Maria Antonelli

Screening and Treatment of Osteoporosis After Hip Fracture: Comparison of Sex and Race

Most patients with osteoporosis (OP) are untreated and remain so even after hip fracture. Outcomes after osteoporotic hip fractures are worse among men and non-Caucasians compared with Caucasian women. We hypothesized that screening and treatment of OP after hip fracture remains low in men and non-Caucasian women. We identified all patients aged 65 yr or older with a primary diagnosis of hip fracture (ICD9-DM code 820.xx) discharged from an urban public hospital between January 1, 2000 and December 31, 2010. Patients with active malignancy (1 yr before or after the fracture) and Pagets disease were excluded. Also, patients were excluded if they had less than 2 encounters for post-event care at the hospital. Patient charts were reviewed to obtain information on demographics, post-fracture OP screening status (dual-energy X-ray absorptiometry [DXA] ordered or resulted), OP treatment status (prescription for oral bisphosphonates, raloxifene, zoledronic acid, calcitonin, or teriparatide), and referral to rheumatology clinic. Data were captured using Research Electronic Data Capture. Differences in frequency of patients who had been evaluated by DXA and/or prescribed antiosteoporotic therapy after hip fractures overall and stratified by sex and race were evaluated using Chi-squared tests. The study was approved by our hospital institutional review board. There were a total of 596 patients discharged with a primary diagnosis of hip fracture during the study period. After exclusions, 417 patients remained and were included in the analyses. The median age was 80yr (range: 65-95), 113 (27%) were men, and 243 were White women (57.9%). Overall, 10.3% of the patients were ordered DXA after their hospital discharge, 5.4% of men and 12.1% of women (p=0.05). A total of 19% received treatment for OP, and women were nearly 3 times more likely to receive treatment than men (23.2% vs 8%, p=0.004). The rates of DXA, treatment, and referral to rheumatology did not differ by race. The frequency of OP screening using DXA scan and the initiation of OP treatment was low in all patients after fragility fractures of hip. Women were more likely than men to receive DXA and significantly more likely to receive OP treatment. Although representative of only 1 hospital, these data suggest that more attention should be paid to possible OP among elderly patients hospitalized for hip fracture, and especially among men.

High Frequency of Fibromyalgia in Patients with Psoriatic Arthritis: A Pilot Study

Background. Widespread pain from fibromyalgia syndrome (FMS) is observed in patients with psoriatic arthritis (PsA). We hypothesized that there is increased frequency of FMS in patients with PsA that contributes to fatigue and pain. Method. We prospectively enrolled patients with PsA based on the Classification criteria for Psoriatic Arthritis and healthy subjects were used as controls. The frequency of FMS was determined using London Fibromyalgia Epidemiologic Study Screening Questionnaire (LFESSQ) and Symptoms Intensity scale (SIs). Results. 34 PsA patients and 44 controls fulfilled the inclusion criteria. Median age of PsA patients was 52 years with 53.33% females. Median age of controls was 50.5 years with 59% females. FMS was present in 53.33% of PsA patients compared to 4.54% of the controls (P < 0.001), based on LFESSQ. 37.50% of PsA had FMS compared to 6.66% of controls (P < 0.001) based on SIs. There was a significant correlation between LFESSQ and SIs in the psoriatic group (P = 0.00243). 76.66% of PsA patients complained of fatigue compared to 40.90% of controls, but the mean fatigue score between the two groups was comparable (5.03 versus 5.18). Conclusion. FMS-associated pain and fatigue are significantly more frequent in patients with PsA compared to controls.

It’s time to redefine inflammation

Inflammation has been defined for many years as the response to tissue injury and infection. We are now forced to reconsider this definition by the avalanche of reports that molecules and cells associated with inflammation are activated or expressed in high concentration in a large variety of states in the absence of tissue injury or infection. Modest increases in concentration of C‐reactive protein, a circulating marker of inflammation, have been reported to be associated with an astounding number of conditions and lifestyles felt to be associated with poor health; these conditions represent or reflect minor metabolic stresses. In recent years we have learned that inflammation is triggered by sentinel cells that monitor for tissue stress and malfunction—deviations from optimal homeostasis—and that molecules that participate in the inflammatory process play a role in restoring normal homeostasis. Accordingly, we suggest that inflammation be redefined as the innate immune response to potentially harmful stimuli such as pathogens, injury, and metabolic stress.—Antonelli, M., Kushner, I. Its time to redefine inflammation. FASEB J. 31, 1787–1791 (2017). www.fasebj.org

Spinal epidural abscess on rituximab.

To the Editor: In December 2009, Vasoo et al. 1 reported a case of staphylococcal epidural abscess in the Journal of Clinical Rheumatology in a patient with psoriatic arthropathy on infliximab and methotrexate therapy. We present a case of spinal epidural abscess on another biologic agent, rituximab. A 65-year-old man with rheumatoid factor and anti-citrullinated protein antibody (antiCCP) positive rheumatoid arthritis (RA) was started on rituximab therapy in March 2009. On September 21, 2009, he presented with back pain. Vital signs at clinic visit were blood pressure of 140/75 mm Hg, temperature of 36.5-C, heart rate of 74 beats/ minute. Physical examination revealed swollen right olecranon bursa with redness and tenderness, and flexion of the lumbar spine was limited and profoundly painful. He had normal strength in all 4 extremities with intact sensations. Bursal aspirate grew rare methicillin-sensitive Staphylococcus aureus. A magnetic resonance imaging of the lumbar spine was done and showed a multiloculated fluid collection in the dorsal epidural space of L4YL5 with moderate mass effect on the thecal sac as well as the right paraspinal muscle. For this epidural abscess, he underwent successful laminectomy and abscess debridement on September 27, 2009. Culture from the abscess also grew methicillin-sensitive Staphylococcus aureus. Our report is the first case of spinal epidural abscess from rituximab. Genentech, the manufacturer and distributor of rituximab in the United States, was contacted, and there were no reports of spinal epidural abscess in their research or postmarketing database. The source of the infection was the right olecranon bursa. There have been reports of spinal epidural abscesses with infliximab and etanercept therapy. In a recent study that evaluated the long-term safety of rituximab in clinical trials of patients with RA, it remained well tolerated. Rates of serious adverse events remained stable over time and over the treatment course. The study reported that the rate of infection with rituximab has been reported as 97.7 per 100 patient-years (95% confidence interval, 95.0Y100.5). The rates of overall infections have been found to be similar between placebo and rituximab-treated groups during 6-month placebo-controlled periods (39% and 40%). Rates of serious infections were similar between the placebo and rituximab groups (1.6% and 1.7%). The most common serious infection was pneumonia (1%). All other serious infections were reported in less than 1% of patients, the most common of which were cellulitis and urinary tract infection. The rates of both overall and serious infections were stable over time and also between courses with a higher rate of overall but not serious infection. However, the assessment of the risks of infection from randomized controlled trials of biologic medications for RA is complicated, because of issues of statistical power, differences in comparator arms between trials, different dosing in randomized clinical trials, and varying durations of follow-up. This case highlights that acute inflammation of olecranon bursa, a common condition, can cause invasive staphylococcal infections in an immunocompromised patient on rituximab therapy. It is imperative that rheumatologists should keep their patients well informed about potential adverse effects from these novel therapies, so patients can seek medical attention promptly. Maria Antonelli, MD

What Should We Regard as an “Elevated” C-Reactive Protein Level?

Background: Clinicians have long used serum C-reactive protein (CRP) levels to reflect the presence and degree of inflammation. More than 3 decades ago, investigators proposed that CRP levels greater than 10 mg/L indicate clinically significant inflammatory processes (1); this recommendation has stood the test of time (2). Recently, it was proposed that levels greater than 3 mg/L indicate a high degree of cardiovascular risk in patients judged to be at intermediate risk (2). Consequently, confusion regarding what constitutes an elevated CRP level has arisen. This confusion has been compounded because reference ranges for CRP differ greatly between laboratories and because serum CRP levels may be reported as either mg/dL or mg/L. One of us has reviewed medical records from across the United States and found that different laboratories cited every whole number between 1.0 and 10.0 mg/L (as well as 4.9, 6.3, 6.5 and 7.5 mg/L) as the upper limit of the reference range for CRP. There can be no biological or technical basis for such inconsistency. Another source of confusion is that standard CRP levels may be reported in mg/dL or in mg/L, whereas results of high-sensitivity assays are reported in mg/L, a problem that is magnified because clinicians generally omit units when describing laboratory results. Objective: To propose the adoption of a single standard to report CRP levels. Methods and Findings: Central to this discussion is the issue of what is meant by the term inflammation. For millennia, the clinical findings of redness, swelling, heat, and pain were taken to indicate this condition. As the mechanisms mediating the inflammatory process have gradually been appreciated, the criteria used to recognize the presence of inflammation have evolved. Recently, increased expression or activation of inflammatory cytokines and transcription factors has been taken as indicating that inflammation is present, as have mildly elevated CRP levelsthat is, those higher than levels found in appropriate control groups. Our concept of what triggers inflammation has similarly evolved. Inflammation has traditionally been considered a defense response induced by infection or tissue injury, but it is now apparent that mild degrees of inflammation can also be induced by metabolic stress and dysfunction (3, 4). Obesity, insulin resistance, and diabetes are well-studied examples. The term low-grade inflammation is generally applied to such instances, but this state differs sufficiently from our traditional view of inflammation that alternative termsmetaflammation and para-inflammationhave been proposed (3, 4). Patients with mild degrees of inflammation commonly have mildly elevated serum CRP levels, as do those with many other conditions that entail some degree of metabolic stress and unhealthy lifestyles (5). Cutoffs are never absolute; however, as a rule of thumb, it seems appropriate to regard serum CRP values between 3 and 10 mg/L as minor CRP elevation and to recognize that these values usually reflect a state distinct from our traditional view of inflammation (5). Discussion: Clearly, reference ranges and units for CRP levels should be standardized. All serum CRP levels (high sensitivity or not) should be reported in mg/L. Because a well-established consensus has persisted for a generation that CRP levels greater than 10 mg/L indicate clinically significant inflammatory processes, regarding values greater than this level as elevated seems appropriate. Such a result should impel clinicians to consider a possible infectious or inflammatory process, and a relevant work-up based on the clinical picture would be warranted. Those physicians who use CRP level to help assess cardiovascular risk will continue to be guided by the criteria that regard CRP levels greater than 3 mg/L in appropriate patients as an indication of a high degree of risk (2). By standardizing the units and upper limit of the reference range for CRP, clinicians will avoid the confusion and unnecessary diagnostic studies that currently prevail.

Sacroiliitis mimics: a case report and review of the literature

BackgroundRadiographic sacroiliitis is the hallmark of ankylosing spondylitis (AS), and detection of acute sacroiliitis is pivotal for early diagnosis of AS. Although radiographic sacroiliitis is a distinguishing feature of AS, sacroiliitis can be seen in a variety of other disease entities.Case presentationWe present an interesting case of sacroiliitis in a patient with Paget disease; the patient presented with inflammatory back pain which was treated with bisphosphonate. This case demonstrates comorbidity with Paget disease and possible ankylosing spondylitis. We also present a review of the literature for other cases of Paget involvement of the sacroiliac joint.ConclusionsIn addition, we review radiographic changes to the sacroiliac joint in classical ankylosing spondylitis as well as other common diseases. We compare and contrast features of other diseases that mimic sacroiliitis on a pelvic radiograph including Paget disease, osteitis condensans ilii, diffuse idiopathic skeletal hyperostosis, infections and sarcoid sacroiliitis. There are some features in the pelvic radiographic findings which help distinguish among mimics, however, one must also rely heavily on extra-pelvic radiographic lesions. In addition to the clinical presentation, various nuances may incline a clinician to the correct diagnosis; rheumatologists should be familiar with the imaging differences among these diseases and classic spondylitis findings.

Differential Adverse Events Between TNF-α Inhibitors and IL-17 Axis Inhibitors for the Treatment of Spondyloarthritis

Opinion statementAvailability of biologics, particularly tumor necrosis factor alpha (TNF-α) inhibitors, has revolutionized the treatment of spondyloarthritis (SpA). The main side effect associated with TNF-α inhibitors is increased rate of infection. Despite significant concerns about tolerability and adverse events of TNF-α inhibitors in treatment of SpA, they have stood the test of time with acceptable safety outcomes. However, there is a subset of patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) who fail to respond to TNF-α inhibitors, lose efficacy over a period of time, or develop serious adverse events, particularly opportunistic infections. Newer therapeutic options have become available for these patients including interleukin-17 (IL-17) axis antagonists. Their safety data is limited to clinical trials only, with no registry data available as yet. There are no large head-to-head comparative trials between TNF-α inhibitors and IL-17 axis inhibitors. Based on data from clinical trials of relatively limited duration, infection rates are quite similar between these two classes of biologics but there are, as yet, no reports of reactivation of opportunistic infections like tuberculosis with IL-17 axis antagonists. However, pre-screening for tuberculosis and prophylaxis in appropriate candidates is still needed. The current available data have shown no other major discrepancies in the adverse events between TNF-α inhibitors and IL-17 axis inhibitors. More data is needed to effectively determine the comparative safety of TNF-α inhibitors versus IL-17 axis antagonists.

Markers of Inflammation and Rheumatology Tests–An Update for Internists

Importance: The rapid proliferation of laboratory tests related to rheumatology, the recent interest in C-reactive protein as a possible marker for cardiovascular disease risk, and the need to contain the costs of medical care by avoiding unnecessary testing have indicated the need for a review of these tests aimed at general internists. Objective: To provide internists with guidance for when to use specific rheumatology related laboratory tests. Evidence Review: Literature reviews as well as important rheumatology references were appraised in order to give an updated review of the rheumatology laboratory tests included in this review. Findings: Certain rheumatology tests should be employed when an internist suspects a particular autoimmune or connective tissue disease. Conclusions and Relevance: A detailed review of symptoms and examination is of primary importance, while laboratory tests usually serve to support or argue against possible diagnoses.

Seronegative Rheumatoid Arthritis: A Case Control Study

Background : Seronegative Rheumatoid Arthritis (RA) is a disorder associated with considerable diagnostic, prognostic and therapeutic uncertainty for many clinicians. Objectives : The aim of this study is to elucidate clinical features at diagnosis, manifestations and treatment of patients with RA with negative serologies, as compared to a control group of patients presenting with similar polyarthralgias but diagnosed with alternative (non-RA) musculoskeletal disorders. Methods : The study was a retrospective chart review of electronic medical records from January 2003 to December 2012. Patients were identified using ICD-9 code Rheumatoid Arthritis 714.0 and at least two rheumatology clinic visits during the specified time. Charts were reviewed individually by two investigators. The inclusion criteria were a diagnosis of RA confirmed by a rheumatologist and normal values for both rheumatoid factor (RF) and anti-cyclic citrullinated protein antibodies (ACPA, third generation assay). Charts were also reviewed for eventual final diagnosis, either seronegative RA or alternate diagnosis (control group). Data were collected on demographics (sex, race, smoking status), family history of RA, and laboratory values (presence of anemia, inflammatory markers) at the time of diagnosis. The presence of erosions and synovitis identified by imaging studies was assessed. In addition, the presence of extra-articular manifestations of RA including nodules, pleural or parenchymal lung disease, eye involvement and osteoporosis was recorded. The therapies (disease modifying anti-rheumatic drug (DMARD), biologic) used to treat the seronegative RA were also reviewed. The family & smoking history and laboratory values of the seronegative RA patients were compared to the control group and analysis was done using Fisher’s exact test. Results : Charts from 107 patients were reviewed. Forty-four patients were eventually classified as having an alternate diagnosis and were considered the control group. Sixty-three patients were considered to have an established clinical diagnosis of seronegative RA. Among all patients at the time of diagnosis, 25% were smokers, 13% had a family history of RA, 54% were anemic, and 76% had abnormal ESR or CRP. The RA patients had statistically higher proportion with anemia compared to controls at presentation, and statistically lower proportion with ESR elevation compared to controls ( p =0.033 and p =0.013, respectively). Seven of the 59 (11%) patients who had hand/wrist films during their care had erosions on radiography, and 6 of 13 (46%) patients who had an MRI of an extremity had findings of synovitis. Extra-articular manifestations were infrequent in this group. Forty-eight of the 62 were initiated on a DMARD, most commonly hydroxychloroquine (16% patients) or methotrexate (29% patients) or a combination of methotrexate and hydroxychloroquine therapy (35%). Of the 63 patients, 17 (27%) patients required a biologic therapy during treatment course. Conclusions : This study supports the hypothesis that clinical history and physical examination can be important determinants in helping to diagnose seronegative RA and distinguish it from other polyarthopathies. In addition to characteristic symptoms, factors which might contribute to diagnosis of RA in a patient without seropositivity include presence of anemia, and results of imaging studies.

AB0326 Characterizing Seronegative Rheumatoid Arthritis

Background Seronegative Rheumatoid Arthritis (RA) is a disorder associated with considerable diagnostic, prognostic and therapeutic uncertainty for many clinicians. Objectives The aim of this study is to provide a deeper understanding of the diagnosis and manifestations of rheumatoid arthritis with negative serologies. Methods The study was a retrospective chart review of electronic medical records from January, 2003 to December, 2012. Patients were identified using ICD-9 code Rheumatoid Arthritis 714.0 and at least two rheumatology clinic visits during the specified time. Charts were reviewed individually by two investigators. The inclusion criteria were a diagnosis of RA confirmed by a rheumatologist with normal values for both rheumatoid factor (RF) and anti-CCP antibodies (CCP, third generation assay). Data were collected on demographics (sex, race, smoking status), family history of rheumatoid arthritis, and laboratory values (presence of anemia, inflammatory markers) at the time of diagnosis. The presence of erosions and synovitis identified by imaging studies was assessed. In addition, the presence of extra-articular manifestations of RA including nodules, pleural or parenchymal lung disease, eye involvement and osteoporosis was recorded. The therapies (DMARD, biologic) used to treat the seronegative RA were also reviewed. Results Charts from 108 patients were reviewed. Forty-five patients were excluded based on incorrect initial diagnosis or low clinical suspicion for seronegative RA by the rheumatologist. Sixty-three patients were included in this analysis. The demographics were similar to that of our patient population with seropositive RA. Of available data, at the time of diagnosis, 25% of the patients were smokers, 13% had a family history of RA, 54% were anemic, and 76% had abnormal ESR or CRP. Seven of the 63 (11%) patients had erosions on radiography, and 6 of 63 (9.5%) patients had MRI findings of synovitis. Initial data suggest that extra-articular manifestations are infrequent in this group. Forty-eight of the 62 were initiated on a DMARD, most commonly hydroxychloroquine (16% patients) or methotrexate (29% patients) with a large percentage of patients with combination of methotrexate and hydroxychloroquine therapy (35%). Of the 63 patients, 17 (27%) patients required a biologic therapy during treatment course. Conclusions This study supports the hypothesis that clinical history and physical examination are the most important determinants in diagnosing seronegative RA. In addition to characteristic symptoms, factors which might contribute to diagnosis of RA in a patient without seropositivity include positive family history, smoking history, acute phase reactants, presence of anemia, and imaging studies. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2163