combined treatment with C-DMARDs or C-DMARD(s)+biological DMARD (40% of patients). Rheumatoid factor and anti-cyclic citrullinated peptide positivity had no effect on DAS-28 scores. Time from diagnosis was inversely correlated with DAS-28 scores.

Conclusions: The achievement of low disease activity and remission in a significant portion of our inception cohort of patients with RA suggests that the treat-to-target strategy is feasible and effective in routine clinical practice. 

Objectives: To review positive temporal artery biopsiese of GCA in an attempt to correlate various histological parameters with clinical features, disease complications and outcome.

Methods: Positive biopsies from 65 GCA patients were randomly selected for review by a single pathologist. In each biopsy the following parameters were scored: intensity and location of the inflammatory infiltrate, presence of giant cells and other cell types, fragmentation and calcification of the internal elastic lamina, intimal thickening, and presence of luminal thrombus. Clinical data were obtained from the patients’ charts. Intensity of the initial systemic inflammatory reaction (ISIR) at the time of diagnosis was scored by the presence of five parameters: fever, anemia, thrombocytosis, leukocytosis, and sedimentation rate > 100 mm/hr.

Results: In cases with bilateral positive biopsy (n=27), there was good correlation between the two sides regarding intensity of inflammation (r = 0.65, P < 0.001), location of the infiltrate (r = 0.7, P < 0.001), degree of intimal thickening (r = 0.54, P < 0.001), and presence of giant cells (r = 0.83, P < 0.001). The rate of corticosteroid discontinuation tended to be quicker in patients with inflammatory infiltrates confined mainly to the adventitia, but other histological parameters did not affect this rate.

Conclusions: Inflammatory infiltrates confined to the adventitia were associated with more neuro-ophthalmic ischemic manifestations, weak/moderate ISIR at the time of diagnosis, and faster rate of corticosteroid discontinuation. No association was found between other temporal artery biopsy histological parameters and clinical features of GCA patients.