Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sj?gren’s syndrome

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sj?gren’s syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American–European criteria) and 89 age–gender–ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (aβ2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney’s criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16?% patients and 5.6?% controls (p?=?0.035). LA was the most common aPL in patients (9?%), followed by aβ2GPI (5?%) and aCL (4?%). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p?=?0.061). Mean age at time of stroke was 35?years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney’s criteria) and were positive exclusively for LA. Comparison of patients with (n?=?16) and without (n?=?84) aPL revealed similar mean age, female predominance, and ethnicity (p?>?=0.387). Frequencies of livedo reticularis (25 vs. 4.8?%, p?=?0.021), stroke (12.5 vs. 0?%, p?=?0.024), and DVT (18.8 vs. 1.2?%, p?=?0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p?≥?0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.     

Prevalence and risk factors for venous thromboembolic complications in the Swiss Inflammatory Bowel Disease Cohort

Objective: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is associated with the occurrence of venous thromboembolism (VTE) such as deep vein thrombosis (DVT) and pulmonary embolism (PE). We aimed to assess the prevalence and associated risk factors for VTE in a large national cohort of IBD patients.

Material and methods: Data from patients of the Swiss IBD Cohort Study (SIBDCS) enrolled between 2006 and 2013 were analyzed.

Results: A total of 2284 IBD patients were analyzed of which 1324 suffered from CD and 960 from UC. VTE prevalence was 3.9% (90/2284) overall and 3.4% (45/1324) in CD patients (whereof 2.4% suffered from DVT and 1.5% from PE) and 4.7% (45/960) in UC patients (whereof 3.2% suffered from DVT and 2.4% from PE). Median disease duration in CD patients with VTE was 12 years [IQR 8–23] compared to eight years [3–16] in CD patients without VTE (p?=?0.001). Disease duration in UC patients with VTE was seven years [4–18] compared to six years [2–13] in UC patients without VTE (p?=?0.051). Age at CD diagnosis ≥40 years (OR 1.851, p?=?0.073) and disease duration >10 years (OR 1.771, p?=?0.088) showed a trend to be associated with VTE. In UC patients, IBD-related surgery (OR 3.396, p?=?0.004) and pancolitis (OR 1.927, p?=?0.050) were significantly associated with VTE.

Conclusions: VTE are prevalent in CD and UC patients. Pancolitis and UC-related surgery are significantly associated with VTE in UC patients.     

Acute pulmonary edema, capillaritis and alveolar hemorrhage: pulmonary manifestations coexistent in antiphospholipid syndrome and systemic lupus erythematosus?

Pulmonary capillaritis and alveolar hemorrhage are rare yet serious and life threatening complications of systemic lupus erythematosus (SLE). Pulmonary manifestations of antiphospholipid syndrome (APS) are similar and include, apart from pulmonary embolism and pulmonary hypertension, pulmonary capillaritis, diffuse alveolar hemorrhage and respiratory insufficiency in patients with catastrophic APS. Herein, we described the radiological features of three patients with pulmonary and SLE-associated APS, manifested with pulmonary edema, capillaritis and alveolar hemorrhage. We observed that the radiological features of pulmonary APS shared close resemblance to those of pulmonary SLE. Based on these findings, we conclude that both entities are not only histologically, but also radiologically indistinguishable from each other, suggesting a mutual pathogenetic mechanism. This raises the question of whether some of the reported lupus pneumonitis cases in the past might be manifestations of APS rather than of SLE.     

The relationship between social support and health-related quality of life in patients with antiphospholipid (hughes) syndrome

Objective: Antiphospholipid (Hughes) syndrome (APS) is recognised as a systemic autoimmune disease defined by recurrent thromboembolic events and/or pregnancy morbidity. Little is known about the psychological burden of this long-term condition. This study aims to explore the relationship between social support and health-related quality of life (HRQoL) in patients with APS.

Methods: A total of 270 patients with a clinical diagnosis of APS participated in a cross-sectional online questionnaire survey. Data included demographics, disease-related information, social support and HRQoL.

Results: Both perceived and ideal social support were associated with HRQoL in APS. Patients reported receiving insufficient social support. Perceived emotional support was related to physical functioning (B?=?7.77, p?=?.006, 95% CI: 2.25, 13.29); perceived instrumental support was associated with bodily pain (B?=?17.52, p? .001, 95% CI: 11.15, 23.90) and perceived informational support with physical and social functioning (B?=??6.30, p?=?.05, 95% CI: ?12.52, ?0.08; B?=?8.06, p?=?.02, 95% CI: 1.17, 14.94). Ideal emotional support was related to physical and social functioning (B?=?5.80, p?=?.04, 95% CI: 0.26, 11.34; B?=?7.53, p?=?.04, 95% CI: 0.55, 14.51); ideal instrumental support was associated with mental health (B?=?4.73, p?=?.03, 95% CI: 0.38, 9.07) and ideal informational support with vitality (B?=?5.85, p?=?.01, 95% CI: 1.23, 10.46).

Conclusion: Social support was linked to HRQoL in patients with APS. Insufficient social support was associated with limitations in various HRQoL domains. Increasing social support especially through provision of disease-specific education might contribute to improving HRQoL in patients with APS. Patient-tailored interventions addressing psychosocial aspects of living with APS are needed to improve patients’ psychological and physical status.     

RV Fractional Area Change and TAPSE as Predictors of Severe Right Ventricular Dysfunction in Pulmonary Hypertension: A CMR Study

Background

The right ventricular ejection fraction (RVEF) is a surrogate marker of right ventricular function in pulmonary hypertension (PH), but its measurement is complicated and time consuming. The tricuspid annular plane systolic excursion (TAPSE) measures only the longitudinal component of RV contraction while the right ventricular fractional area change (RVFAC) takes into account both the longitudinal and the transversal components. The aim of our study was to evaluate the relationship between RVEF, RVFAC, and TAPSE according to hemodynamic severity in two groups of patients with PH: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods and Results

Fifty-four patients with PAH (n?=?15) and CTEPH (n?=?39) underwent right heart catheterization and cardiac magnetic resonance (CMR). The ventricular volumes and areas, TAPSE, and eccentricity index were measured. The RVFAC was more strongly correlated with the RVEF (r?=?0.81, p?<?0.0001) than the TAPSE (r?=?0.63, p?<?0.0001). RVEF?<?35% was better predicted by the RVFAC than the TAPSE (TAPSE: AUC?=?0.77 and RVFAC: AUC?=?0.91; p?=?0.042). In the group with the worse hemodynamic status, the RVFAC correlated much better with the RVEF than the TAPSE. There were no significant differences in the CMR data analyzed between the groups of PAH and CETPH patients.

Conclusions

The RVFAC is a good index to estimate RVEF in PH patients; even better than the TAPSE in patients with more severe hemodynamic profile, possibly for including the transversal component of right ventricular function in its measurement. Furthermore, RVFAC performance was similar in the two PH groups (PAH and CTEPH).

     

Proinflammatory proteins in female and male patients with primary antiphospholipid syndrome: preliminary data

The latest classification criteria for the diagnosis of the antiphospholipid syndrome (APS, an autoimmune disease characterized by thromboses, miscarriages and presence of antiphospholipid antibodies (Abs)) emphasized that thrombotic manifestations of APS should be without any signs of an inflammatory process. However, atherosclerosis (a chronic inflammatory response to the accumulation of lipoproteins in the walls of arteries) and APS are characterized by some similar features. We evaluated whether proinflammatory proteins were associated with the features of the primary APS (PAPS). PAPS patients without obstetric complications and with impaired lipid profile were included in the study. Antiphospholipid antibodies, TNF-alpha, and apo(a) were determined by ELISA. Complement components and hsCRP were measured by immunonephelometry. Decreased C3c was observed in female patients with increased titers of IgG anti-β2gpI (χ²?=?3.939, P?=?0.047) and in male patients with increased IgM anticardiolipin Abs (χ²?=?4.286, P?=?0.038). Pulmonary emboli were associated with interleukin (IL)-6 in male (χ²?=?6.519, P?=?0.011) and in female (χ²?=?10.405, P?=?0.001) patients. Cerebrovascular insults were associated with LDL-cholesterol (P?=?0.05, 95 % CI: 1.003 - 12.739) in female and with apo(a) (P?=?0.016, 95 % CI: 0.000–0.003) in male patients. Older female patients had increased LDL-cholesterol levels and frequency of myocardial infarctions. Proinflammatory proteins were associated with features of primary APS. No real gender differences in regard to proinflammatory protein levels were observed. Premenopausal state of female PAPS patients confers lower cardiovascular risk.     

Identification of chronic thromboembolic pulmonary hypertension on CTPAs performed for diagnosing acute pulmonary embolism depending on level of expertise

BackgroundExpert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at the time of acute pulmonary embolism (PE) presentation preceding CTEPH. Little is known about the accuracy and reproducibility of CTPA reading by radiologists in training in this setting.ObjectivesTo evaluate 1) whether signs of CTEPH or chronic PE are routinely reported on CTPA for suspected PE; and 2) whether CTEPH-non-expert readers achieve comparable predictive accuracy to CTEPH-expert radiologists after dedicated instruction.MethodsOriginal reports of CTPAs demonstrating acute PE in 50 patients whom ultimately developed CTEPH, and those of 50 PE who did not, were screened for documented signs of CTEPH. All scans were re-assessed by three CTEPH-expert readers and two CTEPH-non-expert readers (blinded and independently) for predefined signs and overall presence of CTEPH.ResultsSigns of chronic PE were mentioned in the original reports of 14/50 cases (28%), while CTEPH-expert radiologists had recognized 44/50 (88%). Using a standardized definition (≥3 predefined radiological signs), moderate-to-good agreement was reached between CTEPH-non-expert readers and the experts’ consensus (k-statistics 0.46; 0.61) at slightly lower sensitivities. The CTEPH-non-expert readers had moderate agreement on the presence of CTEPH (κ-statistic 0.38), but both correctly identified most cases (80% and 88%, respectively).ConclusionsConcomitant signs of CTEPH were poorly documented in daily practice, while most CTEPH patients were identified by CTEPH-non-expert readers after dedicated instruction. These findings underline the feasibility of achieving earlier CTEPH diagnosis by assessing CTPAs more attentively.     

Evaluation of the Incidence of Chronic Thromboembolic Pulmonary Hypertension 1 Year After First Episode of Acute Pulmonary Embolism: A Cohort Study

Purpose

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important complication after acute pulmonary embolism (PE) with considerable morbidity and mortality. The aim of this study was to estimate the CTEPH incidence in a cohort after the first occurrence of PE.

Methods

We conducted a 1-year follow-up cohort study between 2015 and 2018 to assess the incidence of CTEPH in 474 patients with their first acute episode of PE. For the diagnosis of CTEPH, patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography, right heart catheterization, ventilation-perfusion lung scanning, and CT pulmonary angiography.

Results

Overall, 317 patients were included in the study. The mean age of the patients was 56.5 ± 16 years. One hundred and three patients (32%) had exertional dyspnea at the 1-year follow-up. Patients with evidence of pulmonary hypertension (PH) on echocardiography underwent right heart catheterization. Eleven patients (18%) had no PH (mPAP < 25 mmHg); 47 patients (81%) had mPAP > 25 mmHg. Fifteen patients had PAWP > 15 mmHg, including those with underlying left heart problems or valvular diseases. There were 32 patients with PAH (mPAP > 25 mmHg and PVR > 3 WU) undergoing CTEPH studies; 22 patients (6.9%) had multiple segmental defects suggesting CTEPH on a perfusion scan.

Conclusion

The incidence of CTEPH observed in this study 1 year after the first episode of acute PE was approximately 6.9%. This incidence seems to be high in our population, and diagnostic and therapeutic strategies for the early identification of CTEPH are needed.

     

Incidence and prevalence of chronic thromboembolic pulmonary hypertension: from acute to chronic pulmonary embolism

The incidence and prevalence of chronic thromboembolic pulmonary hypertension (CTEPH) are yet to be accurately determined and may be significantly underestimated. Historically, the occurrence of CTEPH in patients diagnosed with acute pulmonary embolism (PE) has been considered rare. Data from autopsy studies estimated the incidence of CTEPH at 1-3% overall and at 0.1-0.5% in patients surviving acute PE. Data indicate that each year in the United States, approximately 600,000 individuals suffer an acute pulmonary embolic event and that the annual number of new CTEPH cases in the United States is between 500 and 2,500. This may underestimate the true frequency of CTEPH because the disease is often misdiagnosed due to nonspecific symptoms and variable disease course. A monocenter, prospective, longitudinal study assessing symptomatic CTEPH in patients with acute PE but without prior venous thromboembolism recently estimated the cumulative incidence of CTEPH to be 1.0% 6 mo after PE, 3.1% after 1 yr, and 3.8% after 2 yr; overall post-PE incidence was approximately 3%. Further studies are needed to better define the true rate of CTEPH. Acute embolic events can occur without symptoms, and symptomatic PE is often overlooked or misdiagnosed in practice. CTEPH is often identified during diagnostic work-up in patients with unexplained pulmonary hypertension, many of whom lack medical history suggesting previous PE. In a recent study in 142 consecutive patients with CTEPH, 90 (63%) had no previous history of symptomatic venous thromboembolism. Further prospective epidemiologic studies are needed to better define the incidence and prevalence of CTEPH.     

Antiphospholipid syndrome plus rheumatic fever: a higher risk factor for stroke?

To compare clinical and laboratory findings between patients with primary antiphospholipid syndrome (PAPS) versus secondary APS due to rheumatic fever (APS-RF) (according to Jones criteria). Seventy-three APS patients (Sapporo criteria) were enrolled, and demographic, clinical, and laboratory data were collected. Exclusion criteria were heart congenital abnormalities and previous infectious endocarditis. Patients were divided into two groups: PAPS (n?=?68) and APS-RF (n?=?5). The mean current age, disease duration, frequencies of female gender, and Caucasian race were similar in APS-RF and PAPS patients (P?>?0.05). Remarkably, the frequency of stroke was significantly higher in APS-RF compared to PAPS patients (80% vs. 25%, P?=?0.02). Of note, echocardiogram of these patients did not show intracardiac thrombus. No significant differences were found in peripheral thromboembolic events (P?=?1.0), pulmonary thromboembolism (P?=?1.0), miscarriage (P?=?0.16), thrombocytopenia (P?=?0.36), arterial events (P?=?0.58), and thrombosis of small vessels (P?=?1.0). There were no differences in the frequencies of comorbidities such as diabetes mellitus, hypertension, smoking, and hyperlipidemia in both groups (P?>?0.05). The frequencies of lupus anticoagulant, IgG, and IgM anticardiolipin were similar in two groups. APS patients associated with rheumatic fever without infective endocarditis may imply a high stroke risk as compared with PAPS, and future studies are needed to confirm this finding.     

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism

Background

Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE).

Methods

In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA).

Results

Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH.

Conclusions

CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH.     

Clinical manifestations and antiphosphatidylserine antibodies in patients with systemic lupus erythematosus: is there an association?

Objective: Antiphospholipid antibodies are a group of heterogeneous autoantibodies which have been reported in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) in association with thrombosis, fetal loss, and thrombocytopenia. In this study, we aimed to reveal the prevalence and correlation of IgG, IgA, and IgM isotypes of antibodies to cardiolipin (aCL) and antiphosphatidylserine (aPS) with clinical and laboratory manifestations of SLE patients. Methods: Fifty-nine SLE patients and 41 healthy controls were included. Fifteen of patients (25.4%) had secondary APS. aCL and aPS antibody assays were performed by enzyme-linked immunosorbent assay. Results: All isotypes of aCL and aPS antibodies except IgG were higher in patients with or without APS than those in the healthy controls (p<0.001). The most significant associations were found among migraine and IgA aCL (p<0.001), livedo reticularis and both IgM aCL and IgM aPS (p<0.001), migraine and IgM aCL (p<0.01), pulmonary involvement and IgM aCL (p<0.01), migraine and IgA aPS (p<0.01), and both thrombosis and migraine with IgM aPS (p<0.01). Conclusion: A relatively high prevalence of aCL and aPS antibodies was found in our SLE patients. It seems that isotypes of IgM aCL, IgM aPS, IgA aCL, and IgA aPS antibodies are correlated well with migraine and IgM aPS with thrombosis in SLE patients with secondary APS. The assessment of both IgM and IgA isotypes of aPS and aCL antibodies may be helpful in predicting these manifestations.     

Awareness of thrombotic disease during lockdown: an unusual consequence of the COVID-19 pandemic

The adjusted global antiphospholipid syndrome score (aGAPSS) is a recently developed thrombotic risk assessment score that considers the antiphospholipid antibody (aPL) profile and conventional cardiovascular risk factors. In this retrospective study, we aimed to evaluate the validity of the aGAPSS in predicting clinical manifestations (criteria and extra-criteria) of antiphospholipid syndrome (APS) in a single centre cohort of patients. Ninety-eight patients with APS?±?systemic lupus erythematosus (SLE) were classified according to clinical manifestations as vascular thrombosis (VT), pregnancy morbidity (PM) or both (VT?+?PM). The aGAPSS was calculated for each patient as previously defined. Mean aGAPSS of the cohort was calculated as 10.2?±?3.8. Significantly higher aGAPSS values were seen in VT (n?=?58) and VT?+?PM (n?=?29) groups when compared to PM (n?=?11) group (10.6?±?3.7 vs 7.4?±?2.9, P?=?0.005; 10.7?±?4 vs 7.4?±?2.9, P?=?0.008, respectively), mainly due to lower frequencies of cardiovascular risk factors in PM. Higher aGAPPS values were also associated with recurrent thrombosis (11.6?±?3.7 vs 9.9?±?3.6, P?=?0.04). Regarding extra-criteria manifestations, patients with livedo reticularis (n?=?11) and APS nephropathy (n?=?9) had significantly higher aGAPSS values (12.9?±?3.4 vs 9.9?±?3.7, P?=?0.02; 12.4?±?2.9 vs 10?±?3.8, P?=?0.04, respectively). The computed AUC demonstrated that aGAPSS values ≥10 had the best diagnostic accuracy for thrombosis. Our results suggest that patients with higher aGAPSS values are at higher risk for developing vascular thrombosis (either first event or recurrence) and extra-criteria manifestations, especially livedo reticularis and APS nephropathy.

     

Effect of Balloon Pulmonary Angioplasty on Homogenization of Lung Perfusion Blood Volume by Dual-Energy Computed Tomography in Patients with Chronic Thromboembolic Pulmonary Hypertension

Objective

Balloon pulmonary angioplasty (BPA) is used to treat patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH); the goal is to improve pulmonary perfusion. We aimed to evaluate lung perfusion blood volume (PBV) with haemodynamic and exercise-capacity parameters to assess the efficacy of BPA in the treatment of CTEPH.

Methods

We retrospectively studied 33 patients over a 6-year period. DECT pulmonary angiography was performed before and after BPA. DECT provided iodine distribution maps; whole-lung and regional PBV images and quantification were generated using post-processing software. A mosaic pattern suggesting perfusion inhomogeneity is typical in CTEPH. Hypothetically, BPA treatment would promote homogenization that would be reflected in the calculated standard deviation.

Results

Lung perfusion images showed decreased heterogeneity after BPA. There was a significant difference before and after BPA in the whole-lung PBV and in the regional standard deviation for pulmonary arterial pressure (R = 0.37, p = 0.032 and R = 0.57, p = 0.006), pulmonary vascular resistance (R = 0.51, p = 0.023 and R = 0.60, p = 0.002), transtricuspid pressure gradient (R = 0.50, p = 0.0028 and R = 0.61, p = 0.0001), brain natriuretic peptide (R = 0.54, p = 0.0012 and R = 0.46, p = 0.0078), and 6-min walking distance (R = 0.59, p = 0.003 and R = 0.26, p = 0.14). The effects were especially pronounced after the first BPA procedure.

Conclusion

Decreased lung heterogeneity may suggest BPA efficacy in treating CTEPH. After BPA treatment, improved lung PBV and improved regional standard deviation showed a strong positive correlation with haemodynamic parameters and exercise capacity, which also suggests that BPA is effective in treating CTEPH.

     

Biomarker for nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis: Anti-glycopeptidolipid core antigen immunoglobulin A antibodies

Objective: Nontuberculous mycobacterial (NTM) pulmonary disease is occasionally associated with rheumatoid arthritis (RA), influencing the therapeutic strategy of RA. Since chronic lung diseases are frequently associated with RA, the diagnosis of NTM pulmonary disease is quite difficult in RA patients. Recently, a serological diagnostic test detecting serum immunoglobulin A against the glycopeptidolipid (GPL) core antigen was developed. We investigated the serum levels of anti-GPL antibodies in RA patients to determine the usefulness for detecting NTM pulmonary disease.

Methods: Anti-GPL antibodies were detected in the sera from RA patients with or without NTM pulmonary disease.

Results: The positivity of anti-GPL antibodies in RA patients with NTM pulmonary disease was higher than in RA without (p?=?1.76?×?10^?14, odds ratio 70.29, 95% confidence interval [CI] 22.28–221.83). Anti-GPL Ab titers were increased in RA with NTM pulmonary disease (mean titer?±?standard deviation [U/ml], RA with NTM pulmonary disease: 4.1?±?7.0, RA without NTM pulmonary disease: 0.4?±?1.6, p?=?1.51?×?10^?10). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for anti-GPL antibodies was 0.917 (95%CI 0.860–0.974, p?=?3.32?×?10^?47).

Conclusions: Serum anti-GPL antibodies are useful for detecting NTM pulmonary disease in RA patients.     

Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment

OBJECTIVE: To describe clinical manifestations, laboratory findings, and treatment of patients with the antiphospholipid syndrome (APS) who develop diffuse alveolar hemorrhage. METHODS: Diffuse alveolar hemorrhage is an occasionally reported manifestation of the APS. The diagnosis, however, may be overlooked or manifestations attributed to another disease process. Seven episodes in 5 patients with primary APS were identified and retrospectively reviewed for presenting symptoms and signs, laboratory findings, and response to treatment. RESULTS: The severity of the condition varies, and diffuse alveolar hemorrhage may be the initial manifestation of APS. Patients may present with symptoms ranging from cough, dyspnea, and fever with or without hemoptysis, to symptoms of acute respiratory failure. Hypoxemia and anemia are usually present. Other causes need to be excluded. Bronchoscopy and bronchoalveolar lavage with or without biopsy often aid in confirming the diagnosis. The pathologic abnormality appears to be microvascular thrombosis with or without capillaritis. Treatment with corticosteroids usually leads to marked improvement. CONCLUSION: Patients with APS may present with diffuse alveolar hemorrhage resulting in mild to life threatening symptoms. Prompt and thorough evaluation to confirm the diagnosis and treatment with corticosteroids usually leads to rapid improvement. The clinical setting will dictate whether other therapies such as immunosuppressive agents or intravenous immunoglobulin are required.     

Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 μg/mL (IQR 0.6, 1.4) (p?=?0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p?=?0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p?=?0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p?=?0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p?=?0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p?=?0.02), PT clot acceleration (min 2) 3.6%/s² (IQR 3.2, 4.5) (p?=?0.02) and PT clot deceleration (max2) 2.9%/s² (IQR 2.5, 3.5) (p?=?0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p?=?0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p?=?0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p?=?0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p?=?0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.

     

Cardiac involvement in the antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated with a hypercoagulable state and fetal loss and with other clinical manifestations including cardiac involvement. Cardiac manifestations of APS are valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. Antiphospholipid antibodies (aPLs) may have a role in the accelerated atherosclerotic arterial disease observed in APS, related to their ability to induce endothelial activation. aPLs have been incriminated in the pathogenesis of heart valve lesions in APS patients. Markers of endothelial cell activation are up-regulated with prominent deposition of aPL in heart valves, suggesting aPL deposition initiates an inflammatory process that recruits complement leading to the valve lesion. Autoantibody-mediated endothelial cell activation probably plays a role in sustaining a proadhesive, proinflammatory, and procoagulant phenotype. The heterogeneity of APS clinical manifestations is likely linked to the varied effects that aPL can induce on endothelial cells and to the different functions that endothelial cells display depending on the anatomic localization.     

Wheezes and desert breezes: when asthma and valley fever collide

Objective: To evaluate interactive effects of pulmonary coccidioidomycosis and asthma.

Methods: We identified three groups of 33 age- and sex-matched patients: Group 1 (both asthma and coccidioidomycosis), Group 2 (asthma only), and Group 3 (pulmonary coccidioidomycosis only). Predetermined end points included: rate of disseminated coccidioidomycosis, duration of symptoms and antifungal therapy, hospitalization, death, and escalation of asthma therapies.

Results: Baseline characteristics were similar across groups. Group 1 patients had worsening asthma outcomes (except forced expiratory volume in 1?s) with coccidioidomycosis. They required more asthma medications (median, 2.0 vs 0.0; p?<?0.001), more corticosteroids (mean [SD], 0.9 [4.2] vs 0.3 [0.6]; p?<?0.001), and more healthcare visits (mean [SD], 0.2 [0.4] vs 0.1 [0.3]; p?=?0.03). Groups 1 and 3 had no differences in coccidioidal end points, including rates of dissemination (1 vs 0; p?>?0.99), symptom duration (mean, 15.2 vs 23.6 weeks; p?=?0.24), antifungal treatment (n?=?21 [63.6%] vs n?=?24 [72.7%]; p?=?0.60), and treatment duration (median, 26.5 vs 11 weeks; p?=?0.09). Ten patients in Group 1 versus none in Group 3 required systemic corticosteroids for coccidioidomycosis (p?<?0.001).

Conclusions: Active pulmonary coccidioidomycosis significantly worsens asthma outcomes. Asthma (or its treatment) does not worsen coccidioidal outcomes, despite increasing the likelihood of treatment with systemic corticosteroids.     

Late-onset systemic lupus erythematosus: clinical features, course, and prognosis

There are contradictory opinions if late-onset systemic lupus erythematosus (SLE) is associated with a different, more benign disease course and better prognosis than early-onset SLE. The objective of this study was to evaluate the clinical manifestations, course, treatment, and prognosis of late-onset SLE. Patients who developed SLE after/or at the age of 50 years were considered late-onset SLE and compared to a group of randomly selected patients aged younger than 50 years at the diagnosis, matched for disease duration. Lower frequency of cutaneous manifestations (p?=?0.01) and higher frequency of cytopenias (p?=?0.02) were registrated at the SLE onset in the late-onset group. Atypical clinical presentation of SLE contributed to a longer delay of diagnosis in late-onset SLE patients (p?=?0.005), who fullfiled less American College of Rheumatology criteria at the diagnosis (p?=?0.022). Cumulative incidence of clinical manifestations showed lower frequency of cutaneous (p?=?0.017), neuropsychiatric manifestations (p?=?0.021), lupus nephritis (p?=?0.006), and higher frequency of Sjogren′s syndrome (p?=?0.025) in the late-onset group. Late-onset SLE patients received lower doses of corticosteroid (p?=?0.006) and cyclophosphamide (p?=?0.001) and had more cyclophosphamide-induced complications (p?=?0.005). Higher prevalence of comorbid conditions in the late-onset group (p?=?0.025), and higher Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index was noticed (p?=?0.018). Despite the less major organ involvement and more benign course of disease, late-onset SLE has poorer prognosis, because of the higher frequency of comorbid conditions and higher organ damage, due to the aging and longer exposition to a classical vascular risk factors.