Obliterans with organizing pneumonia (BOOP) is characterized by the presence of fibroblast proliferation within the lumen of the ducts and alveolar spaces, by the projection of inflammatory polyps into the lumen of the respiratory and terminal bronchioles, and by interstitial pneumonitis by mononuclear cells. Obliterans with organizing pneumonia can be idiopathic or secondary and is also reported in the context of chronic graft-versus-host disease (cGVHD) shown after allogeneic hematopoietic stem cell transplant (HSCT). The frequency of BOOP has been shown to vary from 3% to 6% in allogeneic HSCT recipients1,2 and has been shown to be associated with several risk factors, such as cGVHD and infectious respiratory viruses.3-5
In allogeneic HSCT recipients, cGVHD is the leading cause of mortality. The mechanisms involved in cGVHD remain unknown. In 2015, Jagasia and associates published a consensus of criteria for GVHD.6 In 2017, Cooke and associates reviewed the biology and therapies of cGVHD resulting from preclinical studies and those used as a platform for the development of innovative clinical strategies to prevent and treat cGVHD.7
COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which started in December 2019 in Wuhan city, Hubei province, China, was declared a pandemic in March 2020.8 The mechanisms of the pathogenesis of this infection have not yet been elucidated; however, the lungs are the organs most affected, a compromise attributed to the systemic inflammatory process, generating pneumonia with several affected parts of the lung; in the most severe cases, this infection may cause respiratory failure.9,10
In this letter, we report a patient with hypocellular myelodysplastic syndrome (MDS) treated with allogeneic HSCT at the Bone Marrow Transplant clinic at the Hospital Universitário Walter Cantídio (HUWC) in Fortaleza, Ceará, Brazil. The patient developed BOOP associated with COVID-19 infection. It should be noted that the patient did not present with any evidence of GVHD. This case is relevant because it alerts the scientific community to the BOOP entity in allogeneic HSCT recipients with COVID-19 infection, requiring increased surveillance, as it has been often associated with cGVHD after HSCT.
This article describes the case of a 70-year-old male patient who underwent allogeneic HSCT related to hypocellular MDS in December 2019. The patient received busulfan/fludarabine reduced intensity conditioning; peripheral blood was from a male donor with ABO minor incompatibility (A-positive recipient, O-positive donor). Written informed consent was obtained from the patient for their anonymized information to be published in this article.
The patient was given mycophenolate mofetil 500 mg once daily and prednisone 10 mg daily (both at weaning) for prophylaxis of cGVHD, which was replaced by cyclosporine with mycophenolate mofetil and prednisone for the transition by thrombotic microangiopathy (renal dysfunction, mild thrombocytopenia, nonimmune hemolytic anemia) in January 2020. The patient also received acyclovir 400 mg twice a day, trimethoprim-sulfamethoxazole 160/800 mg 3 times per week, allopurinol 300 mg once per day, omeprazole 20 mg once per day, and doxazosin 2 mg once per day. In May 2020, he reported characteristic flu symptoms and had anosmia, which required transportation to an emergency care unit because of dyspnea symptoms. A SARS-CoV-2 examination by reverse transcriptase-polymerase chain reaction (RT-PCR) was ordered, but the result was delayed, and he was hospitalized for 9 days with episodes of hypoxemia.
After 9 days of hospitalization, the patient was discharged with 95% saturation without conclusive results of the RT-PCR, according to a medical discharge report. The patient then underwent chromatographic immunoassay for qualitative detection of immunoglobulin G and immunoglobulin M anti-COVID-19 antibodies, with a reagent result for immunoglobulins G and M, indicating COVID-19 infection.
Several weeks later, the patient attended a follow-up visit at the bone marrow transplant unit and reported that, since discharge, he had pain in the dorsal region associated with movements and dyspnea on small efforts. A physical examination showed tachypnea at rest (respiratory rate: 28) and hypoxemia (saturation between 89% and 90%). The patient underwent chest radiography and computed tomography. The chest radiographic scan showed interstitial infiltrates with clamping of the diaphragmatic domes (Figure 1A), and chest computed tomography showed bilateral matte infiltrate and involvement of the subpleural areas (Figure 1B). All results with the clinical picture were characteristic of BOOP findings.
Obliterans with organizing pneumonia is a clinical syndrome that, in most cases, presents in a subacute or chronic form. Clinical signs in patients can suggest upper respiratory tract infection, which can be accompanied by persistent cough and dyspnea. The chest radiographic and computed tomography scans present themselves in different ways, with the diffuse bilateral alveolar infiltrate pattern being the most frequent.4,5 Less commonly, localized areas of consolidation appear, showing diffuse unilateral infiltrate, diffuse interstitial infiltrates, and isolated nodular densities.
A differential diagnosis of BOOP should be performed with other pathologies such as Hamman-Rich syndrome and adult respiratory distress syndrome. The clinical evolution described in our patient during outpatient HSCT care started with a report of pain in the dorsal region associated with movements and dyspnea on small efforts; physical examination showed tachypnea at rest (respiratory rate: 28) and hypoxemia (saturation between 89% and 90%), with chest scans showing characteristics compatible with BOOP.
In our patient, BOOP was attributed to being secondary to COVID-19 infection after pulmonary GVHD conditions were excluded. Some studies have demonstrated BOOP in patients after allogeneic HSCT1,2; risk factors include cGVHD, advanced age, airflow obstruction before HSCT, and respiratory virus infections.3-5 Therefore, in the current context of a pandemic caused by a new strain of coronavirus called SARS-CoV-2, extra attention should be given to possible causes of BOOP in patients after allogeneic HSCT; in addition, at all levels of health care, this therapeutic possibility should be considered.
This work was aimed to alert to the importance of the diagnosis of BOOP, as shown in a patient with hypocellular MDS after allogeneic HSCT who presented with COVID-19.
DOI : 10.6002/ect.2020.0360
From the 1Hospital Universitário Walter Cantídio (HUWC), Federal University of
Ceará and the 2Research Laboratory in Hemoglobinopathies and Genetics of
Hematologic Diseases, Federal University of Ceará, Ceará, Brazil; and the
3Faculdade Christus (Unichristus), Fortaleza, Brazil
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Fernando Barroso Duarte, Hospital Universitário Walter Cantídio (HUWC), Federal University of Ceara, Pastor Samuel Munguba, street, n. 1210- Rodolfo Teófilo, 60430-370 Fortaleza, Ceará, Brazil
Phone: +55 85 33668623
Figure 1. Chest Radiological and Computed Tomography Scans