Pancreas Vol. 6, No. 4,pp. 4 8 M 9 0 0 1991 Raven Press, Ltd., New York
Case Report
Pancreatitis Caused by Measles, Mumps, and Rubella Vaccine Jay B. Adler, "Sebastian A. Mazzotta, and Jamie S. Barkin University of Miami, School of MedicinelMount Sinai Medical Center, Divisions of Gastroenterology Miami, Florida, U.S.A.,and *Canton Potsdam Hospital, Gastroenterology Section, Potsdam, New York, U.S.A.
~~~
Summary: Acute pancreatitis may result from viral infections, including mumps, coxsackie B, Epstein-Barr, and varicella. However, viral pancreatitis has not been reported after immunization with viral vaccines. We report the occurrence of acute pancreatitis in an adult who had received measles, mumps, and rubella I1 vaccine (MMR 11). Key Words: Pancreatitis-Viral infections-Vaccines.
A 19-year-old woman was in good health and received an MMR I1 (lot #MSD 0144R) on 4/21/89, because of an occurrence of measles on her college campus. Eleven days later, the patient had acute onset of abdominal pain, described as nonradiating , band-like pain across the epigastrium, which awakened her from sleep. This was associated with nausea and bilious vomiting. The patient stated that she drinks minimally at social events and had two wine coolers and a beer one night prior to her abdominal pain. The patient denied cigarette smoking or oral contraceptive use. Physical examination of her abdomen revealed hypoactive bowel sounds, with tenderness to palpation in the epigastrium and right upper quadrant. No organomegaly was noted. No skin rashes were found. Laboratory data obtained upon admission were significant for a WBC of 11.3 cells/mm and an amylase level of 788 U/L (nl22-23 UIL). Her electrolytes and liver function tests were normal. She underwent placement of a nasogastric tube, with intermittent suction, and was given in-
travenous fluids and Demerol. Her amylase increased to 1142 U/L on the second hospital day and then gradually decreased to normal, five days later. A lipase level of 2300 U/L (normal < 140) was noted on the third hospital day. An abdominal ultrasound, performed on the second hospital day, was normal. This was repeated 4 days later and revealed a left pleural effusion; nonvisualization of the pancreas, due to overlying gas; and normal liver, gallbladder, biliary tree, and kidneys. Ascites was visualized on the right side of the abdomen, extending into Morrison's pouch and down to the cul-de-sac. A third ultrasound, ordered 2 days later to follow-up on these acute changes, was normal with no ascites. The patient became febrile on the second hospital day, to 102"C, with a rise in her WBC to 17.2 cells/ mm. Two blood cultures revealed no growth, but a throat culture yielded Staphylococcus aureus. The patient was treated initially with Ancef for 3 days and discharged on Velocef, 500 mg. Her WBC decreased to 14.2 cells/mm on the 7th hospital day. Her abdominal pain resolved and she was discharged on the 9th hospital day. Additional laboratory data during hospitalization included a trigiyceride level of 74 mg/dl (normal 44-187); a negative monospot test on the 3rd hospital day; negative uri-
Manuscript received December 12, 1989; revised manuscript accepted October 2, 1990. Address correspondence and reprint requests to Dr. Jamie S . Barkin at Division of Gastroenterology, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida 33140, U S A .
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nary pregnancy test; negative tests for hepatitis A and B; and TORCH ELISA titers:toxoplasma, < 1 , negative; cytomegalovirus (CMV), 0.25 (low level antibody detected); HSV1, 1 1 , and HSV2, 0.13 (no antibody detected); and rubella, 4.9 (moderate level of antibody detected). Antibodies to mumps and measles viruses were not assayed. The patient apparently did well for 6 months, at which time she was admitted because of another episode of acute pancreatitis. At that time, the patient was noted to have a positive monospot test, which was negative on her last episode. This was thought to be the etiologic factor for her second bout of pancreatitis. The patient improved, was discharged, and has been well for 2 months with no further episodes of pancreatitis.
Drscussrorv The two most common etiologic factors associated with acute pancreatitis are alcohol abuse and biliary disease. Uncommon etiologies include hyperlipoproteinemia, hypercalcemia, drugs, and pancreatic neoplasms. Additionally, acute pancreatitis has been found to be an uncommon complication of viral infections. Viruses that have been implicated include mumps, coxsackie B, Epstein Barr, and varicella viruses (1-7). Viral pancreatitis usually causes nonhemorrhagic pancreatitis, although hemorrhagic pancreatitis has been reported with pancreatitis secondary to mumps (l), and pancreatic pseudocyst has been reported with mumps and varicella viruses (1,2). The mechanism by which viruses cause pancreatitis is unclear. One theory is that they cause edema of the ampulla of Vater and pancreatic ducts, which results in obstructive pancreatitis. However, a more plausible explanation, based on experimental work on rats and mice, is that the virus causes a direct attack on the acinar cell. We believe that our patient had an episode of acute pancreatitis, based on her clinical findings; serologic evidence of pancreatitis, consisting of a greater than fivefold increase in amylase which reverted to normal; and an elevated lipase. In addition, serial abdominal ultrasound examinations initially revealed normal findings, which, when repeated, revealed changes consistent with acute pancreatitis, which reverted to normal. The most logical cause of her episode of pancreatitis was the MMR vaccine, given the temporal relationship between injection of the vaccine and acute illness. This time period corresponds to the Pancreas, Vol. 6,No. 4, 1991
incubation period of the virus. Adverse reactions to MMR vaccine have been attributed to the measles and to the rubella components, occurring 5-1 1 days and 2-8 weeks after immunization, respectively. Adverse reactions that have been reported with measles vaccine include transient rashes and, rarely, subacute sclerosing panencephalitis. Adverse reactions reported with the rubella vaccine include transient arthralgias, arthritis, and paresthetic pains. Recognizable reactions to the mumps component have not been reported (8). The vaccine is a live virus, albeit attenuated and, therefore, the mechanism of the acute pancreatitis is presumably the same as that caused by other viruses. Other etiologies of acute pancreatitis cannot be directly implicated in this case report. Although the patient did consume alcohol the night prior to her illness, she drank only a minimal amount and, by history, was only a minimal social drinker. The patient had no evidence of biliary disease, was on no medications, had no evidence of an active viral infection, and was normocalcemic and normotriglyceridemic. We therefore believe that this episode of pancreatitis was caused by the MMR vaccine. This is the first case report of pancreatitis, secondary to the MMR vaccine, to be reported in the literature. In personal communication with representatives of Merck, Sharp & Dohme, they have stated that anecdotal reports of pancreatitis to MMR vaccine do exist, although none has been reported in the literature as yet. The importance of considering this etiology is that, as more people receive immunization with MMR vaccine secondary to various measles outbreaks, clinicians must be aware that acute pancreatitis is a possible complication of MMR vaccine.
REFERENCES 1. Feldstein JD, Johnson FR, Kallick CA, Doolas A. Acute hemorrhagic pancreatitis and pseudocyst due to mumps. Ann Surg 1974;18085-8. 2. Kirschner S, Raufman JP. Varicella pancreatitis complicated by pancreatic pseudocyst and duodenal obstruction. Dig Dis Sci 1988;33:1192-5. 3 . Everett ED, Volpe JA, Bergin JJ. Pancreatitis in infectious mononucleosis. South Med J 1%9;62:35%60. 4. Hedstrom SA, Belfrage 1. Acute pancreatitis in two cases of infectious mononucleosis. Scand J Infect Dis 1976;8:124-6. 5 . Imrie CW, Ferguson JC, Sommerville RG. Coxsackie and mumps virus infection in a prospective study of acute pancreatitis. Gut 1977;18:534. 6. Upsing B. Acute pancreatitis in coxsackie B infection. Br Ed J 1973;3:52&5. 7 . Witte CL, Schanzer B. Pancreatitis due to mumps. JAMA 1%8;203:1068-9. 8. Behrman RE, Vaughn VC, Nelson WE. Nelson textbook of pediatrics. 13th ed. Philadelphia: WB Saunders, 1987:160.
Case Report
Pancreatitis Caused by Measles, Mumps, and Rubella Vaccine Jay B. Adler, "Sebastian A. Mazzotta, and Jamie S. Barkin University of Miami, School of MedicinelMount Sinai Medical Center, Divisions of Gastroenterology Miami, Florida, U.S.A.,and *Canton Potsdam Hospital, Gastroenterology Section, Potsdam, New York, U.S.A.
~~~
Summary: Acute pancreatitis may result from viral infections, including mumps, coxsackie B, Epstein-Barr, and varicella. However, viral pancreatitis has not been reported after immunization with viral vaccines. We report the occurrence of acute pancreatitis in an adult who had received measles, mumps, and rubella I1 vaccine (MMR 11). Key Words: Pancreatitis-Viral infections-Vaccines.
A 19-year-old woman was in good health and received an MMR I1 (lot #MSD 0144R) on 4/21/89, because of an occurrence of measles on her college campus. Eleven days later, the patient had acute onset of abdominal pain, described as nonradiating , band-like pain across the epigastrium, which awakened her from sleep. This was associated with nausea and bilious vomiting. The patient stated that she drinks minimally at social events and had two wine coolers and a beer one night prior to her abdominal pain. The patient denied cigarette smoking or oral contraceptive use. Physical examination of her abdomen revealed hypoactive bowel sounds, with tenderness to palpation in the epigastrium and right upper quadrant. No organomegaly was noted. No skin rashes were found. Laboratory data obtained upon admission were significant for a WBC of 11.3 cells/mm and an amylase level of 788 U/L (nl22-23 UIL). Her electrolytes and liver function tests were normal. She underwent placement of a nasogastric tube, with intermittent suction, and was given in-
travenous fluids and Demerol. Her amylase increased to 1142 U/L on the second hospital day and then gradually decreased to normal, five days later. A lipase level of 2300 U/L (normal < 140) was noted on the third hospital day. An abdominal ultrasound, performed on the second hospital day, was normal. This was repeated 4 days later and revealed a left pleural effusion; nonvisualization of the pancreas, due to overlying gas; and normal liver, gallbladder, biliary tree, and kidneys. Ascites was visualized on the right side of the abdomen, extending into Morrison's pouch and down to the cul-de-sac. A third ultrasound, ordered 2 days later to follow-up on these acute changes, was normal with no ascites. The patient became febrile on the second hospital day, to 102"C, with a rise in her WBC to 17.2 cells/ mm. Two blood cultures revealed no growth, but a throat culture yielded Staphylococcus aureus. The patient was treated initially with Ancef for 3 days and discharged on Velocef, 500 mg. Her WBC decreased to 14.2 cells/mm on the 7th hospital day. Her abdominal pain resolved and she was discharged on the 9th hospital day. Additional laboratory data during hospitalization included a trigiyceride level of 74 mg/dl (normal 44-187); a negative monospot test on the 3rd hospital day; negative uri-
Manuscript received December 12, 1989; revised manuscript accepted October 2, 1990. Address correspondence and reprint requests to Dr. Jamie S . Barkin at Division of Gastroenterology, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida 33140, U S A .
489
490
J . B. ADLER ET AL.
nary pregnancy test; negative tests for hepatitis A and B; and TORCH ELISA titers:toxoplasma, < 1 , negative; cytomegalovirus (CMV), 0.25 (low level antibody detected); HSV1, 1 1 , and HSV2, 0.13 (no antibody detected); and rubella, 4.9 (moderate level of antibody detected). Antibodies to mumps and measles viruses were not assayed. The patient apparently did well for 6 months, at which time she was admitted because of another episode of acute pancreatitis. At that time, the patient was noted to have a positive monospot test, which was negative on her last episode. This was thought to be the etiologic factor for her second bout of pancreatitis. The patient improved, was discharged, and has been well for 2 months with no further episodes of pancreatitis.
Drscussrorv The two most common etiologic factors associated with acute pancreatitis are alcohol abuse and biliary disease. Uncommon etiologies include hyperlipoproteinemia, hypercalcemia, drugs, and pancreatic neoplasms. Additionally, acute pancreatitis has been found to be an uncommon complication of viral infections. Viruses that have been implicated include mumps, coxsackie B, Epstein Barr, and varicella viruses (1-7). Viral pancreatitis usually causes nonhemorrhagic pancreatitis, although hemorrhagic pancreatitis has been reported with pancreatitis secondary to mumps (l), and pancreatic pseudocyst has been reported with mumps and varicella viruses (1,2). The mechanism by which viruses cause pancreatitis is unclear. One theory is that they cause edema of the ampulla of Vater and pancreatic ducts, which results in obstructive pancreatitis. However, a more plausible explanation, based on experimental work on rats and mice, is that the virus causes a direct attack on the acinar cell. We believe that our patient had an episode of acute pancreatitis, based on her clinical findings; serologic evidence of pancreatitis, consisting of a greater than fivefold increase in amylase which reverted to normal; and an elevated lipase. In addition, serial abdominal ultrasound examinations initially revealed normal findings, which, when repeated, revealed changes consistent with acute pancreatitis, which reverted to normal. The most logical cause of her episode of pancreatitis was the MMR vaccine, given the temporal relationship between injection of the vaccine and acute illness. This time period corresponds to the Pancreas, Vol. 6,No. 4, 1991
incubation period of the virus. Adverse reactions to MMR vaccine have been attributed to the measles and to the rubella components, occurring 5-1 1 days and 2-8 weeks after immunization, respectively. Adverse reactions that have been reported with measles vaccine include transient rashes and, rarely, subacute sclerosing panencephalitis. Adverse reactions reported with the rubella vaccine include transient arthralgias, arthritis, and paresthetic pains. Recognizable reactions to the mumps component have not been reported (8). The vaccine is a live virus, albeit attenuated and, therefore, the mechanism of the acute pancreatitis is presumably the same as that caused by other viruses. Other etiologies of acute pancreatitis cannot be directly implicated in this case report. Although the patient did consume alcohol the night prior to her illness, she drank only a minimal amount and, by history, was only a minimal social drinker. The patient had no evidence of biliary disease, was on no medications, had no evidence of an active viral infection, and was normocalcemic and normotriglyceridemic. We therefore believe that this episode of pancreatitis was caused by the MMR vaccine. This is the first case report of pancreatitis, secondary to the MMR vaccine, to be reported in the literature. In personal communication with representatives of Merck, Sharp & Dohme, they have stated that anecdotal reports of pancreatitis to MMR vaccine do exist, although none has been reported in the literature as yet. The importance of considering this etiology is that, as more people receive immunization with MMR vaccine secondary to various measles outbreaks, clinicians must be aware that acute pancreatitis is a possible complication of MMR vaccine.
REFERENCES 1. Feldstein JD, Johnson FR, Kallick CA, Doolas A. Acute hemorrhagic pancreatitis and pseudocyst due to mumps. Ann Surg 1974;18085-8. 2. Kirschner S, Raufman JP. Varicella pancreatitis complicated by pancreatic pseudocyst and duodenal obstruction. Dig Dis Sci 1988;33:1192-5. 3 . Everett ED, Volpe JA, Bergin JJ. Pancreatitis in infectious mononucleosis. South Med J 1%9;62:35%60. 4. Hedstrom SA, Belfrage 1. Acute pancreatitis in two cases of infectious mononucleosis. Scand J Infect Dis 1976;8:124-6. 5 . Imrie CW, Ferguson JC, Sommerville RG. Coxsackie and mumps virus infection in a prospective study of acute pancreatitis. Gut 1977;18:534. 6. Upsing B. Acute pancreatitis in coxsackie B infection. Br Ed J 1973;3:52&5. 7 . Witte CL, Schanzer B. Pancreatitis due to mumps. JAMA 1%8;203:1068-9. 8. Behrman RE, Vaughn VC, Nelson WE. Nelson textbook of pediatrics. 13th ed. Philadelphia: WB Saunders, 1987:160.
