Systemic lupus erythematosus, drug-induced

A few examples of animal models used in immunotoxicologic testing of drugs include Brown Norway rat and Lewis rat models, which are described in detail below. Other established mouse models of autoimmune diseases, e.g.,systemic lupus erythematosus, collagen-induced arthritis,pristane-induced arthritis and systemic scleroderma, may be considered for potential application in immunotoxicology evaluation. 

Pugh S, Pel ton B, Raftery EB, Denman AM (1976) Abnormal lymphocyte function is secondary to drug induced autoimmunity. Ann Rheum Dis 35 344-348 Raftery EB, Denman AM (1973) Systemic lupus erythematosus syndrome induced by prac-tolol. Br Med J 2 452-455... 

Lundgren R, Back O, Wiman LG (1975) Pulmonary lesions and autoimmune reactions after long-term nitrofurantoin treatment. Scand Respir Dis 56 208 Lynn KL, Little PJ (1976) Reaction to trimoxazole. NZ Med J 377 78 Mackie BS, Mackie LE (1979) Systemic lupus erythematosus-dermatomyositis induced by sulphacetamide eye drops. Aust J Dermatol 20 49 Maddrey W, Boitnott J (1977) Drug-induced chronic liver disease. Gastroenterology 72 1348... 

Mohan, A.K. et al., Drug-induced systemic lupus erythematosus and TNF-alpha blockers, Lancet 360,646, 2002. 

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. 

Certain autoimmune syndromes can be induced by drugs. Examples include systemic lupus erythematosus following hydralazine or procainamide therapy, "lupoid hepatitis" due to cathartic sensitivity, autoimmune hemolytic anemia resulting from methyldopa administration, thrombocytopenic purpura due to quinidine, and agranulocytosis due to a variety of drugs. As indicated in other... 

The drug hydralazine is a vasodilator used for the treatment of hypertension. In a significant proportion of individuals, it causes a serious adverse effect, drug-induced systemic lupus erythematosus (SLE). This is a systemic kind of toxic effect, as there is no particular target organ or tissue. It is an example of immune-media ted toxicity that involves autoimmunity and shows a number of interesting features. 

W8. Weinstein, A., Drug-induced systemic lupus erythematosus. Prog. Clin. Immunol. 4, 1-21 (1980). 

M Siegal, SL Lee, NS Peress. The epidemiology of drug-induced systemic lupus erythematosus. Arthritis Rheum 10 407, 1967. 

Similar antibodies are found in patients with systemic lupus erythematosus and it has been proposed that lupus nephritis results from IgG binding to I(H2A-H2B)-DNA] in nucleosomal material that is deposited in the glomerulus by the circulation (78). Because renal involvement is not a feature of drug-induced lupuS/ it appears that factors other than antibody binding to I(H2A-H2B)-DNA] are responsible for nephritis. However/ the systemic symptoms of drug-induced lupus may result from inflammatory mechanisms involved in the clearance of immune complexes. 

Shakoor N, Michalska M, Harris CA, Block JA. Drug-induced systemic lupus erythematosus associated with etanercept therapy. Lancet 2002 359(9306) 579-80. 

Systemic lupus erythematosus and rheumatoid arthritis The possible role of interferon alfa in the development of rheumatoid arthritis or systemic lupus erythematosus has been described in isolated cases (363,364), and confirmed cases of systemic lupus erythematosus have very occasionally been reported (SED-13, 1096) (SEDA-20, 330). In most of these cases, the predominance of young patients and female sex, the presence of renal or skin involvement, the findings of positive antibodies to double-stranded DNA, and the rapid onset after the start of treatment, as well as persistence of symptoms after interferon alfa withdrawal, are more in keeping with unmasking by interferon alfa of idiopathic lupus rather than with a new drug-induced illness. The reactivation or appearance of inflammatory rheumatological disorders consistent with rheumatoid arthritis or lupus-like polyarthritis were... 

Mohindra SK, Udeani GO, Abrahamson D. Cardiac tamponade associated with drug-induced systemic lupus erythematosus. Crit Care Med 1989 17(9) 961-2. 

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. 

A drug-induced systemic lupus erythematosus (SEE) with proliferative glomerulonephritis has also been described in patients treated with D-penicillamine [111, 157]. Systemic lupus erythematosus syndrome is induced in approximately 2% of patients treated with D-penicillamine [112,158]. Unlike other forms of drug-induced systemic lupus erythematosus, anti-double-strand DNA anhbodies and/or hypocomplementemia are seen in D-penicillamine-induced systemic lupus erythematosus syndrome [111, 156]. Nephropathy is rare in D-penicillamine-induced systemic lupus erythematosus syndrome [111]. Walshe [112] reported that 8 patients developed the serological change of systemic lupus erythematosus of 120 patients with Wilson s disease treated with D-penicillamine, but none of them showed nephropathy. 

In addition to penicillamine nephropathy, other side effects of the drug may be related to the widespread deposition of immune complexes (Figure 3). Dense, granular immunoglobuhn deposits have been identified at the epidermodermal junction in 4 rheumatoid arthritis patients who developed toxic reactions, such as severe rashes, thrombocytopenia, aplastic anemia, and proteinuria. Three of 4 penicillamine-induced systemic lupus erythematosus syndrome patients had similar findings on skin biopsy [161]. 

Drug-induced lupus is a syndrome which shares symptoms and laboratory characteristics with idiopathic systemic lupus erythematosus (SLE). Similarly... 

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