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.

Low Doses of Etanercept Can Be Effective to Maintain Remission in Psoriatic Arthritis Patients.

OBJECTIVES: We realized a longitudinal open-label study to determine if increasing intervals between etanercept (ETN) administration could be effective in maintaining remission with a stable dose in a patient population affected by psoriatic arthritis (PsA) who had achieved sustained remission with ETN 25 mg biweekly. METHODS: Fifty-four PsA patients were recruited at the Rheumatology Unit of Azienda Ospedaliera Universitaria Senese. Patients, who were in clinical sustained remission with biweekly ETN 25 mg at weeks 12 and 16, and were switched to a weekly regimen. If clinical remission persists at weeks 24 and 28, patients were switched to an every-other-week regimen, continuing with this administration schedule for the entire duration of the study if at weeks 36 and 40 clinical remission was maintained. If, on the contrary, in one of the check there was an increase in disease activity, the therapeutic scheme returned to the previous one. RESULTS: The results of our study indicate that a consistent percentage (72%) of subjects with PsA, achieving a sustained remission with ETN 25 mg biweekly, maintains a remission, after a year of starting therapy, despite a progressive dose reduction by an increase in the dosing interval, 21% with a weekly regimen and 51% with an every-other-week regimen. CONCLUSIONS: Our results show that the main reasons that hinder the dosing interval increase in ETN in PsA patients in sustained clinical remission at standard doses are peripheral polyarthritis pattern and exacerbation of cutaneous manifestations.

Obstetric outcome associated with trial of labor in women with three prior cesarean delivery and at least one prior vaginal birth in an area with a particularly high rate of cesarean delivery.

OBJECTIVE: The objective of this study is to evaluate maternal and neonatal outcomes associated with trial of labor after cesarean (TOLAC) in women with three prior cesarean delivery (CD) and at least one prior vaginal delivery. METHODS: This is a retrospective study using data collected from clinical records of women three prior CD and at least one prior vaginal delivery who were referred to our unit. Maternal and perinatal outcomes were compared between women with three prior CD who underwent TOLAC and those who underwent planned repeated CD (i.e. control group). The primary outcome was a composite of maternal complications including at least one of the followings: need for blood transfusion, uterine rupture, hysterectomy, and admission to intensive care unit. RESULTS: Fifty singleton gestations with three prior CD at with at least one prior vaginal birth were analyzed. Of them, 10 accepted to undergo TOLAC. Of the 10 women who underwent TOLAC, nine had vaginal birth and one had CD for non-reassuring pattern. We found no significant differences in the primary outcome, in need for blood transfusion, in the incidence of uterine rupture, hysterectomy, and admission to intensive care unit comparing TOLAC group with controls. CONCLUSION: TOLAC in women with three prior CD and at least one prior vaginal delivery is a viable option and is not associated with higher risk of adverse maternal or fetal outcomes.

Low doses of etanercept can be effective to maintain remission in ankylosing spondylitis patients.

We wanted to do a prospective open-label study to evaluate if ankylosing spondylitis (AS) patients in clinical remission with twice weekly etanercept (ETN) 25 mg therapy could be changed to weekly regimen or even to every other week regimen without increased dose for injection. Thirty-eight AS patients self-administered 25 mg of ETN (Wyett) subcutaneously. According to the protocol, patients who were in clinical partial remission with twice weekly ETN 25 mg at week 12 and 16 changed to a weekly regimen without a change of the dose. If clinical remission, despite the reduction of the dose, persists at week 24 and 28, patients changed to an every-other-week regimen, continuing with this administration schedule for the entire duration of the study if at week 36 and 46 clinical remission was maintained. At the end of the study, 18 patients (47 %) were still in remission, 4 (10 %) with a weekly regimen, and 14 (37 %) with an every-other-weekly regimen. Our study indicates that a consistent percentage of subjects with AS, treated with ETN 25 mg twice weekly, achieved clinical remission within the first 3 months of therapy, and also, a substantial percentage of these patients maintains the partial remission with an every other week regimen.

Comparison of combination therapies in the treatment of rheumatoid arthritis: leflunomide-anti-TNF-alpha versus methotrexate-anti-TNF-alpha.

To compare the efficacy and safety of leflunomide (LEF)-anti-TNF-alpha combination therapy to methotrexate (MTX)-anti-TNF-alpha combination therapy in a group of patients with active rheumatoid arthritis (RA). We have recruited 120 patients with RA with a high disease activity despite being treated with MTX (15 mg/week) or LEF (20 mg/die) for 3 months, without side effects. In each of these patients, therapy with either MTX or LEF was continued and randomly combined with an anti-TNF-alpha drug: etanercept, infliximab, or adalimumab. Patients were assessed at study entry and at 4, 12, and at 24 weeks. The efficacy endpoints included variations in the DAS28-ESR and the ACR20, ACR50, and ACR70 responses. At each visit, any side-effect was recorded. There were no statistically significant differences in the DAS28 variations and in the ACR responses between the two groups or among the six subgroups. The number of discontinuation due to the appearance of serious side effects was higher, but not statistically significant, in the LEF-anti-TNF-alpha group than in the MTX-anti-TNF-alpha group. Other adverse events that did not necessitate the discontinuation of therapy occurred much more frequently in patients treated with MTX than in those treated with LEF. Anti-TNF-alpha drugs can be used in combination not only with MTX, but also with LEF, with the same probability of achieving significant clinical improvement in RA patients and without a significantly greater risk of serious adverse events. In contrast, it seems that combination therapy with LEF-anti-TNF-alpha is more readily tolerated than combination therapy with MTX-anti-TNF-alpha.

Sympathetic skin response in primary Raynaud's phenomenon.

OBJECTIVES: The pathogenetic hypotheses of Raynaud's phenomenon include increased activation of sympathetic noradrenergic nerves controlling muscle tone of digit arteriolar walls. Because acral sympathetic fibres contain vasoactive adrenergic and cholinergic fibres for sweat glands, we tested cholinergic sympathetic fibre function in primary Raynaud's phenomenon (PRP) patients by sympathetic skin response (SSR). METHODS: Twenty-six consecutive patients (19 women, 7 men, mean age 37.8 years) with PRP were enroled prospectively. SSR was obtained by random electrical stimulation of the left ulnar nerve at the wrist recording from the palm (PSSR), third (M3SSR) and fifth fingers (U5SSR) on the right side. For each subject latency of shortest response, area of largest response and grand mean latencies and areas of 12 consecutive responses were calculated. The differences between patients and a control group (15 women, 6 men, mean age 38.9 years) were calculated. SSR habituation was also compared between patients and controls. RESULTS: PSSRs were recorded in all patients and no difference in any PSSR parameter was found between patients and controls. U5SSRs and M3SSRs were absent in two patients. Grand mean area and mean of largest M3SSRs and U5SSRs were significantly lower in patients than in controls. Grand mean latency and mean of shortest M3SSRs and U5SSRs were significantly slower in patients than in controls. M3 and U5SSRs habituated less in patients than in controls. INTERPRETATION: Dysregulation of cholinergic sympathetic fibres innervating the fingers was found in PRP. Abnormal peripheral mechanisms may be the cause. Since SSR habituation was also not normal, even central mechanisms may be implicated.

Combination therapy with montelukast and ketotifen for arthritis and rash resulting from idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (IHES) is a rare condition of uncertain etiology characterized by marked peripheral blood eosinophilia and organ system dysfunction that cannot be explained by any factor other than the presence of eosinophils or their potentially toxic products. Diagnostic criteria include 1) a sustained eosinophilia greater than 1500/mm for longer than 6 months, 2) absence of other causes of eosinophilia, including parasitic infections and allergic diseases, and 3) multiorgan involvement (ie, lungs, heart, central nervous system, skin, liver, joints). Steroids represent the initial therapeutic approach, although for those patients unresponsive to steroids, cytotoxic chemotherapy should be considered. We describe a case of IHES characterized by polyarticular inflammatory joint involvement, hypereosinophilia, and urticarioid skin manifestations without visceral involvement. Synovial fluid smears as well as pathology of skin lesions and knee synovial membrane confirmed the presence of numerous eosinophils. The patient was successfully treated with a combination therapy of a cysteinyl leukotriene receptor antagonist (montelukast) and ketotifen. Hypereosinophilic syndrome like in this patient is a rare cause of polyarthritis.