Eosinophilic Pneumonia Associated With Azacitidine in a Patient With Myelodysplastic Syndrome

Abstract

Eosinophilic pneumonia is characterized by cough, lung infiltrates on imaging, and by the presence of eosinophils in the alveoli and pulmonary interstitium. Azacitidine, a pyramidine nucleoside analog of cytidine, is FDA approved for the treatment of various myelodysplastic syndromes. We present a case of a 76-year-old man with recently diagnosed myelodysplastic syndrome, who developed eosinophilic pneumonia after initiating therapy with azacitidine. There was clinical and radiographic improvement with cessation of the drug and treatment with prednisone. Diagnosis of drug-induced eosinophilic pneumonia is established by having a temporal relationship between onset of symptoms and initiation of therapy, bronchoalveolar lavage or lung biopsy evidence of pulmonary eosinophilia, no other explanation for the disease, and improvement upon cessation of the offending agent. Our case illustrates the need for a high index of suspicion to identify adverse pulmonary reactions associated with newly developed medications.

Azacitidine-Induced Pneumonitis in a Patient with Myelodysplastic Syndrome: First Case Report in Japan

“…However, because the second bone marrow aspiration showed improvement of the MDS, it is unlikely that MDS caused the lung disease in the present patient. Azacitidine-induced pneumonitis has been previously described to produce symptoms of fever, dry cough, dyspnea and radiographic or pathological characteristics that commonly appear to be those of eosinophilic pneumonia (EP) or OP (8)(9)(10)(11)(12)(13). Although the cessation of azacitidine did not resolve our patient's pulmonary infiltrations, such infiltrations may be seen in acute interstitial reactions or pulmonary fibrosis (14).…”

“…To date, only seven cases of azacitidine-induced pneumonitis have been reported (8)(9)(10)(11)(12)(13), including five cases published in the literature that could be confirmed in detail (8-10, 12, 13). To our knowledge, our patient is the first case reported in Japan ( Table 2).…”

“…On the basis of this finding, the United States Food and Drug Administration approved this agent for the treatment of MDS in 2004. Although azacitidine is commonly well tolerated, and interstitial lung disease induced by azacitidine was not reported in the American phase III (4) and Japanese phase I and II (7) trials, it is nevertheless known to rarely cause interstitial pneumonia (8)(9)(10)(11)(12)(13). We herein report a rare case of azacitidine-induced pneumonitis, along with a review of the previous literature related to this adverse effect.…”

Rare Respiratory and Neurologic Adverse Reactions to Azacitidine in the Treatment of Myelodysplastic Syndrome of Patients Treated at the Ottawa Hospital

“…All cases of azacitidine-induced pulmonary toxicity have been described as pneumonitis and eosinophilic pneumonia which are characterized by cough, lung infiltrates, and the presence of eosinophils in the alveolar spaces and pulmonary interstitium [12][13][14][15][16]. Chest CT in all cases showed bilateral airspace disease, nodular opacities, bilateral patchy infiltrates, and en-largement of mediastinal and hilar lymph nodes.…”

Azacitidine-Induced Interstitial Pneumonitis

“…16 High mortality rates are observed due to the lack of specific therapeutic management excepting high-dose corticosteroid or cyclophosphamide indicated for the most severe cases.…”