The Role of Major Salivary Gland Ultrasound in the Diagnostic Workup of Sicca Syndrome: A Large Single-Centre Study.

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren's syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy.

Axial spondyloarthritis in patients with recurrent fever attacks: data from the AIDA network registry for undifferentiated autoInflammatory diseases (USAIDs).

Beckground: Despite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment. Materials and methods: Patients' data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network. Results: A total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARDs were more useful when combined with biotechnological agents. Conclusion: Signs and symptoms referring to axial SpA should be inquired in patients with apparently unexplained recurrent fever episodes. The specific treatment for axial SpA may lead to a remarkable improvement in the severity and/or frequency of fever episodes in patients with unexplained fevers and concomitant axial SpA.

Diagnostic role of minor salivary glands biopsy in Sjögren's syndrome: correlations between histology and autoimmunity in a large, monocentric cohort.

Introduction: Based on ACR/EULAR classification criteria, minor salivary glands biopsy (MSGB) is a useful diagnostic tool for the diagnosis of primary Sjögren's syndrome (SS). The main objective of our study was to evaluate the diagnostic role of MSGB, as well as to highlight correlations between histological findings and autoimmune profiles. Material and methods: We retrospectively evaluated histological and autoimmunity data from patients who underwent MSGB in our department in cases of suspected SS, from March 2011 to December 2018. Salivary gland samples were evaluated using Chisholm and Mason (CM) grading and the focus score (FS). Results: A total of 1,264 patients (108 males, 1,156 females) were included. The median age was 55.22 ±13.51 years (range: 15-87). In univariate binary logistic regression, CM ≥ 3 and FS ≥ 1 were significantly predicted by antinuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-Ro/SSA titer as well as anti-La/SSB, anti-Ro/SSA, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity. In multivariate analysis, CM ≥ 3 and MSGB positivity were significantly associated with ANA titer; FS ≥ 1 was not associated with laboratory findings. A positive biopsy was associated with laboratory findings, as ANA and ENA titers, anti-Ro/SSA, anti-La/SSB, RF and ACPA positivity may discriminate patients with SS-related histological findings. Conclusions: Minor salivary glands biopsy is a useful tool to diagnose SS in cases of highly suggestive clinical symptoms but in the absence of a specific autoimmunity.

Routine IgG4 staining in minor salivary gland biopsy in a cohort of Italian Caucasian patients suffering from xerostomia.

Objectives: IgG4-related disease is a potentially systemic disease mimicking and overlapping with different autoimmune diseases, such as primary Sjögren's syndrome (pSS). The involvement of salivary glands, previously called Mikulicz's disease, has been reclassified as IgG4-related sialadenitis (SA). The aim of this study was to assess the prevalence of IgG4-SA in a cohort of Italian Caucasian patients presenting with xerostomia and to evaluate the eventual overlap between IgG4-SA and pSS. Material and methods: We included 154 patients - 15 males and 139 females, mean age 54.18 ±14.24 years, who underwent minor salivary gland biopsy between March and December 2019 for xerostomia. Histopathology was evaluated using Chisholm-Mason (CM) and focus score (FS) for pSS and immunohistochemical study with IgG4 staining for IgG4-SA were performed. Serum autoantibodies (anti-SSa/RoAb, anti-SSB/LaAb, antinuclear antibodies, rheumatoid factor) were also assessed. Results: In 69 patients (44.8%) FS 0 was found, while FS ≥ 1 was presented in 85 (55.2%). Chisholm-Mason score < 3 and CM ≥ 3 was found in 73 (47.4%) and 81 (52.6%) cases, respectively. IgG4/high-power field level was 20 in 3 pSS patients (1.9%), but none of them had an IgG4/IgG ratio ≥ 40, as well as tissue fibrosis with storiform pattern, obliterative vasculitis, and tissue eosinophilia. The diagnosis of pSS, was confirmed in 92 patients (59.74%). No patient was definitively diagnosed with an IgG4-related disease. Conclusions: In the case of xerostomia, the evaluation of the histopathological specimen for IgG4 should not be routinely performed, at least in an Italian-based Caucasian population. Moreover, immunohistochemistry should not be requested in the case of a negative result of biopsy for pSS.

Inflammatory muscle involvement in systemic vasculitis: A systematic review.

Vasculitis are severe systemic autoimmune diseases which may involve different organs and systems. Conversely, muscles do not represent an organ commonly involved by systemic vasculitis and myositis is not include among any classification or diagnostic criterion of vasculitis. In this regard, we aimed to review the literature in order to report all the available evidence concerning the inflammatory involvement of muscle in patients affected by systemic vasculitis. We collected a total of 108 papers, for a sum of 395 patients affected by muscle vasculitis. Most of them suffered from medium and small vessels vasculitis (mainly polyarteritis nodosa and ANCA-associated vasculitis) or from vasculitis secondary to rheumatoid arthritis. Conversely, muscle involvement in case of large vessel vasculitis occurred seldom, while only few papers reported such occurrence in Kawasaki or Behçet's disease. Histological findings may differ, but the most common ones displayed a necrotizing vasculitis of perimysium vessels, while granulomatous vasculitis was assessed only in case of ANCA-associated vasculitis patients. Creatine kinase were usually within normal range, seldom elevated, while imaging findings were generally undistinguishable from the ones found in idiopathic inflammatory myopathies: magnetic resonance imaging displays signal hyperintensity in T2 and STIR scans, while few data exist for positron emission tomography. The presentation of the disease may be fearsome and severe, sometimes life-threatening, but an overall good response to conventional immunosuppressants and/or glucocorticoids has been reported.

Paraneoplastic arthritides: an up-to-date case-based systematic review.

Among the rheumatic diseases whose symptoms are more often associated with the possibility of cancer and other malignancies are systemic sclerosis, dermatomyositis and rheumatic polymyalgia. However, a differential diagnosis should be performed in each case of non-typical rheumatic disease and/or other neoplastic disease risk factors. The article's aim was based on a literature review of this subject and presentation own a case description and discussion about arthritis as a paraneoplastic syndrome. The conclusions of our analysis were as follows: more often paraneoplastic arthritis occurs in men, in ages higher than 50 years old, in patients who poorly respond to treatment of arthritis with polyarticular symmetrical involvement of the limbs, seronegative type of inflammatory joint disease. In this group of patients, complete remission after treatment of the primary tumor and recurrence of the symptoms in the presence of metastasis was observed.

Atypical Posterior Reversible Encephalopathy Syndrome (PRES) in a Patient with Polymyalgia Rheumatica and Giant Cell Arteritis.

Posterior reversible encephalopathy syndrome (PRES) is a potentially life-threatening condition, composed of focal neurologic symptoms and peculiar magnetic resonance imaging (MRI) findings suggestive for cerebral vasogenic edema. PRES has been predominantly associated with severe hypertension, but a concomitant inflammatory state, common in vasculitis, can contribute to worsening cerebral vasogenic edema towards cytotoxic edema, and it should be promptly treated with glucocorticoids (GC). Atypical cases of PRES should be suspected in cases of focal neurologic symptoms, associated with severe hypertension, and systemic inflammation. We report the first description of a patient with polymyalgia rheumatica and giant cell arteritis who developed PRES after GC discontinuation for arthroscopic surgery.

Ultrasound evaluation of the scapholunate ligament and scapholunate joint space in patients with wrist complaints in a rheumatologic setting.

AIM: The aims of the study were to perform an ultrasound assessment of the dorsal portion of the scapholunate interosseous ligament and scapholunate joint space in patients with wrist complaints in a rheumatologic setting, to describe ultrasound abnormalities about scapholunate interosseous ligament region, and to correlate them with clinical data, presence of dorsal ganglion cysts and diagnoses of rheumatic diseases. MATERIAL AND METHODS: Seventy-four consecutive patients with wrist pain and/or swelling were evaluated by routine power Doppler ultrasound. Forty normal wrists were studied to confirm the normality values of the scapholunate joint. RESULTS: The mean width of the normal scapholunate joint was 2.49 mm (±0.49 SD), with a coefficient of variation on repeated measurements of 3.662%. The best predictors of scapholunate interosseous ligament degeneration were: older age (p <0.0001), male gender (p = 0.0049), and radiocarpal effusion (p = 0.0156). The presence of osteophytosis and calcifications of the scapholunate joint were higher (p <0.001) in rheumatic patients. Scapholunate calcifications showed a sensitivity of 98.2% and a specificity of 61.1% for calcium pyrophosphate deposition disease. Dorsal ganglion cysts were more frequent in younger subjects (p <0.0012) without rheumatic conditions (p <0.0001) or midcarpal synovitis (p <0.0001). Larger cysts often exhibited power Doppler signal (p <0.0001). The best predictors of scapholunate dissociation were: male gender (p = 0.0002), presence of midcarpal synovitis (p <0.0137), and higher grade of scapholunate interosseous ligament degeneration (p <0.0001). Scapholunate widening was greater (p = 0.0419) in calcium pyrophosphate deposition disease or rheumatoid arthritis than in other rheumatic conditions. CONCLUSIONS: Ultrasound findings of scapholunate interosseous ligament degeneration and calcification, scapholunate space enlargement, and dorsal ganglion cysts should be considered in ultrasound reporting, since they add useful information about the diagnosis of associated rheumatic conditions.

Biologic drugs in the treatment of polyarteritis nodosa and deficit of adenosine deaminase 2: A narrative review.

Polyarteritis nodosa (PAN) is a medium vessels vasculitis variously involving different organs and systems, sometimes with an aggressive course, leading to death or disability in a significant number of cases. First-line treatment usually relies on steroids and classical immunosuppressants, but a growing number of case reports and small case series shows the potential role of biologic drugs, mostly anti-tumor necrosis factor (TNF)-α agents, in inducing and maintaining remission in patients affected by PAN. Similarly, the recently described autoinflammatory disease named deficit of adenosine deaminase 2 (DADA2), considered by several experts as a more precocious and aggressive variant of PAN, seems to respond to a prompt treatment with TNF-α inhibitors. The aim of this review is to collect all existing evidences about the use of biologic drugs in PAN and DADA2. Fifty-one articles published during the last 15 years were retrieved, including 58 and 76 patients affected by PAN and DADA2, respectively, and treated with biologic drugs. The majority of subjects was treated with TNF-α inhibitors, whose effectiveness was reported in the treatment of such difficult-to-manage diseases, particularly in DADA2. Among the other biologic drugs, Tocilizumab was successfully employed in some subjects affected by PAN who did not respond to TNF-α inhibitors, while Rituximab did not give substantial benefits neither in PAN nor in DADA2. Only few data exist about the role of Janus-kinase inhibitors and anti-IL1 agents. This study provides the first comprehensive assessment of biologic agents in both PAN and DADA2, with encouraging results especially in the context of TNF-α inhibitors. Nevertheless, due to the lack of prospective, randomized, case control studies, further efforts should be made in order to fully elucidate the role of these drugs in such rare and life-threatening conditions.

Enthesitis of proximal insertion of the deltoid in the course of seronegative spondyloarthritis. An atypical enthesitis that can mime impingement syndrome.

OBJECTIVE: To study the frequence of deltoideal proximal insertion enthesitis (DPIE) in patients affected with spondyloarthritis (SpA) and to evaluate its clinical, sonographic and radiological characteristics. METHODS: A retrospective study of clinical, sonographic and radiological examinations of the shoulders of 100 symptomatic consecutive outpatients with SpA, compared to 4 groups of control patients: 100 with Rheumatoid Arthritis, 100 with Osteoarthritis, 100 with Painful Shoulder, and 50 with shoulders undamaged by local pathological processes. RESULTS: The frequence of DPIE in the course of SpA was 9%. DPIE appears most frequently in Psoriatic Arthritis (PsA) (17%, 7/41). DPIE does not appear to be related to the sex or the age of the patient. The clinical signs and symptoms are similar to those of an impingement syndrome. Sonography reveals thickening and hypoechogenicity of the enthesis, associated or not to the subchondral osseous rearrangement and enthesophytosis. Radiology only reveals the enthesophytosis in the later stages. CONCLUSIONS: DPIE can determine shoulder pain in the course of SpA, and in particular in PsA. The clinical manifestations of DPIE are very similar to those of an impingement syndrome; sonography can differentiate the two conditions.