Abstract Background/Aims Nocardiosis is a rare infectious disease caused by the aerobic bacteria genus Nocardia and can cause severe suppurative disease affecting virtually any organ. It tends to affect the immunocompromised, making rheumatology patients a particular risk group for this infection. It is not normal human flora and is found in soil, decaying vegetable matter and aquatic environments. It can become airborne and the most common means of entry is thought to be dust inhalation. Methods Our patient is a 75-year-old woman with giant cell arteritis (GCA) treated with prednisolone, SC methotrexate and tocilizumab (started 4 months before her acute illness). Symptoms began with a fall in the garden sustaining a nasty laceration to her leg and an injury to her back worsening some chronic lower back pain (X-rays did not show any fracture). Over the next 5 weeks due to a productive cough and sweats she was prescribed oral antibiotics with no improvement. She was then admitted to hospital due to an acute increase in the severity of her lower back pain alongside a change in character to a burning pain. Her presenting CRP was 32, likely due to having held tocilizumab due to a presumed chest infection. MRI showed a collection in the right erector spinae muscle extending from C7 to the iliac crest and another large collection in the right thigh. A mass in the left sub-mammary area led to a chest CT that showed a chest wall abscess alongside a spiculated lesion in the lung, and further nodular changes. Peripheral blood cultures were negative and eventually draining of the erector spinae abscess led to culture of Nocardiosis nova. Imipenam and Septrin were given as per sensitivities. Unfortunately, our patient has had a difficult clinical course. During her hospital stay she has had possible DRESS syndrome/Septrin-induced liver injury alongside drug induced neutropaenia and lymphopaenia and a possible stroke (this was thought less likely to represent CNS Nocardiosis). Results Her rheumatology management initially involved stopping her DMARDs however due to flares in symptoms her doses of prednisolone have been up and down. It has been difficult to separate symptoms that may be due to cervical spine collections and a possible CNS lesion from GCA symptoms. Conclusion This case demonstrates the need to thoroughly investigate immunosuppressed patients when they are not responding as expected to antibiotics or present with atypical symptoms. It also demonstrates the importance of obtaining a microbiological diagnosis. Cellular immunity is generally thought to be key in preventing Nocardia dissemination however in our patient’s case she was only taking 2.5mg prednisolone when admitted. This is one of only a few case reports of patients developing Nocardia infection whilst on tocilizumab. Disclosure R.J. Crowder: None. H. Mills: None. O. Savanovic-Abel: None. J. King: None. O. Moore: None. M. Perry: None. S. Hewagamage: None. M. Gunathilaka: None.

OBJECTIVES:To report the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated interstitial lung disease (SSc-ILD).METHODS:Patients in the Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography (HRCT) chest were identified and their pulmonary function tests (PFTs) retrieved. Individuals with available results for T-1 (12 months prior to treatment commencement), T0 (date of treatment commencement) and at least one subsequent time point were included in the drug efficacy analysis. The Wilcoxon signed-rank test was used to compare absolute FVC at T1, T0, 12 months (T1), 24 months (T2) and 36 months (T3). Analysis of drug tolerability included all identified patients treated with MMF or AZA.RESULTS:18/22 patients treated with MMF and 29/49 treated with AZA had adequate PFTs for inclusion in the drug efficacy analysis. Median absolute FVC at T1 for MMF treatment was 2.50L, declining to 2.12L at T0 (p=0.02). Following MMF therapy, FVC results were stable at T1 (2.13L, p=0.86), T2 (2.17L, p=0.65) and T3 (2.25L, p=0.78). In the AZA group, a statistically significant decline did not occur prior to treatment, however FVC results remained stable at T1, T2 and T3.Adverse events leading to early discontinuation (<12 months treatment) were less common in the MMF group (4/22 vs. 13/49). Gastrointestinal complications were the main cause of discontinuation in both groups.CONCLUSIONS:In patients with SSc-ILD with declining pulmonary function, MMF therapy was associated with stability for up to 36 months. Early adverse events leading to discontinuation occurred less frequently in patients treated with MMF than in AZA treated patients.

Background Non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) (e.g. Methotrexate (MTX), Sulfasalazine (SUZ) and Leflunomide (LEF)) are used as initial treatment for autoimmune conditions; such as rheumatoid arthritis and psoriatic arthritis. However, there is limited evidence upon the proportion of patients who have to stop medication due to side-effects. Infoflex (CIMS) is an electronic system implemented at Derriford Hospital, May 2014. This system was used to record Rheumatology drugs started and stopped and causes for drug cessation1. Objectives Our aim was to determine the proportion of patients who had to stop taking nbDMARDs due to adverse events (AE) or side-effects (SE), document the commonest reactions and examine whether there were gender differences in drug cessation. Methods A retrospective search was performed using Infoflex for all Rheumatology patients at Derriford Hospital for patients who had been started on nbDMARDs for a one year period between 01/12/2014–30/11/2015. Patients were selected for inclusion if they were continuing on the drug or had stopped it due to AE or SE. Patients were excluded if they had stopped their drug due to inefficacy. Results 1424 patient records were documented from a total of 1080 patients that met the inclusion criteria. Patients included were treated for a variety of rheumatological conditions with the following nbDMARDs; MTX (n=588), Hydroxychloroquine (HCQ) (n=385), SUZ (n=303), LEF (n=92), Azathioprine (AZA) (n=29), Mycophenolate Mofetil (MMF) (n=21), Cyclophosphamide (n=2), Gold (n=2), Cyclosporine (n=1), Tacrolimus (n=1). The percentage and number of patient records that ceased medication due to AE or SE was; MTX 13.44% (n=79), HCQ 13.25% (n=51), SUZ 31.68% (n=96), LEF 20.65% (n=19), AZA 31.03% (n=9), MMF 9.5% (n=2). The nbDMARD dosage did not have any relationship to the rate of SE or AE. Mean length of usage for each drug before stopping due to AE or SE was: MTX (95.9 days), HCQ (57.2 days), SUZ (57.1 days), LEF (68.2 days), AZA (69.8 days), MMF (175.5 days). The most common AE or SE was found to be gastrointestinal for all drugs, except MMF. The female to male ratio for those who discontinued MTX, HCQ and SUZ was increased in comparison with the female to male ratio for overall drug usage. Conclusions SUZ had the highest percentage of patients stopping medication (31.68%) with the shortest duration of usage (57.1 days). MMF had the lowest percentage of patients stopping medication (9.5%) with the longest duration of usage (175.5 days). The commonest reported AE or SE for all drugs (except MMF) were within the gastrointestinal category; principally gastrointestinal intolerance and nausea. The strengths of our data lie in the amount of information captured and its real world setting. Its weakness is the characterisation of SE is insufficiently specific and we have been unable to classify by disease. Future data collection is required to fully capture the patients who will discontinue nbDMARDs within the current study population. However, these data could potentially aid clinicians in advising rheumatology patients of the potential risks of different nbDMARDs. References Chameleon Information Management Services Ltd (CIMS). http://www.infoflex-cims.co.uk/cims/news/2015/11/plymouth_rheumatology/p> Acknowledgement We are very grateful for the work of all staff and the help from all patients in our Rheumatology department Disclosure of Interest None declared

Ulster Medical Society Junior Members Forum Thursday 12th December 2013 Whitla Medical Building, Queen’s University Belfast. ASPIRIN THERAPY IS ASSOCIATED WITH REDUCED MORTALITY IN PATIENTS WITH ACUTE LUNG INJURY Boyle AJ, Digangi A, Mottram LJ, Hamid U, McNamee L, White G, Cross LJM, McNamee J, O’Kane C, McAuley DM. Introduction: Platelet activation has a role in the pathogenesis of acute lung injury (ALI). Observational data suggests aspirin treatment may prevent the development of ALI in critically ill patients. However, it is unknown if aspirin usage alters outcomes in patients with established ALI. Methods: All patients with ALI were identified prospectively in a single large regional medical and surgical Intensive Care Unit (ICU) between December 2010 and July 2012. Demographic, clinical, and laboratory variables were recorded. Aspirin usage, both pre-hospital and during Intensive Care Unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate analyses to assess the impact of these variables on ICU mortality. Results: Two hundred and two patients with ALI were included. 56 (28%) of these received aspirin either prehospital, in ICU, or both. Using multivariate logistic regression analysis, aspirin was found to be protective for ICU mortality. Conclusion: Aspirin usage is associated with reduced mortality in patients with ALI. Whilst trials are ongoing to assess if aspirin can prevent ALI, these new data support the need for a clinical trial to investigate if aspirin improves outcomes in patients with established ALI. MALFORMATION RISKS OF ANTIEPILEPTIC DRUG MONOTHERAPIES IN PREGNANCY: AN UPDATE FROM THE UK AND IRELAND EPILEPSY AND PREGNANCY REGISTERS Campbell E, Kennedy F, Russell A, Smithson WH, Parsons L, Robertson I, Irwin B, Liggan B, Delanty N, Morrison PJ, Hunt SJ, Craig J, Morrow J. Aim: To assess risk of major congenital malformations (MCMs) from exposure to anti-epileptic drugs (AEDs) during pregnancy. Methods: Fifteen-year prospective observational study from 1996 until 2012. Outcomes are reported for valproate, carbamazepine, lamotrigine and levetiracetam monotherapy exposures. Main outcome measure is the MCM rate. Results: Informative outcomes were available for 5510 cases. 1290 women were exposed to valproate monotherapy, 1718 to carbamazepine monotherapy, 2198 to lamotrigine monotherapy and 304 to levetiracetam monotherapy. The MCM risk with valproate monotherapy exposure in-utero is 6.7% (95% CI 5.5%-8.3%), compared to 2.6% with carbamazepine (95% CI 1.9%-3.5%), 2.3% with lamotrigine (95% CI 1.8%-3.1%) and 0.70% (95% CI 0.2%-2.5%) with levetiracetam. A significant dose effect is seen with valproate (p= 0.0006) and carbamazepine (p=0.03) exposed pregnancies, but not with exposure to lamotrigine (p=0.26) or levetiracetam (p=0.09). MCM rate for even the highest doses of lamotrigine (>400mg daily) were lower than the MCM rate observed in pregnancies exposed to less than 600mg daily of valproate (3.4% compared to 5.0%, p=0.35). Conclusions: AED exposure during pregnancy increases the risk of MCM in the infants of women with epilepsy. In utero exposure to valproate carries a significantly higher MCM risk than lamotrigine (p=0.0001), levetiracetam (p=0.0001) or carbamazepine (p=0.0001) monotherapy. Our results are in contrast to previous suggestions that the MCM risk with exposure to low doses of valproate is preferable to that seen with exposure to high doses of lamotrigine. Together with recently published neurodevelopmental data, this data suggests that either lamotrigine or levetiracetam should be used as drugs of choice over valproate, even at low dose, in women of childbearing age with epilepsy. THE USE OF HIGHLY CONCENTRATED HYPERTONIC SALINE IN THE TREATMENT OF TRAUMATIC BRAIN INJURY RELATED REFRACTORY INTRACRANIAL HYPERTENSION. Major EH, O’Connor P, Mullan B. Background: In recent years hypertonic saline has attracted increasing interest in the treatment of traumatic intracranial hypertension, and has a number of documented and theoretical advantages over other hyperosmolar agents. To date, no consensus has been achieved on the safest and most effective HTS concentration for administration. Aims: The purpose of this paper was to evaluate the efficacy of intravenous bolus administration of highly concentrated

OBJECTIVES Clinically meaningful change in systemic sclerosis (SSc) related interstitial lung (SSc-ILD) disease is unknown. The aim of this study was to quantify change in pulmonary function as a predictor of outcome in SSc-ILD. METHODS All patients had SSc-ILD defined by HRCT chest. All PFTs during follow-up, including FVC (L), DLCO (ml/min/mmHg) and KCO (DLCO/alveolar volume ratio; DLCO/VA) (ml/min/mmHg/L) were retrieved. The rate of change over the first four years, and percentage change in the first year of follow-up were used in ROC curve analysis to determine the best cut-off points to predict adverse outcome (home oxygen, lung transplantation, or death). RESULTS Among 264 patients, there were 49 events (38 deaths, 10 supplemental oxygen, one lung transplant) over a mean (±SD) follow-up of 3.0 (±1.7) years. The rates of decline over time and percentage change over one year in each of FVC, DLCO and KCO were predictive of adverse outcome. Stable PFTs over four years gave the optimal negative predictive values (NPVs) of 88-96%. The best sensitivity-specificity trade-off was a decline in FVC of 10% and in DLCO and KCO of 15% with NPVs of 92-93%. CONCLUSIONS The course that SSc-ILD takes is evident within the first 1-4 years of follow up. Patients who have no decline in PFTs over 4 years have better outcomes. A decline within one year in DLCO or KCO of 15% or more is a poor prognostic factor, and identifies patients who should be monitored more closely and considered for therapy.

To determine whether rheumatoid arthritis disease activity correlates with changing weather conditions. A longitudinal analysis of 133 patients attending the Department of Rheumatology, Musgrave Park Hospital, Belfast was performed. Participants had a diagnosis of rheumatoid arthritis and were receiving subcutaneous anti-TNF therapy (Adalimumab or Etanercept) for a period of >6 months. Data were collected at five time points. This included tender joint count, swollen joint count, patient visual analogue score (VAS), erythrocyte sedimentation rate, C-reactive protein, VAS, and DAS-28 (Disease Activity Score). Each weather factor (maximum, minimum temperature, pressure, rainfall, sunshine, humidity, and wind-speed) was analysed against each patients' DAS-28 score at five time points, using an analysis of covariance. A significant correlation was noted between low DAS-28 and increased hours of sunshine (p < 0.001). Sunny conditions were associated with a DAS-28 reduction of 0.037 (95 % CI -0.059, -0.016) p < 0.001. A significant correlation between humidity and DAS-28 was also noted (p = 0.016). Increased humidity was associated with an increased DAS-28 of 0.007 (95 % CI 0.001, 0.013) p = 0.016. Higher temperatures were associated with a non-significant decrease in DAS-28 (p = 0.16). In this study, rheumatoid arthritis disease activity (as measured by DAS-28) was significantly lower in both more sunny and less humid conditions.

Background: The incidence and characteristics of tuberculosis (TB) in remote areas of Papua New Guinea (PNG) are largely unknown. The purpose of our study was to determine the incidence of TB in the Gulf Province of PNG and describe disease characteristics, co- morbidities and drug resistance profiles that could impact on disease outcomes and transmission.Methods: Between March 2012 and June 2012, we prospectively collected data on 274 patients presenting to Kikori Hospital with a presumptive diagnosis of TB, and on hospital inpatients receiving TB treatment during the study period. Sputum was collected for microscopy, GeneXpert analysis, culture and genotyping of isolates.Results: We estimate the incidence of TB in Kikori to be 1290 per 100,000 people (95% CI 1140 to 1460) in 2012. The proportion of TB patients co-infected with HIV was 1.9%. Three of 32 TB cases tested were rifampicin resistant. Typing of nine isolates demonstrated allelic diversity and most were related to Beijing strains.Conclusions: The incidence of TB in Kikori is one of the highest in the world and it is not driven by HIV co-infection. The high incidence and the presence of rifampicin resistant warrant urgent attention to mitigate substantial morbidity in the region.

Internal Medicine JournalVolume 44, Issue 1 p. 108-109 Letter to the Editor Whose responsibility is it to assess cardiovascular risk in patients with rheumatoid arthritis? A. Quinlivan, A. Quinlivan Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorO. A. Moore, O. A. Moore Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorE. Romas, E. Romas Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorM. Nikpour, M. Nikpour Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia Department of Medicine, The University of Melbourne at St. Vincent's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this author A. Quinlivan, A. Quinlivan Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorO. A. Moore, O. A. Moore Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorE. Romas, E. Romas Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorM. Nikpour, M. Nikpour Department of Rheumatology, St. Vincent's Hospital Melbourne, Melbourne, Victoria, Australia Department of Medicine, The University of Melbourne at St. Vincent's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this author First published: 23 January 2014 https://doi.org/10.1111/imj.12322Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 2002; 46: 862–873. 2 Maradit Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 2005; 52: 722–732. 3 Nikpour M, Brady SRE, Liew D. The epidemiological and pathogenic association of rheumatoid arthritis with atherosclerotic cardiovascular disease. J Clin Rheum Musculoskelet Med 2011; 2: 34–44. 4 Micha R, Imamura F, Wyler von Ballmoos M, Solomon D, Hernán M, Ridker P et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 2011; 108: 1362–1370. 5 Maki Petaja KM, Elkhawad M, Cheriyan J, Joshi FR, Ostor AJ, Hall FC et al. Anti-tumor necrosis factor-[alpha] therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation 2012; 126: 2473–2480. 6 Peters MJL, Symmons DPM, McCarey D, Dijkmans BAC, Nicola P, Kvien TK et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010; 69: 325–331. 7 Aletaha D, Neogi T, Silman A, Funovits J, Felson D, Bingham C 3rd et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62: 2569–2581. Citing Literature Volume44, Issue1January 2014Pages 108-109 ReferencesRelatedInformation

Objectives. In a multi-centre study, we sought to determine whether extent of disease on high-resolution CT (HRCT) lung, reported using a simple grading system, is predictive of decline and mortality in SSc-related interstitial lung disease (SSc-ILD), independently of pulmonary function tests (PFTs) and other prognostic variables.Methods. SSc patients with a baseline HRCT performed at the time of ILD diagnosis were identified. All HRCTs and PFTs performed during follow-up were retrieved. Demographic and disease-related data were prospectively collected. HRCTs were graded according to the percentage of lung disease: > 20%: extensive; < 20%: limited; unclear: indeterminate. Indeterminate HRCTs were converted to limited or extensive using a forced vital capacity threshold of 70%. The composite outcome variable was deterioration (need for home oxygen or lung transplantation), or death.Results. Among 172 patients followed for mean (s.d.) of 3.5 (2.9) years, there were 30 outcome events. In Weibull multivariable hazards regression modelling, baseline HRCT grade was independently predictive of outcome, with an adjusted hazard ratio (aHR) = 3.0, 95% CI 1.2, 7.5 and P = 0.02. In time-varying covariate models (based on 1309 serial PFTs and 353 serial HRCTs in 172 patients), serial diffusing capacity of the lung for carbon monoxide by alveolar volume ratio (ml/min/mmHg/l) (aHR = 0.4; 95% CI 0.3, 0.7; P = 0.001) and forced vital capacity (dl) (aHR = 0.9; 95% CI 0.8, 0.97; P = 0.008), were also strongly predictive of outcome.Conclusion. Extensive disease (> 20%) on HRCT at baseline, reported using a semi-quantitative grading system, is associated with a three-fold increased risk of deterioration or death in SSc-ILD, compared with limited disease. Serial PFTs are informative in follow-up of patients.

Background Anti-phospholipid antibodies (APLA) are typically associated with thrombosis in systemic lupus erythematosus and anti-phospholipid syndrome. However, little is know about the clinical associations of these antibodies in systemic sclerosis (SSc). Objectives We sought to determine the prevalence and correlates of APLA in a large cohort of patients with SSc. Methods Patients participating in the Australian Scleroderma Cohort Study who fulfilled the ACR or Medsger criteria for SSc, were tested for APLA (anti-cardiolipin IgM [ACA IgM], anti-cardiolipin IgG [ACA IgG] and anti-beta2 glycoprotein antibodies [Anti-β2GP]) using commercial ELISA assays at each annual visit. APLA and various clinical manifestations were defined as present ever from SSc diagnosis. Chi-square and unadjusted logistic regression were used to identify and quantify clinical associations of APLA in SSc. Results One or more types of APLA were present in 226 (24.0%) of 940 patients included in the study. There were no patients with lupus anticoagulant. Type and titre of APLA are summarized in Table 1. Moderate to high titre ACA IgG were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH) (odds ratio 1.6, 95% CI: 1.03-2.52, p=0.038). Both ACA IgM (odds ratio 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA IgG (odds ratio 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). ACA IgG was a marker of coexistent PAH and ILD (odds ratio 2.10, 95% CI: 1.1-4.2, p=0.036). There was no association between APLA and SSc disease subtype (limited v. diffuse), presence of other autoantibodies, or other disease manifestations e.g. renal crisis. Conclusions Anti-phospholipid antibodies are found in 24% of patients with SSc, but in most cases the titres are low (<20 U/ml). Moderate to high titre APLA are associated with a 1.6 to 2-fold increased risk of PAH or ILD, and a 2-fold increased risk of coexistent PAH and ILD in SSc. Disclosure of Interest None Declared

BackgroundPulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). There is emerging evidence that screening may enable the earlier detection and treatment of SSc-PAH, and thereby improve survival.AimsWe undertook a systematic review to evaluate the performance of current screening algorithms in SSc-PAH.MethodsWe searched the Medline and EMBASE databases to 31 March 2012. We selected studies if they applied a screening algorithm to consecutively enrolled SSc patients not known to have PAH; SSc-PAH had to be confirmed on right heart catheterisation (RHC). The performance of each screening algorithm and the methodological quality of each study was evaluated.ResultsNine studies met the inclusion criteria with a total intent-to-screen population of 3504 participants. In studies of patients with prevalent disease, the positive predictive value (PPV) of screening for PAH was 20.4-87.0%. In studies of patients with incident disease, the PPV of screening for PAH was 20.0-30.7%. The PPV of algorithms using echocardiography alone, or in combination with other tests, was comparable. No study enabled an accurate determination of negative predictive value, sensitivity or specificity of the screening algorithm as only patients who screened positive underwent confirmatory testing with RHC. The optimal timing and frequency of repeat screening is unknown.ConclusionThe low to moderate PPV of current screening algorithms, coupled with the inability to determine accurately the negative predictive value, sensitivity and specificity, suggests that there is a need to validate further these algorithms before making recommendations regarding screening for SSc-PAH.

INTRODUCTION:Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test.METHODS:NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH.RESULTS:NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH.CONCLUSION:We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.