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ID PMID Title PublicationDate abstract
19545951 Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune dise 2009 Dec It has been known for more than 20 years that vitamin D exerts marked effects on immune and neural cells. These non-classical actions of vitamin D have recently gained a renewed attention since it has been shown that diminished levels of vitamin D induce immune-mediated symptoms in animal models of autoimmune diseases and is a risk factor for various brain diseases. For example, it has been demonstrated that vitamin D (i) modulates the production of several neurotrophins, (ii) up-regulates Interleukin-4 and (iii) inhibits the differentiation and survival of dendritic cells, resulting in impaired allo-reactive T cell activation. Not surprisingly, vitamin D has been found to be a strong candidate risk-modifying factor for Multiple Sclerosis (MS), the most prevalent neurological and inflammatory disease in the young adult population. Vitamin D is a seco-steroid hormone, produced photochemically in the animal epidermis. The action of ultraviolet light (UVB) on 7-dehydrocholesterol results in the production of pre-vitamin D which, after thermo-conversion and two separate hydroxylations, gives rise to the active 1,25-dihydroxyvitamin D. Vitamin D acts through two types of receptors: (i) the vitamin D receptor (VDR), a member of the steroid/thyroid hormone superfamily of transcription factors, and (ii) the MARRS (membrane associated, rapid response steroid binding) receptor, also known as Erp57/Grp58. In this article, we review some of the mechanisms that may underlie the role of vitamin D in various brain diseases. We then assess how vitamin D imbalance may lay the foundation for a range of adult disorders, including brain pathologies (Parkinson's disease, epilepsy, depression) and immune-mediated disorders (rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus or inflammatory bowel diseases). Multidisciplinary scientific collaborations are now required to fully appreciate the complex role of vitamin D in mammal metabolism.
20472930 IL10 GGC haplotype is positively and HLA-DQA1*05-DQB1*02 is negatively associated with rad 2010 Jul OBJECTIVE: In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and haplotypes in immune response genes and HLA class II alleles are associated with radiographic progression in patients with early UA. METHODS: Progression of radiographic damage was determined in white Dutch patients with early UA after 2 years of followup. Severe progression was defined as an increase in Sharp/van der Heijde Score > or = 5 points after 2 years of followup. The remainder was classified as mild. These SNP were genotyped by Taqman technology: tumor necrosis factor (TNF) -1031, -863, -857, -308, -238; lymphotoxin-alpha (LTA) +368, +252; interleukin 10 (IL10) -2849, -1082, -819; IL1A -889, IL1B -31, +3953; and IL1RN +2018. Carriage of SE alleles and HLA-DQA1*05-DQB1*02 haplotype was established. These markers were analyzed in relation to radiographic progression. RESULTS: Forty-eight out of 151 patients with early UA had severe radiographic progression. Severe radiographic progression was associated with an increased carrier frequency of SE alleles (OR 5.12, 95% CI 2.0-13.1, p < 0.001) and IL10 GGC haplotype (OR 2.8, 95% CI 1.4-5.8, p = 0.003). Mild radiographic progression was associated with the HLA-DQA1*05-DQB1*02 haplotype (OR 0.3, 95% CI, 0.1-0.8, p = 0.013) and with allele TNF -308A (OR 0.4, 95% CI, 0.2-0.9, p = 0.02). CONCLUSION: The SE and the IL10 GGC haplotype are associated with severe progression of radiographic damage, in contrast to the DQA1*05-DQB1*02 haplotype and the TNF -308A allele, which are associated with mild radiographic progression in early UA.
19411396 Effect of musculoskeletal pain on sexuality of male adolescents and adults with juvenile i 2009 Jun OBJECTIVE: To develop a questionnaire for the evaluation of sexuality of male patients with juvenile idiopathic arthritis (JIA). METHODS: A cohort of male patients with rheumatoid factor (RF)-negative polyarticular JIA according to the 2004 revised ILAR criteria and inactive disease was studied. The Health Assessment Questionnaire (HAQ) was applied to all patients. As a control group, 120 age-matched males of the same socioeconomic status were evaluated. A self-administered structured instrument, the Male Sexual Evaluation Questionnaire (MSEQ), was developed by multiprofessional experts to assess sexual life, including satisfaction, practice, and related functional aspects. RESULTS: Thirty-two male patients with RF-negative polyarticular JIA [mean age 20.8+/-3.8 yrs (range 16-26), mean disease duration 15.4+/-3.6 yrs (range 13-20)] were studied. Mean HAQ score was 1.25+/-0.67 (range 0.1-2.1). Masturbation was practiced similarly by patients and controls (87.5% vs 91%; p>0.999), although joint pain was observed in only 2 (7%) patients. Regular sexual intercourse (>or=once/week) was reported by 78% of patients and 62% of controls (p=0.86). Joint pain during intercourse was more frequent in patients (48% vs 3% in controls; p<0.001). The mean HAQ score was higher in the 12 patients with joint pain (hips=3, knees=5, and hips+knees=4) during intercourse compared to the 13 patients without joint pain (1.82+/-0.27 vs 1.43+/-0.32; p<0.05). Preserved desire and satisfaction were universal findings for all JIA patients and controls. CONCLUSION: The MSEQ was applicable to this cohort of male patients with RF-negative polyarticular JIA and showed that sexual life is preserved despite longterm disease, morbidity/functional dysfunction, and joint pain.
20214857 [Our experience with AES total ankle replacement]. 2010 Feb PURPOSE OF THE STUDY: The method of choice for the treatment of severe ankle arthritis is either arthrodesis or joint arthroplasty. Each has its advantages and disadvantages. Arthrodesis is the definitive therapy for severe ankle destruction and instability. Joint arthroplasty has an advantage in maintaining ankle mobility. However, its range of indications and its reliability and durability are more limited. The aim of this study is to present our experience with the AES prosthesis and draw attention to some drawbacks of this surgical treatment. MATERIAL: From September 2003 till June 2008, 51 AES ankle replacements were carried out in 51 patients (33 women and 18 men). Their average age at the time of surgery was 53.8 years. The youngest patient was 23 and the oldest was 88 years old. The indication for surgery was rheumatoid arthritis in 10, primary arthritis in six and post-traumatic ankle arthritis in 35 patients. METHODS: The patients were evaluated in 2008. The follow-up ranged from 4 months to 5 years. The patients were examined for ankle joint mobility and pain. Radiographs were assessed for potential signs of component loosening. RESULTS: The results presented here are short-term ones. The pre-operative AOFAS score of 33.7 increased to 82.3 points post-operatively. The range of motion was on average 20 degrees of plantar flexion and 5 to 10 degrees of dorsiflexion. Thirty- five patients (68.7 %) were free from pain, 11 (21.5 %) experienced slight pain while walking, and five (9.8 %) patients reported more intensive pain in the joint treated. Intra-operative complications included a fracture of the medial malleolus in two (3.9 %) patients subsequently treated with screw osteosynthesis. Post-operatively, seven (13.7 %) patients experienced slow healing of the operative wound. One patient had dislocation of the polyethylene liner at 3 months after surgery. Revision surgery was carried out in seven (13.7 %) patients. Two patients suffering from increasing pain around medial malleolus underwent revision and removal of ossifications. One patient developed necrosis of the talus at 1 year after surgery. She underwent extraction of the prosthesis and ankle arthrodesis with a retrograde locking nail inserted through the heel. A large bony effect arising due to extraction of the necrotic talus was repaired using bone graft. Three (5.8 %) patients developed post-operative instability of the ankle that required revision surgery. The radiographs of another three (5.8 %) patients showed bone cysts and signs of tibial component loosening. Of these, one patient underwent surgical revision with replacement of the polyethylene liner. Cavities were freed from granuloma induced by polyethylene wear debris, and filled with bone graft from the iliac crest. DISCUSSION: Total ankle replacement is a complicated surgical procedure that may results in various technical difficulties and complications. These are inversely proportional to the surgeon's experience, as also shown by literature data. CONCLUSIONS: The longevity of a total ankle replacement depends, much more than in other joint replacements, on an accurate implantation technique and correct indication.
20034551 Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora 2010 Feb 17 ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Sophora flavescens have long been used in Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids. AIM OF THE STUDY: This study was conducted to develop a plant-based anti-inflammatory agent focused on chronic inflammatory disorders. To accomplish this, the alkaloid-free prenylated flavonoid-enriched fraction (PFS) of rhizomes of Sophora flavescens was prepared and its in vitro and in vivo anti-inflammatory activities were then evaluated for the first time. MATERIALS AND METHODS: The inhibitory activity of PFS on PGE(2), NO, IL-6 and TNF-alpha production of lipopolysaccharide (LPS)-treated RAW 264.7 cells was measured. Additionally, adjuvant-induced arthritis in rats was used as an animal model of chronic inflammation to establish the in vivo anti-inflammatory effects of PFS. RESULT: PFS inhibited cyclooxygenase-2 (COX-2)-catalyzed PGE(2) and inducible nitric oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide (LPS)-treated RAW 264.7 cells at 10-50 microg/ml, and these effects primarily occurred via COX-2 inhibition and iNOS down-regulation, respectively. PFS also inhibited IL-6 and TNF-alpha production. When tested against adjuvant-induced arthritis in rats (chronic inflammation), PFS strongly inhibited arthritic inflammation when administered orally at doses of 10-100mg/kg/day. In addition, PFS administered orally potently inhibited acetic acid-induced writhing in mice. CONCLUSIONS: Our results suggest that PFS inhibits chronic inflammatory response and the inhibition of proinflammatory molecules such as COX-2, iNOS and IL-6 may contribute, at least in part, to the anti-inflammatory activity in vivo. Overall, these results indicate that PFS from Sophora flavescens may have the potential for treatment of chronic inflammatory disorders such as rheumatoid arthritis.
19004039 Fibromyalgia, systemic lupus erythematosus (SLE), and evaluation of SLE activity. 2009 Jan OBJECTIVE: To determine if fibromyalgia (FM) or fibromyalgia-ness (the tendency to respond to illness and psychosocial stress with fatigue, widespread pain, general increase in symptoms, and similar factors) is increased in patients with compared to those without systemic lupus erythematosus (SLE); to determine whether FM or fibromyalgia-ness biases the SLE Activity Questionnaire (SLAQ); and to determine if the SLAQ is overly sensitive to FM symptoms. METHODS: We developed a 16-item SLE Symptom Scale (SLESS) modeled on the SLAQ and used that scale to investigate the relation between SLE symptoms and fibromyalgia-ness in 23,321 patients with rheumatic disease. FM was diagnosed by survey FM criteria, and fibromyalgia-ness was measured using the Symptom Intensity (SI) Scale. As comparison groups, we combined patients with rheumatoid arthritis and noninflammatory rheumatic disorders into an "arthritis" group and also utilized a physician-diagnosed group of patients with FM. RESULTS: FM was identified in 22.1% of SLE and 17.0% of those with arthritis. The SI scale was minimally increased in SLE. The correlation between SLAQ and SLESS was 0.738. SLESS/SLAQ scale items (Raynaud's phenomenon, rash, fever, easy bruising, hair loss) were significantly more associated with SLE than FM, while the reverse was true for headache, abdominal pain, paresthesias/stroke, fatigue, cognitive problems, and muscle pain or weakness. There was no evidence of disproportionate symptom-reporting associated with fibromyalgia-ness. Self-reported SLE was associated with an increased prevalence of FM that was unconfirmed by physicians, compared to SLE confirmed by physicians. CONCLUSION: The prevalence of FM in SLE is minimally increased compared with its prevalence in patients with arthritis. Fibromyalgia-ness does not bias the SLESS and should not bias SLE assessments, including the SLAQ.
19825849 Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patien 2010 Mar OBJECTIVE: To evaluate whether treating patients with very early inflammatory polyarthritis (IP) with a 3-week course of intramuscular (IM) methylprednisolone acetate may postpone the need for disease-modifying antirheumatic drugs (DMARDs) and prevent IP from evolving into rheumatoid arthritis (RA). METHODS: Patients with very early IP (4-10 weeks' duration) were randomised to receive three injections of either 80 mg IM methylprednisolone acetate or placebo, given at weekly intervals. Assessments were monthly until 6 months after the first injection, and then concluded at 12 months. The primary outcome was the need to start DMARDs by the 6-month assessment. Secondary outcomes included disease activity and final clinical diagnosis by the rheumatologist at 12 months. RESULTS: Patients in the placebo group (76%) were more likely to need DMARDs during the first 6 months of the trial than patients in the glucocorticoid group (61%) (adjusted OR = 2.11, 95% CI 1.16 to 3.85, p = 0.015). Disease activity did not differ between the two groups at 12 months, probably because many patients in the placebo group started DMARDs early in the study. After 12 months, the arthritis had resolved without the need for DMARDs in 9.9% (11/111) of the patients in the placebo group and in 19.8% (22/111) in the glucocorticoid-treated group (adjusted OR = 0.42, 95% CI 0.18 to 0.99, p = 0.048). CONCLUSION: Treatment of patients with very early IP with IM methylprednisolone acetate appears to postpone the prescription of DMARDs and prevent one in 10 patients from progressing into RA.
19516134 Management of posttraumatic arthritis of the wrist with radiolunate fusion enhanced with a 2009 Jun Although in rheumatoid cases radiolunate fusion presents with satisfying results, in cases with posttraumatic carpal distortion, the variability of injury pattern can influence the type of fixation and the rate of bony union. In this case report, we present an alternative technique of radiolunate fusion for the management of posttraumatic arthritis, which combines the traditional procedure with a corticocancellous autograft, created from the dorsal side of the radius that slides over the bones to be fused. That procedure provides the best environment for the bones to heal and an additional stabilizing effect on the radiolunate construct, thus better preserving the normal intercarpal relationships and wrist height. Patient's clinical and radiological outcome was very satisfactory until the last follow-up.
20388015 The associations of circulating CD4+CD25high regulatory T cells and TGF-β with disease ac 2010 Oct OBJECTIVE: To determine circulating levels of CD4(+)CD25(high) regulatory T (Treg) cells and transforming growth factor-β (TGF-β) in patients with adult-onset Still's disease (AOSD) and to examine the associations with disease activity and clinical course of this disease. METHODS: The frequencies of circulating CD4(+)CD25(high) Treg cells in 52 active AOSD patients, 42 active systemic lupus erythematosus (SLE) patients, and 22 healthy controls (HCs) were determined using flow cytometry analysis. Levels of serum TGF-β and soluble interleukin-2 receptor (sIL-2R) were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly lower levels of circulating CD4(+)CD25(high) Treg cells and serum TGF-β were found in AOSD patients and SLE patients than those found in HCs. Levels of circulating CD4(+)CD25(high) Treg cells and TGF-β were inversely correlated with disease activity scores for AOSD patients and SLE patients. Circulating CD4(+)CD25(high) Treg cell frequencies were positively correlated with serum TGF-β levels for patients with both diseases. Levels of circulating CD4(+)CD25(high) Treg cells and TGF-β significantly increased, paralleling clinical remission and the decrease in levels of C-reactive protein and soluble interleukin-2 receptor after effective therapy in AOSD patients. AOSD patients with monocyclic course had significantly higher levels of circulating CD4(+)CD25(high) Treg cells and TGF-β compared to those with polycyclic and chronic articular course. CONCLUSION: Diminished levels of circulating CD4(+)CD25(high) Treg cells and TGF-β, and inverse correlation with disease activity in patients with AOSD and SLE might be involved in the pathogenesis of both diseases. Increased levels of circulating CD4(+)CD25(high) Treg cells or TGF-β might be associated with a favorable clinical course in AOSD patients.
20007286 Age-related T-cell cytokine profile parallels corneal disease severity in Sjogren's syndro 2010 Feb OBJECTIVES: IL-2ralpha (CD25)(-/-) mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice. METHODS: CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears. RESULTS: Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4(+) and CD8(+) T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-beta1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-gamma mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-gamma spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4(+) T cell infiltrating the cornea. CONCLUSIONS: Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.
19097826 Autoimmune autonomic ganglionopathy with Sjögren's syndrome: significance of ganglionic a 2009 Mar 12 Autoimmune autonomic ganglionopathy (AAG) is a disorder defined by antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. We report two patients with chronically progressing dysautonomia with Sjögren's syndrome (SS). The first case showed elevated titer of ganglionic acetylcholine receptor (AChR) antibody and improved with oral intake of prednisolone. In contrast, the second case showed no elevation of ganglionic AChR antibody titer and had poor response to immunomodulatory therapy. These two cases indicate that chronic AAG may be treatable by immunomodulatory therapy, and have relevance to SS.
20974510 Drug-induced granulomatous interstitial nephritis in a patient with ankylosing spondylitis 2010 Dec Tumor necrosis factor α (TNF-α) inhibitors are used in the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn disease, ankylosing spondylitis, and juvenile idiopathic arthritis. Use of TNF inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, psoriasis, and sarcoidosis/sarcoid-like granulomas). We report a case of interstitial granulomatous nephritis in a patient with ankylosing spondylitis after 18 months of treatment with adalimumab. Previously reported cases of sarcoid-like reactions secondary to the use of TNF-α inhibitors involved the liver, lung, lymph nodes, central nervous system, and skin. Granulomatous nephritis after adalimumab treatment has not been described. Close observation of patients undergoing treatment with TNF inhibitors for evolving signs and symptoms of autoimmunity is required. Organ involvement is unpredictable, which makes correct diagnosis and management extremely challenging.
19110071 Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of 2009 Feb 19 Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report that FA and FNA ameliorate the germ cell toxicity of MTX in mice.
21176260 [Adult-onset Still's disease and haemophagocytic syndrome]. 2010 A 49-year-old woman with a history of adult-onset Still's disease (AOSD) presented with fever, general malaise and a rash. Laboratory blood testing revealed an extremely high level of serum ferritin, essentially restricting the differential diagnosis to either haemophagocytic syndrome as a complication of AOSD, or a flare-up of the latter. Haemophagocytosis as a complication of AOSD was diagnosed in our patient. After treatment with prednisone, she fully recovered and the serum ferritin returned to a normal level. Haemophagocytic syndrome is a rare but potentially life-threatening complication of lymphoproliferative and autoimmune diseases, as well as of viral infections. It is characterised by high fever, hepatosplenomegaly, cytopenia and extremely high levels of serum ferritin. Activation of macrophages and histiocytes induces phagocytosis of erythrocytes in the bone marrow and other parts of the reticuloendothelial system. The fact that haemophagocytic syndrome and AOSD are often described together, and coincide with extremely elevated serum ferritin levels characteristic to both entities, suggests a related pathogenesis.
21044451 Use of methotrexate in patients with systemic lupus erythematosus and primary Sjögren's s 2010 Sep While there is still no convincing evidence that methotrexate is of benefit in primary Sjögren's syndrome, the SLE evidence on this rheumatology anchor drug is substantial. In fact, there are randomised controlled trials showing the benefit for methotrexate on overall SLE activity, reduction in glucocorticoid doses, and effects on lupus arthritis and lupus skin manifestations. In addition, methotrexate may be helpful in vasculitis, haematological manifestations, and perhaps kidney disease. Intrathecal methotrexate was successfully used in neuropsychiatric SLE. Taken together, using methotrexate in SLE is not only a common approach, but, at least in part, supported by evidence from clinical trials.
20533116 Successful treatment of primary Sjögren's syndrome complicated with primary biliary cirrh 2010 Mar A patient with primary Sjögren's syndrome complicated with primary biliary cirrhosis and lymphocytic interstitial pneumonia is presented. She was 38 years old and was admitted to our hospital for generalized pruritus, xerostomia, xerophthalmia, fatigue, and reticulonodular changes on her chest X-ray. With the findings of ground-glass attenuation and centrilobular nodules in high resolution computerized tomography, the diagnosis of lymphocytic interstitial pneumonia was made. Oral methylprednisolone 1 mg/kg/day and ursodeoxycholic acid 15 mg/kg/day were started. At the 6th month follow-up, she had no complaints, and pulmonary function tests and high resolution computerized tomography were normal. This is the first case of Sjögren's syndrome, primary biliary cirrhosis and lymphocytic interstitial pneumonia in the English literature.
20059370 Major salivary gland sonography in Sjögren's syndrome: diagnostic value of a novel ultras 2010 Mar OBJECTIVE: To validate ultrasonographic criteria for examination of the major salivary glands in the diagnosis of primary Sjögren's syndrome (SS). METHOD: A total of 209 consecutive patients with rheumatic diseases were selected according to the American-European Consensus Group (AECG) classification criteria for SS. One hundred and fifteen patients had primary SS, 44 had secondary SS, and 50 had sicca symptoms, and 36 subjects served as asymptomatic controls. This cohort was analysed for size, echogenicity, parenchymal inhomogeneity, focal changes, and posterior borders of the major salivary glands by ultrasonography (US). A novel US score for parenchymal inhomogeneity (0-12) was assigned and its diagnostic accuracy evaluated. RESULTS: Ultrasonographic abnormalities of salivary glands were detected in 107/115 (93.0%) patients with primary SS, in 12/44 (27.3%) with secondary SS, in 25/50 (50.0%) with sicca symptoms, and in 4/36 (11.1%) asymptomatic controls. Area under the receiver operating characteristic curve (AUC-ROC) for US inhomogeneity score was highly significant [0.96 +/- 0.01; 95% confidence interval (CI) 0.94-0.99, p < 0.000] for primary SS, with a sensitivity to specificity ratio of 91/83 for parotid and 93/90 for submandibular glands. Setting the cut-off US inhomogeneity score at 6 resulted in the best ratio of specificity (90.0%) to sensitivity (95.1%), with a positive predictive value of 72% and a negative predictive value of 96%. A US inhomogeneity score >or= 6 was closely correlated with positive biopsy (p < 0.000) and scintigraphy findings (p < 0.000). CONCLUSIONS: We demonstrate the high diagnostic value of a novel US score for parenchymal inhomogeneity (0-12) that could serve as a useful single US criterion in the evaluation of salivary gland involvement in primary SS.
19527988 Helicobacter pylori infection and dermatologic diseases. 2009 Sep Recent evidence suggests that Helicobacter pylori infections play a role in the pathogenesis of a variety of skin diseases. The best evidence for such a link is found for two diseases: chronic urticaria and immune thrombocytopenic purpura. Other diseases that have a purported, but not yet proven link to H. pylori are: cutaneous pruritus, Behçet's disease, nodular prurigo and lichen planus. Based on the current evidence for a relationship between H. pylori and chronic idiopathic thrombocytopenic purpura the European Helicobacter Study Group consensus 2007 recommended the eradication of Helicobacter pylori infection in affected patients. Lastly, single or few case reports have documented associations between Helicobacter pylori infection and rosacea, aphthous stomatitis, atopic dermatitis, alopecia areata, Schoenlein-Henoch purpura and Sjögren syndrome, but these are only descriptive in nature. Systematic studies examining the relationship between dermatologic entities and infection with H. pylori and documentation of the effect of H. pylori eradication are needed to further our understanding on this topic.
20833272 The meaning of anti-Ro and anti-La antibodies in primary Sjögren's syndrome. 2011 Jan Anti-SSA/Ro and anti-La/SSB are the hallmark antibodies in primary Sjögren's syndrome (pSS), being present in 60-70%. These antibodies have been associated with an earlier disease onset, glandular dysfunction and extraglandular manifestations as well as with other B cells activation markers. In addition an immunogenetic background is important for the autoantibody formation, having a stronger association with HLA-DR2 and HLA-DR3. Anti-Ro/SSA and anti-La/SSB antibodies are useful in the diagnosis of pSS and help to identify more "active" patients, however their association with response to treatment is unclear. Herein we review the evidence regarding the association of these antibodies with HLA background, demographic, clinical, glandular dysfunction, other serologic features and response to treatment in patients with pSS.
19949420 Effects of biological drug adalimumab on tumour necrosis factor-alpha-converting enzyme ac 2010 Mar Tumour necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE) is a membrane-bound metalloprotease and disintegrin. It is produced by a number of host cells and is known to shed and release cell-bound cytokines, particularly members of the TNF family. No investigations into the regulation of this enzyme by autoantibodies have been reported. In this study, we tested the hypothesis that anti-Ro/SSA autoantibodies, purified from IgG fractions of patients with primary Sjögren's syndrome, are capable to regulate TACE expression and activation in human salivary gland epithelial cells (SGEC). We also evaluated the potential physiological and therapeutic consequences of TNF-alpha blocking by the biological agent adalimumab, the first fully human (100% human peptide sequences) therapeutic anti-TNF-alpha antibody, on post-translational regulation of TACE. Taken together, our results show a dose-dependent increase in TACE expression in anti-Ro/SSA Abs-treated SGEC, followed by internalization, pro-domain shedding and activation of TACE protein. Adalimumab treatment brought TACE expression to levels than those observed in untreated SGEC. These findings, showing the presence of autoantibodies-dependent mechanisms by which TACE levels are regulated in human SGECs, may have implications in the context of current investigations on the pathological role of autoantibodies.