Drug-induced lupus

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. 

Uetrecht, J.P., Mechanism of drug-induced lupus, Chem. Res. Toxicol., 1, 133, 1988... 

Antonov, D et al., Drug-induced lupus erythematosus, Clin. Dermatol., 22, 157, 2004. 

Uetrecht, J.P., Drug metabolism by leukocytes, its role in drug-induced lupus and other idiosyncratic drug reactions, CRC Crit. Rev. Toxicol., 20, 213, 1990. 

Kretz-Rommel, A., Duncan, S.R., and Rubin, R.L., Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus, J. Clin. Invest., 99,1888, 1997. 

Yung, R. et al., Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice, J. Clin. Invest., 97, 2866, 1996. 

Aucoin, D.P. Propylthiouriacil-induced immune mediated disease syndrome in The cat A novel model for a drug-induced lupus-like disease, in Autoimmunity and toxicology. Immune disregulation induced by drugs and chemicals. Kammuller, M.E., Bloksma, N. and Seinen, W., eds., Elsevier, Amsterdam, 1989, chap. 12. 

Hofstra AH, Li-Muller SM, Uetrecht JP. Metabolism of isoniazid by activated leukocytes. Possible role in drug-induced lupus. Drug Metab Dispos 1992 20(2) 205-210. 

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. 

Anti-TNF therapy can give rise to serious reactions, including anaphylaxis, sometimes fatal blood disorders, tuberculosis and other infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, rare reports of drug induced lupus and rare reports of demyelinating central nervous system disorders, which prompted the FDA to change the respective labeling of these drugs. 

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. 

The spectrum of Systemic Lupus Erythematosus (SLE) includes latent lupus, discoid lupus, drug-induced lupus, neonatal lupus, lupus profundus, neuropsychiatric lupus, lupus vasculitis, pulmonary lupus, etc. The disease course is characterized by unpredictable exacerbations, drug-induced remissions and spontaneous remissions. SLE is characterized by a wide range of variable individual clinical manifestations which are controllable at early stages. 

Superinfection, drug-induced lupus erythematosus, and Stevens-Johnson syndrome occur rarely nephrotoxicity with high dermatologic concentrations. 

Approximately 30% of patients using sulfasalazine discontinue the drug because of toxicity. Common adverse effects include nausea, vomiting, headache, and rash. Hemolytic anemia and methemoglobinemia also occur, but rarely. Neutropenia occurs in 1-5% of patients, while thrombocytopenia is very rare. Pulmonary toxicity and positive double-stranded DNA are occasionally seen, but drug-induced lupus is rare. Reversible infertility occurs in men, but sulfasalazine does not affect fertility in women. The drug does not appear to be teratogenic. 

This case is the first report of drug-induced lupus-like syndrome concomitant with severe autoimmune hepatitis in a genetically predisposed patient (23). 

Graziadei IW. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus 2003 12 409-12. 

Antonov D, Kazandjieva J, Etugov D, Gospodinov D, Tsankov N. Drug-induced lupus erythematosus. Clin Dermatol 2004 22(2) 157-66. 

A particularly good example of a drug inducing SLE is the vasodilator hydralazine, sometimes used for the treatment of hypertension. The drug-induced lupus syndrome... 

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