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 VOLUME 115