Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease

Abstract

The objective of this study was to evaluate the clinical significance of anti-nuclear antibodies (ANA) detected in the early stages of rheumatoid arthritis (RA), by a retrospective comparison of the clinical, laboratory, and therapeutic characteristics of patients with or without ANA. The files of 99 longstanding seropositive RA patients were reviewed. Data relating to demographics, medical history, family history, physical findings, extra-articular complications, laboratory tests, drugs [dosage, duration. efficacy, combinations, adverse effects (AEs)], intra-articular injections, and surgery were recorded. Patients with or without ANA at presentation of their disease were compared using chi-square and t-tests. Fifty-two ANA positive (group 1) and 47 ANA negative (group 2) patients were enrolled in the study. All were comparable in terms of their mean age, age at diagnosis, follow-up duration (approximately 10.5 years), and male:female (M:F) ratio. On admission, pain complaints were more pronounced in group 1 (P = 0.004 in the feet), but the physical findings did not differ. Deformities and nodules developed in similar numbers. Extra-articular complications were evenly distributed; vasculitis, however, was significantly more prevalent in ANA positive (10/52) than in ANA negative (2/47) patients. Thyroid disease was more common in group 2 (10/47 vs 3/52). Laboratory tests (presentation and maximal values) were similar, with the exception of higher anti-DNA (but within normal ranges) and gamma-globulin% in group 1. Group 1 used more drugs prior to diagnosis. Corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) were evenly used. Combination therapy, joint injections, and surgery were more prevalent in group 2. AEs to various DMARDs were more common in group 1. Although similar in many aspects, RA patients with ANA tend to present with more pain complaints, a higher risk of vasculitis and AEs relating to use of DMARDs, while those without ANA needed more aggressive therapeutic modalities.

Pre-treatment antinuclear antibody positivity, therapeutic efficacy and persistence of biologics in rheumatoid arthritis

“…ANA positivity varies greatly (10-70%) in different cohorts (8,12) and the frequency we observed (27%) is consistent with the literature. Our cohort had relatively high mean age (56 years) and relatively high disease duration (a median of 11 years; Table 1), both factors being associated with an increase in the prevalence of ANA positivity.…”

“…Testing ANA status in an observational study which would include only early RA patients (18) (for example before the appearance of bone erosions or with disease duration lower than 2 years) would further substantiate the relationship between this serological marker and treatment outcomes. Our data did not confirm the cited longer disease duration (8) and lower age of onset in ANA-positive RA women compared to ANA-negative women (9) and there were no data regarding the number of drugs used, pain level, extra-articular manifestations and adverse events related to DMARDs to compare with the cited literature (12,13).…”

“…On one hand, advanced or prolonged disease (8), and on the other hand young age of RA onset (< 40 years) (11) are associated with a higher prevalence of ANA positivity in women. ANA-positive RA patients used more drugs prior to diagnosis (12), presented an increased level of pain, had a higher prevalence of vasculitis and of other extra-articular manifestations (13) and presented adverse events caused by disease modifying anti-rheumatic drugs (DMARDs).…”

Prevalência de manifestações oculares em 198 pacientes com artrite reumatóide: um estudo retrospectivo

“…Um estudo analisando uma população feminina com AR de diagnóstico recente e com níveis séricos persistentemente positivos para FR mostrou que tal grupo apresentava mais erosões, nódulos, manifestações extra-articulares, diminuição da capacidade funcional e atividade da doença do que as pacientes soronegativas ou soronegativas intermitentes (21) . Já a presença do FAN no paciente com AR tem um papel menos claro embora existam autores que associam a sua presença a uma doença de pior evolução (8) . Neste trabalho, nenhuma correlação foi possível entre a presença de fator reumatóide ou do fator antinúcleo e as manifestações oculares especificas da AR, inclusive em casos de ceratite ulcerativa.…”

“…A AR é considerada a doença do coláge-no que mais comumente afeta a córnea periférica (5) . Sendo essa uma enfermidade na qual aspectos genéticos são importantes, (principalmente a presença de HLAs DR4 e DR1) (2,6) e na qual o perfil dos auto-anticorpos presente, como fator reumatóide (FR) e fator antinuclear (FAN), influi na gravidade das manifestações apresentadas (7)(8) , depreende-se que exista variabilidade populacional nos achados articulares e extra-articulares.…”