Muscular polyarteritis nodosa.

We present an unusual case of a 26-year-old man with muscular polyarteritis nodosa (PAN) with severe calf pain and gait disturbance. Magnetic resonance imaging of the lower limbs demonstrated highly increased signal intensity in both soleus muscles and the lateral head of the left gastrocnemius muscle. Biopsies of the soleus muscle showed acute necrotizing arteritis. The calf pain and limited range of motion of ankle dorsiflexion subsided from day 1 on administration of oral corticosteroid at high dosage and were completely resolved by 4 months. After tapering corticosteroid to 10 mg, symptoms recurred. A combined regimen of immunosuppressants was found to maintain symptomatic relief.Muscular PAN should be included in the differential diagnosis of a patient presenting with symptoms of acute or subacute calf pain. Although this muscular PAN was so far been benign, complete remission of the underlying process may be difficult to achieve.

Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis.

Associations between polymorphisms of the osteoprotegerin gene (OPG) and bone mineral density (BMD) have been studied by several research groups, but results are mixed. Accordingly, the authors performed a meta-analysis on studies of associations between OPG polymorphisms and BMD. Appropriate studies were identified using MEDLINE and by manual searching. A total of eight separate comparisons were considered in this meta-analysis. Individuals with the GG genotype of G1181C were found to have a significantly lower mean lumbar BMD than subjects with the CC genotype (WMDs -0.051 g/cm(2), 95% confidence interval -0.079--0.023, P < 0.001), and similar results were obtained in European and Asian populations. In contrast to G1181C, no association was found between the A163G and T950C polymorphisms and lumbar BMD. In terms of femoral neck BMD, the GG genotype of G1181C was associated with a significantly lower BMD than the CC genotype in Europeans but not in Asians. Total hip BMD was lower for the GG genotype of G1181C than for the CC or GC genotypes in Europeans. A difference in total hip BMD was found between the AG and GG genotypes of the A163G polymorphism by meta-analyses in Europeans, but no differences were found between the genotypes of the T950C polymorphism and total hip BMD in Europeans. Summarizing, the present study demonstrates that the OPG G1181C polymorphism is associated with lumbar BMD in Europeans and Asians, and with femoral neck and total hip BMD in Europeans only.

Meta-analysis of the combination of TNF inhibitors plus MTX compared to MTX monotherapy, and the adjusted indirect comparison of TNF inhibitors in patients suffering from active rheumatoid arthritis.

This present study was designed to examine (1) whether a combination therapy of TNF (tumor necrosis factor) blockers and methotrexate (MTX) is better than MTX monotherapy, and (2) if the TNF inhibitors such as etanercept, infliximab and adalimumab are all same for treating patients with active rheumatoid arthritis (RA). We performed meta-analysis of a combination therapy of TNF-blockers and MTX compared to MTX monotherapy and we performed adjusted indirect comparison of the TNF-blocking agents for their efficacy and toxicity. Three studies met the inclusion criteria for the analysis. Meta-analysis showed that the combination of MTX with anti-TNF inhibitors was more effective than MTX monotherapy and this indicated that combination therapy of anti-TNF inhibitors and MTX was comparable with MTX monotherapy in terms of withdrawal due to the side effects (RR: 1.05, 95% CI: 0.52-2.09, P = 0.86). The adjusted indirect comparison did not show any differences between infliximab and adalimumab. However, there was a significant difference for clinical efficacy and side effects between etanercept, adalimumab and infliximab. The RRs for achieving ACR20, ACR50 and ACR70 responses and withdrawal due to the side effect in the etanercept group were lower when compared with the adalimumab group. The RR for achieving an ACR20 response in the etanercept group was lower when compared with the infliximab group. The adjusted indirect comparison analysis suggests that the TNF-blocking agents all are not the same with respect to effectiveness and toxicity for the treatment of active RA.

Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis.

Tumor necrosis factor (TNF) antagonists are among the most effective therapies for rheumatoid arthritis (RA), yet not all patients show a response. Using meta-analysis, this present study was designed to investigate whether or not the TNF-alpha promoter -308 A/G polymorphism is associated with responsiveness to anti-TNF therapy in RA patients. We performed an exhaustive search for studies that examined the association of the TNF-alpha promoter -308 A/G polymorphism and responsiveness of anti-TNF therapy in RA using MEDLINE citations and manual review. Meta-analysis was performed for A allele carrier (genotypes A/A + A/G) between responders to anti-TNF therapy and a non-responder group in a random effects model. A total of 6 studies met the inclusion criteria. The number of patients in individual studies ranged from 33 to 123. There were 311 RA patients who were included in this meta-analysis. There was no heterogeneity between studies (I (2) = 0%, P = 0.42). The overall OR for the A allele carrier status was significantly decreased in the responder group (OR = 0.33, 95% confidence interval = 0.17-0.63, P = 0.0008). The frequency of the A allele carrier was 53/240 (22.1%) in responders and 32/71 (45.1%) in non-responders. Patients not responding to anti-TNF therapy showed an increased frequency of the A allele. The meta-analysis of the available data shows a significant association between the TNF-alpha promoter -308 A/G polymorphism and responsiveness to anti-TNF therapy, suggesting that the individuals with RA who carry the A allele have a poorer response to anti-TNF therapy than those with the G allele.

Prostaglandin E2 augments IL-10 signaling and function.

In inflamed joints of rheumatoid arthritis, PGE(2) is highly expressed, and IL-10 and IL-6 are also abundant. PGE(2) is a well-known activator of the cAMP signaling pathway, and there is functional cross-talk between cAMP signaling and the Jak-STAT signaling pathway. In this study, we evaluated the modulating effect of PGE(2) on STAT signaling and its biological function induced by IL-10 and IL-6, and elucidated its mechanism in THP-1 cells. STAT phosphorylation was determined by Western blot, and gene expression was analyzed using real-time PCR. Pretreatment with PGE(2) significantly augmented IL-10-induced STAT3 and STAT1 phosphorylation, as well as suppressors of cytokine signaling 3 (SOCS3) and IL-1R antagonist gene expression. In contrast, PGE(2) suppressed IL-6-induced phosphorylation of STAT3 and STAT1. These PGE(2)-induced modulating effects were largely reversed by actinomycin D. Pretreatment with dibutyryl cAMP augmented IL-10-induced, but did not change IL-6-induced STAT3 phosphorylation. Misoprostol, an EP2/3/4 agonist, and butaprost, an EP2 agonist, augmented IL-10-induced STAT3 phosphorylation and SOCS3 gene expression, but sulprostone, an EP1/3 agonist, had no effect. H89, a protein kinase A inhibitor, and LY294002, a PI3K inhibitor, diminished PGE(2)-mediated augmentation of IL-10-induced STAT3 phosphorylation. In this study, we found that PGE(2) selectively regulates cytokine signaling via increased intracellular cAMP levels and de novo gene expression, and these modulating effects may be mediated through EP2 or EP4 receptors. PGE(2) may modulate immune responses by alteration of cytokine signaling in THP-1 cells.

Acute arthritis of carpal bones secondary to metastatic gastric cancer.

A 39-year-old woman presented with acute onset of arthralgia in both wrists. Although her primary gastric cancer was in remission after previous treatment, carcinomatous arthritis was suggested by the osteolytic radiographic findings and refractoriness to nonsteroidal anti-inflammatory drugs, which was then confirmed by synovial fluid cytopathology. In view of the high incidence of gastric cancer in Korea, gastric cancer involving the carpal bones should be considered when we encounter a patient presenting with inflammatory peripheral joint arthritis, which might be the first sign of recurrence.

The biallelic variable number of tandem repeats of the tumor necrosis factor receptor 2 promoter in systemic lupus erythematosus.

The objective of this study was to investigate whether the variable number of tandem repeats (VNTR) of the tumor necrosis factor receptor 2 (TNFR2) promoter is associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical phenotypes. A biallelic VNTR within a 42-bp region in the TNFR2 gene promoter was determined by polymerase chain reaction in 88 SLE patients and 95 healthy control subjects. Clinical manifestations were analyzed in each patient and correlated with the genotypes. When the TNFR2 promoter VNTR was compared between Korean and Caucasian healthy controls with respect to allele frequencies, there was a significant difference (alleles 1 and 2: 39, 151 in Koreans vs 60, 138 in Caucasians, respectively; chi-squared test 4.38; 2 df; P=0.036). The genotype distribution of the TNFR2 promoter VNTR did not differ between SLE patients and control subjects (1.1, 1.2, and 2.2 genotypes 7, 14, 67 vs 5, 29, and 61 controls, respectively; chi-squared test 5.19; 2 df; P=0.061). According to the TNFR2 promoter genotypes in the lupus patients, clinically there was no significant difference in age at onset, anti-dsDNA titer, C4 level, systemic lupus erythematosus disease activity index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, or autoantibodies. However, the 1.1 genotype group showed the lowest C3 level and more frequent renal involvement than the 1.2 and 2.2 genotype groups. In conclusion, an ethnic difference in the TNFR2 promoter VNTR has been found and the biallelic VNTR of the TNFR2 promoter may be associated with clinical phenotypes in SLE.