Hepatic vasculitis

Fatal hepatotoxicity has also been associated with dacarbazine 500 mg/day for 5 days (5). The cause of this effect is unclear an allergic hepatic vasculitis with thrombosis is possible. 

Adverse reactions The most common adverse effect is maculopapular rash. Rarely, hepatitis, vasculitis, urticarial rash, and arthralgia have been observed. Agranulocytosis can occur in 0.3% to 0.6% of patients. Patients who develop agranulocytosis with one thioamide should not be switched to the alternate thioamide because there is a 50% cross-reactivity between the agents. Methimazole is contraindicated during pregnancy because scalp defeas have been observed in infants bom to mothers using methimazole. 

Lu B, Nelms L, Floyd G, et al. Using correlation analysis and hierarchical clustering to discriminate genes associated with hepatic vasculitis from subsequent hepatic inflammation. Toxicol. Sci. (suppl.) 2004,78 412. 

Numerous drugs have been associated with the development of vasculitis (ten Holder et al. 2002 Cuellar 2002). For example propylthiouracil is associated with cutaneous, renal, and pulmonary vascultis aUopurinol is associated with cutaneous, renal, and hepatic vasculitis hydralazine is associated with cutaneous, renal, and pulmonary vascultis and isotretinoin is associated with cutaneous, renal, pulmonary, and gastrointestinal vascultis (Cuellar 2002 ten Holder et al. 2002). Systemic polyarteritis nodosa, a vasculitis with involvement of small- and mediumsized renal arteries, has been described following minocycline use (Cuellar 2002). Patients may present with hematuria, proteinuria, reduced renal function, and hypertension. Hydralazine, propylthiouracil, aUopurinol, and peniciUamine have been implicated in the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (Choi et al. 2000). Patients exposed to these drugs... 

Neuropathy in human immunodeficiency virus infection has many causes. Multiple mechanisms cause neuropathy in patients with HIV. An immune-mediated, Guillain-Barre-like syndrome (see below) may occur at the time of HIV seroconversion. Later in the course of infection, patients may present with mononeuropathy multiplex, sometimes as a consequence of vasculitis associated with coinfection with hepatitis C. Distal sensory-autonomic axonal polyneuropathy may develop in patients with more advanced HIV, either as a consequence of high titers of HIV itself or of the neurotoxicity of antiretroviral drugs [18,19],... 

The major side effects of allopurinol are skin rash, urticaria, leukopenia, GI problems, headache, and increased frequency of acute gouty attacks with the initiation of therapy. An allopurinol hypersensitivity syndrome characterized by fever, eosinophilia, dermatitis, vasculitis, and renal and hepatic dysfunction occurs rarely but is associated with a 20% mortality rate. 

Zafirlukast and montelukast are generally well tolerated. Rare elevations in serum aminotransferase concentrations and clinical hepatitis have been reported. An idiosyncratic syndrome similar to the Churg-Strauss syndrome, with marked circulating eosinophilia, heart failure, and associated eosinophilic vasculitis, has been reported in a small number of patients a direct causal association has not been established. 

Others Acetazolamide Lithium Thiaazides Phenytoin Rash, fever, autoimmunity Dermatitis autoimmune thyroiditis, vasculitis Hypersensitivity, photosensitivity autoimmunity (diabetes) Rash drug-induced SLE, hepatitis... 

Boyer O, Saadoun D, Abriol J, Dodille M, Piette JC, Cacoub P, Klatzmann D CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 2004 103 3428-3430. 

Hypersensitivity Fever, skin eruptions of various types, including exfoliative dermatitis, infectious mononucleosis-like, or lymphoma-like syndrome, leukopenia, agranulocytosis, thrombocytopenia, Coombs positive hemolytic anemia, jaundice, hepatitis, pericarditis, hypoglycemia, optic neuritis, encephalopathy, Leoffler s syndrome, vasculitis, and a reduction in prothrombin. 

Adverse reactions may also include tachycardia hypertension palpitations syncope cerebrovascular accident vasodilation vasculitis gingivitis dyspepsia oral ulcer/abscess gastritis gastric ulcer hypersalivation dry mouth splenomegaly melena hematochezia esophagitis colitis pancreatitis pancytopenia neutropenia eosinophilia thrombocytopenia hepatitis hepatomegaly hepatic dysfunction renal... 

Adverse effects occur in 3-12% in the form of rash, fever, urticaria, vasculitis, arthralgia, a lupuslike reaction, cholestatic jaundice, hepatitis, lym-phadenopathy and polyserositis but the most dangerous adverse effect is agranulocytosis (it occurs only in 0.3-0.6%). The reaction is readily reversible when the drug is discontinued. Cross-sensitivity between propylthiouracil and methimazole is about 50%, therefore switching drugs in patients with severe reactions is not recommended. 

Adverse reactions include visual disturbances (transient, at the beginning of therapy), nausea and epigastric bloating (rare) and diarrhoea. Hypersensitivity including allergic skin reactions, thrombocytopenia, leucopenia, agranulocytosis, haemolytic anaemia, vasculitis, cholestatic jaundice and hepatitis. 

Adverse reactions to the thioamides occur in 3-12% of treated patients. Most reactions occur early, especially nausea and gastrointestinal distress. An altered sense of taste or smell may occur with methimazole. The most common adverse effect is a maculopapular pruritic rash (4-6%), at times accompanied by systemic signs such as fever. Rare adverse effects include an urticarial rash, vasculitis, a lupus-like reaction, lymphadenopathy, hypoprothrombinemia, exfoliative dermatitis, polyserositis, and acute arthralgia. Hepatitis (more common with propylthiouracil) and cholestatic jaundice (more common with methimazole) can be fatal, although asymptomatic elevations in transaminase levels also occur. 

Trimethoprim produces the predictable adverse effects of an antifolate drug, especially megaloblastic anemia, leukopenia, and granulocytopenia. The combination trimethoprim-sulfamethoxazole may cause all of the untoward reactions associated with sulfonamides. Nausea and vomiting, drug fever, vasculitis, renal damage, and central nervous system disturbances occasionally occur also. Patients with AIDS and pneumocystis pneumonia have a particularly high frequency of untoward reactions to trimethoprim-sulfamethoxazole, especially fever, rashes, leukopenia, diarrhea, elevations of hepatic aminotransferases, hyperkalemia, and hyponatremia. 

A 62-year-old woman with type 2 diabetes, hypertension, and chronic hepatitis C virus infection developed palpable purpura over her legs and buttocks 3 weeks after starting to take repaglinide 500 mg qds (52). The purpura ulcerated and became infected. Repaglinide was withdrawn and the purpura resolved. A biopsy showed leukocytoclastic vasculitis. 

Repaglinide, which is metabolized in the liver, is cleared more slowly in people with liver disease, and hepatitis C may have played a part in this case. Although hepatitis C can cause a leukocytoclastic vasculitis, the clinical correlation and the rapid disappearance of the purpura after the withdrawal of repaglinide makes it likely that this was an adverse effect of the drug. Caution with repaglinide in liver disease is important. 

Margolin N. Severe leucocytoclastic vasculitis induced by repaglinide in a patient with chronic hepatitis C. Clin Drug Invest 2002 22 795-6. 

G20. Gupta, R. C., and Kohler, P. F., Identification of HBsAg determinants in immune complexes from hepatitis B virus-associated vasculitis. J. Immunol. 132, 1223-1228 (1984). 

Christian, C. L., Isolation and characterization of circulating immune complexes in patients with hepatitis B systemic vasculitis. Clin. Immunol. Immunopathol. 21,364-374 (1981). 

Tricyclic antidepressants rarely cause cholestatic jaundice and agranulocytosis due to hypersensitivity reactions. The rare liver necrosis may reflect severe hypersensitivity. Two fatal cases of hypersensitivity myocarditis and hepatitis have been described (1). A variety of dermatological manifestations have been reported (rash, urticaria, vasculitis), but their relation to drug ingestion is often uncertain. A single case of pulmonary hypersensitivity with... 

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