anti-SSA Antibodies Research Articles

Diagnostic Utility of Minor Salivary Gland Biopsy for Primary Sjögren Syndrome in Patients With Negative Anti-SSA Antibodies.

Sjögren syndrome is a systemic autoimmune disease characterized by lacrimal and salivary gland inflammation resulting in dry eyes andmouth. Although it is a common disease, diagnosis can be challenging due to its heterogeneous presentation. A positive minor salivary gland biopsy is mandatory to fulfill the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for primary Sjögren syndrome in patients who are seronegative for anti-SSA/Ro antibodies. The objective of our study was to evaluate the validity of minor salivary gland biopsy for patients who are SSA antibody-negative yet are suspected of having primary Sjögren syndrome because of compelling symptoms. We conducted a retrospective chart review of adult patients with a negative anti-SSA antibody test who underwent minor salivary gland biopsy to assess suspected Sjögren syndrome at Henry Ford Rheumatology Clinics between January 2005 and December 2019. Patient characteristics and clinical features are described. Sensitivity, specificity, positive predictive value, and negative predictive value are assessed. A total of 47 patients were included: 46 (97.9%)females and one (2.1%)male. The mean age was 57.2 ± 13.8 years. There were 14 (29.8%) patients who had a positive minor salivary gland biopsy resultand 15 (31.9%) patients who had a final diagnosis of Sjögren syndrome. Minor salivary gland biopsy had 93.3% sensitivity (95% confidence interval (CI): 68%-99.8%), 100% specificity (95% CI: 89.1%-100%), 100% positive predictive value (95% CI: 76.8%-100%), and 97% negative predictive value (95% CI: 84.2%-99.9%). The diagnostic value of minor salivary gland biopsy is high for patients who do not have anti-SSA antibodies yet are suspected of having Sjögren syndrome. The results of the study support the consideration of routine minor salivary gland biopsy for identifying Sjögren syndrome in these patients.

Endothelial Dysfunction in Primary Sjögren's Syndrome: Correlation with Serum Biomarkers of Disease Activity.

To assess the relationship between endothelial dysfunction and serum cytokines, anti-SSA and anti-SSB antibodies, beta-2 microglobulin levels, focus score and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in primary Sjögren's syndrome (pSS) patients. The study included 90 patients with pSS and 45 healthy subjects, matched for age and gender, as controls. Serum beta-2 microglobulin, total cholesterol, HDL-cholesterol, triglycerides, TNF-α, and IL-6 were analyzed in both the groups. Patients with pSS were also tested for antinuclear antibodies, anti-SAA (anti-Sjögren's syndrome-related antigen A) antibodies, anti-SSB (anti-Sjögren syndrome related antigen B) antibodies, and focus score (the histopathologic one, based on minor salivary gland biopsy). Endothelial dysfunction was assessed by means of flow-mediated dilation (FMD) in the brachial artery. Data are presented as mean ± standard deviation. Statistical analysis was performed using the t-test and the Pearson's correlation. Differences were considered to be statistically significant if the value of p < 0.05. Endothelial dysfunction was identified in pSS patients (p < 0.00001). The serum levels of cytokines (TNF-α, respective IL-6) and beta-2 microglobulin were increased in pSS patients compared with controls (p < 0.00001). Endothelial dysfunction (expressed as FMD%) was correlated with focus score, ESSDAI, levels of anti-SSA and anti-SSB antibodies, beta-2 microglobulin, IL-6, and TNF-α, with statistical significance. Endothelial dysfunction is present in pSS patients and is associated with a high focus score and activity as well as increased concentrations of antibodies, pro-inflammatory cytokines, and beta 2-microglobulin.

Recommendations for the diagnosis and treatment of Sjögren's syndrome in China

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In addition to the impairment of salivary and lacrimal gland function, SS can present with multi-system and multi-organ involvement, accompanied by autoantibodies in serum and hyperimmunoglobulinemia. SS can be divided into primary and secondary forms based on the absence or presence, respectively, of concurrent connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association drafted standardized criteria for the diagnosis and treatment of primary SS. The objectives were to standardize the detection and interpretation of key indicators for the diagnosis of SS, including serum anti-SSA antibody and labial gland pathology, suggest the use of the widely accepted European League Against Rheumatism (EULAR)-SS disease activity index for the evaluation of the disease, and standardize the rational management of SS patients with topical and systemic therapies.

No evidence of increased anti-M3 muscarinic acetylcholine receptor autoantibodies in SSA-positive connective tissue disease patients.

Anti-muscarinic type 3 receptor autoantibodies (M3R) and anti-SSA antibodies are both related to salivary secretion. The presence of M3R antibodies in Sjögren's syndrome is previously demonstrated; nevertheless, the relationship between the anti-SSA antibodies and M3R fragment antibodies, namely the N terminal, first, second, and third extracellular loops, remains to be elucidated. In this study, we analyzed the antibodies against the M3R epitopes in healthy controls and anti-SSA antibody-positive connective tissue disease patients through ELISA method. Antibodies against the first, second, and third extracellular loop (M3R211-230 ) were not increased in anti-SSA positive patients compared to healthy controls. Indeed, antibodies against the N terminal (M3R1-33 ) were found to be high in healthy controls. High levels of M3R1-33 in healthy controls are a novel original finding; further research is needed for the clinical significance. There is no significant difference between SSA-positive patients and healthy controls in terms of autoantibodies against the remainder of the linear M3R fragments.

Systemic Lupus Erythematosus: Female Versus Male

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease, uncommon in men. The study of gender differences in SLE has been the subject of several publications. The main aim of our study is to identify gender differences in terms of clinical manifestations, immunological profile, activity score, and disease evolution in our Moroccan population. Results: We analyzed 279 patients (21 men versus 258 women), with a mean age at diagnosis of 37.54 +/- 23.39 years for women and 42.74 +/- 16.33 years for men. A comparison of clinical and immunological manifestations showed that male patients had a higher prevalence of renal involvement, lymphopenia, leukopenia, and general signs, but the difference was not significant. However, we did establish a significant correlation between male sex and cardiac involvement (P=0.013) as well as neuropsychiatric involvement (P=0.05). We also observed a significant association with anti-SSA antibodies (p=0.007). Dermatological and articular events were more frequent in women than in men, with a statistically significant association between female gender and photosensitivity (p=0.037). There was also a statistically significant correlation between women with RNP antibodies (p = 0.016) and anti-native DNA antibodies (p=0.047). The outcome was good in 67% of men (vs. 86.2% p=0.802), with response to treatment and control of the disease, and poor in 33% of men (vs. 13.9% %, p=0.019). Conclusions: Our study reveals the influence of gender on certain clinical manifestations of SLE. Dermatological and articular manifestations are more frequent in women, whereas men present a more severe disease, with a higher frequency of renal, cardiac, and neurological involvement.

Serum Metabolomics Analysis of Skin-Involved Systemic Lupus Erythematosus: Association of Anti-SSA Antibodies with Photosensitivity.

Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis. The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies. We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody. This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.

Primary Sjögren’s syndrome misdiagnosed as Mikulicz’s disease: a case report

BackgroundSjögren’s Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz’s disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis.Case presentationA 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer’s test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS.ConclusionWhen the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD.

An immuno-lipidomic signature revealed by metabolomic and machine-learning approaches in labial salivary gland to diagnose primary Sjögren's syndrome.

Assessing labial salivary gland exocrinopathy is a cornerstone in primary Sjögren's syndrome. Currently this relies on the histopathologic diagnosis of focal lymphocytic sialadenitis and computing a focus score by counting lym=phocyte foci. However, those lesions represent advanced stages of primary Sjögren's syndrome, although earlier recognition of primary Sjögren's syndrome and its effective treatment could prevent irreversible damage to labial salivary gland. This study aimed at finding early biomarkers of primary Sjögren's syndrome in labial salivary gland combining metabolomics and machine-learning approaches. We used a standardized targeted metabolomic approach involving high performance liquid chromatography coupled with mass spectrometry among newly diagnosed primary Sjögren's syndrome (n=40) and non- primary Sjögren's syndrome sicca (n=40) participants in a prospective cohort. A metabolic signature predictive of primary Sjögren's syndrome status was explored using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the data set into training, validation, and test sets. Among 126 metabolites accurately measured, we identified a discriminant signature composed of six metabolites with robust performances (ROC-AUC = 0.86) for predicting primary Sjögren's syndrome status. This signature included the well-known immune-metabolite kynurenine and five phospholipids (LysoPC C28:0; PCaa C26:0; PCaaC30:2; PCae C30:1, and PCaeC30:2). It was split into two main components: the first including the phospholipids was related to the intensity of lymphocytic infiltrates in salivary glands, while the second represented by kynurenine was independently associated with the presence of anti-SSA antibodies in participant serum. Our results reveal an immuno-lipidomic signature in labial salivary gland that accurately distinguishes early primary Sjögren's syndrome from other causes of sicca symptoms.

Neurological injury in primary Sjogren's syndrome.

Forty-eight patients with primary Sjogren's syndrome, attending outpatient clinics at Damascus Hospital between January 2020 and January 2022 in this cross-sectional study at the outpatient clinics, were interviewed and examined, and the necessary laboratory and radiological examinations were demanded. Information was collected on disease duration, onset time, and patterns of neurological symptoms. Forty-eight patients, including 42 females, aged 56.1±10.3 years were enroled.Central nervous system involvement was found in 34 patients. 85% of patients had generalized nerve manifestations, while local nerve manifestations were found in 77,5% of patients. The common neurological manifestation was headaches, then cognitive disorders, and the most common pattern of headache was migraine. Beck Depression Index showed a significant increase in the apathy evaluation scale.The study of cognitive changes showed a significant increase in the Mini-Mental State Examination (MMSE) index.Carotid Doppler showed the presence of injury in 42.4% of patients. The magnetic resonance imaging showed positive findings in 21 patients and positive evoked potentials in 52% of patients. Studies showing the prevalence of Sjogren's neurological injury patterns are insufficient, but this was changed when the criteria for diagnosing Sjogren's syndrome was modified, and the definition of neurological traits in the context of the syndrome was expanded.The presence of a high rate of headaches, cognitive changes, and fatigue confirms that generalized nervous system injuries are more common than local injuries. Migraine was the most common pattern of headache found in patients with the syndrome compared with other patterns such as tension headaches and headaches due to medications, especially analgesics.This was associated with the presence of anti-SSA antibodies and Raynaud's phenomenon, which suggest that the headache mechanism may be due to vascular endothelial dysfunction or an immune-mediated inflammation injury of the neurovascular system.The changes that appeared on the MRI images suggested premotor cortex involvement rather than mesolimbic cortical impairment, and its presence was also associated with SSA antibody positivity, and it is caused by inflammation. Primary Sjogren's syndrome should be considered as having any unspecified or specific neurological disorder.

Diagnostic dilemma: Multiple Autoimmune Syndrome versus incomplete Graham-Little-Piccardi-Lassueur Syndrome overlap mixed connective tissue disease

Objectives. We present a very rare case of incomplete Graham-Little-Piccardi-Lassueur syndrome (GLPLS) overlap with Mixed Connective Tissue Disease (MCTD) versus Multiple Autoimmune Syndrome (MAS). Case Presentation. A 53- year-old female with a long history of more than two years of patchy hair loss on scalp like “footprints in the snow”, partial loss of eyebrows' hair, face erythema, scaly atrophied red/brown patches on face, grouped follicular papules 2-3 mm in diameter with a pointed or hair-like horny spine extending approximately 1-2 mm around the tip of the follicle on lumbar area. The histopathological results from biopsies of scalp and lumbar areas confirmed the clinical diagnosis of cicatricial alopecia induced by lichen plan pilaris (LPP) and also presence of lichen spinulosus (LS) on lumbar area. The description provided by pathologist is however borderline regarding so called interface dermatosis like chronic cutaneous lupus erythematous (CCLE) or Pseudopelade of Brocq (PPB) as the end stage of CCLE or LPP. Blood tests showed both Antinuclear antibodies and U1-nRNP in high titers and the absence of anti-Sm, anti SS-A, anti SS-B and anti-dsDNA antibodies, and also peculiar antibody patterns of MCTD. Outcome. After thorough investigation, MCTD was proven by antibodies results. After one year of treatment a lot of clinical features dramatically responded under therapy. Conclusions. Clinical manifestations in the pathology with strictly cutaneous or systemic localization in conjunction or overlap with other autoimmune diseases (grouped in the MAS) represent a rare diagnostic in daily practice.

ICOS gene polymorphisms in systemic lupus erythematosus: A case-control study.

The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case-control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (-693 G/A) and rs10932029 (IVS1+173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031>CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p=.001, odds ratio [OR]=2.18 IC [1.36-3.49]); codominant genetic model 2, (C/C vs. T/T) p=.007, OR=15.29 IC [1.97-118.5]); dominant genetic model, (C/C vs. C/T+T/T) p=.0001, OR=2.44 IC [1.53-3.9]). Besides, there was a marginal association between rs11889031>TT genotype and T allele with a protective role from SLE (recessive genetic model, p=.016, OR=0.08 IC [0.01-0.63] and p=7.6904E-05, OR=0.43 IC=[0.28-0.66], respectively). Moreover, statistical analysis indicated that the rs11889031>CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031>CC genotype with SLE, in contrast to a protective effect of rs11889031>TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.

Establishment of a comprehensive diagnostic model for neuromyelitis optica spectrum disorders based on the analysis of laboratory indicators and clinical data.

To establish a comprehensive diagnostic model for neuromyelitis optica spectrum disorders (NMOSDs) based on laboratory indicators and clinical data. A retrospective method was used to query the medical records of patients with NMOSD from January 2019 to December 2021. At the same time, clinical data of other neurological diseases were also collected for comparison. Clinical data of the NMOSD group and non-NMOSD group were analyzed, and the diagnostic model was established based on these data. In addition, the model was evaluated and verified by the receiver operating curve. A total of 73 patients with NMOSD were included, and the ratio of males to females was 1:3.06. The indicators that showed differences between the NMOSD group and non NMOSD group included neutrophils (P = 0.0438), PT (P = 0.0028), APTT (P < 0.0001), CK (P = 0.002), IBIL (P = 0.0181), DBIL (P < 0.0001), TG (P = 0.0078), TC (P = 0.0117), LDL-C (P = 0.0054), ApoA1 (P = 0.0123), ApoB (P = 0.0217), TPO antibody (P = 0.012), T3 (P = 0.0446), B lymphocyte subsets (P = 0.0437), urine sg (P = 0.0123), urine pH (P = 0.0462), anti-SS-A antibody (P = 0.0036), RO-52 (P = 0.0138), CSF simplex virus antibody I-IGG (P = 0.0103), anti-AQP4 antibody (P < 0.0001), and anti-MOG antibody (P = 0.0036). Logistic regression analysis showed that changes in ocular symptoms, anti-SSA antibody, anti-TPO antibody, B lymphocyte subsets, anti-AQP4 antibody, anti-MOG antibody, TG, LDL, ApoB, and APTT had a significant impact on diagnosis. The AUC of the combined analysis was 0.959. The AUC of the new ROC for AQP4- and MOG- antibody negative NMOSD was 0.862. A diagnostic model was successfully established, which can play an important role in differential diagnosis of NMOSD.

Anti-SSA/SSB-negative primary Sjögren’s syndrome showing different clinical phenotypes: a retrospective study of 934 cases

BackgroundCurrently, only a few studies have described the general characteristics of patients with primary Sjögren’s syndrome (pSS) who tested negatives for anti-SSA and anti-SSB antibodies. We aimed to further investigate the clinical characteristics of these patients in a large sample.MethodsData from patients with pSS who were treated at a tertiary hospital in China between 2013 and 2022 were retrospectively analyzed. Clinical characteristics of the patients were compared between those with and without anti-SSA and anti-SSB antibody negativity. Factors associated with anti-SSA and anti-SSB negativity were identified by logistic regression analysis.ResultsOverall, 934 patients with pSS were included in this study, among whom 299 (32.0%) tested negative for anti-SSA and anti-SSB antibodies. Compared with patients testing positive for anti-SSA or anti-SSB antibodies, that testing negative for the two antibodies had a lower proportion of females (75.3% vs. 90.6%, p < 0.001) and thrombocytopenia (6.7% vs. 13.6%, p = 0.002), but a higher proportion of abnormal Schirmer I tests (96.0% vs. 89.1%, p = 0.001) and interstitial lung disease (ILD) (59.2% vs. 28.8%, p = 0.001). Anti-SSA and anti-SSB negativity was positively associated with male sex (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.05, 3.31), abnormal Schirmer I tests (OR = 2.85, 95% CI: 1.24, 6.53), and ILD (OR = 2.54, 95% CI: 1.67, 3.85). However, it was negatively related to thrombocytopenia (OR = 0.47, 95% CI: 0.24, 0.95).ConclusionApproximately one third of pSS patients had anti-SSA and anti-SSB negativity. pSS patients testing negative for anti-SSA and anti-SSB showed a higher risk of abnormal Schirmer I tests and ILD, but a lower risk of thrombocytopenia.

A Curious Case of Cocaine-Induced Hypokalemic Periodic Paralysis Mimicking Guillain-Barre Syndrome (P10-5.003)

<h3>Objective:</h3> To describe a rare cause of progressive ascending paralysis resembling Guillain-Barre Syndrome (GBS). <h3>Background:</h3> Cocaine inhibits the reuptake of monoamines at the synaptic cleft to prolong sympathetic output. This adrenergic hyperresponsiveness mimics thyrotoxicosis as it replicates sodium/potassium ATPase hyperactivity, causing a cellular influx of potassium (hypokalemia), hyperpolarization, and sodium channel inactivation that presents as sudden, painless muscle weakness and paralysis. <h3>Design/Methods:</h3> Consent obtained from patient. <h3>Results:</h3> A 30-year-old female with no past medical history was evaluated in the ED for acute lower extremity weakness that ascended to the upper extremities within &lt; 12 hours. Labs were significant for hypokalemia at 1.6, elevated inflammatory markers, elevated Free T4 at 2.58, and low TSH at &lt; 0.015. Urine drug screen was positive for cannabis and cocaine. Serum toxicology was negative. MRI of the T-spine and L-spine were unremarkable. Lumbar puncture was unremarkable. Cranial nerves were intact. Strength was 1/5 throughout, including at the neck. Flaccid tone. Lower extremity reflexes were 2+. Negative Babinski. Positive Hoffman bilaterally. Preserved sensation. The patient was admitted to the ICU, intubated for impending respiratory distress, and treated with IVIg. MRI of the C-spine was unremarkable. Further labs demonstrated elevated Free T3 at 7.13 and positive anti-TPO antibodies, significant for Grave’s disease. Urine labs were substantial for distal RTA. Anti-SSA and SSB antibodies were positive, indicating likely Sjogren’s syndrome (SS). Ganglioside panel was negative. Potassium was aggressively repleted. By day 1, the patient was moving all four extremities, and IVIg was discontinued. By day 2, she was successfully extubated. She was ambulating without difficulty on discharge. <h3>Conclusions:</h3> Secondary hypokalemic periodic paralysis may mimic Guillain Barre syndrome (GBS), a life-threatening demyelinating neuropathy that presents as rapidly progressive, symmetric, ascending paralysis or paresthesia with loss of reflexes. In our case, cocaine was the most plausible trigger for hypokalemia. <b>Disclosure:</b> Dr. Baumann has nothing to disclose. Dr. Rizvi has nothing to disclose. Ms. Alayon has nothing to disclose. Mr. Kendall has nothing to disclose. Dr. Shaffer has nothing to disclose. Dr. Mouhanna has nothing to disclose. Dr. Kenniff has nothing to disclose.

E022 Effect of upadacitinib in a patient with primary Sjogren syndrome: a case report

Abstract Background/Aims Primary Sjogren syndrome (pSS) is a chronic autoimmune multi-system disease characterized by inflammation of exocrine glands, particularly the lacrimal and salivary glands, as well as multiple extra-glandular involvements. Treatment is often challenging, and until now, no disease-modifying anti-rheumatic drugs (DMARDs) have been approved for this condition. There is a lack of data about the efficacy of Janus kinase inhibitors in pSS. Here we report a patient with pSS successfully responding to upadacitinib. Methods A 68-year-old woman presented with pain in multiple joints for 16 years with intermittent use of NSAIDs. She had no low back pain and no self or family history of psoriasis or red eye. She denied dry mouth but required frequent water drinking during meals to aid swallowing and occasionally used artificial tears. MTX was started for her two-month articular flare and positive rheumatoid factor (RF). MTX caused severe vomiting and hyponatremia, and she was hospitalized. After the correction of hyponatremia, she was put on tofacitinib. We reevaluated the case when she came to us. She had grade 2-3 tenderness of most peripheral joints and was bedridden. Immunological parameters revealed RF 127 IU/ml (reference value &amp;lt;14), anti SSA antibody 147 U/ml (normal &amp;lt;3.2), anti SSB antibody 149 U/ml (reference value &amp;lt;8) and anti CCP antibody; ANA, anti-ds-DNA Ab were negative. There was no erosion on the X-ray hands. Schirmer's test was positive (3 mm bilaterally). Unstimulated salivary flow after five minutes was 0.04 ml/min (≤0.1 ml/min indicates salivary hypofunction). She fulfilled the 2016 ACR/EULAR classification criteria, and we diagnosed her with primary Sjogren syndrome. Hydroxychloroquine was initiated, but she discontinued it for anorexia. Considering her age, she was switched to upadacitinib, as European Medicines Agency restricted the use of tofacitinib beyond 65 years. Results Her EULAR Sjogren Syndrome's Disease Activity Index (ESSDAI) was six at baseline, indicating moderate disease activity. Her joint pain improved significantly within two months with infrequent use of pilocarpine in the sixth month. Six months after treatment with upadacitinib, ESSDAI came down to 2; the Patient's Global Assessment score was 02 and achieved STAR (Sjogren's Tool for Assessing Response) response 7 (STAR responder if score ≥5). Conclusion To our knowledge, this is the first case report on the efficacy of upadacitinib in pSS. Further high-quality clinical trials are required to confirm the benefit of upadacitinib in pSS. Disclosure M. Momen Majumder: None. S. Haq: None.

Rowell’s syndrome: A paediatric case

Rowells syndrome is a rare disease, combining Lupus Erythematosus (LE) and Erythema Multiforme (EM) like lesions with a characteristic immunological pattern, including a speckled pattern of Antinuclear Antibodies (ANA), positive anti Ro SSA or anti La SSB antibodies and positive Rheumatoid Factor (RF)

An unusual clue in the diagnosis of primary Sjogren’s syndrome

Sjogren’s syndrome (SSj) is a chronic autoimmune disease mainly targeting the exocrine glands, but sometimes associating extra-glandular manifestations. Xerosis, purpura, Raynaud’s phenomenon, cutaneous vasculitis, annular erythema are the main forms of skin involvement. A 26-year-old female patient was admitted for diffuse erythematous rash and angioedema, xerophthalmia and symmetrical arthralgia of hand joints. Anti-nuclear antibodies, anti-SSA and anti-Ro52 antibodies were identified, Schirmer’s test was positive, thus the diagnoses of primary SSj and associated urticarial vasculitis were established. Treatment with oral methylprednisolone, azathioprine and hydroxychloroquine was initiated, with favorable response over the next week. Patients with primary SSj that develop cutaneous vasculitis, lymphadenopathies or lymphopenia may be at risk for additional extra-glandular manifestations, including non-Hodgkin lymphoma.

ANTENATAL DIAGNOSIS OF FETAL HEART RHYTHM DISORDERS IN WOMEN WITH LUPUS WITH POSITIVE ANTI-SSA AND ANTI-SSB ANTIBODIES: ABOUT TWO CASES

Lupus erythematosus is a nonorgan-specific autoimmune disease predominantly affecting young women of childbearing age, as well as neonatal lupus is a complication related to the presence of anti-SSA/Ro or anti-SSb/La antibodies in the mother. Cardiac manifestations of neonatal lupus include anti-SSA/Ro-SSB/La-mediated conduction system disease and endocardial/myocardial damage resulting in cardiomyopathy. Pregnancy is a complicating factor in lupus erythematosus in 60% of cases. These complications do not seem to be related to the number of pregnancies or to the duration of remission, but stopping the hydroxychloroquine treatment could be the cause of relapses. Obstetrical complications due to lupus are dominated by intrauterine growth retardation and prematurity in 30% of cases, abortion or fetal death in utero in 20% of cases, especially in the presence of anti-phospholipid antibodies and/or anti-cardiolipin antibodies in the mother, and complete atrioventricular block in 1.6% of cases due to trans-placental passage of anti-SSA antibodies. Some treatments, including hydroxychloroquine, corticosteroids, and certain immunosuppressants (azathioprine) are safe, and can and should be maintained if necessary during pregnancy.

Clinical characteristics and risk factors for primary Sjögren's syndrome complicated with pulmonary arterial hypertension.

Primary Sjögren's syndrome (pSS) is involved in pulmonary tissue. Pulmonary arterial hypertension (PAH) is one of the pulmonary complications caused by pSS. This study aims to investigate the clinical characteristics and risk factors for pSS complicated with PAH. We retrospectively analyzed 165 patients in the Second Xiangya Hospital of Central South University. They were divided into a pSS-PAH group (n=86) and a pSS group (n=79) according to pulmonary artery pressure detected by color doppler echocardiography. The clinical characteristics, laboratory test indexes, and risk factors were compared between the 2 groups. Among 165 patients with pSS, 86 patients (52.12%) had PAH. Females were 79 (91.90%) patients in the pSS-PAH group, more than males. The patients in the pSS-PAH group were older than those in the pSS group (all P<0.05). The incidence of keratoconjunctivitis, alopecia, Raynaud's phenomenon, cough, chest tightness, shortness of breath, and dry skin was higher (all P<0.05), and the incidence of pulmonary infection, pulmonary cystic degeneration, respiratory failure, osteoporosis, arteriosclerosis, and hypertension were higher in the pSS-PAH group than those in the pSS group (all P<0.05). The laboratory indicators of pulmonary artery diameter, right atrium diameter, right ventricular contractile diameter and pulmonary artery systolic pressure were higher in the pSS-PAH group than those in the pSS group (all P<0.05), and the positive rates of anti-nuclear antibody, anti-SSA antibody, and anti-Ro-52 antibody were higher (all P<0.05). The incidence of restrictive ventilatory dysfunction and decreased lung diffusion volume in the pSS-PAH group was higher than that in the pSS group (both P<0.05). Advanced age (OR=1.094, 95% CI 1.053 to 1.137, P<0.001), concomitant keratoconjunctivitis (OR=2.075, 95% CI 1.054 to 4.088, P=0.035), hair loss (OR=2.655, 95% CI 1.368 to 5.152, P=0.004), dry skin (OR=2.696, 95% CI 1.364 to 5.332, P=0.004), high pulmonary artery systolic pressure (OR=1.185, 95% CI 1.125 to 1.248, P<0.001), respiratory failure (OR=2.279, 95% CI 1.137 to 4.570, P=0.020), osteoporosis (OR=2.087, 95% CI 1.025 to 4.248, P=0.043), atherosclerosis (OR=2.251, 95% CI 1.146 to 4.423, P=0.018), hypertension (OR=2.370, 95% CI 1.190 to 4.718, P=0.014), the increased antinuclear antibody (OR=2.155, 95% CI 1.094 to 4.245, P=0.026), the increased anti-SSA antibody (OR=2.565, 95% CI 1.292 to 5.091, P=0.007), the increased anti-RO-52 antibody (OR=2.623, 95% CI 1.278 to 5.383, P=0.009), and the decreased lung dispersion (OR=2.602, 95% CI 1.386 to 4.884, P=0.003), were all risk factors for PAH in pSS patients. The incidence of pSS-PAH is high in this study. The advanced age, elevated pulmonary artery systolic pressure, concomitant keratoconjunctivitis, alopecia, dry skin, respiratory failure, osteoporosis, arteriosclerosis, and hypertension, increased anti-nuclear antibody, anti-SSA antibody, and anti-Ro-52 antibody, and decreased pulmonary dispersion suggest that the risk of PAH is significantly increased in patients with pSS.

Diagnostic Evaluation Using Salivary Gland Ultrasonography in Primary Sjögren's Syndrome.

The purpose of this study is to investigate the clinical manifestations in patients with early primary Sjögren's syndrome (pSS) based on the severity score found by salivary gland ultrasonography. Thirty-five newly diagnosed patients with early pSS were enrolled and divided into mild (score 0-1) and severe (score 2-3) groups according to the salivary gland ultrasonography grade (SGUS) scores at baseline. Clinical evaluation, ESSPRI and ESSDAI index values, sicca symptoms of the mouth, salivary capacity, and serum autoantibodies and cytokines were investigated. The mean age of pSS patients at diagnosis was 49.9 ± 11.9 years, and the mean duration of sicca symptoms was 0.58 years. ESSPRI (EULAR Sjögren's syndrome patient report index) and ESSDAI (EULAR Sjögren's syndrome disease index) scores were 15.97 and 4.77, respectively. Clinical manifestations, including the low production of saliva and autoantibody production, such as antinuclear antibodies, rheumatoid factor, and anti-SSA antibody, were found. A higher prevalence of rheumatoid factor (p = 0.0365) and antinuclear antibody (p = 0.0063) and a higher elevation of total IgG (p = 0.0365) were found in the severe group than in the mild group. In addition, the elevated titer of IL-25 was detected in the severe group than in the mild group. This observation indicated that salivary gland ultrasonography grade (SGUS) scans may help physicians diagnose pSS and the elevated titer of IL-25 in patients may be implicated in the pathogenesis of pSS.