Infectious mononucleosis with atypical presentation

We report the case of a 27-year-old man allergic to dexketoprofen with no medical history of note, who visited his health centre with odynophagia and a fever for the past 10 days. Given that bacterial pharyngotonsillitis was suspected, he was given empirical antibiotic therapy with amoxicillin 500 mg every eight hours. Three days later, his initial signs and symptoms had not improved, and he had developed jaundice, choluria, nausea and diarrhoea with no pathological signs, whereupon he visited the accident and emergency department. He denied using other medicines, recreational drugs or herbal medicines. Physical examination revealed: a fever of 39 °C, jaundice, painful hepatomegaly, bilateral laterocervical oedema and oropharyngeal erythema. Blood testing yielded the following findings: leukocytosis 25.90 × 10⁹/l with lymphocyte predominance (16.20 × 10⁹/l), total bilirubin 15.5 mg/dl (direct bilirubin 9.43 mg/dl), aspartate aminotransferase (AST) 211 U/l, alanine aminotransferase (ALT) 280 U/l, alkaline phosphatase (ALP) 443 U/l, gamma-glutamyl transferase (GGT) 314 U/l, lactate dehydrogenase (LDH) 1,102 U/l and C-reactive protein 24.7 mg/l. Abdominal ultrasound reported hepatomegaly with no focal lesions, splenomegaly measuring 16.7 cm, two enlarged lymph nodes in the hepatic hilum of nonspecific significance and intrahepatic and extrahepatic bile ducts normal in calibre. A decision was made to admit him to gastroenterology. During his admission, he had persistent intermittent fever and developed a morbilliform, maculopapular, erythematous skin rash on his trunk, arms and thighs. Blood cultures were negative. Serology testing for hepatotropic viruses and human immunodeficiency virus (HIV), as well as computed tomography (CT) of the neck, chest and abdomen, ruled out a lymphoproliferative syndrome and revealed enlarged lymph nodes throughout the neck, chest and abdomen (measuring less than 1 cm with no cavitation), homogeneous hepatosplenomegaly and scant ascites. Follow-up laboratory testing four days into the patient’s admission showed worsening of his liver panel, with peak total bilirubin 20.38 mg/dl (direct bilirubin 13.3 mg/dl), AST 263 U/l, ALT 294 U/l, ALP 648 U/l and GGT 513 U/l.

Serology testing was positive for Epstein–Barr virus (EBV) anti-viral capsid antigen (VCA) IgM antibodies (>160 U/mL); the rest of the serology testing ordered was negative (hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV], hepatitis E virus [HEV], cytomegalovirus [CMV], varicella zoster virus [VZV], herpes simplex virus [HSV], HIV and Treponema pallidum). This confirmed a definitive diagnosis of infectious mononucleosis with predominantly hepatic involvement and a skin rash secondary to administration of amoxicillin in a context of acute EBV infection. Symptomatic treatment was administered from the start; ultimately, a decision was made to initiate treatment with intravenous ganciclovir at a dose of 5 mg/kg every 12 h due to the seriousness of the clinical picture. Subsequently, the patient showed rapid clinical and laboratory improvement, with total bilirubin 9 mg/dl (direct bilirubin 6.64 mg/dl), AST 146 U/l and ALT 360 U/l following five days of antiviral treatment, and therefore was discharged after 10 days of admission. Follow-up laboratory testing four weeks after discharge revealed a complete return to normal of the patient’s liver panel.

EBV is a widespread herpes virus with an estimated global seroprevalence of 90%–95% in adults.¹ Most cases of EBV infection are asymptomatic; however, the infection may present with the typical triad of fever, pharyngotonsillitis and lymphadenopathy; this is known as infectious mononucleosis.² Slight elevation of transaminases is common, but jaundice and cholestasis in this context are rare, having an incidence of less than 5%.^1–3 Rare cases of fulminant liver failure, largely in immunocompromised patients, have been published.^4,5 The pathophysiology of jaundice secondary to EBV infection is not well understood, although it is believed that it may be primarily related to immune-mediated mechanisms.^1,2

Treatment for infectious mononucleosis is mainly symptomatic.^1,2 The indication for antiviral agents in this condition is not well established due to a lack of evidence of their efficacy.^1,2 However, the literature does feature case reports with severe hepatic involvement that followed a good clinical course subsequent to administration of antiviral agents.^6,7

In conclusion, EBV infection should be included in the differential diagnosis of acute icteric hepatitis, despite the rarity of this situation. Although there is little evidence, there are several case reports of successful treatment with ganciclovir.