Xinping Tian

Hemophagocytic lymphohistiocytosis: clinical analysis of 103 adult patients.

AbstractTo investigate the clinical features of adult patients with hemophagocytic lymphohistiocytosis (HLH) and to explore possible risk factors for death, we retrospectively reviewed the medical records of 103 adult HLH patients hospitalized from 1997 to 2012. We analyzed the underlying diseases, clinical characteristics, 1aboratory findings, outcomes, and prognostic factors. The most common cause of HLH was hematologic malignancies (n = 49), followed by infectious diseases (n = 24) and autoimmune disorders (n = 14); 24 cases were of unknown etiology. Eight patients had a combination of underlying diseases. HLH was clinically characterized by high fever (96.1%), splenomegaly (79.6%), hepatomegaly (65.0%), lymphadenopathy (53.4%), proteinuria (31.1%), skin rash (25.2%), gastrointestinal hemorrhage (14.6%), disseminated intravascular coagulation (13.6%), increased creatinine (7.8%), and central nervous system involvement (12.6%) including altered mental status (9.7%) and cranial hemorrhage (2.9%). Laboratory abnormalities included cytopenia (99.0%), serum ferritin >500 ug/L (98.4%), liver dysfunction (98.1%), hypertriglyceridemia (88.5%), hemophagocytosis in bone marrow smear (87.4%), and hypofibrinogenemia (60.9%).In addition to the treatment they received for the underlying causes, patients received therapy for HLH consisting of corticosteroids, immunosuppressive drugs, and intravenous immunoglobulin. Twenty-six patients (25.2%) recovered after treatment, and 19 of them achieved long-term remission during follow-up. Seventy-seven patients (74.8%) died because of tumor, sepsis, multiple organ failure, or HLH-related organ hemorrhage and coagulopathy. The deceased patients were more likely to be older at disease onset, male, and to present with splenomegaly and thrombocytopenia, compared to the survivors. Treatment for the underlying diseases combined with corticosteroids, immunosuppressive agents, and immunoglobulin therapy may improve the prognosis of HLH. More attention should be paid to high-risk patients to prevent the development of serious complications associated with HLH.

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.

Expressions of BAFF/BAFF receptors and their correlation with disease activity in Chinese SLE patients.

B-cell activating factor belonging to tumour necrosis factor family (BAFF) is essential for B-cell survival and function through interaction with its receptors BAFF receptor 3 (BR3), B-cell maturation antigen (BCMA) and/or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), though BCMA and/or TACI can also bind to a proliferation-inducing ligand (APRIL). We evaluate the correlation of the expressions of these ligands/receptors with different clinical manifestations of systemic lupus erythematosus (SLE). Levels of BAFF and APRIL in plasma from 73 SLE patients were determined by enzyme-linked immunosorbent assay. Expressions of BR3, TACI and BCMA on CD19+ B cells were detected by flow cytometry. Clinical data were collected and disease activity was evaluated using SLEDAI-2000. SLE patients had elevated BAFF and APRIL levels in their plasma. BAFF levels correlated positively with SLEDAI while negatively with the BR3 protein expression on CD19+ B cells (p < .05). The detected BR3 protein expression in SLE patients was reduced on CD19+IgD+CD27—, CD19+IgD+CD27+ as well as CD19+IgD—CD27+ B cells compared to the counterparts of healthy controls (p < .001), whereas SLE patients did not differ from healthy controls in BR3 mRNA levels. In untreated new-onset patients, the expression rate of BR3 on CD19+ B cells correlated negatively with SLEDAI (p < .05). Elevation of BAFF and reduction of BR3 on CD19+ B cells were more obvious in those with lupus nephritis (LN, p < .05). TACI expression on CD19+ B cells was up-regulated only in those subjects with LN (p < .05). Elevated plasma BAFF and reduced BR3 protein expression on peripheral B cells could act as biomarkers for active disease in SLE patients. High expression of TACI may indicate the occurrence of LN.

Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 ± 6.9 and 3.5 ± 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis. Lupus (2008) 17, 93—99.

Protein-losing enteropathy in systemic lupus erythematosus: analysis of the clinical features of fifteen patients.

Objective:Protein-losing enteropathy (PLE) is an unusual manifestation of systemic lupus erythematosus (SLE), so its clinical manifestations and management are not well understood. In this study, we try to characterize the basic clinical features and the management of PLE by retrospectively analyzing the clinical data of 15 PLE patients and hope this study can improve the awareness of PLE in lupus patients with severe hypoalbuminemia that could not be explained by other causes. Methods:The clinical data of 15 SLE patients with PLE hospitalized during November 2001 and April 2006 in Peking Union Medical College Hospital were retrospectively reviewed. The PLE was diagnosed by Tc-99m albumin scintigraphy (99mTc-HAS). The clinical characteristics, laboratory tests, response to treatment, and the outcome were studied. Results:The mean age of PLE onset was 40.1 ± 15.4 years (19–71 years). Twelve were female and 3 were male. 53.3% (8 of 15) patients had PLE as the initial presentation of SLE. All patients had different degree of peripheral pitting edema. Eleven had ascites, 9 had pleural effusion, and 7 had pericardial effusion. Only 6 patients presented with abdominal pain and diarrhea. Positive antinuclear antibodies (HEP-2) with a speckled pattern were found in all patients, but the antidsDNA antibody was negative in most cases. All patients had marked hypoalbuminemia, 80% had hypocomplementemia, 66.7% had hyperlipoproteinemia, and 40% had hypocalcemia. The liver function tests and the prothrombin time were in normal ranges. The 24-hours urine protein was less than 0.5 g in 60% (9 of 15) and more than 1.0 g in 20% (3 of 15) patients who were renal biopsied but only found to have very mild pathologic changes. Gastrointestinal endoscopy examination discovered generalized edema in the intestinal wall whereas the biopsy showed chronic inflammation only. Most cases had good response to corticosteroid and immunosuppressive therapies. The serum albumin level improved evidently in all patients after treatment and normal scintigraphic finding was found in 9 patients. Conclusion:PLE can be the initial presentation of SLE or can develop a very long time after the diagnosis of SLE. The prominent clinical presentations are caused by hypoalbuminemia. 99mTc-HAS is useful not only for the diagnosis of PLE but is also helpful for monitoring the efficacy of treatment. When a SLE patient presents with evident hypoalbuminemia without evidence of other causes, PLE should be considered. Early diagnosis and treatment may improve the prognosis.

Long-Term Survival and Death Causes of Systemic Lupus Erythematosus in China: A Systemic Review of Observational Studies

AbstractSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with an increased risk of death compared to general population. Although previous studies showed improvement in survival of SLE, the long-term prognosis has not been elaborated in China.This study aims to integrate the observational studies estimating current long-term survival of Chinese SLE patients and analyze the death-cause situation of SLE in China.The study is a systemic review of English and non-English articles using MEDLINE, EMBASE, CNKI, WANFANG, and SINOMED databases. Additional studies were found by consultation with clinical experts, browse of references in selected papers, and search of related textbooks. Our major search terms were SLE, follow-up, prognosis, survival, mortality, and China.We included cohort studies for survival analysis, and both cohort studies and case series for death-cause analysis in China.The extraction of the articles were done by 2 authors independently using predesigned charts, including characteristics of study, clinical data, analyzing data, and study quality indicators.All pooled analyses were conducted both for random-effects model and fixed-effects model. Funnel plots and Egger regression tests were applied to check potential publication bias. Heterogeneity was tested by sensitivity analysis. We identified 5 studies for survival analysis comprising 4469 Chinese patients with SLE (380 observed deaths). Thirty-six studies were suitable for death-cause analysis with 2179 observed deaths (derived from more than 20,000 Chinese patients with SLE). The overall pooled survival rates for SLE in China were 94% for 5-year survival rate and 89% for 10-year survival rate after disease onset from the year 1995 to 2013, which were similar with previous publications in Asia-Pacific area. The proportions of different causes of death showed infection (33.2%), renal involvement (18.7%), lupus encephalopathy (13.8%), and cardiovascular disease (11.5%) as the top 4 causes.The overall survival rates for Chinese patients with SLE resembled previous publications in Asia-Pacific area. But the death causes of SLE in China were of some differences indicating relatively higher proportion of infection and lupus encephalopathy and lower cardiovascular disease. Ethnicity and more aggressive treatment might have contributed to the difference in death composition.

Prevalence, risk factors and outcome of digital gangrene in 2684 lupus patients.

The aim of the study is to assess the clinical characteristics, risk factors and outcome of patients with systemic lupus erythematosus (SLE) complicated with digital gangrene. In all, 2684 consecutive SLE inpatients admitted to Peking Union Medical College Hospital from December 1997 to August 2007 were studied. Demographic data, clinical features, laboratory findings as well as therapeutic regimens were systematically reviewed and a database was established. Cases with digital gangrene were identified and followed up. 1) Eighteen patients with SLE were complicated with digital gangrene, the average age at event was 33.1 ± 11.8 years and the average disease duration was 99.1 ± 60.1 months. 2) Patients with SLE, with long disease duration (≥4 years), Raynaud’s phenomenon and elevated serum C-reactive protein (CRP) were more likely to develop digital gangrene, P = 0.006, 0.001, and 0.031, respectively, OR = 1.03 (95% CI 1.01, 1.04), 35.76 (95% CI 4.67, 273.83) and 9.93 (95% CI 1.23, 80.30), respectively. 3) Fifteen gangrene patients started prednisone ≥1 mg/kg/d, and 18 were treated with cyclophosphamide, although 8 cases failed and ultimately received digital amputation. Prompt corticosteroid treatment (prednisone ≥1 mg/kg/d started within 3 weeks) decreased the hazard of amputation, P = 0.073, HR = 0.13 (95% CI 0.01, 1.21). Long disease duration, Raynaud’s phenomenon and elevated serum CRP were independent predictive factors for SLE to develop digital gangrene. Early and aggressive corticosteroid treatment prevented gangrene from progression and improved prognosis.

Antineutrophil cytoplasmic antibody-associated vasculitis complicated with diffuse alveolar hemorrhage: a study of 12 cases.

Objective:To summarize the clinical features and therapeutic response of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis complicated with diffuse alveolar hemorrhage (DAH). Method:A retrospective chart review of the patients having ANCA-associated vasculitis with DAH was made with regard to their clinical symptoms, laboratory test results, responses to therapy and outcomes. Results:During January 1994 to June 2007, 131 ANCA-associated vasculitis patients were admitted to Peking Union Medical College Hospital. During this period, 12 of these cases consisting of 9 males and 3 females with a mean age of 59.9 ± 16.7 years developed DAH. The mean duration of vasculitis before the onset of DAH was 9.0 ± 14.3 months (range: 0–48 months). Dyspnea was the most consistent presenting symptom, while frank hemoptysis occurred in only 5 cases at the onset of DAH. The most common extrapulmonary findings associated with DAH were glomerulonephritis (100%). Symptoms including fever and arthralgia-myalgia (91.7%) as well as complications involving gastrointestinal (41.7%), mucocutaneous (25%), ear-nose-throat (25%), cardiovascular (16.7%), and nervous system (16.7%) were also frequently seen. The Birmingham Vasculitis Activity Score at the onset of DAH was 21.8 ± 4.9. All patients were treated with systemic corticosteroids combined with cyclophosphamide including methylprednisolone pulse therapy in 7 patients. In addition, plasmapheresis (41.7%), dialysis (25%), and mechanical ventilation (41.7%) were applied. The overall mortality rate was 58.3% (7 patients). Three patients died of fulminant DAH and respiratory failure during the first week of treatment. The other 4 patients died of septic shock (2 patients), severe heart failure (1 patient), and systemic fungus infection with septic shock (1 patient) 10 to 32 days after the onset of DAH. Conclusion:DAH is the most serious complication of ANCA-associated vasculitis. The episode of DAH always occurs simultaneously with multiple system involvement. The most constant signs are newly developed dyspnea and new infiltration of bilateral lungs. Prompt bronchoalveolar lavage can be helpful for timely diagnosis of the patients without overt hemoptysis and a useful tool to exclude pulmonary infection.

Gastrointestinal complications of systemic sclerosis.

Systemic sclerosis is an autoimmune disease characterized by progressive skin thickening and tightness. Pulmonary interstitial fibrosis and kidney damage are the most important indicators for mortality; however, the gastrointestinal tract is the most commonly damaged system. Virtually all parts of the gastrointestinal (GI) tract can be involved, although the esophagus is the most frequently reported. The mechanisms that cause such extensive damage are generally unclear, but vascular changes, immunological abnormalities, excessive accumulation of collagen in the submucosa, smooth muscle atrophy and neuropathy may participate because these are the most common histological findings in biopsies and autopsies. Most patients with GI tract involvement complain about dyspepsia, nausea, vomiting, abdominal bloating/distension, and fecal incontinence. These symptoms are generally mild during the early stage of the disease and are likely ignored by physicians. As the disease becomes more advanced, however, patient quality of life is markedly influenced, whereby malnutrition and shortened survival are the usual consequences. The diagnosis for systemic sclerosis is based on manometry measurements and an endoscopy examination. Supportive and symptomatic treatment is the main therapeutic strategy; however, an early diagnosis is critical for successful management.

Sjögren's syndrome-onset lupus patients have distinctive clinical manifestations and benign prognosis: A case—control study

The objective of this study was to investigate the clinical characteristics and prognosis of Sjögren’s syndrome-onset systemic lupus erythematosus (SS/SLE) patients. Medical charts of 41 consecutive SS/SLE inpatients admitted to Peking Union Medical College Hospital (PUMCH) from February 1998 to February 2008 were systematically reviewed, including demographic data, clinical features, laboratory findings, treatment as well as outcomes. Two hundred and fourteen cases were randomly selected as controls from 2331 SLE-only inpatients treated in PUMCH at the same time period. There were significant differences between SS/SLE and SLE-only patients in the following manifestations (p < 0.05): (1) sex ratio (F/M) (41/0 versus 184/30), age (42.8 ± 41.0 years versus 31.8 ± 31.0 years), disease duration (113.8 ± 84.0 months versus 44.9 ± 18.0 months); (2) clinical features, xerostomia (85.4% versus 6.1%), xerophthalmia (75.6% versus 2.3%), renal tubular acidosis (21.9% versus 0%), interstitial lung disease (12.2% versus 2.8%), facial rash (9.8% versus 46.3%), nephrotic syndrome (7.3% versus 31.3%), central nervous system involvement (4.9% versus 19.6%); (3) laboratory findings, ESR (64.6±75.0mm/h versus 46.5±34.0mm/h), C4 (14.8 ± 12.2 g/dl versus 12.0 ± 10.9 g/dl), IgG elevation (56.4% versus 29.9%) and IgA elevation (38.5% versus 20.4%), RF, anti-SSA and anti-SSB positive rates (70.8% versus 20.3%, 82.9% versus 43.4% and 39.0% versus 7.9%); (4) SLEDAI score (8.0 ± 8.0 versus 10.2 ± 10.0), glucocorticoid treatment (methylprednisolone bolus/1—2 mg kg-1 day-1 prednisone/<1 mg kg-1 day-1 prednisone) (8/26/7 versus 91/102/21), and importantly, rate of death and/or severe irreversible organ failure (2.4% versus 14.9%). SS/SLE patients were followed up for 33.0 ± 34.0 months, 40 cases remained stable at a low dose of corticosteroid. In conclusion, different from SLE-only patients, SS/SLE patients have distinctive clinical manifestations and benign prognosis that require less vigorous treatment with glucocorticoids and/or immunosuppressants. Lupus (2010) 19, 197—200.