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Hepatitis in an adult with rubella
Hepatitis in an Adult with Rubella
JEROME B. ZELDIS, M.D., Ph.D. JAMES G. MILLER, M.D. JULES L. DIENSTAG, M.D. Boston,
l
Massachusetts
Rubella accompanied by serum aminotransferase elevations occurred in a 24-year-old woman. Although not generally recognized, hepatic involvement in adult rubella was the probable cause of her liver function test abnormalities. Sporadic hepatitis labeled as non-A, non-6 may result from infection by common viruses such as rubella. Even though congenital rubella is accompanied regularly by hepatocellular disease, liver involvement in the acquired acute infection in adults has not been recognized [l-4]. We report a case of hepatitis associated with acute rubella infection in an adult. CASE
From the Gastrointestinal Unit (Medical Services), Massachusetts General Hospital, the Department of Medicine, Harvard Community Health Plan, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts. Manuscript accepted July 19, 1984. Current address and address for reprint requests: Gastrointestinal Division, Dana 5, Beth Israel Hospital, Boston, Massachusetts 02215. l
REPORT
A 24-year-old Caucasian female bank employee was in good health until a rash developed on her arms and spread over her face, chest, abdomen, and legs during the next 24 hours. This was accompanied by malaise and generalized lymphadenopathy especially prominent in the head and neck. Seven days later, arthralgias and nausea developed and lasted one week. The patient did not have hepatomegaly or a palpable spleen. A diagnosis of rubella was entertained on the basis of the rash and lymphadenopathy, which lasted one week, and was supported by the occurrence of rubella in one fellow employee before and in another fellow employee after the patient’s illness. Because of the persistence of fatigue after the resolution of the rash and lymphadenopathy and because the patient’s aspartate aminotransferase and alanine aminotransferase levels were both elevated (Table I), a diagnosis of viral hepatitis was considered. Tests for other viral agents that can cause hepatitis either gave negative results or did not demonstrate a change in titer between the acute and convalescent phases of the patient’s illness (Table I). Ultimately, a diagnosis of rubella was established serologically. The rubella antibody titer was noted to rise from I:32 in an acute-phase sample to 1: 160 during the convalescent phase of her illness, after the resolution of the rash. Her aspartate aminotransferase and alanine aminotransferase levels became normal two weeks after the onset of symptoms, and all the patient’s symptoms resolved within a month. The patient had no history of recent intravenous drug use, transfusion, surgery, other percutaneous exposures, frequent intake of alcohol, eating uncooked shellfish, or exposure to patients with hepatitis prior to her illness. COMMENTS This is the first report of hepatitis associated with an acute rubella infection in an adult. Serologic testing ruled out hepatocellular injury from infection with hepatitis A virus, hepatitis B virus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus types I and II.
October
1985
The American
Journal
of Medicine
Volume
79
515
HEPATITIS
FROM
TABLE I
RUBELLA-ZELDIS
Laboratory
ET AL
Values during the Course of Illness in a Patient
and Rubella
Infection*
Day
37 Aspartate aminotransferase (IU/liter) (normal 6-26) Alanine aminotransferase (It-)/liter) (normal O-16) Total bilirubin (mg/pl) (normal 0.1-1.2) Alkaline phosphatase (IUlliter) (normal 21-72) Rubella antibody titer Heterophil antibody Anti-cytomegalovirus IgM anti-hepatitis A virus/anti-hepatitis A virus Anti-herpes simplex I Anti-herpes simplex II Anti-Epstein-Barr virus Ox cell hemolysin method Epstein-Barr virus capsid antigen
with Mild Hepatitis
10
15
26
47
321
94 284 0.7 41
25 9 1.0 31 1:160
17 11 1.0 29
Negative Negative
Negative
1:32
51
Negative
++ +++
Negative ++ +++
1:2,560
1:2,560
Rubella and heterophil antibodies were assayed by hemagglutination inhibition; antibodies to hepatitis A virus by radioimmunoassay (HAVAB and HAVAB-M, Abbott Laboratories, North Chicago, Illinois); anti-herpes simplex by enzyme immunoassay; and antibodies to Epstein-Barr virus capsid antigen by immunofluorescence. t The patient presented for medical attention three days after the onset of symptoms. l
Rubella is a togavirus that may produce a systemic infection involving the skin, lungs, brain, and joints. Although hepatic involvement in the congenital rubella syndrome among newborns is a known clinical and pathologic entity, hepatitis in acquired rubella infection among adults has been said not to occur [l-4]. In the congenital rubella syndrome, the infection is acquired in utero. Cholestatic jaundice with hepatomegaly is observed one to two days after birth. The aminotransferase levels are only mildly elevated, whereas the alkaline phosphatase and bilirubin levels are substantially increased. The patient described in the present report had elevated aminotransferase levels; cholestasis was not observed, and the alkaline phosphatase level was normal. The elevated aminotransferase activity that was found in this patient may be a reflection of the systemic nature of rubella infection. In all likelihood, such mild elevations of aminotransferase activity are not uncommon in adult rubella; however, in most patients with
acute rubella, there is little indication to perform tests of hepatocellular injury, such as determination of alanine aminotransferase and aspartate aminotransferase levels, and hepatic inflammation is rarely recognized. Liver biopsy was not performed in our patient because of the mildness of the biochemical liver abnormalities. Acute rubella infection in adults should be considered another cause of virally induced hepatocellular injury, as has been reported to occur during infections with varicella [5], rubeola [6], adenovirus [ 71, Coxsackie viruses [8,9], and ECHO virus [lo]. Because the viral serology of most cases of “sporadic” acute non-A, non-B hepatitis is not as extensively studied as was done in this case, potentially, a proportion of sporadic hepatitis labeled as non-A, non-B may result from infection with common viruses such as rubella. Such diagnostic considerations are especially worthwhile in mild, transient hepatitis episodes.
REFERENCES 1.
2.
3.
4.
5.
516
Robinson WS: Biology of human hepatitis virus. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. Philadelphia: WB Saunders, 1962; 663-666. Schiff GM: Hepatitis caused by viruses other than hepatitis A, hepatitis B, and non A non B hepatitis viruses. In: Schiff L, Schiff ER, eds. Diseases of the liver, 5th ed. Philadelphia: JB Lippincott, 1962; 61 l-620. Wright R, Millward-Sadler GH: Acute viral hepatitis. In: Wright R, Alberti KGMM, Karran S, Millward-Sadler GH, eds. Liver and biliary disease. Philadelphia: WB Saunders, 1979; 585-646. Sherlock S: Diseases of the liver and biliary system, 6th ed. London: Blackwell Scientific Publications, 1961; 266269. Ortonne JP, Reboul MC, Trepo C, Mallet-Guy Y, Thivolet J:
October
1965
The American
Journal
of Medicine
Volume
6. 7.
6.
9. 10.
79
Hepatite et varicelle. Ann Dermatol Venereol (Paris) 1976; 105: 877-879. McLellan RK, Gleiner JA: Acute hepatitis in an adult with rubeola. JAMA 1962; 247: 2000-2001. Hartwell WV, Love GJ, Eisenbock MD: Adenovirus in blood clots from cases of infectious hepatitis. Science 1966; 152: 1390. Morris JA, Elisberg BL, Pond WL, Webb DA: Hepatitis associated with coxsackie virus group A, type 4. N Engl J Med 1962; 267: 1230-1233. Sun NC, Smith VM: Hepatitis associated with myocarditis. N Engl J Med 1966; 274: 190-193. Schleissner LA, Portnoy B: Hepatitis and pneumonia associated with ECHO virus, type 9 infection in two adult siblings. Ann Intern Med 1966; 66: 13151319.
JEROME B. ZELDIS, M.D., Ph.D. JAMES G. MILLER, M.D. JULES L. DIENSTAG, M.D. Boston,
l
Massachusetts
Rubella accompanied by serum aminotransferase elevations occurred in a 24-year-old woman. Although not generally recognized, hepatic involvement in adult rubella was the probable cause of her liver function test abnormalities. Sporadic hepatitis labeled as non-A, non-6 may result from infection by common viruses such as rubella. Even though congenital rubella is accompanied regularly by hepatocellular disease, liver involvement in the acquired acute infection in adults has not been recognized [l-4]. We report a case of hepatitis associated with acute rubella infection in an adult. CASE
From the Gastrointestinal Unit (Medical Services), Massachusetts General Hospital, the Department of Medicine, Harvard Community Health Plan, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts. Manuscript accepted July 19, 1984. Current address and address for reprint requests: Gastrointestinal Division, Dana 5, Beth Israel Hospital, Boston, Massachusetts 02215. l
REPORT
A 24-year-old Caucasian female bank employee was in good health until a rash developed on her arms and spread over her face, chest, abdomen, and legs during the next 24 hours. This was accompanied by malaise and generalized lymphadenopathy especially prominent in the head and neck. Seven days later, arthralgias and nausea developed and lasted one week. The patient did not have hepatomegaly or a palpable spleen. A diagnosis of rubella was entertained on the basis of the rash and lymphadenopathy, which lasted one week, and was supported by the occurrence of rubella in one fellow employee before and in another fellow employee after the patient’s illness. Because of the persistence of fatigue after the resolution of the rash and lymphadenopathy and because the patient’s aspartate aminotransferase and alanine aminotransferase levels were both elevated (Table I), a diagnosis of viral hepatitis was considered. Tests for other viral agents that can cause hepatitis either gave negative results or did not demonstrate a change in titer between the acute and convalescent phases of the patient’s illness (Table I). Ultimately, a diagnosis of rubella was established serologically. The rubella antibody titer was noted to rise from I:32 in an acute-phase sample to 1: 160 during the convalescent phase of her illness, after the resolution of the rash. Her aspartate aminotransferase and alanine aminotransferase levels became normal two weeks after the onset of symptoms, and all the patient’s symptoms resolved within a month. The patient had no history of recent intravenous drug use, transfusion, surgery, other percutaneous exposures, frequent intake of alcohol, eating uncooked shellfish, or exposure to patients with hepatitis prior to her illness. COMMENTS This is the first report of hepatitis associated with an acute rubella infection in an adult. Serologic testing ruled out hepatocellular injury from infection with hepatitis A virus, hepatitis B virus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus types I and II.
October
1985
The American
Journal
of Medicine
Volume
79
515
HEPATITIS
FROM
TABLE I
RUBELLA-ZELDIS
Laboratory
ET AL
Values during the Course of Illness in a Patient
and Rubella
Infection*
Day
37 Aspartate aminotransferase (IU/liter) (normal 6-26) Alanine aminotransferase (It-)/liter) (normal O-16) Total bilirubin (mg/pl) (normal 0.1-1.2) Alkaline phosphatase (IUlliter) (normal 21-72) Rubella antibody titer Heterophil antibody Anti-cytomegalovirus IgM anti-hepatitis A virus/anti-hepatitis A virus Anti-herpes simplex I Anti-herpes simplex II Anti-Epstein-Barr virus Ox cell hemolysin method Epstein-Barr virus capsid antigen
with Mild Hepatitis
10
15
26
47
321
94 284 0.7 41
25 9 1.0 31 1:160
17 11 1.0 29
Negative Negative
Negative
1:32
51
Negative
++ +++
Negative ++ +++
1:2,560
1:2,560
Rubella and heterophil antibodies were assayed by hemagglutination inhibition; antibodies to hepatitis A virus by radioimmunoassay (HAVAB and HAVAB-M, Abbott Laboratories, North Chicago, Illinois); anti-herpes simplex by enzyme immunoassay; and antibodies to Epstein-Barr virus capsid antigen by immunofluorescence. t The patient presented for medical attention three days after the onset of symptoms. l
Rubella is a togavirus that may produce a systemic infection involving the skin, lungs, brain, and joints. Although hepatic involvement in the congenital rubella syndrome among newborns is a known clinical and pathologic entity, hepatitis in acquired rubella infection among adults has been said not to occur [l-4]. In the congenital rubella syndrome, the infection is acquired in utero. Cholestatic jaundice with hepatomegaly is observed one to two days after birth. The aminotransferase levels are only mildly elevated, whereas the alkaline phosphatase and bilirubin levels are substantially increased. The patient described in the present report had elevated aminotransferase levels; cholestasis was not observed, and the alkaline phosphatase level was normal. The elevated aminotransferase activity that was found in this patient may be a reflection of the systemic nature of rubella infection. In all likelihood, such mild elevations of aminotransferase activity are not uncommon in adult rubella; however, in most patients with
acute rubella, there is little indication to perform tests of hepatocellular injury, such as determination of alanine aminotransferase and aspartate aminotransferase levels, and hepatic inflammation is rarely recognized. Liver biopsy was not performed in our patient because of the mildness of the biochemical liver abnormalities. Acute rubella infection in adults should be considered another cause of virally induced hepatocellular injury, as has been reported to occur during infections with varicella [5], rubeola [6], adenovirus [ 71, Coxsackie viruses [8,9], and ECHO virus [lo]. Because the viral serology of most cases of “sporadic” acute non-A, non-B hepatitis is not as extensively studied as was done in this case, potentially, a proportion of sporadic hepatitis labeled as non-A, non-B may result from infection with common viruses such as rubella. Such diagnostic considerations are especially worthwhile in mild, transient hepatitis episodes.
REFERENCES 1.
2.
3.
4.
5.
516
Robinson WS: Biology of human hepatitis virus. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. Philadelphia: WB Saunders, 1962; 663-666. Schiff GM: Hepatitis caused by viruses other than hepatitis A, hepatitis B, and non A non B hepatitis viruses. In: Schiff L, Schiff ER, eds. Diseases of the liver, 5th ed. Philadelphia: JB Lippincott, 1962; 61 l-620. Wright R, Millward-Sadler GH: Acute viral hepatitis. In: Wright R, Alberti KGMM, Karran S, Millward-Sadler GH, eds. Liver and biliary disease. Philadelphia: WB Saunders, 1979; 585-646. Sherlock S: Diseases of the liver and biliary system, 6th ed. London: Blackwell Scientific Publications, 1961; 266269. Ortonne JP, Reboul MC, Trepo C, Mallet-Guy Y, Thivolet J:
October
1965
The American
Journal
of Medicine
Volume
6. 7.
6.
9. 10.
79
Hepatite et varicelle. Ann Dermatol Venereol (Paris) 1976; 105: 877-879. McLellan RK, Gleiner JA: Acute hepatitis in an adult with rubeola. JAMA 1962; 247: 2000-2001. Hartwell WV, Love GJ, Eisenbock MD: Adenovirus in blood clots from cases of infectious hepatitis. Science 1966; 152: 1390. Morris JA, Elisberg BL, Pond WL, Webb DA: Hepatitis associated with coxsackie virus group A, type 4. N Engl J Med 1962; 267: 1230-1233. Sun NC, Smith VM: Hepatitis associated with myocarditis. N Engl J Med 1966; 274: 190-193. Schleissner LA, Portnoy B: Hepatitis and pneumonia associated with ECHO virus, type 9 infection in two adult siblings. Ann Intern Med 1966; 66: 13151319.