Case Study: Fever and abdominal pain

By Jacquelyn Nohl, MD

A 12-year-old, previously healthy male presented to the emergency room with fever, abdominal pain and emesis. Seven days before the patient had temperatures to 103 degrees Fahrenheit and complained of lethargy. Five days earlier he began vomiting – with three nonbloody, nonbilious emesis per day. He was seen at a local emergency room and diagnosed with gastroenteritis. Fevers persisted. The patient developed nonradiating, 9/10, epigastric pain that localized to the right upper quadrant, prompting return to the emergency room. On review of systems, the patient denied pharyngitis, diarrhea or ill contacts but did report dark urine. 

Other than Tylenol™ and ibuprofen for fever, the patient denied taking medications. There was no family history of hepatitis, gallbladder disease or coagulation defects. 

On physical exam, weight was 32 kg (8th percentile) and height 138 cm (5th percentile). He was afebrile with age-appropriate vital signs. His face was flushed and jaundiced. His sclerae were anicteric. His posterior pharynx was normal. He had bilateral cervical lympadenopathy, posterior greater than anterior. His abdomen was diffusely tender without rebound or guarding. His liver span was 12 cm by percussion, with a tender margin. His spleen tip was palpable. The remainder of his exam was normal.

Initial laboratory studies included: WBC 12.3K/uL, 12 percent segs, 7 percent bands, 28 percent lymphocytes, 2 percent monocytes, 51 percent reactive lymphoctyes, AST 440 IU/L, ALT 285 IU/L, unconjugated bilirubin 0.7 mg/dL, conjugated bilirubin 0.5 mg/dL and LDH 1966 IU/L. Electrolytes, calcium, phosphate, alkaline phosphatase, albumin, PT/PTT, BUN/creatinine, urine analysis, amylase and lipase were all normal. A serum drug screen for acetaminophen, tricyclic antidepressants, alcohol and salicylates was negative. Influenza A and B PCR, rapid strep antigen and monospot tests were negative. Ultrasound of the liver showed inflammation of unclear etiology. He was admitted to the general pediatric team for further care.

Gastroenterology was consulted for hepatitis of unknown etiology. Differential diagnosis included viral etiologies, autoimmune hepatitis, Wilson's disease, portal vein thrombosis and sepsis. Further workup included Hepatitis A, B and C, EBV, CMV and parvovirus serologies; autoimmune hepatitis profile; serum ceruloplasmin; blood and urine cultures; and repeat ultrasound with Doppler flow.

Significant results included normal CRP, ESR and coagulation studies. Autoimmune hepatitis profile including LKM antibodies, anti-actin antibodies, ANA and total IgG was normal. Serum ceruloplasmin and 24-hour urine copper collection were normal. Blood and urine cultures were negative. Repeat liver ultrasound with Doppler showed an abnormal thick-walled, edematous gallbladder with mild hepatomegaly but normal vessel flow. Hepatitis studies, parvovirus and CMV serologies were negative for acute infection. EBV IgM was positive with an elevated IgG of 2.38.

This patient's lymphadenopathy, elevated atypical lymphocyte count, hepatitis, splenomegaly and fatigue were consistent with acute EBV. Supportive care was instituted. Over the next several days fever and abdominal pain resolved. The patient's transaminases peaked at AST 657 IU/L and ALT 410 IU/L with a downward trend at time of discharge. The patient's liver and spleen remained enlarged.   

At his two-week follow-up visit, the patient reported normal appetite and no fevers. He continued to have cervical lymphadenopathy, with a liver span of 8 cm and a palpable spleen tip. Repeat lab testing found AST 133 IU/L and ALT 352 IU/L.

Discussion

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis. The majority of primary infections are subclinical and acquired during childhood with a seropositivity of approximately 90 percent by age 18. The incidence of clinical infection begins to rise in the teenage population. EBV is transmitted by contact with infected saliva and blood transfusions. Symptoms manifest within 30 to 50 days of exposure and classically include fever, exudative pharyngitis and lymphadenopathy. Although less frequently discussed, gastrointestinal manifestations including elevated transaminases, hepatosplenomegaly, abdominal pain, elevated bilirubin and, in rare cases, jaundice do occur. Case reports suggest EBV also can be linked to gallbladder thickening.

The diagnosis of EBV is made based on history and physical exam combined with a positive monospot or positive serology. The monospot detects the presence of heterophile antibody. Only 30 percent of children younger than 4 will have a heterophile antibody, making this test less reliable in young populations. False positive results occur with HIV, leukemia, lymphoma, lupus and rubella. Serology can be used when the monospot is not diagnostic and clinical suspicion remains. Approximately 80 to 90 percent of children with EBV will have IgM antibody to the viral capsid antigen (VCA). VCA IgG levels become positive early after the onset of infection and remain positive for life, making it less helpful in diagnosis of acute infection. PCR techniques are available but primarily are used in the immunosuppressed population.

The majority of otherwise healthy patients with primary EBV infection will spontaneously recover and develop durable immunity. Additional therapy should be decided on an individual basis. In general, steroids only should be used when specific complications such as airway compromise exist. Penicillins should be avoided during the acute phase of illness due to the high likelihood of developing rash. Abnormal liver function tests normalize within two to six weeks of the onset of symptoms. Patients should be instructed to avoid contact sports until splenomegaly resolves due to the risk for splenic rupture.

References 

Aronson M, et al, "Infectious mononucleosis in adults and adolescents," UpToDate online. 16.3, 2009.

Crum NF, "Epstein-Barr virus hepatitis: case series and review," Southern Medical Association. 2006,99(5):544-547

Papesch M and Watkins R, "Epstein-Barr virus infectious mononucleosis," Clincal Otolaryngology. 2001, 26:3-8.

Pitetti R, et al, "Clinical evaluation of a quantitative real-time polymerase chain reaction assay for diagnosis of primary Epstein-Barr virus infection in children." Pediatric Infectious Disease Journal. 2003, 22:736-739.

Place E, et al, "Successful plasmapheresis for extreme hyperbilirubinemia caused by acute Epstein-Barr virus," Journal of Pediatric Hematology Oncology. 2007, 29(5):323-326.

Red Book 27^th edition. 2006, 286-288.

Jacquelyn Nohl, MD, is a pediatric hospitalist at Children's Hospital of Wisconsin, an assistant professor of Pediatrics (Hospital Medicine) at The Medical College of Wisconsin and a member of Children's Specialty Group.

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