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Lupus, Drug-Induced

For further information, see CMDT Part 20-08: Drug-Induced Lupus

Key Features

  • Shares several clinical and serologic features with systemic lupus erythematosus (SLE) but is due to ongoing exposure to a drug

  • Drug-induced lupus resolves when the offending drug is discontinued

  • The sex ratio is nearly equal

  • Incidence of drug-induced lupus

    • 5–8% in patients taking hydralazine for a year or longer

    • < 1% for most other medications

Clinical Findings

  • Fever

  • Arthralgia

  • Myalgia

  • Serositis

  • Unlike in SLE, renal involvement and neurologic symptoms do not occur in drug-induced lupus

Diagnosis

  • Serologic testing reveals elevated titers of antinuclear antibodies in all patients, but antibodies to DNA, Sm, RNP, SS-A, and SS-B are rare (Table 20–7)

  • Antibodies to histones are common but also are seen in SLE and thus do not distinguish drug-induced lupus from SLE

  • Complement levels are usually normal

  • eTable 20–2 outlines medications associated with SLE

Table 20–7.Frequency (%) of autoantibodies in rheumatic diseases.1
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Table 20–7. Frequency (%) of autoantibodies in rheumatic diseases.1
  ANA Anti-Native DNA Rheumatoid Factor Anti-Sm Anti-SS-A Anti-SS-B Anti-SCL-70 Anti-Centromere Anti-Jo-1 ANCA
Rheumatoid arthritis 30–60 0–5 70 0 0–5 0–2 0 0 0 0
Systemic lupus erythematosus 95–100 60 20 10–25 15–20 5–20 0 0 0 0–1
Sjögren syndrome 95 0 75 0 65 65 0 0 0 0
Diffuse systemic sclerosis > 95 0 30 0 0 0 33 1 0 0
Limited systemic sclerosis (CREST syndrome) > 95 0 30 0 0 0 20 50 0 0
Polymyositis/dermatomyositis 80 0 33 0 0 0 0 0 20–30 0
Granulomatosis with polyangiitis 0–15 0 50 0 0 0 0 0 0 93–961

1Frequency for generalized, active disease.

ANA, antinuclear antibodies; Anti-Sm, anti-Smith antibody; Anti-SCL-70, anti-scleroderma antibody; ANCA, antineutrophil cytoplasmic antibody; CREST, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia.

eTable 20–2.Medications associated with lupus erythematosus.
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eTable 20–2. Medications associated with lupus erythematosus.

Definite association

Anti-TNF agents (etanercept, infliximab, adalimumab, golimumab, certolizumab)

Cancer immunotherapy (ipilimumab, nivolumab, pembrolizumab)

Chlorpromazine

Hydralazine

Interferon-alpha

Isoniazid

Methyldopa

 

Minocycline

Procainamide

Quinidine

Possible association

Amiodarone

Beta-blockers

Captopril

Carbamazepine

Cimetidine

Ethosuximide

Hydrochlorothiazide

Levodopa

Lithium

Methimazole

 

Nitrofurantoin

Penicillamine

Phenytoin

Propylthiouracil

Rifampin

Sulfasalazine

Sulfonamides

Ticlodipine

Trimethadione

Unlikely association

Allopurinol

Chlorthalidone

Gold salts

Griseofulvin

Methysergide

Oral contraceptives

 

Penicillin

Reserpine

Streptomycin

Tetracyclines

Modified and reproduced, with permission, from Hess EV et al. Drug-related lupus. Bull Rheum Dis. 1991;40:1.

Treatment

  • Discontinue the offending drug

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