Biliary sclerosis

In 27 patients who received intrahepatic floxuridine, total dose 20-41 mg/kg extrahepatic biliary sclerosis was discovered by CT scan and ultrasound, followed by endoscopic retrograde cholangiopancreatography and/or percutaneous cholangiography in three cases (4). Radiological findings included complete obstruction of the common hepatic duct in one case, common hepatic duct stenosis in two cases, common bile duct obstruction in one case, and intrahepatic bile duct dilatation without identifiable obstruction in one case... 

Intrahepatic infusion of fluorouracil can cause bihary sclerosis (102), believed to result from perfusion of the blood supply to the gall bladder and upper bUe duct with high local concentrations of the drug. The median time to onset of biliary sclerosis is three treatment cycles, and although fluorouracil may be restarted at a lower dose after normalization of serum hepatic enzyme activities, most patients become progressively less tolerant. 

Of 57 consecutive patients treated with implanted hepatic arterial infusion pumps with a regimen of alternating floxuridine (0.1 mg/kg/day for 7 days) followed by a weekly pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks), two developed biliary sclerosis and 12 had mild transient liver function abnormalities (103). The liver alone or in combination with another area was the site of first progression of disease in 40 patients. 

Floxuridine (FUdR) FUdR (fluorodeoxyuridine FUDR) is used primarily by continuous infusion into the hepatic artery for treatment of metastatic carcinoma of the colon or following resection of hepatic metastases, the response rate to such infusion is 40 to 50%, or double that observed with intravenous administration. Intrahepatic arterial infusion for 14 to 21 days may be used with minimal systemic toxicity. However, there is a significant risk of biliary sclerosis if this route is used for multiple cycles of therapy. Treatment should be discontinued at the earliest manifestation of toxicity (usually stomatitis or diarrhea) because the maximal effects of bone marrow suppression and gut toxicity will not be evident until days 7 to 14. 

A recent report by the National Institutes of Health estimated that at 14 to 22 million people in the United States are affected by an autoimmune disease.1 As a group, these diseases represent a leading cause of death among women under age 65, with systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes being the major sources of this impact on mortality.2 The autoimmune thyroid diseases, type 1 diabetes and rheumatoid arthritis are the most common of the autoimmune diseases (Table 25.1).3-5 Most autoimmune diseases disproportionately affect women. In the thyroid diseases, primary biliary cirrhosis, scleroderma, systemic lupus erythematosus, and Sjogren s syndrome, more than 85% of patients are female, but it is not known why the female predominance is so high in these specific diseases. 

Unlabeled Uses Treatment of biliary cirrhosis, chronic acfive hepatitis, glomerulonephritis, inflammatory bowel disease, inflammatory myopathy, multiple sclerosis, myasthenia gravis, nephrotic syndrome, pemphigoid, pemphigus, polymyositis, systemic lupus erythematosus... 

Although CSA has been used for treatment of other autoimmune diseases such as atopic dermatitis, myasthenia gravis, systemic sclerosis and primary biliary cirrhosis, data about chronic structural injury in these situations are scarce. There are occasional reports of end stage renal failure or development of interstitial fibrosis in kidney biopsies in demyelinat-... 

Almost all autoimmune diseases that occur in adults disproportionately affect women. However, there is considerable variability in the extent of female predominance and no clear relation between degree of female predominance and type of disease or age at onset (Table 7). More than 85% of patients with Sjogren syndrome, systemic lupus erythematosus, systemic sclerosis, the autoimmune thyroid diseases, and primary biliary cirrhosis are female, compared with 65-75% of patients with rheumatoid arthritis and multiple sclerosis. Some diseases (e.g. diabetes mellitus type 1, ANCA-associated vasculitis, primary sclerosing cholangitis) occur more often in males than in females. 

Sjogren syndrome. Chronic inflammatory autoimmune disease of the exocrine glands of unknown etiology. Its primary symptoms are keratoconjunctivitis sicca and xerostomia. Two types of Sjogren syndrome are distinguished a primary (isolated) type and a secondary type associated with another underlying autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, autoimmune hepatitis, multiple sclerosis, thyroiditis, autoimmune, etc.). Ro/SS-A and La/SS-B autoantibodies are used as classification criteria. 

Anomalies in the acute phase protein response have been reported in various diseases. Studies in systemic lupus erythematosus, dermatomyositis, systemic sclerosis, mixed connective tissue disease, ulcerative colitis, primary biliary cirrhosis, and chronic active hepatitis have shown low acute phase protein responses for the amount of inflammatory activity present (P6). This may be due either to disease-related unresponsiveness or to down-regulation of the acute phase response in chronic inflammation (Ml, W16). Patients with systemic sclerosis do not mount an appreciable acute phase response to therapeutic infusion of PGE, compared with patients with atherosclerosis (W24), although they do to infections (C20). 

Certain inherited diseases are associated with abnormal trace metal metabolism, and this may be linked to MT synthesis, either directly or indirectly. Zinc, copper, and iron are the target elements in several diseases, and their concentrations may be altered in disorders of the central nervous system or other physiological systems, including Alzheimer-type dementia, amyotrophic lateral sclerosis, acrodermatitis enteropathica, biliary cirrhosis, Wilson s and Menke s diseases (Bremner 1987), epi-... 

Although systemic sclerosis is the most commonly reported disorder occurring following silicone breast implantation, there have also been reports of systemic lupus erythematosus [43,44,46,50], Sjogren s syndrome [45], keratoconjunctivitis sicca [45], rheumatoid arthritis [4,34,43], polymyositis [43], overlap syndromes (including human adjuvant disease) [34,43,46,50,51], morphea [35,43], Hashimoto s thyroiditis [43,52], anticar-diolipin antibody syndrome [53], primary biliary cirrhosis [45] and toxic shock syndrome [54]. Unfortunately, it is impossible to tell, on the basis of case reports, whether the frequency of these events is greater than might be expected on the basis of chance alone (Table 7.1). 

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