Infliximab‐Associated Immunomediated Hepatitis in Children With Inflammatory Bowel Disease

Mostamand, Shikib; Schroeder, Shauna; Schenkein, Jacqueline; Miloh, Tamir

doi:10.1097/mpg.0000000000001137

Cited by 17 publications

(7 citation statements)

References 24 publications

(43 reference statements)

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“…Indeed, effectiveness of infliximab has been reported in both refractory AILD and JDM (62)(63)(64). However, a number of reports on anti-TNF-a-induced AIH and AIM has been published (65)(66)(67)(68), highlighting the dual effects that anti-TNF-a agents might have. This paradox of anti-TNF-a therapy has been mainly attributed to the disruption of the regulatory role of TNF-a signaling in immune pathways (68).…”

Section: Autoimmune Mechanisms and Genetic Predispositionmentioning

confidence: 99%

Case Report: Simultaneously Developed Amyopathic Dermatomyositis and Autoimmune Sclerosing Cholangitis – a Coincidence or a Shared Immunopathogenesis?

et al. 2022

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Inflammatory rheumatic diseases (IRD) and autoimmune liver diseases (AILD) share many similarities regarding epidemiology, genetics, immunology and therapeutic regimens, so it is not surprising that approximately 20% of patients with AILD are diagnosed with an IRD as well. Clinical features and biochemical hallmarks of IRD and AILD often intertwine and cross diagnostic criteria. Therefore, the real distinction of underlying disorders in a patient with these comorbidities may be challenging. The present report is the first report of simultaneously developed juvenile dermatomyositis (JDM) and autoimmune sclerosing cholangitis (ASC) with both entities fulfilling the latest guidelines for a definite diagnosis. Both of these diagnoses are difficult to definitely establish since ASC has a similar serologic profile as autoimmune hepatitis and liver histological analysis is frequently non-specific, whereas clinically amyopathic JDM diagnosis depends mostly on classical dermatological symptoms, while the rest of the diagnostic criteria, including the necessity for skin or muscle biopsy and the presence of myositis specific antibodies, are still not uniformed. In spite of these challenges, our patient clearly met European League Against Rheumatism/American College of Rheumatology classification criteria for CAJDM and The European Society for Pediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria for ASC. Since elevated serum transaminases, the presence of serum antinuclear antibodies and hypergammaglobulinemia could be explained as a part of both JDM and ASC, the underlying pathophysiology remains debatable. Intriguingly, JDM and ASC share genetic predisposition including human leukocyte antigen allele DRB1*0301 and tumor necrosis factor α 308A allele. Furthermore, both humoral and cellular components of the adaptive immune system contribute to the pathogenesis of JDM and ASC. Moreover, recent findings indicate that the loss of the CD28 expression on T-cells plays a significant role in their pathogenesis along with the Th17 immune pathway. Despite these common features that suggest shared autoimmunity, AILD and autoimmune myositis are traditionally studied and managed independently. The lack of therapies that target the underlying cause results in a high rate of adverse events due to unspecific immunosuppressive therapy. Shared autoimmunity is an ideal area to develop new, targeted immunotherapy that would hopefully be beneficial for more than one disease.

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Section: Autoimmune Mechanisms and Genetic Predispositionmentioning

confidence: 99%

Case Report: Simultaneously Developed Amyopathic Dermatomyositis and Autoimmune Sclerosing Cholangitis – a Coincidence or a Shared Immunopathogenesis?

et al. 2022

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“…Albeit rare, anti‐tumor necrosis factor‐α (TNF‐α)‐induced AIH has been described in a number of reports 20 . In case reports of children with IBD, autoimmune features in liver biopsies normalized after discontinuation of anti‐TNF‐α therapy 21,22 . In contrast, refractory AIH was reported to respond to infliximab therapy 2,23 .…”

Section: Ibdmentioning

confidence: 99%

Autoimmune liver disease in gastrointestinal conditions

Nassar

Waisbourd‐Zinman

2022

Clinical Liver Disease

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“…Однако исследование 30 детей с аутоиммунными болезнями печени (AИГ, первичный склерозирующий холангит -ПСХ и аутоиммунный склерозирующий холангит -AСХ) сообщает о снижении показателей качества жизни у пациентов по сравнению со здоровыми людьми. Хуже были результаты обследования у лиц с осложнением хронических заболеваний печени, в частности с асцитом [123]. Показано, что 73 % из 30 исследованных пациентов имели прогрессирование болезни печени.…”

Section: лечение аутоиммунного гепатита у детейunclassified

“…Однако необходимо тщательно оценить возможность использования инфликсимаба, учитывая потенциальные серьезные инфекционные осложнения при его использовании, а также гепатотоксичность [122]. Кроме того, имеются сообщения о ФНО-α-индуцированном АИГ у взрослых и детей, получающих этот препарат по поводу ВЗК [122,123]. Поэтому, прежде чем рекомендовать использование ингибиторов ФНО-α для лечения АИГ у детей, необходимо исследовать его роль в патогенезе АИГ при ВЗК.…”

Section: лечение аутоиммунного гепатита у детейunclassified

Autoimmune Hepatitis in Children: The Current State of the Problem

Волынец

Хавкин

Skvortsova

et al. 2018

Rossijskij žurnal gastroènterologii, gepatologii, koloproktolog

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Aim.To generalize the results of existing research studies carried out to investigate autoimmune hepatitis (AIH) in children, and the contemporary approaches to the diagnosis and therapy of the disease. Key points. According to the results of serological studies, two types of AIH can be distinguished in children. AIH of type 1 is diagnosed, when anti-smooth muscle autoantibodies (ASMA) and/or antinuclear autoantibodies (ANA) have been detected. AIH of type 2 AIH is diagnosed, when liver kidney microsomal autoantibodies (anti-LKM-1) and/ or anti-liver cytosolic autoantibodies (anti-LC-1) have been detected. Liver parenchymal inflammation responds well to a standard immunosuppressive therapy with prednisolone and azathioprine. Disease relapses are observed in about 40% of patients during treatment. It is expedient to treat children at least for 2–3 years before attempting to cancel the treatment, which decision should be considered only when the levels of transaminases have remained normal and IgG has been negative, or autoantibody titers have been low (1:20 using immunofluorescence method) for at least a year. Before attempting to cancel the therapy, liver biopsy and histological study should be repeated in order to exclude the possibility of residual inflammatory changes. For a small number of patients, who do not respond to standard treatment and those who suffer from frequent disease relapses, it is advisable to offer an alternative immunosuppressive treatment, the effectiveness of which is still ambiguous and poorly understood (including, in order of priority, mycophenolate mofetil, calcineurin inhibitors, rituximab, Inhibitor of tumor necrosis factor-alpha). In cases of refractoriness to therapy and the disease progression to liver cirrhosis and its decompensation, liver transplantation is justified. It is shown that AIH might relapse after liver transplantation. De novo AIH develops after liver transplantation as a result of non-autoimmune diseases; it is characterized by the presence of autoantibodies (ANA, ASMA and typical or atypical anti-LKM-1), and histologically characterized by a pattern similar to that of AIH. De novo AIH after liver transplantation responds well to a classical immunosuppressive therapy, but not to a standard antiretroviral therapy. In the review, we discuss issues associated with the clinical manifestations and diagnosis of AIH in children. Approaches to the treatment and long-term observation of such children are reviewed, including, i.e., those formulated by the main group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) members.Conclusion. Autoimmune hepatitis (AIH) in children has a progressive course with the outcome to liver cirrhosis. The presented review has summarized approaches to the diagnosis and selection of AIH therapy in children.

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Infliximab‐Associated Immunomediated Hepatitis in Children With Inflammatory Bowel Disease

Cited by 17 publications

References 24 publications

Case Report: Simultaneously Developed Amyopathic Dermatomyositis and Autoimmune Sclerosing Cholangitis – a Coincidence or a Shared Immunopathogenesis?

Case Report: Simultaneously Developed Amyopathic Dermatomyositis and Autoimmune Sclerosing Cholangitis – a Coincidence or a Shared Immunopathogenesis?

Autoimmune liver disease in gastrointestinal conditions

Autoimmune Hepatitis in Children: The Current State of the Problem

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