Objectives Pulmonary arterial hypertension (PAH) affects up to 15% of patients with connective tissue diseases (CTD). Previous recommendations developed as part of larger efforts in PAH did not provide detailed recommendations for patients with CTD-PAH. Therefore, we sought to develop recommendations for screening and early detection of CTD-PAH. Methods We performed a systematic review for the screening and diagnosis of PAH in CTD by searching the literature. Using the RAND/UCLA methodology, we developed case scenarios followed by 2 stages of voting—first international experts from a variety of specialties voted anonymously on the appropriateness of each case scenario and then the experts met in a face-to-face meeting to discuss and resolve discrepant votes to arrive at consensus recommendations. Results The key recommendations state that patients with systemic sclerosis (SSc) should be screened for PAH. In addition, mixed connective tissue diseases (MCTD) or other CTD’s with scleroderma features should also be screened for PAH (scleroderma-spectrum disorder). Initial screening evaluation in patients with SSc and scleroderma-spectrum disorders include pulmonary function test (PFT) including diffusion capacity carbon monoxide (DLCO), transthoracic echocardiogram (TTE), and NT- Pro BNP. In SSc and spectrum disorders, TTE and PFT should be performed on annual basis. The full screening panel (TTE, PFT, and NT-ProBNP) should be performed as soon as any new signs or symptoms are present. Conclusion We provide consensus-based, evidence-driven recommendations for screening and early detection of CTD-PAH. It is our hope that these recommendations will lead to earlier detection of CTD-PAH and ultimately improve patient outcomes.

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Purpose of review Gastrointestinal tract (GIT) involvement in systemic sclerosis (scleroderma, SSc) is the most common internal complication. This review discusses the outcome measures to measure GIT involvement in clinical care and trials. Recent findings Patient-reported outcome measures have been validated (UCLA SCTC GIT 2.0 and NIH PROMIS® scales) in SSc-GIT. Multiple objective measures are available to assess mucosal involvement and motility in GIT. However, these need to validated in SSc for trials. Summary GIT is a common cause of morbidity and has negative impact on quality of life in SSc. Recommendations are given for trial design and evaluation of GI involvement in SSc.

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examinedHLAassociations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominantHLA-DRB1*08:04andHLA-DRB1*11:02alleles were associated with overall SSc risk, and theHLA-DRB1*08:04allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, theHLA-DPB1*13:01andHLA-DRB1*07:01alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance ofHLAin defining autoantibody subtypes. The association of theHLA-DPB1*13:01allele with the ATA+subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence andHLA-DPB1*13:01allele frequency in multiple populations was observed (r= 0.98,P= 3 × 10−6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA α/β allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link betweenHLAalleles, autoantibodies, and environmental triggers in the pathogenesis of SSc.

GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.