Saddle pulmonary embolus and bronchiolitis obliterans with organizing pneumonia develop simultaneously after first cyclophosphamide, methotrexate, 5FU chemotherapy for breast cancer

Discussion

Massive PE is a catastrophic entity that often results in acute right ventricular failure, hemodynamic instability, and death.1 The diagnosis of massive PE relies mainly upon clinical suspicion followed by the appropriate investigation.2 Spiral CT of the chest is the diagnostic modality that is most often used in ventilated patients, although pulmonary angiogram remains the gold standard.3 Clinical instability may interfere with the institution of an effective diagnostic strategy, and could therefore delay early therapy. In our case, pulmonary artery catheter data led to the suspicion of PE and subsequent appropriate investigation and early therapeutic intervention. Thrombolysis is currently the standard treatment of massive PE with hemodynamic instability.2

Bronchiolitis obliterans with organizing pneumonia is another distinct clinical entity of unknown etiology. It is also called cryptogenic organizing pneumonia, and is defined pathologically by the presence in the distal air spaces of buds of granulation tissue progressing from fibrin exudates to loose collagen containing fibroblasts.4,5 It is commonly presented with pneumonia-like symptoms that do not respond to antibiotics. Organizing pneumonia (BOOP) may be classified into 3 categories according to its cause: organizing pneumonia of determined cause, organizing pneumonia of undetermined cause but occurring in a specific and relevant context, and cryptogenic (idiopathic) organizing pneumonia. Several possible causes and/or associated disorders may co-exist in the same patient. There are no clear distinguishing clinical and radiological features between cryptogenic and secondary organizing pneumonia.5,6

With drug-induced organizing pneumonia, it is sometimes difficult to determine causality since organizing pneumonia may also be associated with the underlying disease. In many cases however, it is not possible to determine whether the drug is responsible or not, for example, in patients with cancer or hematological malignancies who may be treated with several drugs that are able to induce organizing pneumonia.6 Bleomycin and busulphan are the most common chemotherapy drugs associated with BOOP. However, on MEDLINE review, we were unable to source CMF described in the literature as a cause of BOOP after the first cycle of chemotherapy. Chemotherapy, particularly cyclophosphamide, has been used as a second line treatment after steroids for BOOP. Though cyclophosphamide and methotrexate treatment have been rarely reported in the literature to cause BOOP, 5-FU has not been reported to cause BOOP.7,8 Systemic corticosteroid therapy is the mainstay of treatment with initial doses of 0.75 to 1 mg/kg per day, and gradual weaning over 6 to 12 months.9 Because of her respiratory failure requiring mechanical ventilation, our patient received a pulse of steroids over 3 days followed by 1 mg/kg of prednisone daily.10

This case highlights the importance of using the new chemotherapy regimen for breast cancer with fewer side effects including lung toxicities. In our case, BOOP was suspected after ruling out active infection and following an adequate course of antibiotic coverage. Open lung biopsy provided the definite diagnosis. Corticosteroids remain the mainstay of therapy.

In conclusion, multiple primary causes for respiratory failure in a single patient are not uncommon. In a patient at risk for PE, the diagnosis should be pursued further in the presence of unexplained high PAP and PVR. Bronchiolitis obliterans with organizing pneumonia is being increasingly diagnosed as a cause of respiratory failure and should, in the classical setting be commonly included in the differential diagnosis. The presence of an evident cause for respiratory failure should not deter further investigation.