Clinical characteristics and outcome of IgG4-related disease with hypocomplementemia: a prospective cohort study

Abstract Background Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease. Objectives This study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia. Methods 312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels (< 0.73 g/L) and/or C4 levels (< 0.10 g/L) were defined as hypocomplementemia. Demographic data, clinical characteristics, laboratory parameters, treatment, and outcome of two groups were analyzed and compared. Results Hypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p < 0.05). Serum C3 and C4 showed a significant positively correlation with each other. Both C3 and C4 were negatively correlated with the number of involved organs, IgG, IgG3, IgG4, and IgG4-RD RI, as well as positively correlated with IgA and hypersensitive C reactive protein (hsCRP). 64 (98.5%) patients responded quickly to initial therapy at a 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2 ± 13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.401). Conclusions Clinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.

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Clinical characteristics and outcome of IgG4-related disease with hypocomplementemia: a prospective cohort study

10.21203/rs.3.rs-150733/v1 ◽

2021 ◽

Author(s):

linyi peng ◽

Hui Lu ◽

Jiaxin Zhou ◽

Panpan Zhang ◽

Jieqiong Li ◽

...

Keyword(s):

Relapse Rate ◽

Prospective Cohort ◽

Clinical Characteristics ◽

Recurrence Time ◽

Normal Complement ◽

Laboratory Parameters ◽

Related Disease ◽

Igg4 Related Disease ◽

Significant Difference

Abstract Background Immunoglobulin G4 related disease (IgG4-RD) is a newly recognized systemic, immune-mediated and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease. Objectives This study aimed to clarify the clinical features, treatment efficacy and outcome in IgG4-RD patients with hypocomplementemia. Methods 312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking union medical college hospital. Patient’s demographic data, clinical characteristics, laboratory parameters, treatment and outcome were analyzed. Results Hypocomplementemia was identified in 65(20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85±10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs,higher IgG4-RD responder index (IgG4-RD RI), higher laboratory parameters such as counts of eosinophils, inflammatory markers༌immunoglobulin G(IgG), IgG1, IgG3, IgG4 and IgE. In addition, lymph nodes, lacrimal gland༌submandibular gland༌parotid gland༌paranasal sinus༌bile ducts and prostate gland were more commonly affected(p < 0.05). Serum C3 and C4 were negatively correlated with the number of involved organs, IgG4-RD RI, hypersensitive C-reactive protein (hsCRP), IgG, IgG1, IgG3 and IgG4. 64(98.5%) patients responded quickly to initial therapy at 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2±13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.7559). Conclusions Clinical characteristics of IgG4-related disease with hypocomplementemia differs from normal complement group.Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.

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Needle biopsy compared with surgical biopsy: pitfalls of small biopsy in histologial diagnosis of IgG4-related disease

Arthritis Research & Therapy ◽

10.1186/s13075-021-02432-y ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Yanying Liu ◽

Fei Yang ◽

Xiying Chi ◽

Yuxin Zhang ◽

Jiangnan Fu ◽

...

Keyword(s):

Needle Biopsy ◽

Plasma Cells ◽

Classification Criteria ◽

Histological Diagnosis ◽

Obliterative Phlebitis ◽

Surgical Biopsy ◽

Related Disease ◽

Igg4 Related Disease ◽

Significant Difference ◽

Storiform Fibrosis

Abstract Objective The growing utilization of needle biopsy has challenged the current pathology consensus of IgG4-related disease (IgG4-RD). The aims of this study were to identify the histological characteristics of needle biopsy and surgical specimens and evaluate the ability of needle biopsy in histological diagnosis of IgG4-RD. Methods Biopsies from patients who were referred to as IgG4-RD by the 2019 ACR/EULAR IgG4-RD classification criteria in Peking University People’s Hospital from 2012 to 2019 were re-evaluated. Typical histological features and diagnostic categories were compared between needle biopsy and surgical biopsy. Results In total, 69 patients met the 2019 ACR/EULAR classification criteria and 72 biopsies of them were re-evaluated. All cases showed lymphoplasmacytic infiltrate, while storiform fibrosis and obliterative phlebitis were only present in 35 (48.6%) and 23 (31.9%) specimens, respectively. Storiform fibrosis was more likely to be seen in retroperitoneum lesion (P = 0.033). Surgical biopsy showed significantly higher IgG4+ plasma cells/high-power field (IgG4/HPF) count (P < 0.01) and higher proportion of IgG4/HPF > 10 (P < 0.01). No significant difference was observed with regard to the ratio of IgG4+ plasma cells/IgG+ plasma cells (IgG4/IgG) (P = 0.399), storiform fibrosis (P = 0.739), and obliterative phletibis (P = 0.153). According to the 2011 comprehensive diagnostic criteria, patients who performed a needle biopsy were less likely to be probable IgG4-RD (P = 0.045). Based on the 2011 pathology consensus, needle biopsy was less likely to be diagnosed as IgG4-RD (P < 0.01), especially to be highly suggestive IgG4-RD (P < 0.01). Only 1/18 (5.6%) needle salivary specimens fulfilled the cutoff of IgG4/HPF > 100, which was significantly less than 15/23 (65.2%) of surgical ones (P < 0.01). Conclusions Needle biopsy shows an inferiority in detecting IgG4/HPF count but not in IgG4/IgG ratio, storiform fibrosis, and obliterative phlebitis. Compared with surgical samples, needle biopsy is less likely to obtain a histological diagnosis of IgG4-RD. A different IgG4/HPF threshold for needle biopsy of the salivary glands may be considered.

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A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab

Journal of Clinical Medicine ◽

10.3390/jcm10061329 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1329

Author(s):

Johanna Backhus ◽

Christian Neumann ◽

Lukas Perkhofer ◽

Lucas A Schulte ◽

Benjamin Mayer ◽

...

Keyword(s):

Disease Activity ◽

Clinical Activity ◽

Inflammatory Disorder ◽

International Consensus ◽

Steroid Pulse ◽

Related Disease ◽

Igg4 Related Disease

Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. Methods: We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. Results: Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. Conclusion: RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6–9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy.

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Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort

Rheumatology ◽

10.1093/rheumatology/kez669 ◽

2020 ◽

Vol 59 (8) ◽

pp. 2115-2123 ◽

Cited By ~ 1

Author(s):

Yanying Liu ◽

Qiaozhu Zeng ◽

Lijuan Zhu ◽

Jingyuan Gao ◽

Ziqiao Wang ◽

...

Keyword(s):

Risk Factors ◽

Relapse Rate ◽

Unstable Condition ◽

Serum Igg4 Level ◽

Related Disease ◽

Igg4 Related Disease ◽

Younger Age ◽

Serum Igg4 ◽

History Of ◽

Igg4 Level

Abstract Objectives Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition. Methods We performed a retrospective study of 277 IgG4-RD patients at Peking University People’s Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition. Results The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different. Conclusion The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.

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Clinical phenotypes of IgG4-related disease reflect different prognostic outcomes

Rheumatology ◽

10.1093/rheumatology/keaa221 ◽

2020 ◽

Vol 59 (9) ◽

pp. 2435-2442 ◽

Cited By ~ 4

Author(s):

Marco Lanzillotta ◽

Corrado Campochiaro ◽

Gaia Mancuso ◽

Giuseppe Alvise Ramirez ◽

Gabriele Capurso ◽

...

Keyword(s):

Cumulative Dose ◽

Disease Onset ◽

Recurrence Time ◽

Clinical Judgement ◽

Clinical Phenotypes ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Group 3 ◽

Group 1

Abstract Introduction Four clinical phenotypes of IgG4-related disease (IgG4-RD) have been recently identified by latent class analysis (LCA): pancreato-biliary (group 1); retroperitoneum/aortitis (group 2); head and neck limited (group 3); and Mikulicz/systemic (group 4). The reproducibility of this classification in clinical practice and its relevance for patient management, however, remain unknown. Methods The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA-derived phenotypes based on clinical judgement. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on an additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index (RI); history of atopy, diabetes, osteoporosis, relapses and malignancy; cumulative dose of glucocorticoids; and use of rituximab. Results Clinical judgement replicated LCA classification with strong agreement among IgG4-RD experts (κ = 0.841, P < 0.0005). At disease onset, group 1 showed the highest levels of serum IgG4 and IgE. Groups 2 and 4 had the lowest and highest IgG4-RD RI, respectively. At 2 years’ follow-up, group 3 received the highest cumulative dose of glucocorticoids, but higher incidences of diabetes mellitus were observed in groups 1 and 4, consistent with the higher likelihood of pancreatic involvement in groups 1 and 4. No difference among the four groups was observed in terms of disease recurrence, time to relapse and frequency of rituximab infusion. Conclusion Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.

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SAT0525 EFFICACY AND SAFETY OF MZR FOR IgG4-RELATED DISEASE.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1983 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1219-1220

Author(s):

S. Kawaai ◽

S. Fukui ◽

T. Nakai ◽

G. Kidoguchi ◽

H. Ozawa ◽

...

Keyword(s):

Adverse Events ◽

Retention Rate ◽

Case Reports ◽

Efficacy And Safety ◽

Related Disease ◽

Igg4 Related Disease ◽

Number Of Patients ◽

Serum Igg4 ◽

Over Time

Background:IgG4-Related Disease (IgG4RD) is known to cause multiple organ lesions with infiltration of IgG4-positive plasma cells, and patients often have relapses with tapering treatments despite an initial good response to glucocorticoids therapy. Mizoribine (MZR) is an immunosuppressant working as an inhibitor of purine synthesis, which mechanism of action is similar to mycophenolate mofetil. Data regarding the efficacy and safety of MZR on IgG4RD is limited although some previous case reports1showed effectiveness for IgG4RD.Objectives:This study aims to assess the efficacy and safety of MZR in patients with IgG4RD.Methods:We retrospectively reviewed charts of IgG4RD patients who used MZR between January 2004 and December 2019 at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. We investigated basic demographics, involved organs, results of blood tests including IgG and IgG4 titer, and medications used including glucocorticoid and other immunosuppressants (IS). We followed IgG4 titer, dose of glucocorticoid, flare of disease and retention of MZR at the beginning, 6 and 12months after starting MZR. We compared changes in PSL (prednisolone) doses and IgG4 titers over time using Friedman test with Bonferroni correction. We also checked adverse events during follow up.Results:Twenty-two patients with IgG4RD who used MZR were included. Median age was 62 years old, and 15 (68.2%) patients are male. Lacrimal and salivary glands, pancreatitis and retroperitoneal fibrosis were common lesions. All patients were initially treated with glucocorticoids. Flare was observed in 5 (22.7 %) patients before initiation of MZR. The number of patients who continued MZR without flare are 19 (86.4 %) at 6 months, and 14 (73.7 %) at 12 months. IgG4 titer significantly declined at 6 and 12 months from baseline although significant consecutive decrease in PSL dose (Figure 1, 2). Liver dysfunctions are commonest adverse events (n=16, 72.7%) but mild (grade1; n=15, 68.2%) and most cases are apparently due to other reasons. Serious infection (SI) occurred in 3 (13.6%) patients in total follow up, however no SI were observed during 1 year after MZR treatment.Conclusion:MZR can be safely used in patients of IgG4RD with high retention rate, and seemed to have steroid-sparing effect. Prospective comparative studies are needed.References:[1]Nanke Y, Kobashigawa T, Yago T, Kamatani N, Kotake S. A case of Mikulicz’s disease, IgG4-related plasmacytic syndrome, successfully treated by corticosteroid and mizoribine, and then by mizoribine alone. Intern Med 49: 1449-1453, 2010.Table 1.Patient characteristics Table 2.Disease and treatment status before and after initiation of MZR Figure 1.Serum IgG4 level changesFigure 2.Changes in the PSL dose over timeDisclosure of Interests:None declared

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Efficacy and safety of cladribine: Subcutaneous versus intravenous administration in hairy cell leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7013 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7013-7013

Author(s):

Tarek Yakout Mohamed ◽

Mosaad El Gammal ◽

Alfred Elias Namour ◽

Raafat Ragaie Abdel Malek ◽

Ola Khorshid

Keyword(s):

Complete Remission ◽

Adverse Events ◽

Hairy Cell Leukemia ◽

Route Of Administration ◽

Similar Response ◽

Hairy Cell ◽

Cell Leukemia ◽

Laboratory Parameters ◽

Significant Difference

7013 Background: Hairy cell leukemia (HCL) is rare B-cell lymphoproliferative disorder. Its treatment has evolved from splenectomy with time to failure (TTF) of 19 months to Cladribine that increased complete remission (CR) rate to 90%, with only small percentage of patients relapsing at 30 months. Cladribine (CDA) is originally administered intravenously as continuous infusion for 7 days; Subsequently, it was administered subcutaneously. This study aims at comparing efficacy and toxicity of Subcutaneous (SC) versus Intravenous (IV) administration of CDA in treatment of HCL. Methods: This retrospective study included HCL patients presented to National Cancer Institute and Nasser Institute, Cairo, Egypt, during period 2004-2010. Included patients received CDA as 1st or 2nd line with minimum follow up of 12 months. All files were reviewed for baseline clinical & laboratory parameters, route of administration, response, adverse events and survival. Results: This study included 49 eligible patients, 41 patients received CDA as 1st line treatment, while 8 patients as 2nd line. Eighteen patients were treated by continuous IV infusion whereas 31 patients by SC injections. Both groups were comparable regarding baseline clinical and laboratory parameters with no statistically significant difference. At median follow up period of 33.5 months, complete remission rate was 94% in IV group versus 97% in SC group (p=0.691); median TTF for IV group was 52.9 months while that for SC group was not reached (p=0.035). The median time to achieve CR in both arms was similar. By analyzing different factors affecting TTF using multivariate analysis, route of administration proved to be the only statistically significant factor (P=0.006). Regarding adverse events, there was no difference between both groups in hematological toxicities. IV route was associated with a significant higher incidence of mucositis (p=0.02) and viral infections (p=0.01). Hepatotoxicity and neurotoxicity were higher in SC group but difference was not statistically significant. Conclusions: SC administration of cladribine is an alternative route to IV in treatment of HCL with similar response rate, longer time to treatment failure and better tolerability.

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Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Blood ◽

10.1182/blood-2021-145549 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1124-1124

Author(s):

Jiang Ji ◽

Ziqi Wan ◽

Jing Ruan ◽

Yali Du ◽

Miao Chen ◽

...

Keyword(s):

Adverse Events ◽

Aplastic Anemia ◽

Median Time ◽

Relapse Rate ◽

Real World ◽

Reticulocyte Count ◽

Efficacy And Safety ◽

Overall Response ◽

Significant Difference

Abstract Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P>0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

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Lung nodules and IgG4 related disease: a single-center based experience

10.21203/rs.3.rs-46476/v1 ◽

2020 ◽

Author(s):

Yan Xie ◽

Anji Xiong ◽

Tony Marion ◽

Yi Liu

Keyword(s):

Lung Diseases ◽

Immunosuppressive Agents ◽

Ground Glass Opacity ◽

Lung Nodules ◽

Bronchial Wall ◽

West China Hospital ◽

West China ◽

Related Disease ◽

Igg4 Related Disease

Abstract Background and objective: This study was undertaken in an attempt to characterize the frequency and clinical features of lung nodules in IgG4 related disease (IgG4-RD) patients as an insight for help with the diagnosis of lung nodules.Methods: A retrospective study was carried out in West China Hospital, Sichuan University from January 2012 to December 2018, 89 patients with definite IgG4-RD were enrolled.Results: Fifty of 89 patients with definite IgG4-RD had radiologically confirmed lung nodules, 6 of whom were diagnosed with definite IgG4 related lung disease. Lung nodules detected in more than 40 patients were small and solid, always with regular margins. Multiple (41/50) and bilateral (34/50) distributions was also a major characteristic of these lung nodules. Lobulation and speculation were simultaneously detected in 3 patients, including 2 patients combined with pleural indentation. Calcification of nodules was detected in only one patient. Thirty-seven patients also had additional radiological abnormalities of lungs, including ground-glass opacity (21/50), thickening of pleura (9/50), thickening of interlobular septa (4/50), thickening of bronchial wall (3/50), pleural effusion (4/50), mass (3/50), interstitial changes (5/50), and mediastinal or hilar lymphadenopathy (32/50). Most patients (44/50) were treated with glucocorticoids alone or combined with immunosuppressive agents. Sixteen patients received a re-examination by chest computed tomography (CT) scan after treatment, 10 of whom showed a decrease in the size and/or the number of nodules.Conclusions: The incidence of lung nodules in IgG4-RD patients can be high. For an IgG4-RD patient with lung nodules, the possibility that the lung nodules related to IgG4-RLD is high. It is hard to differentiate IgG4 related lung nodules from other lung diseases, in particular, lung cancer. Radiological characteristics and positive responses to glucocorticoids and immunosuppressive agents can help with the differential diagnosis. For these patients, regular follow-up is also important.

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P0456LONG TERM PATIENT SURVIVAL AND RELAPSE RATE IN ANCA ASSOCIATED PATIENTS WITH RENAL INVOLVMENET - DATA FROM CROATIAN REFERRAL CENTER

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0456 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Matija Crnogorac ◽

Ana Brechelmacher ◽

Ivica Horvatić ◽

Patricia Kacinari ◽

Miroslav Tišljar ◽

...

Keyword(s):

Relapse Rate ◽

Interstitial Fibrosis ◽

Renal Involvement ◽

Induction Treatment ◽

Tubular Atrophy ◽

Free Survival ◽

Acute Dialysis ◽

Significant Difference ◽

Stage Renal Disease

Abstract Background and Aims The aim of the research was to evaluate patient and renal as well as relapse free survival in ANCA associated vasculitis (AAV) patients in our center. Despite the advances in understanding pathogenesis of AAVs and advances in treatment, the outcomes of AAV patient differ in various centers. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. All the patients were treated with cyclophosphamide and steroids in induction treatment with adjuvant PLEX and dialysis depending on renal function and lung manifestations. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV),There were 14 (13%) PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Histologically (Berden classification) 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Results During follow up 21 (19,8%) patients died, 26 (24,5%) patients reached ESRD and 10 (9,4%) patients relapsed. There was no significant difference in outcomes between clinical, serological or histological phenotypes. In multivariant analysis independent predictors for death were age (HR = 1,059, 95% CI =1,001-1,120; p = 0,046), anemia (HR = 0,952, 95% CI =0,908-0,998; p = 0,040) and BVAS (HR = 1,093, 95% CI =1,030-1,159; p = 0,003), for ESRD. the need for acute dialysis (HR = 4,674, 95% CI =1,996-10,946; p = < 0,001), and interstitial fibrosis and tubular atrophy (IFTA) percentage over 50% (HR = 2,652, 95% CI =1,157-6,081; p = 0,021). and for relapse rate younger age (HR = 0,924, 95% CI = 0,870-0,981; p =0,010), lower serum creatinine levels (HR = 0,996, 95% CI = 0,992-1,000; p = 0,033), and the need for acute dialysis (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Event free survival after 12, 24, 36 and 60 months was for death 83,9, 81,2, 79 and 74,7%, for ESRD 80,6, 77,9, 76,1 and 71% and for relapse 95,3, 88,4, 88,4 and 85%. Conclusion Timely diagnosis and treatment can ensure better outcomes in AAV patients. Though there is an overlap in predictive factors between different cohorts, there are still distinctive differences especially between cohorts from clinical trials and those from observational studies. Our study is among few to show significance of anemia as clinical predictor and IFTA percentage as pathohistological predictor.

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