Induced Lupus Erythematosus

A few years ago Maas and Schubothe (1973) and Maas et al. (1974,1975) described a syndrome clinically resembling LE in which antimitochondrial antibodies were present, but not antinuclear antibodies. Skin manifestations were, however, absent. Not long afterwards it was pointed out that in many of these cases of pseu-do-LE syndrome there was probably a link with the substance Venopyronum (intended for diseases of veins and containing l,4-diphenyl-3,5-dioxo-pyrazolidine together with certain plant extracts). The reported data show that the patients involved had been taking this product for several months or years (Maas and Schubothe 1973 Maas et al. 1974, 1975 Muller-Schoop et al. 1975 Schwarz and JosT 1975). 

As drug-induced LE is not a genuine allergic condition, it will be apparent that conventional methods of identifying the cause, such as skin tests and detection of antibodies, are of no value. The cause of the condition can be ascertained only by analyzing the patient s history and the course of the disease. 

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

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. 

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

There is an increase in the incidence of hydralazine-induced lupus erythematosus (LE) in the exposed population with increasing dose as can be seen in Table 7.9. However, patients who develop LE do not have a significantly different cumulative intake of hydralazine from those patients who do not develop the syndrome. This latter observation is consistent with the absence of a clear dose-response relationship in many cases of toxicity with an immunological basis. 

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

Simvastatin-induced lupus erythematosus was suspected in a 79-year-old white man after 3 months (35). He had signs of pleuropericarditis that resolved within 2 weeks of withdrawal. 

Khosla R, Butman AN, Hammer DF. Simvastatin-induced lupus erythematosus. South Med J 1998 91(9) 873 1. 

More than 80 drugs have been associated with drug-induced lupus erythematosus, including procainamide, hydralazine, isoniazid, and minocycline (Box 35-7). 

Modified from Sarzi-Puttini P, Atzeni F, Capsoni F, et al. Drug-induced lupus erythematosus. Autoimmunit/ 2005 38 507-51 8. 

Drug-induced lupus erythematosus, caused by hydralazine, procainamide, sulfasalazine. 

Kushner W, Jones C, Schmid FR, Askenazi J. Remission of procainamide-induced lupus erythematosus with N-acetylprocainamide therapy. Ann Intern Med 1979 90(5) 799-801. 

Sheikhzadeh A, Schafer U, Schnabel A. Drug-induced lupus erythematosus by amiodarone. Arch Intern Med 2002 162(7) 834-6. 

Patel GK, Anstey AV. Rifampicin-induced lupus erythematosus. Clin Exp Dermatol 2001 26(3) 260-2. 

Enzenauer RJ, West SG, Rubin RL. D-penicillamine-induced lupus erythematosus. Arthritis Rheum 1990 33(10) 1582-5. 

Sherertz EF. Lichen planus following procainamide-induced lupus erythematosus. Cutis 1988 42(l) 51-3. 

Murphy M, Barnes L. Terbinafine-induced lupus erythematosus. Br J Dermatol 1998 138(4) 708-9. 

Zonisamide-induced lupus erythematosus has been reported in a 5-year-old child taking zonisamide and etho-suximide (15). He had raised titers of antinuclear antibodies and anti-DNA antibodies and presented with fever, pericarditis, pleurisy, and arthralgia. Clinical recovery and a reduction in the anti-DNA-antibody titer promptly followed withdrawal. A lymphocyte transformation test against zonisamide was positive. 

Sarzi-Puttini P, Atzeni F,Capsoni F, Fubrano E, Doria A Drug-induced lupus erythematosus, Autoimmunity 2005,38 507-518 Vielhauer V, Mayadas TN Functions of TNF and its receptors in renal disease distinct roles in inflammatory tissue injury and immune regulation, Semin Nephrol 2007,27 286-308... 

Minocycline has better gastrointestinal absorption than tetracycline and may be less photosensitizing than either tetracycline or doxycycline. Side effects of minocycline include dizziness and hyperpigmentation of the skin and mucosa, serum-sickness-like reactions, and drug-induced lupus erythematosus. With all the tetracyclines, vaginal candidiasis is a common complication that is readily treated with local administration of antifungal drugs. 

A. Hydralazine and Minoxidil These older vasodilators have more effect on arterioles than on veins. They are orally active and suitable for chronic therapy. Hydralazine apparently acts through the release of nitric oxide. However, it is rarely used at high dosage because of its toxicity therefore, its efficacy is limited, fts toxicities include compensatory responses (tachycardia, salt and water retention Table 11-2) and drug-induced lupus erythematosus, which is reversible upon stopping the drug. However, this effect is uncommon at dosages below 200 mg/d. 

Donker AJ, Venuto RC, Vladutiu AO, Brentjens JR, Andres GA (1984) Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Brown Norway rats treated with D-penicillamine develop autoantibodies, circulating inunune complexes, and disseminated intravascular coagulation. Clin Immunol biununopathol 30 142-155 Enzenauer RJ, West SG, Rubin RL (1990) D-penicillamine-induced lupus erythematosus. Arthritis Rheum 33 1582-1585... 

B. Chronic therapeutic INH use may cause peripheral neuritis, hepatitis, hypersensitivity reactions inciuding drug-induced lupus erythematosus, and pyri-doxine deficiency. 

Procainamide therapy is the most frequent cause of drug-induced lupus erythematosus. About 100 cases have so far been reported the largest series, 44 cases, was by Blomgren et al. (1972), but there have been several smaller series (Siegel et al. 1967 Hope and Bates 1972 Swerbrick and Grey 1973 Bareis 1974). 

It is difficult to derive an overall figure for the incidence of procainamide-induced lupus erythematosus, mainly due to the difficulty of accurately diagnosing some of the early clinical signs which often cause the patient to stop taking the drug. But in one series more than 10% of patients taking procainamide developed severe lupus erythematosus and another 10% developed a milder form of the syndrome (Fakhro et al. 1967). In the series by Hope and Bates (1972) 3 out of 61 patients who had taken procainamide for more than 4 weeks were found to have the full lupus syndrome, and another 3 had some features of the condition. 

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