The Journal is included in Russian and International Library and Abstract Databases
Russain Science Index (Russia)
EBSCO
DOI Registration Agency (USA)

On hepatotoxicity of drugs used in dermatology

DOI: https://doi.org/10.29296/25877305-2020-09-09
Issue: 
9
Year: 
2020

E. Denisova(1, 4), Candidate of Medical Sciences; M. Denieva(2, 3), Candidate of Medical
Sciences; E. Dvoryankova(1), MD; K. Plieva(4); V. Sobolev(1), Candidate of Biological Sciences; Professor I.
Korsunskaya(1), MD (1)Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of
Sciences, Moscow (2)Chechen State University, Groznyi (3)Republican Dermatovenereology Dispensary, Groznyi
(4)Moscow Research and Practical Center for Dermatovenereology and Cosmetology, Moscow Healthcare
Department, Moscow

Cutaneous reactions to various drugs are quite common, whereas hepatic reactions occur less frequently and may go unnoticed. Many drugs can damage the liver injuries; antiepileptic drugs, allopurinol, sulfonamides, antibiotics, and nevirapine are among the top 5 most common causes of drug-induced liver injuries. But let us not forget that the list of such drugs is much longer and it includes drugs that are widely used in different fields of medicine. Thus, systemic retinoids used long-term cause changes in blood biochemical parameters; these changes are often transient and do not require treatment discontinuation. Cyclosporine used to treat autoimmune diseases can cause increased creatinine levels and acute cholecystitis. Long-term use of methotrexate, even at low doses, or administration of systemic glucocorticosteroids can induce steatosis and other liver injuries. When prescribing medications that can cause disturbances in the hepatobiliary system, it is necessary to take into account a patient’s medical history and concomitant diseases, to regularly monitor blood biochemical parameters, and to incorporate hepatoprotective agents in therapy. The physician should also take into consideration possible drug interactions with the medications that the patient is already taking; this is particularly important in terms of the widespread use of polypharmacy. In our practice, we often give preference to a medication containing glycyrrhizic acid and essential phospholipids, since this combination has not only a hepatoprotective effect, but also has an anti-inflammatory effect. The inclusion of hepatoprotective agents in therapy on the first days allows avoidance of unwanted hepatotoxic effects that may be asymptomatic or irreversible in some cases.

Keywords: 
hepatology
dermatology
hepatotoxicity
hepatoprotectors
glycyrrhizic acid
essential phospholipids
liver injuries



References: 
  1. Devarbhavi H., Raj S. Drug-induced liver injury with skin reactions: Drugs and host risk factors, clinical phenotypes and prognosis. Liver Int. 2019; 39 (5): 802–11. DOI: 10.1111/liv.14004
  2. Andrade R.J., Chalasani N., Björnsson E.S. et al. Drug-induced liver injury. Nat Rev Dis Primers. 2019; 5 (1): 58. DOI: 10.1038/s41572-019-0105-0
  3. Liu L.U., Schiano T.D. Vitamin A (retinol). Hepatotoxicity of herbal medications, vitamins and natural hepatotoxins. In, Kaplowitz N., DeLeve L.D., eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007; pp. 744–6.
  4. Grimaud J.C., Langier R., Costa-Legre M.C. et al. Hepatitis due to etretinate. Presse Med. 1985; 14: 844–5.
  5. Kreiss C., Amin S., Nalesnik M.A. et al. Severe cholestatic hepatitis in a patient taking acitretin. Am J Gastroenterol. 2002; 97: 775–7.
  6. Pang M.L., Murase J.E., Koo J. An updated review of acitretin-a systemic retinoid for the treatment of psoriasis. Expert Opin Drug Metab Toxicol. 2008; 4: 953–64. DOI: 10.1517/17425255.4.7.953
  7. Chalasani N., Fontana R.J., Bonkovsky H.L. et al. Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008; 135: 1924–34.
  8. Sauder M.B., Cheung L., Beecker J. Acitretin-induced hepatitis: when to monitor cholestatic enzymes. J Cutan Med Surg. 2015; 19: 115–20. DOI: 10.2310/7750.2014.14051
  9. Kragballe K., Jansen C.T., Geiger J.M. et al. A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study. Acta Dermatol Venereol. 1989; 69: 35–40.
  10. Lérisson M., Ripault M.P., Pageaux G.P. et al. Hepatitis after retinoid percutaneous administration. Clin Res Hepatol Gastroenterol. 2014; 38: e99-e101.
  11. Pona A., Cardenas-de la Garza J.A., Haidari W. et al. Abnormal liver function tests in acne patients receiving isotretinoin. J Dermatolog Treat. 2019; 1–4. DOI: 10.1080/09546634.2019.1662882
  12. Colombo D., Cassano N., Altomare G. et al. Psoriasis relapse evaluation with week-end cyclosporine A treatment: results of a randomized, double-blind, multicenter study. Int J Immunopathol Pharmacol. 2010; 23 (4): 1143–52. DOI: 10.1177/039463201002300418
  13. Khattri S., Shemer A., Rozenblit M. et al. Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology. J Allergy Clin Immunol. 2014; 133 (6): 1626–34. DOI: 10.1016/j.jaci.2014.03.003
  14. Klintmalm G.B., Iwatsuki S., Starzl T.E. Cyclosporin A hepatotoxicity in 66 renal allograft recipients. Transplantation. 1981; 32 (6): 488–9. DOI: 10.1097/00007890-198112000-00007
  15. Kahan B.D., Flechner S.M., Lorber M.I. et al. Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years. Transplantation. 1987; 43 (2): 197–204. DOI: 10.1097/00007890-198702000-00007
  16. Lorber M.I., Van Buren C.T., Flechner S.M. et al. Hepatobiliary and pancreatic complications of cyclosporine therapy in 466 renal transplant recipients. Transplantation. 1987; 43 (2):35–40. DOI: 10.1097/00007890-198701000-00009
  17. Chalasani N., Bonkovsky H.L., Fontana R. et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015; 148: 1340–52.e7. DOI: 10.1053/j.gastro.2015.03.006
  18. Harper J.I., Ahmed I., Barclay G. et al. Cyclosporine for severe childhood atopic dermatitis: short course versus continuous therapy. Br J Dermatol. 2000; 142 (1): 52–8. DOI: 10.1046/j.1365-2133.2000.03241.x
  19. Walker D, Jacobe H. Phototherapy in the age of biologics. Semin Cutan Med Surg. 2011; 30: 190–8. DOI: 10.1016/j.sder.2011.08.004
  20. Berg M., Ros A.M. Treatment of psoriasis with psoralens and ultraviolet A. A double-blind comparison of 8-methoxypsoralen and 5-methoxypsoralen. Photodermatol Photoimmunol Photomed. 1994; 10: 217–20.
  21. Choi H.J., Kim S., Hann S.K. et al. The effect on liver transaminases of 5-methoxypsoralen used in systemic photochemotherapy. Ann Dermatol. 1995; 7: 51–3.
  22. McNeely W., Goa K.L. 5-methoxypsoralen: a review of its effects in psoriasis and vitiligo. Drugs. 1998; 56: 667–90. DOI: 10.2165/00003495-199856040-00015
  23. 23. Wenk K.S., Arrington K.C., Ehrlich A. Psoriasis and non-alcoholic fatty liver disease. J Eur Acad Dermatol Venereol. 2011; 25: 383–91. DOI: 10.1111/j.1468-3083.2010.03841.x
  24. Langman G., Hall P.M., Todd G. Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol. 2001; 16: 1395–401. DOI: 10.1046/j.1440-1746.2001.02644.x
  25. Haustein U.F., Rytter M. Methotrexate in psoriasis: 26 years’ experience with low-dose long-term treatment. J Eur Acad Dermatol Venereol. 2000; 14: 382–8. DOI: 10.1046/j.1468-3083.2000.00058.x
  26. Ng L.C., Lee Y.Y., Lee C.K. et al. A retrospective review of methotrexate-induced hepatotoxicity among patients with psoriasis in a tertiary dermatology center in Malaysia. Int J Dermatol. 2013; 52: 102–5. DOI: 10.1111/j.1365-4632.2011.05436.x
  27. Ros S., Juanola X., Condom E. et al. Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis patients receiving long-term methotrexate therapy. Scand J Rheumatol. 2002; 31: 330–6. DOI: 10.1080/030097402320817040
  28. Candelli M., Nista E.C., Pignataro G. et al. Steatohepatitis during methylprednisolone therapy for ulcerative colitis exacerbation. J Intern Med. 2003; 253: 391–2. DOI: 10.1046/j.1365-2796.2003.01108.x
  29. Stravitz R.T., Sanyal A.J. Drug-induced steatohepatitis. Clin Liver Dis. 2003; 7: 435–51. DOI: 10.1016/s1089-3261(03)00027-8
  30. Dourakis S.P., Sevastianos V.A., Kaliopi P. Acute severe steatohepatitis related to prednisolone therapy. Am J Gastroenterol. 2002; 97: 1074–5. DOI: 10.1111/j.1572-0241.2002.05644.x
  31. Shiota G., Harada K., Oyama K. et al. Severe exacerbation of hepatitis after short-term corticosteroid therapy in a patients with «latent» chronic hepatitis B. Liver. 2000; 20: 415–20.
  32. Takahashi A., Kanno Y., Takahashi Y. et al. Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis: a case report. World J Gastroenterol. 2008; 14 (35): 5474–7. DOI: 10.3748/wjg.14.5474
  33. Marinó M., Morabito E., Brunetto M.R. et al. Acute and severe liver damage associated with intravenous glucocorticoid pulse therapy in patients with Graves’ ophthalmopathy. Thyroid. 2004; 14: 403–6. DOI: 10.1089/105072504774193276
  34. Mehtiev S.N., Mehtieva O.A., Smirnova M.N. Fibroz pecheni kak pokazanie dlja terapii u bol'nyh hronicheskimi gepatitami. Effektivnaja farmakoterapija. 2015; 2: 22–33 [Mehtiyev S.N., Mehtiyeva O.A., Smirnova M.N. Liver fibrosis as an indication for therapy in patients with chronic hepatitis. Effektivnaya farmakoterapiya. 2015; 2: 22–33 (in Russ.)].
  35. Vasilenko I.A., Dolgova G.V., Sorokoumova G.M. i dr. Sravnitel'noe izuchenie gepatoprotektivnyh preparatov Essentsiale® forte N, Fosfogliv, Essliver forte. RMZh. 2013; 21 (13): 681–4 [Vasilenko I.A., Dolgova G.V., Sorokoumova G.M. et al. Sravnitel’noe izuchenie gepatoprotektornykh preparatov Essentsiale® forte N, Fosfogliv, Essliver forte. RMZh. 2013; 21 (13): 681–4 (in Russ.)].
  36. Nedogoda S.V., Chumachek E.V., Sanina M.S. i dr. Preparat «Fosfogliv®» v terapii nealkogol'noj zhirovoj bolezni pecheni: predvaritel'nye rezul'taty mnogotsentrovogo randomizirovannogo dvojnogo slepogo platsebokontroliruemogo issledovanija «Gepard» (PHG-M2/ P02-12). Klinicheskie perspektivy gastroenterologii, gepatologii. 2015; 5: 16–22 [Nedogoda S.V., Chumachek Ye.V., Sanina M.S. et al. «Phosphogliv®» for non-alcoholic fatty liver disease: multicenter randomized double blind placebo-controlled trial «Cheetah» (PHG-M2/P02-12). Pilot report. Klinicheskie perspektivy gastroenterologii, gepatologii. 2015; 5: 16–22 (in Russ.)].
  37. Denisova E.V., Dvorjankova E.V., Plieva K.T. i dr. Patologii gepatobiliarnoj sistemy u bol'nyh psoriazom. Effektivnaja farmakoterapija. 2018; 21: 18–23 [Denisova Ye.V., Dvoryankova Ye.V., Pliyeva K.T. et al. Pathology of the Hepatobiliary System in Patients with Psoriasis. Effektivnaya farmakoterapiya. 2018; 21: 18–23 (in Russ.)].
  38. Denisova E.V., Dvorjankova E.V., Denieva M.I. i dr. Obosnovanie primenenija gepatoprotektorov pri psoriaze. Vrach. 2018; 29 (9): 85–8 [Denisova E., Dvoryankova E., Denieva M. et al. Rationale for the use of hepatoprotective agents in the treatment of psoriasis. Vrach. 2018; 29 (9): 85–8 (in Russ.)]. https://doi.org/10.29296/25877305-2018-09-20
  39. Piruzjan A.L., Denisova E.V., Dvorjankova E.V. i dr. Vlijanie lipidnogo profilja na komorbidnye sostojanija pri psoriaze. Vrach. 2019; 30 (10): 32–4 [Piruzyan A., Denisova E., Dvoryankova E. et al. Combination pathogenetic therapy for psoriasis: relief of inflammation and correction of metabolic disorders. Vrach. 2019; 30 (10): 32–4 (in Russ.)]. https://doi.org/10.29296/25877305-2019-10-06