Autoimmune disease aggregation in families with primary Sjögren's syndrome

OBJECTIVE: Diverse autoimmune diseases may coexist in the same individual and in families, implying a common etiology. We examined the aggregation of autoimmune diseases among first-degree relatives (FDR) of patients with primary Sj?gren's syndrome (pSS). METHODS: This was a population-based case-control family study in which 101 families of women classified as having pSS according to the revised American-European criteria and 124 families of matched controls without autoimmune disease were enrolled to investigate the presence of autoimmune diseases. We performed a genetic analysis that included familial correlation and recurrent risk ratios. RESULTS: In family cases, 38% had at least one FDR with an autoimmune disease, versus 22% in control families [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-3.9, p = 0.01]. An autoimmune disease was registered for 7.3% of 876 patients' FDR as compared with 3.85% of 857 controls' FDR (OR 1.97, 95% CI 1.28-3.03, p = 0.002). The most frequent autoimmune diseases registered among the pSS patients' FDR were autoimmune thyroid disease (AITD), systemic lupus erythematosus, and rheumatoid arthritis, which disclosed aggregation. The proband phenotype (i.e., pSS) was correlated with AITD, systemic sclerosis, and all autoimmune diseases when considered together as a trait. Maternal transmission of the autoimmunity trait was observed in cases but not in controls. CONCLUSION: Our results indicate that autoimmune diseases cluster within families of patients with pSS. This familial aggregation of autoimmune diseases adds further evidence that clinically different autoimmune phenotypes might share common susceptibility gene variants, which acting in epistatic pleitropy may represent risk factors for autoimmunity.     

Cutaneous mastocytosis in a patient with primary Sjögren's syndrome

Mast cells have been linked to rheumatoid arthritis (RA) and are essential to the pathogenesis of RA-like disease in a mouse model. We describe a 34-year-old woman who developed Sj?gren's syndrome concurrently with telangiectasia macularis eruptiva perstans (TMEP), a rare form of cutaneous mastocytosis. The patient had sicca symptoms with an abnormal minor salivary gland biopsy and decreased salivary flow, peripheral neuropathy, an 80 pound weight loss, and a macular erythematous rash that exhibited superficial perivascular mast cell infiltrates on biopsy of lesional skin. This case further underscores the link between mast cells and the development of autoimmunity.     

Sjögren's syndrome in the elderly

Sj?gren's syndrome is an immune exocrinopathy. This paper will deal with the primary Sjogren's syndrome non associated with another rheumatologic disease (polyarthritis or systemic lupus erythematosus). Its prevalence is claimed to increase with age. The main clinical manifestation is salivary and/or ocular dryness due to a lymphocytic infiltration of the salivary or lacrimal glands or both. However, sicca symptoms are very frequent in the elderly, most often iatrogenic. The problem, particularly in this population, is the diagnosis of Sj?gren's syndrome. There are yet no consensual criteria, the most used in the literature are the European criteria, published in 1993 and revised in 1996. Some tests, such as the Schirmer's test and non stimulated salivary flow, are not specific over 60 years. The results of other tests are discussed as the focus score on the lip salivary glands biopsy. The diagnosis of Sj?gren's syndrome should be envisaged in the elderly, when systemic manifestations are associated with sicca symptoms.     

Autoimmune cholangitis in patients with primary Sjögren's syndrome. A case report

Sj?gren's Syndrome is a very frequent autoimmune disease, characterised by exocrine gland involvement. Immunologic disorders are also responsive for extraglandular manifestations of the disease, mostly for the digestive involvement. We report a case of primary Sj?gren's syndrome with multiple extraglandular manifestations: vasculitis, cryoglobulinaemia, hepatic involvement and presumably neurologic involvement. The particularities of the case are the typical pattern of autoimmune cholangitis, hypogammaglobulinaemia, the absence of antinuclear antibodies and the association with vasculitis. To the best of our knowledge, this is the first case report of autoimmune cholangitis in Sj?gren's syndrome     

Multiple fibrotic lung nodules in a patient with primary Sjögren's syndrome

Evaluation of bilateral lung nodules noted on imaging poses a diagnostic challenge to clinicians as it can have many differentials from benign to malignant causes. It becomes especially critical to identify them right when there are underlying autoimmune conditions and risk factors for infection. However, a thorough investigation can lead to the recognition of rare associations as described below. We present here a 57-year-old woman who was admitted to the hospital with shortness of breath. Imaging with a computed tomography (CT) scan showed that she had 8 bilateral cystic pulmonary nodules with focal areas of ground-glass opacity and mediastinal lymphadenopathy. Fibrobronchoscopy and histopathological studies were done on the right middle lobe lung nodule demonstrated that the lung nodule was fibrotic with reactive inflammation but showed no malignant cells. Upon further detailed history and chart review, it was noted that the patient had a history of dry eyes leading to an autoimmune workup showing positive antinuclear antibodies (ANA), anti-Ro, and anti-La antibodies with no follow-up since then. This lead to the suspicion that these nodules could be related to underlying Sjögren's syndrome. Initial inpatient management with intravenous steroids showed significant improvement in her symptomatology. Hence, we present this rare association of lung nodules with Sjögren's syndrome and its management for awareness of this condition.     

Gluten sensitivity in patients with primary Sjögren's syndrome

Objective. To evaluate the rectal mucosal response to gluten as an indication of gluten sensitivity in patients with primary Sjögren's syndrome (pSS). Material and methods. Rectal challenges with wheat gluten were performed in 20 patients with pSS and 18 healthy control subjects. Fifteen hours after challenge the mucosal production of nitric oxide (NO) was measured. Results. Five patients with pSS had a significant increase in the luminal release of NO after the rectal gluten challenge, indicating gluten sensitivity. All were HLA-DQ2 and/or -DQ8-positive. Two of the patients with increased NO had antibodies against transglutaminase and a duodenal biopsy showed an absolutely flat mucosa consistent with coeliac disease in one of the patients. Before gluten challenge, 15 of the Sjögren's syndrome (SS) patients reported gastrointestinal symptoms, and 8 reported intolerance to various food products. No correlation was found between gluten sensitivity and self-reported food intolerance or gastrointestinal symptoms. Conclusions. Rectal mucosal inflammatory response after gluten challenge is often seen in patients with pSS, signifying gluten sensitivity. However, this reactivity is not necessarily linked to coeliac disease.     

Gluten sensitivity in patients with primary Sjögren's syndrome

OBJECTIVE: To evaluate the rectal mucosal response to gluten as an indication of gluten sensitivity in patients with primary Sj?gren's syndrome (pSS). MATERIAL AND METHODS: Rectal challenges with wheat gluten were performed in 20 patients with pSS and 18 healthy control subjects. Fifteen hours after challenge the mucosal production of nitric oxide (NO) was measured. RESULTS: Five patients with pSS had a significant increase in the luminal release of NO after the rectal gluten challenge, indicating gluten sensitivity. All were HLA-DQ2 and/or -DQ8-positive. Two of the patients with increased NO had antibodies against transglutaminase and a duodenal biopsy showed an absolutely flat mucosa consistent with coeliac disease in one of the patients. Before gluten challenge, 15 of the Sj?gren's syndrome (SS) patients reported gastrointestinal symptoms, and 8 reported intolerance to various food products. No correlation was found between gluten sensitivity and self-reported food intolerance or gastrointestinal symptoms. CONCLUSIONS: Rectal mucosal inflammatory response after gluten challenge is often seen in patients with pSS, signifying gluten sensitivity. However, this reactivity is not necessarily linked to coeliac disease.     

Psychological well-being in patients with primary Sjögren's syndrome

OBJECTIVES: To evaluate quality of life and psychological symptoms in patients with primary Sj?gren's syndrome and to compare this with patients with rheumatoid arthritis. METHODS: A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine the quality of life and psychological symptoms in patients with primary Sj?gren's syndrome (pSS; n = 34). Patients with rheumatoid arthritis (RA; n = 32) were used as patient controls. RESULTS: The total mean score +/- SD for PGWB was 84.9 +/- 16.2 in pSS patients and significantly lower (p = 0.001) than in RA patients (97.7 +/- 17.5). Patients with pSS had an increased propensity for depressed mood (p = 0.0009), and suffered from reduced well-being (p = 0.002) and impaired vitality (p = 0.003). CONCLUSION: The results suggest that patients with pSS have a reduced quality of life, a higher degree of distress and a lower sense of well-being than patients with RA.     

Pulmonary MALT lymphoma with amyloid production in a patient with primary Sjögren's syndrome

A 53-year-old woman was admitted to our hospital complaining of cough, low grade fever, chest pain and sicca symptoms. A chest radiograph showed an abnormal shadow and chest computed tomography revealed a tumor in left S6. She was diagnosed as Sj?gren's syndrome by sialography and histological findings of labial biopsy. The surgically resected tumor specimen showed proliferation of lymphoid cells with lymphoepithelial lesions, which were positive for CD20 and kappa light chain. Kappa light chain-positive amyloid was found within the tumor. The tumor showed rearranged kappa light chain genes. The diagnosis was pulmonary mucosa associated lymphoid tissue lymphoma with amyloid production.     

Monozygotic twins with primary Sjögren's syndrome

Sj?gren's syndrome (SS) is a chronic autoimmune disease mainly characterized by dry mouth and dry eyes due to an inflammatory process in the exocrine glands. We describe a pair of Caucasian monozygotic twin sisters and their mother, all having primary SS. The twins had very similar clinical presentation and almost identical serological data, and histological examination of lower labial salivary glands gave a focus score of 3 in both twins. We also present their family medical history, which shows aggregation of immunological disorders among family members, although the twins and their mother were the only individuals with primary SS.     

Sympathetic dysfunction in patients with primary Sjögren's syndrome

OBJECTIVE: To investigate autonomic nervous system function in patients with primary Sj?gren's syndrome (SS) and relate the findings to clinical variables. METHODS: Autonomic nervous system function was determined in 30 patients with primary SS using the finger skin blood flow test [vasoconstrictory (VAC) index], deep-breathing test [expiration/inspiration (E/I) ratio], and the tilt table (orthostatic) test [acceleration index (AI), brake index (BI), and orthostatic blood pressure]. The results were compared with age matched control materials (finger skin blood flow test, n = 80, and deep-breathing and tilt table tests, n = 56). RESULTS: The VAC index was found to be significantly increased and the E/I ratio significantly decreased in patients compared to controls, indicating both a sympathetic and a parasympathetic dysfunction. Further, the patients, especially the anti-SSA and anti-SSB antibody seropositives, were found to have an abnormal blood pressure reaction to tilt compared to controls. No correlations were found between autonomic nerve function variables measured and the clinical ophthalmologic or the oral tests, performed at the time of diagnosis. CONCLUSION: Patients with primary SS show signs of both sympathetic and parasympathetic dysfunction. Further, immunological mechanisms seem to influence blood pressure in patients with primary SS.     

Successful treatment of a patient with primary Sjögren's syndrome with Rituximab

We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome and distal renal tubular acidosis but without lymphoma to be treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion, remarkable improvement in xerostomia occurred, while serological findings and tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin 1 (AQP-1) expression in myoepithelial cells was very low before treatment and increased noticeably. Apical AQP-5 in acinus cells likewise increased following Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity before and following Rituximab. The improvement has been sustained and still is most gratifying 10 months after treatment. B-cell depletion may be effective treatment in Sjögren's syndrome. Likewise, it may now be possible to separate the immunologic phenomena in Sjögren's syndrome from the consequences of prolonged hyposalivation when studying the pathophysiology of xerostomia.     

Membraneous glomerulonephritis and non-Hodgkin's lymphoma in a patient with primary Sjögren's syndrome

The most common renal manifestation of Sj?gren's syndrome is tubulointerstitial nephritis, and glomerular disease is rare (3). A 62-year-old woman with primary Sj?gren's syndrome developed nephrotic syndrome. Kidney biopsy was consistent with membraneous glomerulonephritis. Steroid pulse therapy was not effective. Three months later she was diagnosed with non-Hodgkin's lymphoma of the tongue, and she was given CHOP therapy and radiation. Both the lymphoma and membraneous glomerulonephritis were resolved.     

Exacerbation of autoimmune neutropenia to agranulocytosis in association with severe autoimmune thrombocytopenia and hemolytic anemia in a patient with Sjögren's syndrome

A 73-year-old woman with Sj?gren's syndrome and autoimmune neutropenia (AIN) associated with large granular lymphocytosis of the polyclonal T cell type, demonstrated autoimmune thrombocytopenia (AIT) at diagnosis of sigmoid colon cancer. Ten months later, both AIN and AIT had exacerbated to agranulocytosis and severe thrombocytopenia below 10×10(9)/L, respectively. There were no dysplastic features of bone marrow hematopoietic cells. Furthermore, an in vitro assay of hematopoietic progenitors showed normal granuloid and erythroid colony formation. Although we serially treated her with prednisolone (oral), filgrastim, intravenous high-dose immunoglobulin infusion, cyclophosphamide (oral), danazol, cyclosporine A (oral), and rituximab, number of neutrophils and platelets elevated only temporarily. During the course of agranulocytosis and severe thrombocytopenia, the patient also developed autoimmune hemolytic anemia (AIHA). She died of pneumonia 5 months after the onset of agranulocytosis. This case is very unique and novel in terms of autoimmune phenomena simultaneously directed to granulocytes, platelets, and red blood cells under the background of Sj?gren's syndrome.     

Nailfold videocapillaroscopy in primary Sjögren's syndrome

Nailfold videocapillaroscopy was performed in 2 groups of subjects: 14 healthy volunteers (C) and 15 patients with primary Sj?gren's syndrome (PSS). This was a controlled clinical trial, matched by age and sex. The aims of this study were to evaluate (1) functional capillary density (number of capillaries with flowing red blood cells per mm(2), FCD); (2) capillary red blood cell velocity at rest (RBV), maximum capillary red blood cell velocity (RBV(max)) after 1 minute ischemia, and the time to reach it (TRBV(max)), taking into account the presence or absence of Raynaud's phenomenon (RP) in the analysis; (3) nailfold capillary morphology; and (4) afferent (AFD), apical (APD), and efferent (EFD) capillary diameters. The mean values obtained for controls versus patients, respectively, were (mean +/- SD): FCD (per mm(2)) 8.0 +/-1.6 and 10.1 +/-3.6; RBV (mm/s) 0.9 +/-0.4 and 0.7 +/-0.2; RBV(max) (mm/s) 1.7 +/-0.9 and 1.3 +/-0.3; TRBV(max) (s) 4.5 +/-0.8 and 5.8 +/-1.6 (p=0.02); and TRBV(max) (s) in patients with RP=6.7 +/-1.6 and without RP=5.6 +/-1.6 (p=0.52). The correlation between RBV and RBV(max) for each group, using the Pearson's coefficient, was significant only for the control group (p=0.007), estimated correlation coefficient = 0.68. Controls and patients showed, in the majority of fields examined, normal morphologic patterns of capillaries. The capillary diameters were AFD (mum) 10.8 +/-1.5 and 11.3 +/-1.8; APD (mum) 16.3 +/-2.4 and 16.8 +/-2.9; and EFD (mum) 12.3 +/-1.4 and 13.7 +/-1.9. These results indicate that these patients have longer time to reach RBV(max), suggesting an impairment of the reactive hyperemia response, which could correlate with clinical features of the disease, ie, abnormal macrovascular and microvascular reactivity.     

Precocious intima-media thickening in patients with primary Sjögren's syndrome

OBJECTIVE: Systemic lupus erythematosus and rheumatoid arthritis represent independent risk factors for atherosclerosis (ATS), although this may be confounded by continuous pharmacologic treatment. Primary Sj?gren's syndrome (SS) shares several features of these diseases and may therefore represent an interesting model for verifying the presence of accelerated ATS in the absence of pharmacologic interference. The present study therefore used this model to describe the presence of accelerated ATS in a group of young women. METHODS: Thirty-seven untreated white women with primary SS were evaluated clinically and serologically. Carotid and femoral artery intima-media thickness (IMT) was evaluated in the patients and in 35 age-matched healthy women who served as controls. RESULTS: The patients had a higher IMT than did the controls at both the carotid (mean +/- SD 0.82 +/- 0.24 mm versus 0.63 +/- 0.20 mm; P < or = 0.001) and the femoral (0.81 +/- 0.26 mm versus 0.67 +/- 0.23 mm; P < or = 0.019) levels, and had a higher prevalence of carotid intima-media thickening (49% versus 11% of controls; P < or = 0.001). The patient subset with high carotid IMT showed an increased prevalence of leukopenia and circulating anti-SSA antibodies; interestingly, the number of leukocytes was inversely correlated with the level of arterial IMT in patients with SS. Multivariate analysis demonstrated that anti-SSA antibodies were independent predictors of carotid artery thickening, while leukopenia was a predictor of both carotid and femoral artery thickening. CONCLUSION: Subclinical ATS was evident in about one-half of the patients with SS. Its association with some features typical of connective tissue diseases, such as the presence of anti-SSA and leukopenia, suggests that the immune dysregulation characterizing this autoimmune disorder may play a key role in inducing early ATS.