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ID PMID Title PublicationDate abstract
21921151 Attending rounds: patient with hypokalemia and metabolic acidosis. 2011 Oct Hypokalemic paralysis represents a medical emergency requiring both rapid diagnosis and treatment. In this Attending Rounds a patient with hypokalemia and metabolic acidosis is presented to emphasize the role of routine laboratory studies in the assessment of such patients so that a correct diagnosis can be made and appropriate treatment can be initiated promptly.
21715359 Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the de 2011 Aug OBJECTIVE: The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker. METHODS: Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ(2) or Fisher's exact tests. RESULTS: At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001). CONCLUSIONS: The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.
21504661 Serum dehydroepiandrosterone sulphate levels and laboratory and clinical parameters indica 2011 Mar OBJECTIVES: The aim of this study was to compare serum dehydroepiandrosterone sulphate (DHEAS) levels and clinical and laboratory parameters reflecting expression of disease between female patients with primary Sjögren's syndrome (pSS) and age-matched healthy women and to examine in pSS patients the correlation of these variables with fatigue, well-being, and functioning. METHODS: Comparisons were made between 60 female pSS patients and 60 age-matched healthy women. We assessed questionnaire scores of general fatigue, depressed mood, mental wellbeing, and physical functioning, tear production (Schirmer I test), tender point counts, serum DHEAS level, haemoglobin concentration, erythrocyte sedimentation rate, and serum immunoglobulin G. RESULTS: As compared to healthy participants, patients had more fatigue and depressed mood, reduced well-being and functioning, more dryness and pain, lower serum DHEAS levels, and more expression of disease as reflected by laboratory assessments (p≤0.001). In pSS patients, fatigue, well-being, and functioning correlated with tender point counts, but not with the extent of dryness and also not with laboratory assessments including serum DHEAS levels. CONCLUSIONS: The high prevalence of fatigue and reduced functioning in pSS patients might suggest a mediating role of generalised autoimmune processes. In the present study, clinical observations and laboratory assessments are not correlated with persistent fatigue and reduced functioning. Our results suggest that treatment of fatigue, well-being, and functioning, should target other variables than those examined in this study, preferably psychological variables or perhaps specific immunologic parameters.
21841340 Tocilizumab improved both clinical and laboratory manifestations except for interleukin-18 2011 A patient with adult-onset Still's disease (AOSD) resistant to multiple drugs was treated in our hospital. Even biologics that block tumor necrosis factor (TNF) were ineffective. However, this patient responded quite well to tocilizumab, an interleukin (IL)-6 receptor blocker, suggesting that it is among the promising candidate drugs for multiple-drug resistant AOSD. Although the serum levels of most inflammatory markers such as C-reactive protein (CRP) and ferritin were reduced promptly by tocilizumab, that of IL-18 remained high. Thus, IL-18 is considered to have a further upstream position than IL-6 or to be at the same level as IL-6 in the inflammatory cascade of AOSD. This finding casts light on the pathogenesis of AOSD, and drugs that target IL-18 may prove beneficial in the treatment of this inflammatory disease.
21568728 Defining salivary biomarkers using mass spectrometry-based proteomics: a systematic review 2011 Jun Recent advancements in mass spectrometric proteomics provide a promising result in utilizing saliva to explore biomarkers for diagnostic purposes. However, the issues of specificity or redundancy of disease-associated salivary biomarkers have not been described. This systematic review was therefore aimed to define and summarize disease-related salivary biomarkers identified by mass spectrometry proteomics. Peer-reviewed articles published through July 2009 within three databases were reviewed. Out of 243 articles, 21 studies were selected in this systematic review with conditions including Sjögren's syndrome, squamous cell carcinoma, dental caries, diabetes, breast cancer, periodontitis, gastric cancer, systemic sclerosis, oral lichen planus, bleeding oral cavity, and graft-versus-host disease. The sample size ranged from 3-41 in both diseased and control subjects, with no consensus on sample collection protocol. One hundred eighty biomarkers were identified in total; 87 upregulated, 63 downregulated, and 30 varying based on disease. Except for Sjögren's syndrome, the majority of studies with the same disease produce inconsistent biomarkers. Larger sample size and standardization of sample collection/treatment protocol may improve future studies.
19882158 Interstitial inflammation in visceral organs is a pathologic feature of adult-onset Still' 2011 Jul The pathological features of adult-onset Still's disease remain unclear. An original case study of the histopathological changes in various organs of a patient with the disorder is presented. Interstitial inflammation was found in the heart, lung, liver, mucosa of total alimentary canal, and urinary bladder. Previous reports that involved the pathology of visceral organs are also reviewed.
21716006 FDG PET/CT in evaluation of pyrexia of unknown origin. 2011 Aug Pyrexia of unknown origin (PUO) is defined as fever above 38.5°C lasting for 3 weeks, of which at least 1 week has been spent in thorough investigation without a conclusive cause. Tuberculosis remains an important cause of PUO, particularly with the rising incidence of human immunodeficiency virus infection. It may strike virtually any organ in the body and can even mimic metastases especially in a known treated case of carcinoma. Bacterial infections, human immunodeficiency virus, hidden malignancy, sarcoidosis, and autoimmune disorders are some other important causes of PUO. Initial investigations include examination of blood, urine, stool, blood biochemistry, culture, etc. Typical radiologic investigations include chest radiography, computed tomography, and magnetic resonance imaging. Presented here is an atlas of cases where these investigations had been inconclusive but fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography demonstrated the site of pathology and directed histologic diagnosis.
22513175 Anti-M(3) peptide IgG from Sjögren's syndrome triggers apoptosis in A253 cells. 2012 Jan Primary Sjögren's syndrome (pSS) is an autoimmune disease that targets salivary and lachrymal glands, characterized by anti-cholinergic autoantibodies directed against the M(3) muscarinic acetylcholine receptor (mAChR). The aim of this work was to evaluate if cholinergic autoantibodies contained in IgG purified from Sjögren sera could trigger apoptosis of A253 cell line. We also determined if caspase-3 and matrix metalloproteinase-3 (MMP-3) are involved in the induction of A253 cell death. Our results demonstrated that anti-cholinergic autoantibodies stimulate apoptosis and inositol phosphate (InsP) accumulation accompanied by caspase-3 activation and MMP-3 production. All of these effects were blunted by atropine and J104794, indicating that M(3) mAChRs are impacted by the anti-cholinergic autoantibodies. The intracellular pathway leading to autoantibody-induced biological effects involves phospholipase C (PLC), calcium/calmodulin (CaM) and extracellular calcium as demonstrated by treatment with U-73122, W-7, verapamil, BAPTA and BAPTA-AM, all of which blocked the effects of the anti-cholinergic autoantibodies. In conclusion, anti-cholinergic autoantibodies in IgG purified from pSS patient's sera mediates apoptosis of the A253 cell line in an InsP, caspase-3 and MMP-3 dependent manner.
22355977 Adult onset still's disease with autoimmune haemolytic anaemia: two rarities in combinatio 2011 Dec Adult Onset Still's Disease with Autoimmune Haemolytic anaemia is a rare combination, difficult to diagnose but easy to manage. Literature to date reports only two cases. Hereby, we describe first of such a case from Pakistan. A 35 year old male, known case of Autoimmune Haemolytic Anaemia, presented with the complaints of high grade fever, fatigue, myalgia, skin rash and joint pain. After thorough investigation he was diagnosed as Adult Onset Still's Disease, according to the Yamaguchi criteria, and methylprednisolone (40 mg/day) was initiated. While his fever was relieved, dramatic improvement was seen with patient joint complaints and his anaemia was also under control. Prognosis is good with regular medication, and it is necessary to educate both patient and family, to enable them to have a complete understanding of the disease and its effects on their life.
22827855 Gene therapy using IL-27 ameliorates Sjögren's syndrome-like autoimmune exocrinopathy. 2012 Jul 24 INTRODUCTION: Sjögren's syndrome (SjS) is a systemic autoimmune disease characterized by decreased salivary and lacrimal gland secretions, resulting in severe dry mouth and dry eyes. Recent studies have suggested that TH17 cells and its signature cytokine IL-17 are involved in the underlying pathogenic mechanisms leading to destructive inflammation and autoimmunity. In the present study, we examined whether IL-27, a natural inhibitor of TH17 activity, could down-regulate or reverse SjS in C57BL/6.NOD-Aec1Aec2 mice, a model of primary-SjS. METHODS: Recombinant serotype 2 adeno-associated viral (AAV2) vectors expressing either IL-27 (rAAV2-IL27) or LacZ (rAAV2-LacZ) were injected into 6 or 14 week-old C57BL/6.NOD-Aec1Aec2 mice. Changes in IL-27, IL-17, and IL-10 cytokine levels in peripheral blood were determined by ELISAs, while flow cytometry analyses were used to quantify cytokine-positive splenocytes. Histological assessment of salivary glands, anti-nuclear autoantibody (ANA) staining, and stimulated saliva flow rates were used to profile SjS disease severity. RESULTS: Mice systemically treated with intravenous rAAV2-IL27 injections at either 6 or 14 weeks of age exhibited long-term elevated levels of serum IL-27 with concomitantly reduced levels of IL-17 compared with sera from mice injected with rAAV2-LacZ or saline out to 20 weeks post-inoculation. Most importantly, disease profiles revealed that rAAV2-IL27 treatment had little effect on lymphocytic focus (LF) scores, but resulted in structural changes in LF, lower titers of ANAs with changes in staining patterns, and a less severe clinical disease as determined by saliva flow rates. CONCLUSIONS: These data support the concept that IL-27, when provided exogenously, can induce a suppressive effect on SjS development and thus may be an effective therapeutic agent for regulating TH17 pro-inflammatory activity in autoimmune diseases where the TH17 system has been shown to play an important role in their pathogenesis.
22270347 A case of adult-onset Still's disease (AOSD)-like manifestations abruptly developing durin 2012 Sep A 68-year-old Japanese man was admitted to our hospital suffering from abrupt onset of high fever accompanied by arthralgia, myalgia, sore throat, macular eruption, and liver dysfunction. Six months before the onset of these manifestations, (18)F-fluoro-deoxy-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) had detected, unexpectedly, three calcified thyroid lesions without (18)F-FDG uptake. Two months before the onset of the present manifestations, ultrasonography-guided fine-needle aspiration had led to a diagnosis of papillary thyroid carcinoma (PTC). Soon after the occurrence of the rheumatic manifestations, a subsequent (18)F-FDG PET/CT scan showed not only the three thyroid lesions, the same as those in the previous scan, but also (18)F-FDG uptake in the thyroid lesion. A diagnosis of adult-onset Still's disease (AOSD)-like manifestations associated with PTC was made, and treatment with 40 mg/day of prednisolone (PSL) resolved the symptoms promptly. PSL was gradually tapered, without recurrence of the (AOSD)-like manifestations. Five months after the initiation of treatment with PSL, total thyroidectomy, followed by (131)I thyroid ablation treatment, was performed while the patient was on a PSL dose of 18 mg/day. Seven months after the thyroidectomy, the dose of PSL was tapered to 2 mg/day, and neither the AOSD-like manifestations nor the PTC relapsed. On confirming a diagnosis of AOSD, it may be necessary to consider the presence of an associated malignancy, including solid tumors such as PTC.
22068614 Lipid infiltration in the parotid glands: a clinical manifestation of metabolic syndrome. 2012 Feb BACKGROUND: The clinical features of lipid infiltration in the parotid glands (LIPG) have not been studied. Monitoring of atomic-bomb survivors for late effects of radiation exposure has provided the opportunity to review the clinical findings of LIPG. METHODS: A total of 992 atomic-bomb survivors in Nagasaki, Japan underwent lachrymal and salivary secretion tests and anthropometric, biochemical, and abdominal ultrasonographic examinations between 2002 and 2004. Among 465 subjects who had reduced tear and/or salivary excretion, 176 subjects took a salivary magnetic resonance imaging (MRI) examination. RESULTS: LIPG was detected in 53 of the 176 subjects who had salivary MRI. LIPG cases showed a preponderance of females and fatty liver compared with the subjects without LIPG. Age-and-sex-adjusted regression analysis revealed that body mass index (BMI), low-density lipoprotein cholesterol, triglycerides, hemoglobin A1c, and C-reactive protein were higher, whereas high-density lipoprotein cholesterol and adiponectin were lower, in the subjects with LIPG. Multivariate logistic regression analysis showed that BMI and fatty liver were mutually associated with LIPG independently from radiation dose. CONCLUSIONS: LIPG associated with BMI, fatty liver, and coronary risk factors was a clinical manifestation of metabolic syndrome.
23111856 Impaired functional status in primary Sjögren's syndrome. 2012 Nov OBJECTIVE: Several studies have demonstrated that primary Sjögren's syndrome (SS) is associated with reduced productivity; however, the impact of primary SS on daily function is not fully understood. This study aims to assess the physical function of primary SS patients and determine the relationship between the functional impairment experienced by primary SS patients and disease activity, patient-reported symptoms, and quality of life. METHODS: Sixty-nine primary SS patients from a specialist clinical service were assessed for their functional ability (Improved Health Assessment Questionnaire [HAQ]), dryness, pain, and overall primary SS-related symptom burden; systemic disease activity; levels of fatigue, daytime somnolence, anxiety, and depression symptoms; quality of life; and systemic inflammation (erythrocyte sedimentation rate, C-reactive protein [CRP] level). Data were compared to 69 healthy volunteers matched for age and sex. RESULTS: Primary SS patients experienced greater functional impairment than controls (Improved HAQ total scores: mean ± SD 24 ± 25 for primary SS versus 9 ± 19 for controls; P = 0.0002) across all domains of activity. In primary SS, functional impairment was significantly associated with physical fatigue (P < 0.0001, R(2) = 0.3), pain (P < 0.0001, R(2) = 0.3), depression (P < 0.0001, R(2) = 0.3), total symptom burden (P < 0.0001, R(2) = 0.3), systemic disease activity (P = 0.002, R(2) = 0.15), quality of life (P < 0.0001, R(2) = 0.3), dryness (P = 0.002, R(2) = 0.12), daytime somnolence (P = 0.02, R(2) = 0.08), anxiety score (P = 0.03, R(2) = 0.07), and CRP level (P = 0.04, R(2) = 0.06). Only CRP level is independently associated with functional impairment (β = 0.38, P = 0.025). CONCLUSION: Primary SS patients experience significant functional disability compared to age-matched healthy controls. Impaired function is associated with reduced quality of life and symptoms such as pain, fatigue, and depression, as well as disease activity, illustrating the importance of optimal management of all aspects of the disease.
22568275 Neuromyelitis optica--complication or comorbidity in primary Sjögren's syndrome? 2011 We report two cases of neuromyelitis optica (NMO) associated with primary Sjögren's syndrome (pSS), comparing the clinical and laboratory features of these predominant neurological patients and reporting their different outcome. NMO - a severe demyelinating disorder of the central nervous system - primarily affects the spinal cord and optic nerves, resulting in longitudinally extensive transverse myelitis and/or optic neuritis. Our patients had a late pSS diagnosis, due to the absence of sicca syndrome and specific Sjögren serology in the early stages of their diseases, when the neurological symptoms prevailed. Many NMO patients have an accompanying autoimmune disease, most commonly Sjögren syndrome and systemic lupus erythematosus or a related profile of non-organ-specific autoantibodies. Neurologic involvement occurs in approximately 20% of patients with pSS, usually preceding the diagnosis (in 75-80% of the cases) [1,2]. The frequency of both neurologic manifestations (revealing pSS) and negative autoimmune serology, especially in the event of CNS involvement, could explain why underlying pSS is misdiagnosed [3,4]. Screening for pSS should be systematically performed in cases of acute or chronic myelopathy and/or cranial nerve involvement, mainly because these patients have a severe outcome. The presence of the anti-aquaporin4 antibodies, besides anti-Ro and anti-La, in both reported cases, is intriguing and raises the question of whether we are facing two distinct diseases or the NMO is just complicating an unusually less expressive Sjögren's syndrome subtype.
22670185 Hemophagocytic syndrome secondary to adult-onset Still's disease but very similar to lymph 2012 Hemophagocytic syndrome (HPS) is a clinicopathologic entity characterized by increased proliferation and activation of benign macrophages with hemophagocytosis throughout the reticuloendothelial system. HPS may be primary, or secondary to malignancy, infections, auto-immune diseases and pharmacotherapy. In patients with adult-onset Still's disease (AOSD), HPS is a rare but life-threatening complication. Herein, we described a female patient with HPS secondary to AOSD. During the therapy, giant gastric ulcer similar to lymphoma developed after treatment with corticosteroid and nonsteroidal anti-inflammatory drugs.
20480165 Polyarteritis nodosa and Sjögren's syndrome: overlap syndrome. 2012 Dec Polyarteritis nodosa (PAN) belongs to a group of necrotic angiitis. During the illness, necrotic changes are found in small and middle dimensions arteries. Primary Sjögren's syndrome is a chronic, autoimmunological systematic illness of connective tissue with characteristic infiltration of lymphocytes and plasmatic cells in endocrine glands. Despite the fact that both disease entities are well known and primary Sjögren's syndrome is the second most commonly appearing autoimmunological sickness, the coexistence of both simultaneously is described very rarely. So far only three such cases have been presented. The case of 53-year-old woman is presented, who since 2003 has been hospitalized due to her ailments several times, at surgery, internal medicine, and rheumatology wards. In 2006, she was admitted to rheumatology clinic of Pomeranian Medical University (PAM) to be diagnosed both subjectively and objectively. Additional examinations proved that she had been suffering from overlapping PAN and primary Sjögren's syndrome (PSS). She fulfilled 5 out of 10 criteria for PAN and all criteria for PSS. For treatment the boluses of methyloprednisolon and cyclophosphamid every 4 weeks were used what resulted in curing the patient.
22423500 A case of refractory adult-onset Still's disease with high serum interleukin-18 levels tre 2012 Jan We report the case of a 31-year-old woman who developed adult-onset Still's disease (AOSD) with a high level of serum interleukin (IL)-18. Although treated with high dose steroids, she suffered repeated remissions and her condition deteriorated. After we administered oral cyclosporine A (CsA), 200 mg/d, monitoring C2 and trough levels, her symptoms improved significantly. We decreased the dose of methylprednisolone slowly without noting a relapse. The use of CsA accompanied by C2 and trough level monitoring should be considered for refractory AOSD patients with high levels of serum IL-18.
20740616 Tocilizumab in refractory adult Still's disease. 2011 Jan OBJECTIVE: There is an unmet need for the treatment of adult Still's disease (ASD), the pathogenesis of which may involve interleukin-6 (IL-6). We report the first series of patients with ASD treated with tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody. METHODS: All ASD patients treated with TCZ in France between July 2006 and July 2009 after failure to all available therapies were included in this cohort study. The main outcome measures were the European League Against Rheumatism (EULAR) improvement criteria and resolution of systemic symptoms at the 3- and 6-month followup periods. RESULTS: Fourteen patients with refractory ASD were included. At the start of TCZ treatment, despite a mean prednisone dosage of 23.3 mg/day, based on a 28-joint count, mean tender joints were 10.5, mean swollen joints were 7.9, and the mean Disease Activity Score in 28 joints was 5.61. Recurrent systemic involvement, including fever and rash, was present in 7 patients. TCZ was administered at 5-8 mg/kg every 2 or 4 weeks (8 mg/kg/month, n = 9). Eleven patients successfully completed the 6-month study; 1 withdrew due to necrotizing angiodermatitis, another due to chest pain at each TCZ infusion, and a third due to systemic flare. A good EULAR response was observed in 64% of patients (9 of 14) at 3 months and EULAR remission was observed in 57% (8 of 14) at 6 months. Systemic symptoms were resolved in 86% of patients (6 of 7). Moreover, corticosteroid dose was reduced by 56%. No other severe adverse effects occurred. CONCLUSION: TCZ is a promising new treatment for ASD.
23268916 [A case of a patient with rheumatoid vasculitis who was successfully transferred to home-c 2012 Dec We investigated a case of a patient with rheumatoid vasculitis who was successfully transferred to home-care services through regional cooperation. The patient was a 63-year-old woman with rheumatoid vasculitis complicated by small bowel necrosis, cerebral infarction, heart failure, scleritis, etc. In the present system, admission of such patients to acute or long-term care hospitals is difficult. It is also difficult to provide care at welfare facilities.Although symptom control and prognosis have improved owing to medical advances, the care system lags behind in terms of improvement. In the future, strengthening the seamless coordination between the medical and care systems is needed.
22171489 [A long-term case of Sjögren's syndrome with pulmonary multiple cystic lesions]. 2011 Nov A 68-year-old woman was admitted to our institution's respiratory section because of dyspnea on effort in January, 2007. She had previously received a diagnosis of Sjögren's syndrome because of dryness in her eyes in 1991. Chest radiography and chest CT in 2001 revealed diffuse multiple cystic lesions in both lungs which had progressed gradually for 6 years. Biopsy specimens obtained by video-assisted thoracoscopy showed lymphoid hyperplasia with follicular bronchiolitis and lymphocytic alveolitis. Narrowing of the small airways and obstructive lung disease with multiple bullae were observed and we suspected them to be related to peribronchiolar lymphocytic infiltration. These were lung involvements associated with Sjögren's syndrome. The patient's cystic lesions gradually worsened despite the administration of corticosteroid and cyclophosphamide. Cystic lesions in Sjögren's syndrome may be a treatment-resistant finding.