Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

The association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome.

BACKGROUND: This study analyzed the association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome (pSS). METHODS: A retrospective analysis was performed on patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital from January 1, 2010 to May 31, 2021, and who were diagnosed with pSS. Out of 191 patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria, 50 were positive for both anti-Ro/SSA and anti-La/SSB, whereas 97 had anti-Ro/SSA but not anti-La/SSB antibodies. Forty-four patients for whom neither anti-Ro/SSA nor anti-La/SSB antibodies were found were diagnosed with Sjögren's syndrome by minor salivary gland biopsy. RESULTS: The anti-Ro/SSA antibody-positive group showed higher rheumatoid factor (RF) levels than the anti-Ro/SSA antibody-negative group. The anti-La/SSB antibody-positive group showed lower unstimulated whole saliva (UWS), stimulated whole saliva (SWS), higher erythrocyte sedimentation rate and RF level than the anti-La/SSB antibody-negative group. In addition, the group with both anti-Ro/SSA and anti-La/SSB antibodies showed lower UWS than the group with only anti-Ro/SSA antibodies. However, there were no significant differences in UWS or SWS after taking pilocarpine, and C-reactive protein. CONCLUSIONS: UWS and SWS were lower when a patient was positive for anti-La/SSB, showing that anti-La/SSB is more likely to be involved in salivary gland hypofunction than anti-Ro/SSA in patients with pSS. Therefore, performing laboratory tests, including anti-La/SSB, helps predict the prognosis of salivary gland function in patients with suspected pSS.

A case of Sjögren syndrome and anti-neutrophil cytoplasmic antibody-associated vasculitis.

Sjögren's syndrome (SS) is a rare disease with the highest reported prevalence of 0.01-0.09%. Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is another rare auto-immune disease (prevalence of 0.0009-0.01%). The co-occurrence of these two separate clinical entities in one patient might rarely be encountered as an overlap syndrome. Here, we present the case of a 60-year-old female patient who had complaints of headache, nausea, weakness, gritty sensation in her eyes, and dry mouth [unstimulated saliva production of 0.033 mL/minute (normal; >0.1 mL/minute)] with a blood pressure of 190/110 mmHg, hypertensive retinopathy, proteinuric kidney disease, positivity of myeloperoxidase anti-neutrophil cytoplasmic antibodies, anti-Ro-52, anti-Ro, and anti-La antibodies. Pauci-immune crescentic proliferative glomerulonephritis was found in a kidney biopsy and successfully treated with cyclophosphamide and methylprednisolone. The co-occurrence of these diseases was first reported in 1992 by Böttinger et al. Since then, nearly 37 cases of SS and AAV have been reported. By reporting this case of primary SS and AAV, we emphasize the importance of auto-antibody tests in searching for the etiology of patients with proteinuria.

Therapeutic effects of cationic liposomes on lupus-prone MRL/lpr mice are mediated via inhibition of TLR4-triggered B-cell activation.

We previously reported that co-delivery of dihydroartemisinin and high mobility group box 1 (HMGB1) siRNAs, using cell penetrating peptide (TAT)-modified cationic liposomes (TAT-CLs-DHA/siRNA), resulted in promising activity for the treatment of inflammatory disease through TLR4 signaling pathway. In the current study, we further investigated the therapeutic effects of TAT-CLs-DHA/siRNA on lupus-prone MRL/lpr mice and explored its effects on B cell responses. In vitro, we found that TAT-CLs-DHA/siRNA suppressed the proliferation and activation of B cells through the TLR4 signaling pathway. Following parenteral administration every 4 days, TAT-CLs-DHA/siRNA significantly reduced proteinuria, glomerulonephritis, serum anti-dsDNA antibody and secretion of interleukin (IL)-6, IL-10, IL-17 and IL-21. Moreover, Western blotting showed that TAT-CLs-DHA/siRNA modulated the B-cell intrinsic pathway by downregulating expression of HMGB1, TLR4, MyD88 and NF-κB. This co-delivery system thus represents a promising treatment option for lupus nephritis, and also highlights a novel target of lupus treatment through B cell TLR4 signal pathway.

Chronic Ulcerative Stomatitis (CUS) as an Interdisciplinary Diagnostic Challenge: A Literature Review.

Chronic ulcerative stomatitis (CUS) is a rarely reported disease affecting the oral cavity, most often affecting middle-aged Caucasian females. The aim of the present study is to present the diagnosis, differentiation, and interdisciplinary treatment of this rare disease. CUS is characterized by the presence of an oral erosive or ulcerative lesion. The autoimmune pathogenesis of CUS includes affecting the antigen's activity by DNA-breaking and protein-hydrolyzing enzymes. The stratified epithelium-specific antinuclear antibodies (SES-ANA) are associated with CUS development. Clinically, the lesions presented in oral mucosa might resemble an erosive form of oral lichen planus, whereas gingival lesions seem to be similar to desquamative gingivitis related to dermatological diseases manifested in the oral cavity. Patients often report subjective symptoms related to oral mucosa and general symptoms. Histopathological presentation of CUS is often non-specific and includes sub-epithelial separation from underlying connective tissue, atrophic epithelium, and inflammatory infiltrate with an increased number of plasma cells and lymphocytes. Direct immunofluorescence (DIF) might be used in CUS diagnostics. CUS generally remains nonsusceptible to corticosteroid treatments; however, antimalarial drugs and calcineurin inhibitors are more effective. Further research should be conducted in order to implement a diagnostic protocol and observe the long-term results of CUS management.

Improvement of renal and non-renal SLE outcome measures on sirolimus therapy - A 21-year follow-up study of 73 patients.

The safety, tolerance, and selected renal and non-renal outcome measures were evaluated in 73 SLE patients who received sirolimus therapy for more than 3 months in our institution over the past 21 years. In 12 patients who had lupus nephritis, proteinuria (p = 0.0287), hematuria (p = 0.0232), anti-DNA antibody levels (p = 0.0028) and steroid use were reduced (p = 0.0200). In the non-renal cohort of 61 patients, anti-DNA antibody levels (p = 0.0332) and steroid use were reduced (p = 0.0163). Both in the renal and non-renal cohorts, C3 (renal p = 0.0070; non-renal p = 0.0021) and C4 complement levels were increased (renal p = 0.0063; non-renal p = 0.0042) Adverse effects of mouth sores (2/73), headaches (1/73), and gastrointestinal discomfort were noted in a minority of patients (6/73). Sirolimus was only discontinued in two of 73 patients due to headache and recurrent infections, respectively. This study suggests that sirolimus is well tolerated and exerts long-term therapeutic efficacy in controlling renal and non-renal manifestations of SLE.

The relevance between anti-rods/rings antibody and different treatment regimens in chronic hepatitis C virus infection.

The antibodies and other issues associated with immunity in chronic hepatitis C virus (HCV) have been widely investigated, especially non-organ-specific antinuclear antibodies. Rods-rings (RR) antibody patterns are frequently observed due to pegylated IFN-α (PEG-IFN)/ribavirin (RBV) treatment by indirect immunofluorescence (IIF). We evaluated the relevance between anti-RR and PEG-IFN/RBV and/or direct-acting antiviral (DAA) regimens in chronic HCV. Sampling was done after achieving a sustained virological response (SVR) for 178 patients (aged >18 years). Patients were grouped according to treatment protocols (Group 1 [G1]: PEG-IFN/RBV [n = 53], Group 2 [G2]: PEG-IFN/RBV and Telaprevir or Boceprevir [n = 31], Group 3 [G3]: second- and third-wave DAA and previously received PEG-IFN/RBV (n = 38), and Group 4 [G4]: second- and third-wave DAA [n = 56]). Anti-RR was investigated by IIF (Euroimmun AG) test. Overall, 27 (15.16%) patients were anti-RR positive and received PEG-IFN/RBV. The numbers of anti-RR positivity for G1/2/3/4 (%) were 16/3/8/0 (30.2/9.6/21/0), respectively (p < .001). The anti-RR positivity rate for G1/2/3 was 22.13% (27/122, p = .088). Anti-RR was positive in 17.5% (11/63) of G1/2/3 patients who did not achieve SVR after the first treatment. This rate was 27.1% (16/59) in patients with SVR after the first treatment in G1/2 and there was no difference between these two classified groups in terms of antibody titers (p = .915). Anti-RR was detected up to 172 months after SVR. In summary, anti-RR was positive in high rates in patients receiving PEG-IFN/RBV therapy. Frequent monitoring is needed during patient follow-up to get more data on the relationship between anti-RR titer, treatment regimens, and SVR.

Scleroderma en Coup de Sabre, Parry-Romberg Hemifacial Atrophy and Associated Manifestations of the Eye, the Oral Cavity and the Teeth: A Danish Follow-Up Study of 35 Patients Diagnosed between 1975 and 2015.

BACKGROUND: Scleroderma en coup de sabre (ECDS) and Parry-Romberg idiopathic hemifacial atrophy (IHA) may affect the eyes, oral cavity, teeth and possibly the brain. OBJECTIVE: Systematic follow-up study of ECDS/IHA-associated manifestations including ophthalmic and dental status. METHODS: Medical records of ECDS and IHA patients diagnosed in a 40-year period (1975-2015) were reviewed, and patients were re-examined. RESULTS: Thirty-five patients were included. Twenty-two patients (63%) had ECDS and 4 patients (11%) IHA. In 9 cases (26%), ECDS and IHA were found in the same patient. The ipsilateral eye was affected in 9 patients (26%). Ipsilateral abnormalities of the teeth and the tongue were found in 13 (46%) out of 28 examined. Eleven (31%) had extrafacial scleroderma on the trunk or the extremities. Neurological findings were not verified as ECDS/IHA related. CONCLUSION: ECDS and IHA are related and often overlap with concomitant affections of the connective tissues of the face on the ipsilateral side. Ocular and dental abnormalities are common and follow the distribution of the primary affection, for example, a paramedian line in the front and segmental affection of the maxilla and the mandible. The affections point to predisposing dysmorphogenetic events in embryonal life affecting the face, with abnormality of crest cells at the stage when they migrate from behind over the scalp or laterally to the face to mix up with mesenchymal tissues of the frontonasal, maxillary and mandibular processes. The study emphasizes that routine evaluation of ECDS and IHA should include ophthalmological and dental specialist examinations.

Defective Efferocytosis in a Murine Model of Sjögren's Syndrome Is Mediated by Dysfunctional Mer Tyrosine Kinase Receptor.

Sjögren's syndrome (SjS) is a chronic autoimmune disease primarily involving the exocrine glands in which the involvement of the innate immune system is largely uncharacterized. Mer signaling has been found to be protective in several autoimmune diseases but remains unstudied in SjS. Here, we investigated the role of Mer signaling in SjS. Mer knockout (MerKO) mice were examined for SjS disease criteria. SjS-susceptible (SjSS) C57BL/6.NOD-Aec1Aec2 mice were assessed for defective Mer signaling outcomes, soluble Mer (sMer) levels, A disintegrin and metalloprotease 17 (ADAM17) activity, and Rac1 activation. In addition, SjS patient plasma samples were evaluated for sMer levels via ELISA, and sMer levels were correlated to disease manifestations. MerKO mice developed submandibular gland (SMG) lymphocytic infiltrates, SMG apoptotic cells, anti-nuclear autoantibodies (ANA), and reduced saliva flow. Mer signaling outcomes were observed to be diminished in SjSS mice, as evidenced by reduced Rac1 activation in SjSS mice macrophages in response to apoptotic cells and impaired efferocytosis. Increased sMer was also detected in SjSS mouse sera, coinciding with higher ADAM17 activity, the enzyme responsible for cleavage and inactivation of Mer. sMer levels were elevated in patient plasma and positively correlated with focus scores, ocular staining scores, rheumatoid factors, and anti-Ro60 levels. Our data indicate that Mer plays a protective role in SjS, similar to other autoimmune diseases. Furthermore, we suggest a series of events where enhanced ADAM17 activity increases Mer inactivation and depresses Mer signaling, thus removing protection against the loss of self-tolerance and the onset of autoimmune disease in SjSS mice.

Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner.

According to the literature, the autoantigen La is involved in Cap-independent translation. It was proposed that one prerequisite for this function is the formation of a protein dimer. However, structural analyses argue against La protein dimers. Noteworthy to mention, these structural analyses were performed under reducing conditions. Here we describe that La protein can undergo redox-dependent structural changes. The oxidized form of La protein can form dimers, oligomers and even polymers stabilized by disulfide bridges. The primary sequence of La protein contains three cysteine residues. Only after mutation of all three cysteine residues to alanine La protein becomes insensitive to oxidation, indicating that all three cysteines are involved in redox-dependent structural changes. Biophysical analyses of the secondary structure of La protein support the redox-dependent conformational changes. Moreover, we identified monoclonal anti-La antibodies (anti-La mAbs) that react with either the reduced or oxidized form of La protein. Differential reactivities to the reduced and oxidized form of La protein were also found in anti-La sera of autoimmune patients.

[Spontaneous remission of follicular bronchiolitis with nonspecific interstitial pneumonia: A case report and literature review].

A 41-year-old female patient was admitted in Department of Respiratory and Critical Care Medicine, Peking University Third Hospital because of having cough for a year. Multiple subpleural ground grass and solid nodules could be seen on her CT scan. Four months before admission, she began to experience dry mouth and eyes, blurred vision, finger joints pain, muscle pain and weakness in both lower limbs and weight loss. At the time of admission, the patient's vital signs were normal, no skin rash was seen, breath sounds in both lungs were clear, no rales or wheeze, no deformities in her hands, no redness, swelling, or tenderness in the joints. There was no edema in both lower limbs. Some lab examinations were performed. Tumor markers including squamous cell carcinoma (SCC) antigen, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), Cyfra21-1, pro-gastrin-releasing peptide (proGRP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were all normal. The antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, anti-dsDNA antibody, anti-Sm antibody, anti-SSA/SSB antibody, anti-ribonucleoprotein (RNP) antibody, anti-Jo-1 antibody, anti-SCL-70 antibody and anti-ribosomal antibody were all negative. The blood IgG level was normal. The blood fungal ß-1.3-D glucose, aspergillus galactomannan antigen, sputum bacterial and fungal culture, and sputum smear test for acid-fast staining were all negative. Lung function was normal. Bronchoscopy showed the airways and mucosa were normal. To clarify the diagnosis, she underwent thoracoscopic lung biopsy, the histopathology revealed follicular bronchiolitis (FB) with nonspecific interstitial pneumonia (NSIP). She did not receive any treatment and after 7 months, the lung opacities were spontaneously resolved. After 7 years of follow-up, the opacities in her lung did not relapse. To improve the understanding of FB, a literature research was performed with "follicular bronchiolitis" as the key word in Wanfang, PubMed and Ovid Database. The time interval was from January 2000 to December 2018. Relative articles were retrieved and clinical treatments and prognosis of FB were analyzed. Eighteen articles concerning FB with complete records were included in the literature review. A total of 51 adult patients with FB were reported, including 18 primary FB and 33 secondary FB, and autoimmune disease was the most common underlying cause. Forty-one (80.4%) patients were prescribed with corticosteroids and/or immunosuppressive agents, 6 (11.8%) patients were treated with anti-infective, 5 (9.8%) patients did not receive any treatment. The longest follow-up period was 107 months. Among the 5 patients without any treatment, 1 patients died of metastatic melanoma, the lung opacities were unchanged in 1 patient and getting severe in 3 patients. In conclusion, FB is a rare disease, the treatment and prognosis are controversial. Corticosteroid and immunosuppressive agents could be effective. This case report suggests the possibility of spontaneous remission of FB.

Idiopathic multicentric Castleman disease with Sjögren's syndrome and secondary membranous nephropathy: a case report and review of the literature.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren's syndrome (SS) and secondary membranous nephropathy (SMN). CASE PRESENTATION: A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were "reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia". Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission. CONCLUSIONS: Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission.

[The clinical significance of serum autoantibodies and HLA-B(27) molecule testing in Uygur patients with human immunodeficiency virus infection].

Objective: To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B(27)) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection. Method: A total of 727 HIV-infected Uygur patients who visited Kuche infectious diseases hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA), anti-cyclic citrullinated peptide (CCP) antibody, anti-extractable nuclear antigen (ENAs) antibody and HLA-B(27) molecule were tested. Result: Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05) years. There were 697 (95.87%) patients receiving highly active antiretroviral therapy (HAART) with mean duration of treatment (5.52±3.47) years. The mean CD4(+)T cell count was (520±271) cells/µl in 202 HIV-infected patients, and mean virus load was (108 139±20 498) copies/ml in 20 HIV-infected patients. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%) , alopecia (9.90%) , arthralgia (8.94%) , ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.43% vs. 17.43%, P<0.001) with low titers (ANA titer:1∶100) . HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (32.71% vs. 50.00%, P=0.049). There were no correlations between ANA and duration of HAART, CD4(+)T cell counts and virus load (r values 0.061, 0.047, 0.121, respectively. P>0.05). Only one female patient was HLA-B(27) positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA). Conclusion: Autoimmune manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It's noted that patients with autoimmune manifestations should be considered as a differential diagnosis of HIV infection.

Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report.

The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients-health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren's syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection.

Anti-centrosome antibodies: Prevalence and disease association in Chinese population.

Anti-centrosome antibodies are rare findings with undefined clinical significance in clinical research. We aimed at investigating the prevalence and clinical significance of anti-centrosome antibodies in Chinese population. Testing results of total of 281,230 ANA-positive sera were retrospectively obtained from West China Hospital Sichuan University in China between 2008 and 2017. We retrospectively collected and analysed the clinical and laboratory data of the patients with positive anti-centrosome antibody. Of the 356 453 patients tested, 281 230 patients had positive antinuclear antibodies (ANAs, 78.9%), but only 78 patients with positive anti-centrosome antibodies (0.022%), of which 74.4% are females. Diagnoses were established in 69 of 78 patients: 37 cases were autoimmune diseases, mainly including undifferentiated connective tissue diseases (UCTD, 9/37), rheumatoid arthritis (RA, 6/37), Sjögren's syndrome (SS, 5/37) and primary biliary cirrhosis (PBC, 5/37), and the remaining were other autoimmune conditions. The most frequent clinical symptoms of the anti-centrosome-positive patients were arthralgia and eyes and mouth drying. Additionally, 86.7% of anti-centrosome antibodies were not associated with other ANA profiles; however, when associated, the most frequent ANA was anti-U1RNP. Anti-centrosome antibodies are featured by a low prevalence and female gender predominance. They are correlated with some specific diseases, both autoimmune diseases, especially UCTD, RA, SS and PBC, and non-autoimmune diseases, such as infection and cancer, which suggests that they might be potential supporting serological markers of these diseases.

Distinct clinical characteristics of anti-Ro/SSA-negative primary Sjögren's syndrome: data from a nationwide cohort for Sjögren's syndrome in Korea.

OBJECTIVES: To investigate clinical characteristics of patients with primary Sjögren's syndrome (SS) who were negative for anti-Ro/SSA antibody but positive for minor salivary gland biopsy (MSGB) compared to patients who presented positivity for anti-Ro/SSA antibody. METHODS: The data of 355 patients from the Korean Initiative of primary Sjögren's Syndrome (KISS), a nationwide prospective cohort for primary SS in Korea, were analysed. All patients fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria. Of these patients, 326 were positive for anti-Ro/SSA antibody and 29 were antibody-negative, although they had positive findings in MSGB. Various clinical features including all kinds of tests for evaluating secretory function, disease-related clinical indices and serological values available in the cohort were compared between the two groups. RESULTS: The anti-Ro/SSA-negative group showed less rheumatoid factor positivity (p<0.001), leucopenia (p=0.003), hyper-gammaglobulinaemia (p<0.001), lower serum ß2-microglobulin level (p=0.034), more anti-centromere antibody positivity (p<0.001), higher score in dryness domain of EULAR SS patient-reported index (p=0.048) and more positivity for peripheral nervous system domain in EULAR SS disease activity index and loss of teeth in SS disease damage index (p=0.021 and 0.041, respectively) than patients who were positive for anti-Ro/ SSA antibody. CONCLUSIONS: Primary SS patients who are negative for anti-Ro/SSA antibody have different clinical characteristics compared to patients who are positive for such antibody in Korea. Therefore, clinicians should consider MSGB in patients with suspicious symptoms who are anti-Ro/SSA-negative.

Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria.

Chronic ulcerative stomatitis (CUS) is an immune-mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle-aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non-specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium-specific antinuclear antibodies (SES-ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ∆Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200 mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria.

Recurrent aseptic meningitis: A rare clinical presentation of Sjogren's syndrome.

Sjogren's syndrome most commonly presents with dry eyes, dry mouth, joint pain and fatigue. However, recurrent aseptic meningitis, reported as the most uncommon initial symptom, was the presenting feature in our case. We present the case of a 19-year-old female with recurrent episodes of aseptic meningitis. She presented with fever, headache, vomiting and photophobia. Neurological examination showed neck stiffness. Fundoscopy was normal. On two previous occasions her cerebrospinal fluid analysis was consistent with meningitis; however, it was normal at this presentation. Review of system revealed history of fatigue and sicca symptoms since early childhood. Autoimmune workup showed antinuclear antibodies with a titer of 1:400 and positive anti SSA (Ro) antibodies that led to the diagnosis of Sjogren's syndrome. She responded well to intravenous steroids, followed by oral prednisolone and hydroxychloroquine. To conclude, diagnosis of Sjogren's syndrome may also be considered in a patient presenting with recurrent aseptic meningitis.

Primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterized by focal lymphocytic infiltration of the exocrine glands causing dry eyes and dry mouth. Similar glandular features can also occur as a late complication in patients with other rheumatic disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and scleroderma ('secondary' Sjögren's syndrome).1 Anti-Ro and/or anti-La (ENA) antibodies are found in approximately 70% of pSS patients, generally with ANA positivity. Hypergammaglobulinaemia is also common. Systemic features also occur in some patients with pSS. A positive rheumatoid factor (RF) is often seen and so if patients present with arthritis, dryness and a positive RF a diagnosis of pSS should be considered as a possible alternative to RA. Anti-CCP antibodies are more specific for RA.

[Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome].

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.