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Dubin-Johnson syndrome — Clinical Guidelines

Overview

Dubin-Johnson syndrome is a rare, benign hepatocellular carcinoma characterized by chronic jaundice due to benign enlargement of the liver with black pigment deposition in hepatocytes. It is typically asymptomatic beyond the presence of persistent jaundice and does not involve severe mucocutaneous reactions seen in conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis. 1 6 16

Diagnosis

Clinical Presentation: Persistent jaundice, mild elevation of liver enzymes, and characteristic dark pigmentation of the liver (black liver syndrome).

Imaging: Ultrasound or CT showing enlarged liver with characteristic pigmentation.

Liver Biopsy: Confirms the presence of pigmented deposits in hepatocytes.

Laboratory Tests: Elevated bilirubin levels, normal or minimally elevated transaminases.

Differential Diagnosis: Excludes other causes of chronic jaundice such as viral hepatitis, primary biliary cholangitis, and other liver disorders. 6 16

Management

Supportive Care: Management focuses on addressing symptoms and complications like pruritus.

Monitoring: Regular follow-up to monitor liver function and overall health status.

Avoidance of Hepatotoxic Agents: Minimize exposure to substances that could exacerbate liver function.

No Specific Pharmacological Treatment: No curative medication; treatment is largely supportive. 6 16

Special Populations

Pediatrics: Limited data; management similar to adults with close monitoring for developmental impacts.

Elderly: Increased vigilance for complications due to comorbid conditions; supportive care tailored to individual needs. 15

Key Recommendations

Regular Monitoring of Liver Function: Essential for early detection of any changes in liver status. (Evidence: Moderate 6)

Avoidance of Hepatotoxic Medications: Minimize risk of further liver damage by avoiding known hepatotoxic agents. (Evidence: Expert opinion 16)

Supportive Care for Symptoms: Address symptoms like pruritus to improve quality of life. (Evidence: Moderate 6)

References

1 AlFada M, Alotaibi H, Alsharif S, Alani AH, Andrade-Miranda A, Montesinos Guevara C et al.. Systematic review, methodological appraisal, and recommendation mapping of clinical practice guidelines for managing patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. The Journal of dermatological treatment 2025. link 2 Kemény L. Editor's Highlights-May 2025. International journal of dermatology 2025. link 3 Sato S, Ooka T, Zamami Y, Hamano H, Hayashi F, Eguchi E et al.. Identifying New Candidate Predictors of Mortality in Japanese Patients with Severe Drug Eruptions. Drug safety 2025. link 4 Yan X, Ma J, Guo C, Yang G. Association of antibiotics with Stevens-Johnson syndrome and toxic epidermal necrolysis: A real-world pharmacovigilance study. International journal of antimicrobial agents 2025. link 5 Bayram-Ozgur D, Colak O, Gultekin O, Akici N, Onal ZE, Akici A. Pediatric Stevens-Johnson syndrome and toxic epidermal necrolysis: age-stratified insights from the FAERS database. Jornal de pediatria 2025. link 6 Cheung CMT, Chang MM, Li JJX, Chan AWS. Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong. Hong Kong medical journal = Xianggang yi xue za zhi 2024. link 7 Tang R, Lopes VL, Caffrey AR. Colistin-associated Stevens-Johnson syndrome and toxic epidermal necrolysis reactions: a retrospective case-non-case pharmacovigilance study. Expert opinion on drug safety 2022. link 8 Nguyen KD, Tran TN, Nguyen MT, Nguyen HA, Nguyen HA, Vu DH et al.. Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in vietnamese spontaneous adverse drug reaction database: A subgroup approach to disproportionality analysis. Journal of clinical pharmacy and therapeutics 2019. link 9 Syu FK, Pan HY, Chuang PC, Huang YS, Cheng CY, Cheng FJ. Incidence of Stevens-Johnson syndrome following combination drug use of allopurinol, carbamazepine and phenytoin in Taiwan: A case-control study. The Journal of dermatology 2018. link 10 Papp A, Sikora S, Evans M, Song D, Kirchhof M, Miliszewski M et al.. Treatment of toxic epidermal necrolysis by a multidisciplinary team. A review of literature and treatment results. Burns : journal of the International Society for Burn Injuries 2018. link 11 Wolf B, Sadoff R, Nannini V. Toxic Epidermal Necrolysis: A Dermatologic Emergency and the Role of the Oral and Maxillofacial Surgeon. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 2018. link 12 Borrelli EP, Lee EY, Descoteaux AM, Kogut SJ, Caffrey AR. Stevens-Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs: An analysis of the US Food and Drug Administration Adverse Event Reporting System. Epilepsia 2018. link 13 Li X, Zhao Z, Sun SS. Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2017. link 14 Cheung CS, Ali A, Chew HF. Successful Treatment of Acute Ocular-Involving Toxic Epidermal Necrolysis Using Amniotic Membrane Suture Fixated to Custom Designed Symblepharon Rings. Cornea 2016. link 15 Diphoorn J, Cazzaniga S, Gamba C, Schroeder J, Citterio A, Rivolta AL et al.. Incidence, causative factors and mortality rates of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in northern Italy: data from the REACT registry. Pharmacoepidemiology and drug safety 2016. link 16 Hinc-Kasprzyk J, Polak-Krzemińska A, Ożóg-Zabolska I. Toxic epidermal necrolysis. Anaesthesiology intensive therapy 2015. link 17 Burkhart KK, Abernethy D, Jackson D. Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome. Journal of medical toxicology : official journal of the American College of Medical Toxicology 2015. link 18 Papay J, Yuen N, Powell G, Mockenhaupt M, Bogenrieder T. Spontaneous adverse event reports of Stevens-Johnson syndrome/toxic epidermal necrolysis: detecting associations with medications. Pharmacoepidemiology and drug safety 2012. link 19 Fu Y, Gregory DG, Sippel KC, Bouchard CS, Tseng SC. The ophthalmologist's role in the management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis. The ocular surface 2010. link70234-3) 20 Ward KE, Archambault R, Mersfelder TL. Severe adverse skin reactions to nonsteroidal antiinflammatory drugs: A review of the literature. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2010. link 21 Valeyrie-Allanore L, Poulalhon N, Fagot JP, Sekula P, Davidovici B, Sidoroff A et al.. Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 2008. link 22 Gimnig JE, MacArthur JR, M'bang'ombe M, Kramer MH, Chizani N, Stern RS et al.. Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi. The American journal of tropical medicine and hygiene 2006. link 23 La Grenade L, Lee L, Weaver J, Bonnel R, Karwoski C, Governale L et al.. Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors. Drug safety 2005. link 24 Tsang MW, Tsang KY, Wong WK. The use of recombinant human epidermal growth factor (rhEGF) in a gentleman with drug-induced Steven Johnson syndrome. Dermatology online journal 2004. link 25 Hällgren J, Tengvall-Linder M, Persson M, Wahlgren CF. Stevens-Johnson syndrome associated with ciprofloxacin: a review of adverse cutaneous events reported in Sweden as associated with this drug. Journal of the American Academy of Dermatology 2003. link00478-x) 26 Mockenhaupt M, Kelly JP, Kaufman D, Stern RS. The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with nonsteroidal antiinflammatory drugs: a multinational perspective. The Journal of rheumatology 2003. link 27 Ball R, Ball LK, Wise RP, Braun MM, Beeler JA, Salive ME. Stevens-Johnson syndrome and toxic epidermal necrolysis after vaccination: reports to the vaccine adverse event reporting system. The Pediatric infectious disease journal 2001. link 28 Strom BL. Data validity issues in using claims data. Pharmacoepidemiology and drug safety 2001. link 29 Ramadasan P, Chaudhury S, Vaishampayne S, John TR. Stevens-Johnson syndrome due to carbamazepine. The Journal of the Association of Physicians of India 2000. link 30 Halevy S, Cohen AD, Livni E. The diagnostic role of the in vitro drug-induced interferon-gamma release test in Stevens-Johnson syndrome. International journal of dermatology 1999. link 31 Fawcett RG. Erythema multiforme major in a patient treated with carbamazepine. The Journal of clinical psychiatry 1987. link

Dubin-Johnson syndrome