Renal involvement and followup of 130 patients with primary Sjögren's syndrome

OBJECTIVE: To identify the clinical characteristics, pathological changes, and outcome of patients with primary Sj?gren's syndrome (pSS). METHODS: All patients with pSS and renal involvement who were admitted to Ruijin Hospital from April 1993 to December 2006 were included. All the data of clinical features and pathological changes were retrospectively analyzed. Forty-one patients underwent renal biopsies. RESULTS Our study included 130 patients with pSS: 122 women and 8 men. Ages ranged from 16 to 68 years (mean 44.1 +/- 11.52). Ninety-five patients (73.1%) developed renal tubular acidosis (RTA); 91 were found to have distal RTA. Nine patients presented with hypokalemic paralysis. Four patients developed Fanconi syndrome and 3 were proved to have nephrogenic diabetes insipidus. Twenty-seven of 130 patients (20.8%) developed tubular proteinuria and 18/130 (13.8%) presented glomerular involvement. Thirty-five patients (27.7%) developed renal failure (serum creatinine > 115 micromol/l). Most patients (70.8%) had increased serum IgG levels. The incidence of chronic interstitial nephritis was 80.5% among all the biopsy materials. Immunofluorescent staining was negative in most renal tissue. Ninety-six patients were treated with corticosteroids and/or immunosuppressant. Eighteen recovered renal function. CONCLUSION: Patients with pSS commonly present with renal impairment, mainly from renal tubular dysfunction. The combination of corticosteroids and immunosuppressors significantly improves the renal function of patients with pSS. There is a correlation between hypergammaglobulinemia and distal RTA. The renal acidification capacity for patients with hypergammaglobulinemia. should be monitored.     

Platelet involvement in salivary gland inflammation in patients with primary Sjögren's syndrome

Summary Seventeen consecutive patients under evaluation for Sjögren's syndrome (SS) had a lower lip salivary gland biopsy performed. Using a monoclonal mouse immunoglobulin against human platelet glycoprotein Ib in an indirect immunoperoxidase technique, it was found that platelets accumulate intravascularly in the inflamed salivary glandular areas. Platelets were demonstrated in the interstitial tissue of inflammed salivary glands from two patients. Saliva from 17 consecutive patients with previously well-established primary SS and 11 healthy controls, and blood from 11 of the patients and all controls were then examined for platelets and the platelet-specific release product -thromboglobulin (-TG). Platelets were not demonstrated in saliva from patients or controls. -TG was detected in saliva from five patients (11–150 ng/ml), but in none of the controls. There were no correlations between saliva -TG levels and saliva secretion rates or plasma -TG levels. We conclude that platelet release of -TG into saliva in patients with primary SS most likely is a result of immunoinflammatory reactions in salivary glands. Measurement of -TG in saliva may be of value in the estimation of disease activity.     

Anxiety and depression in patients with primary Sjögren's syndrome

OBJECTIVE: To examine the degree of anxiety and depression and to assess well being and general symptoms in patients with primary Sj?gren's syndrome (SS). METHODS: A standardized questionnaire, the Hospital Anxiety and Depression Scale, was used to examine the degree of anxiety and depression in patients with primary SS (n = 62) and in age matched healthy female controls. The Gothenburg quality of life instrument (GQOL) was used to assess well being and general symptoms. Patients with rheumatoid arthritis (RA; n = 38) were used as patient controls. RESULTS: The patients with primary SS had significantly higher scoring rate for "possible" clinical anxiety (48%) and for "possible" clinical depression (32%) compared with reference groups (p<0.05). The physical and mental well being of the patients with primary SS were significantly reduced compared with controls. Furthermore, patients with primary SS complained more commonly of low mood, irritability, headache, gastrointestinal symptoms, and impaired concentration and memory than the patients with RA. CONCLUSION: The results indicate that patients with primary SS often have psychiatric symptoms and worse well being, which may affect their quality of life.     

Sjögren's syndrome complicated with autoimmune hepatitis and antiphospholipid antibody syndrome

A 56-year-old Japanese female simultaneously developed thrombocytopenia, sicca symptoms, and an elevation of transaminase. Antiphospholipid antibodies were detected in her serum. The presence of anti-SS-A antibodies in the serum and sialectasis, disclosed by sialography, suggested the presence of primary Sjogren's syndrome (SjS). The laboratory data and the biopsy of the liver showed compatible findings with autoimmune hepatitis (AIH). Thrombocytopenia and liver dysfunction satisfactorily responded to corticosteroid. To our knowledge, this is the first reported case of SjS with AIH and antiphospholipid antibody syndrome (APAS). Analysis of serum cytokine levels showed a predominance of Th0-Th1 response, which is not compatible with AIH, in this complicated autoimmune state.     

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.     

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.     

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.     

Autonomic and orthostatic dysfunction in primary Sjögren's syndrome

OBJECTIVE: Exocrine function always is and autonomic nervous function may be impaired in primary Sj?gren's syndrome (pSS). Since autonomic nervous signaling is a prerequisite for exocrine secretion we wanted to assess autonomic nervous function in pSS and relate it to diagnostic measures of exocrine function. METHODS: Autonomic nervous function was determined in 46 patients with pSS using the deep breathing test [expiration/inspiration (E/I) ratio], orthostatic test [acceleration index (AI), orthostatic systolic and diastolic blood pressure response (lSBP ratio and lDBP ratio)], and finger skin blood flow test [vasoconstrictory (VAC) score]. The results were corrected for age and expressed as z-scores by comparison with 3 control groups (E/I ratio and AI, n = 56; lSBP ratio and lDBP ratio, n = 238; and VAC score, n = 80). Exocrine gland function was determined in patients with pSS using the objective functional Schirmer-I test and rose-bengal staining (van Bijsterveld score) for the lacrimal glands and unstimulated whole sialometry for the salivary glands. RESULTS: The E/I ratio and orthostatic systolic and diastolic blood pressures were significantly decreased and the VAC score was significantly increased in patients with pSS compared to controls, indicating both parasympathetic and sympathetic dysfunction. Autonomic and exocrine function measures were found to associate poorly. CONCLUSION: Patients with pSS showed signs of both parasympathetic and sympathetic dysfunction. However, an association between cardiovascular autonomic and exocrine function in pSS was not detected.     

Sjögren's syndrome - not just Sicca: renal involvement in Sjögren's syndrome

OBJECTIVE: To present a case of severe interstitial nephritis with proteinuria in primary Sj?gren's syndrome (pSS) and review the literature regarding renal disease and its management in pSS, aiming to suggest recommendations for treatment. METHODS: A search of MEDLINE (PubMed) was performed for review articles and case reports using the MESH terms: Sj?gren syndrome; renal disease; interstitial nephritis (IN); glomerulonephritis (GN). RESULTS: We describe a rare case of pSS presenting with hypokalaemic tetraparesis and proteinuria due to severe IN, successfully treated with high-dose steroids and azathioprine. Reviewing the literature, we identified 180 reported cases of renal involvement in pSS (selected based on the European criteria for pSS), 89 of which underwent renal biopsies revealing IN in 49 cases, GN in 33 samples, and both IN and GN in seven. Eighteen studies reported treatment experience of renal disease in 32 pSS cases. Seventeen patients were treated with corticosteroids and cyclophosphamide, and 15 patients received only steroids with improvement in the majority of cases. CONCLUSION: The present case, as well as the limited number of reports in the literature, suggest that renal involvement, including IN, in pSS may improve with immunosuppressive therapy. Further studies are required to determine indications for and dosages of immunosuppressive treatment in patients with renal involvement of pSS.