P1126PLASMAPHERESIS TREATMENT FOR SEVERE PEMPHIGUS: 10 YEARS' EXPERIENCE OF A SINGLE CENTER IN CHINA

Abstract Background and Aims Pemphigus is a potentially life-threatening autoimmune bullous disorder. The pathogenesis involves with IgG antibodies against desmogleins (Dsg) (Dsg 1 and Dsg 3) on epithelial cell surface. Systemic corticosteroid is considered as the basis of the treatment for pemphigus. As an interventional treatment, plasmapheresis was introduced for treating severe or refractory pemphigus. The literature in this field is limited. This study aimed to review our 10 years’ experience in a single center. Method We retrospectively analyzed 17 patients with severe pemphigus who were unresponsive to high-dose prednisone and received double-filtration plasmapheresis (DFPP) treatment between January 2010 and January 2020. The information on demographic characteristics, clinical and laboratory data, treatment regimens, and clinical outcomes were collected. Results 1. Clinical characteristics: Among 17 patients, 11 patients had pemphigus vulgaris (PV), 3 patients had pemphigus foliaceus (PF), 2 patients had paraneoplastic pemphigus (PNP) and 1 patient had pemphigus herpetiform (PH). The mean age of patients was 47.8±10.0 years; 8 male patients and 9 female patients. All seventeen patients were suffering from severe pemphigus and had a period of at least one week of high-dose prednisone (1∼1.5mg/kg/d), but they were unresponsive to corticosteroid and immunosuppressants treatment. 2. As an adjuvant therapy, they received DFPP treatment with 1 to 4 sessions for each patient. Most of the patients (7 patients) received 2 sessions every other day, 5 patients received 3 sessions, 4 patients just received 1 session and only one patient received 4 sessions. For each session, the exchange volume was 1∼1.5 plasma equivalent. After DFPP treatment, the titers of Dsg antibodies significantly decreased (p<0.001, Figure 1), Nikolsky’s sign became negative and no new blisters appeared. The erosions showed reepithelialization and started healing gradually. The dosage of corticosteroid could begin to taper down rapidly in 1 to 2 weeks. On discharge, the dosage of prednisone was 0.8-1mg/kg/d. 3. As to adverse events, 4 patients had transient hypotension during the procedure, but they could recover spontaneously after parameter adjustment. No major adverse events happened. Conclusion Plasmapheresis is an effective and relatively safe treatment for severe pemphigus. Plasmapheresis can also contribute to the dosage reduction of steroid to avoid more drug-related side effect.

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A 60-Year-Old Woman with Pemphigus Vulgaris Refractory to High-Dose Prednisone

Clinical Cases in Autoimmune Blistering Diseases ◽

10.1007/978-3-319-10148-4_9 ◽

2014 ◽

pp. 65-73

Author(s):

Elizabeth S. Robinson ◽

Victoria P. Werth

Keyword(s):

Pemphigus Vulgaris ◽

High Dose ◽

Dose Prednisone

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Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A

Thrombosis and Haemostasis ◽

10.1160/th11-09-0642 ◽

2012 ◽

Vol 107 (06) ◽

pp. 1072-1082 ◽

Cited By ~ 19

Author(s):

Guenter Auerswald ◽

Alexis Thompson ◽

Michael Recht ◽

Deborah Brown ◽

Raina Liesner ◽

...

Keyword(s):

Family History ◽

Adverse Events ◽

Prospective Trial ◽

High Dose ◽

Haemophilia A ◽

Severe Haemophilia ◽

Serious Adverse Events ◽

Inhibitor Development ◽

Treatment Regimens ◽

History Of

SummaryWe report a prospective trial of 55 previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe/moderately severe haemophilia A (baseline factor VIII [FVIII] ≤2%) treated with a single FVIII replacement product. It was the objective of this study to evaluate the immunogenicity, efficacy, and safety of rAHF-PFM (Advate®). Ondemand or prophylactic treatment regimens were determined at the discretion of the investigator. rAHF-PFM was also permitted for perioperative management. There were 633 bleeding episodes (BEs), including 517 treated, and 466 rated for efficacy. Haemostatic efficacy was considered excellent/good in 93% of 466 rated treatments. Of 517 treated BEs, 463/517 (90%) were managed with one (356/517 [69%]) or two infusions (107/517 [21%]). There were 27 surgeries. Intraoperative (n=22) and postoperative (n=25) haemostatic efficacies were considered excellent or good in 100% of rated surgeries. Related serious adverse events (SAEs) were inhibitor development in 16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM. Nonserious, related adverse events (AEs) were few in number (14 in eight subjects). The odds ratio (OR [95% Confidence Interval, CI]) of developing inhibitors was significantly higher in subjects with a family history of inhibitor (4.95 [1.29–19.06]), non-Caucasian ethnicity (4.18, [1.18–14.82]), and intensive treatment at high dose (4.5 [1.05–19.25]) within ≤20 exposure days (EDs). In conclusion, rAHF-PFM was safe and effective for the management and perioperative coverage of PUPs/MTPs with severe/moderately severe haemophilia A. This report supports previous findings from studies in which family history of inhibitor, non-Caucasian ethnicity, and high intensity treatment were associated with high risk of inhibitor development.

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Features and associated factors of bacterial skin infections in hospitalized patients with pemphigus: a single-center retrospective study

10.21203/rs.3.rs-37433/v2 ◽

2020 ◽

Author(s):

Furong Li ◽

Yejun Wu ◽

Wenjie Bian ◽

Lei Huang ◽

Xuejun Zhu ◽

...

Keyword(s):

Associated Factors ◽

Bacterial Species ◽

Laboratory Data ◽

Pemphigus Vulgaris ◽

Pemphigus Foliaceus ◽

Skin Infections ◽

Gram Negative ◽

Peking University ◽

Binary Regression Analysis ◽

Bacterial Skin Infections

Abstract Background: Infections were the primary cause of death (34.3%-55.5%) in patients with pemphigus. Skin was usually the origin of infections. The study aimed to explore features and associated factors of bacterial skin infections (BSIs) in inpatients with pemphigus. Methods: One hundred and eighty-four inpatients with pemphigus hospitalizing from November 2014 to April 2019 were continuously recruited through Peking University First Hospital’s inpatient records. Then, we retrieved the clinical and laboratory data to explore the characteristics and associated factors of BSIs.Results: Of patients enrolled, pemphigus vulgaris (PV, n=142) and pemphigus foliaceus (PF, n=9) were most common, followed by pemphigus erythematosus (PE, n=25) and pemphigus vegetans (Pveg, n=1). Eighty-seven of 177 (49.2%) inpatients developed BSIs, and they had a longer length of stay compared with inpatients without BSIs (median: 18.9 days vs. 14.1 days, p = 0.008). Staphylococcus aureus was the most common bacteria(71.3%, 62/87) and highly resistant to penicillin (91.9%, 57/62). Higher levels of anti-Dsg1 autoantibodies (>124.2U/mL) (p<0.001, odds ratio [OR]=3.564, 95% confidence interval [CI]: 1.784-7.123) and anti-Dsg3 autoantibodies (>169.5U/mL) (p = 0.03, OR=1.074, 95% CI: 1.084-3.969) were underlying risk factors of BSIs when analyzed by binary regression analysis. As for Gram’s stain of bacteria, females had a lower rate of Gram-positive infections (p = 0.03). Patients using oral antibiotics (p = 0.05) had a higher rate of Gram-negative infections. Inpatients who were hospitalized in other hospitals within two weeks before the current admission had a higher rate of Gram-negative and co-infections (p = 0.03). Conclusions: Inpatients with pemphigus had a high incidence of BSIs. Some factors were associated with the susceptibility of BSIs and bacterial species.

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First-in-Human Trial of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine with Adjuvant of Aluminum Hydroxide and CpG 1018

10.1101/2021.03.31.21254668 ◽

2021 ◽

Author(s):

Szu-Min Hsieh ◽

Wang-Da Liu ◽

Yu-Shan Huang ◽

Yi-Jiun Lin ◽

Erh-Fang Hsieh ◽

...

Keyword(s):

Adverse Events ◽

Aluminum Hydroxide ◽

Phase 1 ◽

Geometric Mean ◽

Laboratory Data ◽

Spike Protein ◽

High Dose ◽

Protein Vaccine ◽

Open Label ◽

Mean Values

Design This is a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a recombinant stabilized prefusion SARS-CoV-2 spike (S-2P) protein vaccine with adjuvant of aluminum hydroxide and CpG 1018. Methods We enrolled 45 healthy adults from 20 to 49 years of age to be administered with two vaccinations of MVC-COV1901 in a low dose (LD), middle dose (MD), and high dose (HD) of spike protein at 28 days apart. There were 15 participants in each dose group, and all of them were followed up for 28 days after the second vaccination at the time of interim analysis. Adverse events (AEs) and laboratory data were recorded for safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays as well as SARS-CoV-2 spike-specific immunoglobulin G (IgG) at various times. Overall, the study duration will be 7 months. Results Solicited events were mostly mild and similar in the participants of all three dose groups. No subject experienced fever. There were no serious nor adverse events of special interest at the time point of this interim report. After the second vaccination, the SARS-CoV-2 spike specific IgG titers increased with peak geometric mean titers at 7178.245 (LD), 7746.086 (MD), and 11220.58 (HD), respectively. Serum neutralizing activity was detected by two methods in all participants of MD and HD groups, with geometric mean values generally comparable to those of a panel of control convalescent serum specimens. All of the participants in the MD and HD groups were seroconverted after the second vaccination. Conclusions The MVC-COV1901 vaccine is safe and elicits remarkable immune responses especially in the MD and HD groups.

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Features and associated factors of bacterial skin infections in hospitalized patients with pemphigus: a single-center retrospective study

Annals of Clinical Microbiology and Antimicrobials ◽

10.1186/s12941-020-00388-6 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Furong Li ◽

Yejun Wu ◽

Wenjie Bian ◽

Lei Huang ◽

Xuejun Zhu ◽

...

Keyword(s):

Associated Factors ◽

Bacterial Species ◽

Laboratory Data ◽

Pemphigus Vulgaris ◽

Pemphigus Foliaceus ◽

Skin Infections ◽

Gram Negative ◽

Peking University ◽

Binary Regression Analysis ◽

Bacterial Skin Infections

Abstract Background Infections were the primary cause of death (34.3–55.5%) in patients with pemphigus. Skin was usually the origin of infections. The study aimed to explore features and associated factors of bacterial skin infections (BSIs) in inpatients with pemphigus. Methods One hundred and seventy-seven inpatients with pemphigus hospitalizing from November 2014 to April 2019 were continuously recruited through Peking University First Hospital’s inpatient records inpatients with pemphigus hospitalizing from November 2014 to April 2019 were continuously recruited through Peking University First Hospital’s inpatient records. Then, we retrieved the clinical and laboratory data to explore the characteristics and associated factors of BSIs. Results Of patients enrolled, pemphigus vulgaris (PV, n = 142) and pemphigus foliaceus (PF, n = 9) were most common, followed by pemphigus erythematosus (PE, n = 25) and pemphigus vegetans (Pveg, n = 1). Eighty-seven of 177 (49.2%) inpatients developed BSIs, and they had a longer length of stay compared with inpatients without BSIs (median: 18.9 vs. 14.1 days, p = 0.008). Staphylococcus aureus was the most common bacteria (71.3%, 62/87) and highly resistant to penicillin (91.9%, 57/62). Higher levels of anti-Dsg1 autoantibodies (> 124.2 U/mL) (p < 0.001, odds ratio [OR] = 3.564, 95% confidence interval [CI]: 1.784–7.123) and anti-Dsg3 autoantibodies (> 169.5 U/mL) (p = 0.03, OR = 2.074, 95% CI: 1.084–3.969) were underlying risk factors of BSIs when analyzed by binary regression analysis. As for Gram’s stain of bacteria, females had a lower rate of Gram-positive infections (p = 0.03). Patients using oral antibiotics (p = 0.05) had a higher rate of Gram-negative infections. Inpatients who were hospitalized in other hospitals within 2 weeks before the current admission had a higher rate of Gram-negative and co-infections (p = 0.03). Conclusions Inpatients with pemphigus had a high incidence of BSIs. Some factors were associated with the susceptibility of BSIs and bacterial species.

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Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation

Journal of Clinical Medicine ◽

10.3390/jcm10061316 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1316

Author(s):

Johan Noble ◽

Antoine Metzger ◽

Hamza Naciri Bennani ◽

Melanie Daligault ◽

Dominique Masson ◽

...

Keyword(s):

Kidney Transplantation ◽

Adverse Events ◽

Mean Fluorescence Intensity ◽

Single Center ◽

Hla Antibodies ◽

Specific Antibodies ◽

Double Filtration Plasmapheresis ◽

Donor Specific Antibodies ◽

Double Filtration ◽

Hla Incompatible

Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.

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