Methotrexate-Induced Lung Injury: A Rare Cause of Significant Hypercalcemia

Abstract

SESSION TITLE: Drug-induced Lung Disease SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Prolonged methotrexate (MTX) use is known to carry risk of inflammatory and fibrotic lung disease. However, MTX-induced granulomatous pneumonitis with associated hypercalcemia is a very rare complication. CASE PRESENTATION: A 76-year-old Indian male with a past medical history of severe eczema on low-dose MTX for the past three years presented with worsening nonproductive cough, exertional dyspnea, and gastric reflux for one week. Pertinent medications included recent use of calcium carbonate for gastric reflux, and chronic hydrochlorothiazide (HCTZ) use for hypertension. He presented to an urgent care center, where he was found to be hypoxic with diffuse pulmonary infiltrates. Evaluation in the emergency department revealed normal vitals, excepting SpO2 94% on 2L nasal cannula. Physical exam was remarkable for rhonchi in bilateral upper lung fields. Initial labs showed a high corrected total serum calcium at 15.4 mg/dL. MTX and HCTZ were held, and aggressive IV normal saline with empiric ceftriaxone and azithromycin were administered. Additional labs revealed a low parathyroid hormone (PTH) at 4.8 pg/mL and high 1,25-OH2 vitamin D level at 164 pg/mL. Otherwise, phosphorus, PTH-related protein, 25-OH vitamin D, and angiotensin converting enzyme were unremarkable. Bronchoscopy showed mixed inflammatory cells with 90% mononuclear cells. All subsequent workup for atypical infections, plasma cell dyscrasias, neoplasm, and rheumatologic disorders were negative, thus a presumptive diagnosis of subacute MTX-induced pneumonitis was made on day seven of his admission. By this point, the serum calcium had normalized. To treat his lung injury, his antibiotics were discontinued and he was started on a prednisone taper for 2 weeks. At his three month follow-up with pulmonology he was asymptomatic, with normal spirometry and total resolution of his pulmonary infiltrates. DISCUSSION: Although calcium carbonate and HCTZ can lead to hypercalcemia, the extreme elevation here in conjunction with inappropriately elevated 1,25-OH2 vitamin D and suppressed PTH levels support the diagnosis of granulomatous disease. Per Cook et al., macrophages may autonomously produce extrarenal 1,25-OH2 vitamin D unresponsive to normal feedback mechanisms. Thus, along with discontinuation of MTX, glucocorticoid therapy may accelerate recovery from MTX-induced lung injury and reverse hypercalcemia. CONCLUSIONS: Although exceedingly rare, it is important to consider MTX-induced granulomatous injury as a primary cause of hypercalcemia. Reference #1: Jacobs, T, Bilezikian J. Rare Causes of Hypercalcemia. J Clin Endocrinol Metab. 2005;90(11): 6316-6322. Reference #2: Cook NJ, Lake FR. Hypercalcaemia with methotrexate pneumonitis, possible association with pulmonary granulomata. Aust N Z J Med. 1996 Oct;26(5):715. DISCLOSURE: The following authors have nothing to disclose: Prashant Patel, Matthew Siuba, Chris Jacob, Richard Roach No Product/Research Disclosure Information