ORAL MEDICINE Editor: H. Dean Millard

Primary biliary cirrhosis Sole presentation with rampant dental caries

Andrea Richards, MSc FDS,a Jane Rooney, FDSb Stephen Prime, PhD, FDSRCPS, MRCPath,C and Crispian Scully, PhD, MD, MDS, FDSRCPS, FFDRCSI, FDSRCS, FRCPath,d Bristol, U.K. CENTRE FOR THE STUDY OF ORAL DISEASE, UNIVERSITY DEPARTMENT OF ORAL MEDICINE,

PATHOLOGY AND MICROBIOLOGY, BRISTOL DENTAL SCHOOL AND HEAl.TH

A 55-year-old woman was referred by her general dental practitioner for management of rampant dental caries of

recent onset. Examination revealed a very dry mouth, angular stomatitis, and multiple carious lesions. Labial salivary gland biopsy

showed features consistent with Sjiigren’s syndrome. Hematologic investigations showed antimitochondrial antibodies at a titer

of 1 in 320, highly suggestive of primary biliary cirrhosis that was confirmed by liver biopsy. (ORAL SURC ORAL MED ORAL PATHOL

1994;77:16-18)

Primary biliary cirrhosis (PBC) is an autoimmune chronic destructive nonsuppurative cholangitis char- acterized by progressive inflammatory destruction of intrahepatic bile ducts. Over 90% of patients are fe- male. PBC may be associated with a variety of other autoimmune disorders such as scleroderma, CRST syndrome (calcinosis cutis, Raynaud’s phenomenon, sclerodactyly, and telangiectasia), CREST syndrome (CRST syndrome plus esophageal dysmotility), or rheumatoid arthritis. ‘3 2 Over 90% of PBC patients have serum antimitochondrial antibodies, l, 3 and some also express antibodies directed against ribosomal, smooth muscle, nuclear, double stranded deoxyribo- nucleic acid (DNA), and thyroid components. ‘3 4, 5 Serum immunoglobulin levels are raised and circu- lating immune complexes present. Granulomas are frequently found in the liver, lymph nodes, lung, and bone marrow.‘, 2

A connection exists between PBC and a sicca syn- drome of dry mouth and dry eyes although the exact

“Lecturer. bSenior Registrar. cProfessor.

dProfessor and Department Head. Copyright @ 1994 by Mosby-Year Book, Inc. 0030-4220/93/$1.00 + .lO 7/13/51337

16

nature is unclear. In 1970 Golding6 found that 72% of patients with PBC had sicca symptoms, and in 1988 Hansen7 found evidence of focal sialadenitis in 93% of PBC patients although only 30% to 33% had objective signs of keratoconjunctivitis sicca or abnor- mal sialometry results. Conversely, however, only 6% to 13% of patients with Sjiigren’s syndrome (SS) have antimitochondrial antibodies or biochemical evidence of liver disease.8, 9

Other oral conditions that may be associated with PBC include lichen planus,“* I1 gingival xanthoma- tosis,” green staining of teeth and mucosa, and enamel hypoplasia.”

We present a case of primary biliary cirrhosis that appeared as rampant caries consequent to the xe- rostomia.

CASE REPORT A 55-year-old married post office clerk was referred by

her general dental practitioner for management of rapid breakdown of her teeth as a result of dental caries. She had previously been a regular attender for dental care, had good oral hygiene, and a well-restored dentition. However, over the preceding 6-month period she had lost a number of res- torations and had evidence of new carious lesions.

Questioning revealed an S-year history of an uncomfort- able dry mouth that had been worse during the last 6 months, and she had been in the habit of sucking confec-

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Richards et al. 17 Volume 77, Number 1

tionary in an attempt to relieve the oral discomfort. She also complained of dry, itchy eyes but had no systemic symp- toms, and apart from a history of hiatus hernia and osteoarthritis and use of ranitidine and hormone replace- ment therapy, her medical history was clear.

On examination she was normotensive, and the results of a urinalysis were negative. She had bilateral angular stomatitis and her oral mucosa, in particular the upper an- terior gingiva, was smooth, red, and shiny with a parched appearance. Her saliva was frothy and stringy. She had multiple carious lesions at the margins of restorations in both anterior and posterior teeth. Her mouth was obviously dry, with no pooling of saliva in the floor, no saliva expressed from the major duct orifices, and a mirror passed across the buccal mucosa adhered to the surface. The unstimulated whole saliva flow rate was markedly reduced to below 0.1 ml in 15 minutes (normal > 1.5 ml/l 5 min). A Schirmer’s test showed virtually no tear production after 5 minutes. A provisional diagnosis of SS was made.

Hematologic investigations showed a microcytic hy- pochromic anemia with markedly reduced serum ferritin. Antibodies to SS-A (Ro) and SS-B (La) were absent, but antimitochrondrial antibodies were present at a titer of 1 in 320, highly suggestive of PBC. Results of liver function tests were normal however. An oral smear was positive for Can- dida albicans, and labial gland biopsy showed the typical lymphocytic infiltrate of the minor salivary glands consis- tent with a diagnosis of SS.

The following regimen was prescribed: ferrous sulphate tablets, nystatin suspension, and cream and saliva substi- tutes of carboxymethyl cellulose. An intensive course of preventive and restorative dental care was begun, including dietary advice and fluoride mouthwashes.

She was referred for a liver biopsy that showed features suggestive both of PBC and of chronic active hepatitis. In the absence of abnormal liver function tests, the antihista- mine terfenadine was prescribed for relief of pruritus. Over the following year, she became intermittently jaundiced with severe pruritus and genera1 malaise, the serum alkaline phosphatase and asparatate transaminase levels became raised, and the titer of antimitochondrial antibody rose to 1 in 640. An ultrasound scan of the liver showed no abnor- malities. Despite treatment with cholestyramine, ursodeox- ycholic acid, and prednisolone, her condition continued to deteriorate, and she was therefore treated with azathio- prine. Her pruritus remained severe and difficult to control, and she was therefore referred for consideration of a liver transplant.

DISCUSSION The symptoms of PBC are typically insidious early

in the disease; pruritus and fatigue are the typical presenting features. Jaundice, hyperpigmentation of the skin, and steatorrhoea subsequently develop, and the liver and spleen become enlarged. Progressive fi- brosis and cirrhosis of the liver eventually result in spontaneous hemorrhage, osteoporosis, osteomalacia, portal hypertension, fluid retention, and hepatic en-

cephalopathy. Patients are also at risk of developing hepatocellular carcinoma. l4 Many more patients are being diagnosed in an asymptomatic state, possibly because of increased routine blood screening.‘, l5 The present patient falls into this category. One fifth of patients present with jaundice, gastrointestinal bleed- ing, or ascites and 5% with symptoms suggestive of vas- cular disease or autoimmune disease.r5 In one series, one third of patients, who were asymptomatic at the time of diagnosis, did progress clinically and histolog- ically, and their survival was no different from those patients who presented with symptomatic disease. l6

The initial hepatic lesion is an often focal destruc- tion of bile ducts of 50 to 100 pm in diameter.15 T-lymphocytes predominate in the mixed cellular in- filtrate. As bile duct destruction continues, portal fi- brosis results in mechanical obstruction to the flow of bile. Hepatocyte destruction and cirrhosis follow. There may be histologic features compatible with overlap with chronic active hepatitis in 23% of patients. I7 Histologic staging does not appear to cor- relate well with clinical features.

Antimitochondrial antibodies (AMA) are a spe- cific serologic marker for PBC. Great progress has been made in recent years in the identification and characterization of this diverse group of antibodies, and now nine different antibody types have been identified,‘* four of which are closely associated with PBC, but at present it is unknown whether the type and titer of AMAs found in PBC have prognostic value. AMAs have been reported in other autoim- mune disorders but with a far lower incidence. The approximate incidence of AMAs in chronic active hepatitis is 11% to 24%,8 sicca syndrome 6% to lo%, Sjogren’s syndrome with rheumatoid arthritis 1.5%, and rheumatoid arthritis alone less than 1.5% to 4%.‘9-2’

A number of studies of different drug therapies for PBC has so far yielded contradictory and often disappointing results’, l5 and point to the difficulties of assessing treatment of a disorder with such diverse presentation and clinical course. However, liver trans- plantation is being increasingly used, and survival is improving.

The present patient had dental caries of recent on- set. It is most unusual for an adult with a previously well-maintained dentition to develop rampant caries in the absence of significant salivary gland hypofunc- tion or dietary change. Both factors were at play here, but although this patient had been aware of an uncomfortably dry mouth for many years, it was not thought by her dental practitioner to be sufficiently severe to warrant further investigation. Her dental practitioner was unaware of her understandable but

18 Richards et al. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOCY January I994

misguided efforts to relieve her symptoms by sucking confectionary.

Xerostomia can have many causes, particularly drugs and salivary gland disease, most notably SS. SS associated with PBC is rare, however.*, 9 In the absence of such a connective tissue disorder, the dis- ease is primary SS. Secondary SS is most frequently associated with rheumatoid arthritis or systemic lupus erythematosus. The ratio of women to men af- fected is 9 to 1, and any age group may be affected al- though secondary SS is more common in the elderly. Symptoms of SS are frequently insidious in onset, and xerostomia is occasionally the presenting symptom although not all patients complain of dry mouth at the time of presentationz2 and the xerostomia appears to vary in severity over time.

Although liver disease is rare in SS, sicca symptoms seem to be common among PBC patients, but there is little clear association with salivary gland hypofunc- tion measured objectively, and the finding of serologic markers of SS is inconsistent and frequently unrelated to the sicca symptoms. We are not aware of any pre- vious reports of PBC presenting with dental caries as a result of xerostomia.

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Mrs. A. Richards Centre for the Studv of Oral Disease University Department of Oral Medicine, Pathology,

and Microbiology Bristol Dental School and Hospital Lower Maudlin Street Bristol BSl 2LY U.K.