Sjogren’s syndrome (SS) and the liver

Sjogren’s syndrome (SS) and the liver

J. Reichen M.D.

Definition

Chronic autoimmune disorder affecting exocrine glands resulting in xerostomia and xeroophthalmia (sicca syndrome). Diagnostic requirements (1):

Objective evidence of dryness
Biopsy of a salivary gland (usually lip)
Presence of SS-A

Of note: Low complement levels are associated with grave prognosis in SS (2)

Liver involvement

In 180 patients meeting these criteria, 58 % were ANA, 39 % SMA and 45 % AMA positive (3). However, only 2/3 patients with AMA developed PBC and 4 AIH (3). In another series with ‘primary’ SS, hepatitis C was found in 14 %; in contrast, in patients free of hepatitis C liver involvement was seen in 8 % (4). In another large (n=410) cohort of primary SS, 8.8 % had a cholestatic enzyme pattern and 5.1 % were AMA positive; on biopsy, disease was mild (5). 44 % of patients with SS had abnormal liver enzymes and 20 % clinical liver disease (6); the etiology is given in figure 1.

Comments with respect to associated liver diseases:

Autoimmune hepatitis (7)
Primary biliary cirrhosis (7)

Anti-Ro characteristic and pathogenetic (8) in particular SS-B while SS-A is more widespread in primary Sjogren’s syndrome (9)
On functional testing, Xerophthalmia quite frequent (10)

Hepatitis C

HCV-RNA detectable in salivary glands (11;12)
Negative for SS-B (12), in another study for both SS-A and SS-B (13)
17/22 patients with HCV had mild sialadenitis while 8/10 with SS had severe disease; ANA positivity and HLA-DR3 prevalence much higher in SS (14).
On functional testing, Xerophthalmia is frequent (37 % vs 10 % in normal controls) in hepatitis C (15)

Autoimmune cholangitis (16) and probably pancreatitis related to antibodies against carbonic anhydrase (17;18)
Primary sclerosing cholangitis (19)
Sarcoidosis (20;21).

Treatment
For symptomatic relief artificial tears, anethol trithione (Sialor) (22), oral pilocarpine (23). Immunosuppressive treatment according to the severity of symptoms (1).

Reference List

1. Fox RI. Sjogren's syndrome. Lancet 2005; 366: 321-31.

2. Ramos-Casals M, Brito-Zeron P, Yague J, Akasbi M, Bautista R, Ruano M, Claver G, Gil V, Font J. Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome. Rheumatology (Oxford) 2005; 44: 89-94.

3. Csepregi A, Szodoray P, Zeher M. Do Autoantibodies predict autoimmune liver disease in primary Sjogren's syndrome? Data of 180 patients upon a 5 year follow-up. Scand J Immunol 2002; 56: 623-9.

4. García-Carrasco M, Ramos M, Cervera R, Font J, Vidal J, Muñoz FJ, Miret C, Espinosa G, Ingelmo M. Hepatitis C virus infection in 'primary' Sjogren's syndrome: Prevalence and clinical significance in a series of 90 patients. Ann Rheum Dis 1997; 56: 173-5.

5. Hatzis GS, Fragoulis GE, Karatzaferis A, Delladetsima I, Barbatis C, Moutsopoulos HM. Prevalence and longterm course of primary biliary cirrhosis in primary Sjogrens syndrome. J Rheumatol 2008; 35: 2012-6.

6. Montano-Loza AJ, Crispin-Acuna JC, Remes-Troche JM, Uribe M. Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjogren's syndrome. Ann Hepatol 2007; 6: 150-5.

7. Matsumoto T, Morizane T, Aoki Y, Yamasaki S, Nakajima M, Enomoto N, Kobayashi S, Hashimoto H. Autoimmune hepatitis in primary Sjogren's syndrome: pathological study of the livers and labial salivary glands in 17 patients with primary Sjogren's syndrome. Pathol Int 2005; 55: 70-6.

8. Dorner T, Held C, Trebeljahr G, Lukowsky A, Yamamoto K, Hiepe F. Serologic characteristics in primary biliary cirrhosis associated with sicca syndrome. Scand J Gastroenterol 1994; 29: 655-60.

9. Dörner T, Feist E, Held C, Conrad K, Burmester GR, Hiepe F. Differential recognition of the 52-kd Ro(SS-A) antigen by sera from patients with primary biliary cirrhosis and primary Sjogren's syndrome. Hepatology 1996; 24: 1404-7.

10. Uddenfeldt P, Danielsson A, Forssell A, Holm M, Oestberg Y. Features of Sjoegren's syndrome in patients with primary biliary cirrhosis. J Intern Med 1991; 230: 443-8.

11. Arrieta JJ, Rodríguez-Iñigo E, Ortiz-Movilla N, Bartolomé J, Pardo M, Manzarbeitia F, Oliva H, Macías DM, Carreño V. In situ detection of hepatitis C virus RNA in salivary glands. Am J Pathol 2001; 158: 259-64.

12. Jorgensen C, Legouffe MC, Perney P, Coste J, Tissot B, Segarra C, Bologna C, Bourrat L, Combe B, Blanc F, Sany J. Sicca syndrome associated with hepatitis C virus infection. Arthritis Rheum 1996; 39: 1166-71.

13. Loustaud-Ratti V, Riche A, Liozon E, Labrousse F, Soria P, Rogez S, Babany G, DeLaire L, Denis F, Vidal E. Prevalence and characteristics of Sjogren's syndrome or sicca syndrome in chronic hepatitis C virus infection: A prospective study. J Rheumatol 2001; 28: 2245-51.

14. Pirisi M, Scott C, Fabris C, Ferraccioli G, Soardo G, Ricci R, Toniutto P, Avellini C, Vitulli D, Miotti AM, Beltrami CA, Bartoli E. Mild sialoadenitis: A common finding in patients with hepatitis C virus infection. Scand J Gastroenterol 1994; 29: 940-2.

15. Siagris D, Pharmakakis N, Christofidou M, Petropoulos JK, Vantzou C, Lekkou A, Gogos CA, Labropoulou-Karatza C. Keratoconjunctivitis sicca and chronic HCV infection. Infection 2002; 30: 229-33.

16. Archimandritis A, Tjivras M, Tsirantonaki M, Hatzis G, Delladetsima I. Sjogren's syndrome with antimitochondrial antibody-negative primary biliary cirrhosis: A case of autoimmune cholangitis. J Clin Gastroenterol 1995; 20: 268-70.

17. Kino-Ohsaki J, Nishimori I, Morita M, Okazaki K, Yamamoto Y, Onishi S, Hollingsworth MA. Serum antibodies to carbonic anhydrase I and II in patients with idiopathic chronic pancreatitis and Sjogren's syndrome. Gastroenterology 1996; 110: 1579-86.

18. Lindgren S, Manthorpe R, Eriksson S. Autoimmune liver disease in patients with primary sjogren's syndrome. J Hepatol 1994; 20: 354-8.

19. Nieminen U, Koivisto T, Kahri A, Färkkilä M. Sjogren's syndrome with chronic pancreatitis, sclerosing cholangitis, and pulmonary infiltrations. Am J Gastroenterol 1997; 92: 139-42.

20. Drosos AA, Constantopoulos SH, Psychos D, Stefanou D, Papadimitriou CS, Moutsopoulos HM. The forgotten cause of sicca complex; sarcoidosis. J Rheumatol 1989; 16: 1548-51.

21. Mayor JC, Cabrera J, Garcia J, Romero T. Chronic intrahepatic cholestasis and sicca syndrome of sarcoidosis. J Hepatol 1993; 18: 379-80.

22. Epstein JB, Decoteau WE, Wilkinson A. Effect of Sialor in treatment of xerostomia in Sjogren's syndrome. Oral Surg Oral Med Oral Pathol 1983; 56: 495-9.

23. Bell M, Askari A, Bookman A, Frydrych S, Lamont J, McComb J, Muscoplat C, Slomovic A. Sjogren's syndrome: a critical review of clinical management. J Rheumatol 1999; 26: 2051-61.

February 27^th 2009