Hepatitis penicillamine

Penicillamine (29) can be effective in patients with refractory RA and may delay progression of erosions, but adverse effects limit its useflilness. The most common adverse side effects for penicillamine are similar to those of parenteral gold therapy, ie, pmritic rash, protein uria, leukopenia, and thrombocytopenia. Decreased or altered taste sensation is a relatively common adverse effect for penicillamine. A monthly blood count, platelet count, and urinalysis are recommended, and also hepatic and renal function should be periodically monitored. Penicillamine is teratogenic and should not be used during pregnancy. 

Hepatotoxicity Penicillamine has been associated with a mild elevation of hepatic enzymes that usually returns to normal even with continuation of the drug. Autoimmune syndromes Autoimmune syndromes that may be caused by penicillamine include polymyositis, diffuse alveolitis and dermatomyositis, Goodpasture s syndrome, myasthenic syndrome, pemphigus, and obliterative bronchiolitis. 

In the case of hepatitis associated with Wilsons disease D-penicillamine, initially 1.5-2 g daily is indicated, then reducing to half after one year. 

Penicillamine had a small effect on urinary glucaric acid excretion in patients with rheumatoid arthritis (923). This effect was thought to be the result of an indirect effect on hepatic metabolism and not to be related to disease activity. 

Hepatitis with cholestasis Chlorpromazine, tricyclics, erythromycin, flucloxacillin, co-amoxiclav, ACE inhibitors, phenytoin, NSAIDs, ranitidine, propafenone, ketoconazole, azathioprine, gold salts, penicillamine... 

Chan, C.-Y., Baker, A.L. Penicillamine hypersensitivity successful desensitization of a patient with severe hepatic Wilson s disease. Amer. J. Gastroenterol. 1994 89 442-443... 

Several case reports have demonstrated that penicillamine can cause hver damage (SEDA-13, 199) (184), mainly cholestatic hepatitis, often associated with other signs of hypersensitivity such as fever, rash (185), and pulmonary (159,186) or hematological reactions (162). In two children with Wilson s disease, penicillamine was thought to have caused persistence of a pre-existing increase in aminotransferase activity (187). 

Porzio S, lorio R, Vajro P, Pensati P, Vegnente A. Penicillamine-related neurologic syndrome in a child affected by Wilson disease with hepatic presentation. Arch Neurol 1997 54(9) 1166-8. 

Kumar A, Bhat A, Gupta DK, Goel A, Malaviya AN. D-penicillamine-induced acute hypersensitivity pnenmoni-tis and cholestatic hepatitis in a patient with rhenmatoid arthritis. Clin Exp Rheumatol 1985 3(4) 337-9. 

MultzCV. Cholestatic hepatitis caused by penicillamine. JAMA 1981 246 674-675. 

Acebutolol Alpha-methyl-dopa Captopril Carbimazole Chlorpromazine Dihydralazine Fludarabine Hydralazine Infliximab Interferons-alpha Iproniazid Isoniazid Nomifensine Penicillamine D-Penicillamine Practolol Procainamide Propylthiouracil rlL-2 Simvastatin Tienilic acid Tryptophan contaminants Zimeldine Lupus syndrome Autoimmune haemolytic anaemia Pemphigus ANCA-associated vasculitis Lupus syndrome Autoimmune hepatitis Autoimmune haemolytic anaemia Lupus syndrome, ANCA-associated vasculitis Lupus syndrome Wide range of autoimmune diseases Autoimmune hepatitis Lupus syndrome Autoimmune haemolytic anaemia Myasthenia, dermatomyositis Anti-GBM (Goodpasture) disease Oculocutaneomucous syndrome Lupus syndrome ANCA-associated vasculitis Autoimmune thyroiditis Lupus syndrome Autoimmune hepatitis Eosinophilia myalgia syndrome (see section 9.3.5) Guillain-Barre syndrome... 

Some drugs such as hydralazine or procainamide may induce lupus like diseases with antinuclear antibodies and proteinuria. D-penicillamine not only causes glomerulopathies, but also myasthenia, polymyositis or lupus, suggesting that this compound provokes immune disregulation. Gold salts also are capable of inducing various immunopathological disorders such as pneumonitis, anemia, thrombocytopenia and hepatitis. 

D-penicillamine is so named because it was first isolated as an amine, from the degradation products of penicillin by Abraham et al [87]. Later studies showed the characteristic chemical behavior of D-penicillamine which involve three types of reactions, formation of disulphide links, formation of thiazolidine rings, and formation of metal complexes and chelates [67]. It was first used in 1956 in the treatment of Wilson s disease [88]. D-penicillamine has since been used in the treatment of many diseases, such as cystinuria [89], rheumatoid arthritis [90-92], systemic sclerosis [93], primary bdiary cirrhosis [94], heavy metal poisoning due to lead [95], cadmium [%], and mercury [97], and hyperviscosity syndrome [99]. In rheumatoid arthritis, D-peni-cdlamine has been widely accepted as an effective second line treatment. Despite of its effectiveness, it causes many adverse effects, such as skin rashes [99,100], taste abnormalities [100,101], hepatic dysfunction [102-104], gastrointestinal toxiciiy [99,105], proteinuria [100,106], hematuria [107, 108], thrombocytopenia [92, 109], aplastic anemia [110], lupus-like syndrome [111, 112], Goodpasture s-tike pulmonary renal syndrome [113-115], vasculitis [116,117], myasthenia gravis [118-122], polymyositis [123, 124], and dermatomyositis [125]. 

Lead (tap water, leaded paint chips, herbal remedies, gas-sniffing, glazed kitchenware, etc.) Acute N and V, GI distress and pain, malaise, tremor, tinnitus, paresthesias, encephalopathy (red or black feces) Chronic multisystem effects—anemia (X heme synthesis), neuronathv (wrist dronL nephropathy (proteinuria, failure), hepatitis, mental retardation (from pica), >1 fertility and 1 stillbirths Decontamination—gastric lavage + dimercaprol (severe) or EDTA or succimer (penicillamine if unable to use dimercaprol or succimer) Children succimer PO... 

Penicillamine is contraindicated in patients with a history of penicillamine-related aplastic anemia or agranulo-cystosis in patients with significant renal or hepatic insufficiency in pregnant women and in patients receiving gold salts, immunosuppressants, antimalarials, or phenylbutazone because of the increased risk of serious hematologic effects. 

---