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ID PMID Title PublicationDate abstract
11559930 Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrop 2001 Sep The underlying mechanisms of reactive macrophage activation syndromes (rMAS) are not understood in detail, and there is no specific treatment. This observational study was prompted by intravenous immunoglobulin (IVIG), dramatically halting two distinct rMAS episodes in the same patient. We evaluated the potential benefits of IVIG administration in treating fulminant rMAS and the usefulness of monitoring serum ferritin levels as an indication for emergency treatment with IVIG. Ten females and 10 males experiencing 22 episodes of rMAS were recruited on the basis of serum ferritin levels >or=10,000 microg/l and/or direct evidence of haemophagocytosis in 11 intensive care units in secondary and tertiary care hospitals in Switzerland between October 1993 and May 2000. In individual patients, serially measured ferritin was closely related to disease activity. Abrupt increases of up to >100,000 microg/l could be observed within hours. Rapid and profound beneficial effects of emergency IVIG treatment were seen in 12 episodes of rMAS accompanied by a prompt decrease of serum ferritin. IVIG produced partial or delayed improvements in 5 patients. No apparent effects were seen in 5 patients. IVIG was only successful if started early during the ferritin run-up to peak values. In conclusion, IVIG is effective in at least a subgroup of adult rMAS when started at the beginning of the macrophage activation process. The monitoring of serum ferritin levels might be helpful in detecting macrophage activation in order to commence IVIG treatment early enough.
10863329 [A case of subclinical Sjögren syndrome associated with high levels of serum IgM, thrombo 2000 Apr A 13-years-old girl was admitted to our hospital with high levels of serum IgM, thrombocytopenia and splenomegaly. Not only IgG but also IgM were found on the surface of platelets by flow-cytometry. Direct Coombs' test was positive, and IgG was also found on the surface of red blood cells. After splenectomy, platelet count was increased and serum IgM was decreased. The biopsy of salivary glands showed infiltration of lymphocytes around the ducts, and Shirmer test revealed slightly decreased secretion of tears, suggesting subclinical Sjögren syndrome.
10827414 Annular erythema of Sjögren's syndrome in a white woman. 2000 Jun Annular erythema of Sjögren's syndrome (AE-SS) is believed to be the Asian counterpart of subacute cutaneous lupus erythematosus (SCLE) in white persons. We report the second case of a white person with AE-SS, diagnosed by clinical and serologic findings, as well as the absence of histologic criteria for SCLE. The diagnosis of AE-SS was established by symptoms of xerophthalmia and xerostomia, as well as by examination of skin and salivary gland biopsy specimens. Evaluation showed the presence of anti-Ro(SS-A) and anti-La(SS-B) autoantibody, with the presence of anti-Ro(SS-A) antibody against the 60-kd, but not the 52-kd, epitope, a pattern frequently seen in both the Asians with AE-SS and in white patients with SCLE. Both skin and sicca symptoms were alleviated with combination antimalarial therapy, which included hydroxychloroquine and quinacrine. This case demonstrates that AE-SS can occur in white patients and that the autoantibody profile is similar to that described in Asians with this disease.
10446879 Malignant lymphoma in primary Sjögren's syndrome: a multicenter, retrospective, clinical 1999 Aug OBJECTIVE: Several reports have noted an increased incidence of malignant lymphoma in patients with Sjögren's syndrome (SS). Each case series has consisted of a limited number of patients with malignant non-Hodgkin's lymphoma (MNHL). In this report, we describe the disease characteristics, the clinical course, and the evolution in 33 patients followed up in 9 European medical centers. METHODS: The pool of MNHL patients from participating centers in a European Concerted Action on SS were analyzed. We report on the disease characteristics, its evolution, prognosis, current treatment practices, and survival. RESULTS: The MNHLs in this study were primarily situated in the marginal zone (48.5%), with the manifestations mostly extranodal (78.8%) and most often identified in the salivary glands (54.6%). Lymphadenopathy (65.6%), skin vasculitis (33.3%), peripheral nerve involvement (24.2%), low-grade fever (25.0%), anemia (48.1%), and lymphopenia (78.6%) were observed significantly more frequently than in the general SS population. Patients with high-to-intermediate grade lymphoma had significantly worse survival (P = 0.041). The presence of B symptoms (fever, night sweats, and weight loss) and a large tumor diameter (>7 cm) were additional independent risk factors for death. CONCLUSION: The novel observations of this study were those related to the type of MNHL, the survival prognosis, and the very high frequency of skin vasculitis, peripheral nerve involvement, anemia, and lymphopenia. Some of the previously reported results on extranodal manifestations were confirmed.
9785987 [A case of Sjögren's syndrome associated with advanced hemolytic anemia caused by worseni 1998 Aug We report a rate case of autoimmune cholangiopathy (AIC) and autoimmune hemolytic anemia (AIHA) in a patient with Sjögren's syndrome. A 59-year-old woman was admitted to Matsuyama Red Cross Hospital in September 1996 because of worsening liver dysfunction. She had suffered from keratoconjunctivitis sicca and xerostomia and had been diagnosed as having Sjögren's syndrome in February 1994, based on histological examination of the minor salivary gland and sialography, and positivity for SS-A and SS-B antibody. Liver dysfunction had first become evident in September 1995. Histological examination of a liver biopsy specimen obtained by laparoscopy showed that the structure of the hepatic lobules was mostly preserved, whereas most of the biliary ducts were transformed, being consistent with AIC. On admission, the patient was given 40 mg of prednisolone. Although the serum transaminase level decreased, jaundice persisted and hemolytic anemia developed. Further administration of 60 mg of prednisolone and plasmapheresis ameliorated the hemolytic anemia and cured the jaundice. We consider that an increased immunological response caused by the worsening AIC might have played a role in the development of AIHA in the present case.
10672880 Sicca syndrome and HTLV-I-associated myelopathy/tropical spastic paraparesis. 1999 Nov PURPOSE: The objective of this study is to describe the clinical and immunological aspects observed in patients with both human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and ocular dryness. METHODS: In 15 such patients, clinical and biological examinations completed with a biopsy of secondary salivary glands were performed to assess the etiology of the ocular dryness. RESULTS: Histological study of the biopsy specimens indicated that 80% of the patients had grade 3 or grade 4 lesions, according to the Chisholm scale. Polyclonal hypergammaglobulinemia was found in 60% of patients and lymphocytic alveolitis in 80%. Three patients had past medical history of chronic uveitis. CONCLUSIONS: All findings in these patients were compatible with Sjögren's syndrome; however, no immunological disorders characteristic of the syndrome were found. Tests for antinuclear antibodies and rheumatoid factor proved negative in all cases.
10410268 Lack of Fas and Fas-L mutations in patients with lymphoproliferative disorders associated 1999 May OBJECTIVE: Murine models (MRL/gld/gld mice) and recent evidence in humans suggest a possible role of Fas and Fas ligand (Fas-L) germline mutations in the pathogenesis of autoimmune-related lymphoproliferation, including adult cases. In this study, the presence of Fas and Fas-L germline mutations was investigated in a consecutive series of adult patients with lymphoproliferative disorders occurring in the context of Sjögren's syndrome (SS) and type II mixed cryoglobulinemia (MC). METHODS: 11 patients (8 primary SS and 3 type II MC; F/M: 10/1; mean age 64 yrs.) were investigated. All patients were suffering from atypical lymphoproliferative disorders or MALT lymphoproliferative lesions (mean duration 3.5 yrs.). Four patients later developed a malignant lymphoma. DNA from peripheral blood mononuclear cells from 11 patients and 10 controls was tested for germline mutations in the Fas gene (exons 4, 8 and 9) and Fas-L gene (exon 4) by the polymerase chain reaction-single strand conformation polymorphism (SSCP) method. RESULTS: All DNA samples from both patients and controls showed amplification of Fas and Fas-L specific fragments. Identical SSCP migration patterns were observed in all the cases, indicating the lack of mutations in the whole series. CONCLUSION: Although it cannot be excluded that Fas and Fas-L mutations might be present in exons different from those analyzed, our data do not support the hypothesis that germline mutations in these genes are responsible for a major subset of lymphoproliferative syndromes in adult patients with SS and type II MC. Additional studies would be worthwhile in SLE-related lymphoproliferation, which is, however, a subset of limited clinical relevance when considering all cases with autoimmune-related lymphoproliferation.
9779303 Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients wi 1998 Sep OBJECTIVE: To evaluate the role of Fas-Fas ligand system-mediated apoptosis in the sialoadenitis and interstitial nephritis of Sjögren's syndrome. METHODS: The expression of Fas antigen and Fas ligand in sialoadenitis and interstitial nephritis was examined by immunoperoxidase staining and the reverse transcriptase-polymerase reaction (RT-PCR) in patients with Sjögren's syndrome and in normal subjects. The appearance of DNA strand breaks during apoptosis was detected in the tissue by DNA nick end labeling methods. RESULTS: In patients with severe sialoadenitis, Fas antigen was strongly expressed on the ductal epithelial cells. In contrast, Fas antigen was not seen in the minor salivary glands of normal subjects nor in patients with mild sialoadenitis. In patients with massive mononuclear cell infiltration, some of the infiltrating cells showed the Fas ligand. In patients with interstitial nephritis associated with Sjögren's syndrome, Fas was expressed on the tubular epithelial cells, while such expression was not observed in control subjects without interstitial nephritis. In the patients with interstitial nephritis, some of the infiltrating cells showed the Fas ligand. Apoptotic changes were observed in the ductal epithelial cells, tubular epithelial cells and some infiltrating cells by DNA nick end labeling methods. mRNA for the Fas antigen and Fas ligand was found to be expressed in the labial salivary glands from all SS patients by RT-PCR. CONCLUSION: The findings of this study suggest that the Fas-Fas ligand system may play a role in the pathogenesis of the sialoadenitis and interstitial nephritis of Sjögren's syndrome.
11260029 Subacute cutaneous lupus erythematosus and life-threatening hypokalaemic tetraparesis: a r 2001 Mar We describe a patient with lesions of subacute cutaneous lupus erythematosus associated with high titres of anti-Ro and anti-La antibodies who developed a rapidly progressive flaccid tetraparesis due to profound hypokalaemia. After investigation she was found to have distal renal tubular acidosis (dRTA) without pathological evidence of lupus nephritis. It is likely that her dRTA was a manifestation of associated Sjögren's syndrome, which had been otherwise asymptomatic. This is the first report of such a complication in the dermatological literature.
11155716 [Pulmonary hypertension in a patient with primary Sjogren's syndrome, Hashimoto's disease, 2000 Oct A 53-year-old woman was admitted to our hospital in May 1999, because of progressive dyspnea and liver dysfunction. She had been receiving the replacement therapy of thyroid hormone for thirteen years and suffering from Raynaud's phenomenon for 9 years. She experienced exertional dyspnea and sicca symptom for 3 years, and had an episode of syncope 4 months before admission. An echocardiogram showed dilation of the right ventricle, tricuspid regurgitation and the estimated mean pressure of the pulmonary artery was higher than 120 mmHg. She was diagnosed as having severe pulmonary hypertension (PH) complicated with primary Sjogren's syndrome and primary biliary cirrhosis without portal hypertension She was treated with anticoagulant (warfarin) and oral prostagrandin I2 (prostacyclin). However, right heart failure and jaundice gradually progressed and she suddenly died in December 1999. At autopsy, the heart was enlarged with right ventricular hypertrophy. Small arteries and arterioles in the lung showed concentric intimal proliferation and severe plexogenic vascular disease. Deposition of immunoglobulin was not observed in the pulmonary arteries. Since the prognosis of PH is poor, it is important to analyze the etiology of the disease for the development of the treatment.
11138335 Hearing loss in Sjögren's syndrome patients. A comparative study. 2000 Nov OBJECTIVE: In an attempt to investigate the presence of hearing loss in primary Sjögren's syndrome (SS) patients and to determine the factors that might be involved in its pathogenesis, we prospectively evaluated 45 female SS patients with a mean age of 56.8 +/- 9.23 years and a mean disease duration of 8.32 +/- 5.39 years. METHODS: Forty patients underwent a complete ear-nose-throat physical examination and audiological evaluation with: (a) pure tone audiometry thresholds at octave frequencies of 250 to 8000 Hz; (b) impedance audiometry (tympanogram, static compliance, acoustic reflexes, reflex decay; and (c) speech audiometry and auditory brainstem response where indicated. In addition, glandular and extraglandular manifestations of the disease and drug therapy were recorded. Finally, all patients were tested for the presence of autoantibodies, including: rheumatoid factor, antinuclear antibodies, antibodies to Ro(SSA), La(SSB) nuclear antigens, anticardiolipin antibodies and antineutrophil cytoplasmatic antibodies. The results were compared with those of 40 healthy, age-matched women. RESULTS: We found sensorineural hearing loss (SNHL) in 9 patients (22.5%): 4 patients bilaterally, 4 patients in the left ear only and one in the right ear only. In all cases the site of the ear damage was cochlear. A correlation between SNHL and the duration of the disease was found, while there was no correlation with age, systemic manifestations of the disease or the presence of autoantibodies. In addition, no correlation was found between SNHL and drug therapy. CONCLUSION: Approximately one-fourth of our SS patients presented SNHL of cochlear origin affecting mainly the high frequencies. This prevalence was lower than that reported by other investigators. SNHL was associated only with disease duration. Further investigation is needed to attain a better understanding of the mechanism of inner ear involvement in SS patients.
9884547 Effective treatment of autoimmune diseases with extremely low dose cyclosporine. 1998 Feb The dosage of cyclosporine administered in the treatment of autoimmune diseases has generally been comparable to those required in cases of transplantation. Here we report on the successful treatment using an extremely low dose cyclosporine (1 mg/kg/day) on four patients, involving thrombocytopenia with systemic lupus erythematosus, and interstitial pneumonitis with Sjögren's syndrome, and discuss the optimal dose of cyclosporine for autoimmune-mediated manifestations.
10408493 Myocarditis and primary Sjögren's syndrome. 1999 Jul 10 We describe congestive heart failure caused by autoimmune myocarditis in a patient with primary Sjögren's syndrome. Only after corticosteroids were given did the symptoms and laboratory abnormalities disappear.
10072487 Fas ligand-mediated exocrinopathy resembling Sjögren's syndrome in mice transgenic for IL 1999 Mar 1 Although IL-10 has been implicated in the pathogenesis of several autoimmune diseases, the mechanisms by which this cytokine mediates inflammatory lesions remain to be elucidated. Exocrine gland destruction is an important early step in the development of Sjögren's syndrome. To better understand the role of IL-10 in Sjögren's syndrome, we made transgenic mice in which the mouse IL-10 gene was regulated by the human salivary amylase promoter. Transgenic expression of IL-10 induced apoptosis of glandular tissue destruction and lymphocyte infiltration consisting primarily of Fas-ligand (FasL)+ CD4+ T cells, as well as in vitro up-regulation of FasL expression on T cells. These data suggest that overexpression of IL-10 in the glands and their subsequent Fas/FasL-mediated bystander tissue destruction is a causal factor in the development of this disease.
9433413 Primary Sjögren's syndrome associated with hyaline-vascular type of Castleman's disease a 1997 We describe a case of primary Sjögren's syndrome complicated by hyaline-vascular type of Castleman's disease and autoimmune idiopathic thrombocytopenia. This type of Castleman's disease was diagnosed by biopsy of a right axillary lymph node 7 years after the onset of Sjögren's syndrome. The specimen showed small hyaline-vascular lymphoid follicles and interfollicular capillary proliferation. Serum IL-6 was slightly increased, but systemic manifestations, such as fever or weight loss, were not present. Hyaline-vascular type of Castleman's disease should be considered a lymphoproliferative disorder associated with Sjögren's syndrome.
9385358 Disturbances of autonomic nervous function in primary Sjögren's syndrome. 1997 Autonomic nervous function was evaluated by deep breathing [expiration/inspiration (E/I) ratio] and tilt table tests [acceleration (AI) and brake indices (BI)] in 19 patients with primary Sjögren's syndrome (pSS) and in 56 age matched controls. The E/I-ratio and systolic blood pressure (at rest, 1, and 8 min after tilt) were found to be significantly reduced (p < 0.001, p < 0.05, p < 0.01, p < 0.01 respectively) in patients with pSS whereas neither AI, BI nor diastolic blood pressure did differ significantly between patients and controls (NS). The van Bijsterveld's score correlated negatively with the AI (r = -0.77, p< 0.001) as well as the BI (r = -0.60, p < 0.01). No correlations were found between the 3 autonomic nerve function parameters (E/I-ratio, AI, BI) and unstimulated whole sialometry or salivary gland scintigraphy. We conclude that autonomic disturbances, mainly affecting the parasympathetic nerves are associated with pSS.
11302870 Polymorphisms of the mannose binding lectin gene in patients with Sjögren's syndrome. 2001 May OBJECTIVE: To investigate polymorphisms of both codon 54 allele and promoter variants of the mannose binding lectin (MBL) gene in patients with primary Sjögren's syndrome (SS). METHODS: Polymorphisms of codon 54 allele and promoter variants of the MBL gene in 104 patients with SS and 143 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism and allele specific polymerase chain reaction respectively. RESULTS: The allele frequency of the wild type of MBL codon 54 was significantly higher in patients with SS than in controls (0.836 v 0.741; p=0.011), and the frequency of the homozygous wild type of MBL codon 54 was significantly higher in patients with SS than in controls (0.692 v 0.539; p=0.024). On the other hand, the allele frequencies of the MBL promoter gene did not differ between patients and controls (chi(2)=4.01, df=2, p=0.135). CONCLUSION: The polymorphism of the MBL gene may be one of the genetic factors that determines susceptibility to SS.
10870523 Quantitation of rat lacrimal secretion: a novel sandwich ELISA with high sensitivity. 2000 May Modulation of lacrimal acinar cell tear secretion may involve multiple factors acting both in subtle and pronounced ways. Functional screens of recombinant protein products arising from gene array technologies, or protein fractions derived from lacrimal conditioned media or extracellular matrix, will require a highly sensitive assay capable of monitoring tear protein secretion by small replicate cultures. To improve significantly on current methods, a rat- and mouse-specific sandwich ELISA was developed. For this purpose, chickens and rabbits were immunized with serum-free secretion media from carbachol and VIP-stimulated rat lacrimal acinar cell cultures. Immune sera were characterized by ELISA, Western blotting and immunohistochemistry, and subsequently optimized for use in a sandwich ELISA. Both antisera detected a wide range of different rat tear proteins, and immunostained only the secretory granule-rich juxtalumenal region in sections of rat lacrimal gland. Chicken, but not rabbit, antiserum cross-reacted with rabbit and human tears. In sandwich ELISA, capture with purified chicken immunoglobulin fraction and detection with rabbit antiserum detected as little as 1 ng ml-1 tear protein in 10,000-fold diluted rat secretion medium--a level of sensitivity 8000 times greater than the rat tear peroxidase assay. Such specificity and sensitivity greatly reduce the quantity of media needed for assay, and makes feasible functional screens for scarce factors that may influence lacrimal secretory processes, and in turn possibly play a role in human lacrimal insufficiency syndromes.
10326815 Prognostic value of the pilocarpine test to identify patients who may obtain long-term rel 1999 May BACKGROUND: Xerostomia (dry mouth) is a clinical symptom due to a number of factors, including Sjögren syndrome and radiation treatment to the head and neck region. It has been reported that acupuncture increases the salivary flow rate (SFR) in healthy subjects and in patients with xerostomia. A prognostic tool that would allow the care provider to identify patients who may respond to acupuncture treatment will aid in early intervention and thus lead to normalized SFR or relief of symptoms. OBJECTIVES: To determine the prognostic value of a test using pilocarpine chloride to identify those patients with xerostomia who may achieve a long-term increase in SFR in response to acupuncture. DESIGN: Cohort clinical study of 10 months' duration. SETTING: School of dentistry in a large, urban, research institute. PATIENTS: Thirty-two consecutive patients with xerostomia due to radiation treatment (n = 21) or Sjögren syndrome (n=11). INTERVENTION: Salivary flow rates for unstimulated whole saliva and paraffin-chewing stimulated whole saliva were measured before and after the administration of individualized doses of pilocarpine. All patients were then given 24 acupuncture treatments and followed up at 1 and 6 months. The effects of acupuncture treatment on SFR were recorded and response compared with the results of the pilocarpine test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive value of the pilocarpine test based on changes in SFR, defined as a 20% increase or greater, following acupuncture treatment, compared with response to the pilocarpine test. RESULTS: At the 1-month follow-up, 18 (72%) of 25 patients with a positive pilocarpine test result had defined significant changes in SFR; 4 (67%) of 6 patients with a negative pilocarpine test result had an unchanged SFR. At this point, the sensitivity of the pilocarpine test was 0.90 (95% confidence interval [CI], 0.68-0.99) and the specificity was 0.36 (95% CI, 0.11-0.69). The positive predictive value was 0.72 (95% CI, 0.51-0.88), and the negative predictive value was 0.67 (95% CI, 0.22-0.96). At the 6-month follow-up, 17 (74%) of 23 patients with a positive pilocarpine test result had defined significant changes in SFR; 3 (60%) of 5 patients with a negative pilocarpine test result had an unchanged SFR. At this point, the sensitivity of the pilocarpine test was 0.89 (95% CI, 0.67-0.99), and the specificity was 0.33 (95% CI, 0.07-0.70). The positive predictive value was 0.74 (95% CI, 0.52-0.90), and the negative predictive value was 0.60 (95% CI, 0.15-0.95). CONCLUSION: The pilocarpine test was found to have a high sensitivity and good positive predictive value in identifying patients who may respond to acupuncture for the treatment of xerostomia.
9866230 [MALT lymphoma of the parotid gland associated with Sjögren syndrome. A case report and r 1998 Oct Sjögren syndrome (SS) is a chronic inflammatory process involving the exocrine glands. Its association with the development of lymphomas is well documented, and this risk has estimated to be 44 times that of the general population. A MALT lymphoma of the parotid gland in a patient with Sjögren syndrome is reported. We review the literature and comment the clinical and histopathological features of these tumors.