Analysis of distribution and severity of inflammation in patients with osteoarthitis compared to rheumatoid arthritis by ICG-enhanced fluorescence optical imaging and musculoskeletal ultrasound: a pilot study.

BACKGROUND: In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US). OBJECTIVE: Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). METHODS: FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0-3) for each imaging method. RESULTS: GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding. CONCLUSIONS: US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases.

Small joint involvement in psoriatic arthritis is associated with onycholysis: the Reykjavik Psoriatic Arthritis Study.

OBJECTIVES: Psoriasis and psoriatic arthritis (PsA) are associated with nail changes. Recent reports suggest that nail changes may be a part of the enthesitis of PsA and that they predict the onset of arthritis among patients with psoriasis, but they have not reported on subclasses of nail changes. However, earlier reports suggested that onycholysis is the nail change most strongly associated with PsA. If nail changes in PsA are a sign of enthesitis, they might be associated with small joint disease in general and the objective of this study was to test this hypothesis. METHODS: A total of 154 patients recruited through the Reykjavik Psoriatic Arthritis Study had a joint, skin, and nail evaluation. Associations with small joint disease were tested using univariate analysis, and confirmed in a multivariate model. RESULTS: Onycholysis had a strong association with small joint involvement [odds ratio (OR) 3.42, 95% confidence interval (CI) 1.41-8.92], while other types of nail changes did not. The number of swollen joints and shorter disease duration were also associated with small joint disease. CONCLUSIONS: Onycholysis is associated with small joint disease in PsA. Future studies of PsA should report the subtypes of nail changes. Longitudinal studies are needed to determine whether onycholysis predicts PsA.

Contribution of anti-CCP antibodies, proximal interphalangeal joint involvement, HLA-DRB1 shared epitope, and PADI4 as risk factors for the development of rheumatoid arthritis in palindromic rheumatism.

OBJECTIVES: To determine which variables at baseline are predictive for the development of rheumatoid arthritis (RA) from palindromic rheumatism (PR) in a Japanese population. METHODS: Anti-cyclic citrullinated peptide (anti-CCP) antibodies, joint involvement pattern, genotypes of HLA-DRB1, peptidylarginine deiminase (PADI4), and protein tyrosine phosphatase (PTPN22) were examined in 28 patients with PR at baseline, and their clinical outcome was prospectively evaluated. The same variables were also investigated in 38 healthy controls. RESULTS: Eleven out of 28 patients with PR developed RA. The prevalence of anti-CCP antibodies in the PR patients who developed RA was significantly higher compared to the patients who did not. Proximal interphalangeal (PIP) joint involvement at baseline was also predictive towards the development of RA. Compared with the controls, differences in the frequency of single-nucleotide polymorphism (SNP) on padi4_104 [T(RA susceptible)-->C(RA non-susceptible)] and the presence of an RA susceptible homozygote of the PADI4 haplotype were detected in patients with PR whereas we could not find any further difference in PR patients who developed RA compared to PR patients who do not develop RA in PADI4. None of the subjects possessed the PTPN22 SNP (1858C-->T). Cox regression analysis revealed that anti-CCP antibodies as well as PIP involvement are the most relevant variables for the development of RA from PR. None of the PR patients with either HLA-DRB1*SE alleles (or the HLA-DRB1*0405 allele) or anti-CCP antibodies developed RA. CONCLUSIONS: Anti-CCP antibodies, in relation to HLA-DRB1*SE carriership, and PIP involvement are predictive for the development of RA from PR in the Japanese population.

Combinational effect of low-dose oral corticosteroid and mizoribine for ulcerative colitis in a patient with systemic sclerosis.

The combinational effect of oral corticosteroid and mizoribine for ulcerative colitis is presented in a patient with systemic sclerosis (SSc). A 64-year-old woman came to our clinic complaining of a 30-year history of Raynaud's phenomenon. She had past history of ulcerative colitis with the continued medication of mesalazine without success. She was presented with sclerodactyly and finger joint swelling. She also showed epigastric discomfort. Laboratory study showed positive anti-nuclear antibody and positive anti-centromere antibody. Histological examination showed mild perivascular mononuclear cell infiltrates in the whole dermis and increased deposition of collagen fibers in the middle and lower dermis. Chest X-ray film showed mild bibasilar pulmonary fibrosis. An upper gastrointestinal series study showed reflux esophagitis and atrophic gastritis. These findings led to the diagnosis of systemic sclerosis (limited type) complicated with ulcerative colitis. Treatment with oral corticosteroid (5 mg/day) and mizoribine (150 mg/day) in the morning was started. She showed remarkable improvement for sclerodactyly and lower intestinal bleeding stopped after 6 months. She is under the same treatment without exaggeration and adverse effect of the drug until now.

Psoriatic arthritis sine psoriasis.

In about 20% of patients with psoriatic arthritis (PsA) the rheumatological manifestations precede the onset of the cutaneous lesions. If there is a family history of psoriasis these patients are diagnosed as having psoriatic arthritis sine psoriasis. In the past, they were also classified among patients with undifferentiated spondyloarthritis. The clinical spectrum of PsA sine psoriasis is wide and identified by dactylitis and/or distal interphalangeal arthritis, HLA-Cw6, and a family history of psoriasis. The ClASiffication of Psoriatic ARthritis (CASPAR) criteria of PsA include PsA sine psoriasis.

Hypocomplementemic urticarial vasculitis with Jaccoud's arthropathy and valvular heart disease: case report and review of the literature.

We describe a female Japanese patient with concomitant hypocomplementemic urticarial vasculitis, Jaccoud's arthropathy and valvular heart disease. In 1996, she developed arthritis with swelling of both proximal interphalangeal joints and urticarial vasculitis on both arms that was resolved by administration of glucocorticoid (prednisolone 30 mg/day). Tests for antineutrophil cytoplasmic antibodies, antinuclear antibody and rheumatoid factor gave negative results. The findings of a skin biopsy examination were consistent with 'leukocytoclastic vasculitis'. During 10 years of observation, the patient manifested polyarthritis leading to progressive deformity of the joints of the hands and feet (without loss of cartilage or erosion of bone), persistent urticaria exacerbated by cold and accompanied by hypocomplementemia and progressive cardiac valvular disease with mitral valve regurgitation. There are only three reports described previously documenting five patients with this rare combination of manifestations.

A paraneoplastic case of palmar fasciitis and polyarthritis syndrome.

BACKGROUND: A 58-year-old woman presented with arthritis of the small joints of her hands and rapidly progressive joint contractures. She was wheelchair bound within 2 months of the onset of her symptoms. Physical examination revealed synovitis of the small joints of her hands and palmar fasciitis. The patient had been diagnosed with pancreatic carcinoma approximately 1 year before the presentation of her rheumatic symptoms, and had undergone radical pancreatico-duodenectomy. INVESTIGATIONS: Physical examination; routine laboratory work, including full blood count and measurement of erythrocyte sedimentation rate and C-reactive protein; serological tests for rheumatoid factor, antinuclear antibodies and extractable nuclear antibodies; measurement of serum tumor markers; radiological investigations, including X-rays of her hands and feet, whole-body CT-scans and radioisotope bone scan. DIAGNOSIS: The patient's rheumatic presentation was diagnosed as a paraneoplastic syndrome associated with pancreatic carcinoma. MANAGEMENT: The patient's condition was managed with corticosteroids and methotrexate. No residual tumor or evidence of metastatic disease have been detected in the 1.5 years since the initial presentation of her rheumatic symptoms.

Defining remission in psoriatic arthritis.

Driven in part by the introduction of highly effective agents, there has been growing interest in the overall therapeutic approach to patients with psoriatic arthritis (PsA). As with any form of arthritis, the goal of treatment for PsA would be to improve the outcome to the greatest extent possible. In other conditions, such as rheumatoid arthritis, recent discussions have centered on how best to define "remission." For patients with PsA, the heterogeneity among disease manifestations as well as the need to validate outcome measures make definition of remission challenging. In this paper we present a number of key principles and considerations critical to laying the groundwork for defining remission in PsA.

A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint inflammation in rheumatoid arthritis.

OBJECTIVE: To develop an ultrasonographic (US) synovitis scoring system suitable for evaluation of finger joint inflammation in patients with active rheumatoid arthritis (RA) and to compare semiquantitative US scoring with quantitative US measurements. METHODS: US was performed at the palmar and dorsal sides of the second through fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in 10 healthy subjects and in the clinically more affected hand in 46 RA patients. Ten patients additionally underwent magnetic resonance imaging (MRI). Synovitis was measured, standardized, and scored according to a semiquantitative method. The 2 methods (semiquantitative US scoring, quantitative US) were compared and statistical cutoffs were identified using receiver operating characteristic (ROC) curve analysis. MRI results were compared with semiquantitative US scoring and quantitative US results. The optimal US scoring method from 6 joint combinations was identified (ROC curve analysis). RESULTS: Synovitis was most frequently detected in the palmar proximal area (86% of affected joints). We found no significant differences between individual PIP joints or between individual MCP joints, indicating that all fingers within each of these joint groups should be treated equally for statistical calculations, although each joint group as a whole should be treated separately. The optimal cutoff point to distinguish between "health" and "pathology" was 0.6 mm both for MCP joints (sensitivity 94%, specificity 89%) and for PIP joints (sensitivity 90%, specificity 88%). There was no significant difference between semiquantitative US scores and quantitative US measurements. The best results for joint combinations were achieved using the "sum of 4 fingers" (second through fifth MCP and PIP joints) and "sum of 3 fingers" (second through fourth MCP and PIP joints) methods. Comparison of MRI results with semiquantitative US scores revealed high concordance. CONCLUSION: US evaluation of finger joint synovitis can be considerably simplified by focusing on the palmar side and by applying semiquantitative grading instead of quantitative measurements. For evaluation of treatment efficacy based on synovitis in RA patients, we recommend using the "sum of 3 fingers" method in longitudinal trials.

Manifestaciones clínicas articulares en la artritis reumatoide / Clinical articular manifestations in rheumatoid arthritis

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Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA).

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest.

The B lymphocyte in rheumatoid arthritis: recirculation of B lymphocytes between different joints and blood.

In order to search for further evidence for a pathogenetic role of recirculating, antigen-driven B cell clones in rheumatoid arthritis (RA) rearranged VH genes were analysed for clonal relationship and somatic mutations from synovial tissue and peripheral blood of a patient with RA undergoing synovectomy of several finger joints. DNA was prepared from the synovial tissue of two finger joints and blood. PCR for the different VH families was performed with one specific oligonucleotide for each VH family and a mixture of JH-specific oligonucleotides. The PCR products were separated on a high resolution acrylamide gel differentiating one base pair difference of length. Transfer of the products onto a nylon membrane and hybridization with an oligonucleotide specific for the FR3 region revealed a polyclonal representation of rearranged VH1, VH3, VH4 and VH5 genes. The VH6 family, which is encoded by a single germline gene, was represented by few distinct bands, with some bands of identical height for both joints and blood. DNA from these bands of interest was eluted, reamplified by PCR, cloned and sequenced. Sequence analysis of 27 independent bacterial colonies allowed distribution of the different VH genes to seven B cell clones (A-G). Members of clone A were found in both joints and blood, clones B and C in one joint and blood, clone D in both joints, and clones E, F and G only in one joint. The VH regions were somatically mutated with characteristic patterns for the different clones. In conclusion, our findings confirm the systemic character of RA, because they show that not only expansion and affinity maturation of B cells occur in synovial membranes but antigen-specific B cells recirculate between different joints and blood.