Acute hepatitis due to infectious mononucleosis in a 21-year-oldman

A 21-year-old male was admitted because of fever, fatigue, headache, pharyngitis, abdominal pain, loss of appetite, vomiting and dark urine for three days. The patient denied recent use of medicines or any other drug. His physical examination disclosed jaundice, hepato-splenomegaly, whitish-yellow covered tonsils, bilateral anterior and posterior cervical lymph node enlargement associated with edema on the face and neck. Routine blood tests detected abnormalities in serum bilirubins and liver enzymes (total bilirubin: 14.5 mg/dl, direct-reacting bilirubin: 12.9 mg/dl, AST: 697 U/l, ALT: 619 U/l, alkaline phosphatases: 260 U/l, and GGT: 413 U/l). Serological tests showed negative results for viral hepatitis, cytomegalovirus, HIV-1 and HIV-2, and toxoplasmosis markers, while serology for recent infection by EBV was positive (IgM: 70 and 29 U/ml; EBV IgG: 25 and 156 U/ml). Although infrequently, EBV infection can cause acute hepatitis with accentuated cholestatic jaundice (5% of cases), which may constitute an additional diagnostic challenge for primary care physicians. The patient improved with supportive management and was discharged after 12 days. This case study might contribute to increase the suspicion index about acute hepatitis related to EBV. (Rev Med Chile 2013; 141: 917-921).


Case report
A 21-year-old male was admitted because of fever, fatigue, headache, pharyngitis, abdominal pain, loss of appetite, vomiting and dark urine for three days.He did not take any medicine previously to admission, and denied use of illicit drugs, alcohol abuse or tobacco smoking.A vaccinated cat is his pet, and his girl-friend had a recent "flu-like" condition.His physical examination disclosed hepatomegaly, splenomegaly, enlarged tonsils with white exudates and injection, intense jaundice in the skin and in conjunctival mucosa, and bilateral enlargement of supraclavicular and cervical lymph nodes with conspicuous facial and cervical edema resembling a "proconsular" or "bull" neck (Figure 1).The painless lymph nodes had a fibroelastic consistency, with major diameters ranging from 0.5 to 2.0 cm, and were also palpated with similar features on both axillary regions.Abdominal ultrasound images confirmed the moderate hepatic and spleen enlargements.Laboratory findings are showed in Table 1, characterizing an acute hepatitis associated with a recent infection by EBV.Worth of note was leukocytosis and lymphocytosis with a high rate (24%) of atypical cells; the initial low platelet count, the elevated serum levels of aminotransferases as well as of the canalicular hepatic enzymes, and the very high (near 13 mg/dl) direct-reacting hyperbilirubinemia.The diagnosis was acute hepatitis associated with infectious mononucleosis due to EBV.He was successfully managed with clinical and nutritional support, and symptomatic medicines.After clinical improvement, and tendency to normalization of laboratory data, the patient was discharged home on Day 15, and was further referred to specialized outpatient surveillance.On Day 34, rev Med Chile 2013; 141: 917-921 acute hepatitis due to infectious mononucleosis -V.Modesto dos santos et al   his physical examination was unremarkable, with absence of jaundice and lymph node enlargement (Figure 2) or visceromegaly.On the same occasion, almost all control laboratory tests were within the normal ranges, except for low indices of red cells and elevated GGT.The serology tests showed an increased level of EBV IgG, while the IgM level had lowered.Actually, the patient is asymptomatic, performing his normal daily activities.

Discussion
Adolescents and adults usually develop the classical features of IM, with an incubation period from 30 to 50 days 10 , followed by a symptomatic phase of variable duration.Fever, asthenia, headache, myalgias, pharyngitis and lymph node enlargement are the most common signs and symptoms 10 , and our patient presented most of them.There was an absolute lymphocytosis, as observed in 70% of cases with a peak between the second and third weeks.He had a large number (11 to 24%) of atypical lymphocytes, which constitutes a major characteristic of IM, although it is not pathognomonic.His serum levels of ALT and AST were moderately elevated, as described in 80 to 90% of acute infections 10 ; and alkaline phosphatases were also elevated, as found in 60% of the patients with IM 4 .Discrete elevations of bilirubin occur in about 45% of patients 4 , but clinical jaundice is observed in only 5% of cases 10 , in contrast with the very high level of direct-reacting bilirubin observed in the case here reported.Notably, intense cholestasis may affect elderly patients, and can mimic biliary obstruction 4 .Differential diagnoses of IM include other infections (e.g.cytomegalovirus, toxoplasmosis, HIV, rubella, viral hepatitis, leptospirosis, and scratch-cat disease), lymphoma, and leukemia.Interestingly, household contact with cat might raise the hypotheses of toxoplasmosis and scratch-cat disease.However, diagnosis of IM in the patient described herein was based on typical clinical and hematological data, and was confirmed by significant EBV-specific IgM and IgG antibodies 10 .Although acyclovir can inhibit the EBV replication and may reduce viral excretion, it has no significant effects on the clinical manifestations 4 .Uncomplicated cases of IM are usually managed by symptomatic and nutritional support 10 .Mechanisms of liver injuries related to EBV infections are not entirely clear, and include: products of immune responses to viral antigens (interferon γ, TNFα, Fas ligand), infected CD8+ T cells, and infiltrating cytotoxic T lymphocytes 10 , in addition to immunodeficiency syndromes, complement deficiency, X-linked lymphoproliferative disease, or treatment 8 .Because the prevalence of IM is very high worldwide 7,8,10 , there is a concern about possible under diagnosis, misdiagnosis, or underreporting of EBV-induced liver changes 8 .Although EBV-related acute hepatitis with jaundice has been scarcely reported, this condition may be under diagnosed in young patients 9 , because clinical and laboratory features (except for serology data) may be identical to that associated with the classic hepatotropic viruses 4 .Kang et al described two cases of acute hepatitis by EBV in Korean adults (aged 20 and 24 years) and, worth of note, one of them presented concomitant infection by hepatitis A virus 10 .Clinical findings and laboratory data were similar in both cases; however, the patient with hepatitis A virus coinfection showed two times higher levels of total (4.0 versus 2.1 mg/dl) and of direct-reacting (2.4 versus 1.2 mg/dl) bilirubin, and lower levels of GGT (69 versus 235 U/l).Interestingly, both patients improved with clinical management in a period of two weeks 10 .Cybulska et al reviewed three cases of EBV-related acute hepatitis in Canadian pediatric patients aged from 5 to 14.4 years.Their clinical course was benign, with abdominal pain, jaundice and ALT levels ranging between 126 and 196 U/ml, which normalized with time 11 .Other authors have emphasized that many discharge diagnosis of viral hepatitis in children have no confirmed etiology, contributing to under detection of other hepatotropic viruses like EBV 11 .Kofteridis et al reviewed 41 cases of acute hepatitis by EBV in Greek adults with a median age of 18.5 (15-51) years, and described a self-limiting condition, mainly cholestatic 12 .Similar to the laboratory findings in our patient, the levels of AST and ALT started to rise early in the onset of IM, and normalized in about three weeks, as well as the bilirubin and alkaline phosphatases, while the levels of GGT normalized later (after a period of 30 days) 12 .Vine et al reviewed 17 patients with diagnosis of acute hepatitis by EBV in the UK and found an age range of 18-68 years (median of 40 years).Seven patients (41%) were aged ≤ 30 years, similar to the present report.Brief hospitalization was necessary for three of the 17 patients, and the course of acute hepatitis was anicteric in two cases.They concluded that EBV hepatitis is an uncommon self-limiting entity, mainly detected among people aged ≥ 60 years 9 .The purpose of this case study is to highlight the intense jaundice (bilirubin > 14 mg/dl) due to an acute hepatitis caused by EBV, which occurred in a young adult with classical IM.We also emphasize that EBV infections can origin acute hepatitis with cholestasis, and can contribute to diagnosis pitfalls in primary care settings.Case studies may enhance the suspicion index about acute hepatitis by EBV, possibly under recognized in young patients.

Figure 2 .
Figure 2. Face and cervical region with normal aspect (a and B), and absence of ocular jaundice (C) on Day 34.

Figure 1 .
Figure 1.Bilateral enlarged cervical lymph nodes in addition to prominent facial and cervical swelling mimicking a "proconsular neck" or "bull neck" (a and B), and intense conjunctival jaundice in detail (C) on Day 8.

Table 1 .
Laboratory data of a young male with infectious mononucleosis and acute hepatitis HaV: hepatitis a virus; HB: hepatitis B virus; HCV: hepatitis C virus; nD: not done.abnormal findings are shown in bold.