A rare case of Steven’s-Johnson Syndrome with overt hepatitis

Introduction

Steven’s- Johnson syndrome is a severe mucocutaneous reaction, mostly due to medications. It is characterized by extensive epidermal necrosis and detachment. It involves atleast two mucous membranes such as oral, genital or conjunctiva.

Steven’s-Johnson syndrome and Toxic epidermal necrolysis are considered as a disease continuum and are distinguished by the severity and body surface area of epidermal separation. SJS is less severe condition with less than 10% epidermal detachment.¹

SJS can occur at any age. It is more common in women than men with an incidence ratio of 1:2.

The incidence is more in HIV affected individuals and patients with various neoplasms than in general population. The mortality in SJS is approximately 10% and may go up to 50% in TEN cases.

Risk factors

1. HIV infection due to multitude of drugs used and immune dysregulation.
2. Malignancies.
3. Genetic factors- Certain HLAs are associated with a susceptibility to specific group of drugs. HLA-B*1202, HLA-B*1511,HLA-A*3101, HLA-A*2402 exhibit an increased susceptibility to carbamazepine and other aromatic anticonvulsants. HLA-B*1301 is associated with dapsone sensitivity. HLA-B*5801 is associated with allopurinol sensitivity 6-8. Gene polymorphism involving CYP2C19 gene is associated with an increased risk for SJS/TEN to anticonvulsants like phenytoin, phenobarbital and carbamazepine.
4. Other risk factors include systemic lupus erythematosus.²

Aetiology

1. Medications are the leading cause of SJS in both adults and children. The risk of SJS seems to be limited to first 8 weeks of treatment. Drugs used for a longer duration are less likely to cause SJS. It typically presents anytime between four days to four weeks after starting the drug administration. Most common group of drugs involved are anticonvulsants, antibiotics, analgesics, antiretroviral drugs and allopurinol.
2. Other causes include Mycoplasma pneumoniae infection, vaccinations, radio- contrast medium, systemic diseases, herbal medication and food.³

Clinical presentation

1. Prodrome with fever often more than 390 C and flu-like symptoms precede by one or three days the development of mucocutaneous lesions.

2. Cutaneous lesions typically begin with illdefined, erythematous macules that coalesce with purpuric centres or may present with diffuse erythema. Atypical target lesions with darker centres can be present. With disease progression vesicles and bullae may develop and within days begin to slough.

3. Mucosal involvement is seen in 90% cases of SJS and can precede or follow the skin eruption. Painful crusting and erosions can occur. It can involve oral, ocular and urogenital mucosa.⁴

Laboratory investigations

• Haematological abnormalities such asanemia, lymohopenia.

• Hypoalbuminemia, electrolyte imbalance and increased blood urea nitrogen.

• In severe cases raised glucose.⁵ 

Mild elevation of serum aminotransferases (two to three fold raise above normal levels) may be noted in about 50% cases of TEN. Overt hepatitis is seen approximately in 10% cases. In SJS overt hepatitis is quite rare.⁶

Case report

A 22-years female presented with redness and discharge from the eyes, crusting of lips from 2 days and reddish rashes on the body since 1 week. She gave history of fever and cough 1 week back for which she was treated with Tab. Diclofenac and Tab. Amoxicillin.  2 days later she developed redness and watery discharge from the eyes, which became mucopurulent and developed crusting of lips. She was then treated with Tab. Oseltamavir, Tab. Pantoprazole and a combination tablets containing paracetamol, phenylephrine and chlorpheniramine. She then developed crusting of lips and reddish rashes over the body.

On examination, she was febrile and she had icterus and cervical lymphadenopathy. Cutaneous examination showed erythematous maculopapular lesions with target lesions distributed over the face, neck, trunk and few over the extremities with few flaccid bullae over the trunk (Fig. 1 & 2). Oral examination showed erosions over the buccal mucosa and palate with haemorrhagic crust over the lips. Genital mucosa, hair and nail were normal (Fig.3).

Investigations showed raised total leucocyte count and ESR and deranged serum electrolytes and liver function tests with serum bilirubin being 5.36 (upper limit 1.2), SGOT of 646(upper limit 35), SGPT of 1438 (upper limit 40) and alkaline phosphatase levels of 176 (upper limit 110). HSV IgG and IgM were done since she had target lesions. Since the liver enzymes were elevated more than thrice the normal upper limit, viral titres for HBsAg , HAV, HCV,HEV were done to rule out viral hepatitis and ANA global to rule out autoimmune hepatitis. As all of these tests were negative, it was concluded that this severe hepatitis is secondary to drug reaction and the patient was diagnosed with Steven’s- Johnson syndrome with a SCORTEN of¹.

The patient was managed by the dermatologists with involvement of the physician, gastroenterologist and ophthalmologist. She was started on IV fluids and inj. Betamethasone 4 mg TID and was tapered. Proper eye care was given and she was put on hepatoprotective drugs. The levels of liver enzymes started to fall the following day which indicates that the liver injury was transient. The patient was followed up for 8 weeks after the discharge until the liver function tests were normal. 

Discussion

Hepatic involvement in SJS

Medications are the common cause of SJS and drug induced liver injury. But the concomitant occurrence of SJS and DILI is a rare phenomenon. In a retrospective study of 748 patients with DILI, only 36 cases had both SJS and DILI (4.8%) and it was associated with a higher mortality rate of 22%. Patients affected are typically young females, and only a small number of high risk drugs such as antiepileptics, sulphonamdies and antiretroviral drugs accounted for majority of cases.⁷

SGPT is more specific for viral or drug induced liver injury than SGOT which is elevated more often in alcoholic hepatitis. Elevation of both serum aminotransferases and bilirubin with clinical jaundice indicate sub-fulminant hepatitis as was seen in our patient. Elevated serum alkaline phosphatase levels indicate acute intrahepatic cholestasis. The liver function tests should be repeated after 72 hours after initial investigations to determine if the levels are increasing or decreasing. The liver function tests should be monitored till the levels reaches the normal range .Persistent elevation of serum alkaline phosphatase levels beyond 30 days is a predictor of chronicity of hepatic injury.⁸

Conclusion

Drug induced liver injury is rare in SJS cases. Presence of liver injury with raised bilirubin increases the mortality rate. Early identification and discontinuation of offending drug is the main stay of management. Practice of polypharmacy has increased the incidence of drug reaction and also poses a challenge for identification of offending drug, which is crucial to prevent catastrophic occurrence of drug reactions in future. From this case report it is imperative that serious liver injuries can occur in SJS cases and has to be watched for.