Jan Lenaerts

Diagnostic Ability of a Dynamic Multidisciplinary Discussion in Interstitial Lung Diseases: A Retrospective Observational Study of 938 Cases

Background: The advice of a dynamic multidisciplinary discussion (MDD) is believed to be important in the diagnosis of interstitial lung diseases (ILDs). However, to what extent MDD diagnoses differ from the preliminary diagnoses before formal workup and MDD (preMDD diagnoses) is still insufficiently studied. Methods: We compared preMDD and MDD diagnoses in patients discussed at the Leuven University Hospitals MDDs between January 2005 and December 2015. Results: Of 938 consecutive patients discussed in an MDD, 755 (80.5%) received a specific diagnosis. From the 183 patients with unclassifiable ILD, 150 patients (16.0%) received suggestions concerning further investigations to establish a definite diagnosis. In 191 patients (41.9% of patients with a preMDD diagnosis), the MDD changed the diagnosis. In 384 patients (79.5% of patients without preMDD diagnosis), MDD provided a diagnosis when the referring physician did not. MDD diagnosis showed a trend toward better prognostic discrimination between idiopathic pulmonary fibrosis and other ILDs compared with preMDD diagnosis (Harrell C‐index, 0.666 vs 0.631; P = .08), which was particularly clear in patients with discordant MDD and preMDD diagnoses (hazard ratio, 2.68 vs 0.84; P = .012 vs .768). Conclusions: The MDD provided a definite diagnosis in 80.5% of presented cases, suggesting further investigations in almost all others. Given the high number of patients without preMDD diagnosis, the rate of change in preMDD diagnoses (41.9% of patients with a preMDD diagnosis) probably is an underestimation. The better prognostic discrimination among ILDs by using MDD indicates the added value of MDD in ILD.

Detection of myositis-specific antibodies

It was with much interest that we read the recent European League Against Rheumatism/American College of Rheumatology classification criteria for idiopathic inflammatory myopathies.1 These criteria include Jo-1 autoantibodies, and the authors discussed that future updates of the criteria should also include the more recently identified myositis-specific autoantibodies.1 2 The interest in autoantibodies for classification is also illustrated by a recent proposal for a new clinicoserological classification of adult autoimmune myositis, which is based on the association of autoantibodies with distinct clinical phenotypes.3 4 For example, antibodies to synthetases (eg, Jo-1, PL-7xa0and PL-12) define the antisynthetase syndrome, anti-MDA-5 antibodies are associated with myositis with overlap features such as interstitial lung disease, anti-TIF-1γ and anti-NXP-2 define a subgroup of dermatomyositis and anti-SRP and anti-HMGCR are associated with necrotising autoimmune myositis.2nnAs autoantibodies play a role in the newly proposed classifications,1 …

High prevalence of occupational exposure to solvents or silica in male systemic sclerosis patients: a Belgian cohort analysis

Increasing evidence supports a relation of some occupational exposures to systemic sclerosis pathogenesis. We aimed to evaluate occupational exposure and clinical characteristics in male patients with systemic sclerosis followed in two Belgian academic hospitals. One hundred and three male patients, included in the Belgian Systemic Sclerosis Cohort, were identified. An expert in occupational medicine reviewed the occupational history and allocated the patients to one of the following groups: probable exposure to crystalline silica, probable exposure to solvents, probable exposure to other toxins, or no suspected occupational exposure. Clinical characteristics were extracted from the Belgian Systemic Sclerosis Cohort database. Sufficient data were available for 96/103 patients. Most of these male patients (70/96, 72.9%) had a history of occupational exposure, 55 patients were likely exposed to crystalline silica, 11 patients to solvents, 2 patients to both silica and solvents, and 2 patients to asbestos. Only 26 patients had no suspected occupational exposure (27.1%). We noticed a significant difference in smoking status between exposed and non-exposed patients, with the highest percentage of ever smokers in the group with solvent exposure (pu2009=u20090.011). We found no significant differences in disease phenotype between exposed and non-exposed patients. However, we noted a trend to a higher prevalence of anti-Scl70 antibodies, cardiac dysfunction, and higher disease activity score in patients with occupational exposure. We observed a strikingly high prevalence of occupational exposure to both silica and solvents in male systemic sclerosis patients. Occupational exposure to silica or solvents is highly prevalent in male systemic sclerosis patients.

Mechanic's hands in a woman with undifferentiated connective tissue disease and interstitial lung disease - anti-PL7 positive antisynthetase syndrome: a case report

IntroductionInterstitial lung disease can be idiopathic or occur in the setting of connective tissue diseases. In the latter case it requires a different treatment approach with a better prognosis. Interstitial lung disease can precede the onset of typical connective tissue disease features by many years, and therefore meticulous multidisciplinary follow-up is crucial. This case highlights the diagnostic challenge and the need for intensified attention for subtle clinical features when faced with interstitial lung disease in patients with characteristics of a hitherto undifferentiated connective tissue disease.Case presentationA 44-year-old Caucasian woman presented to our pulmonology department with dyspnea, Raynaud’s phenomenon and subtle swelling of fingers and eyelids. Laboratory analysis and autoantibody screening was negative. She was diagnosed with nonspecific interstitial pneumonia with a concurring undifferentiated connective tissue disease. After four years of stable disease, she presented with rapid pulmonary deterioration, myalgia, periorbital edema, arthritis and a cracked appearance of the radial sides of the fingers of both her hands. This clinical sign was recognized as mechanic’s hands and a specific search for the presence of antisynthetase antibodies was performed. She was found to harbor anti-threonyl-tRNA synthetase antibodies. A diagnosis of antisynthetase syndrome was made and she was treated with glucocorticoids and immunosuppressives.ConclusionsThis case highlights the difficulty in fine-tuning the diagnosis when confronted with a patient with interstitial lung disease and the suspicion of an underlying, yet undifferentiated connective tissue disease. There is a strong need for clinical multidisciplinary follow-up of these patients, with a high level of alertness to rare and specific clinical signs. The diagnosis of the underlying connective tissue disease profoundly influences the management of the interstitial lung disease. Recent data stress that identification of the autoantibody specificity allows for further prognostic stratification and therefore should be pursued.

Treatment adherence in systemic sclerosis: A cross-sectional study

BACKGROUNDnTreatment adherence is an important medical and pharmaco-economical phenomenon, influenced by multiple variables. Treatment adherence in systemic sclerosis (SSc) has been poorly studied.nnnOBJECTIVEnThe aim of the present study was to assess treatment adherence in SSc patients and to identify factors associated with good and poor adherence.nnnMETHODSnWe conducted a monocentric, cross-sectional, observational study. Treatment adherence was evaluated by the Compliance Questionnaire of Rheumatology (CQR). The necessity of treatment and concerns about treatment were investigated using the Beliefs about Medicines Questionnaire-Specific (BMQ-S). The Illness Perception Questionnaire-Revised (IPQ-R) assessed illness perceptions. Disease-related characteristics were collected retrospectively.nnnRESULTSnA total of 66 patients were enrolled in this study. Of these, 47 (71.2%) had a weighted CQR score of ≤80% (poor adherence) and 19 (28.8%) had a weighted CQR score of >80% (good adherence). No significant relationship between demographic, clinical or psychological factors and overall adherence could be found, except with the IPQ subscale timeline acute/chronic (p = 0.042). Our patient population estimated the necessity of their medication high (mean necessity score 20.5), with moderate concern beliefs (mean concern score 15.1). Subjective adherence, as self-reported by patients, was high.nnnCONCLUSIONSnThis study demonstrated low treatment adherence rates in SSc patients. We could not identify demographic, clinical or psychological factors associated with treatment adherence, except with the IPQ subscale timeline acute/chronic. This suggests a correlation between poor adherence and the belief that the disease will be chronic without improvement over time. Symptom relief was an important motivating factor for taking medication. The treatment necessity was scored higher than treatment concerns, but the necessity beliefs were not associated with adherence.

Rituximab in systemic autoimmune rheumatic diseases: indications and practical use

ABSTRACT Objectives: To review the therapeutic option of Rituximab, a chimeric anti-CD20 antibody, in systemic autoimmune rheumatic diseases (SARDs) such as systemic lupus erythematosus, systemic sclerosis, primary Sjögren syndrome and idiopathic inflammatory myopathy. Methods: A non-systematic review was conducted. Results: The specific role and indication of rituximab in SARDs has been the subject of multiple trials in recent years. Evidence supports the use of rituximab in moderate-to-severe refractory systemic lupus erythematosus, diffuse skin involvement in systemic sclerosis and systemic involvement in primary Sjögren syndrome. Several guidelines have adopted these indications. In addition, there is a consensus about the use of rituximab in refractory myositis. The role of rituximab in interstitial lung disease associated with these SARDs needs to be further explored. Conclusion: Rituximab is a treatment option in several SARDs. Upcoming trials, use in daily practice and the safety profile are elaborated on.

Diverging illness perceptions between physicians about patients with systemic lupus erythematosus and systemic sclerosis: a vignette-based study

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are complex chronic auto-immune diseases characterized by multiple organ involvement, comorbidities, and complications. This complexity results in a need for a multidisciplinary management and treatment of SLE and SSc by physicians from a number of medical disciplines, all of who may have different perceptions concerning the condition of a particular patient. The aim of this study was to explore differences in physicians’ perceptions on the illness of SLE and SSc patients. Physicians from nine disciplines working at three hospitals in Belgium completed illness perception questionnaires for healthcare professionals based on four patient vignettes, i.e., two vignettes per disease (SLE-SSc). Statistical analysis was carried out by a k-means clustering technique for clustering physicians according to their illness perceptions. Fifty physicians, 62% men with a mean age of 42.8 years (SD 11.3) and mean working experience of 12.7 years (SD 11.6), participated. For each disease, three clusters of physicians with different scores in illness perceptions were identified. For SLE, these clusters were specified as the ‘optimistic’ group, the ‘realistic’ group, and the ‘overwhelming impact by disease’ group. For SSc, the clusters were characterized as the ‘optimistic’ group, the ‘realistic’ group, and the ‘skeptical’ group. We found divergent illness perceptions across physicians of the same and other disciplines. Our study yielded three clusters of physicians per disease with a large variability in illness perceptions. Further studies should focus on the factors that determine these differences and their consequences for patient care.

FRI0393 Prevalence of myositis-specific antibodies in idiopathic inflammatory myopathy compared to disease and healthy controls

Background Myositis-specific autoantibodies (MSA) are increasingly recognized as important diagnostic and prognostic markers in idiopathic inflammatory myopathies (IIM) (polymyositis, dermatomyositis, sporadic inclusion body myositis and necrotizing autoimmune myositis). The prevalence of these MSAs in other systemic autoimmune rheumatic diseases and neuromuscular diseases is unclear. Objectives To compare positivity of MSA in a cohort of IIM patients to positivity in healthy controls and different systemic autoimmune rheumatic diseases (SARD) or chronic inflammatory demyelinating polyneuropathy (CIDP). Methods A line immunoassay (Myositis 12 IgG DOT for BlueDiver) for IgG autoantibodies against Jo-1, PL-7, PL-12, EJ, SRP, Mi-2, MDA-5, TIF1-γ, HMGCR, SSA/Ro52kD, SAE1/2 and NXP-2 antigens was performed in patients with IIM (n=146), healthy controls (blood donors, n=40) and disease controls (n=200). The disease control group consisted of patients with other SARD (rheumatoid arthritis, RA; systemic sclerosis, Ssc; Sjögrens syndrome, SjS; and systemic lupus erythematosus, SLE) (n=40 for each disease group) and CIDP (n=40). A result >10 arbitrary units was considered significantly positive. Results 50% of 146 patients with IIM tested positive for an MSA (table 1), compared to 3,5% of 200 disease controls (table 1). 1 SSc patient was positive for Jo-1, 1 CIDP patient was positive for PL12, 2 SSc patients were positive for TIF1-gamma, 2 patients (1 SSc and 1 SjS patient) were positive for SAE1/2, and 1 SjS patient was positive for NXP2. The prevalence of SAE1/2 and TIF1-gamma positivity was similar in the IIM and disease control group. No healthy control had a significantly positive MSA. Antibody detected IIM Disease controls Healthy controls (n=146) (n=200) (n=40) 1 positive (>10 AU) MSA detected 68 (47%) 7 (3,5%) 0 (0%) u2003Jo-1 28 (19%) 1 (0,4%) 0 (0%) u2003PL12 3 (2%) 1 (0,4%) 0 (0%) u2003PL7 1 (1%) 0 (0%) 0 (0%) u2003EJ 2 (1%) 0 (0%) 0 (0%) u2003Mi-2 7 (5%) 0 (0%) 0 (0%) u2003MDA-5 7 (5%) 0 (0%) 0 (0%) u2003SAE1/2 3 (2%) 2 (0,8%) 0 (0%) u2003TIF1-gamma 2 (1%) 2 (0,8%) 0 (0%) u2003NXP2 5 (3%) 1 (0,4%) 0 (0%) u2003SRP 3 (2%) 0 (0%) 0 (0%) u2003HMGCR 7 (5%) 0 (0%) 0 (0%) >1 positive (>10 AU) MSA detected 4 (3%) 0 (0%) 0 (0%) u2003Jo-1 + EJ 1 u2003Jo-1 + NXP2 1 u2003SAE1/2 + NXP2 1 u2003Jo-1 + SAE1/2 + NXP2 1 Conclusions MSA positivity in patients with a clinical non-IIM diagnosis (other SARD or CIDP) is infrequent compared to positivity in the IIM group. For TIF1-gamma and SAE1/2 assay performance may need to be optimized. The distribution of subtypes of MSA in this IIM cohort is consistent with data of previous studies.1 References Allenbach Y, Benveniste O. Diagnostic Utility of Autoantibodies in Inflammatory Muscle Diseases. J Neuromuscul Dis. 2015; 2:13–25. Disclosure of Interest None declared

AB0638 Cardiac transplant in systemic sclerosis-associated cardiomyopathy: monocentric experience of 3 cases

Background Cardiac involvement in systemic sclerosis (SSc) is a frequent complication, but end-stage cardiac failure remains uncommon and represents a poor prognosis. Heart-lung and lung transplant is an established treatment option for SSc-related pulmonary disease. Due to the limited published data, no recommendations exist for cardiac transplant in the context of SSc. Objectives We present our monocentric experience of 3 patients with SSc who underwent cardiac transplant for SSc-related end-stage heart disease (multiple hospitalisations due to failure of medical therapy and life-threatening complications). Results Case 1 is a 59-year-old male with limited cutaneous SSc. Antinuclear antibody (ANA) was negative. He had vascular (digital ulcers) and cardiac (heart failure (left ventricular ejection fraction (LVEF) 20%, NYHA class IV)) involvement, without major gastrointestinal or pulmonary involvement (no interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH: assessed by right heart catheterization (RHC))). He underwent a cardiac transplant at the age of 51, after a disease duration of 6 years. Post-transplantation immunosuppressant therapy consists of tacrolimus and mycophenolic acid, initially associated with methylprednisolon, which is the standard immunosuppression protocol at our institution. Case 2 is a 55-year-old male with limited cutaneous SSc. ANA was positive, 1/320, speckled pattern, but no SSc-related autoantibody has been identified. He had gastrointestinal (upper gastrointestinal tract dysmotility), muscular (myositis) and cardiac (heart failure with secondary cardiac cirrhosis (LVEF 40%, NYHA class III)) involvement, without major pulmonary involvement (no ILD or PAH). He underwent a cardiac transplant at the age of 54, after a disease duration of 7 years. Standard immunosuppressants were initiated. Case 3 is a 50-year-old male with diffuse cutaneous SSc. ANA was negative. He had vascular (digital ulcers), gastrointestinal (upper gastrointestinal tract dysmotility) and cardiac (heart failure with secondary cardiac cirrhosis (LVEF 40%, NYHA class III)) involvement, without major pulmonary involvement (no ILD or PAH). He underwent a cardiac transplant at the age of 49, after a disease duration of 4 years. Standard immunosuppressants were initiated. At present, 1,5 years (case 2 and 3) and 8 years (case 1) after transplant, the donor hearts are still functioning well. No other SSc-related organ manifestations have occurred. Case 1 Case 2 Case 3 Sex, age Male, 59 years Male, 55 years Male, 50 years Type of SSc Limited Limited Diffuse Disease duration at Tx 6 years 7 years 4 years ANA Negative 1/320, speckled, no SSc-specific antibody Negative Pre-Tx NYHA class IV III III LVEF 20% 40% 40% RHC: mPAP in mmHg 26 20 31 RHC: PCWP in mmHg 20 14 28 Post-Tx NYHA class I I I LVEF 60% 55% 60% RHC: mPAP in mmHg 19 13 21 RHC: PCWP in mmHg 12 8 12 Tx: Transplant; mPAP: Mean pulmonary artery pressure; PCWP: Pulmonary capillary wedge pressure. Conclusions We present 3 patients with SSc who successfully underwent cardiac transplant for SSc-related end-stage heart disease. None had other major SSc-related organ involvement. This supports the limited published data that cardiac transplant is feasible and can be considered in end-stage SSc-related cardiomyopathy. Disclosure of Interest None declared