Primary biliary cirrhosis accompanied by CREST syndrome.

ABSTRACT

CREST syndrome, a relatively benign, slowly progressive variant of systemic scleroderma consists of calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Although the association of this syndrome with primary biliary cirrhosis (PBC) is recognized in women, it has never been described in a man. We report the rare case of a male patient with CREST syndrome accompanied by PBC, manifested by acute cholecystitis and mild jaundice. The association of the two conditions is clinically and etiologically important. Clinicians must be aware of this association, since the clinical features of CREST syndrome may be mild and may be thought to be complications of the underlying liver disease.

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PRIMARY BILIARY CIRRHOSIS (PBC) is a chronic, usually progressive liver disease of unknown cause that affects predominantly young to middle-aged women. The presence of autoantibodies and circulating immune complexes (1) and the recognized association of PBC with diseases of probable autoimmune origin (2) suggest a possible autoimmune pathogenesis. The association between PBC and the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) is well recognized in women. We report the first case of CREST syndrome accompanied by PBC in a man.

CASE REPORT

A 69-year-old male patient was admitted to our hospital with acute cholecystitis. Physical examination at the time of admission revealed pain in the right upper quandrant, temperature of 38[degrees]C (100.4[degrees]F), and mild jaundice. He was known to have had CREST syndrome since age 45, with a positive test for anticentromere antibody. He had Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Barium swallow in the past had shown a dilated esophagus and diminished peristalsis. There was no previous history of liver disease, and he had taken no medication.

Biochemical and serologic values were hemoglobin concentration 13.2 g/dL, white blood cell count 16,000/[mm.sup.3], serum aspartate transaminase 78 U/L (normal, 5 to 45 U/L), serum bilirubin 39 [micro]mol/L (normal, <22 [micro]mol/L serum alkaline phosphatase 352 U/L (normal, <250 U/L), serum albumin 41 g/L (normal, 35 to 45 g/L), and prothrombin time 15 seconds (control 14 seconds). Serum IgG and IgA concentrations were normal, while IgM was markedly elevated at 4.9 g/L (normal, 0.5 to 2.0 g/L). Serologic tests for hepatitis B surface antigen were negative. The antimitochondrial antibody test was positive at a high titer (1:500 dilution) and that for antiDNA antibody was negative. Ultrasonography showed a thick-walled gallbladder full of small stones and sludge; the common bile duct was normal.

At operation, the spleen was slightly enlarged, and the liver was cholestatic. Cholecystectomy was done, and a wedge biopsy specimen was taken from the liver for histologic examination. Postoperative recovery was uneventful. Two months later, liver tests continued to show evidence of mild cholestasis even after the operation. Liver biopsy revealed typical changes of nonsuppurative destructive cholangitis and histologic features consistent with PBC (stage I to II by Scheuer's classification).

DISCUSSION

CREST syndrome was described first in 1964 as a combination of features mimicking hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome), but it has since been recognized as a relatively benign, slowly progressive variant of systemic scleroderma. (3) The association of CREST syndrome with liver disease was first recognized in 1970 by Murray-Lyon et al, (4) who described two cases of PBC and CREST syndrome. Further cases were added by Reynolds et al, (5) and subsequently other case reports have emerged linking CREST syndrome to PBC. The association between systemic scleroderma and PBC, though well recognized in women, has been described in only three men, (6) none of whom had the CREST variant. To our knowledge, our case is the first recorded in the English-language literature.

The pathogenetic mechanisms in the development of PBC are unknown, but associations have been described with a number of autoimmune diseases. Portal hypertension is an early feature in PBC and is predominantly sinusoidal in type, being characterized by a raised wedged hepatic vein pressure. (7) Nodular hyperplasia may contribute to the development of portal hypertension. Even though our case fulfilled the histologic criteria for the diagnosis of PBC, the patient did not have associated portal hypertension.

CONCLUSION

The case presented emphasizes that CREST syndrome may be associated with PBC and that the two conditions may occur in a man. Clinicians must be aware of this association since the clinical features of CREST syndrome may be mild and may be thought to be complications of the underlying liver disease.

References

(1.) Gupta RC, Dickson ER, McDuffie FC, et al: circulating IgG complexes in primary biliary cirrhosis: a serial study in forty patients followed for two years. Clin Exp Immunol 1978; 34:19-27

(2.) Randle HW, Millns JL, Schroeter AL, et al: Cutaneous immunofluorescence in primary biliary cirrhosis. JAMA 1981; 246:1679-1681

(3.) Winterbauer RH: Multiple telangiectasia, Raynaud's phenomenon, sclerodactyly, and subcutaneous calcinosis: a syndrome mimicking hereditary haemorrhagic telangiectasia. Bull Johns Hopkins Hosp 1964; 114:361-383

(4.) Murray-Lyon IM, Thompson RPH, Ansell ID, et al: Scleroderma and primary biliary cirrhosis. BMJ 1970; 3:258-259

(5.) Reynolds TB, Denison EK, Frankl H, et al: Primary biliary cirrhosis with scleroderma, Raynaud's phenomenon and telangiectasia--new syndrome. Am J Med 1971; 50:302-312

(6.) Douglas JG, Dewhurst NG, Finlayson NDC: Primary biliary cirrhosis and scleroderma occurring in a man. Br J Clin Pract 1981; 35:284-285

RELATED ARTICLE: KEY POINTS

(7.) Babbs C, Warnes TW, Cope V, et al: Bleeding varices--a significant problem in early biliary cirrhosis. J Hepatol 1986; 3:S1023

* The association between PBC and CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) is well recognized in women. We report the association of the two conditions in a man.

* The association between systemic scleroderma and PBC, though well recognized in women, has been described in only three men, none of whom had the CREST variant.

* Our case emphasizes that CREST syndrome may be associated with PBC and indicates the presence of this association in a man.

From the Second Department of Propedeutic Surgery, Medical School University of Athens, Athens, Greece.

Reprint requests to Gregory Kouraklis, MD, PhD, 122 Vasilisis Sofias Ave, Athens 11526, Greece.