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Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0–2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SS) is a multisystem autoimmune disease, primarily targeting salivary and lacrimal glands; skin, nasal and vaginal dryness, along with musculoskeletal pain and fatigue are the most commonly reported symptoms. Hearing loss is hypothesized to be frequent as well. The purpose of this systematic review was to estimate the prevalence of Hearing loss and its different subtypes in patients with Sjögren syndrome. PRISMA guidelines were followed to ensure highest quality for our systematic review. A random effects model meta-analysis and meta-regression was conducted using I2 as heterogeneity indicator. Eleven observational studies were included in this systematic review. Ten of them were cross-sectional, while one study was case–control. Studies were assessed for risk of bias: all were rated to a moderate level, except for two rated to a low level. Pooled prevalence of any type of hearing loss was 52.2%. After excluding studies rated to moderate bias, the pooled prevalence of hearing loss was 36.7%. We also conducted a subgroup analysis depending on type of hearing loss. Pooled prevalence of sensorineural hearing loss was 42.6%., while pooled prevalence of conductive hearing loss and mixed hearing loss were 5% and 2.3%, respectively. Meta-regression was conducted in an effort to identify possible variables capable to explain high heterogeneity between studies. Sample size and year of study were separately found to account for a portion of heterogeneity between studies of sensorineural hearing loss. Year of study was also found to account for a portion of heterogeneity between studies of conductive hearing loss. In conclusion, sensorineural hearing loss, is highly prevalent in patients with Sjögren syndrome. On this basis, early screening and follow-up of patients with Sjögren syndrome by pure tone audiometry is important. [ABSTRACT FROM AUTHOR]

10% of rheumatoid arthritis (RA) cases are associated to so-called secondary Sjögren's syndrome (SS). These RA cases have higher DAS, fewer remissions. Is this linked to a poor response to DMARDs (disease-modifying anti-rheumatic drugs)? No study has addressed this question to date. Does the association between secondary Sjögren's syndrome (SS) and rheumatoid arthritis (RA) affect the therapeutic response to DMARDs and long-term prognosis? We conducted a retrospective case–control study: 39 RA associated with SS was (anti-SSA antibodies and/or Chisolm stage III or IV) were compared to 39 isolated cases of erosive RA matched by age, duration of progression and gender. The DAS CRP was higher in the RA + SS group in patients with disease progression of 16 years: 2.6 (1.5–4.5) compared to the RA group: 1.6 (1.3–2.8) (p = 0.0001) while fewer patients were in remission: 61 vs. 92% (p = 0.002). A higher number of B DMARDs have been prescribed: RA + SS = 3.04 (1–7); RA = 1.7 (1–5) (p = 0.004). Anti-TNFs are less effective when RA is associated with SS: 30 vs. 70%. Conversely, Rituximab is more effective when RA is associated with SS: 80 vs. 30%. Erosive RA-related SS exacerbates the clinical course of the condition: higher DAS, fewer remissions. This is linked to reduced treatment efficacy: higher number of DMARDs prescribed, reduced efficacy of anti-TNF drugs. RA-related SS could modify sensitivity to biotherapies: lower percentage of remissions and resistance to anti-TNF drugs. [ABSTRACT FROM AUTHOR]

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51–64 age range (menopausal women), the OR measured 9.993 (95% CI 2301–43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679–90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008–1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271–5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51–64 age group, OR measured 5.068 (1.117–22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675–35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003–1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029–1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS. [ABSTRACT FROM AUTHOR]

The objective of this study is to review the ocular surface changes and complications of patients with Sjögren syndrome and assess their visual impact. A retrospective, cross-sectional, observational, and descriptive study of patients with Sjögren syndrome diagnosed according to the American–European Consensus Group criteria was designed. Data including age, gender, the reason for consultation, associated systemic disease, visual acuity, and ocular complications were recorded. Dry eye tests including tear meniscus thickness; tear film break-up time; ocular surface staining (fluorescein and lissamine green); and Schirmer I test were performed. A total of 249 patients, 233 women (93.6%) and 16 men (6.4%) were studied. Meibomian gland dysfunction was found in 46% (n = 229 eyes) patients; shortened tear film break-up time in 44% (n = 220 eyes); decreased tear meniscus in 49% (n = 243 eyes); significant superficial punctate keratopathy in 49% (n = 242 eyes); a mean ocular surface staining score of 5.92 points; and a low score for Schirmer I test (mean = 5.4 mm). Eyes with a 4 + corneal fluorescein score showed the worst BCVA (mean = 0.63 ± 0.66 LogMAR, ≤ 20/80 Snellen eq., 95% CI 0.29–0.97), compared to 1 + to 3 + scores (mean = 0.211 ± 0.37 LogMAR, 20/32 Snellen eq., 95% CI 0.53–1.15). Ten eyes (4.0%) presented central corneal ulceration with a mean visual acuity of 20/500 (96% visual loss). Ocular surface alterations related to severe dry eye and complications from Sjögren syndrome may have a significant impact on visual acuity. Secondary Sjögren syndrome to rheumatoid arthritis had the worse dry eye prognosis, visual outcome, and ocular complications. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder associated with a variety of systemic presentations. Varied neurological dysfunctions of newly diagnosed adult patients with pSS have been observed in recent years. We aimed to describe a rare case of acute bilateral facial paralysis diagnosed with pSS for the first time and review the previous studies including similar cases. A 69-year-old female, who had experienced ocular and oral dryness for more than 10 years, presented with bilateral facial palsy. Her laboratory test results showed positive anti-Ro (SSA) and anti-Ro-52 antibodies. Ophthalmic examination and test of saliva secretion verified xerophthalmia and xerostomia, respectively. Other possibilities of Lyme disease, Möbius syndrome, tumor, bilateral temporal bone fracture, Guillain–Barré syndrome, central nervous system lymphoma and HIV infection were ruled out. A diagnosis of pSS associated with bilateral facial paralysis was made. The literature review revealed one article describing a similar patient. Our case was the only one suffering from acute bilateral facial palsy without other nerve involvement. The presence of such patients reveals that pSS is an underlying cause of acute bilateral facial paralysis. [ABSTRACT FROM AUTHOR]

Primary Sjögren syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and tear glands, and autoantibody secretion, in the absence of other systemic autoimmune disorder. Among autoimmune diseases, it is a relatively common disease, but the burden of central nervous system (CNS) involvement is controversial. This retrospective study evaluates the prevalence, clinical patterns and outcomes of CNS involvement in a cohort of patients with primary Sjögren syndrome. We evaluated 93 patients with pSS diagnosed according to American-European Consensus Group criteria. Fourteen patients (15.1 %) had CNS involvement. All were women with an average age of onset of the disease of 42.1 ± 14.7 years (average ± SD) and an average age of onset of neurological involvement of 47.29 ± 16 years. Three had parkinsonian syndrome, two epilepsy, two motor and sensory deficits, two headache with brain magnetic resonance abnormalities, two neuromyelitis optica, two chronic progressive myelitis and one aseptic meningitis. Neurological involvement preceded Sjögren syndrome diagnosis in nine of the patients (64 %), and neurological outcome was good in 11 patients (78.6 %). Central nervous involvement was not as rare as expected, and the frequency was similar to the frequency of peripheral nervous system involvement. In half of the patients, this was the first symptom of the disease, emphasizing the importance of considering this diagnosis, especially in young female with neurological symptoms without other evident cause. [ABSTRACT FROM AUTHOR]

To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources. [ABSTRACT FROM AUTHOR]

Anti-cyclic citrullinated peptide antibody (anti-CCP) is a specific marker for the diagnosis of rheumatoid arthritis. However, this antibody can be detected in other rheumatic diseases and even in healthy people. This study aims to determine the prevalence and the clinical significance of anti-CCP in patients with primary Sjögren syndrome (pSS). We analyzed the clinical and laboratory data of 95 patients with pSS by retrospective review of their medical records. Anti-CCP was measured by ELISA kit. Anti-CCP, rheumatoid factor (RF), anti-nuclear antibody, anti-Ro and anti-La antibodies, and clinical data were investigated. We analyzed clinical and serologic characteristics of anti-CCP-positive patients. Twenty-one patients (22.1%) had positive anti-CCP (mean titer 61.6 ± 15.6 U/ml) and 40 patients (42.1%) had positive RF (mean titer 98.8 ± 22.7 IU/ml). Seventy-nine patients (83.1%) had arthralgia, and 31 patients (32.6%) had non-erosive arthritis on physical examination and radiologic images. Anti-CCP-positive patients had more frequently positive RF (71.4% vs. 41.8%, P = 0.01) and anti-Ro antibody (85.7% vs. 60.8%, P = 0.03). Anti-CCP-positive patients had non-erosive arthritis more frequently than anti-CCP-negative patients (76.1% vs. 21.6%, P < 0.01). The prevalence of anti-CCP was 22.1% in pSS, and anti-CCP was associated with non-erosive arthritis, and positivity of RF and anti-Ro antibody. [ABSTRACT FROM AUTHOR]

Five per cent of patients with primary Sjogren's syndrome (pSS) develop malignant non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. Rituximab (RTX), a chimeric monoclonal antibody against the CD20 molecule expressed on the surface of mature B cells that has been approved for the treatment of NHL, has been used to treat pSS-associated lymphoma. We have described two cases: one with MALT lymphoma in the parotid glands and the other with a rare thymus lymphoma accompanied by the rare complication of a bullous pneumopathy. Both were treated with RTX at haematological doses, which was unsuccessful in the patient with a salivary lymphoma; in the case of the patient with a thymus lymphoma, the mediastinum mass disappeared and did not relapse. Both patients experienced an improvement in the subjective symptoms of dryness, and their Schirmer's test and scialoscintigraphy results stabilised. The pulmonary bullae remained unchanged. [ABSTRACT FROM AUTHOR]

Primary Sjögren syndrome (pSS) is an autoimmune disease that is characterized by infiltration of lymphocytes in exocrine glands, followed by hypofunction of the glands. Dry mouth and eyes are main symptoms, but there are various extraglandular manifestations in pSS. Nine to 75% of patients have pulmonary involvement such as interstitial lung diseases. Pulmonary alveolar proteinosis (PAP) is also a kind of autoimmune disorder, characterized by the presence of anti-granulocyte/macrophage colony-stimulating factor antibody. A 45-year-old nonsmoking woman was admitted with dyspnea and dry cough. She was diagnosed as having PAP, based on characteristic computed tomography, bronchoalveolar lavage, and lung biopsy findings. At the same time, she was diagnosed with pSS, based on dry mouth, xerophthalmia, positive anti-Ro/La antibodies, and scintigraphic finding of salivary glands. Whole lung lavages and monthly intravenous cyclophosphamide had slight improvement in PAP. [ABSTRACT FROM AUTHOR]

The risk of malignant non-Hodgkin lymphoma is increased in primary Sjögren syndrome. In the literature, most studies evaluating this risk were conducted in tertiary reference university hospital. So, selection bias in series exists, in particular selection of the most severe cases in tertiary reference university care centers. Some studies had also a selection bias because patients were hospitalized (data were obtained from hospital discharge registries) and therefore the more severe cases were considered. Between October 1999 and November 2009, 109 adult patients were admitted to our department of internal medicine (non-university hospital, secondary level of the healthcare system, hospitalized patients and outpatient) with diagnosis of primary Sjögren syndrome. Two cases of parotid gland lymphoma occurred during the period of follow-up. No other lymphoma was detected. In this study, clinically identifiable parotid gland non-Hodgkin lymphoma occurs in 1.8% of patients with primary Sjögren syndrome. Because most non-Hodgkin lymphoma initially involves the neck organs, meticulous imaging studies mainly focused on the cervical regions are recommended in the follow-up of patients with primary Sjögren syndrome. Patients whose main complaint is persistent parotid gland swelling may have a parotid biopsy in order to diagnose non-Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of a thermo-sensitive punctum plug, (SmartPlug™) in Primary Sjogren's Syndrome (pSS) patients with dry eyes, whose symptoms persist despite preservative-free artificial tear treatment. In this study, 22 Primary Sjögren's Syndrome (pSS), as defined by American-European Consensus Group Classification Criteria. All patients being followed up by Ege University Departments of Rheumatology and Ophthalmology. The patients had positive Schirmer test results (<5 mm without anesthesia). SmartPlug™ (Medennium, Irvine, California, USA) was inserted into the inferior lacrimal canaliculi of both eyes. Visual acuity measurements, Schirmer I test measurements, lissamine green staining scores, and tear-film breakup times (BUT) were noted before plug insertion and at the 1st, 6th, and 12th months following the procedure. Minimum follow-up period was 6 months for 19 patients and 12 months for 16 patients. Significant improvements were seen in the Schirmer I test scores (before insertion: 1.98 ± 2.67; 1st month: 5.68 ± 6.69; 6th month: 5.35 ± 5.38; 12th month 6.43 ± 5.14 P = 0.006), tear-film BUT in seconds (before insertion: 4.64 ± 3.7; 1st month: 5.80 ± 2.36; 6th month: 7.53 ± 2.92; 12th month 7.50 ± 2.52, P < 0.0001), respectively. Thermodynamic punctum plug insertion only in inferior canaliculus is a simple, effective, and comfortable option for treatment of severe aqueous tear deficiency that cannot be controlled using preservative-free tears. [ABSTRACT FROM AUTHOR]

Autoimmune diseases (AID) are caused by the loss of immunological tolerance against self-antigens. The deoxyribonuclease I (DNASE1) gene seems to participate in the genetic susceptibility of some AID. In fact, two mutations were reported among systemic lupus erythematosus (SLE) patients from Japan and Spain (the 172 A → T mutation (K5X) and the 46_72 deletion, respectively). The aim of our work was to evaluate the DNASE1 contribution in the genetic susceptibility of rheumatoid arthritis (RA, n = 151), Sjögren syndrome (SS, n = 55) and SLE ( n = 34) in Tunisia. DNA from patients and healthy subjects ( n = 232) were explored. Both reported mutations were absent among patient and control subjects. The DNASE1 exon2 sequence was analysed among 26 control subjects to identify new polymorphic variations that are possible. Five known SNPs were explored. The G/T transversion (rs8176927: R2S) was the most polymorphic functional nonsynonymous SNP. Using PCR-RFLP method, all DNAs were genotyped for rs8176927 for a case–control design. The statistical analysis showed no significant differences between patients and controls genotype data. In conclusion, our study showed, on the one hand, the absence of the K5X mutation and the 46_72 deletion in Tunisian patients affected with RA, SS and SLE and healthy subjects, and, on the other hand, the absence of association between the R2S polymorphism and the genetic susceptibility of RA, SS and SLE. [ABSTRACT FROM AUTHOR]

The objective of the study was to analyze retrospectively the clinical, laboratory and imaging findings of multiple sclerosis (MS), such as the manifestations in a cohort of 132 patients referred to the neurology in and outpatient clinic. The proposed clinical and laboratory diagnostic criteria for MS and connective tissue disorders were systematically assessed in 132 consecutive patients. Cerebrospinal fluid serology and brain or spinal cord MRI were studied in all cases. In patients suspected for connective tissue disorder, schirmer test, rose bengal staining and biopsy of minor salivary glands were performed. A total of 115 (87%) patients were diagnosed to have definite MS, while 17 (13%) were diagnosed to have connective tissue disorder. Positive neurological and MRI findings were observed in both groups. The majority of patients with connective tissue disorder demonstrated extra-neurological manifestations like Raynaud’s phenomenon, arthritis, livedo reticularis, purpura and presence of multiple autoantibodies in their sera. All patients with MS should be screened systematically for connective tissue disorder. In the absence of pathognomonic clinical and laboratory findings, the diagnosis of MS is a diagnosis of exclusion. [ABSTRACT FROM AUTHOR]

The Sjögren syndrome often gives rise to complications such as pseudolymphomas and/or mucosa-/skin-associated lymphocytic tumors (MALT/SALT lymphomas). This paper presents a 74-year-old female patient with the Sjögren syndrome complicated by cutaneous plaques/tumors as cutaneous lymphoid hyperplasia over a 7-year follow-up study period. Immunohistochemical examination disclosed B-cell rich lymphoid follicle formation in the skin with the presence of T and B cells and a varied assortment of features to include abundant plasma cell infiltration. Based on the clinical course and histopathological findings, patient condition was considered benign and arises from reaction toward certain unknown microbes. [ABSTRACT FROM AUTHOR]