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Objective: To evaluate the efficacy and safety of ustekinumab (UST) in giant cell arteritis (GCA).Methods: We conducted a prospective, open-label trial of UST in patients with active new-onset or relapsing GCA. Active disease was defined as the presence of GCA symptoms and elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level within 6 weeks of baseline. All patients received a 24-week prednisone taper and subcutaneous UST 90 mg at baseline and at weeks 4, 12, 20, 28, 36, and 44. The primary endpoint, prednisone-free remission, was defined as the absence of relapse through week 52 and normalization of the ESR and CRP level. Relapse was defined as the recurrence of GCA symptoms requiring treatment intensification. A sensitivity analysis excluding ESR/CRP level normalization from the prednisone-free remission definition was performed.Results: The study enrolled 13 patients (target sample size 20). Enrollment was closed prematurely after 7 of the initial 10 patients relapsed. Five patients (39%) had new-onset disease. The initial prednisone doses were 20 mg (1 patient), 40 mg (9 patients), and 60 mg (3 patients). All patients entered disease remission within 4 weeks of baseline. Only 3 (23%) achieved the primary endpoint. Of the 10 patients (77%) who failed to achieve the primary endpoint, 7 relapsed after a mean period of 23 weeks. The remaining 3 patients met the alternative definition of prednisone-free remission that did not require ESR/CRP level normalization. One serious adverse event occurred.Conclusion: UST combined with 24 weeks of prednisone was associated with a high rate of treatment failure in this prospective GCA trial. [ABSTRACT FROM AUTHOR]

Objective. IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. Prior studies have focused on individual cases of IgG4-RD or small case series. This study was undertaken to report detailed clinical and laboratory findings in a larger group of patients with IgG4-RD whose diagnosis was established by strict clinicopathologic correlation. Methods. The baseline features of 125 patients with biopsy-proven IgG4-RD were reviewed. The diagnosis was confirmed by pathologists' review, based on consensus diagnostic criteria and correlation with clinicopathologic features. Disease activity and damage were assessed using the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts. Results. Of the 125 patients, 107 had active disease and 86 were not receiving treatment for IgG4-RD. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher IgG4-RD RI score, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 concentrations (P < 0.01 for all comparisons). The correlation between IgG41 plasmablast levels and the IgG4-RD RI of disease activity (Spearman's r50.45, P50.003) was stronger than the correlation between total plasmablast levels and the IgG4-RD RI. Seventy-six (61%) of the patients were male, but no significant differences according to sex were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Treatment with glucocorticoids failed to produce sustained remission in 77% of patients. Conclusion. Nearly 50% of this patient cohort with biopsy-proven, clinically active IgG4-RD had normal serum IgG4 concentrations. Elevations in the serum IgG4 concentration appeared to identify a subset of patients with a more severe disease phenotype. In addition, the levels of IgG41 plasmablasts correlated well with the extent of disease activity. [ABSTRACT FROM AUTHOR]

The article present case studies of three patients with laryngopharyngeal lesions, who were diagnosed with Immunoglobulin G4-related disease (IgG4-RD), manifested in the head and neck. The manner of diagnosis and effective treatment for the disease is discussed. Result suggests IgG4-related disease as a fibroinflammatory disorder, with the head and neck regions as among of the most common areas of involvement.

Objective To determine the frequency of the prozone effect in patients with IgG4-related disease (IgG4-RD). Methods After identifying the prozone effect in an index patient with IgG4-RD, we examined additional samples to determine the frequency of this phenomenon. Thirty-eight serum samples obtained from patients with IgG4-RD whose results had been reported previously were retested. The serum IgG4 concentrations determined by this repeat analysis were compared with the originally reported values. Results In 10 (26%) of 38 patients, the originally reported IgG4 values were falsely low; the prozone effect was identified in each of these 10 samples. Correction of the prozone effect by sample dilution led to revision of the mean serum IgG4 concentration in the 10 samples, from 26 mg/dl to 2,008 mg/dl (normal range 2.4-121 mg/dl). All 10 patients whose samples were affected by the prozone effect had active IgG4-RD. Failure to detect the elevated serum IgG4 concentrations had a direct impact on the decision not to institute treatment in these patients. Conclusion The prozone effect may lead to major underestimations of IgG4 concentrations in patients with IgG4-RD and offers a potential explanation for the poor correlation observed between disease activity and serum IgG4 levels in some patients. This phenomenon should be considered if the serum IgG4 measurement appears discordant with the clinicopathologic diagnosis and the clinical assessment of disease activity. [ABSTRACT FROM AUTHOR]

The article offers recommendations reported by the organizing committee at the International Symposium on IgG4-related diseases held in Boston, Massachusetts on October 4–7, 2011, related to the terminology for overall disease, emphasizing on individual organ system manifestations. IgG4-related organ system nomenclature and the associated problems including the pancreatic manifestation of IgG4-related disease, ophthalmic disease and tubulointerstitial nephritis (TIN) are also discussed.

Cosmogenic-nuclide exposure ages for 13 glacially transported boulders atop the Martha''s Vineyard moraine, MA, USA, indicate that the southeastern margin of the Laurentide ice sheet reached its maximum extent during the last glaciation 23,200±500 yr ago. Another 10 age determinations from the younger Buzzards Bay moraine near Woods Hole, MA, indicate that this moraine complex was formed 18,800±400 yr ago. These ages correlate approximately with the terminations of cooling cycles recorded in Greenland ice cores and coeval ice-rafting events, suggesting that the marginal position of this sector of the ice sheet was tightly coupled to North Atlantic climate during the last glacial maximum. [Copyright &y& Elsevier]

The authors discuss a retrospective study which indicated that patients with giant cell aortitis of the ascending aorta who lacked signs or symptoms of systemic vasculitis were at an increased risk of subsequent distal aortic events. The study identified cases from the Pathology Service database at Massachusetts General Hospital. Also discussed are the study's limitations which include relatively small number of patients.

Objective: To evaluate the association between cigarette smoking and the odds of IgG4-related disease (IgG4-RD)., Methods: We performed a case-control study of patients with IgG4-RD compared in a 1:5 ratio with age-, race- and sex-matched controls. We included cases evaluated at the Massachusetts General Hospital, a hospital within the Mass General Brigham (MGB) System. Controls were identified from the MGB Biobank. Smoking status at the date of IgG4-RD diagnosis or corresponding index date was determined. Conditional logistic regression was used to estimate the association between cigarette smoking and the odds of having IgG4-RD., Results: There were 234 IgG4-RD cases and 1170 controls. The mean age (59 years), sex (62% male) and race (75% white) were well balanced. IgG4-RD cases were more likely to be current smokers compared with controls [25 (11%) vs 70 (6%); odds ratio (OR) 1.79 (95% CI 1.08, 2.95)]. This association was strongest among female cases [13 (14%) vs 19 (4%);, OR 3.79 (95% CI 1.71, 8.39)] and those with retroperitoneal fibrosis [RPF; 13 (28%) vs 13 (6%);, OR 6.93 (95% CI 2.78, 17.26)] or normal IgG4 concentrations [21 (21%) vs 21 (4%); OR 6.22 (95% CI 3.09, 12.49)]. When RPF cases were excluded, there was no longer an association between current smoking and the odds of having IgG4-RD [12 (6%) vs 57 (6%); OR 0.95 (95% CI 0.49, 1.86)]., Conclusion: Being a current smoker is associated with greater odds of having IgG4-RD, especially among women and those with RPF or normal IgG4 concentrations. Current smoking is the first recognized modifiable risk factor for IgG4-RD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)