Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy

Rheumatology ◽  
2019 ◽  
Vol 59 (4) ◽  
pp. 767-771 ◽  
Author(s):  
Yoshiyuki Abe ◽  
Makio Kusaoi ◽  
Kurisu Tada ◽  
Ken Yamaji ◽  
Naoto Tamura
Keyword(s):  
Survival Rate ◽  
Interstitial Lung Disease ◽  
Adverse Events ◽  
Lung Disease ◽  
Plasma Exchange ◽  
Immunosuppressive Therapy ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Intensive Immunosuppressive Therapy

Abstract Objectives We examined the effectiveness of plasma exchange (PE) therapy to reduce the mortality of rapidly progressive interstitial lung disease (RP-ILD) in patients positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. Methods Among 142 patients newly diagnosed with PM/DM or clinically amyopathic DM from 2008 to 2019 at our hospital, 10 were diagnosed with refractory RP-ILD and were positive for anti-MDA5 antibodies. PE was used as an adjunct to standard therapy and consisted of fresh frozen plasma as replacement solution. The primary outcome was non-disease-specific mortality. Results Anti-MDA5 antibodies were detected in 28 patients, of whom 21 were diagnosed with RP-ILD and 10 were refractory to intensive immunosuppressive therapy. Six patients received PE (PE group) and four did not (non-PE group). The 1-year survival rate of the PE group was higher than that of the non-PE group (100% and 25%, respectively, P = 0.033). Regarding adverse events associated with PE, two patients had anaphylactic shock, one had high fever due to fresh frozen plasma allergy and one had a catheter infection. All adverse events resolved with appropriate treatment. Conclusion We evaluated the association between 1-year survival rate and PE for refractory RP-ILD in patients positive for anti-MDA5 antibodies. Intensive immunosuppressive therapy improved the survival rate in RP-ILD patients with anti-MDA5 antibodies, but 20–30% of cases were still fatal. PE could be administered to patients with active infectious disease who were immunocompromised by intensive immunosuppressive therapy. PE may be considered in refractory RP-ILD patients positive for anti-MDA5 antibodies.

THU0337 THE EFFECTIVENESS OF PLASMA EXCHANGE THERAPY FOR ANTI-MDA5 ANTIBODY-POSITIVE REFRACTORY INTERSTITIAL LUNG DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 399.1-400
Author(s):  
Y. Abe ◽  
T. Kuga ◽  
M. Kusaoi ◽  
K. Tada ◽  
K. Yamaji ◽  
...  
Keyword(s):  
Survival Rate ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Plasma Exchange ◽  
Immunosuppressive Therapy ◽  
Fresh Frozen Plasma ◽  
Plasma Exchange Therapy ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Intensive Immunosuppressive Therapy

Background:This is an extended report of our study [1]. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, which are closely related to interstitial lung disease (ILD) with or without rapid progression, are a type of myositis-specific autoantibody. Since rapid progressive-ILD (RP-ILD) with anti-MDA5 antibodies is refractory and fatal, intensive immunosuppressive therapy with combination calcineurin inhibitor, and intravenous pulse cyclophosphamide was developed, and was shown to improve patient survival and prognosis [2]. However, 20–30% of cases were still fatal, and several additional therapies have been reported e.g. tofacitinib [3] and plasma exchange therapy (PE) [1, 4, 5].Objectives:We evaluated the effect of plasma exchange (PE) on survival in patients with refractory RP-ILD who were positive for anti-MDA5 antibodies.Methods:Among 167 patients newly diagnosed with PM/DM, clinically amyopathic DM, or cancer associated myositis from 2008 to 2019 at our hospital, 12 were diagnosed with refractory RP-ILD and were positive for anti-MDA5 antibodies. PE was used as an adjunct to standard therapy and consisted of fresh frozen plasma as replacement solution. The primary outcome was non-disease-specific mortality. anti-MDA5 antibody titres were measured by ELISA using the MESACUP anti-MDA5 test in 155 patients whose serum was frozen and stored at the time of diagnosis.Results:Anti-MDA5 antibodies were detected in 35 patients, of whom 26 were diagnosed with RP-ILD and 11 were refractory to intensive immunosuppressive therapy. Seven patients received PE (PE group) and four did not (non-PE group). The 1-year survival rate of the PE group was higher than that of the non-PE group (100% and 25%, respectively, P = 0.011). Regarding adverse events associated with PE, two patients had anaphylactic shock, one had high fever due to fresh frozen plasma allergy and one had a catheter infection. All adverse events resolved with appropriate treatment.Conclusion:We evaluated the association between 1-year survival rate and PE for refractory RP-ILD in patients positive for anti-MDA5 antibodies. Intensive immunosuppressive therapy improved the survival rate in RP-ILD patients with anti-MDA5 antibodies, but 20-30% of cases were still fatal. PE could be administered to patients with active infectious disease who were immunocompromised by intensive immunosuppressive therapy. PE may be considered in refractory RP-ILD patients positive for anti-MDA5 antibodies.References:[1]Nakashima R, Hosono Y, Mimori T. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus. 2016;25:925-33.[2]Kurasawa K, Arai S, Namiki Y et al. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology. 2018;57:2114-9.[3]Silveira MG, Selva-O’Callaghan A, Ramos-Terrades N et al. Anti-MDA5 dermatomyositis and progressive interstitial pneumonia. QJM. 2016;109:49-50.[4]Endo Y, Koga T, Suzuki T et al. Successful treatment of plasma exchange for rapidly progressive interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis: A case report. Medicine (Baltimore). 2018;97:e0436.[5]Abe Y, Kusaoi M, Tada K et al. Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy. Rheumatology. 2019.Acknowledgments:Funding: This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number JP18K15433.Disclosure of Interests:None declared

scholarly journals Successful Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis-Associated Rapidly Progressive-Interstitial Lung Disease by Plasma Exchange: Two Case Reports

2021 ◽  
Vol 14 ◽  
pp. 117954762110363
Author(s):  
Rina Takahashi ◽  
Tadashi Yoshida ◽  
Kohkichi Morimoto ◽  
Yasushi Kondo ◽  
Jun Kikuchi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Plasma Exchange ◽  
Immunosuppressive Therapy ◽  
Muscle Weakness ◽  
Case Reports ◽  
Ground Glass Opacity ◽  
Case Presentation ◽  
Intensive Immunosuppressive Therapy

Background: Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) are frequently accompanied by rapidly progressive-interstitial lung disease (RP-ILD). They are often refractory to intensive immunosuppressive therapy and have poor prognosis. Case presentation: A 73-year-old woman presented with fever, cold symptoms, and skin eruption for a month. She also exhibited muscle weakness on upper extremities slightly. The titer of anti-MDA5 antibody was extremely high, and computed tomography showed ground glass opacity and reticular shadows in the lungs. She was diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD and treated with intensive immunosuppressive therapy. However, the titer of anti-MDA5 antibody did not decrease satisfactorily, and plasma exchange was alternatively initiated. The titer decreased remarkably, and she obtained disease remission. Similarly, a 63-year-old woman presented with stiffness of the neck and hands, fever and cough. She was also diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD, because she had skin eruptions, slight muscle weakness, an elevation in anti-MDA5 antibody, and RP-ILD. She was unresponsive to intensive immunosuppressive therapy, but plasma exchange successfully improved the titer of anti-MDA5 antibody, the symptoms, and the findings of computed tomography. Conclusions: Although anti-MDA5 antibody-positive DM-associated RP-ILD has a high mortality rate, this report suggests the usefulness of plasma exchange to improve the prognosis.

SP787SELECTIVE PLASMA EXCHANGE IN ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION: EFFICACY OF PARTIAL SUBSTITUTION WITH FRESH FROZEN PLASMA

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Toshihide Naganuma ◽  
Yoshiaki Takemoto ◽  
Ako Hanaoka ◽  
Junji Uchida ◽  
Tatsuya Nakatani
Keyword(s):  
Kidney Transplantation ◽  
Plasma Exchange ◽  
Fresh Frozen Plasma ◽  
Partial Substitution ◽  
Fresh Frozen ◽  
Frozen Plasma

scholarly journals Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1232-1236 ◽  
Author(s):  
JL Moake ◽  
JJ Byrnes ◽  
JH Troll ◽  
CK Rudy ◽  
SL Hong ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Fresh Frozen Plasma ◽  
Plasma Samples ◽  
Fresh Frozen ◽  
Normal Human ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Frozen Plasma

Abstract Remission plasma samples of some patients with chronic relapsing thrombotic thrombocytopenic purpura (TTP) contain unusually large von Willebrand factor (vWF) multimers similar to those produced by normal human endothelial cells in culture. The infusion of the cryosupernatant fraction of normal plasma is as effective as normal fresh-frozen plasma (FFP) in the treatment or prevention of TTP episodes in patients with the chronic relapsing form of TTP. Three patients with chronic relapsing TTP during remission have unusually large vWF multimers present in their plasma. Two of the patients were transfused once with FFP, one of the two received cryosupernatant on three occasions, and the third patient was studied before and immediately after plasma exchange. Unusually large vWF multimers decreased or disappeared from patient plasma samples within 1/2 to 1 1/2 hours following the transfusion of FFP (on two occasions) or cryosupernatant (on two of three occasions), and immediately after plasma exchange (on one occasion). The patient who received cryosupernatant was studied serially after the infusions. Unusually large vWF multimers returned to her plasma within ten to 24 hours and persisted thereafter. Unusually large vWF multimers did not disappear from patient remission plasma samples, or from the culture medium removed from normal human endothelial cells, when these fluids were incubated in vitro with either normal FFP or cryosupernatant. We conclude that an activity in FFP, and its cryosupernatant fraction, promoted the rapid in vivo disappearance of unusually large vWF multimers from the plasma of two patients with chronic relapsing TTP in remission, and plasma exchange reversed the abnormality in a third patient who was in partial remission. Neither FFP nor cryosupernatant directly converted unusually large multimers to smaller vWF forms in vitro in the fluid phase. These results indicate that an activity in the cryosupernatant fraction of normal plasma is involved in vivo in controlling the metabolism of unusually large vWF multimers, and that this process is defective in some chronic relapsing TTP patients.

scholarly journals Combination of Fresh Frozen Plasma and Cryosupernatant Plasma for Therapeutic Plasma Exchange in Thrombotic Thrombocytopenic Purpura: A Single Institution Experience

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Qiuyan Lin ◽  
Liping Fan ◽  
Haobo Huang ◽  
Feng Zeng ◽  
Danhui Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Dominant Group ◽  
Thrombocytopenic Purpura ◽  
Replacement Fluid ◽  
Fresh Frozen ◽  
Frozen Plasma

Purpose. To evaluate the impact of a combination of fresh frozen plasma (FFP) and cryosupernatant plasma (CP) as a replacement fluid in therapeutic plasma exchange (TPE) on early therapeutic response and long-term survival of patients with thrombotic thrombocytopenic purpura (TTP). Materials and Methods. A total of 44 patients with suspected TTP were screened by Bentley and PLASMIC scores. Twenty-seven patients treated with TPE using the FFP and CP combination as the replacement fluid were enrolled and divided into two groups: 11 patients who received TPE with CP-dominant replacement fluid (FFP/CP<1) and 16 patients who received TPE with FFP-dominant replacement fluid (FFP/CP>1). Results. There were no significant differences in the demographic and clinicopathological characteristics between the two groups except for the international normalized ratio (INR). The number of TPE procedures was lower, and time to achieve complete response was shorter in the CP-dominant group than in the FFP-dominant group. There were no significant differences in overall survival between the two groups. Conclusion. The CP-dominant replacement fluid was superior to the FFP-dominant replacement fluid in early response to TPE in patients with TTP, but did not impact the patients’ overall survival.

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