Extraglandular Complications Research Articles

The difficult way in diagnostics of neurological manifestations of Sjogren's disease. Case report

Sjogren's disease is an immunoinflammatory rheumatic disease that is characterized by damage to the secreting epithelial glands with the development of parenchymal sialadenitis with xerostomia and keratoconjunctivitis sicca with hypolacrymia. Due to the high heterogeneity of clinical manifestations of this disease, diagnosis is difficult. This article presents a clinical case of a patient with a detailed description of the manifestation, course, and treatment of Sjogren's disease with a rare combination of extraglandular complications in the form of polymyositis and secondary polyneuropathy.

Severe extra-glandular involvement and pleural effusions complicating primary Sjogren’s syndrome: a case report

BackgroundSjogren’s syndrome, an autoimmune disease of the exocrine glands, results in keratoconjunctivitis sicca, xerostomia, and dental caries. It is often overlooked, considered by clinicians to be a benign disease. However, it can cause life-threatening extra-glandular complications that affect multiple organ systems.Case presentationHere we present a 78-year-old Caucasian woman with a history of primary Sjogren’s syndrome (pSS) whose symptoms of keratoconjunctivitis sicca were managed managed conservatively. She was evaluated for sub-acute shortness of breath. Imaging showed severe bronchiectasis with features of lymphocytic interstitial pneumonia. She also had exudative bilateral pleural effusions and skin ulcers, likely vasculitic in origin. The workup was significant for anti-Ro antibody, pancytopenia, hypocomplementia, cryoglobulinemia and monoclonal gammopathy, all of which reflect disease severity. Although there was no evidence of malignancy, she developed B-cell non-Hodgkin lymphoma during follow-up.ConclusionsPrimary Sjogren’s syndrome can result in severe multi-organ disease. Pleural effusions are a rare complication of pSS, with only ten cases reported in the literature over the last 30 years, and tend to respond well to steroids. Prognostic biomarkers for disease severity include hypocomplementia, cryoglobulinemia, monoclonal gammopathy, and hypergammaglobulinemia. In this report we review the literature and the management of the disease.

Chest high-resolution computed tomography in primary Sjögren's syndrome: an up-to-date primer for rheumatologists.

Pulmonary manifestations, including airway involvement and interstitial lung disease, are the most frequent extra-glandular complications of primary Sjögren's syndrome (pSS). Chest high-resolution computed tomography (HRCT) is a cornerstone of pulmonary diagnostic imaging, aiming to detect, characterise, and quantify such conditions. In patients with pSS-related lung abnormalities, HRCT proved helpful in various clinical scenarios, including baseline and follow-up evaluation, assessment of superimposed infections, suspected progressive interstitial lung diseases, and acute exacerbation. This review aims to provide a primer for rheumatologists on chest HRCT, illustrating the up-to-date technique, imaging findings, and clinical indications in pSS and highlighting the importance of rheumatologist-radiologist constructive collaboration in the clinical management of such patients.

Reduced tear thrombospondin‐1/matrix metalloproteinase‐9 ratio can aid in detecting Sjögren's syndrome etiology in patients with dry eye

Differentiating patients with Sjögren's syndrome (SS)‐associated dry eye from non‐SS dry eye is critical for monitoring and appropriate management of possible sight‐ or life‐threatening extraglandular complications associated with SS. We tested whether reduced tear levels of immunoregulatory thrombospondin (TSP)‐1, which also inhibits matrix metalloproteinase (MMP)‐9, would reflect SS pathogenesis aiding the identification of patients with SS‐dry eye. Total of 61 participants, including healthy controls (n = 20), patients with non‐SS dry eye (n = 20) and SS‐dry eye (n = 21) were enrolled prospectively. Tear TSP‐1 and MMP‐9 levels were measured using a custom magnetic bead‐based multi‐plex assay in a masked manner. Analyte concentrations were assessed further according to ocular surface and tear film parameters. Relative to median tear TSP‐1 (308 ng/ml) and MMP‐9 (1.9 ng/ml) levels in the control group, significantly higher proportion of patients with SS‐dry eye than non‐SS had lower tear TSP‐1 levels (55% vs. 29%, odds ratio [OR] = 3, 95% confidence interval [CI] = 1.64 to 5.35, p < 0.05) and higher tear MMP‐9 levels (65% vs. 24%, OR = 5.8, 95% CI = 4.46 to 19.81, p < 0.05), respectively. The tear TSP‐1/MMP‐9 ratio was significantly reduced in patients with SS‐dry eye compared to non‐SS (B = −2.36, 95% CI = −3.94 to −0.0.79, p < 0.05), regardless of tear MMP‐9 levels. Patients with a lower ratio were 2.3 times more likely to have SS (OR = 0.28, 95% CI = 0.1 to 0.75, p < 0.05). This ratio showed significant inverse correlations with clinical parameters (conjunctival and corneal staining scores). Our results denote that tear TSP‐1/MMP‐9 ratio can be useful in identifying patients with dry eye with underlying SS and used as a screening test.

Cannabidiol (CBD) oil toxicity mimicking extraglandular complications of Sjögren's syndrome.

Cannabidiol (CBD) oil toxicity mimicking extraglandular complications of Sjögren's syndrome.

Chest HRCT findings in patients with primary Sjögren's syndrome.

Pulmonary manifestations (PMs) in primary Sjögren's syndrome (pSS) are among the most frequent extraglandular complications, with reported prevalence varying widely (9-75%), depending on the methods of detection. The aim of this study was to assess the incidence of PMs in pSS and to determine the factors predisposing to the occurrence of this complication. The study group consisted of 68 patients with pSS. Among the patients who were possibly affected by PMs, chest High Resolution Computed Tomography (HRCT) was performed. In the group of all patients afflicted with pSS, 30 people indicated the need to expand medical imaging via chest HRCT scan. (The most frequent reason, in 80%, was persistent, dry cough periodically waking up patients at night). The chest HRCT scan revealed lung tissue changes in the course of 29% of all examined patients (of 68). No correlation was found between the occurrence of HRCT changes and the age of patients (p = 0.8), increased CRP > 5 mg/1 (p = 0.1) or ESR > 20 mm/h (p = 0.9), focus score (p = 0.8), leucopenia (p = 0.5), RF value (p = 0.3), gamma globulin value (p = 0.5), intensity of eye and oral cavity dryness (p = 0.6; 0.3) and smoking cigarettes. Additionally, no correlation was found between more frequent occurrences of antibodies anti-SSA, anti-SSB or anti-Ro52 and HRCT changes (p = 0.3; 0.07; 0.4). Pertaining to the clinical signs, HRCT changes occurred more often only in patients suffering from peripheral arthritis (p < 0.01). PM is a frequent symptom of pSS. A factor predisposing to the development of changes in the respiratory system was not found. Changes in HRCT occur more frequently in patients with peripheral arthritis.

Mikuliczs Disease and its Extraglandular Lesions

Mikuliczs disease has been considered a part of primary Sjogrens syndrome since Morgans 1953 report. Mikuliczs disease is a unique condition involving enlargement of the lacrimal and salivary glands, as is also seen in Sjogrens syndrome; however, Mikuliczs disease is clinically characterized by infrequent autoimmune reactions and responsiveness to glucocorticoid. Fifty years after Morgans study, the understanding of Mikuliczs disease has changed considerably. We first found elevated levels of serum IgG4 and prominent infiltration by plasmacytes bearing IgG4 in the lacrimal and salivary glands in Mikuliczs disease. These findings do not occur in Sjogrens syndrome. The various extraglandular complications of Mikuliczs disease, including autoimmune pancreatitis, tubulointerstitial nephritis, have gradually been clarified in recent reports. These conditions show similar histopathological findings to Mikuliczs disease, indicating that Mikuliczs disease is a part of a broader entity of systemic IgG4-related disease. We herein describe the clinical features of Mikuliczs disease and its extraglandular lesions. Keywords: Immunoglobulin G4, Mikulicz's disease, autoimmune pancreatitis, tubulointerstitial nephritis, Sjogren's syndrome, IgG4-related disease, submandibular glands, Enlargement of lacrimal gland, lymphadenopathy, IgG4-producing plasmacytes

Peripheral Nervous System Manifestations of Sjögren Syndrome

Sjögren syndrome is among the most common autoimmune diseases affecting adults in the United States, and is frequently regarded as an immune-mediated exocrinopathy exclusively causing dry eyes and dry mouth. However, as a systemic rheumatic disease, there can be various "extraglandular" complications. The eclectic permutation of peripheral nervous system (PNS) syndromes which occur in Sjögren patients are among the most common and severe extraglandular complications. This review article highlights the evaluation, differential diagnosis, immunopathogenic mechanisms, and potential treatment options of these PNS complications encountered by neurologists. The sensory neuropathies constitute the most frequent PNS complication. Sjögren patients can suffer from severe neuropathic pain, with small-fiber neuropathy causing lancinating or burning pain which can disproportionately affect the proximal torso or extremities, and the face (ie, in a "non-length-dependent distribution"). The technique of skin biopsy, assessing for the intraepidermal nerve fiber density of unmyelinated nerves, provides a useful technique for neurologists to diagnose small-fiber neuropathies, especially when there is such a non-length-dependent distribution. Other diagnostic techniques (ie, electromyography/nerve-conduction studies, evoked potentials, nerve and muscle biopsy) may be useful in specific subtypes of neuropathies. A rational approach to treatment requires a careful appraisal of the clinical subtype of the neuropathy, as well as a familiarity with such discriminating immunopathogenic mechanisms. The application of the traditional armamentarium used for neuropathic pain can be especially challenging. Sjögren patients can suffer from debilitating fatigue, sicca symptoms, and autonomic findings; as such manifestations can be complications of various neuropathic agents, neurologists should understand how to minimize such iatrogenic complications. Therefore, this article will empower neurologists to more effectively collaborate with rheumatologists, in the diagnosis and treatment of Sjögren patients with PNS complications.

Emerging biotherapies for Sjögren's syndrome

Importance of the field: Sjögren's syndrome (SS) is an autoimmune epithelitis. This exocrinopathy is frequently associated with extraglandular complications, and the patients are at risk of developing B cell lymphoma. Given the lack of disease-modifying drugs, and the fact that SS is a quintessential B-cell mediated disease, attention has recently been focused on biotherapies.Areas covered in this review: Despite negative grounds, TNF-α antagonists have been tested in the disease, and proven not be efficient. However, B-cell depleting therapy using anti-CD20 antibodies such as rituximab, which is a chimeric mAb, has shown promise in the field, while anti-CD22 mAb seems to be less active.What the reader will gain: New treatments against the B-cell activating factor of the TNF family are about to be tested, or replaced by receptor immunoglobulin decay protein.Take home message: B-cell depleting therapies seem promising in SS, but no data are, thus far, available on treatments targeting B-cell activating factor of the TNF family.

Increased levels of circulating microparticles in primary Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity

IntroductionCell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).MethodsWe measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA.ResultsPatients with pSS showed increased plasma level of total MPs (mean ± SEM 8.49 ± 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 ± 1.05 n PS Eq, P = 0.004) and SLE (7.3 ± 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 ± 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum β2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P ≤ 0.006).ConclusionsPlasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.

Syndrome cérébelleux isolé révélant un syndrome de Gougerot-Sjögren primaire

Primary Sjogren's syndrome is an autoimmune exocrinopathy with various extraglandular complications. Central neurological manifestations were described in 20 percent of cases. Cerebellar syndrome is uncommon in Sjogren's syndrome, but can occur after diagnosis, or rarely as an inaugural sign of the disease. We report the case of a 54-year-old man who presented a cerebellar syndrome with xerostomy and xerophthalmos. The diagnosis of primary Sjorgren's syndrome was confirmed on the accessory salivary gland biopsy. The patient received oral and intravenous corticosteroid therapy associated with cyclophosphamide monthly. Outcome was good.

Prédominance de la sous-classe IgG1 parmi les anticorps anti-Ro/SSA, mais pas parmi les anticorps anti-La/SSB, au cours du syndrome de Gougerot-Sjögren primaire

Isotype-specific enzyme-linked immunosorbent assays have been developed to assess anti-Ro/SSA and anti-La/SSB IgG subclasses in 31 patients with primary Sjögren's syndrome. The anti-Ro/SSA antibody production was largely restricted to IgG1, whilst the anti-La/SSB subclass distribution varied from one patient to another. IgG2 and IgG3 anti-La/SSB were more frequent in those patients with extraglandular complications.

Primary Sjögren's syndrome in men: Clinical, serologic, and immunogenetic features

Although primary Sjögren's syndrome is a common rheumatic disorder in women, it is not well recognized in men. This study represents the first report of the clinical, serologic, and immunogenetic features of a group of 36 men with primary Sjögren's syndrome, which are contrasted with those of a group of 69 women with primary Sjögren's syndrome. The majority of male patients had extraglandular involvement including articular (78 percent), neurologic (39 percent), inflammatory vascular (25 percent), and lymphoproliferative disorders (17 percent). Although men were at the same risk for the development of extraglandular complications, there were significant serologic and immunogenetic differences. In sharp contrast to women with Sjögren's syndrome, men with Sjögren's syndrome were seronegative with respect to the presence of serum rheumatoid factor (p = 0.008) and antibodies to Ro(SS-A) (p = 0.016). The supertypic specificity, MT2 (DRw52), as in women, was strongly associated with primary Sjögren's syndrome in men when compared with race-matched control subjects (p = 0.0015). In men, however, the frequency of HLA-B8 and HLA-DR3, the most common DR locus specificity observed in women, was not statistically different from that observed in the normal control group.