Eric Heffernan

High Prevalence of Metabolic Syndrome and of Insulin Resistance in Psoriatic Arthritis is Associated with the Severity of Underlying Disease

Objective. To investigate the prevalence of metabolic syndrome (MetS) and of insulin resistance (IR) in an ethnically homogeneous cohort of established psoriatic arthritis (PsA), and to identify clinical associations of MetS and IR in patients with PsA. Methods. A cohort of 283 patients with PsA all meeting ClASsification for Psoriatic ARthritis (CASPAR) criteria was included. All underwent detailed skin and rheumatologic assessments, along with cardiovascular risk factor evaluation. IR was defined as an elevated homeostasis model assessment (HOMA-IR) value of > 2.5. Severe PsA was defined as the presence of 1 or more of the PsA-related radiographic damage features (peripheral joint erosions, osteolysis, sacroiliitis), and PsA requiring tumor necrosis factor inhibitor therapy. Results. The demographic and clinical characteristics of the cohort were mean age 54.6 ± 12 years, 52% female, mean PsA duration 19 ± 9 years. MetS was present in 44% of the studied patients (n = 283). On multiple regression analysis, a significant association of MetS was noted with more severe PsA (OR 4.47, p < 0.001), higher smoking pack-years (OR 1.03, p = 0.02), and worse EQ-5D scores (OR 1.28, p = 0.02). Data on IR were available for 263 patients, and among them, the mean HOMA-IR was 1.43 ± 1.09. Forty-one patients (16%) had IR. On multiple regression analysis, a significant association of IR was noted with more severe PsA (OR 3.49, p = 0.03), later psoriasis age of onset (OR 1.07, p = 0.001), and higher body mass index (OR 1.22, p < 0.001). Conclusion. Among patients with PsA, MetS and IR are highly prevalent, and are independently associated with the severity of underlying PsA.

Certain class I HLA alleles and haplotypes implicated in susceptibility play a role in determining specific features of the psoriatic arthritis phenotype

Objectives Psoriatic arthritis (PsA) susceptibility is associated with several different class I alleles, suggesting separate patterns of MHC effect. This exploratory study was based on the hypothesis that heterogeneity of the clinical phenotype of PsA might be explained by differing associations of clinical features with these susceptibility genes. Methods The clinical phenotype of 282 PsA patients in a cohort previously studied for associations with human leukocyte antigen (HLA)-B and HLA-C genotypes was first preliminarily assessed by univariate associations of susceptibility genes with specific clinical characteristics. To explore the potential genotypic effects of pairwise combinations of different HLA-B and C alleles/haplotypes, we created a series of allele/haplotype risk scores combining single alleles/haplotypes separately associated with being in the highest PsA severity propensity tertile based on the features studied by univariate analysis. Results In exploratory univariate analyses, B*27:05:02 was positively associated with enthesitis, dactylitis and symmetric sacroiliitis, whereas B*08:01:01-C*07:01:01and its component alleles were positively associated with joint fusion and deformities, asymmetrical sacroiliitis, and dactylitis. HLA-C*06:02:01 was negatively associated with asymmetrical sacroiliitis. The highest propensity score for severe PsA was with B*27:05:02-C*02:02:02, B*08:01:01-C*07:01:01 and B*37:01:01-C*06:02:01, but not the B*27:05:02-C*01:01:01 or B*57:01:01-C*06:02:01 haplotypes. In contrast, B*44 haplotypes were associated with presence of milder disease, and in univariate analysis with a decreased frequency of enthesitis, joint fusion, deformities and dactylitis. Conclusions Different HLA susceptibility genes were associated with particular features that defined the PsA phenotype of a given patient. Additive interactions between different susceptibility HLA alleles defined the propensity for a more severe or milder musculoskeletal phenotype.

Tumor necrosis factor blocking therapy alters joint inflammation and hypoxia.

OBJECTIVE To examine the effect of tumor necrosis factor (TNF) blocking therapy on hypoxia in vivo, macroscopic and microscopic inflammation, and magnetic resonance imaging (MRI) results in patients with inflammatory arthritis. METHODS Patients with inflammatory arthritis (n = 20) underwent full clinical assessment, arthroscopy, synovial biopsy, and MRI before and after initiation of biologic therapy. Macroscopic synovitis/vascularity was assessed with a visual analog scale, and tissue PO(2) (tPO(2) ) was measured at arthroscopy using a Licox probe. Cell-specific markers (CD4, CD8, CD68, CD20, and CD19) and blood vessel maturity were quantified by immunohistologic analysis and dual-immunofluorescence factor VIII/α-smooth muscle actin staining, respectively. Contiguous gadoteric acid-enhanced MRI of the target knee was used to assess synovial enhancement. RESULTS Biologic therapy responders showed a significant increase of tPO(2) in vivo (P < 0.05). This response was associated with significant reductions in 28-joint Disease Activity Score using the C-reactive protein level (DAS28-CRP) (P = 0.012), macroscopic synovitis (P = 0.017), macroscopic vascularity (P = 0.05), CD4+ T cells (P < 0.041), and CD68+ macrophages (P < 0.011). Blood vessel numbers were also reduced in responders; however, this did not reach statistical significance. Strong inverse correlations were demonstrated between changes in tPo(2) levels and changes in DAS28-CRP (r = -0.53, P < 0.001), CD4 (r = -0.44, P < 0.026), CD68 (r = -0.46, P < 0.003), and macroscopic vascularity (r = -0.314, P = 0.049) after therapy. Furthermore, changes in inflammation as measured by MRI showed a strong inverse correlation with tPO(2) levels (r = -0.688, P < 0.002) and positive correlations with CRP levels (r = 0.707, P = 0.001), macroscopic synovitis (r = 0.457, P = 0.056), macroscopic vascularity (r = 0.528, P= 0.017), CD4 (r = 0.553, P < 0.032), and CD68 (r = 0.670, P < 0.002) after therapy. CONCLUSION This is the first study to show that successful biologic therapy significantly improves in vivo synovial hypoxia. Changes are strongly associated with changes in macroscopic and microscopic measures of joint inflammation and MRI improvement. These data further strengthen the concept that hypoxia is an important event driving synovial inflammation.

Incomplete Atypical Femoral Fractures: Assessing the Diagnostic Utility of DXA by Extending Femur Length

Atypical femoral fractures (AFFs) are associated with prolonged bisphosphonate therapy. A feature of incomplete AFF is a localized periosteal reaction. It has been suggested that extending the length of the femur image at the time of dual-energy X-ray absorptiometry (DXA) may diagnose an incomplete AFF. In patients older than 50 yr on bisphosphonate therapy for more than 5 yr, we extended femur length at the time of routine DXA. Abnormal DXA images were suggested in 19 of 257 patients (7.4%). On X-ray, 7 patients (2.7%) showed no abnormality, 7 patients (2.7%) showed evidence of AFF, and 5 patients (2.0%) showed an unrelated radiographic abnormality. Of the 7 cases with X-ray evidence of AFF, 5 had a periosteal flare and 2 had a visible fracture line, both of whom needed insertion of an intramedullary nail. We demonstrated that it is feasible to detect incomplete AFF early using extended femur length imaging with a prevalence in our sample of 2.7% (95% confidence interval: 1.7%-3.7%).

Cystic Fibrosis below the Diaphragm: Abdominal Findings in Adult Patients

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in the white population. Mutation of the CF transmembrane conductance regulator gene on chromosome 7 results in production of abnormally viscous mucus and secretions in the lungs of patients with CF. A similar pathologic process occurs in the gastrointestinal tract, pancreas, and hepatobiliary system. Inspissated mucus causes luminal obstruction and resultant clinical and radiologic complications associated with the disease process. Pancreatic involvement can result in exocrine and endocrine insufficiency, pancreatic atrophy, fatty replacement, or lipomatous pseudohypertrophy. Acute and chronic pancreatitis, pancreatic calcification, cysts, and cystosis also occur. Hepatic manifestations include hepatic steatosis, focal biliary and multilobular cirrhosis, and portal hypertension. Biliary complications include cholelithiasis, microgallbladder, and sclerosing cholangitis. The entire digestive tract can be involved. Distal ileal obstruction syndrome, intussusception, appendicitis, chronic constipation, colonic wall thickening, fibrosing colonopathy, pneumatosis intestinalis, gastroesophageal reflux, and peptic ulcer disease have been described. Renal manifestations include nephrolithiasis and secondary amyloidosis. The educational objectives of this review are to reveal the abdominal manifestations of CF to facilitate focused analysis of cross-sectional imaging in adult patients. Life expectancy in patients with CF continues to improve because of a combination of aggressive antibiotic treatment, improved emphasis on nutrition and physiotherapy, and development of promising new CF transmembrane conductance regulator modulators. As lung function and survival improve, extrapulmonary conditions, including hepatic and gastrointestinal malignancy, will be an increasing cause of morbidity and mortality. Awareness of the expected abdominal manifestations of CF may assist radiologists in identifying acute inflammatory or neoplastic conditions. (©)RSNA, 2015.

Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial

BackgroundThere is increasing evidence linking vitamin D deficiency to both susceptibility to, and severity of, multiple sclerosis (MS). Patients with the clinically isolated syndrome represent the initial presentation of a demyelinating disorder, and those with asymptomatic lesions on magnetic resonance imaging (MRI) are at risk of progression to clinically definite MS. The aims of this study are to examine the immunologic effects of vitamin D in both healthy individuals and in patients with clinically isolated syndrome, and in the latter group the effects on disease progression assessed by MRI and clinical measures.Methods/DesignThis is a single-center double-blind randomized placebo-controlled clinical trial. The primary endpoint is the immunologic effects of two doses of vitamin D compared with placebo over 24 weeks in both healthy control participants and patients presenting with the clinically isolated syndrome. Healthy control participants (n = 39) and patients with clinically isolated syndrome (n = 45) will be randomized to one of three arms, namely 1) vitamin D 5,000 IU daily, 2) vitamin D 10,000 IU daily, or 3) placebo, and followed up for 24 weeks. In both patients and healthy control participants, the primary outcome will be immunologic measures of the frequency of CD4 T-cell subsets and cytokine responses in peripheral blood mononuclear cells, assessed at baseline, and after 16 and 24 weeks of treatment. Secondary endpoints, in the patients with clinically isolated syndrome, will be relapse activity, and the number of new T2 lesions and gadolinium-enhancing lesions assessed by MRI in the two vitamin D-treated groups compared with the placebo-treated group over the 24 weeks of the study.Trial registrationEU Clinical Trials Register: EudraCT: 2012-000635-68. ClinicalTrials.gov identifier: NCT01728922

Clinician approach to diagnosis of stress fractures including bisphosphonate-associated fractures

Stress fractures are repetitive strain injuries that occur in normal bones and in abnormal bones. Stress fractures share many features in common but differences depend on the status of the underlying bone. This review article for clinicians addresses aspects about stress fractures with particular respect to fatigue fractures, Looser zones of osteomalacia, atypical Looser zones, atypical femoral fractures associated with bisphosphonate therapy and stress fractures in Pagets disease of bone.

Pancreaticoduodenectomy: expected post-operative anatomy and complications

Pancreaticoduodenectomy is a complex, high-risk surgical procedure performed for tumours of the pancreatic head and other periampullary structures. The rate of perioperative mortality has decreased in the past number of years but perioperative morbidity remains high. This pictorial review illustrates expected findings in early and late post-operative periods, including mimickers of pathology. It aims to familiarize radiologists with the imaging appearances of common and unusual post-operative complications. These are classified into early non-vascular complications such as delayed gastric emptying, post-operative collections, pancreatic fistulae and bilomas; late non-vascular complications, for example, biliary strictures and hepatic abscesses; and vascular complications including haemorrhage and ischaemia. Options for minimally invasive image-guided management of vascular and non-vascular complications are discussed. Familiarity with normal anatomic findings is essential in order to distinguish expected post-operative change from surgical complications or recurrent disease. This review summarizes the normal and abnormal radiological findings following pancreaticoduodenectomy.

Striking difference of periarticular bone density change in early psoriatic arthritis and rheumatoid arthritis following anti-rheumatic treatment as measured by digital X-ray radiogrammetry

OBJECTIVES To examine changes in hand BMD as measured by digital X-ray radiogrammetry (DXR-BMD) in early PsA compared with RA patients prior to and 3 and 12 months after introducing an antirheumatic treatment. Further, to identify predictors for hand bone loss at the time of disease presentation. METHODS Recent-onset, active, treatment-naïve patients were recruited. Clinical assessment, hand X-rays and DXR were obtained at 0, 3 and 12 months. Mean DXR-BMD for both hands and changes in DXR-BMD (mg/cm(2)/month) were compared between the two groups. We compared baseline disease characteristics of patients with normal hand DXR-BMD with those with bone loss. Logistic regression analyses were performed to identify predictors of hand BMD loss. RESULTS A total of 64 patients were included. Hand DXR-BMD decreased in RA throughout the study (P = 0.043). Changes in periarticular bone density over 12 months differed between PsA and RA (P = 0.001). Hand bone loss at 3 months was associated with elevated BMI [odds ratio (OR) = 3.59, P = 0.041] and heavier alcohol intake (OR = 1.13, P = 0.035). Diagnosis of RA (OR = 57.48, P = 0.008), heavier alcohol intake (OR = 1.27, P = 0.012) and higher swollen joint count (SJC28) (OR = 1.5, P = 0.036) were independent predictors for hand bone loss in the first year. CONCLUSION Following treatment, we found ongoing hand bone loss in RA and unchanged periarticular bone density in PsA, supporting the hypothesis that different pathomechanisms are involved in hand bone remodelling in PsA. Presence of RA, heavier alcohol intake and higher SJC were identified as independent predictors for hand bone loss over 1 year.

Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial:

Background Lowserum vitamin D levels are associated with susceptibility to, and severity of, multiple sclerosis. High dose vitamin D has been proposed as a potential immunomodulator in multiple sclerosis. Objectives We performed a single centre, investigator-led, exploratory, double-blind, randomised, placebo controlled, trial of vitamin D3 in clinically isolated syndrome and healthy control participants to assess its immunological effects. Secondary end-points included clinical and magnetic resonance imaging outcomes and safety. Methods Clinically isolated syndrome patients and healthy control participants were randomised to: placebo, 5000 IU or 10,000 IU vitamin D3/day (Vigantol oil). Study duration was 24 weeks. Results The trial did not meet its primary end point, with no difference in the frequency of pro-inflammatory CD4+ T cells (interleukin (IL)-17+/interferon (IFN)-γ+) seen. A higher level of disease freedom (67% versus 50%) was seen in those with serum 1,25 (OH) vitamin D levels>100 nmol/l but this did not reach significance. High dose vitamin D3 was well tolerated with no safety signal. Conclusions High dose vitamin D3 over 24 weeks was well tolerated but without immunological, magnetic resonance imaging or clinical evidence of benefit. The hypothesised therapeutic effects in clinically isolated syndrome or multiple sclerosis patients may require longer periods of administration or may only be seen in patients treated with vitamin D3 as an adjunct to established disease modifying therapies.