Lupus syndrome, drug-induced

Finding antibodies which react with nuclear components of xenogenic tissue is a positive indication that a drug may be responsible for a lupus-like syndrome. Drug-induced lupus is a complex disease while the mechanism, despite detailed investigation, is still unclear. 

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. 

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. 

Although rare, cases of renal lupus syndrome and pemphigus blisters have also been reported as a consequence of D-penicillamine-induced immune complexes (Ntoso et al., 1986 Bigazzi, 1988), as well as with other drugs. With renal lupus syndrome, secondary glomerulonephritis may result if granular IgG antibodies are produced and deposited on the basement membranes. In patients with pemphigus blisters, autoantibodies to the intercellular substance of the skin have been recovered from the sera, and dermal biopsies have demonstrated intracellular deposits or... 

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. 

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

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. 

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... 

Drug-induced lupus-like syndrome has been associated with lamotrigine (59). 

Other case reports of interest include pulmonary eosino-philia in association with montelukast (13) and the clinical exacerbation of ulcerative colitis in a patient with steroid-dependent asthma after the introduction of zafirlukast (14). Drug-induced lupus syndrome has been reported in a child with an onset 10 days after beginning treatment with zafirlukast. The child had not been taking oral glucocorticoids (15). 

In a retrospective review of drug safety databases, minocychne was the only tetracychne derivative that caused drug-induced lupus (SEDA-22, 268) (38). The authors proposed that the propensity of minocycline to cause drug-induced lupus may be due to the presence of a functional group that is easily oxidized to a reactive metabolite. However, the chemicaUy modified tetracycline CMT-3, which has also reportedly caused a lupus-like syndrome (39), lacks this group, so another theory is needed. 

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. 

Table 1 The contrast between drug-induced lupus-like syndrome and idiopathic lupus erythematosus...

Thymus function in 10 patients with sjmiptomatic procainamide-induced lupus has been compared with that in 13 asymptomatic patients who only developed drug-induced autoantibodies (45). Newly generated T cells were detected in all the subjects. Although there was no overall quantitative difference between the sjmp-tomatic and asymptomatic patients, there was a correlation between the level of T cell receptor rearrangement excision circles in peripheral lymphocytes and serum IgG antichromatin antibody activity in patients with drug-induced lupus. These results support the hypothesis that the thymus is important in the genesis of drug-induced lupus-like syndrome and that the production of autoreac-tive T cells starts in the thymus when procainamide hydroxylamine alters T cell tolerance. 

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). 

A 300 mg dose of rifabutin is usually well tolerated. Adverse effects include neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances (nausea, flatulence). Myositis (12) and uveitis (13) are rarely observed. The drug-induced lupus-like syndrome has been linked in a few cases with rifampicin and rifabutin. 

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