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Danieli MG, Antonelli E, Gammeri L, Longhi E, Cozzi MF, Palmeri D, Gangemi S, Shoenfeld Y. Intravenous immunoglobulin as a therapy for autoimmune conditions. Autoimmun Rev 2025; 24:103710. [PMID: 39592027 DOI: 10.1016/j.autrev.2024.103710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 11/22/2024] [Indexed: 11/28/2024]
Abstract
Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.g. myositis and vasculitis), and hematological disorders. Since the role of immunoglobulins in fields other than replacement therapy is now consolidated, in this study we carried out a review of the literature to evaluate the main uses of IVIg therapy. We have focused our attention on the treatment of autoimmune, neurological, hematological, dermatological and pediatric diseases. Furthermore, our analysis of the literature also extended to the potential use of IVIg as an adjuvant treatment of long COVID-19. From our analysis, we found consistent data about IVIg's effectiveness in treating numerous clinical conditions. Treatment with IVIg represents a second-line approach or a valid adjuvant to standard therapies capable of positively influencing the clinical course of many pathologies and reducing or avoiding side effects of standard therapies, with a good safety profile.
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Affiliation(s)
- Maria Giovanna Danieli
- SOS Immunologia delle Malattie Rare e dei Trapianti. AOU delle Marche & Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, via Tronto 10/A, 60126 Torrette di Ancona, Italy; Postgraduate School of Allergy and Clinical Immunology, Università Politecnica delle Marche, via Tronto 10/A, 60126 Ancona, Italy.
| | - Eleonora Antonelli
- Postgraduate School of Internal Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Luca Gammeri
- Postgraduate School of Allergy and Clinical Immunology, University of Messina, 98121 Messina, Italy
| | - Eleonora Longhi
- Postgraduate School in Clinical Pathology and Clinical Biochemistry, Università Politecnica delle Marche, via Tronto 10/A, 60126 Ancona, Italy.
| | - Maria Francesca Cozzi
- Postgraduate School of Internal Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy
| | - Davide Palmeri
- Postgraduate School of Allergy and Clinical Immunology, Università Politecnica delle Marche, via Tronto 10/A, 60126 Ancona, Italy
| | - Sebastiano Gangemi
- Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat Gan 52621, Israel; Reichman University, Herzelia 46101, Israel.
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Maggiore G, Sciveres M. Giant cell hepatitis associated with autoimmune hemolytic anemia: More evidence for B-cell depletion therapy for a rare immune mediated disease of infancy. Clin Res Hepatol Gastroenterol 2024; 48:102435. [PMID: 39084551 DOI: 10.1016/j.clinre.2024.102435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 07/28/2024] [Indexed: 08/02/2024]
Abstract
Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare but severe disease of infancy defined by an acute liver injury, histologically characterized by a widespread giant cell transformation and by an autoimmune hemolysis. GCH-AHA is thought to be immune-mediated being however a distinct entity from juvenile autoimmune hepatitis. In particular, GCH-AHA displays a less favorable response to conventional immunosuppressive treatment compared to classical juvenile autoimmune hepatitis, carrying a higher risk of mortality. In fact, since his first description, conventional therapy with prednisone with azathioprine has been used as first line treatment, however with frequent relapses during tapering, as well as severe side effects related to its prolonged use at high doses in early age. Due to the frequent occurrence of relapse, several immunosuppressive drugs have been tried as second line therapy with doubtful success. In case of severe liver dysfunction and/or severe anemia, transitory remission has been achieved with intravenous immunoglobulins administration, however with temporary response. B-cell depletion treatment, mostly with chimeric anti-CD20 monoclonal antibody (rituximab; RTX) has been used since 2004 with encouraging results mostly in refractory cases as second-line therapy. In this issue, the report of a series of 20 children with GCH-AHA from Shanghai, China, confirms the previous treatment experiences of a greater efficacy in obtaining complete remission of RTX or RTX treatment regimens compared to conventional regimens, with a good safety. To date, published experience with this rare disease suggests that RTX should be considered the cornerstone of treatment for complicated or relapsing cases of GCH-AHA and given the increasing evidence on its efficacy and safety, RTX might be even an acceptable option as first line therapy beside conventional treatment, to drastically reduce the cumulative steroids exposure and its side effects.
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Affiliation(s)
- Giuseppe Maggiore
- Hepatology and Liver Transplant Unit IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
| | - Marco Sciveres
- Hepatology and Liver Transplant Unit IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
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Zhang XY, Gong JY, Wang JS, Feng JY, Chen L, Xie XB, Lu Y. Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study. Clin Res Hepatol Gastroenterol 2024; 48:102392. [PMID: 38897557 DOI: 10.1016/j.clinre.2024.102392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/27/2024] [Accepted: 06/05/2024] [Indexed: 06/21/2024]
Abstract
OBJECTIVE To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). METHODS This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. RESULTS Twenty patients (8 females and 12 males; age range 1-26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3-8) versus 14 (5-25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2-101) and 22 (4-41) months, respectively. Two patients in conventional group died of disease progression and infection. CONCLUSIONS RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.
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Affiliation(s)
- Xue-Yuan Zhang
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China
| | - Jing-Yu Gong
- Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China
| | - Jian-She Wang
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China
| | - Jia-Yan Feng
- Department of Pathology, Children's Hospital of Fudan University, Shanghai, China
| | - Lian Chen
- Department of Pathology, Children's Hospital of Fudan University, Shanghai, China
| | - Xin-Bao Xie
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China
| | - Yi Lu
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
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Csernus K, Tészás A, Ottóffy G, Dezsőfi-Gottl A, Tárnok A. [Association of giant cell hepatitis and autoimmune hemolytic anemia in infancy]. Orv Hetil 2023; 164:1432-1436. [PMID: 37695715 DOI: 10.1556/650.2023.32848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/06/2023] [Indexed: 09/13/2023]
Abstract
Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AIHA) is a rare disorder with unfavorable prognosis, affecting infants and young children. The mortality rate is high, complications of acute liver failure, sepsis, or liver transplantation can be responsible for fatal outcomes. An 18-month-old child who was diagnosed previously with autoimmune hemolytic anemia, developed acute hepatitis and acute liver failure concomitant to the relapse of the disease. GCH-AIHA is characterized by Coombs positive hemolytic anemia and progressive liver injury, histologically defined by widespread giant cell transformation. Liver biopsy was performed to establish the diagnosis, histological examination confirmed the presence of multinuclear, giant cell hepatocytes. Corticosteroid and azathioprine treatment were started. As a result of subsequent rituximab treatment and intravenous immunoglobulin therapy, acute liver failure and anemia gradually resolved. The exact background of the association of the two entities is still unknown, an autoimmune mechanism is suspected. Conventional immunosuppressive treatment with corticosteroid and azathioprine seems to be ineffective in most cases, therefore second- and third-line therapies are required. Since the introduction of the anti-CD20 rituximab therapy, the prognosis of GCH-AIHA has improved significantly. Orv Hetil. 2023; 164(36): 1432-1436.
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Affiliation(s)
- Katalin Csernus
- 1 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika Pécs, József Attila út 7., 7623 Magyarország
| | - Alexandra Tészás
- 1 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika Pécs, József Attila út 7., 7623 Magyarország
| | - Gábor Ottóffy
- 1 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika Pécs, József Attila út 7., 7623 Magyarország
| | - Antal Dezsőfi-Gottl
- 2 Semmelweis Egyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika Budapest Magyarország
| | - András Tárnok
- 1 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika Pécs, József Attila út 7., 7623 Magyarország
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Hemolysis in Early Infancy: Still a Cause of Cholestatic Neonatal Giant Cell Hepatitis. Am J Surg Pathol 2021; 46:801-808. [PMID: 34856569 DOI: 10.1097/pas.0000000000001841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Before the prophylactic use of anti-D antibodies in pregnancy, hemolytic anemia of the newborn was the most common cause of hyperbilirubinemia. Nowadays, given the rarity of hemolytic anemia of the newborn, hepatobiliary abnormalities, perinatal infections, and metabolic disorders have become the most common conditions in the differential diagnosis of neonatal cholestasis. Here, we report 3 instances of cholestatic giant cell hepatitis in 3 infants who had Coombs' positive hemolysis due to ABO incompatibility in 1, Rh incompatibility in another, and combined ABO and Rh incompatibility in the third. Although rare, cholestatic neonatal giant cell hepatitis associated with hemolysis still needs to be considered in patients with neonatal cholestasis. A marked elevation of aspartate aminotransferase over alanine aminotransferase can be a helpful clue to an early diagnosis.
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Matarazzo L, Nastasio S, Sciveres M, Maggiore G. Pregnancy outcome in women with childhood onset autoimmune hepatitis and autoimmune sclerosing cholangitis on long-term immunosuppressive treatment. Eur J Obstet Gynecol Reprod Biol 2021; 268:7-11. [PMID: 34788721 DOI: 10.1016/j.ejogrb.2021.10.030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 10/15/2021] [Accepted: 10/26/2021] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Autoimmune hepatitis and autoimmune sclerosing cholangitis may lead to maternal and fetal complications in pregnant women diagnosed during childhood and treated long-term with immunosuppressive drugs. Immunosuppressive treatment with azathioprine is usually employed during pregnancy to maintain remission but his safety is still controversial. The aim of our study is to investigate pregnancy outcomes after maternal long-term immunosuppressive treatment for autoimmune hepatitis/sclerosing cholangitis. METHODS We conducted a retrospective cohort study including all pregnant women who received a diagnosis of autoimmune hepatitis or autoimmune sclerosing cholangitis during childhood and followed-up from 1989 to 2021. RESULTS Fifteen pregnancies in 12 women were observed. The median follow-up from disease onset was 26.7 years. All patients had been treated with prednisone and azathioprine (AZA) as first line therapy. At the beginning of the pregnancy, 11/12 (91.6%) patients were in spontaneous or pharmacologically induced clinical and biochemical remission and one had received a liver transplant. During pregnancy, 8 patients continued azathioprine. No relapse during pregnancy occurred in any patient. One woman presented a flare five months after delivery and a second one, one year after delivery when AZA was discontinued. The 15 pregnancies resulted in 13 livebirths (86.6%) with 9 (69.2%) full-term healthy neonates. Two miscarriages (13.3%) were recorded and cesarean section was performed in 3 women (23%). No congenital malformations were observed. CONCLUSIONS Pregnancy in women diagnosed during pediatric age with autoimmune hepatitis or autoimmune sclerosing cholangitis and treated long-term with immunosuppressants is possible with good maternal and neonatal outcomes. Azathioprine allows, in most cases, to maintain remission with a good safety profile. Careful monitoring of these patients during pregnancy is, however, mandatory.
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Affiliation(s)
- Lorenza Matarazzo
- Department of Medical, Surgery, and Health Sciences, University of Trieste, Trieste, Italy.
| | - Silvia Nastasio
- Department of Pediatrics, Harvard Medical School, Boston's Children Hospital, MA, USA
| | - Marco Sciveres
- Pediatric Hepatology and Pediatric Liver Transplantation, ISMETT, University of Pittsburgh Medical Center Italy, Palermo, Italy
| | - Giuseppe Maggiore
- Hepatogastroenterology, Nutrition and Liver Transplant Unit, IRCCS Pediatric Hospital Bambino Gesù, Rome, Italy
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Poddighe D, Madiyeva A, Talipova D, Umirbekova B. Infantile giant cell hepatitis with autoimmune hemolytic anemia. World J Hepatol 2021; 13:411-420. [PMID: 33959224 PMCID: PMC8080548 DOI: 10.4254/wjh.v13.i4.411] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/26/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically associated with autoimmune hemolytic anemia in the absence of any other systemic or organ-specific autoimmune comorbidity. The etiology is unknown; concomitant viral infections (as potential trigger factors) have been identified in a few patients. The pathogenesis reportedly relies upon immune-mediated/ autoimmune mechanisms. This condition should be considered in any infant developing Coombs-positive anemia; indeed, anemia usually precedes the development of hepatitis. The clinical course is usually aggressive without the appropriate immunosuppressive therapy, which may include steroids, conventional immunosuppressors (e.g., azathioprine and cyclophosphamide as first-line treatments), intravenous immunoglobulin, and biologics (rituximab). Improvements in medical management (including the availability of rituximab) have significantly reduced the mortality of this condition in the last decade.
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Affiliation(s)
- Dimitri Poddighe
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
- Department of Pediatrics, National Research Center for Maternal and Child Health, Nur-Sultan 010000, Kazakhstan.
| | - Aidana Madiyeva
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
| | - Diana Talipova
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
| | - Balzhan Umirbekova
- Department of Pediatrics, National Research Center for Maternal and Child Health, Nur-Sultan 010000, Kazakhstan
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Nastasio S, Matarazzo L, Sciveres M, Maggiore G. Giant cell hepatitis associated with autoimmune hemolytic anemia: an update. Transl Gastroenterol Hepatol 2021; 6:25. [PMID: 33824929 DOI: 10.21037/tgh.2020.03.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 03/02/2020] [Indexed: 11/06/2022] Open
Abstract
Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe disease characterized by autoimmune hemolysis associated with acute liver injury, histologically defined by widespread giant cell transformation. It occurs after the neonatal period, most commonly in the first year of life and uniquely affects pediatric patients. It is still poorly understood and likely underdiagnosed, although in recent years there have been advances in the understanding of its pathogenesis and the liver injury is now hypothesized to be secondary to a humoral immune mechanism. Although no laboratory test specific for the diagnosis currently exists, given its severity, it is fundamental to rule out GCH-AHA when evaluating a patient in the first year of life presenting with AHA and/or with acute liver disease of unknown etiology. While GCH-AHA is progressive in nature as other autoimmune liver disorders, it differs significantly from juvenile autoimmune hepatitis (JAIH) in that a cure can be achieved after several years of intensive treatment in a portion of patients. Conventional first line therapy consist of prednisone/prednisolone combined with azathioprine, however, several immunosuppressive drugs, commonly used in the treatment of JAIH have been tried as second line therapy, including cyclosporine, cyclophosphamide, mycophenolate mofetil, 6-mercaptopurine, calcineurin inhibitors, and sirolimus. Intravenous immunoglobulins have also been used in cases of severe liver dysfunction and/or severe anemia allowing for transitory remission. More recently treatment with B-cell depletion has been attempted in some patients and encouraging results have been reported in refractory cases. Although what constitutes optimal treatment has yet to be determined, the recent progress in the understanding of the pathogenetic mechanisms of GCH-AHA have made positive strides, cautiously pointing toward a hopeful prognosis for some of these patients.
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Affiliation(s)
- Silvia Nastasio
- Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lorenza Matarazzo
- Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy
| | - Marco Sciveres
- Pediatric Hepatology and Pediatric Liver Transplantation, ISMETT, University of Pittsburgh Medical Center Italy, Palermo, Italy
| | - Giuseppe Maggiore
- Pediatric Hepatology and Pediatric Liver Transplantation, ISMETT, University of Pittsburgh Medical Center Italy, Palermo, Italy.,Department of Medical Sciences, University of Ferrara, Ferrara, Italy.,Division of Gastroenterology, Hepatology and Nutrition, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
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Kim YH, Kim JW, Lee EJ, Kang GH, Kang HJ, Moon JS, Ko JS. Successful Treatment of a Korean Infant with Giant Cell Hepatitis with Autoimmune Hemolytic Anemia Using Rituximab. Pediatr Gastroenterol Hepatol Nutr 2020; 23:180-187. [PMID: 32206631 PMCID: PMC7073370 DOI: 10.5223/pghn.2020.23.2.180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/28/2020] [Indexed: 12/13/2022] Open
Abstract
Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine. Physical examination showed generalized icterus and splenomegaly. The laboratory findings suggested warm-type AHA with cholestatic hepatitis. Liver biopsy revealed giant cell transformation of hepatocytes and moderate lobular inflammation. The patient was successfully treated with four doses of rituximab. Early relapse of hemolytic anemia and hepatitis was observed, which prompted the use of an additional salvage dose of rituximab. He is currently in clinical remission.
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Affiliation(s)
- Young Ho Kim
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Ju Whi Kim
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Gyeong Hoon Kang
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Hyoung Jin Kang
- Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children's Hospital, Seoul, Korea
| | - Jin Soo Moon
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
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Matarazzo L, Di Chio T, Nastasio S, Tommasini A, Ventura A, Maggiore G. B-cell depletion induces prolonged remission in patients with giant cell hepatitis and autoimmune hemolytic anemia. Clin Res Hepatol Gastroenterol 2020; 44:66-72. [PMID: 31076361 DOI: 10.1016/j.clinre.2019.03.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 03/17/2019] [Accepted: 03/19/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe immune-mediated disorder. Despite aggressive immunosuppressive treatments, the mortality is high. Prednisone has been effectively employed to achieve remission, but with a risk of relapse, if discontinued, and with severe side effects. A possible causative role of humoral immune response has paved the way to anti CD-20 monoclonal antibody (rituximab; RTX). Nevertheless, data about timing of remission and long-term side effects are sparse. METHODS AND MATHERIALS We have retrospectively evaluated 3 refractory GCH-AHA patients in whom a prolonged remission has been achieved with RTX. In all patients, response to first and second line therapy was incomplete or transitory and severe steroid side effects occurred. RESULTS A stable and sustained remission was achieved after multiple doses of RTX allowing withdrawing all the other treatments. No life-threatening infections have been recorded, however two patients developed persistent, paucisymptomatic hypogammaglobulinaemia. The only patient who did not develop hypogammaglobulinemia received IgG replacement during RTX. CONCLUSION RTX induced complete and long-lasting remission allowing discontinuing all the other immunosuppressive drugs. A persistent, paucisymptomatic hypogammaglobulinaemia has been the unique side effect. Although further studies need to replicate our data, RTX can be considered as an effective and safe therapy for sustained remission in patients with severe refractory GCH-AHA.
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Affiliation(s)
- Lorenza Matarazzo
- Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy.
| | - Teresa Di Chio
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Silvia Nastasio
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, USA
| | - Alberto Tommasini
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo" Trieste, Trieste, Italy
| | - Alessando Ventura
- Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy; Institute for Maternal and Child Health, IRCCS "Burlo Garofolo" Trieste, Trieste, Italy
| | - Giuseppe Maggiore
- Section of Pediatrics, Department of Medical Sciences University of Ferrara, Ferrara, Italy
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Should Giant Cell Hepatitis With Autoimmune Haemolythic Anaemia Be Considered a Paediatric Autoimmune Liver Disease? J Pediatr Gastroenterol Nutr 2018; 66:e138. [PMID: 29688999 DOI: 10.1097/mpg.0000000000001911] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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12
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Should Giant Cell Hepatitis With Autoimmune Hemolytic Anemia Be Considered a Pediatric Autoimmune Liver Disease? J Pediatr Gastroenterol Nutr 2018; 66:e137. [PMID: 29394216 DOI: 10.1097/mpg.0000000000001910] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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13
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Watad A, Amital H, Shoenfeld Y. Intravenous immunoglobulin: a biological corticosteroid-sparing agent in some autoimmune conditions. Lupus 2017; 26:1015-1022. [DOI: 10.1177/0961203317696589] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases. This compound is effective in a wide range of clinical conditions other than primary immunodeficiency, including autoimmune diseases, inflammatory disorders, infections, organ transplantation, and possibly supportive therapy for cancer. Systemic corticosteroids remain the gold standard treatment for many autoimmune diseases, but their long-term use is associated with complications in diverse organs and systems. Osteoporosis, osteonecrosis, cardiovascular disease, infections, and cancer have been associated with this treatment. Therefore, physicians are occasionally forced to withdraw the treatment with steroids. Biological agents may represent a good alternative, but in addition to being very expensive, these agents may have serious side effects. This review aimed to cover the major advances in the use of IVIg as a steroid-sparing agent in some relevant autoimmune diseases.
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Affiliation(s)
- A Watad
- Department of Medicine ‘B’, Sheba Medical Center, Israel
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - H Amital
- Department of Medicine ‘B’, Sheba Medical Center, Israel
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Y Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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