Antinuclear antibodies, drug-induced

The answer is c. (Hardman, p 868. Katzung, pp 231—232) Procainamide blocks open Na+ channels. Long-term therapy can result in drug-induced lupus syndrome, identified by circulating antinuclear antibodies. Many patients may develop a facial rash and joint pains. Pericarditis can occur, but renal involvement is rare. 

Lupus erythematosus Certain patients will develop a positive antinuclear antibody (ANA) test and some may show a lupus erythematosus-like syndrome similar to other drug-induced lupus, but it is not associated with hypocomplementemia and may be present without nephropathy. A positive ANA test does not mandate drug discontinuance however, a lupus erythematosus-like syndrome may develop later. Sensitivity reactions Once instituted for Wilson s disease or cystinuria, continue treatment with penicillamine on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy. 

CNS toxicity occurs because isoniazid has structural similarities to pyridoxine (vitamin Be) and can inhibit its actions. This toxicity is dose-related and more common in slow acetylators. Manifestations include peripheral neuropathy, optic neuritis, ataxia, psychosis and seizures. The administration of pyridoxine to patients receiving INH does not interfere with the tuberculostatic action of INH but it prevents and can even reverse neuritis. Hematological effects include anaemia which is also responsive to pyridoxine. In some 20% of patients antinuclear antibodies can be detected but only in a minority of these patients drug-induced lupus erythematosus becomes manifest. 

Statin-induced lupus-like syndrome is characterized by a long delay between the start of therapy and the skin eruption. Antinuclear antibodies can persist for many months after drug withdrawal. The causal relation may be therefore difficult to establish, and probably many cases are unrecognized. Early diagnosis may avoid unnecessary immunosuppressive therapy. 

Minocycline-induced lupus usually occurs some months, or even years, after the start of therapy, and it usually resolves when the drug is withdrawn. The diagnosis can easily be overlooked, especially in patients with rheumatoid arthritis (37). It would always be wise to foUow the recommendation that a patient s antinuclear antibody be checked before starting minocycline and when drug-induced lupus is suspected. 

According to the authors, the patient fulfilled all the criteria for a diagnosis of drug-induced lupus-like syndrome, that is no history of lupus erythematosus before minocycline therapy, the presence of antinuclear antibodies, at least one clinical feature of lupus erythematosus, and prompt recovery after withdrawal of minocycline. She also had positive antihistone antibodies, compatible with drug-induced lupus-like syndrome. 

The antinuclear antibody is positive in virtually all cases and the ESR is often raised. Antihistone antibodies are also present in most cases. The prevalence of serum autoantibodies to high-mobility group (HMG) proteins in the serum of patients with drug-induced lupus-like syndrome varies from protein to protein 67% for HMG-14 and/or HMG-17 compared with 21% for HMG-1 and/or HMG-2. Procainamide-induced lupus is also associated with antibodies to the H2A-H2B dimer (55,56). 

Several cases of a reaction resembUng systemic lupus erythematosus have been described (24-26). One patient taking hydrochlorothiazide developed unequivocal antinuclear antibody (ANA) positivity, with the homogeneous pattern most commonly found in drug-induced lupus (27). It is uncertain whether thiazides cause a lupuslike syndrome or activate latent disease in predisposed individuals. 

An abnormal titer of antinuclear antibody by immunofluorescence or an antibody equivalent assay at any point in time in the absence of drugs known to be associated with "drug-induced lupus" syndrome... 

The exact phenotype of the regulatory T cells in the case of low-dose D-penicillamine tolerance is not known, and non-lymphoid cells probably play a role as well. In another example of drug-induced autoimmune responses, the phenotype of regulatory T cells was identified as CD4+CD25+ (Layland et ah, 2004). In this study, CD4+CD25+ cells isolated from mice (A/J strain) exposed to procainamide, mercuiy(II) chloride, or gold salts were capable of preventing antinuclear antibody formation in similarly treated recipient mice, but also in mice subsequently treated with one of the other two chemicals. 

Dogs are a species frequently used in toxicity studies. However, there are only few reports in the open literature on dog studies with respect to chemical- or drug-induced hypersensitivity reactions or autoimmune effects, and studies are also often contradictory. For instance, procainamide has been shown to induce mainly an increase in antinuclear antibodies in one study (Balazs Robinson, 1983), but not in another study with younger dogs (Dubois Strain, 1972). Similar discrepancies were observed for hydralazine-induced effects in mice (Kammuller et al., 1989a). 

Autoimmune hepatitis (AIH). Chronic autoimmune-mediated hepatic inflammation characterized by antinuclear (ANA), smooth muscle (SMA)/anti-F-actin, liver-kidney microsomal (LKM), and soluble liver antigen (SLA) antibodies. Autoimmune hepatitis constitutes 10-20% of all cases of chronic hepatitis, ft may be idiopathic (Alff type 1, 2, and 3), part of autoimmune polyendocrine syndrome type 1 (APECED hepatitis), or drug-induced. See also -liver-kidney microsomal antibodies, liver-specific antigens. 

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. 

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