Frederick B. Vivino

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

We propose new classification criteria for Sjögrens syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.

Primary Sjögren's Syndrome: health experiences and predictors of health quality among patients in the United States

ObjectiveTo assess the health related quality of life of patients with primary Sjögrens Syndrome (PSS) in a large US sample.MethodsQuestionnaires were mailed to 547 patients with a confirmed diagnosis of PSS (PhysR-PSS) and all active members of the Sjögrens Syndrome Foundation USA (SSF-PSS), half of whom identified a friend without PSS to also complete the survey.Results277 PhysR-PSS patients were compared to 606 controls. The mean age was 62 years in the PhysR-PSS group and 61 years in the control group. 90% in both groups were women. Time from first symptom to diagnosis of PSS was a mean of 7 years. Sicca related morbidity, fatigue severity, depression and pain (assessed by validated questionnaires, PROFAD-SSI, FACIT-F, CES-D, BPI) were significantly greater, and all eight SF-36 domains were significantly diminished, in patients compared to controls. Somatic fatigue was the dominant predictor of physical function and of general health. Depression was the dominant predictor of emotional well being. Health care utilization was higher in patients than controls, including out of pocket dental expenses (mean: PhysR-PSS =

Primary Sjögren’s Syndrome as a systemic disease: a study of participants enrolled in an international Sjögren’s Syndrome registry

1473.3, controls =

Rituximab Therapy for Primary Sjögren’s Syndrome: An Open-Label Clinical Trial and Mechanistic Analysis

503.6), dental visits (mean: PhysR-PSS = 4.0, controls = 2.3), current treatments (mean: PhysR-PSS = 6.6, controls = 2.5), and hospitalizations (53% PhysR-PSS, vs. 40% controls).ConclusionDiminished health quality and excess health costs are prevalent among PSS patients. Health experiences and functional impact of PSS is similar among US and European patients. Delayed diagnosis, sicca related morbidity, fatigue, pain and depression are substantial suggesting unmet health needs and the importance of earlier recognition of PSS.

Diagnostic accuracy of salivary scintigraphic indices in xerostomic populations.

To study the prevalence of extraglandular manifestations in primary Sjögrens syndrome (SS) among participants enrolled in the Sjögrens International Collaborative Clinical Alliance (SICCA) Registry.

Hydralazine-induced autoimmune disease: comparison to idiopathic lupus and ANCA-positive vasculitis

OBJECTIVE To study the safety and clinical efficacy of rituximab therapy for primary Sjögrens syndrome, as well as to investigate its mechanisms. METHODS Patients with primary Sjögrens syndrome were enrolled in an open-label trial, were given rituximab (1 gm) infusions on days 1 and 15, and were monitored through week 52. The primary end point was safety, with secondary end points evaluating clinical and biologic efficacy. Blood was obtained for enumeration of lymphocyte subsets, measurement of serum autoantibody and BAFF levels, and analysis of gene expression. RESULTS Twelve female patients with primary Sjögrens syndrome were administered rituximab. They had a median age of 51 years (range 34-69 years) and a median disease duration of 8.0 years (range 2-18 years). We observed no unexpected toxicities from the rituximab therapy. Modest improvements were observed at week 26 in patient-reported symptoms of fatigue and oral dryness, with no significant improvement in the objective measures of lacrimal and salivary gland function. The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells. While blood B cell depletion was associated with an increase in serum BAFF levels, no significant changes were observed in the levels of serum anti-Ro/SSA, anti-La/SSB, and anti-type 3 muscarinic acetylcholine receptor autoantibodies or in the blood interferon signature. CONCLUSION In patients with primary Sjögrens syndrome, a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells.

The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sjögren's syndrome

PURPOSE Three decades of work to enhance the diagnostic accuracy of salivary scintigraphy have generated various plausible decision criteria. This study evaluates four commonly cited numeric indices in studies of xerostomic populations and how accurately they identify Sjögrens syndrome, chronic sialadenitis, radiation sialadenitis, and drug effects and distinguish each from the other. METHODS Stimulated dynamic salivary scintigraphy was performed on 295 xerostomic patients and on 31 controls. The nonparametric area under the receiver operating characteristic curves expressed the diagnostic accuracy of the following scintigraphic indices: the parotid:submandibular ratio of unstimulated glandular activity, the peak:baseline uptake ratio, its time of occurrence, and the stimulated excretion fraction. RESULTS The stimulated excretion fraction distinguished Sjögrens syndrome and radiation sialadenitis from healthy states with respective accuracies of 0.78 and 0.90. The maximum diagnostic payoff in Sjögrens syndrome occurred at a cutoff of 73%, yielding a 73% rate of test sensitivity and a 73% rate of specificity. The other three indices were not useful. Even the stimulated excretion fraction performed indifferently or poorly in most other diagnostic tasks. CONCLUSIONS In the scintigraphic examination of xerostomic and healthy populations, an acceptable diagnostic utility of the stimulated excretion fraction was evident only in Sjögrens syndrome and radiation sialadenitis. When presented with differential diagnostic alternatives not involving radiation sialadenitis, none of the four numeric indices performed acceptably.

Tear osmolarity in Sjögren syndrome.

We report two cases of hydralazine-induced vasculitis with rare complications: pulmonary renal syndrome and digital gangrene. We also review 68 published cases of hydralazine-induced vasculitis. Hydralazine-induced vasculitis mimics idiopathic antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. However, it also produces other autoantibodies, such as antinuclear antibodies, antihistone antibodies, anti-dsDNA antibodies, and antiphospholipid antibodies. Patients with hydralazine-induced vasculitis typically have a more severe course than those with hydralazine-induced lupus, predominantly due to renal vasculitis, and require a more aggressive treatment.

New Treatment Guidelines for Sjögren's Disease

Objective To determine whether the Sjögrens syndrome B (SSB)-positive/Sjögrens syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. Methods Among registrants in the Sjögrens International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. Results Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. Conclusions The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

Treatment Guidelines for Rheumatologic Manifestations of Sjögren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain

Purpose: The Schirmer test is one of the 2 ocular surface tests included in the current classification criteria for Sjögren syndrome (SS). Tear osmolarity may also be a useful test for the diagnosis of dry eye disease. The purpose of this study was to examine the relationship between tear osmolarity, the Schirmer test I, and dry eye symptoms in SS. Methods: Patients with a diagnosis of SS were assessed for tear osmolarity with the TearLab Osmolarity System, tear production with Schirmer testing, symptoms with the Ocular Surface Disease Index (OSDI), and discomfort associated with each test. Results: Forty-nine patients with a mean age of 53.7 years and a female (92%) predominance were enrolled. The majority of patients (86%) were receiving systemic therapy for severe SS. Higher tear osmolarity was moderately associated with lower scores on the Schirmer test I (&rgr; = −0.39, P < 0.01) and OSDI (&rgr; = −0.45, P < 0.01). Schirmer test I results and lower OSDI scores were not correlated significantly (&rgr; = 0.20, P = 0.17). Tear osmolarity testing was significantly less painful than Schirmer testing (P < 0.01). Conclusions: Signs and symptoms of dry eye in SS patients were not strongly correlated. An unexpected finding was that higher tear osmolarity was associated with lower symptom severity. Tear osmolarity testing in the clinical setting was feasible and was associated with significantly less discomfort than Schirmer testing in patients with severe SS.