Table Info

Table 1.

Characteristics of the patients

Case	Clinical presentation	Drug possibly involved	Skin rash present	Day of definite diagnosis	Total WBC/Eosinoph (G/L)	AST/ALT (IU/L)	ALP pANCA/GGT (IU/L)	Bilirubin (umol/L)	INR	Negative screening Tests	Day starting steroids	Clinical outcome	RegiSCAR Score (points)
1. Male 34 years old	Cough, fever (39.3°C) and severely impaired liver function test	Oral amoxicillin/clavulanic acid for 7 days 2 weeks before admission	Not on onset Pruritic rash is seen by day 10 (thorax and legs)	5, by histology findings based on a transjugular liver biopsy + rising eosinophilia (10.7 G/L)	14.60/1.53 (max. 18.41)	2,124/2,504	113/180	26	1.9	HAV, HBV, HCV, HEV, HSV-1, HSV-2 VZV, CMV, EBV, HIV 1 + 2, Parvovirus B 19, HHV-6, HHV-7, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila (Urine), Influenza A, Influenza B, RSV, Strongyloides, intestinal protozoa and helminths. ANA, pANCA, SMA, SLA, LKM-1, AMA, IgG and IgM, ceruloplasmin, alpha-1-antitrypsin	Day 5; prednisone 60 mg and tapered	It was rapidly improved on steroids. Flare at day 10: increase of steroids. Discharged on day 12.	4 (fever = 0, rash = 1, eosinophilia = 1, liver involved = 1, other causes excluded = 1)
2. Male 61 years old	Fever (39°C), exanthema, severely impaired liver function test	Ciprofloxacin	Diffuse maculopapular rash	5, based on liver biopsy	12.0/0.8	650 (max. 18.473)/680 (max. 6,745)	180/423	46	1.8	HAV, HBV, HCV, HEV, HSV-1, HSV-2 VZV, CMV, EBV, HIV 1 + 2, HHV-6, Parvovirus B 19, Strongyloides, intestinal protozoa and helminths. ANA, pANCA, SMA, SLA, LKM-1, AMA, IgG and IgM, ceruloplasmin, alpha-1-antitrypsin, Aspergillus (Galactomannan antigen), β-d-Glucan	Day 5; prednisone 25 mg Day 17; methylprednisolone, 250 mg i.v.	Rapidly progressive deterioration of liver function and multiorgan failure. Liver trans-plantation at day 20. Exitus letalis 16 days after LT.	4 (fever = 0, rash = 1, eosinophilia = 1, liver involved = 1, other causes excluded = 1)
3. Male 60 years old	Fever, rash, cough, and vomiting	Phenytoin Levetiracetam	Pruritic maculopapular rash	4, on histology findings	12.0/4.24 (max. 13.6)	135/308	317/1,688	75	1.16	HAV, HBV, HCV, HEV, HSV-1, HSV-2, VZV, CMV, EBV, HIV 1 + 2, Parvovirus B 19, HHV-6, HHV-7, Mycoplasma pneumoniae, Chlamydia pneumonia, TBC, Strongyloides, intestinal protozoa and helminths.ANA, pANCA, SMA, SLA, LKM-1, AMA, IgG and IgM, ceruloplasmin, alpha-1-antitrypsin	Day 4; prednisone 1 mg/kg	Progressive improved on steroids.	6 (fever = 0, rash = 2, eosinophilia = 1, atypical lymphocytes = 1, liver involved = 1, other causes excluded = 1)
4. Female 62 years old	Jaundice and rash	Cefuroxime	Diffuse maculopapular Rash	2, on histology findings based on a liver biopsy	6.3/1.31	383/497	756/550	217	< 1.0	HAV, HBV, HCV, HEV, HSV-1, HSV-2 VZV, CMV, EBV, HIV 1 + 2, HAV, HHV6, intestinal protozoa and helminths.ANA, pANCA, SMA, SLA, LKM-1, AMA, IgG and IgM, ceruloplasmin, alpha-1-antitrypsin	Day 2; prednisone 40 mg and tapered)	Rapidly improved on steroids.	4 (rash = 1, eosinophilia = 1, liver involved = 1, other causes excluded = 1)
5. Male 65 years old	Progressive exanthema and elevation of ASAT, ALAT, GGT and AP	Lamotrigine	Diffuse maculopapular rash	The diagnosis was suspected by clinical mani-festations, it was not confirmed by biopsy	10.8/1.18	264/659	219/106	8	1.2	HBV, HCV, HEV, HSV-1, HSV-2 VZV, CMV, EBV, HIV 1 + 2, HAV, intestinal protozoa and helminths.ANA, pANCA, SMA, SLA, LKM-1, AMA, IgG and IgM, ceruloplasmin, alpha-1-antitrypsin	Day 14; 125 mg methylprednisolone i.v., then prednisone 60 mg and tapered	Progressive improved on steroids.	4 (rash = 1, eosinophilia = 1, liver involved = 1, other causes excluded = 1)

WBC: white blood cells; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; GGT: gamma-glutamyl transferase; INR: international normalized ratio; LT: Liver transplantation; i.v: intravenous; HAV: hepatitis A virus; HBV: hepatitis B virus; HCV, hepatitis C virus; HEV: hepatitis E virus; HSV: herpes simplex virus; VZV: varicella-zoster virus; CMV: cytomegalovirus; EBV: Epstein-Barr virus; HIV: human immunodeficiency virus; HHV: human herpes virus; ANA: antinuclear antibodies; SMA: smooth muscle antibodies; SLA: anti-soluble liver antigen antibodies; LKM-1: liver kidney microsome type 1 antibodies; pANCA: anti-neutrophil cytoplasmic antibodies; AMA: antimitochondrial antibodies; IgG: total immunoglobulin G; IgM: total immunoglobulin M

Declarations

Author contributions

The authors confirm contribution to the paper as follows: study conception and design: MGD, FB, AB, JFD. Data collection: MGD, FB, SC, MM. Analysis and interpretation of results: MGD, JFD, AB. Draft manuscript preparation: MGD, JFD, AB, SC, FB. All authors reviewed the results and approved the final version of the manuscript.

Conflicts of interest

No author has any conflict of interest.

Ethical approval

All patients provided written consent to the use of their health-related data for research. The hospital ethics committee approved collection of patient information and the study protocol, which was consistent with the principles of the current version of the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, and local regulatory requirements.

Consent to participate

All patients provided written consent to the use of their health-related data for research.

Consent to publication

Not applicable.

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

Not applicable.

Copyright

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