Case Report A 64-Year-Old Male With Fever and Persistent Lung Infiltrate Tajender S Vasu MD, Rodrigo Cavallazzi MD, Amyn Hirani MD, and Paul E Marik MD Acute fibrinous and organizing pneumonia is a newly recognized pattern of lung injury. It may be idiopathic or secondary to a variety of lung injuries. In this case report we describe a 64-year-old male with acute fibrinous and organizing pneumonia caused by decitabine. He had substantial clinical and radiological improvement after the discontinuation of decitabine and a course of corticosteroids. Key words: acute respiratory distress syndrome, ARDS, acute lung injury, ALI, decit- abine, myelodysplastic syndrome, drug induced pneumonitis, acute fibrinous and organizing pneumonia. [Respir Care 2009;54(9):1263–1265. © 2009 Daedalus Enterprises] Introduction A wide variety of drugs can cause pulmonary injury and should be considered during the evaluation of lung infil- trate.1 Early diagnosis is important because unrecognized toxicity can be progressive and even fatal. Drug-induced lung injury may manifest in a variety of histological pat- terns.1 Acute fibrinous and organizing pneumonia is a dis- tinct pattern of reaction of the lung to injury.2 It is char- acterized by intra-alveolar fibrin balls and organizing pneumonia. The absence of hyaline membranes, granulo- matous inflammation, and eosinophilic deposition are im- portant distinguishing features. Case Report A 64-year-old male came to our hospital with dry cough, fever, and chills, of 2 weeks duration. He had a history of myelodysplastic syndrome, developing after the successful treatment of acute myelogenous leukemia. Four weeks earlier he had received 50 mg of intravenous decitabine daily for 5 days. At the time of hospitalization he had just completed a second course of decitabine. On examination his temperature was 102°F, blood pressure was 134/ 62 mm Hg, heart rate was 98 beats/min, oxygen saturation was 88% on room air, and respiratory rate was 18 breaths/ min. His lung examination had inspiratory crackles in the left lung base. The rest of his physical examination was unremarkable. He had pancytopenia, with white-blood-cell count of 0.7�109 cells/L (normal range of 4 –10�109 cells/ L), hemoglobin of 7.9 g/dL (normal range of 14 –17 g/dL), and platelets of 12,000 cells/L (normal range of 140,000 – 400,000 cells/L). His differential count showed 20% neu- trophils, 70% lymphocytes, and 10% monocytes. His se- rum sodium, potassium, creatinine, magnesium, calcium, and liver function test were all within normal limits. Blood and urine cultures were negative. The chest radiograph showed an ill-defined left-lower-lobe infiltrate. He was started on broad-spectrum antibiotics, including an anti-fungal agent. The computed tomography scan of his chest (Fig. 1) revealed a left-lower-lobe consolidation. Computed-tomography-guided needle aspiration of the left lower lobe was non-diagnostic. He underwent bronchos- copy with bronchoalveolar lavage, which was non-diag- nostic. His bronchoalveolar lavage fluid showed 48% mac- rophages, 32% neutrophils, and 20% lymphocytes. He remained febrile despite treatment with antibiotics. A re- peat computed tomography of the chest (Fig. 2) 10 days later showed worsening of the left-lower-lobe consolida- tion. The patient underwent video-assisted thoracoscopic wedge biopsy of the left lower lobe. The open-lung biopsy from the left-lower lobe (Fig. 3) showed patchy areas of organizing pneumonia with fibrin balls within the alveoli and air spaces. There was no hyaline membrane. The di- agnosis of acute fibrinous and organizing pneumonia sec- Tajender S Vasu MD, Rodrigo Cavallazzi MD, Amyn Hirani MD, Paul E Marik MD are affiliated with the Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, Pennsylva- nia. The authors have disclosed no conflicts of interest. Correspondence: Tajender S Vasu MD, Division of Pulmonary and Crit- ical Care Medicine, Thomas Jefferson University, 834 Walnut Street, Suite 650, Philadelphia PA 19107. E-mail: tajender.vasu@ jeffersonhospital.org. RESPIRATORY CARE • SEPTEMBER 2009 VOL 54 NO 9 1263 ondary to decitabine was established. He was started on methylprednisone 60 mg intravenously, every 6 hours, fol- lowed by 40 mg of oral prednisone daily. He had substan- tial clinical and radiological improvement after discontin- uation of decitabine and a course of corticosteroids. Discussion Acute fibrinous and organizing pneumonia was first de- scribed by Beasley et al2 in 2002. In their paper they noted several conditions associated with acute fibrinous and or- ganizing pneumonia, including collagen-vascular disease, lymphoma, amiodarone, and infections caused by Hae- mophilus influenzae and Acinetobacter baumannii. Re- cently, acute fibrinous and organizing pneumonia has also been reported in patients with dermatomyositis,3 acute lym- phocytic leukemia,4 severe acute respiratory syndrome,5 and secondary to drugs, including abacavir6 and busulfan.7 Patients with acute fibrinous and organizing pneumonia may have an acute or subacute clinical course. The pattern of the acute form resembles the clinical picture of acute lung injury. Decitabine8 is a hypomethylating agent that was recently approved by the Food and Drug Administra- tion for the treatment of myelodysplastic syndrome. The major adverse effect of decitabine is myelosuppression. Other adverse effects, including fever, nausea, vomiting, diarrhea, bone aches, hyperbilirubinemia, and skin rash, have also been described. To the best of our knowledge this is the first case describing acute fibrinous and orga- nizing pneumonia pattern of lung injury secondary to de- citabine. The classic histological findings of acute fibrinous and organizing pneumonia include intra-alveolar fibrin balls with organizing pneumonia. This pattern must be distin- guished from diffuse alveolar damage, bronchiolitis oblit- erans organizing pneumonia,9 and eosinophilic pneumo- nia.10 Fibrin deposits are found in diffuse alveolar damage and bronchiolitis obliterans organizing pneumonia, but, Fig. 1. Computed tomogram shows a left-lower-lobe consolida- tion. Fig. 2. Repeat computed tomography 10 days later shows wors- ening of the left-lower-lobe consolidation. Fig. 3. Micrograph from the open-lung biopsy of the left-lower lobe shows patchy areas of organizing pneumonia with fibrin balls in the alveoli and air spaces. A 64-YEAR-OLD MALE WITH FEVER AND PERSISTENT LUNG INFILTRATE 1264 RESPIRATORY CARE • SEPTEMBER 2009 VOL 54 NO 9 unlike acute fibrinous and organizing pneumonia, these deposits do not represent the major findings. The air-space involvement in acute fibrinous and organizing pneumonia is patchy in distribution, as opposed to diffuse involve- ment in diffuse alveolar damage. Hyaline membranes, gran- ulomatous inflammation, and eosinophilic infiltrates are absent in acute fibrinous and organizing pneumonia. The retrospective review by Beasley et al2 demonstrated that approximately 30% of patients with acute fibrinous and organizing pneumonia required mechanical ventila- tion. Notably, all those patients who needed mechanical ventilation died. The acute fibrinous and organizing pneu- monia pattern portends a poor prognosis, with a mortality rate of more than 50%. The clinical course of these pa- tients is similar to those with diffuse alveolar damage, and, indeed, acute fibrinous and organizing pneumonia may be a fibrinous variant of diffuse alveolar damage. Treatment with corticosteroids and discontinuation of the underlying drug may be attempted. REFERENCES 1. Erasmus JJ, McAdams HP, Rossi SE. Drug-induced lung injury. Semin Roentgenol 2002;37(1):72-81. 2. Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002;126:1064-1070. 3. Prahalad S, Bohnsack JF, Maloney CG, Leslie KO. Fatal acute fi- brinous and organizing pneumonia in a child with juvenile dermato- myositis. J Pediatr 2005;146(2):289-292. 4. Kim BC, Servi R, Sucai BI, Ramsey R. 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Medi- cine (Baltimore) 1969;48(4):251-282. A 64-YEAR-OLD MALE WITH FEVER AND PERSISTENT LUNG INFILTRATE RESPIRATORY CARE • SEPTEMBER 2009 VOL 54 NO 9 1265