J Korean Med Sci.  2020 Jul;35(28):e228. 10.3346/jkms.2020.35.e228.

A Case of Autoimmune Hepatitis after Occupational Exposure to N,N-Dimethylformamide

• Jang Bo
• Choi GH
• Jang HY
• Ahn S
• Choi JK
• Kim S
• Lee K
• Jang ES
• Kim JW
• Jeong SH

• KMID: 2504363
• DOI: http://doi.org/10.3346/jkms.2020.35.e228

Abstract

N,N-dimethylformamide (DMF), a widely used solvent in the chemical industry, is known to induce toxic hepatitis. However, there have been no reported cases of DMF-associated autoimmune hepatitis. A 31-year-old healthy man working at a glove factory since July 2015 had intermittently put his bare hands into a diluted DMF solution for his first 15 days at work. After 2 months, he felt nausea, fatigue, and hand cramping, and a jaundice followed. His laboratory findings showed positive autoantibodies and elevated immunoglobulin G (IgG), and his liver biopsy pathology was typical of autoimmune hepatitis (AIH). Prednisolone and azathioprine therapy began, and he recovered rapidly without adverse events. Though his liver chemistry was normalized, the IgG level remained persistently upper normal range. His 2nd liver biopsy performed in April 2019 showed mild portal activity, and he was well under a low dose immunosuppressive therapy up to April 2020. This case warns of the hazard of occupational exposure to DMF, and clinicians should be aware of DMF-related AIH for timely initiation of immunosuppressive therapy.

Keyword

Autoimmune Hepatitis; N,N-dimethylformamide; Occupational Health; Toxic Hepatitis

Figure

• 

  Fig. 1 Clinical course of the case. Initial laboratory results showed elevated ALT and IgG levels with typical pathology of AIH by liver biopsy. He responded well to prednisolone and azathioprine.ALT = alanine aminotransferase, IgG = immunoglobulin G, AIH = autoimmune hepatitis, PD = prednisolone, AZA = azathioprine, TB = total bilirubin.

• 

  Fig. 2 Microscopic findings of the first and second liver biopsy specimens (hematoxylin and eosin staining). First biopsy-(A) inflammation concentrated at portal tract (×40); (B) lymphoplasmacytic infiltration in hepatic lobule (×200); (C) interface activity (×400). Second biopsy-(D) mild nonspecific portal inflammation (×200).

Reference

1. Li MJ, Zeng T. The deleterious effects of N,N-dimethylformamide on liver: a mini-review. Chem Biol Interact. 2019; 298:129–136. PMID: 30576622.

2. International Agency for Research on Cancer. N,N-dimethylformamide. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 115. Some Industrial Chemicals. Lyon, France: International Agency for Research on Cancer;2018. p. 119–170.

3. National Institute for Occupational Safety and Health. Dimethylformamide. Updated 2019. Accessed March 30, 2020. https://www.cdc.gov/niosh/topics/dimethylformamide.

4. Rui D, Daojun C, Yongjian Y. Liver and heart toxicity due to 90-day oral exposure of ICR mice to N,N-dimethylformamide. Environ Toxicol Pharmacol. 2011; 31(3):357–363. PMID: 21787705.

5. Kelich SL, Mercieca MD, Pohland RC. Developmental toxicity of N-methylformamide administered by gavage to CD rats and New Zealand white rabbits. Fundam Appl Toxicol. 1995; 27(2):239–246. PMID: 8529819.

6. Hansen E, Meyer O. Embryotoxicity and teratogenicity study in rats dosed epicutaneously with dimethylformamide (DMF). J Appl Toxicol. 1990; 10(5):333–338. PMID: 2254584.

7. Massmann W. Toxicological investigations on dimethylformamide. Br J Ind Med. 1956; 13(1):51–54. PMID: 13293318.

8. Jeong SH. Current epidemiology and clinical characteristics of autoimmune liver diseases in South Korea. Clin Mol Hepatol. 2018; 24(1):10–19. PMID: 29307132.

9. Kil JS, Lee JH, Han AR, Kang JY, Won HJ, Jung HY, et al. Long-term treatment outcomes for autoimmune hepatitis in Korea. J Korean Med Sci. 2010; 25(1):54–60. PMID: 20052348.

10. Mieli-Vergani G, Vergani D, Czaja AJ, Manns MP, Krawitt EL, Vierling JM, et al. Autoimmune hepatitis. Nat Rev Dis Primers. 2018; 4(1):18017. PMID: 29644994.

11. Yeong TT, Lim KH, Goubet S, Parnell N, Verma S. Natural history and outcomes in drug-induced autoimmune hepatitis. Hepatol Res. 2016; 46(3):E79–88. PMID: 25943838.

12. Chieli E, Saviozzi M, Menicagli S, Branca T, Gervasi PG. Hepatotoxicity and P-4502E1-dependent metabolic oxidation of N,N-dimethylformamide in rats and mice. Arch Toxicol. 1995; 69(3):165–170. PMID: 7717872.

13. Koh SB, Cha BS, Park JK, Chang SH, Chang SJ. The metabolism and liver toxicity of N,N-dimethylformamide in the isolated perfused rat liver. Yonsei Med J. 2002; 43(4):491–499. PMID: 12205738.

14. Gong W, Liu X, Zhu B. Dimethylacetamide-induced occupational toxic hepatitis with a short term recurrence: a rare case report. J Thorac Dis. 2016; 8(6):E408–11. PMID: 27293868.

15. Hamada M, Abe M, Tokumoto Y, Miyake T, Murakami H, Hiasa Y, et al. Occupational liver injury due to N,N-dimethylformamide in the synthetics industry. Intern Med. 2009; 48(18):1647–1650. PMID: 19755767.

16. Zhang XT, Kuang XY, Feng YM. Clinical report of occupational acute dimethylformamide poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011; 29(6):445–446. PMID: 22096861.

17. Zhang H, Liu Q, Duan Y, Dong H, Zhou Y. Chronic occupational N, N-dimethylformamide poisoning induced death: a case report. Forensic Sci Med Pathol. 2015; 11(4):584–588. PMID: 26335788.

18. Lei Y, Xiao S, Chen S, Zhang H, Li H, Lu Y. N,N-dimethylformamide-induced acute hepatic failure: a case report and literature review. Exp Ther Med. 2017; 14(6):5659–5663. PMID: 29285107.

19. He J, Zhai MF, Shi YX. Eight cases of chronic severe liver diseases in workers exposed to dimethylformamide. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2005; 23(6):471–472. PMID: 16405796.

20. Wu HC, Fang J, Li DL. Clinical analysis of acute liver failure induced by dimethylformamide. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2018; 36(3):216–218. PMID: 29996228.