The Journal of the Arkansas Medical Society Med Journal May 2019 Final 2 | Page 10

Figure 2. Mesangial C1q positivity (1+) by direct IF staining, FITC, 400X.
Bicarbonate 12 mmol/L (nl= 22-32)
BUN 92 mg/dl (nl= 6-20)
Creatinine 6.2 mg/dl (nl= 0.4-1.0)
Calcium 7.8 mg/dl (nl= 8.6-10.2)
Phosphorus 6.3 mg/dl (nl= 2.5-4.5)
Magnesium 1.8 mg/dl (nl= 1.6-2.6)
AST 32 IU/L (nl= 15-41)
ALT 7 IU/L (nl= 5-45)
LDH 469 IU/L (nl= 100-248)
TSH: 2.07 IU (nl= 0.34-5.6)
CK 38 IU/L (nl= 38-234)
Aldolase: 18.8 U/L (nl= 1.5-8.1)
Myoglobin 402.3 ng/ml (nl= 3-70)
UA: Blood large; RBC >100 (nl= 0-2); WBC 0-2 (nl=
0-2); Dysmorphic RBCs present; Urine protein/cre-
atinine: 1840 mg/24 hours
Immunology
ANA-positive (no titer was performed)
Anti histone antibody: >8.0 units (nl < 0.9)
Anti ds DNA antibody: 14 IU/ml (nl< 9),
Anti smith antibody: negative.
C3- 33.1 mg/dl (nl= 90-180)
C4- <10.0 mg/dl (nl= 15-45)
ANCA 1:5120   (nl < 1:20)
Anti MPO 137 AU/ml (nl< 19)
Anti PR3 40 AU/ml (nl< 19)
Cryoglobulin: negative
Figure 3. Electron microscopy showing small mesangial densities (Arrow).
rophy. Additionally, her biopsy indicated a low-grade
mesangiopathic glomerulonephritis with immuno-
fluorescence showing full-house staining (Figure 2)
and electron microscopy showing mesangial small,
electron-dense deposits (Figure 3), favoring autoim-
mune etiology (such as lupus).
Because she began hydralazine six months
prior to developing serositis, leukopenia, thrombo-
cytopenia, positive ANA, positive antihistone anti-
body, hypocomplementemia (indicative of active
lupus), and features of an ANCA-associated renal
vasculitis (a strongly positive ANCA in a perinuclear
staining pattern, anti MPO antibody and a pauci im-
mune crescentic glomerulonephritis), we diagnosed
this patient with simultaneous hydralazine-induced
ANCA-positive glomerulonephritis and hydralazine-
induced lupus.
DISCUSSION
Because neither denovo lupus nor denovo
ANCA-associated pauci immune glomerulonephritis
are likely in this 81-year-old patient and she took a
drug known to cause these complications, we con-
clude that she had both hydralazine Drug-induced
lupus (DIL) and hydralazine Drug-induced ANCA as-
sociated vasculitis (DIAV).
Renal ultrasound: markedly echogenic kidneys
suggesting medical renal disease without hydrone-
phrosis DIL more commonly affects older individuals
(mean age > 50 years) without gender predomi-
nance. Most rheumatologists agree that patients
with suspected DIL should develop lupus manifes-
tations and a positive antinuclear antibody after be-
ginning a suspected medication. Furthermore, these
abnormalities should resolve after discontinuing the
medication. 3 The following abbreviated drug list has
been linked with DIL development and grouped into
“Definite” and “Possible” categories (Table 1).
With a normal haptoglobin and rare schisto-
cytes, HUS was less likely. Thus, she underwent
a renal biopsy, revealing a crescentic glomerulo-
nephritis (Figure 1) consistent with pauci-immune
(ANCA related) glomerulonephritis; 80% global scle-
rosis; and cortical interstitial fibrosis with tubular at- Patients with DIL tend to have milder disease
and may experience fever, myalgias, rash, arthral-
gias, arthritis, serositis, cytopenias, hypocomple-
mentemia, and anti-histone antibodies with rare
renal, central nervous system involvement, or pul-
monary hemorrhage. Up to 50% of patients on hy-
Infectious disease
HIV and hepatitis antibodies: negative
Diagnostic Radiology tests
Chest radiograph: large, left pleural effusion
250 • THE JOURNAL OF THE ARKANSAS MEDICAL SOCIETY
dralazine can develop a positive ANA, but only 5-8%
will develop DIL. 8
DIAV has been reported for propylthiouracil, hy-
dralazine, minocycline, and levamisole-cut cocaine,
and is the most common forms of vasculitis. Con-
trasting with the idiopathic vasculitides, DIAV is usu-
ally milder, and the effects are often reversible once
the offending agent is withdrawn. However, patients
may develop more severe organ involvement with
permanent damage if the drug is not withdrawn
soon enough.
Patients with DIAV frequently present with sub-
jective fever, nausea, vomiting, myalgias, arthral-
gias, rash (including palpable purpura), malaise, and
weight loss or with hematuria, proteinuria, and an
elevated serum creatinine representing acute kid-
ney injury that rapidly progresses to renal failure. 9
Hemoptysis, indicating alveolar hemorrhage, is the
Table 1. Drug-Induced Lupus
Definite
Possible
Procainamide
hydralazine
penicillamine
quinidine
Isoniazid
Minocycline 5
diltiazem
(subacute
cutaneous lupus
rash) 6
anti-TNF-α
agents 7
α-methyldopa
chlorpromazine
4
β interferon
γ interferon
anticonvulsants
(esp phenytoin)
rifampin
nitrofurantoin
lithium
captopril
hydrochlorothiazide
sulfasalazine
terbinafine
amiodarone
docetaxel
HMG-CoA reductase
inhibitors
tetracycline
griseofulvin
gemfibrozil
lamotrigine
reserpine
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