Bilateral striopallidodentate calcinosis associated with Sjögren's syndrome and IgDλ monoclonal gammopathy of undetermined significance

We presented the first case of bilateral striopallidodentate calcinosis secondary to Sjögren's syndrome. Further consideration should be given to the association between Sjögren's syndrome and bilateral striopallidodentate calcinosis, because Sjögren's syndrome is latent, but more frequent than other autoimmune diseases.     

Efficacy and safety of biological DMARDs modulating B cells in primary Sjögren's syndrome: Systematic review and meta-analysis

Objective

In this review, we summarise the clinical efficacy and safety of B-cell targeted therapies for primary Sjögren's syndrome (pSS).

Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between clinical examination and ultrasonography

ObjectiveParotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment.MethodsOutpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement.ResultsThirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76–1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42–0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found.ConclusionClinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.     

Diagnostic utility of a second minor salivary gland biopsy in patients with suspected Sjögren's syndrome: A retrospective cohort study

ObjectiveTo determine whether repeated minor salivary gland biopsy (MSGB) has a clinical diagnostic utility in patients with suspicion of Sjögren's syndrome (SS).MethodsClinical, biological, pathological data and physician's diagnosis after each MSGB from patients with suspected primary or secondary SS who had benefited from 2 MSGB at Brest University Hospital between January 1st, 1990 and January 14th, 2015, were retrospectively collected. We compared the characteristics of patients with and without first positive MSGB, concordance between the MSGB, and analyzed the modifications of diagnosis after the second MSGB.ResultsNinety-three patients were included, first MSGB was positive for 23 and negative for 70. Patients with first positive MSGB had more often renal involvement (P < 0.05) and hypergammaglobulinemia (P = 0.01), anti-SSA antibodies (P < 0.05) and positive second biopsy with focus score ≥ 1 or Chisholm > 2 (P < 0.01). The mean time between the 2 MSGB was 5.7 ± 4.3 years. The concordance between the results of the 2 biopsies was low (κ = 0.34). MSGB influenced diagnostic's change in 10 cases where the second MSGB was always guided by new specific clinical manifestations.ConclusionWe observed a low concordance between 2 MSGB in patients with suspected pSS in our study. Despite this variability, performing a second MSGB changed the initial diagnosis in only a minority of the patients and was particularly useful when clinical manifestations had deeply evolved.     

Diagnosis of pathological minor salivary glands in primary Sjogren’s syndrome by using Raman spectroscopy

The lip biopsy is essential for the diagnosis of primary Sjogren’s syndrome (SS) but an invasive method can cause some disadvantages. The purpose of this study is to apply Raman spectroscopy to detect the pathological minor salivary glands in primary SS and establish the diagnostic model of Raman spectra of the primary SS samples. Raman spectra from the primary samples and control samples were obtained by Raman microscope and were compared to find the differences. The principal component analysis (PCA) and discrimination function analysis (DFA) were employed to analyze the spectra and establish the diagnostic model. The differences of Raman spectra demonstrated the biochemical molecular alterations between the different samples. Compared with the control samples, the content of proteins, nucleic acids, and keratin increased in the primary SS samples but the content of lipids decreased. PCA and DFA displayed a powerful role in the classification of the Raman spectra. The sensitivity and specificity of the diagnostic model reached above 91 and 92 %, respectively. The total accuracy is 92.4 %. Raman spectroscopy combined with PCA-DFA algorithm will provide an effective and accurate technology for the diagnosis of the pathological minor salivary glands in primary SS, which may replace the lip biopsy in the future.     

Geoepidemiology of Sjögren's syndrome in Latin America

ObjectiveTo evaluate the geoepidemiology of Sjögren's syndrome (SS) in Latin America.MethodsThis was a three phase study in which original data from a Colombian cohort of patients with SS is presented, followed by a systematic review of Colombian and Latin American studies. Lastly, the geoepidemiology of SS in Latin America was assessed by comparing the clinical characteristics of the region with those of the rest of the world by means of a meta-analysis approach.ResultsData from 2970 patients from Latin America and 18019 patients from Europe, North America and Asia were analyzed. Colombian patients have a lower age at disease onset than those from other Latin American countries and a higher rate of positivity of antinuclear antibodies and rheumatoid factor. A significant difference in the proportion of female patients in Latin America compared with Europe and North America was observed. The spectrum of disease in Latin American was similar to North American patients, while strong differences were noticed between Latin American and European and Asian patients. Noteworthy, a paucity of reports including African and African-descendent patients was observed.ConclusionsThe clinical spectrum of SS differs between countries and continents. Genetic differences relying upon ancestry could explain these findings. However, environmental factors have proven to be important determinants in the development of autoimmune diseases (i.e., autoimmune ecology). Thus, ancestry and the autoimmune ecology should be considered in studies aimed to evaluate the geoepidemiology of SS and other autoimmune diseases.     

Autoimmune epithelitis in primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is characterized by an autoimmune epithelitis associated with chronic inflammation of the exocrine glands. Alterations of extra-glandular functions in pSS is associated with lymphocytic infiltrates that invade the epithelial structures of affected organs. Within epithelial tissue, the expression of class II major histocompatibility complexes and costimulatory molecules by epithelial cells acting as non-professional antigen presenting cells, leads to the activation of T and B lymphocytes through multiple cellular crosstalk pathways. Although the pathogenetic mechanisms underlying pSS have not yet been elucidated, it is accepted that glandular epithelial cells are central regulators of the local autoimmune response.     

Elderly-onset primary Sjögren's syndrome focused on clinical and salivary gland ultrasonographic features

ObjectiveTo assess the clinical, laboratory, and salivary gland ultrasound (SGUS) characteristics of elderly-onset of primary Sjögren's syndrome (EopSS).MethodsWe included pSS patient from two referral hospitals over a 4-year period. The SGUS scores (0–48) and SG volumes were assessed. Clinical, laboratory, and SGUS data were compared according to age at onset: EopSS (≥ 65 years), adult-onset (AopSS) (≥ 40 and < 65 years), and young-onset (YopSS) (< 40 years).ResultsThis cross-sectional study included a total of 221 patients, 43 (19.5%) of which had EopSS. Subjective sicca symptoms, results of the Schirmer's test, and unstimulated salivary flow rate revealed no significant differences between the groups. EopSS patients presented a significantly higher frequency of interstitial lung disease (ILD) (EopSS: 51.2% vs. AopSS: 13.5% vs. YopSS: 8.7%, P < 0.001) and lower frequency of arthritis (7% vs. 22.6% vs. 39.1%, P < 0.01). They also had significantly lower positivity of anti-Ro/SSA (51.2%) and anti-La/SSB (7.0%) and lower levels of rheumatoid factor, C4, and IgG. The EopSS group had significantly lower SGUS positivity (defined as total scores ≥ 14) (44.2% vs. 64.5% vs. 78.3%, P < 0.05), lower SGUS scores, and smaller submandibular gland volume.ConclusionWe report a specific phenotype of EopSS, characterised by high prevalence of ILD, less involvement of the peripheral joint, and low biological activity. SGUS evaluation showed less parenchymal abnormalities but more atrophic changes in major SGs in EopSS patients. Considering the low positivity of anti-Ro/SSA and SGUS in EopSS, SG biopsy remains the only way to confirm the diagnosis of pSS, especially in elderly patients.     

Epidemiology and diagnostics of primary Sjögren's syndrome

This review paper contains selected aspects of Sj?gren's syndrome. It consists of epidemiology, ultrasound of salivary glands and antimuscarinic antibodies. The first part present studies aimed to determine the prevalence and the incidence of the disease with special emphasize on epidemiological studies performed in Slovenia. This is followed by the demonstration of the role of ultrasound of salivary glands in the diagnosis of Sj?gren's syndrome and the value of antimuscarinic antibodies in global assesment of the secretory failure.     

Factors predictive of renal involvement in patients with primary Sjögren's syndrome

AIM: To identify clinical and immunological risk factors underlying the development of renal involvement in primary Sj?gren's syndrome (pSS). SUBJECTS AND METHODS: Seventy-eight patients (75 females, 3 males) with pSS were carefully interviewed and clinical and laboratory data from the time of diagnosis recorded. The baseline data on patients shown to have either latent or overt distal renal tubular acidosis (dRTA), mild proteinuria or increased urinary excretion of alpha-1 microglobulin (alpha1m) after a mean disease duration of 9 +/- 4 years, were compared to the baseline data on those who did not have these manifestations at follow-up. RESULTS: Patients with subsequent latent or overt dRTA were found to have significantly higher baseline levels of serum total gamma-globulin (24 +/- 7 vs. 19 +/- 6 g/l, p = 0.011) and serum protein (84 +/- 7 vs. 79 +/- 7 g/l, p = 0.024) compared to those with normal renal acidification capacity. The baseline levels of serum beta-2 microglobulin (beta2m) were higher in patients with an acidification defect than in those with normal acidification capacity (3.1 +/- 1.1 vs. 2.6 +/- 0.8 mg/l, p = 0.072). In those with subsequent proteinuria the levels of serum beta2m were almost significantly higher at baseline as compared to those with normal urinary protein excretion (3.1 +/- 1.4 vs. 2.5 +/- 0.8 mg/l, p = 0.052). The subgroup of pSS patients who had increased urinary alpha1m excretion as a sign of tubular proteinuria, had higher baseline levels of ESR (55 +/- 27 mm/h vs. 40 +/- 23 mm/h, p = 0.076) and significantly higher baseline levels of serum beta2m (4.6 +/- 1 .8 vs. 2.6 +/- 0.8 mg/l, p = 0.029) as compared to those with normal urinary alpha1m excretion. CONCLUSIONS: High levels of serum total gamma-globulin, serum protein and serum beta2m were the best predictors of the development of dRTA in pSS patients. High baseline levels of serum beta2m were also associated with the subsequent occurrence of mild proteinuria and increased urinary alpha1m excretion in patients with pSS.     

Analysis of TNFalpha microsatellites in 35 patients with primary Sjögren's syndrome

OBJECTIVES: Although the cause of Sj?gren's syndrome remains unknown, many arguments suggest a role for both environmental and genetic factors. An association with HLA molecules has been established. Other genes on the short arm of chromosome 6 may be involved, most notably the TNF gene, which may be pivotal in the development of the epithelial lesions. METHODS: We investigated TNFalpha microsatellites in 35 patients with primary Sjogren's syndrome and in 146 healthy controls. RESULTS: The frequency of the TNFalpha10 allele showed a non-significant increase in the Sj?gren's disease group (28.6% vs 15.8%; P = NS). We found significant increases when we considered only those Sj?gren's disease patients with joint manifestations (N = 24; 37.5% vs 15.7%; P < 0.05) or only those with anti-Ro(SSA) antibodies (N = 10; 50% vs 15.7%; P < 0.05). CONCLUSION: Our data support a role for the TNFalpha10 allele in primary Sj?gren's syndrome, particularly those forms with joint symptoms and anti-Ro(SS-A) antibodies.     

Fibromyalgia in Italian patients with primary Sjögren's syndrome

OBJECTIVE: To assess the prevalence of fibromyalgia in primary Sj?gren's syndrome and to evaluate the clinical differences between patients affected with both primary fibromyalgia and primary Sj?gren's syndrome and those affected only with primary fibromyalgia. METHODS: Clinical features of fibromyalgia were evaluated in 100 consecutive outpatients with primary Sj?gren's syndrome and, as controls, in 90 patients with non-insulin-dependent diabetes mellitus, in 75 patients with primary fibromyalgia and in 30 healthy subjects. RESULTS: Fibromyalgia was recorded in 22% of patients with primary Sj?gren's syndrome, in 12.2% with diabetes and in 3.3% of healthy controls. In the primary Sj?gren's syndrome group the prevalence was significantly higher than in healthy controls (P < 0.01), but not significantly different than in diabetes. Moreover, primary Sj?gren's syndrome with fibromyalgia and primary fibromyalgia patients did not differ with respect to the number of tender points, while the mean pain threshold was lower in the latter (P = 0.05). Purpura, hypergammaglobulinemia, rheumatoid factor, and a focus score > or = 1 on lip biopsy were significantly more frequent in primary Sj?gren's syndrome patients without than with fibromyalgia. CONCLUSIONS: As recently reported by other authors, our study confirms the moderate increase of fibromyalgia prevalence in primary Sj?gren's syndrome. Typical fibromyalgic findings are quite similar to those of primary fibromyalgia, but surprisingly, primary Sj?gren's syndrome patients with fibromyalgia show a less severe global involvement than those with primary Sj?gren's syndrome alone.     

Thrombotic microangiopathy complicating newly diagnosed Sjögren’s syndrome in a dialysis patient

Thrombotic microangiopathy (TMA) is rarely associated with Sjögren’s syndrome (SS). This is the first documented case of a patient undergoing chronic hemodialysis with SS who developed TMA. TMA is an infrequent, life-threatening multisystem disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. It is important to make a quick diagnosis of TMA to cure the reported case as early as possible. The patients with TMA should be diagnosed quickly, and in this case plasma exchange and corticosteroids in combination with cyclophosphamide have been associated with a recurrence free period. Cyclophosphamide has led to the development of treatment protocols using alternative immunosuppressive agents in patients with SS showing a poor response to plasmapheresis and potentially life-threatening manifestations. Further research is required to ascertain the sensitivity, specificity, efficacy, timing, cost-benefit ratio, and necessity of cyclophosphamide in the setting of TMA complicating SS.     

Pelvic floor dysfunction in female Sjögren’s syndrome: an 8-year audit

Introduction and hypothesis

The classic triad of dry eyes, mouth and vagina is known to most gynaecologists as pathognomonic of Sjögren’s syndrome, but rheumatologists seldom consider vaginal symptoms. Our hypothesis was that women with Sjögren’s syndrome would have an increased likelihood of postoperative voiding dysfunction, severe vaginal stenosis or poor response to anticholinergics compared with the general urogynaecology patient.

Methods

All patients with Sjögren’s syndrome were prospectively recorded from July 2007 to June 2015. Presenting complaint, pelvic examination findings, previous/subsequent pelvic surgery, voiding dysfunction and response to anticholinergics were noted. The denominator, all new urogynaecology patients, was prospectively recorded.

Results

Fifteen patients were identified over 8 years (0.5 % of 2794 new presentations). Of the seven patients who had previously undergone surgery elsewhere, all had demonstrable pelvic tissue fibrosis; five had such severe fibrosis that no speculum could be passed. Anticholinergic medications were completely intolerable in 10/11 (91 %) women, and severe postoperative voiding dysfunction occurred in 6/9 (67 %) women. Only 2/15 (13 %) women were unaffected by fibrosis, postoperative voiding dysfunction or intolerance to anticholinergics.

Conclusions

This audit demonstrates a substantial risk of vaginal stenosis, postoperative voiding dysfunction or severe intolerance to anticholinergics in women with Sjögren’s syndrome.

     

End-stage renal failure in adolescence with Sjögren’s syndrome autoantibodies SSA and SSB

We describe two adolescents who presented with end-stage renal failure and clinical features suggestive of Sjögren’s syndrome (SS). They both demonstrated severe, chronic, tubulointerstitial inflammation on renal biopsy, high-titre antinuclear antibodies, high immunoglobulin A and G concentrations, positive anti-SSA and anti-SSB antibodies, and negative anti-double-stranded DNA antibodies. One had subjective and objective evidence of the sicca complex (dry eyes and/or dry mouth) and fulfilled the commonly accepted SS consensus criteria. The other showed no evidence of the sicca complex but fulfilled modified criteria for juvenile SS. SS may be underrecognised as a cause of end-stage renal failure in childhood.