Isoniazid Induced Lupus  Presenting as Oral Mucosal  Ulcers with Pancytopenia

Shah, Ria; Ankale, Padmaraj; Sinha, Kanishk; Iyer, Aparna; Jayalakshmi, T.K.

doi:10.7860/jcdr/2016/22543.8629

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…On the other hand, larvae treated with INH after the liver is functional (5-7 dpf) had hepatomegaly without any apparent toxicity in the rest of the larval body. Hepatomegaly is a known clinical manifestation of liver injury induced by INH administration (Nanton et al, 2004;Shah et al, 2016;Wolf & Lavine, 2000). To our knowledge, this is the first study demonstrating INH induced hepatomegaly in the zebrafish model.…”

Section: Discussionmentioning

confidence: 80%

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

Çakan Akdoğan,

Bilgi

2024

Biotech Studies

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Prediction of drug-induced liver injury (DILI) potential of drugs is one of the most challenging issues of drug development. Zebrafish larvae provide an in vivo and robust test platform. Due to the ease of handling developing larvae between 2 - 5 days post fertilization (dpf) has been extensively used as a DILI test model. However, the liver is not fully functional at this stage. Here, the importance of larval liver maturation was tested by applying selected known DILI-rank drugs to liver reporter zebrafish between 2-5 dpf and 5-7 dpf. Acetaminophen (most-DILI) treatment caused a significant dose-dependent reduction in liver size only at the early stage. Isoniazid (most-DILI) administration after liver maturation induced hepatomegaly, while it induced liver size reduction between 2-5 dpf. Chlorambucil (less-DILI) treatment induced opposing effects on liver size, in the two stages tested. A non-DILI agent chloramphenicol did not induce any liver size change in either larval stage. Clinical observations were better reproduced when isoniazid and chlorambucil were administered after liver maturation. Our findings show that often-overlooked liver maturity status is a critical parameter for the evaluation of DILI.

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Section: Discussionmentioning

confidence: 80%

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

Çakan Akdoğan,

Bilgi

2024

Biotech Studies

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“…Dysregulation of the liver immune environment is thought to play a critical role in the initiation and progression of DILI ( Segovia-Zafra et al, 2021 ). One previous study had shown that lupus erythematosus developed in patients with INH-ILI ( Shah et al, 2016 ). Lupus erythematosus is a well-known disease of the immune system, thus INH-ILI may be also related to the immune response.…”

Section: The Molecular Mechanism Involved In Isoniazid-induced Liver ...mentioning

confidence: 99%

Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review

Zhuang

Liu

et al. 2022

Front. Pharmacol.

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Isoniazid (INH) and rifampicin (RFP) are the first-line medications for tuberculosis treatment, and liver injury is the major adverse effect. Natural medicinal ingredients provide distinct benefits in alleviating patients’ symptoms, lowering the liver injury risk, delaying disease progression, and strengthening the body’s ability to heal. This paper summarises the recent research on the mechanisms of INH and RFP-induced liver injury and the effects of natural medicinal ingredients. It is believed that INH-induced liver injury may be attributed to oxidative stress, mitochondrial dysfunction, drug metabolic enzymes, protoporphyrin IX accumulation, endoplasmic reticulum stress, bile transport imbalance, and immune response. RFP-induced liver injury is mainly related to cholestasis, endoplasmic reticulum stress, and liver lipid accumulation. However, the combined effect of INH and RFP on liver injury risk is still uncertain. RFP can increase INH-induced hepatotoxicity by regulating the expression of drug-metabolizing enzymes and transporters. In contrast, INH can antagonize RFP-induced liver injury by reducing the total bilirubin level in the blood. Sagittaria sagittifolia polysaccharide, quercetin, gallic acid, and other natural medicinal ingredients play protective roles on INH and RFP-induced liver injury by enhancing the body’s antioxidant capacity, regulating metabolism, inhibiting cell apoptosis, and reducing the inflammatory response. There are still many gaps in the literature on INH and RFP-induced liver injury mechanisms and the effects of natural medicinal ingredients. Thus, further research should be carried out from the perspectives of liver injury phenotype, injury markers, in vitro and in vivo liver injury model construction, and liver-gut axis. This paper comprehensively reviewed the literature on mechanisms involved in INH and RFP-induced liver injury and the status of developing new drugs against INH and RFP-induced liver injury. In addition, this review also highlighted the uses and advantages of natural medicinal ingredients in treating drug-induced liver injury.

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“…[8][9][10] Efek yang ditimbulkan ADR dapat berupa eritema sampai efek samping berat yang mengancam jiwa seperti Stevens Johnson Sindrome (SJS) 11 dan ADR juga dapat memicu terjadinya sistemik lupus eritematous (SLE) pada penderitanya. [12][13][14][15] SJS merupakan reaksi mukokutan akut, ditandai oleh nekrosis epidermis luas dengan keterlibatan minimal 2 membran mukosa yang dipicu oleh obat, jarang karena infeksi dan keganasan. 16 SLE adalah suatu kondisi inflamasi yang berhubungan dengan gangguan autoimun, sistem tubuh menyerang jaringannya sendiri yang menyebabkan kerusakan multiorgan ditandai dengan 4 dari 11 kriteria seperti ruam malar, ruam diskoid, fotosensitifitas, ulser pada rongga mulut, artritis, serositis, gangguan renal, gangguan neurologi, gangguan hematologi, gangguan imunologis, antibodi antinuclear (ANA).…”

Section: Pendahuluanunclassified

<p>Terapi lesi oral pasien sindrom Stevens-Johnson disertai lupus eritematosus sistemik</p><p>Oral lesion therapy in patients with Stevens-Johnson syndrome with systemic lupus erythematosus</p>

Tamigoes

Dewi

2018

JKG

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ABSTRAKPendahuluan: Adverse drug reaction (ADR) merupakan salah satu respon tubuh manusia tidak diinginkan dan berbahaya yang disebabkan penggunaan obat meskipun dalam dosis normal. ADR dapat menyebabkan terjadinya sindrom Stevens-Johnson (SJS) serta dapat memicu lupus eritematosus sistemik (SLE), yang salah satu manisfestasinya sebagai krusta hemoragik dan erosi yang luas pada mulut dan peri-oral, dapat mengganggu fungsi mulut sehingga terganggunya asupan makanan. Laporan kasus ini bertujuan untuk menjelaskan terapi lesi oral pasien sindrom Stevens-Johnson disertai lupus eritematosus sistemik. Laporan kasus: Seorang pasien wanita berusia 57 tahun dengan riwayat penyakit meningitis tuberkulosis dirujuk ke Bagian Penyakit Mulut dari departemen Ilmu Kesehatan Kulit dan Kelamin dengan diagnosis SJS, pasien mengeluhkan kesulitan untuk membuka mulutnya, sakit menelan dan sakit pada bibir. Terdapat riwayat pemakaian obat ofloxacin, streptomysin, dan OAT. Pemeriksaan ekstraoral menunjukkan beberapa lesi diskret pada wajah, konjungtiva anemis, lesi erosif dan krusta hemoragik pada bibir. Pemeriksaan intraoral ditemukan lesi erosif pada mukosa bukal dan palatal serta plak putih pada dorsal lidah. Pemeriksaan darah rutin menunjukkan hemoglobin, hematokrit, leukosit, MCV, MCH, eosinofil, netrofil, limfosit, protein total dan albumin rendah sedangkan uji ANA positif, sehingga diagnosis ditegakkan sebagai lesi oral terkait SJS disertai SLE dan kandidiasis oral. Medikasi yang diberikan adalah Chlorhexidine gluconate 0,1%, nistatin suspensi oral, vitamin B12, asam folat, dan topikal kortikosteroid. Lesi oral menunjukkan perbaikan dalam waktu 3 minggu, pada pasien terjadi SJS dan SLE secara bersamaan hal ini menunjukkan adanya keterlibatan mekanisme imunologi Simpulan: Terapi non farmakologi berupa pemberian kortikosteroid topikal,obat kumur Chlorhexidine gluconate 0,1%, vitamin B12, asam folat, dan nistatin yang menunjukkan perbaikan pada lesi oral dalam 3 minggu perawatan, ditambah dengan terapi non farmakologi berupa pemeliharaan kebersihan rongga mulut dengan obat kumur Chlorhexidine gluconate 0,1% sebagai antiseptik untuk meningkatkan kenyamanan pasien, untuk memfasilitasi epitelisasi dan mencegah komplikasi seperti infeksi.Kata kunci: Adverse Drug Reaction, lesi oral, sindrom Stevens-Johnson, lupus eritematosus sistemik Oral lesion therapy in patients with Stevens-Johnson syndrome with systemic lupus erythematosus ABSTRACT Introduction: Adverse drug reaction (ADR) is one of the unwanted and dangerous human body responses caused by the use of medications even in regular doses. ADR can cause Stevens-Johnson syndrome (SJS) and trigger systemic lupus erythematosus (SLE), with manifestation such as extensive haemorrhagic and erosive crusts in the mouth and peri-oral, which can interfere the oral function and disrupt the food intake. This case report was aimed to explain the treatment of oral lesions in patients with Stevens-Johnson syndrome with systemic lupus erythematosus. Case report: A 57-years-old female patient with a his...

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Isoniazid Induced Lupus Presenting as Oral Mucosal Ulcers with Pancytopenia

Cited by 5 publications

References 7 publications

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

The developmental stage is a critical parameter for accurate assessment of the drug-induced liver injury (DILI) potentials of drugs with the zebrafish larval liver model

Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review

<p>Terapi lesi oral pasien sindrom Stevens-Johnson disertai lupus eritematosus sistemik</p><p>Oral lesion therapy in patients with Stevens-Johnson syndrome with systemic lupus erythematosus</p>

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