Severe chronic bronchiolitis as the presenting feature of primary Sjögren's syndrome

Sj?gren's syndrome is a frequent auto-immune disorder with a pulmonary location in almost 10% of the patients. Although bronchial involvement is very common, most patients only complain of cough and this involvement rarely results in severe symptoms or chronic respiratory failure are rarely observed. We describe here 5 patients with severe chronic bronchiolitis revealing primary Sj?gren's syndrome. The lung involvement resulted in chronic bronchorrhea, recurrent sinusitis, diffuse bronchiolar nodules with bronchiectasis on the CT scan, and a severe obstructive airway pattern on lung function tests. Improvement was obtained in 4 patients with combination of inhaled corticosteroids, inhaled long acting beta-agonists, and a low dose of erythromycin.     

Metabolic bone disease as a presenting manifestation of primary Sjögren's syndrome: Three cases and review of literature

Primary Sj?gren's syndrome (pSS) is a chronic autoimmune disease characterized by a progressive lymphocytic infiltration of the exocrine glands with varying degrees of systemic involvement. Chronic inflammation compromises the glands' function that leads to dry symptoms in the mouth/eyes. Renal involvement is a well recognized extraglandular manifestation of pSS. Metabolic bone disease (MBD), however, rarely occurs as the primary manifestation of a renal tubule disorder due to pSS. To the best of our knowledge there are only 6 reported cases of metabolic bone disease as the primary manifestation of pSS to date. Four of these had distal renal tubular acidosis (RTA), and 2 had a combined picture of distal and proximal tubular dysfunction. We herein present our experience of 3 cases who presented to us with a clinical picture suggestive of MBD. While investigating these patients, we found evidence of RTA, which was found to be secondary to pSS.     

Nephrocalcinosis: initial manifestation of primary Sjögren's syndrome

INTRODUCTION: Nephrocalcinosis is a rare complication of chronic tubulointerstitial nephritis observed in primary Sj?gren's syndrome. It can precede subjective sicca symptoms. OBSERVATION: We report the case of a 50-year-old woman who presented with a primary Sj?gren's syndrome. The first symptoms appeared 10-years-ago while she was affected with a nephrocalcinosis. CONCLUSION: Autoimmune investigations for Sj?gren's syndrome should be initiated in any patient presenting with nephrocalcinosis and distal renal tubular acidosis.     

Primary Sjögren's syndrome presenting as autonomic neuropathy: Case report

Abnormalities of the autonomic nervous system have been described in several connective tissue diseases, but the relation with primary Sjögren's syndrome is unclear. This report describes a patient with primary Sjögren's syndrome who presented with severe autonomic failure. The present knowledge on dysfunction of the autonomic nervous system in primary Sjögren's syndrome and other connective tissue diseases is shortly reviewed.     

Corneal melt as the initial presentation of primary Sjögren's syndrome

Corneal melting is a rare complication of S ogren's syndrome (SS). Previously reported cases of corneal ulceration occurred in patients with established SS, usually secondary to RA. We describe the first case of corneal ulceration with stromal melting as the initial presentation of primary SS. A 79-year-old man without prior sicca symptoms developed a large sterile corneal ulcer that required extensive treatment over several months with ocular lubricants, systemic immunosuppressives, and surgical repair. Evaluation for an underlying connective tissue disease revealed positive antinuclear antibodies (1:640 speckled) and anti-SSA antibody. A lip biopsy established the diagnosis of SS. Ulceration later occurred in the contralateral eye. Two years after the last corneal ulcer and no longer taking prednisone, the patient's ocular disease remained quiescent taking azathioprine 175 mg and hydroxychloroquine 400 mg daily. This case highlights the potential for primary SS to present with serious ocular complications despite lack of a priori sicca symptoms, as well as the importance of immunosuppressive therapy in the treatment of this complication.     

Primary Sjögren's syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest

We report a case of hypokalaemic, flaccid quadriparesis with sudden respiratory arrest in a 27-year-old Japanese woman in whom the discovery of distal renal tubular acidosis led to the diagnosis of primary Sjo¨gren’s syndrome (SS). Hypokalaemic periodic paralysis as the initial manifestation of primary SS is rare, but when it occurs it may precede symptoms of xerostomia and xerophthalmia. The diagnosis of primary SS should be considered in premenopausal women who present with rapidly progressive weakness and hypokalaemia, with or without the sicca complex. Received: 19 June 2000 / Accepted: 14 March 2001     

Sjögren's syndrome induced by estrogen therapy

OBJECTIVE: To describe a possible role for estrogen in the induction or acceleration of Sj?gren's syndrome (SS). METHOD: Two healthy young women who received estrogen-increasing therapy and then developed full-blown SS are described. The relationship between SS and estrogen therapy is discussed and the available literature reviewed. RESULTS: Both women developed SS 3 years after starting estrogen-increasing treatment. The syndrome was severe in the first patient, who was treated with a high dosage of estrogen; the disease was moderate in the second patient, who received a lower estrogen dosage. CONCLUSION: Estrogen may play a role in the pathogenesis of SS in some patients.     

Immunogenetics of Sjögren's syndrome

The etiology for SS remains unknown where multifactorial influences contribute to the pathogenesis of subsequent development of the disease. The genetic influence is also multifactorial and the data suggests a familial component indicative of autosomal-dominant genes as well as genetic contributions associated with class-I and class-II HLA alleles. Various auto-antibodies found with increased frequency in SS (anti-Ro and anti-La) were shown to be associated with HLA class-II alleles at the DQA1 and DQB1 loci that were also found to have in common specific amino acid residues (10). Ethnic groups have also been studied and show varying HLA associations with primary SS. Multiple ethnic groups, however, share a DQ allele supporting the idea that the majority of SS patients carry a common allele which may predispose to primary SS. In some cases, the HLA-DR antigen may be induced and cause to appear on epithelial cells where they present antigen to CD 4+ T-cells, which then go on to aid in the destruction of salivary gland epithelial cells specifically. The further elucidation of disease associations as well as possible immunogenetic pathogenic mechanisms may help to explain the causes for the development of various autoimmune diseases such as Sj?gren's Syndrome. This may eventually result in the ability to immunomodulate these abnormal immune responses. In so doing, an approach to treatment by genetic engineering may also be possible once a further understanding of the genetic influences and mechanisms in the causation of autoimmune disease is further elucidated.     

Immunopathology of Sjögren's syndrome

Sj?gren's syndrome is a chronic autoimmune disorder characterized by mononuclear cell infiltration around epithelial cells of exocrine glands. In recent years, several studies have tried to elucidate the components of the immunopathologic interaction in Sj?gren's syndrome as well as the function of these components. The majority of the mononuclear infiltrating cells are CD4 positive T lymphocytes (60-70%) whereas B cells constitute one fourth of the infiltrating cells. Macrophages and natural killer cells are poorly represented in the lesion. Epithelial cells of minor salivary glands of patients with Sj?gren's syndrome express several cytokines (IL-1 beta, IL-6, NO), protooncogenes (c-myc), autoantigens (Ro, La, Fodrin) and costimulatory molecules (B71, B72). The characteristic destruction of epithelial cells of Sj?gren's syndrome patients is probably due to activation of several apoptotic pathways since epithelial cells express different apoptosis related molecules such as Fas, FasL, Bax, while mononuclear cells express Perforin and Granzymes. Finally epithelial cells seem to exert a regenerative effort since they express trefoil proteins (pS2). The above mentioned properties give epithelial cells the leading role in the pathophysiology of the syndrome but the exact causative agent which drives the immune system towards an autoimmune reaction still remains obscure.     

Pathophysiology of Sjögren's syndrome

Sj?gren's syndrome (SS) is an excellent model for understanding the pathophysiology of autoimmune diseases and the relationships between autoimmunity and lymphoma. Recently discovered new elements probably play a role in the pathogenesis of this multifactorial disease: genetic predisposition remains largely unknown, but there isa link between certain HLA molecules and the type of autoantibodies secreted; sometimes called autoimmune epithelitis, SS is associated with abnormal apoptosis activity in epithelial cells leading to an abnormal accumulation of degradation products of the cytoskeleton proteins such as alpha- and beta-fordrine and also to the presentation of numerous antinuclear autoantigens to the immune system; significant polyclonal activation of B lymphocytes is probably mediated, at least in part, by a major increase in molecules of the TNF family (e.g. BlyS or BAFF) which play an important role in the production of autoantibodies; cytokine inhibition of healthy glands or anti-muscarin receptor antibodies and abnormal function of certain water pumps such as aquaporine could explain the perturbed function of the remaining healthy glands; permanent stimulation of autoreactive B cells favors oncogenic events and could lead to the development of B lymphoma with autoantibody activity. The links between these different elements are progressively falling into place. A better understanding of the pathophysiology of SS can be expected to lead to the development of much needed new therapeutic tools.     

Nephrocalcinosis: a rare presenting manifestation of primary Sjögren’s syndrome

Abstract

Renal involvement in primary Sjögren’s syndrome (pSS) is not uncommon. Autoimmune tubulointerstitial disorders and distal renal tubular acidosis (dRTA) account for majority of the cases of renal involvement. While dRTA may precede the onset of sicca syndrome in pSS, nephrocalcinosis as a presenting manifestation of pSS is rare. Here, to emphasize the need for initiating investigations for pSS in any patient presenting with nephrocalcinosis due to dRTA, we report a 21-year-old woman presenting with nephrocalcinosis long before pSS was objectively diagnosed.     

Nephrocalcinosis: a rare presenting manifestation of primary Sjögren’s syndrome

Renal involvement in primary Sjögren’s syndrome (pSS) is not uncommon. Autoimmune tubulointerstitial disorders and distal renal tubular acidosis (dRTA) account for majority of the cases of renal involvement. While dRTA may precede the onset of sicca syndrome in pSS, nephrocalcinosis as a presenting manifestation of pSS is rare. Here, to emphasize the need for initiating investigations for pSS in any patient presenting with nephrocalcinosis due to dRTA, we report a 21-year-old woman presenting with nephrocalcinosis long before pSS was objectively diagnosed.     

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.     

Pseudolymphoma of the liver associated with Sjögren's syndrome

Sj?gren's syndrome (SS) is known to be associated with pseudolymphoma in several organs. We describe a patient with SS complicated by a hepatic pseudolymphoma. Although the development of a hepatic pseudolymphoma is extremely rare, this disorder should be taken into consideration in the differential diagnosis of space occupying lesions related to autoimmune diseases such as SS.     

New concepts in the pathogenesis of Sjögren's syndrome

Sj?gren's syndrome (SS) is a rheumatic disease in which the salivary and lacrimal glands are the principal targets of a pathologic autoimmune reaction. SS is manifested by xerostemia and keratoconjunctivitis sicca and marked by persistent focal mononuclear cell infiltration within the salivary glands, often accompanied by glandular atrophy and fibrosis. A challenge is to clarify the roles of genetic backgrounds and environmental trigger. Advanced bioanalytic platforms have enabled identification of potential biomarkers with the intent to improve diagnosis, promote development of prognostic tools, and identify processes for therapeutic treatment. Such approaches allow a glimpse at the apparent complexity of SS.