Several conditions predispose to acute pancreatitis and among them infectious agents such as bacteria, viruses, fungi and parasites constitute a small percentage. Viral pancreatitis is mainly attributed to common viruses such as mumps, Coxsackie, and cytomegaloviruses (CMVs), although HIV, Epstein–Barr virus (EBV), rubella and adenoviruses have also been reported in a few cases . Viral pancreatitis because of herpes simplex virus (HSV) is a very rare entity and has been reported only in immunocompromised individuals. To our knowledge, this is the first case in the literature of acute viral pancreatitis associated with herpes simplex viral infection in an immunocompetent and otherwise healthy 22-year-old man.
A 22-year-old man was admitted to the emergency department of our hospital with acute midepigastric pain, radiating to the right upper quadrant of the abdomen, vomiting (four times the last 24 h) and fever (maximum 39.6°C). The pain had a colicky character resulting in restlessness, agitation and nausea. Symptoms started at least 24 h before admission and were gradually worsening. The patient did not report any similar symptoms in the past or any other medical history and denied any alcohol or smoke consumption or any drug intake.
On admission, physical examination revealed abdominal distension and tenderness and a normal rectal examination. Sore throat, pharyngotonsillitis, cervical lymphadenopathy, mild nasal congestion and icteric conjunctivae were also recorded. Vital signs were as follows: heart rate 95/min, blood pressure 135/78 mmHg, temperature 39.3°C, respiratory rate 18/min. Pulse oximetry showed a normal (98%) O2 saturation whereas heart and chest auscultation did not reveal any findings.
Abnormal laboratory findings included WBC: 18 500/μl (neutrophils: 79%), amylase: 720 IU/l, alanine aminotransferase: 306 IU/l, aspartate aminotransferase: 353 IU/l, total bilirubin: 3.07 mg/dl, direct bilirubin: 2.05 mg/dl, γGT: 278 IU/l, alanine aminotransferase: 203 IU/l. Pharyngeal smear, urine culture and three blood cultures were negative for both aerobic and anaerobic bacteria. Lipidemic profile, renal function and coagulation tests, were within normal range whereas autoantibodies were all negative. Given that the abdominal ultrasound revealed a dilated cystic and common hepatic bile duct, a computed tomography scan was also performed after oral and intravenous contrast administration and additionally revealed diffuse oedema of the pancreatic head, dilatation of the intrahepatic biliary tract and narrowing of the intrapancreatic part of the common bile duct without evidence of intraluminal obstacle (Fig. 1). Computed tomography scan as well as abdominal ultrasound revealed no stones or sludge either in the gallbladder or in the common bile duct.
The aforementioned clinical and laboratory data were indicative of a combination of acute pancreatitis and hepatitis while a cholestatic syndrome, because of external compression of the biliary tree by the oedematous pancreatic head, could not be excluded. Serum sample was also tested for hepatotropic virus infection and included IgM and IgG antibodies for EBV, CMV, adenovirus, hepatitis A, B and C viruses, echo virus, Coxsackie A and B viruses, HIV and HSV type I and II (enzyme-linked immunosorbent assay).
Since admission, the patient remained fasted and was treated supportively from his general practitioner. This included pancreatic enzymes (Creon 10 000, Solvay Pharma, Athens, Greece) per os three times a day, which were discontinued. Oral intake was initiated 48 h after admission with administration of 150–200 ml chamomile every 4 h for the first 24 h. Chamomile was well tolerated and, therefore, feeding was continued with soft and gradually solid food. Diet consisted of 50% carbohydrate and the total caloric intake gradually increased from 150 to 800 kcal per meal.
Owing to cholestatic jaundice persistence for 6 days after admission, and despite patient's gradual clinical improvement regarding symptoms from the gastrointestinal system and upper respiratory tract, a magnetic resonance cholangiopancreatography was performed. Dilation of the common hepatic and the proximal bile duct (maximum diameter 1.1 cm) with a diffuse, smooth and benign-looking narrowing of the distal bile duct, because of a local oedema of the pancreatic head, were noted. Also, no sludge or stones were observed (Fig. 2).
The same day, serology results suggested an acute herpetic viral infection (IgMHSV: 15I IU/l and IgGHSV: 30 IU/l) and immunization (high IgG titrates) for EBV and CMV. Moreover, blood test revealed WBC: 5500/μl, with 50% lymphocytes and 44.4% neutrophils, findings compatible with viral infection.
The patient was discharged 11 days after admission with normal biochemical parameters. Four days after discharge, serologic blood tests were repeated. His convalescent serum sample (drawn 2 weeks after the onset of the disease) showed seroconversion with IgMHSV: 2 IU/l and IgGHSV: 250 IU/l. During the follow-up the patient was doing well, lymphadenopathy disappeared completely, while his abdominal ultrasound was turned into normal within a few weeks.
Predisposing conditions for acute pancreatitis, such as gallstones, chronic alcohol abuse, hyperlipidemia and hypercalcemia, account for almost 75% of the cases in the USA . The causative role of infectious agents remains a controversial issue. Mumps infection as a cause of pancreatic disease was speculated as early as 1817 . Currently, it is not yet clear whether infectious agents can cause pancreatitis alone or in combination with at least one of the aforementioned conditions. Mumps virus, Coxsackie virus, adenovirus, hepatitis B virus and CMV have been reported as rare causes of acute pancreatitis in the literature .
HSV is an enveloped, double strained DNA virus that causes infection of the mucosal surfaces and infrequently leads to disseminated infection, at least in immunocompetent hosts. HSV is transmitted from person-to-person through infected oral secretions during close contact. The incubation period, for oral infections, ranges from 1 to 26 days (median 6–8 days) and lesions persist for 1–8 days. Although primary infection may be reactivated throughout life, it is rarely fatal in the immunocompetent host, producing either asymptomatic or mild clinical disease [4,5]. To date, it is the most infrequent viral cause of acute pancreatitis and, according to our knowledge, only three relevant publications can be found in the literature [6–8]. The first two reports [6,7] describe three cases of viral acute pancreatitis because of HSV but in individuals with comorbidity (allergic granulomatous angiitis, invasive pulmonary aspergillosis, HIV infection). The third report  describes an individual with acute idiopathic pancreatitis and HSV isolation from gastric contents with no seroconversion. Thus, our case is the first report of acute pancreatitis in an immunocompetent patient without comorbidity.
The clinical and laboratory findings our patient had during his admission were both suggestive of a cholestatic syndrome and pancreatitis, which could be easily attributed to a gallstone. The additional findings of hepatitis, however, pointed to the possibility of a common viral cause for both pancreatitis and hepatitis. Dilatation of the proximal biliary tree, a finding usually compatible with a biliary cause of acute pancreatitis, resulted from external compression of the intrapancreatic part of the bile duct by the enlarged head of the inflamed pancreas as there has not been any evidence of biliary stones or sludge.
Hepatitis caused by HSV is a common and subclinical condition during primary infection in adults but may become clinically evident, especially during pregnancy or in immunosuppressed patients (e.g. AIDS, posttransplant infections, etc.). Jaundice is usually absent whereas fever, fatigue, high serum aspartate aminotransferase and alanine aminotransferase levels and leukopenia are among the clinical and biochemical markers at the onset of the disease . Herpetic hepatitis, although common, rarely coexists with pancreatitis and to our knowledge, there is only one case of herpetic infection of both liver and pancreas. That case was attributed to dissemination from primary genital herpes infection during pregnancy .
In conclusion, although rare, viral agents including HSV should be considered in the differential diagnosis of acute pancreatitis, especially when hepatic infection coexists and no other common cause of the disease (mechanical, toxic, metabolic or traumatic) is evident. Dilatation of the biliary tree is not invariably compatible with a biliary cause of acute pancreatitis.
Conflict of interest: none declared.
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