Hydralazine‐Induced Lupus Erythematosis

Abstract

A 65-year-old woman was seen in our hypertension clinic following recovery from hydralazine-induced lupus erythematosis. She had been taking antihypertensive medication for 15 years and was evaluated by the rheumatology department a year prior to her hypertension consultation for joint pain and swelling associated with positive serologies.A month prior to her rheumatology appointment she developed acute pain and swelling in the left fifth proximal interphalangeal joint (PIP), followed by painful swelling of the fourth and fifth PIP joints allowing minimal flexion. Subsequent joint involvement progressed to the right fifth PIP joint, bilateral wrists, right shoulder, bilateral knees, bilateral ankles, and both forefeet. Laboratory tests were significant for a diffuse pattern antinuclear antibody 1:2560 and a low positive rheumatoid factor of 17 IU ⁄ mL (normal <11 IU ⁄ mL). A complete blood cell count and renal function were normal. She denied fever, rash, pleuritic chest pain, or shortness of breath.Rheumatology examination noted swelling and tenderness of the left third, fourth, and fifth PIP joints with dactylitis, swelling and tenderness of the right fifth PIP, and bilateral tender wrists. Additional serologies revealed antidouble stranded deoxyribonucleic acid antibody (anti-ds DNA ab) 15 IU ⁄ mL (normal <25.0 IU ⁄ mL), antihistone antibody 1.8 UOM ⁄ U (normal <1.0 UOM ⁄ U), C3 complement 153 mg ⁄ dL (normal 90-180 mg ⁄ dL), C4 complement 21 mg ⁄ dL (normal 10-40 mg ⁄ dL), and Westergren erythrocyte sedimentation rate 43 mm ⁄ h (normal 0-33 mm ⁄ h). Her 4-drug antihypertensive drug regimen included hydralazine 50 mg twice a day for 5 years.Hydralazine was discontinued and azulfidine was initiated and advanced to 1000 mg twice a day with meloxicam 15 mg daily. Painful joints rapidly abated and 6 months later azulfidine was discontinued without a recurrence of her inflammatory arthritis. Losartan, amlodipine, and atenolol were continued. When chlorthalidone was substituted for furosemide, elevated blood pressures off of hydralazine became controlled.

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction

“…Hydralazine can occasionally cause serious side effects, such as drug-induced lupus erythematosus and vasculitis. 14,15 Patients who exhibit signs of this should immediately contact their healthcare provider. Sildenafil, vardenafil, and tadalfil, which are selective inhibitors of cyclic guanosine monophosphateYspecific phosphodiesterase type 5 used for erectile dysfunction, may increase the hypotensive effects of nitrates and are contraindicated with concomitant nitrate use.…”

The Management of Hypertension in Pregnancy

“…62 It is also associated with a lupus-like syndrome and peripheral neuropathy. The lupus-like syndrome is usually seen with higher oral daily doses (> 200 mg daily) 63 , though has been seen with doses as low as 50 mg daily when the exposure is prolonged (months to years) 64 . Due to these potential side effects, labetalol is increasingly viewed as a safer agent for inpatient management of hypertension.…”

Acute Low-Dose Hydralazine-Induced Lupus Pneumonitis

“…Since then, multiple forms of DIA have been described, including autoimmune hemolytic anemia, vasculitis, and autoimmune vasculitis, but drug-induced lupus (DIL) remains the most common form of DIA [ 1 ]. Of the dozens of agents known to cause DIL, procainamide and hydralazine remain the most common, with an incidence of 20% for procainamide and 5–8% for hydralazine [ 1 , 2 ].…”

“…Hydralazine was first introduced as an antihypertensive in 1951, with the first cases of HIL observed two years later in 1953 [ 1 , 2 ]. The temporal relationship between initiation of hydralazine and symptoms of HIL varies but tends to be following months to years of treatment.…”