Coexistence of IgG4-related disease and ANCA-associated vasculitis: case report and review of the literature.

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that is characterized by storiform fibrosis, infiltration of IgG4-positive lymphocytes, obliterative phlebitis, and high IgG4 levels. Since IgG4-RD affects a wide variety of organs, a differential diagnosis must include multiple conditions. IgG4-RD is also believed to coexist with certain diseases. In recent years, case reports and case series describing the co-occurrence of IgG4-RD and ANCA-associated vasculitis (AAV) have been published. We intended to evaluate patients with IgG4-RD and AAV overlap in the literature using a case similar to one that was diagnosed and monitored in our department. We searched the databases of Web of Science, Scopus, and Google Scholar as well as PubMed with the keywords ANCA, IgG4, IgG4-RD, granulomatosis with polyangiitis, Wegener's granulomatosis, microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis, and Churg-Strauss syndrome. Cases and Case series addressing the coexistence of IgG4-RD and AAV have been selected. Comprehensive diagnostic criteria are used to diagnose IgG4-RD. The Chapel Hill Consensus Conference nomenclature criteria were used for the inclusion of AAV. Out of a total of 910 publications, 20 articles, including 65 cases, were found to be eligible. Forty-seven cases with IgG4-RD were evaluated as definitive (71.2%), 10 cases as probable (15.1%), and 9 cases as possible IgG4-RD (13.6%). 26 patients were diagnosed with GPA, 1 patient with localized GPA, 23 patients with MPA, and 4 patients with EGPA. The aorta, lacrimal tissue, pancreas, and retroperitoneum are the sites of IgG4-RD rather than AAV. AAV and IgG4-RD might coexist in the same patient. IgG4-RD is mainly associated with GPA.

Familial Mediterranean fever: the molecular pathways from stress exposure to attacks.

FMF is an autoinflammatory disease characterized by recurrent attacks and increased IL-1 synthesis owing to activation of the pyrin inflammasome. Although knowledge of the mechanisms leading to the activation of pyrin inflammasome is increasing, it is still unknown why the disease is characterized by attack. The emergence of FMF attacks after emotional stress and the induction of attacks with metaraminol in previous decades suggested that stress-induced sympathoadrenal system activation might play a role in inflammasome activation and triggering attacks. In this review, we will review the possible molecular mechanism of stress mediators on the inflammation pathway and inflammasome activation. Studies on stress mediators and their impact on inflammation pathways will provide a better understanding of stress-related exacerbation mechanisms in both autoinflammatory and autoimmune diseases. This review provides a new perspective on this subject and will contribute to new studies.

Lymphopenia as a risk factor for neurologic involvement and organ damage accrual in patients with systemic lupus erythematosus: A multi-center observational study.

OBJECTIVE: Detailed analysis of hematological manifestations (HM) in systemic lupus erythematosus (SLE) are limited and their clinical impact on disease remain obscure. Here, we aimed to decipher factors associated with different hematological abnormalities in SLE patients and to assess their impact on disease related outcomes. METHODS: A dataset (GIPT) originating from SLE patients of six European tertiary centers was assessed. Six-monthly visits of each patient for at least 2 years were registered. The association between hematologic manifestations (HM; per ACR-1997criteria) and clinical/serologic variables, as well as the impact of HM on disease related outcomes (damage, infection and hemorrhage) were explored. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI2K), the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and events for any infection and hemorrhage were recorded. Results were compared with a cross-sectional, well-characterized SLE dataset from Sweden. Descriptive statistics, the generalized estimating equations (GEE), general linear models (GLM), Cox regression models were applied. RESULTS: We monitored 1425 longitudinal visits in 286 SLE patients with HM (GIPT dataset: 88% female, 95% Caucasian, 68% dsDNA positive). Thrombocytopenia (regression coefficient [95% confidence interval] 1.86[1.1-3.13]) and neurologic involvement (ACR-8) (2.1[1.10-3.89]) were associated with lymphopenia (<1000/mm3); the latter was an independent predictor of organ damage accrual (1.68[1.2-2.62]). These associations were confirmed in an independent dataset of 1348 SLE patients (86% female, 93% Caucasian, 61% dsDNA positive) in Sweden.Severe lymphopenia (<500/mm3) and severe thrombocytopenia (<20 K/mm3) were associated with increased risk for infection (hazard ratio [95% confidence interval] 2.56[1.23-5.31]) and hemorrhage (4.38[2.10-11.1]), respectively, independent of the effect of other predictors. CONCLUSION: Lymphopenia in SLE is independently associated with neurologic involvement and organ damage accrual, and thus, may be considered as a marker of severe/progressive disease.

Risk factors for urolithiasis in patients with ankylosing spondylitis: a prospective case-control study.

It has been reported that renal stone formation increased in patients with ankylosing spondylitis (AS). However, its reason remains unclear. The aim of this study was to evaluate serially the possible risk factors for renal stone formation in AS patients. Two groups consisted of AS patients with renal stone (n = 30), AS patients without renal stone (n = 30), and 20 healthy controls (HC) were included to the study. Parathyroid hormone, calcium, magnesium, phosphorus and immunoglobulin A levels and 24 h urine were evaluated at baseline, and three times monthly. Serum calcium levels were higher in AS patients with urolithiasis than those without at baseline and third-month evaluation (baseline: 9.53 ± 0.3 vs 9.32 ± 0.3 mg/dl; p < 0.03; at third-month evaluation: 9.74 ± 0.2 vs 9.56 ± 0.3 mg/dl; p < 0.01). No significant differences were found between groups in terms of PTH and magnesium levels. In all evaluation times, although urinary calcium excretion was higher in AS patients with urolithiasis than in those without, it did not reach a statistical significance. IgA levels were significantly higher in renal stone sufferers than HC patients in all evaluation times.AS patients with urolithiasis also had high IgA levels compared with AS patients without renal stone at the second-month evaluation time (276 ± 102 vs 219 ± 104 mg/dl, p < 0.002). Increased levels of serum calcium and IgA levels as well as family history for urolithiasis may be an indicator of the development of urolithiasis in AS patients.

Retrospective evaluation of 22 patients with Takayasu's arteritis.

Takayasu's arteritis (TA) is a rare, idiopathic, inflammatory, granulomatous vasculitis that affects the aorta and its primary branches. Clinical features and the pattern of arterial involvement show differences in different regions of the world according to ethnic influences. Our aim in this retrospective study was to evaluate the demographic, clinic, laboratory, and angiographic findings of 22 patients with TA followed by our clinic and also compare our results with series from the literature. The hospital files of the 22 patients followed by our clinic between 1998 and 2009 were retrospectively evaluated. We also compared our results with the series from the literature that we were able to reach by US National Library of Medicine, National Institute of Health. Gender distribution, age at diagnosis, and type of aortic involvement were similar with the study from Turkey. Different clinical manifestations of Takayasu's arteritis have been described in different ethnic groups. We also want to underline the coincidence of TA and other rheumatic diseases such as sarcoidosis, SLE, RA, and psoriatic arthritis, different from other published series.

Disease-modifying antirheumatic drugs increase serum adiponectin levels in patients with rheumatoid arthritis.

BACKGROUND: Adiponectin is an adipocyte-derived adipokine with immunosuppressive and anti-inflammatory properties. It also decreases expression of adhesion molecules. In terms of its relationship with acute-phase reactants, there are conflicting results in patients with rheumatoid arthritis (RA). OBJECTIVES: The objectives of this study were to evaluate the levels of adiponectin in RA patients before and after the treatment with disease-modifying antirheumatic drugs (DMARDs) and to evaluate whether there is a correlation between adiponectin levels and disease activity and acute-phase-response reactants (APRRs). METHODS: Serum adiponectin levels, APRRs, total and high-density lipoprotein cholesterol (HDL-C), body mass index, and body fat mass were measured in 27 patients with RA before and after the treatment with DMARDs plus prednisolone. An inclusion criterion for RA patients was to be DMARD naive for at least 6 months or to have been newly diagnosed with RA. Twenty patients with osteoarthritis were included in this study as a disease control. RESULTS: No significant difference was found between RA and osteoarthritis group in terms of baseline adiponectin level. Mean adiponectin level and mean HDL-C level increased significantly compared with mean baseline level after the treatment with DMARDs plus prednisolone (10 [SD, 4.9] vs. 13.9 [SD, 8.7] µg/mL; P < 0.001; 56.8 [SD, 19] vs. 65 [SD, 18] mg/dL, P < 0.004, respectively). APRRs and the 28-joint-count disease activity score decreased significantly at the end of the 3 months of therapy. The adiponectin levels tended to be negatively correlated with acute-phase reactants and disease activity, although no changes were significant. There was a positive correlation between HDL-C and adiponectin levels at 3 month (r = 0.53, P < 0.001). No correlation was found between erythrocyte sedimentation rate and adiponectin levels both at baseline and at 3 months. CONCLUSION: Adiponectin levels can be modified by effective treatment of rheumatoid arthritis. This suggests that active inflammation may decrease serum adiponectin levels. In consideration of the antiatherogenic and anti-inflammatory features of adiponectin, increased adiponectin levels in patients with RA may result in a more favorable cardiovascular profile.

Combined thrombophilic factors increase the risk of recurrent thrombotic events in Behcet's disease.

This retrospective study aims to seek a relationship between the number of thrombotic events and presence of thrombophilic factors in Behcet's disease (BD). Any patient with a vascular problem evaluated for at least one thrombophilic factor was deemed eligible for the present study. Upon an evaluation of their medical records, 96 (23.9%) of the 402 patients diagnosed with BD were determined to have a history of thrombosis. Of these 96 patients, 72 (75%) had only one thrombotic attack, while the remaining 24 (25%) had two or more thrombotic attacks. Thrombophilic parameters were evaluated in only 36 of the 72 patients (50%) who had one thrombotic event (Group I) and in 18 of the 24 patients (75%) who had more than one thrombotic event (Group II). The patients with recurrent thrombotic events had a significantly higher incidence of combined thrombophilias than those patients with only one thrombotic event (8/18, 44%; 4/36, 11%; p < 0.01). The number of the patients free from thrombophilic risk factors was significantly higher in Group I than in Group II (21/36, 58%; 4/18, 22%; p < 0.02). Group II had an increased frequency of combined thrombophilic risk factors (OR 6.4; 95% CI 1.5-25.8) when compared to Group I. No significant differences were found between Groups I and II with respect to clinical features of BD. In conclusion, combined thrombophilias in patients with BD may have a role in the development of recurrent thrombotic events.

The development of primary cutaneous adenoid cystic carcinoma in a patient with ankylosing spondylitis treated with etanercept.

The tumor necrosis factor-alpha (TNF-alpha) inhibitors are widely used in the treatment of some autoimmune disorders with promising results. However, their safety has been questioned with multiple postmarketing reports of increased risk for malignancies. The case of a patient with ankylosing spondylitis who developed cutaneous adenoid cystic carcinoma after three years of treatment with anti-TNF-alpha therapy is discussed.

The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis.

The objective of this study was to investigate the frequency of sacroiliitis in familial Mediterranean fever (FMF) patients and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis. The study group consisted of 256 FMF patients (male 128, female 128, mean age 27.2 +/- 6.3 years). After evaluation of the medical records, 70 patients (27.4%) were determined to have one or more of musculoskeletal manifestations. Sacroiliitis was determined in 18 (32.7%) FMF patients. The frequency of sacroiliitis among all FMF patients was found to be 7%. HLA-B27 was 47% and 6.3% in FMF patients with and without sacroiliitis, respectively. The frequency of M694V mutations in FMF patients with sacroiliitis was 93.7%. Sacroiliitis may be seen more frequently in FMF patients than expected. HLA-B27 positivity and/or M694V mutation may play a role in the development of sacroiliitis and the severity of seronegative spondyloarthropathy.

Short-term course of chronic hepatitis B and C under treatment with etanercept associated with different disease modifying antirheumatic drugs without antiviral prophylaxis.

OBJECTIVE: To evaluate the short-term course of chronic hepatitis B and C under treatment with etanercept (ETN) associated with different disease modifying antirheumatic drugs (DMARD). METHODS: Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) receiving anti-tumor necrosis factor-a (TNF-a) were retrospectively reviewed for the presence of hepatitis B or C serology, liver function tests, liver biopsy findings, and the relevant outcomes in terms of viral load. RESULTS: We identified 5 relevant cases receiving ETN, 3 RA patients with chronic hepatitis C, another RA patient with dual infection by B and C, and one AS patient with hepatitis B. Four patients met the American College of Rheumatology criteria for RA. The patient with AS fulfilled the modified New York diagnostic criteria for AS. In Case 1, ETN was started after having discontinued a-interferon and ribavirin due to viral clearance of hepatitis C. These patients had not received prophylactic antiviral therapy while being treated with ETN. Viral replication increased in 2 patients to an insignificant level, remained negative in 2, and decreased in the remaining one. No significant rise in patients' liver transaminases could be determined during followup. CONCLUSION: We observed reactivation of hepatitis C virus infection in 2 of 4 patients while they were receiving ETN with DMARD without antiviral prophylaxis.