Eoghan M. McCarthy

Treatment of relapsing polychondritis in the era of biological agents.

Relapsing polychondritis (RP) is a rare disorder, often requiring high doses of immunosuppressive therapy to control its potentially life-threatening consequences. The advent of biological agents has added to the armamentarium available to treat RP, but the lack of controlled trials, along with the small numbers of patients and disease heterogeneity means that new therapies are prescribed without the benefits of rigorous clinical research. Thus, information on individual cases is of value in expanding our knowledge of the use of biologic agents in rare conditions. We report on the use of rituximab in a patient who subsequently developed catastrophic aortic incompetence, and we review the literature in relation to the use of this drug in RP.

Knowledge, Attitudes, and Clinical Practice of Rheumatologists in Vaccination of the At-risk Rheumatology Patient Population

BackgroundPatients with inflammatory arthritis are at increased risk of infection. Much of the burden of infection in this population is vaccine preventable. A number of international rheumatology organizations have published expert recommendations for vaccination in adult patients. Despite this, reported vaccination rates remain low among patients with inflammatory arthritis. ObjectivesWe sought to establish the knowledge, attitudes, and clinical practice of rheumatologists with respect to vaccination. MethodsRheumatologists practicing in Ireland in 2009 were surveyed by postal questionnaire. Data collected was entered into Microsoft Excel and statistical analysis was carried out using SPSS18 software. ResultsEighty (100%) practicing rheumatologists were surveyed. Response rate was 55% (44/80). Of those surveyed, 57% (25/44) had no written departmental vaccination guidelines. Although 90% of those surveyed agreed that the responsibility for ensuring vaccine compliance rests with health professionals, only 5% considered that the rheumatology clinic was the best setting in which to accomplish this. Half (50%, n = 22) of practicing rheumatologists do not inquire about vaccination history in the clinic, with a minority (9%, n = 4) recording vaccination history in their clinical notes. A significant percentage of rheumatologists do not perform screening about prior vaccination before initiation of either anti–tumor necrosis factor (34%) or disease-modifying antirheumatic disease (42%) therapy. Moreover, 57% (n = 25) considered the responsibility for vaccination the domain of the patients’ general practitioners with the favored strategy to improve vaccine compliance being led by the primary care physicians (48%, n = 21). ConclusionsThe practice of Irish rheumatologists with regard to vaccination in this survey was suboptimal. Most neither recommend nor record vaccination history in their clinical notes, with the majority feeling that the rheumatology clinic is not the appropriate setting in which to target strategies to improve vaccine compliance. Although a more proactive role needs to be taken by rheumatologists as the principal prescribers of immunosuppressive therapy on this issue, our survey respondents suggest that strategies to improve vaccine uptake should be developed outside the rheumatology clinic and, in particular, involve primary care. The circulation of currently available international guidelines on vaccination specific for rheumatology patients to primary care physicians should be used to inform practices to ensure improved vaccine compliance.

Giant Iliopsoas Bursitis: A Complication of Chronic Arthritis

Iliopsoas bursitis is a poorly recognized cause of hip pain that requires early recognition to avoid potentially serious complications caused by compression of adjacent structures. It can occur in the setting of trauma in athletes or those who engage in heavy labor and is also associated with acute or chronic arthritis. We describe the cases of 2 patients, one of whom developed a femoral neuropathy, while the other had marked venous compression of the lower limb resulting from enlargement of the iliopsoas bursa. Magnetic resonance imaging offers the most accurate information on the extent of the problem. Recalcitrant cases may require bursectomy in addition to treatment of the underlying cause.

Plasma Fibrinogen Along with Patient-reported Outcome Measures Enhances Management of Polymyalgia Rheumatica: A Prospective Study

Objective. We sought to prospectively examine the responsiveness of a number of patient-reported outcome (PRO) measures in polymyalgia rheumatica (PMR), as well as their relationship to the biomarkers erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma fibrinogen. Methods. Sixty patients with PMR were divided into active (n = 25) or inactive (n = 35) disease groups based on symptoms; physician assessment; and the biomarkers ESR, CRP, and plasma fibrinogen. Groups underwent assessment at baseline and 6 weeks. Disease activity measures and relevant PRO measures were recorded. Measures of responsiveness were compared for all PRO and biomarkers. Results. Visual analog scale disease activity (VASDA) and VAS quality of life (VASQOL) are more responsive to change in disease activity than VAS pain, morning stiffness, Health Assessment Questionnaire (HAQ), and PMR-activity score (AS). Analysis of PMR-AS versus VASDA, VASQOL, and HAQ showed correlation coefficients of 0.87 (p < 0.001), 0.80 (p < 0.001), and 0.68 (p < 0.001), respectively. Receiver-operating curve (ROC) analysis revealed VASDA to be more specific than either HAQ (0.95 vs 0.85; p < 0.001) or VASQOL (0.95 vs 0.93; p < 0.001) for the detection of response to treatment in active PMR. Overall, fibrinogen showed superior correlation coefficients with the various PRO than either of the standard biomarkers ESR or CRP. In addition, standardized response means for fibrinogen, ESR, and CRP were 1.63, 1.2, and 1.05, respectively, indicating that plasma fibrinogen was the most responsive biomarker for assessment of change in disease activity. Conclusion. VASDA and VASQOL are the most responsive PRO to changes in disease activity in PMR. In addition, plasma fibrinogen demonstrated greater responsiveness to changes in disease activity and superior correlation with the various PRO measures recorded than did the standard biomarkers ESR and CRP.

Extra-cranial giant cell arteritis: early and late consequences

Dear Editor, Giant cell arteritis (GCA) is an inflammatory process of large and medium-sized vessels, typically affecting the cranial arteries and putting the patient at risk of sudden, irreversible blindness due to anterior ischemic optic neuropathy. Extra-cranial involvement is less well-appreciated and is associated with a poorer prognosis because of the potential life-threatening location of the vasculitis. Recent studies have suggested that although the pathology of cranial and extra-cranial GCA is similar, the etiology of these two entities may be different. We present the case of a middle-aged woman who presented with catastrophic bowel and ovarian ischemia, with evidence of GCA on histology. Subsequent investigations revealed no additional lesions, thus obviating the need for immunosuppressive therapy. However, the patient later succumbed to ametastatic lung tumor.

Infrapatellar bursitis: an occupational legacy.

A n 81-year-old retired cleaning lady presented with bilateral knee pain. Clinical examination revealed a tender, firm, 2 cm 1 cm swelling inferior to both patellae associated with crepitus and reduced motion of the knees. Radiographs demonstrated bilateral medial compartment narrowing and aggregated calcified masses anterior to the tibial tubercle, consistent with chronic infrapatellar bursitis (Figs. A, B). With physiotherapy, analgesics, and advice regarding joint protection, she noted a gradual improvement in her symptoms, although the masses did not change in size. The infrapatellar bursa is a synovial-lined structure that does not communicate with the knee joint. It is located between the inferior aspect of the patellar tendon and the skin. It functions to minimize trauma to the patellar tendon, which may occur during kneeling or jumping. In the absence of disease, it contains minimal fluid and is thus invisible on imaging.

IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute SLE-like lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.

FRI0224 Plasma fibrinogen is an accurate marker of disease activity in patients with polymyalgia rheumatica

Background Determination of disease activity in polymyalgia rheumatica (PMR) is challenging due to the subjective nature of symptoms and prevalence of concurrent musculoskeletal complaints in an elderly population. Traditionally the non specific inflammatory markers ESR and CRP have been used to guide therapeutic decisions. CRP and ESR may be normal in up to 20% of patients with PMR at the time of diagnosis. Normal ESR or CRP values have been observed in 27% and 14% of relapses, respectively. Any biomarker than assists physicians in more accurately determining patients disease status and therefore enabling accurate adjustment of glucocorticoid dose would be welcomed. Previously we have demonstrated the enhanced specificity of plasma fibrinogen over both ESR and CRP for the detection of response to treatment in patients with active PMR. Objectives To prospectively evaluate the utility of the biomarkers ESR, CRP and Fibrinogen for identifying different disease states in patients with known PMR. Methods Patients with PMR (as per Jones-Hazleman criteria) were divided into high/medium (Group 1) or low (Group 2) disease activity as per the Polymyalgia Rheumatica Activity Score (PMR-AS). A PMR-AS >7 indicates medium/high disease activity with a PMR-AS <7 indicating low disease activity1. Plasma fibrinogen, CRP and ESR were also assayed. An ESR value of 30mm/hr (lab normal <20mm/hr) and CRP of 8mg/L (lab normal <5mg/l) were considered the upper limit for detection of low disease activity. The upper limit of the lab normal for Fibrinogen (4g/L) was used. Sensitivity, specificity, positive predictive values and likelihood ratios were calculated for all biomarkers. Results Data was available from 120 patient visits. Demographic data was similar in both groups. Mean age was 71.8 years. All patients were receiving glucocorticoids with a median steroid dose of 10mg in Group 1 and 5mg in Group 2.There were significant differences in steroid dose between the two groups (p<.001). 70 patients were defined as having low disease activity as per the PMR-AS. Of these 6/70 had an elevated plasma fibrinogen with 14/70 having an ESR >30mm/hr and 18/70 a CRP >8mg/L. The specificity, sensitivity, positive predictive values and likelihood ratios for the different biomarkers as calculated for all 120 patient visits are shown in the table below. Specificity Sensitivity PPV Likelihood Ratio Fischers Exact Test Fibrinogen 91% 52% .81 6.06 P<.001 CRP 74% 90% .73 3.73 P<.001 ESR 64% 50% .64 2.5 P<.001 Whilst CRP was the most sensitive biomarker, plasma fibrinogen was more specific than either ESR or CRP for differentiating between low disease activity and moderate/high disease activity in PMR. It also demonstrated a superior positive predictive value and likelihood ratio than ESR and CRP for identifying patients with moderate/high disease activity. Conclusions Elevated Plasma fibrinogen more accurately indicates that patients are in a persistent moderate or high disease activity state than elevation of ESR or CRP. Measurement of fibrinogen as an adjunct to ESR and CRP in patients with PMR may therefore help treating physicians more accurately identify patients’ disease status and guide decisions with regards glucocorticoid dosage. References A disease activity score for polymyalgia rheumatica. Leeb BF, Bird HA. Ann Rheum Dis. 2004 Oct;63(10):1279-83. Disclosure of Interest None Declared

Localized osteoporosis and its consequences.

A 77-year-old Caucasian woman, who did not smoke or drink alcohol, presented with severe back pain following a fall. Spine radiograph demonstrated wedge-compression fractures of T11 and T12 (Fig. 1A). Magnetic resonance imaging showed the fractures and no neurologic compromise or evidence of bony malignancy. Dual-energy x-ray absorptiometry (DXA) scanning revealed a Tscore of 4.2 at her spine and 1.3 at her hip. In addition to her background risk factors for osteoporosis (female, postmenopausal, low body weight, resident in Ireland), her 25-OH vitamin D levels were noted to be low at 43 nmol/L (normal: 80 nmol/L). Routine laboratory tests, including inflammatory markers, glucose, thyroid function, and tissue transglutaminase antibodies, were within normal limits. She underwent vertebroplasty to help reduce pain and prevent further vertebral collapse (Fig. 1B). She was also treated with calcium, vitamin D, and bisphosphonate therapy and advised regarding weight-bearing exercise. However, she had lost significant height, reported daily back pain, and struggled to maintain independent living. The key points demonstrated by this case include the presentation of osteoporosis with a complication rather than as a preemptive diagnosis, the identification of a contributing cause (hypovitaminosis D) with therapeutic consequences, the surgical procedure used in addition to medical treatment, and the marked discrepancy between her vertebra and hip T-scores on DXA scanning. Although osteoporosis is considered a disease of the elderly, the process begins in early life where diet and lifestyle greatly impact on later bone health. A search for secondary causes is invariably fruitful and these are frequently modifiable. Minimally invasive procedures such as vertebroplasty or kyphoplasty may help ease pain, maintain height, and prevent further bony collapse. Vertebroplasty involves the percutaneous injection of a radiopaque polymethylmethacrylate cement into a painful compressed vertebra, while in kyphoplasty, a balloon is inflated inside the collapsed vertebra to help restore its original shape before the cement is injected. Pain relief is achieved in 90% of patients with osteoporotic fractures. Contraindications include coagulopathies, unstable vertebrae, neurologic signs, and infection. Complications are rare but include leakage of the cement into vascular or neural structures. Furthermore, there may be an increase in the fracture rate of adjacent vertebrae due to altered local tissue mechanics. The discrepancy in T-scores between vertebrae and hip, as noted in this case, has been previously described. Reduced strength of the core muscles compared with the legs may account for lower bone mineral density at the spine. Furthermore, vertebral trabecular bone may be more susceptible to the influences of systemic/nutritional abnormalities. The technological advances in DXA scanning and selection of accurate regions of interest for imaging make artifactual reasons unlikely to account for this difference. Improved awareness, diagnosis, and treatment options greatly help the quality of life of patients with osteoporosis. However, it behooves all health professionals to actively engage in prevention and early diagnosis before complications, such as those demonstrated in this case, become manifest.