A validation of register-derived diagnoses of interstitial lung disease in patients with inflammatory arthritis: data from the NOR-DMARD study.

OBJECTIVE: There is a lack of knowledge concerning the validity of the interstitial lung disease (ILD) diagnoses used in epidemiological studies on rheumatic diseases. This paper seeks to verify register-derived ILD diagnoses using chest computed tomography (CT) and medical records as a gold standard. METHOD: The Norwegian Anti-Rheumatic Drug Register (NOR-DMARD) is a multicentre prospective observational study of patients with inflammatory arthritis who start treatment with disease-modifying anti-rheumatic drugs. NOR-DMARD is linked to the Norwegian Patient Registry (NPR) and Cause of Death Registry. We searched registers for ILD coded by ICD-10 J84 or J99 among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. We extracted chest CT reports and medical records from participating hospitals. Two expert thoracic radiologists scored examinations to confirm the ILD diagnosis. We also searched medical records to find justifications for the diagnosis following multidisciplinary evaluations. We calculated the positive predictive values (PPVs) for ILD across subsets. RESULTS: We identified 71 cases with an ILD diagnosis. CT examinations were available in 65/71 patients (91.5%), of whom ILD was confirmed on CT in 29/65 (44.6%). In a further 10 patients, medical records confirmed the diagnosis, giving a total of 39/71 verified cases. The PPV of a register-derived ILD diagnosis was thus 54.9%. In a subset of patients who had received an ILD code at two or more time-points and had a CT scan taken within a relevant period, the PPV was 72.2%. CONCLUSION: The validity of register-based diagnoses of ILD must be carefully considered in epidemiological studies.

The influence of ERAP1 gene variants on clinical phenotype in ankylosing spondylitis.

OBJECTIVES: Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene variants diminish the risk of developing ankylosing spondylitis (AS) through a reduction in ERAP1 activity. We investigated whether disease expression was altered in patients who developed AS despite the presence of two protective ERAP1 variants. METHOD: We conducted a cross-sectional and longitudinal cohort study of patients with established AS (n = 334, 90% B27+, mean age at study 45 years) for whom clinical data and biological samples were collected during a research visit. Genotyping for the single nucleotide polymorphisms (SNPs) rs27044 and rs30187 was performed on genomic DNA by reverse transcription polymerase chain reaction (RT-PCR) with interleukin (IL)-6 and tumour necrosis factor (TNF) levels determined by a sandwich enzyme-linked immunosorbent assay (ELISA). Associations between genotypes and haplotypes, clinical and serological findings were analysed using SNPstats. RESULTS: Both SNPs were in strong linkage disequilibrium and formed three common haplotypes (C/C 0.65, G/T 0.30, and C/T 0.04). Haplotype C/T carried a lower risk for uveitis [odds ratio (OR) 0.32, p = 0.03] and elevated C-reactive protein (CRP) levels (OR 0.26, p = 0.04). There was no effect of ERAP1 haplotypes on cytokine levels or major outcomes after 8 years of follow-up. CONCLUSIONS: The ERAP1 rs27044/rs30187 haplotype C/T is associated with lower risk of extraspinal disease and systemic inflammation in Nordic AS patients but has no impact on IL-6 or TNF levels.

The distribution of HLA-B27 subtype in patients with ankylosing spondylitis in Northern Norway.

BACKGROUND: Although the high prevalence of human leucocyte antigen (HLA)-B27 and ankylosing spondylitis (AS) in Northern Norway is now well documented, data on the distribution of HLA-B27 subtypes and their potential impact on disease presentation and course are lacking. METHOD: We conducted a cross-sectional study of patients (n = 124) with established (modified New York criteria) AS participating in a longitudinal disease registry. Clinical data at the time of sample collection were recorded and genotyping for HLA-B27 was performed by low-resolution polymerase chain reaction (PCR) screening. Subtyping was then performed with sequence-specific primers (PCR-SSP) and direct exon 2 and 3 sequencing. The results were analysed with SCORE and Seqscape software. RESULTS: Four patients (3%) were HLA-B27 negative in all genetic analyses. In the remaining 120 HLA-B27-positive patients, HLA-B27*05 was present in 117 (98%) and HLA-B27*02 in three patients (2%). There was complete concordance between the screening and subtyping results. The three patients with HLA-B27*02 had no distinguishing clinical characteristics. CONCLUSIONS: HLA-B27*05 is the predominant subtype of HLA-B27 in Northern Norway. This supports the concept of a North-South gradient for HLA-B27 subtypes with little regional drive to adapt to environmental challenges. Low-resolution HLA-B27 PCR screening captures all relevant subtypes in this region.

Efficacy of methylprednisolone pulse therapy versus infliximab in the treatment of severe flares of chronic polyarthritis.

BACKGROUND: To compare short term efficacy of pulse intravenous (iv) Methylprednisolone (MP) versus Infiximab in flares of polyarthritis. PATIENTS-METHODS: Observational study of consecutive patients admitted with flares of chronic polyarthritis. Treatment consisted of three iv doses of MP 1000mg on alternate days (MP-group, n = 10) or of Infliximab will be 3 mg/kg at baseline, two, and six weeks later (I-group, n=9). DMARD therapy was initiated/continued in all patients. Disease parameters at baseline (t=0), two weeks (t=1) and twelve weeks (t=2) were compared by non-parametric testing. RESULTS: Reductions in disease parameters at both t=1 and t=2, the occurrence of side effects and the proportion of patients reaching ACR 20, 50 or 70% response criteria were similar in both groups. CONCLUSION: Pulse MP resulted in a symptomatic response similar to Infliximab in our patients. The benefit of MP was observed for up to 3 months.