Outpatient healthcare utilization among incident cases of systemic sclerosis: results from a population-based US cohort (1988-2016).

OBJECTIVE: Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease with multiorgan dysfunction. This study aimed to compare healthcare utilization among incident cases of SSc versus age- and gender-matched comparators. METHOD: A population-based cohort of physician-diagnosed patients with SSc in Olmsted County, MN, USA, from 1 January 1988 to 31 December 2016 was assembled. A 2:1 cohort of age- and gender-matched non-SSc subjects was randomly selected for comparison. Patients were followed until death, migration from Olmsted County, or 31 December 2017. Outpatient utilization data were obtained beginning 12 months before the SSc incidence/index date and compared using negative binomial and multinomial models. Services were summarized as visit-days to avoid overestimation of services provided. RESULTS: The study included 69 incident SSc cases and 138 non-SSc comparators (mean ± sd age 57 ± 16 years at diagnosis/index, 90% female). Patients with SSc had higher utilization of outpatient physician, laboratory, and combined radiology visit-days annually for the year before and for each of the first 5 years after diagnosis than comparators. Among patients with SSc, healthcare utilization was highest during the year of SSc diagnosis. Rate ratios comparing utilization in patients with and without SSc ranged from 1.8 to 3.0 for all comparisons. CONCLUSION: Higher utilization of outpatient physician, laboratory, and radiology visit-days was observed among patients with SSc compared to non-SSc subjects throughout 5 years of disease duration, indicating high and continued care needs in this patient population. The highest utilization of services among SSc patients occurred during the year of SSc diagnosis.

Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study.

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn's disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

Incidence and predictors of thoracic aortic damage in biopsy-proven giant cell arteritis.

Objective: To describe the frequency and predisposing factors of aortic structural disease among patients with biopsy-proven giant cell arteritis (GCA).Method: A retrospective review identified all patients with biopsy-proven GCA from 1998 to 2013 with aortic imaging. Kaplan-Meier methods were used to estimate cumulative incidence and Cox models were used to examine potential predictors of development of aneurysm/dilatation of the thoracic aorta.Results: The cohort included 114 patients with aortic imaging performed within a median time of 1.8 months from GCA diagnosis. Fifty-seven patients (50%) had at least one additional follow-up imaging study. At the first imaging study, 8% had evidence of aneurysm/dilatation and 25% thickening of the thoracic aorta. Excluding prevalent cases, the cumulative incidence for aneurysm/dilatation of the thoracic aorta during follow-up was 0% at both 1 year and 2 years but increased to 10% at 5 years. The sole predictor for development of thoracic aortic aneurysm/dilatation was current smoking (hazard ratio 28.8, 95% confidence interval 1.62, 511.4; p = 0.02).Conclusion: Thoracic aortic aneurysm/dilatation was seen in 8% of patients at baseline. Among patients without aortic disease, the cumulative incidence of aortic disease was 10% at 5 years after diagnosis. Current smokers were at an increased risk for developing thoracic aortic damage. Surveillance for aortic damage should be pursued in patients with GCA, particularly those with a smoking history.

Glucocorticoid usage in giant cell arteritis over six decades (1950 to 2009).

OBJECTIVES: To evaluate the trends in glucocorticoid (GC) therapy in patients with giant cell arteritis (GCA). METHODS: Using a population-based inception cohort, GC therapy details were collected for all patients with GCA diagnosed between 1950-2009. GC usage for patients diagnosed with GCA between 1980-2009 was compared to those diagnosed between 1950-1979. RESULTS: The mean starting dose was similar in both time-periods but the mean cumulative dosages at different time points were significantly higher for patients diagnosed between 1980-2009 than in 1950-1979 (at 1-year: 6.3 vs. 4.1g; and at 5 years 10.7 vs. 7.6g, respectively, p<0.001). The median time to permanent discontinuation of GC was 2.6 years for 1980-2009 vs. 1.5 years for 1950-1979 (p=0.004). The risk for GC-associated adverse events was similar in both time periods (p=0.52). CONCLUSIONS: GCA patients diagnosed in the last three decades were treated with higher cumulative GC doses and were less likely to achieve GC discontinuation. However, their risks for GC-related complications were not significantly higher than their earlier counterparts.

The incidence of giant cell arteritis in Olmsted County, Minnesota, over a 60-year period 1950-2009.

OBJECTIVE: To assess the incidence of giant cell arteritis (GCA) in the era from 2000 to 2009. METHOD: We extended the previously identified population-based cohort of Olmsted County, Minnesota residents who fulfilled 1990 American College of Rheumatology (ACR) criteria for GCA for earlier decades during 1950-1999. RESULTS: In 2000-2009, 74 cases of GCA were identified (mean age 78.1 years; 80% women; 79% temporal artery biopsy positive; seven included based on radiological criteria). The incidence of GCA was 19.8 per 100,000 population. CONCLUSIONS: The GCA incidence rates have remained steady since 1970 and the age at incidence, which was progressively increasing, seems to have reached a plateau.

Management guidelines and outcome measures in giant cell arteritis (GCA).

Giant cell arteritis (GCA) is a common form of vasculitis that predominantly affects the elderly. Cranial symptoms and elevated inflammatory markers are suggestive of the condition and the diagnosis is usually established by temporal artery biopsy. Corticosteroids are the mainstay of treatment for GCA and prolonged therapy is often necessary. Disease relapses and steroid-related adverse effects, however, are common. Serious complications of the disease may include visual loss, stroke, and aortic involvement with aneurysm formation.

Pamidronate infusion in patients with systemic sclerosis results in changes in blood mononuclear cell cytokine profiles.

A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta1, tumour necrosis factor (TNF)-alpha and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-gamma and TNF-alpha and reduced levels of TGF-beta1 for up to 24 weeks after the infusion. gammadelta T cells from patients with SSc were activated in vitro and produced increased IFN-gamma. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study.

CD4+,CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems.

OBJECTIVE: To determine whether CD4+,CD28- T cells, which are expanded in patients with rheumatoid arthritis (RA), express receptors that typically regulate the function of natural killer (NK) cells. METHODS: Expression of the NK cell surface molecules CD158, p70, CD94, CD161, and CD8alpha on T cell subsets was determined by multicolor flow cytometric analysis of peripheral blood mononuclear cells from 36 RA patients. Expression of CD161 on tissue-infiltrating CD4 T cells was determined by 2-color immunohistochemistry analysis of synovial tissue samples. RESULTS: Killer cell-inhibitory receptors (KIR) and killer cell-activating receptors (KAR) were exclusively expressed on CD4+,CD28- T cells, with the CD158b molecule being the most frequently detected isoform. A coordinated mechanism inducing KIR/KAR expression was suggested by similarities in the expression of CD158b on CD4 and CD8 T cells. CD4+,CD28- T cells were also positive for CD8-alphaalpha homodimers, another characteristic shared with NK cells. Of the C-type lectin NK cell receptors (NK receptors), CD94 was consistently absent, but CD161 was found on a CD4 T cell population that is significantly expanded in RA patients (P = 0.01). Involvement in disease of NK receptor-expressing CD4 T cells was suggested by the presence of CD4+,CD161+ T cells in follicular microstructures typical of rheumatoid synovitis. CONCLUSION: Patients with RA have an expanded and unusual subset of CD4 T cells that infiltrates the tissue lesions and is characterized by a deficiency of CD28, the expression of CD8-alphaalpha homodimers, and the expression of several types of HLA class I-recognizing NK receptors. CD4 T cells bearing NK receptors can bridge functions of the innate and adaptive immune systems, such as responsiveness to specific antigen, rapid release of interferon-gamma, cytotoxicity, independence from classic costimulatory pathways, and integration of multiple activating and inhibitory signals to control effector functions.

The shrinking lungs syndrome in systemic lupus erythematosus.

A comprehensive review of the literature on shrinking lungs syndrome (SLS) in systemic lupus erythematosus involved a MEDLINE search (1965-1997) of case reports and clinical series of patients with the diagnosis of SLS. A total of 49 well-documented cases of SLS were reviewed. Shrinking lungs syndrome is characterized by unexplained dyspnea, a restrictive pattern on pulmonary function test results, and an elevated hemidiaphragm. The cause of SLS remains controversial, with several authors attributing the disorder to diaphragmatic weakness and others suggesting that chest wall restriction accounts for the clinical syndrome. No definitive therapy exists. Corticosteroids have been reported to lessen symptoms and improve pulmonary function in some patients with SLS, but other methods of treatment have occasionally been found to be helpful. Clinical presentation, method of diagnosis, pathogenesis, and treatment modalities are summarized in this review. An uncommon complication of systemic lupus erythematosus, SLS causes significant morbidity and, occasionally, mortality.