Maximum standardized uptake value for parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis using salivary gland SPECT/CT.

Recently, SPECT/CT plays an important role in assessing patients with head and neck lesions. The aim of this study was performed to investigate the maximum standardized uptake value (SUVmax) for parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis using salivary gland SPECT/CT. A prospective study was performed in 45 patients with 32 Sjögren's syndrome and 13 submandibular sialolithiasis who underwent salivary gland SPECT/CT. The SUVmax of parotid and submandibular glands was obtained using a workstation and software. The salivary secretion function of parotid and submandibular glands was defined as ratio of pre- to post-stimulation on SUVmax. A p value lower than 0.05 was considered as statistically significant. The SUVmax for parotid glands in patients with Sjögren's syndrome at pre-stimulation (18.0 ± 14.3), post-stimulation (12.0 ± 9.4), and ratio of pre- to post-stimulation (1.46 ± 0.52) were significantly lower than those of submandibular sialolithiasis (44.9 ± 8.4 (p < 0.001), 17.8 ± 6.5 (p < 0.001), and 2.75 ± 0.79 (p < 0.001), respectively). The SUVmax for submandibular glands in patients with Sjögren's syndrome at pre-stimulation (16.9 ± 18.7) were significantly lower than those with sialolithiasis (36.7 ± 27.8, p = 0.004) and without sialolithiasis (39.7 ± 16.0, p = 0.001) in patients with submandibular sialolithiasis. The salivary gland SPECT/CT SUVmax can be useful in clinical practice for the quantitative management of parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis.

Podoplanin expressing macrophages and their involvement in tertiary lymphoid structures in mouse models of Sjögren's disease.

Tertiary lymphoid structures (TLSs) are formed in tissues targeted by chronic inflammation processes, such as infection and autoimmunity. In Sjögren's disease, the organization of immune cells into TLS is an important part of disease progression. Here, we investigated the dynamics of tissue resident macrophages in the induction and expansion of salivary gland TLS. We induced Sjögren's disease by cannulation of the submandibular glands of C57BL/6J mice with LucAdV5. In salivary gland tissues from these mice, we analyzed the different macrophage populations prior to cannulation on day 0 and on day 2, 5, 8, 16 and 23 post-infection using multicolored flow cytometry, mRNA gene analysis, and histological evaluation of tissue specific macrophages. The histological localization of macrophages in the LucAdV5 induced inflamed salivary glands was compared to salivary glands of NZBW/F1 lupus prone mice, a spontaneous mouse model of Sjögren's disease. The evaluation of the dynamics and changes in macrophage phenotype revealed that the podoplanin (PDPN) expressing CX3CR1+ macrophage population was increased in the salivary gland tissue during LucAdV5 induced inflammation. This PDPN+ CX3CR1+ macrophage population was, together with PDPN+CD206+ macrophages, observed to be localized in the parenchyma during the acute inflammation phase as well as surrounding the TLS structure in the later stages of inflammation. This suggests a dual role of tissue resident macrophages, contributing to both proinflammatory and anti-inflammatory processes, as well as their possible interactions with other immune cells within the inflamed tissue. These macrophages may be involved with lymphoid neogenesis, which is associated with disease severity and progression. In conclusion, our study substantiates the involvement of proinflammatory and regulatory macrophages in autoimmune pathology and underlines the possible multifaceted functions of macrophages in lymphoid cell organization.

Clinical characteristics of chronic sclerosing sialadenitis as a distinctive entity from primary Sjögren's syndrome.

Objective: This study aimed to elucidate the clinical and laboratory differences between chronic sclerosing sialadenitis (CSS) and primary Sjögren's syndrome (pSS), highlighting CSS as a distinct pathological entity within the spectrum of salivary gland pathology. Methods: This retrospective, single-center study was conducted at Seoul St. Mary's Hospital between January 2000 and December 2022. Patients diagnosed with CSS via salivary gland biopsy were included, and those with IgG4-related disease (IgG4-RD) or other confounding factors were excluded. Clinical and laboratory CSS profiles were compared with those of a control group of patients with typical pSS from the Korean Initiative of Primary Sjögren's Syndrome (KISS) prospective cohort study. Twenty-one with CSS and 501 patients with pSS from Seoul St. Mary's Hospital were retrospectively analyzed. Results: Patients with CSS were older at diagnosis, had a lower prevalence of ocular symptoms, and exhibited distinct immunological markers compared to those with pSS. Logistic regression analysis revealed that anti-Ro antibody positivity, elevated erythrocyte sedimentation rate levels, low serum complement 3 levels, and accompanying dry eye symptoms were factors distinguishing pSS from CSS. Conclusion: Even after excluding IgG4-RD, CSS was significantly different from pSS in terms of clinical and laboratory findings. Recognition of these differences is crucial for the accurate diagnosis and management of CSS, underscoring its status as a distinct pathological entity among salivary gland pathologies.

A pilot study of skin barrier function in patients with systemic sclerosis and primary Sjögren's syndrome.

Objective: Although the close interactions between the epidermis and dermis of the skin have been widely explored, the skin barrier functions of the stratum corneum (SC) in patients with systemic sclerosis (SSc) and primary Sjögren's syndrome (pSS) are not well known. We aimed to investigate the biophysical characteristics of the skin, including transepidermal water loss (TEWL), the SC water content, erythema, and the melanin index, in patients with SSc and pSS. Methods: This case-control study included 34 patients with SSc, 31 patients with pSS, and 25 healthy controls. All parameters were measured on the extensor surface of the forearm and compared between patients and healthy controls. In patients with SSc, we performed subgroup analyses by disease subtype (diffuse and limited cutaneous SSc), the modified Rodnan skin sclerosis score (>6 or ≤6), and comorbid secondary SS status. In patients with pSS, subgroup analyses were performed by anti-Ro/SSA antibody status and the findings of salivary gland ultrasound. Results: No statistically significant differences were observed in TEWL or skin hydration between patients with SSc and pSS and healthy controls. In the pSS group, only the erythema index was significantly increased compared to the control group. In subgroup analyses, no significant differences were observed in the extent of TEWL or skin hydration by disease subtype, severity, autoantibody profile, or comorbidities. Conclusion: Patients with SSc or pSS did not exhibit specific impairments of skin barrier function or skin hydration. Further studies with larger sample sizes and age-matched controls are required.

"An update on the approach to treatment of Sjogren's Disease in pregnancy".

BACKGROUND: Women with Sjögren's Disease are more likely to experience pregnancy complications compared to their counterparts without the disease. Attention to detail and familiarity with the most recent research and guidelines in this field are required to achieve optimal maternal and fetal outcomes. Such complications include pregnancy induced hypertension, fetal growth restriction, thromboembolic events, and preterm delivery. Among the most life-threatening sequela of maternal Sjogren's Disease is fetal autoimmune congenital heart block (ACHB), which has high potential to cause intrauterine fetal death, neonatal mortality, developmental delay, and other long-term pediatric complications. Currently, surveillance with weekly echocardiograms and obstetric sonograms in the second trimester are recommended to screen for ACHB with the goal of early detection and intervention before progression from first- or second- of heart block to complete heart block. OBJECTIVE: We describe a case of maternal Sjogren's Disease, which prompted us to raise questions regarding the optimal frequency of obtaining fetal echocardiograms, and the ideal management in case a prolonged PR interval was to be found. We use this case to provide a springboard for discussion on updated antenatal management strategies for ACHB prevention. METHODS: To conduct this analysis, we searched PubMed for articles published over the last 10 years, with attention focused on articles written since 2016. Additionally, updated guidelines by other specialties such as Rheumatology, Cardiology and Pediatrics on this issue were reviewed. RESULTS: Thorough search of the literature yielded several meta-analyses concurring that the mothers with Sjogren's Disease had increased rates of premature birth, pregnancy induced hypertension, increased risks of delivering infants with intrauterine growth restriction (IUGR), with the most life-threatening risk being that of congenital heart block. Literature supporting prophylactic hydroxychloroquine and the use of steroids to reverse or halt the progression of congenital heart block at the time of diagnoses appeared at the forefront of search results. CONCLUSION: Pregnant women with SS have an increased risk for complications such as intrauterine growth restriction, thromboembolic events, pregnancy-induced hypertension, preterm delivery, and cesarean delivery and should prioritize obtaining pre- or peri-conceptional counseling. In women with anti SSA/SSB antibodies, a medication regimen should be considered with the object of decreasing the concentration of these antibodies, and hence decrease the risks of ACHB. Current literature supports the inclusion of hydroxychloroquine for this purpose, even prior to conception. Although the most recent studies recommend against prophylactic use of steroids, their potential to prevent progression to complete block should be weighed against their potential negative effects. Short and long-term treatment with corticosteroids has been associated with increased maternal risk of infection, weight gain, osteonecrosis, hypertension and bone mineral density disorders. Intrauterine growth restriction, oligohydramnios, and adrenal suppression have been among the fetal risks associated with steroids while improved infant survival or decreased need for pacing have not been demonstrated. Management of these pregnancies is complex and should include a multidisciplinary approach involving a maternal-fetal medicine sub-specialist, a rheumatologist, a pediatrician, a neonatologist, and the patient herself with her family in a model of shared decision-making.

Immunoglobulin G4 in primary Sjögren's syndrome and IgG4-related disease - connections and dissimilarities.

Primary Sjögren's syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases.

Development of a web-based ecological momentary assessment tool to measure day-to-day variability of the symptoms in patients with Sjögren's disease.

OBJECTIVES: To develop and validate a web-based ecological momentary assessment (EMA) tool to enhance symptoms monitoring among patients with Sjögren's disease (SjD). METHODS: Consecutive adults with SjD were enrolled in this pilot observational study. Participants used the WebApp over a 3-month period, for the daily collection of individual EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) scales and separate assessment of eyes and mouth dryness, using 0-10 numerical scales. Primary outcome was the measure of the interdaily variability of symptoms. Data collected through the WebApp were compared with those obtained with paper-based questionnaires administered during a final visit, using distinct approaches (predicted error, maximum negative error and maximum positive error). User experience was assessed using the System Usability Scale (SUS) score. RESULTS: Among the 45 participants, 41 (91.1%) were women. Median age was 57 years (IQR: 49-66). Daily variability of symptoms ranged between 0.5 and 0.8 points across the scales. Over the 3-month period, the predicted error ranged between -1.2 and -0.3 points of the numerical scales. The greatest differences were found for fatigue (-1.2 points (IQR: -2.3 to -0.2)) and ESSPRI score (-1.2 points (IQR: -1.7 to -0.3)). Over the last 2 weeks, the predicted error ranged between - 1.2 and 0.0 points. Maximum negative error ranged between -2.0 and -1.0 points, and maximum positive error between -0.3 and 0.0 points. Median SUS score was 90 (IQR: 85-95). CONCLUSION: Our results demonstrate the usability and the relevance of our web-based EMA tool for capturing data that closely reflects daily experiences of patients with SjD.

Novel Inflammatory Markers Associated With Cutaneous Leukocytoclastic Vasculitis Etiology.

Objectives: We aimed to compare inflammatory markers and determine their potential role in distinguishing secondary leukocytoclastic vasculitis (SLV) from idiopathic leukocytoclastic vasculitis (ILV). Materials and Methods: We included in this cross-sectional study patients with cutaneous leukocytoclastic vasculitis (CLV) diagnosed on cutaneous biopsy. We assessed clinical and laboratory data and then calculated platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP)-to-albumin ratio (CAR), and fibrinogen-to-albumin ratio (FAR). We have also defined the number of positive etiological examination (NPE) as the sum in a unique patient of the positive paraclinical examinations involved in the etiological assessment of CLV. Results: In total 77 patients were included, with 52 SLV group patients and 25 in the ILV group, mean age was 44+/-18 vs 49+/-21, and gender ratio was 29/23 vs 11/14. Comparison of PLR, NLR, CAR, and FAR showed significant differences in mean values between SLV and ILV groups with 199.1 (117.3-309.8) vs 126.8 (79-193) (P = 0.01) for PLR, 3.6 (1.9-5.1) vs 2.3 (1.7-3.4) (P = 0.048) for NLR, 1.9 mg.g-1 (0.4-3.6) vs 0.6 mg g-1 (0.2-1.9) (P = 0.043) for CAR, and 155.8 mg.g-1 (90.7-192.3) vs 108.7 mg.g-1 (82.2-148.1) (P = 0.034) for FAR. PLR, CAR, and FAR were positively correlated to NPE (r = 0.463, P < 0.001; r = 0.434, P < 0.001; and r = 0.411, P < 0.001, respectively), and there was no significant correlation between NLR and NPE (r = 0.165, P = 0.151). Conclusion: This is the first study to investigate PLR, NLR, CAR, and FAR in CLV, and it demonstrates that elevation of these ratios is associated with SLV, which leads us to suggest to exhaustively explore patients with elevated ratios.

A Rare Presentation of Cryoglobulinemic Vasculitis Associated with Primary Sjögren's Syndrome.

INTRODUCTION: Sjögren's syndrome is a chronic autoimmune disorder that results in dry eyes and mouth. It is rarely associated with cryoglobulinemia, the agglutination of cryoglobulins at cold temperatures that leads to systemic inflammation and organ damage. We have, herein, presented a case of Cryoglobulinemic Vasculitis (CryoVas), which presents as cryoglobulinemic glomerulonephritis and Central Nervous System (CNS) vasculitis and peripheral neuropathy. CASE REPORT: A 52-year-old woman with a past medical history of Sjögren's syndrome was admitted to the intensive care unit with severe hyponatremia, orthopnea, and progressive lower extremity weakness, and was found to have an intradural extramedullary hematoma with mass effect in the thoracic spine and diffuse hyperintense cord signal abnormality in thoracic spine suggestive of intermixed proteinaceous or hemorrhagic material. Further testing demonstrated that the patient experienced worsening neuropathy, proteinuria, hematuria, declining renal function, and the presence of cryoglobulins in the blood. After a thorough examination and a renal biopsy, the patient was diagnosed with cryoglobulinemic glomerulonephritis and cryoglobulinemic vasculitis of the spine. The patient was treated with rituximab and pulse-dose steroids, with which the patient exhibited improved renal function and resolution of a previously seen intradural hematoma on repeat MRI. CONCLUSION: We have, herein, discussed a rare case of cryoglobulinemic vasculitis that has led to a rare CNS manifestation and concomitant cryoglobulinemic glomerulonephritis. This suggests that clinicians should consider cryoglobulinemic vasculitis as the etiology that could manifest with multiorgan involvement, especially in patients with underlying rheumatic diseases.