Overlap Syndrome of Autoimmune Hepatitis and Primary Biliary Cirrhosis in a Patient with Limited Scleroderma: Case Report and Review of Literature

Abstract

Purpose: Limited cutaneous scleroderma (lcSSc) associated with overlap of Autoimmune Hepatitis (AIH) and Primary Biliary Cirrhosis (PBC) has never been reported. There are few reported cases of systemic sclerosis (SSc) associated with PBC also called Reynold's Syndrome. Methods: We report the case of a 69-year-old female patient with past history of scleroderma, hypothyroidism and abnormal liver profile. The diagnosis of SSc was made at an outside hospital where she also had a liver biopsy. She then transferred her care to our hospital. Her presenting symptoms were weight loss, dysphagia, pruritus and color change of fingers to cold exposure. Physical exam was remarkable for sclerodactyly of distal extremities, cool to touch fingers and telangiectasia over both palms. Laboratory investigations revealed abnormal LFTs, with cholestatic index positive for alkaline phosphatase rising 4 fold and necrotic index positive for ALT rising 3 fold above the upper limit, with no hyperbilirubinemia. Immunological work up revealed positive ANA (1:1280), anticentromere Ab (1:640), antimitochondrial Ab (AMA) (1:40) and Anti smooth muscle Ab (1:20). Liver biospy slides were reviewed by our pathologist showing mild interface hepatitis with necroinflammatory activity and bile duct damage. Based on these overlap features it was reported as possible overlap syndrome of AIH and PBC. She was started on amlodipine for Raynaud's phenomenon and ursodeoxycholic acid with symptomatic improvement. Results: An overlap of PBC and SSc (PBC-SSc) characterized by jaundice, elevated alkaline phosphatase, calcinosis cutis, telangiectasias, and pruritus was first described by Telfer B. Reynolds. PBC-SSc is not uncommon with prevalence from 7.4 to 12.5 percent. Most of the patients with PBC-SSc have lcSSc and higher positivity for anticentromere and AMA. They also have slower progression of liver disease and significantly lower risk of liver transplantation or death from diagnosis. But association of SSc with AIH is very rare with only few reported cases. Among the overlap syndromes of autoimmune liver diseases 7 to 14 percent of patients with PBC may have immunological or clinical features suggestive of AIH while bile duct damage can be seen in upto 25 percent of patients with AIH. Studies have shown that patients with this overlap resemble more to PBC patients in terms of disease course and response to ursodeoxycholic acid. Conclusion: Our patient has lcSSc with serological, biochemical and pathological features of both AIH and PBC. In our patient four fold elevation of alkaline phosphatase with milder elevation of transaminases along with low titres of AMA favors a diagnosis of overlap syndrome of AIH and PBC.