The Journal of the Arkansas Medical Society Med Journal May 2019 Final 2 | Page 9

CASE REPORT
Hydralazine-induced Rheumatologic
Disease: Back to the Future
Sruthi Kanu ru, MD; 1 Neriman Gokden, MD; 2 Shirin Trisha, MD; 3 Seth Mark Berney, MD 4
1
Assistant Professor of Medicine, Central Arkansas Veterans Healthcare System, UAMS
2
Professor of Pathology and Urology, Director of Anatomic Pathology, Vice-Chair for Faculty Affairs, UAMS
3 rd
3 year Medicine-Pediatrics Resident, UAMS
4
Professor of Medicine, Chief, Division of Rheumatology, Director, Rheumatology Fellowship Program, UAMS
ABSTRACT
W
e present a patient who devel-
oped both drug-induced lupus
and vasculitis after taking hy-
dralazine. Additionally, we review the literature
about these disorders. An 81-year-old hypertensive
female developed serositis, leukopenia, thrombo-
cytopenia, positive ANA (Antinuclear antibody) and
antihistone antibodies, hypocomplementemia, a
pauci immune glomerulonephritis, and positive
ANCA (Anti-Neutrophilic Cytoplasmic Autoantibody)
after six months of hydralazine. Although lupus and
vasculitis are known side effects of hydralazine,
their frequency decreased significantly 25 years
ago, as angiotensin-converting enzyme inhibitors
replaced hydralazine. However, use of hydralazine
increased recently after heart-failure patient sur-
vival improved with the combination of hydralazine
and nitrates. It is important to recognize the auto-
immune complications of hydralazine, especially in
the setting of its increased clinical use.
INTRODUCTION
Hydralazine is an arterial vasodilator to treat
hypertension and heart failure since 1953. 1 Al-
though lupus and vasculitis are well described
side effects of hydralazine, 2 their frequency has
decreased significantly because angiotensin-
converting enzyme inhibitors replaced hydralazine,
resulting in several generations of physicians who
are unfamiliar with its complications. In 2004, the
recognition that heart-failure patients treated with
hydralazine and nitrates survive longer has caused
increased use of hydralazine and the possibility of
a resurgence of its adverse effects.
We present a patient with hypertension who
developed both lupus and ANCA positive pauci-
immune glomerulonephritis after six months of
hydralazine therapy.
CASE PRESENTATION
An 81-year-old female with renal insufficiency
(baseline creatinine= 1.5 mg/dl), hypertension
(treated with hydralazine for the prior six months),
hypothyroidism, and hyperlipidemia was admitted to
an outside hospital with four months of intermittent,
subjective fever; malaise; fatigue; weakness; nau-
sea; diarrhea; vomiting; 40 pounds of unintentional
weight loss; and two weeks of decreased urination
and leg swelling.
Her physical exam and diagnostic laboratory
test results on admission to the outside hospital:
Temp: 98.1; BP: 137/71; HR: 75; RR: 20
Skin: morbilliform eruption of the neck and upper
chest, arms and forearms bilaterally
Lung exam: rales at left lower base
Heart sounds: normal
Muscle strength: 4/5 in proximal upper and lower
extremities
WBC: 1000/mm3  (nl= 3-12,000)
Hemoglobin: 9.1 g/dL (nl= 11.5-16)
Platelet: 76000/mm3 (nl= 150,000-500,000)
Potassium: 6.6 mmol/L (nl= 3.5-5.1)
Bun: 44 mg/dl (nl= 6-20)
Cr: 2.6 mg/dl (nl= 0.4-1.0)
UA: 40-50 RBCs/hpf (nl= 0-2/)
LDH: 986 IU/L (nl= 100-248)
Blood and urine cultures: sterile
daily, megestrol acetate 400 mg daily, calcium/
vitamin D 600mg/400 IU daily, simvastatin 40 mg
nightly.
Her physical exam and diagnostic laboratory
test results on arrival:
Vitals: Temp 98.2; RR 14; BP 135/75; P 75
General: patient appeared sick but in no acute
distress
Lungs: clear to auscultation bilaterally
Skin: morbilliform eruption of the neck, upper chest
and bilateral upper extremities, sparing the
hands; Ecchymoses on her forearms
Cardiac: regular rate of S1 S2 without S3, S4, mur-
murs.
Abdomen: bowel sounds present, soft, nontender,
without hepatosplenomegaly
Extremities: diffuse 4+ pitting edema
Neurologic: 3/5 proximal muscle strength; 4+/5
distal muscle strength
WBC 8840/mm 3 (nl= 3-12,000)
Hemoglobin 9.3 mg/dL  (nl= 11.5-16 g)
Platelet count 37000/mm 3  (nl= 150,000-500,000)
Peripheral smear: rare schistocytes
Haptoglobin: 165 mg/dl (nl= 30-200)
Sodium 134 mmol/L (nl= 135-145)
Potassium 6.6 mmol/L (nl= 3.5- 5.1)
She underwent dialysis to treat her hyperka-
lemia, received filgrastim for the leukopenia with
improvement (5000/mm 3 ) but a worsened throm-
bocytopenia (35000/mm 3 ). Because of her acute
kidney injury, thrombocytopenia, and elevated LDH,
her doctors transferred her to our hospital to undergo
plasmapheresis for atypical hemolytic uremic syn-
drome (HUS).
Her medications on transfer included: aspirin 81
mg daily, levothyroxine 75 mcg daily, hydralazine 25
mg TID, triamterene/hydrochlorothiazide 75/50 mg
Figure 1. Partial-cellular crescent present in
a normocellular glomerulus, PAS stain, 400X
NUMBER 11
> Continued on page 250.
MAY 2019 • 249