Two Diseases, One Treatment: The Challenges Faced When Treating an Overlap Syndrome

Abstract

Introduction: A 53-year-old female with arterial hypertension and bronchial asthma complained of abdominal pain for the past 4 months. The pain was epigastric, stabbing, 10/10, irradiating to the lower abdomen, lasting hours to days, not associated to food, and without any improving or worsening factors. This was accompanied by nausea and 2-3 episodes of vomiting per day, of gastric content without blood or bile. She had anorexia with an 8-pounds loss in 6 months, general malaise, weakness, fatigue, itching, joint pain (wrist, elbow, and knee), dry mouth and eyes, and occasional swelling of her legs. She also complained of a red rash throughout the body, and hyperpigmentation of the arms. She used alcohol daily for 30 years and smoked 10-15 cigarettes each day, but quit both 5 years ago. Physical exam showed an overweight patient with a body mass Index of 28.7 kg/m2. Scattered bilateral forearm hyperpigmented areas and erythematous blanching papules were present in the chest and extremities. The abdomen showed no distention, normal bowel sounds, diffuse tenderness to deep palpation, no rebound tenderness, no palpable spleen, resonant percussion, a liver span of 11 cm, and no shifting dullness. Laboratories showed normal CBC, prothrombin time, and partial thromboplastin time. Aspartate and alanine aminotransferases were 308 and 407 IU/L respectively, alkaline phosphatase was 467 IU/L, total bilirubin was 1.25 mg/dL, and globulins were 8.3 g/dL. Hepatitis serology, lipid panel, iron studies, and anti-nuclear antibody were normal. Anti-mitochondrial antibody titers were 1:640 and immunoglobulin M was 425 mg/dL. Abdominal sonogram showed a liver normal in size, echotexture, and echogenicity without any focal mass. Liver biopsy showed chronic portal inflammation (confluent necrosis) with lymphocytes and plasma cells suggestive of autoimmune hepatitis, and bile duct destruction and loss suggestive of primary biliary cirrhosis. The diagnosis of overlap syndrome was made. On follow-up, improvement of liver enzymes without any therapy was noted. It was decided to start the patient only on ursodiol 15 mg/kg. After 4 months, there was a complete normalization of all liver chemistry. Deciding whether to target the autoimmune hepatitis or the biliary component is a challenging decision for the clinician. Individual features usually guide the decision, and close observation of the response is necessary. Adequate response to therapy is not always obtained, even when combined therapy is given. Randomized clinical trials comparing single versus combined therapy for both diseases are necessary to define therapeutic guidelines for the overlap syndrome. Disclosure - Dr. Torres - Advisory board: AbbVie.