Yong Hou

Clinical characteristics of immunoglobulin G4–related disease: a prospective study of 118 Chinese patients

OBJECTIVE To characterize the clinical features of IgG4-related disease (IgG4-RD) in China. METHODS A prospective cohort study of IgG4-RD was carried out in Peking Union Medical College Hospital between 2011 and 2013. Patients with newly diagnosed IgG4-RD were enrolled. RESULTS A total of 118 patients with IgG4-RD were enrolled, including 82 males and 36 females, aged 53.1 (s.d. 13.6) years. The most common symptom at onset was lacrimal gland swelling (38/32.2%). A range of organs were involved: 77 patients (65.3%) had lymphadenopathy, 76 (64.4%) had sialadenitis, 60 (50.8%) had dacryoadenitis, 45 (38.1%) had autoimmune pancreatitis, 32 (27.1%) had pulmonary involvement, 31 (26.3%) had periaortitis/retroperitoneal fibrosis, 29 (35.4% of male patients) had prostatitis and 29 (24.6%) had renal involvement. In addition, there were 21 (17.8%) cases of sclerosing cholangitis, 15 (12.7%) of sinusitis and 10 (8.5%) of inflammatory pseudotumour. Uncommon manifestations included mediastinal fibrosis, skin involvement, sclerosing thyroiditis, hypophysitis, orchitis and colitis. Multiple organ involvement was observed in 93 patients, whereas only 4.2% had only a single organ involved. A history of allergy was reported in 73 (61.9%) patients. The serum IgG4 level was elevated in 97.5% and was correlated with the number of organs involved. Most patients were treated with glucocorticoids alone or in combination with immunosuppressive drugs, and the majority usually improved within 3 months. CONCLUSION IgG4-RD is a systemic inflammatory and sclerosing disease. Parotid and lacrimal involvement (formerly called Mikuliczs disease), lymphadenopathy and pancreatitis are the most common manifestations. Patients with IgG4-RD showed favourable responses to treatment with glucocorticoids and immunosuppressive agents.

Elevated Levels of CD4+CD25+FoxP3+ T Cells in Systemic Sclerosis Patients Contribute to the Secretion of IL-17 and Immunosuppression Dysfunction

Objective Immune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this study was to investigate the role of Treg subsets in the immune imbalance in naïve SSc. Methods Peripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, CTLA-4, FoxP3, and IL-17 using flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA was measured by real-time PCR. Results The frequency of CD4+CD25+FoxP3+ Treg cells was significantly elevated in patients with SSc (3.62±1.14 vs 1.97±0.75, p<0.001) with diminished immunosuppression capacity. In SSc, the proportion of FoxP3highCD45RA− activated Treg cells (aTreg) was decreased, the proportion of FoxP3lowCD45RA− T cells was increased, and the proportion of FoxP3lowCD45RA+ resting Treg cells (rTreg) was decreased. The immune suppression capacity of aTreg and rTreg was diminished, while FoxP3lowCD45RA− T cells exhibited a lack of suppression capacity. The immune dysfunction of aTreg was accompanied by the abnormal expression of CTLA-4. Th17 cell numbers were elevated in SSc, FoxP3lowCD45RA− T cells produced IL-17, confirming their Th17 potential, which was consistent with the elevated levels of FoxP3+IL-17+ cells in SSc. Conclusion A decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3lowCD45RA− T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.

Serum IgG Subclasses in Autoimmune Diseases

Abstract To characterize serum IgG subclass levels in several autoimmune diseases, including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to analyze serum IgG subclass distribution and to test whether serum IgG4 levels are elevated in these diseases. Serum IgG subclass levels from 102 pSS, 102 SSc, 100 SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured using the immunonephelometric assay. The distribution of IgG subclasses among these autoimmune diseases was analyzed. In this cross-sectional study, serum IgG1 (IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There were no significant differences in the frequency of elevated serum IgG4 levels between patients and HC. In pSS, serum IgG1 levels were much higher than those in other disease groups, whereas serum IgG2 and IgG3 levels were most prominently increased in PBC. A strikingly different serum IgG subclass distribution was detected in patients with autoimmune diseases compared with HCs. Serum IgG subclass levels also showed distinct characteristics among different autoimmune diseases. Serum IgG4 levels in these patients were lower or not much higher than those in HCs, which differed from IgG4-related diseases.

A Preliminary Study of Acoustic Radiation Force Impulse Quantification for the Assessment of Skin in Diffuse Cutaneous Systemic Sclerosis

Objective. To investigate skin elasticity using acoustic radiation force impulse (ARFI) quantification in systemic sclerosis (SSc), and compare the modified Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of the skin. Methods. Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age-matched and sex-matched healthy controls were evaluated. The SWV and thickness of skin were measured at 17 sites corresponding to those assessed in the mRSS in each participant. The SWV measurements of skin were compared between patients with dcSSc and healthy controls. The correlations between the mRSS and the skin SWV and thickness were explored using Spearman’s correlation. Results. The SWV values were higher in patients with dcSSc compared with healthy controls at right hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum, and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of uninvolved skin were higher than those of controls (p < 0.001), and the SWV values increased with increasing skin scores except for skin score 3 (p < 0.05). The sum of the SWV values correlated with total clinical skin score (r = 0.841, p < 0.001), and the sum of the skin thickness correlated with total clinical skin score (r = 0.740, p = 0.002). Conclusion. ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc. ARFI quantification could identify early skin change that may precede palpable skin involvement, and may be a valuable adjunct to skin evaluation in patients with SSc.

Polyarteritis nodosa with multiple aneurysms and renal arteriovenous fistula successfully diagnosed by colour Doppler sonography

Polyarteritis nodosa (PAN) is a vasculitis that typically affects small- and middle-sized arteries of multiple organs. The kidney is most commonly involved. To date, few cases of PAN involving the celiac artery and no cases of iliac artery or internal carotid artery involvement have been published. The most frequent lesions reported were due to occlusions and aneurysms. Finally, no cases of PAN causing arteriovenous fistula have been reported. Here we present a case of PAN with multiple aneurysms and renal arteriovenous fistula that was successfully diagnosed and followed-up by ultrasound. This case report describes the challenges in diagnosing PAN and highlights the importance of a holistic approach when encountering patients with multiple vascular diseases. Ultrasound should be considered the first-line approach in the diagnosis of PAN.

Clinical Features, Morbidity, and Risk Factors of Intestinal Pseudo-obstruction in Systemic Lupus Erythematosus: A Retrospective Case-control Study

Objective. To analyze the epidemiology, clinical characteristics, and risk factors for systemic lupus erythematosus-related intestinal pseudo-obstruction (SLE-IPO). Methods. We retrospectively examined 85 patients with SLE with IPO as the case group and 255 randomly matched patients with SLE without any gastrointestinal manifestations as the control group, out of 4331 inpatients at the Peking Union Medical College Hospital (PUMCH) from 2003 to 2014. Results. Over the last 11 years at PUMCH, the prevalence of IPO in patients with SLE was 1.96% and the in-hospital fatality rate was 7.1%. Of these patients, 57.6% presented with IPO as the initial affected system of SLE, and the rate of misdiagnosis was about 78%. Pyeloureterectasis was the most common complication (58.9%) in patients with SLE-IPO and the incidence of biliary tract dilation was 7.1%. Patients with SLE with IPO were always diagnosed at an earlier stage of SLE with a higher frequency of hematological disturbance, polyserositis, and hypocomplementemia. Pyeloureterectasis, hypocomplementemia, and elevated C-reactive protein levels in serum were independent risk factors for IPO in SLE disease. Patients with SLE-IPO with long IPO duration and those diagnosed during late stages of SLE or concurrent with pyeloureterectasis and megacholedochus always had an unfavorable outcome. Conclusion. IPO is a rare complication, but commonly presents as the initial affected system of SLE, which can lead to a difficult diagnosis and delayed treatment. SLE-IPO occurrence concomitantly with pyeloureterectasis and megacholedochus showed a severe clinical situation in our cohort. Thus, patients with SLE-IPO with systemic smooth muscular involvement should be diagnosed early and treated aggressively.

Clinical analysis of 61 systemic lupus erythematosus patients with intestinal pseudo-obstruction and/or ureterohydronephrosis: a retrospective observational study.

AbstractThe objective of this article is to investigate the clinical features of intestinal pseudo-obstruction (IPO) and/or ureterohydronephrosis in systemic lupus erythematosus (SLE).Sixty-one SLE patients with IPO and/or ureterohydronephrosis were analyzed retrospectively. A total of 183 cases were randomly selected as controls from 3840 SLE inpatients without IPO and ureterohydronephrosis during the same period. Patients were assigned to 1 of the 3 groups (SLE with IPO and ureterohydronephrosis, SLE with IPO, and SLE with ureterohydronephrosis). The clinical characteristics, treatments, and prognosis were compared between the 3 groups.There were 57 females and 4 males, with a mean age of 32.0 years. IPO was the initial manifestation of SLE in 49.1% of the cases, whereas ureterohydronephrosis in 32.5%. All patients were initially treated with a high-dose steroid. Thirty-one of these patients (50.8%) also received intravenous methylprednisolone pulse therapy. Two patients died of bowel perforation and lupus encephalopathy, and the other 59 patients (96.7%) achieved remission after treatment. The incidences of fever, glomerulonephritis, nervous system involvement, serositis, erythrocyte sedimentation rate elevation, hypoalbuminemia, hypocomplementemia, and anti-SSA antibody positivity were significantly higher in patients with IPO and/or ureterohydronephrosis than in the control group (without IPO and ureterohydronephrosis). Also, patients with IPO and/or ureterohydronephrosis had higher SLE Disease Activity Index scores than control patients. Compared with SLE patients with IPO, the patients with IPO and ureterohydronephrosis had a significantly higher incidence of gallbladder wall thickening, biliary tract dilatation, and serositis, whereas the patients with ureterohydronephrosis had less mucocutaneous involvement and serositis. Eight of the 47 IPO patients who initially responded well to immunotherapy relapsed; however, all responded well to retreatment with adequate immunotherapy. Of these 8 patients, 4 relapsed following poor compliance and self-discontinuation of steroid or immunosuppressant therapy. The rate of poor compliance with immunotherapy and the number of organ systems involved in patients in the recurrent IPO group were significantly higher than those in the nonrecurrent IPO group.IPO and ureterohydronephrosis are severe complications of SLE. As patients usually respond readily to early optimal steroid treatment, early diagnosis and timely initiation of glucocorticoid are important to relieve symptoms, prevent complications, and improve prognosis.

Red blood cell distribution width as a related factor of pulmonary arterial hypertension in patients with systemic sclerosis

The aim of this study was to investigate the utility of red blood cell distribution width (RDW) as a simple and readily available marker of occurrence of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). One hundred and forty-five consecutive patients with SSc were recruited to the single-center cross-sectional study. Demographic characteristics, hematological parameters, Modified Rodnan Skin Score, and World Health Organization functional classification were determined. Diagnosis of PAH was based on screening by echocardiography and was confirmed by right heart catheterization. Interstitial lung disease (ILD) was diagnosed based on chest high-resolution computed tomography findings. There were no significant differences in gender, age, or disease duration between limited and diffused SSc groups. PAH was detected in 28 of lcSSc (33.3%) and 14 of dcSSc (23.0%) subjects. Patients with higher RDW values were more likely to be men with high anti-u1RNP titers and PAH. A significant correlation was found between RDW and high-sensitivity C-reactive protein (p = 0.375, p < 0.01) and the diffusing capacity of the lungs for carbon monoxide (ρ = − 0.396, p < 0.01). The SSc-PAH group had significantly higher RDW values compared to the SSc group without pulmonary disease (15.7 ± 2.2 and 13.7 ± 1.0, p < 0.001). The mean RDW in the SSc-PAH-ILD group was significantly higher than that in the SSc-ILD group (16.3 ± 2.2% and 14.0 ± 1.5%, p < 0.001). Besides the recognized risk factors, high RDW was an independent predictor of PAH in patients with SSc (OR = 3.314 [95%CI 1.038–10.580], p < 0.05). RDW may be a related factor for identifying the pulmonary arterial hypertension in SSc patients.

The 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis Could Classify Systemic Sclerosis Patients at Earlier Stage: Data from a Chinese EUSTAR Center

Objectives To evaluate the performance of the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in clinical practice in a Chinese patient cohort, and to compare outcomes with the 1980 ACR criteria. Methods Patients clinically diagnosed with SSc between September 2013 and May 2015 were prospectively recruited from the EUSTAR database of the Peking Union Medical College Hospital. Diagnosis of SSc was based on the evaluation of three experienced rheumatologists. Patients diagnosed with other connective tissue diseases were recruited as disease controls. The 1980 ACR and 2013 ACR/EULAR criteria were applied to the cohort, and patients who fulfilled the criteria were classified as definite SSc patients. Sensitivity and specificity were analyzed for the 2013 and 1980 criteria. Results A total of 143 SSc patients and 87 patients with other connective diseases were recruited. 41 (28.7%) and 102 (71.3%) cases were diffuse cutaneous SSc and limited cutaneous SSc, respectively. Although the sensitivity of the 2013 criteria (94.4%) exceeded the 1980 criteria (72.7%) (P<0.001), the 1980 and 2013 criteria sets showed no significant difference in specificity (97.7% and 93.1%, respectively, P = 0.278). The sensitivity of the 2013 criteria was significantly higher than the 1980 criteria in some SSc subgroups (e.g., lcSSc, abnormal pattern of nailfold videocapillaroscopy [NVC] and presence of Raynaud’s phenomenon [RP]) compared to others. Conclusions Relative to the 1980 ACR criteria, in Chinese SSc patients the new 2013 ACR/EULAR criteria had similar specificity and higher sensitivity, especially for patients with mild skin thickening or prominent microvascular diseases.

A preliminary study of skin ultrasound in diffuse cutaneous systemic sclerosis: Does skin echogenicity matter?

Objective To evaluate the usefulness of skin ultrasound and acoustic radiation force impulse (ARFI) quantification in diffuse cutaneous systemic sclerosis (dcSSc). Patients and methods 28 patients with dcSSc, and 15 age gender matched normal controls were recruited. Skin echogenicity, thickness, and ARFI quantification were measured by ultrasound at 17 sites corresponding to the modified Rodnan skin score (mRSS) in each participant. Compared with controls, skin echogenicity of dcSSc patients was classified into isoechoic, hypoechoic, and hyperechoic. The skin thickness, ARFI quantification and mRSS were compared between isoechoic, hypoechoic, hyperechoic and controls. Results In patients with dcSSc, the skin thickness increased as the echogenicity changed on the order of isoechoic, hypoechoic and hyperechoic. ARFI quantification was significantly higher in hyperechoic than isoechoic (p<0.001). The mRSS were significantly higher in hyperechoic and/or hypoechoic than isoechoic. For isoechoic patients and healthy controls, the skin echogenicity or thickness was no significant different, however, the ARFI quantification was significantly higher in isoechoic than controls. Conclusion Skin ultrasound is feasible for assessing the skin involvement in dcSSc. Skin echogenicity correlates with skin thickness, stiffness, and mRSS. ARFI quantification may be more sensitive to detect skin changes, compared with skin echogenicity and thickness.