Longitudinal assessment of interstitial lung disease in single lung transplant recipients with scleroderma.

OBJECTIVE: To investigate the natural history of fibrotic lung disease in recipients of a single lung transplant for scleroderma-associated interstitial lung disease (ILD). METHODS: Global ILD (including ground glass, nodular opacities and fibrosis) was categorized into severity quintiles on first and last post-transplant CT scans, and percent fibrosis by manual contouring was also determined, in nine single lung transplant recipients. Quantitative mean lung densities and volumes for the native and allograft lungs were also acquired. RESULTS: In the native lung, global ILD severity quintile worsened in two cases and percent fibrosis worsened in four cases (range 5-28%). In the lung allograft, one case each developed mild, moderate and severe ILD; of these, new fibrotic ILD (involving <10% of lung) occurred in two cases and acute cellular rejection occurred in one. The average change in native lung density over time was +2.2 Hounsfield Units per year and lung volume +1.4 ml per year, whereas the allograft lung density changed by -5.5 Hounsfield Units per year and total volume +27 ml per year (P = 0.011 and P = 0.039 for native vs allograft density and volume comparisons, respectively). CONCLUSIONS: While the course of ILD in the native and transplanted lungs varied in this series, these cases illustrate that disease progression is common in the native lung, suggesting that either the immune process continues to target autoantigens or ongoing fibrotic pathways are active in the native lung. Mild lung disease may occur in the allograft after several years due to either allograft rejection or recurrent mild ILD.

Association between sinusitis and incident rheumatic diseases: a population-based study.

OBJECTIVES: To determine whether antecedent sinusitis is associated with incident rheumatic disease. METHODS: This population-based case-control study included all individuals meeting classification criteria for rheumatic diseases between 1995 and 2014. We matched three controls to each case on age, sex and length of prior electronic health record history. The primary exposure was presence of sinusitis, ascertained by diagnosis codes (positive predictive value 96%). We fit logistic regression models to estimate ORs for incident rheumatic diseases and disease groups, adjusted for confounders. RESULTS: We identified 1729 incident rheumatic disease cases and 5187 matched controls (mean age 63, 67% women, median 14 years electronic health record history). After adjustment, preceding sinusitis was associated with increased risk of several rheumatic diseases, including antiphospholipid syndrome (OR 7.0, 95% CI 1.8 to 27), Sjögren's disease (OR 2.4, 95% CI 1.1 to 5.3), vasculitis (OR 1.4, 95% CI 1.1 to 1.9) and polymyalgia rheumatica (OR 1.4, 95% CI 1.0 to 2.0). Acute sinusitis was also associated with increased risk of seronegative rheumatoid arthritis (OR 1.8, 95% CI 1.1 to 3.1). Sinusitis was most associated with any rheumatic disease in the 5-10 years before disease onset (OR 1.7, 95% CI 1.3 to 2.3). Individuals with seven or more codes for sinusitis had the highest risk for rheumatic disease (OR 1.7, 95% CI 1.3 to 2.4). In addition, the association between sinusitis and incident rheumatic diseases showed the highest point estimates for never smokers (OR 1.7, 95% CI 1.3 to 2.2). CONCLUSIONS: Preceding sinusitis is associated with increased incidence of rheumatic diseases, suggesting a possible role for sinus inflammation in their pathogenesis.

Myhre syndrome in adulthood: clinical variability and emerging genotype-phenotype correlations.

Myhre syndrome (MS, MIM 139210) is a rare multisystemic disorder caused by recurrent pathogenic missense variants in SMAD4. The clinical features have been mainly documented in childhood and comprise variable neurocognitive development, recognizable craniofacial features, a short stature with a pseudo-muscular build, hearing loss, thickened skin, joint limitations, diverse cardiovascular and airway manifestations, and increased fibrosis often following trauma or surgery. In contrast, adults with MS are underreported obscuring potential clinical variability. Here, we describe 24 adults with MS, including 17 diagnosed after the age of 18 years old, and we review the literature on adults with MS. Overall, our cohort shows a milder phenotype as well as lower mortality rates compared to what has been published in literature. Individuals with a codon 500 variant in SMAD4 present with a more pronounced neurodevelopmental and systemic phenotype. However, in contrast to the literature, we observe cardiovascular abnormalities in individuals with the p.(Arg496Cys) variant. In addition, we describe scoliosis as a new manifestation and we report fertility in two additional males with the p.(Arg496Cys). In conclusion, our study contributes novel insights into the clinical variability of MS and underscores the importance of variant-specific considerations, and we provide recommendations for the management of MS in adulthood.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Scleredema in the Setting of Monoclonal Gammopathy of Unknown Significance With Progression to Multiple Myeloma: A Case Report.

Type 2 scleredema on the background of monoclonal gammopathy of undetermined significance (MGUS) is a rare and progressive connective tissue disorder with very few cases reported to date. It is characterized by chronic and diffuse induration of the skin that begins in the upper back and neck and progresses proximally to distally, involving the shoulders, trunk, and arms; the hands are usually spared. Here, we present an unusual case of long-standing scleredema that progressed to involve the hands and fingers. This case was further complicated by new-onset Raynaud's phenomenon, splenomegaly, lymphadenopathy, the development of a plasmacytoma, and eventual progression to multiple myeloma. We highlight the differential diagnoses for his complex presentation, the workup that was completed, and current treatment options.

Diastolic Dysfunction in Systemic Sclerosis: Risk Factors and Impact on Mortality.

OBJECTIVE: To determine the independent risk factors for diastolic dysfunction (DD) in patients with systemic sclerosis (SSc) and to evaluate the impact of DD on mortality. METHODS: SSc patients enrolled in the Johns Hopkins Scleroderma Center Cohort between November 1, 2006 and November 1, 2017 with ≥1 analyzable 2-dimensional (2-D) echocardiogram in our system were included (n = 806). DD risk factors and SSc disease characteristics were prospectively obtained, and the presence or absence of DD was determined using the most recent 2-D echocardiogram. Logistic regression models examined associations between clinical risk factors and DD, and Cox proportional hazards models were used to assess survival. RESULTS: DD was present in 18.6% of participants. The majority of participants were female (84%) with a median age of 58.4 years (interquartile range 48.8-68.1). Older age (odds ratio [OR] 1.12 [95% confidence interval (95% CI) 1.09-1.15], P < 0.001), coronary artery disease (OR 3.69 [95% CI 1.52-8.97], P = 0.004), obesity (OR 4.74 [95% CI 2.57-8.74], P < 0.001), longer SSc disease duration (OR 1.04 [95% CI 1.01-1.06], P = 0.004), diffusing capacity for carbon monoxide ≤60% of predicted (OR 2.41 [95% CI 1.40-4.16], P = 0.002), and history of scleroderma renal crisis (OR 3.18 [95% CI 1.12-9.07], P = 0.031) were all independently associated with an increased risk of DD. Anti-Scl-70 positivity (OR 0.49 [95% CI 0.26-0.93], P = 0.03) and severe gastrointestinal disease (OR 0.48 [95% CI 0.30-0.79], P = 0.004) were associated with a reduced risk of DD. The presence of DD was independently associated with an increase in the risk of mortality (hazard ratio 1.69 [95% CI 1.07-2.68], P = 0.027). CONCLUSION: DD is independently associated with an increased risk of mortality in patients with SSc. Potentially modifiable risk factors, including coronary artery disease and obesity, should be addressed in patients with SSc to reduce mortality risk.

Essential Hypertension Worsens Left Ventricular Contractility in Systemic Sclerosis.

OBJECTIVE: Primary cardiac involvement in systemic sclerosis (SSc) is prevalent and morbid; however, the influence of traditional cardiovascular (CV) risk factors, such as essential hypertension (HTN), are unclear. In the present study, we sought to understand the effects of HTN on left ventricular (LV) contractility in patients with SSc using echocardiographic speckle-derived global longitudinal strain (GLS). METHODS: Fifty-six SSc patients with HTN (SSc+HTN+) and 82 SSc patients without HTN (SSc+ HTN-) were compared with 40 non-SSc controls with HTN (SSc-HTN+) and 40 non-SSc controls without HTN (SSc-HTN-), matched by age and sex. All HTN patients were on stable antihypertensive therapies. Echocardiographic measures included LV (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and LV diastolic function. LV contractility was assessed by GLS, averaged across the 18 LV segments. RESULTS: Patients with SSc had diminished GLS regardless of HTN status when compared to both control groups, despite normal LVEF (P < 0.001). SSc+HTN+ had the highest prevalence of diastolic dysfunction, with significantly higher septal E/e´, a marker of LV filling pressures (P < 0.05), as well as the largest reduction in GLS compared to SSc+HTN- and both control groups. CONCLUSION: Speckle-derived strain revealed diminished LV contractility in patients with SSc, despite normal LVEF. SSc+HTN+ had more prominent reductions in GLS associated with evidence of LV remodeling and worsened diastolic function. Our findings demonstrate the presence of subclinical LV contractile dysfunction in SSc that is further exacerbated by concomitant HTN, thereby identifying HTN as an important modifiable CV risk factor that should be managed aggressively in this at-risk population.

Pharmacotherapy Options in the Management of Raynaud's Phenomenon.

PURPOSE OF REVIEW: Multiple classes of medications have been studied for the treatment of Raynaud's phenomenon (RP) with or without digital ischemia. The goal of this review is to discuss the outcomes of recent studies and to report on our approach to the management of RP in light of the available evidence. RECENT FINDINGS: Comparing treatments for RP remains a challenge as efficacy endpoint vary widely among trials. While calcium channel blockers are used first-line in the pharmacologic management of RP, phosphodiesterase 5 inhibitors have also been shown to be beneficial in reducing symptoms. In the setting of digital ischemia, administration of intravenous prostanoids is the standard of care. Bosentan has shown benefit in the prevention of future ulcers in patients with scleroderma. Botulinum toxin therapy was ineffective in a clinical trial involving scleroderma patients; more controlled studies are needed in other subsets of patients. Digital sympathectomy may be beneficial in cases of critical digital ischemia, though recurrence of symptoms is common. SUMMARY: Comparative effectiveness studies are needed to determine which therapeutic interventions are most beneficial in patients with RP. Based on the available evidence, we start with CCBs and add a phosphodiesterase inhibitor if symptoms are not controlled, or intravenous prostacyclin in the setting of severe critical digital ischemia. We may additionally add an endothelial receptor antagonist in cases of recurrent digital ulcers. A surgical sympathectomy may be used in refractory cases of digital ischemia. A digital block may also be a less invasive, but temporary, intervention allowing for titration of medical therapy.

Osteoporosis Management in Ankylosing Spondylitis.

Low bone mineral density (BMD) is increasingly recognized as a common comorbid condition in ankylosing spondylitis (AS). As low BMD increases fracture risk, it is important to identify and treat low BMD in patients with AS who have been shown to be at increased risk for fractures above the population normal. Since low BMD occurs early in disease, we screen during the first year of diagnosis with dual energy x-ray absorptiometry (DXA). If patients are found to have osteoporosis by T-score of less than -2.5 or if their Z-score on DXA is more than two standard deviations below the mean, we initiate therapy with bisphosphonates in males and in females who are not planning any future pregnancies. While reduction in fracture risk with bisphosphonate therapy has not been clearly defined in patients with AS, reduction in vertebral and hip fractures has been well established in primary osteoporosis and thus it is our first line treatment. If there are contraindications to the use of bisphosphonates in the treatment of low BMD, we will consider the use of denosumab. If the patient is not receiving a TNF-alpha inhibitor (TNFi) and has active disease, we also favor early initiation of TNFi due to their positive effects on BMD though the outcome on reduction in vertebral fractures remains unclear. We counsel all patients regarding the importance of adequate intake of vitamin D and calcium per the Institute of Medicine guidelines. All patients should be encouraged to participate in weight-bearing activities with a focus on core strength and gait training.