Raynaud’s phenomenon and blood rheology: comments on the article “Raynaud’s phenomenon—an update on diagnosis, classification and management”

Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry Abstract Introduction We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs). Methods We studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95% CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics. Results Among 1272 analyzed subjects, mean age was 56.3 years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared with seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95% CI 1.30–4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95% CI 1.26–4.87), 3.12 (95% CI 1.28–7.61), and 2.30 (95% CI 1.09–4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality OR 1.99, 95% CI 1.21–3.27 for RF+ vs. RF−; OR 1.67, 95% CI 1.03–2.69 for CCP+ vs. CCP−) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend < 0.05). Conclusions Seropositive RA patients had two-fold increased risk for abnormalities on PFTs performed for clinical indications compared with seronegative RA. Patients with seropositive RA, particularly those with high-titer RF positivity, may be more likely to have obstructive and restrictive abnormalities, independent of smoking. Key points • Due to the known excess pulmonary morbidity/mortality in RA, we studied the relationship of rheumatoid arthritis (RA)-related autoantibodies with pulmonary function test (PFT) abnormalities using a large RA registry. • We evaluated whether presence and levels of cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were associated with restriction, obstruction, and diffusion abnormalities on PFTs among 1272 subjects with RA. • Seropositivity was associated with two-fold increased risk for any PFT abnormality, independent of confounders including smoking. Higher titers of RF conferred greatest risk for all PFT outcomes: obstruction, restriction, and diffusion abnormality. • These results provide evidence that patients with RA should be closely monitored for pulmonary involvement, particularly those with high-titer RF seropositivity.

The clinicopathological characteristics of Kimura disease in Chinese patients Abstract Introduction Kimura disease (KD) is a rare idiopathic inflammatory disorder of unknown etiology. Unusual presentations of KD might cause diagnostic difficulty or be misdiagnosed as malignancy if clinical suspicion is insufficiently high. Here, we aimed to determine the clinicopathological features of Chinese KD patients to reveal further insights into the natural history and treatment of this disease. Method The clinical data of 46 cases of KD diagnosed at Peking Union Medical College Hospital from January 1980 to December 2018 were analyzed retrospectively through case record review. Results Of 46 cases, 40 were male and six were female. The age at onset ranged from 2 to 56 years (median 27 years). All patients presented with either single (26.1%) or multi-focal (73.9%) subcutaneous masses. Twenty-nine (63.0%) cases presented with head and neck subcutaneous masses, and 9 cases (19.6%) involved different parts of the body. Parotid, submandibular, and lacrimal gland involvement occurred in 17 (37.0%), 3 (6.5%), and 2 cases (4.3%), respectively. Nephrotic syndrome was present in three cases (6.5%), and thromboembolism was present in five cases (10.9%). During follow-up, thirteen patients (13/28, 46.4%) relapsed over 1–13 years (median 8.5 years). The recurrence rate in patients receiving corticosteroids, surgery, and combined surgery and radiotherapy was 30.8%, 66.7%, and 50.0%, respectively. One patient was diagnosed with T cell lymphoma 1 year after diagnosis of KD. Conclusions KD is characterized by subcutaneous masses but it is also a systemic disease. Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up. Key Points • Kimura disease (KD) is a rare inflammatory disorder of unknown etiology that is endemic in Asia. • Clinicians must regard and manage KD as a systemic disease. • There is no consensus on optimal treatments and further studies are necessary to improve outcomes. • Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.

Clinical outcome of HCV-associated cryoglobulinemic glomerulonephritis following treatment with direct acting antiviral agents: a case-based review Abstract Newer treatment protocols involving direct-acting antiviral agents (DAAs) have been associated with high rates of sustained virologic response (SVR) and clinical remission in patients with hepatitis C virus (HCV) associated cryoglobulinemic vasculitis (HCV-CV), but clinical response in those with renal involvement is less clear. Our goal was to evaluate the clinical course following DAA therapy in one of the largest cohorts of patients with HCV-associated cryoglobulinemic glomerulonephritis (HCV-GN) reported to date. This is an observational study of patients with chronic HCV infection and circulating cryoglobulins (CC) treated with DAAs in our department from January 2015 to January 2019. We identified a total of 67 patients with HCV and CC out of which nine patients fulfilled the criteria of HCV-GN and had adequate clinical follow-up time. We describe a cohort of nine patients with a mean age of 57 years and known duration of HCV infection ranging 3–20 years (four with evidence of compensated cirrhosis). All patients received the ritonavir-boosted paritaprevir/ombitasvir/dasabuvir regimen for 12 weeks and achieved SVR without subsequent viral relapse. Following DAAs completion, one patient developed “new-onset” cryoglobulinemic glomerulonephritis, six showed either persistent or worsening glomerulonephritis, and only two patients had a complete clinical response (CCR). Of the six patients with either persistent or worsening CV, 67% received additional immunosuppressive (IS) therapy for uncontrolled CV. Of the two patients that had a CCR, one patient received prior IS therapy while the other one improved without any additional intervention. Newer HCV treatment protocols involving DAAs are highly successful in eradication of HCV infection; however, in our experience, DAA treatment alone is insufficient in improving the renal outcomes of patients with HCV-GN and additional IS therapies should be considered.

Clinical features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis complicated by spontaneous pneumomediastinum Abstract Background Dermatomyositis (DM) with autoantibody against melanoma differentiation-associated gene-5 (MDA5) is characterized by elevated risk of rapidly progressive interstitial lung disease (RP-ILD) with a potentially fatal course. Pneumomediastinum (PNM) is a common pulmonary manifestation which accompanies ILD. However, the clinical features of the patients with anti-MDA5 antibody-positive DM who develop PNM remain unclear. Methods We retrospectively examined 31 patients with DM having anti-MDA5 antibody and compared the clinical features between patients with PNM (PMN(+)) (n = 11) and those without (PNM(−) (n = 20). In addition, we evaluated the treatment-related prognoses in PNM(+) group. Results CT score (total ground-glass opacity (GGO) score, P = 0.02; total fibrosis score, P = 0.02) before treatment, and mortality (P = 0.04) were significantly higher in PNM(+) group. The cumulative survival rate as assessed by Kaplan–Meier method was significantly lower for the PNM(+) group (P = 0.02). Among 11 PMN(+) patients, 9 patients (9/11, 81.8%) underwent intensive immunosuppression therapy for RP-ILD, and 5 patients (5/11, 45.5%) did not respond to it and died from the respiratory failure. At the time of diagnosis of PNM, nonsurvivors had worse liver function (ALT, P = 0.03; LDH, P = 0.01), worse respiratory status (A-aDO2, P = 0.01), and worse CT score (total GGO score, P < 0.01). Conclusions A subgroup of patients with DM having anti-MDA5 antibody complicated by PNM as well as RP-ILD did respond to intensive immunosuppression therapy. Initial aggressive immunosuppressive therapy should be considered for these patients. Key Points • This study clearly demonstrate the presence of PNM was associated with elevated risk of death due to respiratory failure from RP-ILD among patients with DM having circulating anti-MDA5-antibody. •This study demonstrate evaluation of CT image may be helpful to find patients with better response to the intense immunosuppression therapy for the patients with DM having circulating anti-MDA5-antibody and PNM.

Hypertensive disorders of pregnancy associated with adverse pregnant outcomes in patients with systemic lupus erythematosus: a multicenter retrospective study Abstract Background Hypertension disorders in pregnancy (HDP) were common complications in women with systemic lupus erythematosus (SLE). However, the impact of HDP and the measures to prevent HDP-related fetal adverse pregnancy outcomes (APOs) remained to be explored. Methods A multicenter retrospective study of 342 pregnant women with SLE was performed. Variables related to SLE and APOs were recorded. Fetal development was evaluated by umbilical artery Doppler ultrasonography. Results HDP was diagnosed in 45 (13.2%) patients, including pre-eclampsia in 42 and gestational hypertension in 3. Patients with HDP had higher incidence of preterm birth (71.1% vs 20.9%, P < 0.001), intrauterine growth retardation (IUGR) (37.8% vs 11.8%, P < 0.001), low-birth-weight infants (62.2% vs 17.2%, P < 0.001), and very-low-birth-weight infants (37.8% vs 2.7%, P < 0.001), compared with lupus patients without HDP. A total of 35 (77.8%) HDP patients had disease activation during pregnancy. All the events occurred during the second and third trimesters, mainly presenting as moderate-to-high activity (65.7%). Active disease [odds ratios (OR) = 3.9, 95% confidential interval (CI) 1.5–9.7, P = 0.004] and positive anticardiolipin (aCL) antibody (OR = 7.6, 95% CI 2.7–18.6, P < 0.001) were independent risk factors for HDP in lupus patients. Doppler RI and S/D ratio predicted APOs in patients with HDP. The optimal cut-off values for RI and S/D ratio were 0.7 (sensitivity 48.1%, specificity 53.3%) and 3.4 (sensitivity 66.7%, specificity 100%), respectively. Conclusions HDP was a common pregnant complication and caused various fetal and maternal adverse outcomes in patients with SLE. Umbilical artery Doppler ultrasonography was effective in predicting fetal APOs in lupus patients with HDP. Key Points • HDP induced preterm birth, IUGR, low-birth-weight infants, and very-low-birth-weight infants in patients with SLE. • HDP led to lupus activation during the second and third trimesters. • Disease activation and aCL positivity were predictors for HDP. • RI and S/D ratio from umbilical artery Doppler predicted APOs in patients with HDP.

High prevalence of abnormalities on chest radiography in rheumatoid arthritis Abstract Introduction Chest radiography (CXR) is commonly performed in rheumatoid arthritis (RA), particularly for the diagnosis of pulmonary disease. However, other structures are visible on CXR, abnormalities of which may contribute to morbidity and early mortality. This study was undertaken to evaluate the extent of CXR abnormalities in RA patients. Methods Consecutive out-patients meeting the 2010 ACR/EULAR classification criteria for RA were included. The most recent CXR was assessed by two independent reviewers. Abnormalities identified were recorded and compared to the formal CXR report. Predictors of abnormalities on CXR were assessed using chi-squared tests. SPSS 18.0 was used for statistical analysis. Results One hundred and ninety-eight patients were included. Mean age was 62 years (range 18–90). One hundred and nine (55.1%) were current or ex-smokers. One hundred and fifty-six (79%) patients were seropositive and 123 (62.1%) had joint erosions. A recent CXR was available in 163 (82%) cases. Abnormalities were identified in 129 (79.1%). Ninety-seven (60%) had bony abnormalities. Seventy-one (43.6%) had pulmonary abnormalities; old tuberculosis in 34 (20.9%), hyperinflation in 24 (14.7%), interstitial changes in 20 (13.3%), nodules in 4 (2.4%), consolidation in 2 (1.2%), and pneumothorax in 1 (0.6%). Cardiomegaly was identified in 37 (22.7%) and aortic calcification in 24 (14.7%). Age (p = 0.001), male gender (p = 0.01), and seropositivity (p = 0.04) were significantly associated with lung abnormalities. Cardiomegaly was associated with hypertension (p = 0.012) and ischaemic heart disease (p = 0.018). Conclusion Abnormalities were identified in 79% of chest radiographs in RA patients. Sixty-six percent of these were not reported. Clinicians need to be aware of the need to check for abnormalities. Key Points • RA patients have a high prevalence of CXR abnormalities. • Many of these are of clinical significance. • Age, being male, and seropositivity were associated with lung abnormalities.

Evaluation of 12 different assays for detecting ANCA in Chinese patients with GPA and MPA: a multicenter study in China Abstract Objective Due to lack of comprehensive evaluation for various detection methods for antineutrophil cytoplasmic antibody (ANCA) in Chinese population, we evaluate the diagnostic performance of 12 established analysis methods in Chinese patients having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods Sera were collected from 209 patients with GPA or MPA and 243 diseases controls from 15 centers. Twelve different reagents were employed for C-ANCA, P-ANCA, myeloperoxidase (MPO)-ANCA, and proteinase 3(PR3)-ANCA detection. The accuracy, sensitivity, and specificity of each method were analyzed. Results The accuracy of the two indirect immunofluorescence (IIF) and two line immunoassay (LIA) was 0.838 and 0.874, 0.869, and 0.862, respectively. The accuracy of the eight quantitative antigen-specific immunoassays was varied from 0.867 to 0.967. The sensitivity of ANCA-associated vasculitis (AAV) was 0.770 and 0.761 for the two IIF, 0.727 and 0.718 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the sensitivity varied from 0.79 to 0.967. The specificity was 0.897 and 0.971 for the two IIF, 0.992 and 0.988 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the specificity of AAV varied from 0.963 to 0.983. Conclusion For Chinese patients suspected of having GPA and MPA, both the first-generation enzyme-linked immunosorbent assay (ELISA) and high-quality antigen-specific immunoassay can be used to detect MPO-ANCA and PR3-ANCA alone, without the combined detection with IIF to have good diagnostic performance. The chemiluminescent immunoassay (CLIA) seems to be a method worth recommending. Key points • Quantitative antigen-specific immunoassays can be used to detect MPO-ANCA and PR3-ANCA without IIF in Chinese. • CLIA has the maximum AUC value and the minimum LR (−) value, which seems to be a method worth recommending.

Nailfold videocapillaroscopy alterations in dermatomyositis, antisynthetase syndrome, overlap myositis, and immune-mediated necrotizing myopathy Abstract Introduction/objectives The aim of our study was to investigate possible differences in nailfold videocapillaroscopy (NVC) features between patients with dermatomyositis (DM), overlap myositis (OM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM). Methods We performed a cross-sectional monocentric study. All patients with inflammatory myopathies (IMs) over a 6-month period were analyzed by NVC for giant and ramified capillaries, tortuosities, capillary density, disorganization, and scleroderma pattern. Clinical, biological, and pathological characteristics were retrospectively recorded. Patients were classified as having DM, OM, ASS, or IMNM for comparison. Patients were also compared with a group of patients with systemic sclerosis (SSc). Results NVC was analyzed in DM (n = 17), OM (n = 8), ASS (n = 12), and IMNM (n = 6). Vascular disorganization and avascular zones were observed only in DM (11.8%) and OM (62.5%). The percentage of patients with giant capillaries was higher in OM (n = 4/8) than in DM (n = 3/17) and absent in ASS and IMNM. Frequency of ramified capillaries, tortuosities, hemorrhages, or thrombosis was not different between subgroups. A scleroderma pattern was only observed in OM patients. Conclusion In this limited series of patients, we observed that DM and OM NVC abnormalities are different from ASS and IMNM. We could not determine NVC specific patterns associated with myositis-specific antibody subtypes of DM because of the small number of patients. Key Points • Nailfold videocapillaroscopy abnormalities are different in subgroups of inflammatory myopathies. • Giant capillaries, disorganization, and major capillary loss are observed in overlap myositis and dermatomyositis but not in antisynthetase syndrome (ASS) or immune-mediated necrotizing myopathy. • Nailfold videocapillaroscopy abnormalities in overlap myositis (with the exclusion of ASS) are close to systemic sclerosis.

Low bone mineral density of vertebral lateral projections can predict spinal radiographic damage in patients with ankylosing spondylitis Abstract Objectives To investigate the association between bone mineral status and spinal radiographic damage in patients with ankylosing spondylitis (AS) and determine whether bone mineral status can predict further spinal radiographic damage after 2 years. Methods Bone mineral density (BMD) of the lumbar spine (anteroposterior and lateral projections), femoral neck, and total hip and trabecular bone score (TBS) of the lumbar spine were measured in AS patients (n = 54) who fulfilled the modified New York criteria. Spinal radiographic damage was scored on cervical and lumbar spine radiographs using modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline and after 2 years. Simple and multiple linear regression analyses were performed to examine predictors of spinal radiographic damage. Results Patients with advanced AS exhibited low BMD on lumbar spine lateral projections, femoral neck, and total hip and low TBS. Low vertebral bone mass at baseline, assessed by BMD of the lateral projections or TBS, was independently associated with baseline mSASSS. After 2 years, mSASSS change from baseline was significantly associated with high baseline mSASSS, high baseline erythrocyte sedimentation rate and C-reactive protein (CRP) levels, and low baseline BMD of the lumbar spine lateral projections. The best predictive model for spinal radiographic progression consisted of baseline mSASSS, baseline CRP, and low BMD of lateral lumbar spine (area under curve = 0.826). Conclusions BMD at vertebral lateral projections and TBS were inversely associated with baseline mSASSS in AS patients. Low BMD at vertebral lateral projections, as well as baseline mSASSS and inflammatory markers, might predict spinal radiographic damage in AS. Key Points • Vertebral bone mineral density of lateral projections and trabecular bone score are inversely associated with baseline mSASSS in patients with ankylosing spondylitis. • Baseline mSASSS, inflammatory markers, and low vertebral bone mineral density might predict spinal radiographic progression in patients with ankylosing spondylitis.